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Soft Tissue

Superpage 4

Revised: 17 November 2014
Copyright: (c) 2001-2014, PathologyOutlines.com, Inc.

Skeletal muscle

Skeletal muscle-normal


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 18 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Normal skeletal muscle arises from mesectoderm in head and neck and from myotomes (group of skeletal muscles supplied by a specific segmental spinal nerve), and elsewhere via formation of myoblasts and myotubes (muscle fibers)
● Contains myofibrils composed of thin (actin) and thick (myosin) filaments

Terminology
=========================================================================

● Skeletal muscle cells are also called myofibers or myocytes

Embryologic images
=========================================================================



Various images

Diagrams
=========================================================================



Various images


Section of myofibrils with sarcoplasmic reticulum (SR) and T-tubules (T)

Various images

Micro description
=========================================================================

● Long cylindrical cells, unbranched and striated
● Multinucleated syncytia, formed by fusion of single cells
● Nuclei are peripheral to the myofiber

Micro images
=========================================================================


Various images

Longitudinal and transverse sections

Skeletal muscle vasculature

Normal striated muscle

Electron microscopy description
=========================================================================

● Electron microscopy reveals structural components:
I (isotropic) band: thin filaments only
A (anisotropic) band: overlapping thin and thick filaments
H band: thick filaments only
Z line: divides center of I band; serves as attachment site for the sarcomere, the repeating individual unit of the muscle fiber

Electron microscopy images
=========================================================================



Various images

Additional references
=========================================================================

Wikipedia, Slideshow of the sliding filament model (ppt)



Skeletal muscle

Neuromuscular hamartoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 18 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Rare developmental lesion of mature skeletal muscle and nerve

Terminology
=========================================================================

● Not a WHO diagnosis
● Also called benign Triton tumor (malignant Triton tumor refers to rhabdomyosarcoma plus MPNST), neuromuscular choristoma

Clinical features
=========================================================================

● Usually < 2 years old, affects brachial plexus or sciatic nerve
● May involve large cranial nerve trunks and present as intracranial mass
● Very rarely involves peripheral nerve and presents as small nodules
● Aggressive behavior

Case reports
=========================================================================

● 15 year old boy with tumor of trigeminal nerve (AJNR Am J Neuroradiol 2005;26:967)
● 36 year old woman with tumor of trigeminal nerve (Acta Neurochir (Wien) 2006;148:83)
● 51 year old man with migraine (Cephalalgia 2012;32:171)
● 61 year old man with bilateral exophthalmos and lid retraction (Orbit 2010;29:168)

Treatment and prognosis
=========================================================================

● Biopsy for diagnosis plus observation, may develop fibromatosis after biopsy or complete excision
● May recur, mandating regular followup after excision

Gross description
=========================================================================

● Circumscribed, firm, gray-brown-white, multinodular, attached to nerve

Micro description
=========================================================================

● Multiple nodules, each 3-5 mm, separated by narrow bands of connective tissue
● Nodules are composed of fascicles of striated muscle of varying size with nerve fibers (myelinated or not) within same perimysial fibrous sheath
● Stroma may be more cellular with bland spindle cells and resemble fibromatosis

Micro images
=========================================================================


Nodules of skeletal muscle and neural elements that subdivide into smaller nodules by narrow bands of connective tissue

Nodules contain fascicles of striated muscle fibers of variable size and nerve fibers (with or without myelination) in same perimysial fibrous sheath

Rare case with haphazardly distributed skeletal muscle and nerve fibers, cellular stroma and bland spindle cells with scant cytoplasm and oval nuclei

Nerve fibers are S100+

Positive stains
=========================================================================

Striated muscle: desmin and muscle specific actin
Nerve: S100, neuron specific enolase, neurofilament protein

Differential diagnosis
=========================================================================

Embryonal rhabdomyosarcoma: poorly and moderately differentiated cells
Fetal rhabdomyoma: usually not intimately associated with nerves, S100 negative



Other tumors
Myxoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 13 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See subtypes below: cardiac, Carney complex, fibromyxoma, intramuscular, jaw, Mazabraud syndrome, superficial acral fibromyxoma

General
=========================================================================
Sites
=========================================================================
Clinical description
=========================================================================
Diagnosis
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Periocular
Mandibular
Maxillary
Site unknown
Cytology description
=========================================================================
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Electron microscopy images
=========================================================================
Conjunctival myxoma: cell has infolding of nuclear membrane, forming membrane bound vacuoles (v);
nuclei has 2 nucleoli; prominent rough endoplasmic reticulum is in lower left; inset-membranous vacuole
Molecular / cytogenetics description
=========================================================================
Differential diagnosis
=========================================================================


Cardiac myxoma

See also Heart tumor chapter

General
=========================================================================
Case reports
=========================================================================
Gross / clinical images
=========================================================================
Atrial myxoma
Mitral valve mxyoma
Atrial myxoma
Micro images
=========================================================================
Myxomatous stroma
Anterior mitral valve leaflet
Myxomatous embolus


Carney complex associated
General
=========================================================================
Case reports
=========================================================================
Gross / clinical images
=========================================================================
Roof of atrium
Cardiac myxoma


Fibromyxomas
General
=========================================================================


Intramuscular myxoma
General
=========================================================================
Case reports
=========================================================================
Gross images
=========================================================================
Intramuscular myxoma
Gluteal tumor
Micro description
=========================================================================
Micro images
=========================================================================
Cellular tumor
Intramuscular tumors
Molecular / cytogenetics description
=========================================================================
Differential diagnosis
=========================================================================


Jaw myxomas
General
=========================================================================
Gross images
=========================================================================
Jaw tumor
Micro images
=========================================================================
Bland stellate cells in myxoid stroma


Mazabraud syndrome associated
General
=========================================================================
Case reports
=========================================================================
Micro images
=========================================================================
Femur and tibia


Superficial acral fibromyxoma
General
=========================================================================
Case reports
=========================================================================
Gross / clinical images
=========================================================================
Index finger
Micro images
=========================================================================
Index finger
Lobular spindle cell tumor with fascicular growth pattern, moderately cellular, fills dermis
Spindle and stellate cells arranged in loose storiform pattern embedded in myxocollagenous stroma
CD10 staining in neoplastic cells



Skeletal muscle

Adult type rhabdomyoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 12 November 2014, last major update November 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Benign tumor of mature skeletal muscle
● Extracardiac rhabdomyomas are divided into fetal, adult (below) and genital histologic types (eMedicine)
● Extracardiac tumors are not associated with tuberous sclerosis
● Some cases may be due to degeneration and regeneration, and not be neoplastic (Am J Surg Pathol 1989;13:791), but see Head Neck 2006;28:275

Clinical description
=========================================================================

● Very rare
● Usually head and neck, particularly oral cavity
● Median age 60 years, 75% male (Hum Pathol 1993;24:608)
● May be multifocal (25%)

Case reports
=========================================================================

● 43 year old man with midline swelling in upper neck (Acta Cytol 2010;54:968)
● Elderly woman with multifocal oral tumor (Arch Pathol Lab Med 1983;107:638)
● 13 cm tumor in extremity (Hum Pathol 2000;31:1074)
● Parapharyngeal tumor (Dysphagia 2008;23:202)

Treatment
=========================================================================

● Excision is curative, but may recur if incompletely excised

Gross description
=========================================================================

● Median 3 cm, circumscribed, soft, tan-red-brown
● Nodular or lobulated

Micro description
=========================================================================

● Well circumscribed, not encapsulated, sheets of large, well differentiated skeletal muscle cells
● Cells are round or polygonal with abundant eosinophilic fibrillar or granular cytoplasm with frequent cross striations and intracytoplasmic rod-like inclusions
● Nuclei are small, round and vesicular, may have prominent nucleoli
● May have spider cells with vacuolated cytoplasm (cells resemble spider webs)
● Variable glycogen and lipid
● No mitotic activity, no atypia

Micro images
=========================================================================


Large closely packed polygonal cells up to 150 microns

Cells have abundant eosinophilic and granular cytoplasm, often with peripheral vacuoles, giving a spiderweb appearance to some cells, nuclei are round with vesicular chromatin and prominent nucleoli

Distinct well demarcated lobules of polygonal cells

Large closely packed polygonal cells up to 150 microns

Haphazardly arranged crystalline material resembling sarcomeric bands

Crystalline material resembles rods

Various images



Actin+

Desmin+

Cytology description
=========================================================================

● Fragments of tumor cells, which are large, polygonal cells
● Cytoplasm is eosinophilic and finely granular, may resemble granular cell tumor, which is S100+, muscle markers- (Diagn Cytopathol 2009;37:483)
● Eccentrically placed nuclei
● Cross striations and inclusions are not conspicuous (Acta Cytol 2010;54:968)

Cytology images
=========================================================================


Parapharyngeal mass

Cohesive syncytial group of cells with abundant cytoplasm (200X Diff- Quick)

Bland round to oval nuclei with smooth borders (1000X OIL Diff- Quick)

Myoglobin immunostain- Strongly positive neoplastic cells (400X Cell block)

Desmin immunostain- Strongly/diffusely positive neoplastic cells (400X Cell block)

Positive stains
=========================================================================

● Muscle specific actin, desmin and myoglobin (100%)
● PAS+, diastase sensitive (detects glycogen)
● PTAH and Masson trichrome highlight cross striations and rod-like inclusions

Negative stains
=========================================================================

● Keratin, EMA, CD68, S100 (or weak)

Electron microscopy description
=========================================================================

● Myofilaments, Z bands, glycogen granules

Differential diagnosis
=========================================================================

Alveolar soft part sarcoma
● Crystal storing histiocytosis
Granular cell tumor: no skeletal muscle differentiation, no glycogen, smaller cells have poorly defined cell borders, often overlying pseudoepitheliomatous hyperplasia, S100+
Hibernoma: no skeletal muscle differentiation, no glycogen
● Paraganglioma: NSE+, synaptophysin+, chromogranin+
Well differentiated rhabdomyosarcoma



Skeletal muscle

Fetal type rhabdomyoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 21 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Rare benign tumor of immature skeletal muscle differentiation, usually head and neck
● Extracardiac rhabdomyomas are divided into fetal (below), adult and genital histologic types
● Extracardiac tumors are not associated with tuberous sclerosis
● Retroauricular in ages 0-3 years

Epidemiology
=========================================================================

● 70% male, median age 4.5 years, range 3-58 years (Hum Pathol 1993;24:754)
● Usually head and neck, post auricular region is the most common site
● Slightly male predominance
● Multiple cases of fetal rhabdomyoma have been reported in patients with nevoid basal cell carcinoma syndrome (Virchows Arch 2011;459:235)

Case reports
=========================================================================

● 1 month old infant girl with swelling in submandibular region (Indian Pediatr 2004;41:839)
● 1 year old girl with skin tumor (Am J Surg Pathol 2008;32:485)
● 9 year old boy with cellular fetal rhabdomyoma of thigh (Pediatr Blood Cancer 2009;52:881)
● Congenital tumor with recurrence (Int J Pediatr Otorhinolaryngol 2006;70:1115)

Treatment
=========================================================================

● Complete excision
● Only rare recurrences (Pediatr Pathol Lab Med 1996;16:673)
● No metastases

Gross description
=========================================================================

● Median 3-5 cm
● Solitary, well circumscribed mass of soft tissue or mucosa
● Gray-white-tan-pink, soft with glistening cut surface

Micro description
=========================================================================

● Circumscribed but not encapsulated
● Myxoid or cellular

Myxoid:
● Bundles or fascicles of immature slender skeletal muscle with delicate cytoplasmic cross striations and thin tapering eosinophilic processes, resembling myotubules at week 7-12 of gestation
● Also undifferentiated round/oval or spindled mesenchymal cells
● Stroma is myxoid or fibromyxoid
● Skeletal muscle cells mature towards periphery, may have “pseudocambium” layer of plasma cells and lymphocytes under mucosal epithelium

Cellular:
● Bundles or fascicles of cells in parallel or plexiform patterns
● Sparse collagenous or myxoid stroma
● Cells have variable skeletal muscle differentiation ranging from immature cells of myxoid pattern (but in larger numbers) to ganglion cell-like rhabdomyoblasts with prominent nucleoli, or strap cells with abundant basophilic or eosinophilic cytoplasm and prominent cross-striations
● Infiltration of skeletal muscle may make margins difficult to determine
● Variable glycogen containing vacuoles
● No/rare mitotic figures

Micro images
=========================================================================


Immature muscle cells and mesenchymal cells are often in central portion of tumor, with better differentiated skeletal muscle cells and mesenchymal cells at periphery

Undifferentiated round mesenchymal cells and immature skeletal muscle cells within myxoid or edematous stroma

Various images

The bipolar, immature skeletal muscle cells have tapered eosinophilic cytoplasmic processes and closely resemble the myotubular stage of striated muscle development, and the undifferentiated cells have minimal cytoplasm and round or oval nuclei

The fetal rhabdomyoma is comprised of less mature, somewhat pleomorphic, polygonal muscle cells admixed with spindle-shaped cells

Mucosal tumors have a pseudocambium layer of plasma cells and lymphocytes resembling embryonal rhabdomyosarcoma, but there is no atypia and no mitotic figures
Cellular fetal type rhabdomyoma:

Tumor cells are arranged in fascicles with less stroma

Immature skeletal muscle cells

Ganglion cell-like rhabdomyoblasts

Strap cells with abundant eosinophilic cytoplasm and cross striations

Myxoid tumor of tongue (various images)

PTAH shows cross striations

Ganglion cell like rhabdomyoblasts or strap cells are arranged in patternless pattern with undifferentiated mesenchymal cells

Cytology description
=========================================================================

● Spindle cells and rhabdomyoblasts with abundant eosinophilic cytoplasm (Singapore Med J 2009;50:e138)

Positive stains
=========================================================================

● Muscle specific actin, desmin and myoglobin (100%), GFAP (40%)

Negative stains
=========================================================================

● Keratin, EMA, CD68

Electron microscopy description
=========================================================================

● Hypertrophied Z band material, thick and thin filaments, numerous mitochondria, some with inclusions

Differential diagnosis
=========================================================================

Botyroid variant of embryonal rhabdomyosarcoma: resembles myxoid variant of fetal rhabdomyoma but has deep location, true cambium layer, atypia, numerous mitotic figures, tumor cell necrosis, infiltrative margins, no maturation of cells at periphery
● Infantile fibromatosis: deep location, fascicles of spindle cells, no cross striations, no undifferentiated cells
Neuromuscular hamartoma: S100+ nerve fibers and skeletal muscle in same perimysial sheath
Spindle cell variant of embryonal rhabdomyosarcoma: resembles cellular variant of fetal rhabdomyoma but has cellular pleomorphism and tumor cell necrosis



Skeletal muscle

Genital type rhabdomyoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 21 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Rare benign tumor with skeletal muscle differentiation in vagina, vulva or cervix, usually in middle aged women and rarely urethra
● Extracardiac rhabdomyomas are divided into adult, fetal, and genital (below) histologic types
● Extracardiac tumors are not associated with tuberous sclerosis

Epidemiology
=========================================================================

● Rarely occurs in males in paratesticular region or epididymis or in the tunica vaginalis of the testis or prostate
● Mean age 42 years

Case reports
=========================================================================

● Infant girl with genital rhabdomyoma of the urethra (Hum Pathol 2012;43:597)
● 17 year old boy with locally invasive tumor (J Pediatr Surg 2007;42:E5)
● 19 year old man with testicular tumor (Mod Pathol 1997;10:608)
● 20 year old man with epididymal tumor (Arch Pathol Lab Med 2000;124:1518)
● 48 year old woman with lower abdominal pain and vaginal bleeding (Hum Pathol 2005;36:433)

Treatment
=========================================================================

● Local excision is curative

Gross description
=========================================================================

● Well circumscribed, solitary, up to 3 cm
● Resembles polyp
● Covered by smooth mucosa

Micro description
=========================================================================

● Submucosal, polypoid, well circumscribed, no capsule
● Haphazard strap-like or round striated muscle fibers in fibrous stroma with dilated vessels
● Cells have abundant eosinophilic cytoplasm with glycogen, cross striations, longitudinal myofibrils
● Nucleus is round, vesicular, central and uniform
● May have bi- or multinucleated cells
● No/rare mitotic figures, no cambium layer, no spider cells, no spindle cells or rhabdomyoblasts, no necrosis, no nuclear pleomorphism

Micro images
=========================================================================



Submucosal proliferation of haphazard skeletal muscle cells with prominent cross striations and fibromyxoid stroma


Epididymis

Cervix (various images)

Positive stains
=========================================================================

● Muscle specific actin and desmin highlight rod-like structures; myoglobin (100%)

Negative stains
=========================================================================

● Keratin, EMA, CD68

Differential diagnosis
=========================================================================

Botyroid variant of embryonal rhabdomyosarcoma: usually <25 years old with rapidly growing mass, cambium layer, atypia, mitotic activity
● Vaginal polyp: may have atypical cells, but no cross striations



Skeletal muscle

Rhabdomyosarcoma - general


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 21 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Primitive malignant soft tissue sarcoma with skeletal muscle phenotype by H&E, immunohistochemistry or EM
● Subtypes: alveolar, anaplastic, embryonal, pleomorphic, sclerosing (Mod Pathol 2001;14:506), although mixtures are common
● Note: some alveolar and embryonal tumors have similar gene expression (Am J Pathol 2009;174:550)

Epidemiology
=========================================================================

● Most common soft tissue sarcoma of childhood/adolescence (5-8% of solid pediatric tumors, 50% of pediatric soft tissue sarcomas)
● 50% at 0-9 years
● Children 2-6 years usually have head, neck or GU tumors
● Teenagers usually have paratesticular, trunk or abdominal tumors
● Relatively rare in adults, who often have pleomorphic and NOS subtypes
● Slight male predominance (M/F: 1.3:1)
● Head and neck tumor are more often embryonal types
● Extremity tumors more often have alveolar histologic type
● 80% of genitourinary RMS are embryonal type
● Usually >5 cm at diagnosis

Rhabdomyoblast
=========================================================================

● Cell of origin for rhabdomyosarcomas
● Eccentric eosinophilic granular cytoplasm rich in thick and thin filaments
● If round and elongate, are called strap cells or tadpole cells

Clinical description
=========================================================================

● Needle biopsies may be sufficient for accurate diagnosis (Pediatr Blood Cancer 2009;53:356)
● Usually aneuploid

Treatment and prognosis
=========================================================================

● International Classification of Rhabdomyosarcoma (Cancer 1995;76:1073)
  - Superior prognosis: botryoid, spindle cell
  - Intermediate prognosis: embryonal
  - Poor prognosis: alveolar, undifferentiated sarcoma
● Adults have poorer 5 year survival (27%) than children (61%, J Clin Oncol 2009;27:3391)
● Poorer overall 5 year survival in hand/foot (33% versus 56% overall) due to marked tendency to spread and inability to completely excise (Pediatr Hematol Oncol 2009;26:321)
● Poorer survival in childhood embryonal (intermediate-risk) tumors if anaplasia is present (Cancer 2008;113:3242)
● Five year survival has increased from periods 1976-1980 to 1996-2000 for rhabdomyosarcoma overall (53% to 62%), embryonal (61% to 73%) and alveolar subtypes (40% to 48%, Cancer 2009;115:4218)
● Pathologists should compare post-treatment to pre-treatment specimens (Am J Clin Pathol 2005;123:75)

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Recommended panel contains myogenin, sarcomeric actin (90%) and desmin (95%)
● Desmin: reliable for solid variant of alveolar rhabdomyosarcoma, tumors with round or strap cell rhabdomyoblasts, also smooth muscle tumors
● Myoglobin: specific, but only found in better differentiated tumors, may be non-specific due to diffusion from adjacent injured skeletal muscle cells
● Myogenin: sensitive and specific, particularly useful for alveolar subtype (Mod Pathol 2000;13:988)
● MyoD1
● Vimentin (not specific)

Negative stains
=========================================================================

● FLI-1

Electron microscopy description
=========================================================================

● Rhabdomyoblasts contain sarcomeres (thick and thin filaments) and Z bands

Additional references
=========================================================================

Arch Pathol Lab Med 2006;130:1454, Arch Pathol Lab Med 2003;127:1290, ISRN Oncol 2012;2012:674523



Skeletal muscle

Alveolar rhabdomyosarcoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 21 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Subtypes discussed below: anaplastic variant, solid variant

Definition
=========================================================================

● High grade round cell malignancy with solid and alveolar growth and partial skeletal muscle differentiation
● Resembles lymphoma

Sites
=========================================================================

● Deep muscles of extremities, axial muscles or perineum

Clinical features
=========================================================================

● 20% of all rhabdomyosarcomas
● More common in early to mid-teens but all ages affected
● Neonatal cases have poor prognosis, are associated with skin and brain metastases (Cancer 2001;92:1613)
● Rapid growing, often high stage at presentation

Case reports
=========================================================================

● Infant with perineal tumor (Arch Pathol Lab Med 2002;126:982)
● 2 year old girl with pleural effusion and ovarian mass (Arch Pathol Lab Med 2003;127:e56)
● 2 year old girl with tumor of face (An Bras Dermatol 2011;86:363)
● 51 year old woman with cerebral tumor (Rare Tumors 2011;3:e26)
● 60 year old woman with primary cutaneous tumor of leg (Am J Surg Pathol 2002;26:938)
● 72 year old woman with tumor of uterine corpus (Pathol Int 2011;61:377)

Treatment and prognosis
=========================================================================

● Overall poorer prognosis than embryonal subtype
● Intergroup Rhabdomyosarcoma Study grouping (staging) is predictive of outcome
Poor prognostic factors: N-myc amplification, PAX3 fusion transcripts (J Clin Oncol 2002;20:2672)
● Mixed forms with alveolar component are classified as alveolar for staging and diagnosis

Clinical images
=========================================================================


Multiple nodules on foot

Progressive enlargement of skin lesions

Paranasal lesion

Gross description
=========================================================================

● Fleshy, tan-gray, mean 5 cm

Gross images
=========================================================================



Congenital post-auricular tumor

Micro description
=========================================================================

● Thin fibrous septae lined by small round blue cells (resembling lymphoma) in an alveolar growth pattern (resembles pulmonary alveoli)
● Loss of cellular cohesion so cells appear to float in alveolar spaces
● Also peripheral cracking artifact at borders of cell clusters
● Amount of alveolar tissue present is NOT significant (i.e. diagnose as alveolar even if only focal alveolar pattern)
● Deep eosinophilic cytoplasm and presence of occasional multinucleated giant cells are important diagnostic features
● 1/3 have rhabdomyoblasts with cytoplasmic cross striations
● Often foci of coagulative tumor cell necrosis
● May have neuroendocrine differentiation (Int J Surg Pathol 2009;17:135)
● Mixed embryonal / alveolar: have foci with embryonal histology (spindle cell myoblasts, myxoid stroma)
● Rarely has rhabdoid features (pink, ground-glass or fibrillar round to oval cytoplasmic bodies, large eosinophilic nucleoli)

Micro images
=========================================================================



Tumor cells grow in nests or clusters separated by fibrous septa (AFIP)


Solid growth (AFIP)


Alveolar type spaces contain desquamated small, round and poorly differentiated skeletal muscle cells. Fibrovascular stroma is lined by undifferentiated round cells and differentiating cells with abundant eosinophilic cytoplasm, but only rare cross striations (AFIP)

Various images

Solid growth with giant cells

Desquamated multinuclear giant cells (AFIP)

Predominantly solid areas with only focal alveolar pattern resembles embryonal rhabdomyosarcoma (AFIP)

May resemble lipoblasts

Focal rhabdoid cells

May resemble embryonal RMS due to small round spindled cells with hyperchromatic nuclei and vacuolated spider cells

Perineal skin of infant

Various images

Various images

Desmin

Myogenin

Myogenin

Cytology images
=========================================================================


Cellular exudate with reactive mesothelial cells (double arrow), lymphocytes (arrowhead), bizarre giant cells (single arrow) and mitotic figures (double arrowhead), cells have vacuolated cytoplasm (inset), tumor cells are desmin+ (3A), myogenin+ (3B), karyotype shows t(2;13) (fig 4)

Various images

Positive stains
=========================================================================

● Muscle specific actin, desmin, myogenin (strong nuclear staining, Am J Surg Pathol 2001;25:1150)
● Myo-D1 (Am J Surg Pathol 2006;30:962), ALK1
● Also CAM 5.2 and broad spectrum cytokeratin (50%), neuroendocrine markers (43% express at least one, Mod Pathol 2008;21:795), p80 (25%, cytoplasmic dot-like pattern, Mod Pathol 2002;15:931), PAX5 (67%, Am J Surg Pathol 2009;33:775)

Electron microscopy description
=========================================================================

● Skeletal muscle differentiation

Molecular / cytogenetics description
=========================================================================

● t(2;13)(q35;q14): PAX3-FKHR in 60-85% (note: FKHR is now known as FOXO1)
● t(1;13)(p36;q14): PAX7-FKHR in 15-20%
● PAX/FKHR fusion negativity in 20% (associated with totally solid alveolar architecture, Am J Surg Pathol 2007;31:895)
● N-myc amplification in 50%
● P-cadherin is a direct PAX3-FOXO1A transcriptional target involved in alveolar RMS aggressiveness (Oncogene 2012 Jun 18 [Epub ahead of print])

Molecular images
=========================================================================


2;13 translocation; G-banding (above); R- banding (below)

t(2;13)(q35;q14) and t(1;13)(p36;q14)

Comparison of wild-type and fusion products associated with t(2;13) and t(1;13)

FISH

FISH

Videos
=========================================================================



Dr. Minarcik reviews skeletal muscle of face and alveolar rhabdomyosarcoma

Differential diagnosis
=========================================================================

Alveolar soft parts sarcoma: PAS+ intracytoplasmic crystalline rods and granules; no pleomorphism, no giant cells, no fibrous septa, negative for muscle specific actin and myoglobin
● Merkel cell carcinoma: negative for muscle specific actin, desmin, myogenin and Myo-D1, lacks fusion gene
● Metastatic neuroendocrine carcinoma: keratin+, EMA+, desmin-, muscle specific actin-, lacks fusion gene



Anaplastic variant

Definition
=========================================================================

● Alveolar rhabdomyosarcoma with anaplastic nuclei
● Not a well characterized entity

Treatment and prognosis
=========================================================================

● Prognosis may be worse than typical alveolar rhabdomyosarcoma

Micro description
=========================================================================

● Anaplastic nuclei are 3x larger than surrounding nuclei

Micro images
=========================================================================



Foci of anaplastic cells (nuclei are hyperchromatic and 3x larger than surrounding cells)



Solid variant

Clinical features
=========================================================================

● Rarely occurs in adults in head and neck (Hum Pathol 2009;40:341)

Case reports
=========================================================================

● 16 year old girl with chest and foot masses (Univ Pittsburgh Case #256)
● 68 year old man with mediastinal tumor (J Cancer Res Ther 2011;7:353)

Micro description
=========================================================================

● Poorly developed alveolar pattern, lacks fibrovascular septa
● Alveolar pattern may be missed on small biopsies
● May resemble lymphoma (J Pediatr Hematol Oncol 2008;30:772)
● Solid component may be spindled sarcomatous to epitheloid cells (J Cancer Res Ther 2011;7:353)

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Desmin and muscle specific actin
● May be CD56+ (J Clin Exp Hematop 2008;48:61)
● MyoD1 and myogenin may be positive

Molecular description
=========================================================================

● Associated with lack of fusion gene (Am J Surg Pathol 2007;31:895)

Molecular images
=========================================================================



FISH and karyotype show t(2;13)



Skeletal muscle

Anaplastic rhabdomyosarcoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Terminology
=========================================================================

● In children (but not adults), includes cases previously called pleomorphic rhabdomyosarcoma
● Not a WHO diagnosis
● Most cases represent a variant of embryonal rhabdomyosarcoma

Treatment and prognosis
=========================================================================

● Poor prognosis, particularly if anaplastic cells are aggregated in a clone-like cluster

Case reports
=========================================================================

● 13 year old girl with mass in cervix (Arch Gynecol Obstet 2004;270:278)

Micro description
=========================================================================

● Cells have enlarged, pleomorphic, hyperchromatic nuclei
● Atypical polar mitotic figures

Micro images
=========================================================================



Cluster of cells with enlarged, pleomorphic, hyperchromatic nuclei (Mod Pathol 2001;14:506)



Skeletal muscle

Embryonal rhabdomyosarcoma-general


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 12 November 2014, last major update November 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

Subtypes: embryonal-NOS, anaplastic, botryoid, spindle cell

Definition
=========================================================================

● Primitive soft tissue sarcoma with small blue cells resembling embryonic skeletal muscle
● Most common rhabdomyosarcoma subtype (65%)

Epidemiology and sites
=========================================================================

● Usually children ages 3-10 years, in nasal and oral cavities, orbit, middle ear, prostate, paratesticular region
● Median age of GU presentation is 13 years (Mod Pathol 2012;25:602)
● Rare in skin, thoracic cavity, esophagus and stomach
● Associated with prenatal Xrays in one study (Cancer Epidemiol Biomarkers Prev 2009;18:1271)
● May be associated with hypercalcemia thorough increased parathormone production
● Metastasizes to soft tissue, serosa, lung, lymph nodes and bone marrow
● Extremity involvemen is uncommon and associated with more relapses and lower survival

Treatment and prognosis
=========================================================================

● Excision, chemotherapy, radiation therapy
● Favorable prognostic factors are younger age, spindle and botyroid variants in young patients, GU location (survival of 90%+ after excision and chemotherapy), localized tumor (survival of 80%); also hyperdiploid
● Presence of diffuse anaplasia is negative prognostic factor

Case reports
=========================================================================

● 2 year old boy with parotid mass - gangliorhabdomyosarcoma (Case of the Week #268)
● 11 year old boy with tonsillar mass - embryonal rhabdomyosarcoma (Case of the Week #276)
● 16 year old girl with mass of cervix (Afr J Paediatr Surg 2011;8:95)
● 19 year old Caucasian man with jaw swelling (Head Neck Pathol 2010;4:334)
● 24 year old woman with laryngeal tumor (Arch Otolaryngol Head Neck Surg 2011;137:635)
● 30 year old woman with botyroid variant in mesentery (Turk Patoloji Derg 2011;27:84)
● 32 year old woman with soft palate tumor (Indian J Pathol Microbiol 2011;54:136)
● 33 year old man with laryngeal tumor (BMC Cancer 2011;11:166)

Clinical images
=========================================================================


Large exophytic mass emanating from right arytenoid,
obstructing laryngeal inlet and obscuring true vocal cords

Gross description
=========================================================================

● Poorly circumscribed mass, white, soft or firm, infiltrative

Gross images
=========================================================================


Various images

Case of the Week #268

Micro description
=========================================================================

● Composed of primitive mesenchymal cells in various stages of myogenesis
● Sheets of small, spindled or moderate to poorly differentiated round cells with scant or deeply eosinophilic cytoplasm and eccentric, small oval nuclei
● Highly cellular areas around blood vessels alternate with parvicellular mucoid regions (resembles normal embryonal myogenesis)
● Cross striations in 50%
● Rarely has anaplastic features (see anaplastic variant), clear cell change, rhabdoid features, neuronal, melanocytic or schwannian differentiation (ectomesenchymoma)
● More differentiation typically occurs post-chemotherapy or radiotherapy

Micro images
=========================================================================



Mandible


Soft palate


Myogenin+

Case of the Week #268:


Case of the Week #276:


Actin

Desmin

Myogenin

MyoD1

Positive stains
=========================================================================

● Vimentin in all cells (even most primitive)
● Some cells should stain for desmin, MyoD1 or myogenin
● Actin, desmin, myoglobin, myosin, and creatine kinase M staining in more differentiated cells
● PAS highlights glycogen in most tumors
● C-kit (15%), myogenin (rare to 25% of tumor cells, Mod Pathol 2000;13:988)
● Aberrantly these tumors may show immunoreactivity to cytokeratin, S100 protein, neurofilaments, and B cell proteins such as CD20 and immunoglobulins

Cytology description
=========================================================================

● Cellular with features of a small round cell tumor
● Rarely intranuclear cytoplasmic inclusions (Diagn Cytopathol 2009;37:740)

Electron microscopy description
=========================================================================

● Developing striated muscle, thick and thin filaments

Molecular / cytogenetics description
=========================================================================

● Loss of 11p15
● +2q, +8, +12, +13, +20
● No N-myc amplification
● Congenital cases are associated with t(2;8)(q35;q13) involving PAX3 gene (Cancer Genet Cytogenet 2009;191:43)
● Inactivating mutations of TP53 and CDKN2A and activating mutations of RAS family genes
● No diagnostic translocation found to date

Differential diagnosis
=========================================================================

Desmoplastic small round cell tumor: tumor nodules on serosal surfaces, strongly keratin+ and EMA+, may be desmin+ but muscle specific actin-
Ewing’s / PNET: often rosettes, nuclei are uniform and pale, not dense and hyperchromatic; CD99+, desmin-, muscle specific actin-, t(11;22)+
Large cell lymphoma: CD45+, B/T cell markers present, desmin-, muscle specific actin-
Neuroblastoma: elevated urinary catecholamines, rosettes, granular chromatin, S100+ (often), chromogranin+, GFAP+
Rhabdomyoma
● Undifferentiated sarcoma: negative for muscle markers



Skeletal muscle

Pleomorphic rhabdomyosarcoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● High grade sarcoma of adults with bizarre polygonal, round or spindle cells, with skeletal muscle differentiation and no alveolar or embryonal component
● Rarely has smooth muscle or fibrohistiocytic differentiation (Ultrastruct Pathol 2010;34:42)

Epidemiology
=========================================================================

● Rare, but common rhabdomyosarcoma subtype in adults
● Usually age 50+; can occur in children (Ann Diagn Pathol 2001;5:199), but then called anaplastic
● 70% male

Clinical features
=========================================================================

● Rapidly growing painful mass, most commonly of lower extremity, abdomen / retroperitoneum, chest / abdominal wall or spermatic cord / testes, uterine corpus, upper extremity, orbit
● Similar behavior to other pleomorphic sarcomas

Case reports
=========================================================================

● 18 year old man with painless scrotal mass (Diagn Cytopathol 2010;38:121)
● 34 year old man with scrotal tumor (Nihon Hinyokika Gakkai Zasshi 2009;100:545)
● 59 year old man with painful inguinal swelling and deep vein thrombosis (Case Rep Oncol 2012;5:74)
● 71 year old woman with retroperitoneal tumor with osteoclast-like giant cells (Arch Pathol Lab Med 2005;129:703)

Treatment and prognosis
=========================================================================

● Poor prognosis
● 70% die of disease after mean follow-up of 20 months (Mod Pathol 2001;14:595)

Diagnosis
=========================================================================

● Must prove skeletal muscle differentiation by cross striations or skeletal muscle marker immunoreactivity
● No alveolar or embryonal component
● Common errors involve entrapped skeletal muscle, non-specific myoglobin immunoreactivity or skeletal muscle differentiation of other tumors

Gross description
=========================================================================

● Mean 7 cm, up to 30 cm
● May be confined to fascial compartment and assume shape of muscle from which it arises
● White, firm cut surface with variable hemorrhage and necrosis

Gross images
=========================================================================



Various images

Gross images
=========================================================================



Hand

Micro description
=========================================================================

● Well circumscribed
● Large, multinucleated, bizarre, eosinophilic tumor cells
● Should see cross striations or have immunohistochemical evidence of skeletal muscle differentiation
● No alveolar or embryonal component (by definition)
Classic type: predominantly atypical rhabdomyoblasts in sheets
Round cell type: clusters of rhabdomyoblasts in background of slightly atypical, medium sized, round blue rhabdomyoblasts
Spindle cell type: scattered rhabdomyoblasts with predominantly atypical spindled rhabdomyoblasts in storiform pattern

Micro images
=========================================================================

Classic, round cell and spindle cell variants

Fascicular pattern

Storiform pattern

Patternless pattern

Hemangiopericytoma-like pattern

Spindle cells

Pleomorphic and polygonal cells

Epithelioid cells with abundant eosinophilic cytoplasm

Clear cytoplasm due to washing out of glycogen

Psoas muscle tumor cells have abundant eosinophilic cytoplasm with hyaline like inclusions, osteoclast-like giant cells

Various images

Positive stains
=========================================================================

● Myoglobin (>90%), desmin (>90%), muscle specific actin (70%)
● MyoD1 (50%), skeletal muscle myogenin (50%), smooth muscle actin (50%)
● Rarely CD 10 and CD 56

Negative stains
=========================================================================

● Cytokeratin 7, synaptophysin, epithelial membrane antigen, placental-like alkaline phosphatase, chromogranin, and a pan-keratin

Electron microscopy description
=========================================================================

● Skeletal muscle differentiation with rudimentary sarcomeres containing Z bands or Z band material with thick and thin filaments

Electron microscopy images
=========================================================================



Thick and thin filaments from primitive Z bands

Molecular / cytogenetics description
=========================================================================

● Complex karyotype (Cancer Genet Cytogenet 2009;192:1)
● Comparative genomic in situ hybridization (CGH) reveals eight highly amplified regions at 1p36.1-p36.2, 1p31-p32, 1q21-q31, 8q12-q21, 8q24-qter, 11q12-q13, 12q13-q14 and 18q12-q22 (Am J Cancer Res 2012;2:141)

Differential diagnosis
=========================================================================

Embryonal or alveolar rhabdomyosarcoma with pleomorphism
MFH-pleomorphic: diagnosis of exclusion, no evidence of skeletal muscle differentiation
Pleomorphic liposarcoma
● Sarcoma with heterologous rhabdomyosarcomatous differentiation: differentiated features are characteristic of primary tumor



Skeletal muscle

Sclerosing rhabdomyosarcoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Rhabdomyosarcoma with extensive hyalinized matrix production (Am J Surg Pathol 2002;26:1175, Am J Clin Pathol 2008;129:410)
● Not a WHO diagnosis
● First described in 2000 (Virchows Arch 2000;436:305)

Clinical features
=========================================================================

● Adults and children (Int J Surg Pathol 2006;14:193)
● Often in head and neck (Laryngoscope 2005;115:48)

Case reports
=========================================================================

● 62 year old man with leg tumor (Virchows Arch 2006;449:572)
● Parotid gland swelling (Ann Diagn Pathol 2009;13:334)

Gross description
=========================================================================

● 4 to 8 cm

Micro description
=========================================================================

● Lobules and infiltrating cords of small round malignant cells embedded in densely hyalinized matrix with chondroid and osteoid-like appearance
● May have pseudovascular growth pattern, rhabdomyoblastic differentiation with strap cells, areas suggestive of spindle cell rhabdomyosarcoma, extensive mitotic activity (>20 mitotic figures/20 high power fields)
● No / focal embryonal or alveolar patterns
● No tumor giant cells
● No definite lacunae or matrix calcification present

Micro images
=========================================================================



Various images

Virtual slides
=========================================================================



Back mass

Positive stains
=========================================================================

● MyoD1 (100%, almost every cell), actin, desmin (focal), myogenin (focal)

Negative stains
=========================================================================

● Cytokeratin, S100

Molecular / cytogenetics description
=========================================================================

● No t(2;13) of alveolar rhabdomyosarcoma
● Specific MDM2/HMGA2 amplification at 12q13-15 in 1 case (Hum Pathol 2009;40:1347)
● Loss of 10q22, loss of chromosome Y and gain of #18 in one case (Virchows Arch 2006;449:572)
● Pattern of numerical changes similar to embryonal rhabdomyosarcoma in one case (Virchows Arch 2005;446:64)
● Hyperdiploidy, tetraploidy, del 1, Trisomy 11, 16, monosomy 22

Electron microscopy description
=========================================================================

● Irregularly distributed disorganized filament in richly collagenized matrix
● No Z-bands

Differential diagnosis
=========================================================================

Alveolar rhabdomyosarcoma: different morphology; has PAX3 and PAX7-FKHR fusion transcripts (Pediatr Dev Pathol 2004;7:583)
Angiosarcoma
Chondrosarcoma: has neoplastic chondroid cells
Osteosarcoma: has neoplastic osteoid
Sclerosing epithelioid fibrosarcoma



Smooth muscle

Smooth muscle tumors - general


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Micro description
=========================================================================

● Tumor cells resemble smooth muscle with easily visible, often fibrillar and eosinophilic cytoplasm, usually in long bundles or fascicles
● Nucleus is long, oval and round at both ends, often with cytoplasmic vacuole at one end, nucleoli are indistinct
● Minimal collagen present between smooth muscle cells
● Smooth muscle cells may resemble myofibroblasts with less cytoplasm, thinner nuclei, denser chromatin
● Note: smooth muscle tumors of skin, vulva/vagina, scrotum, nipple and other locations are described in these chapters

Micro images
=========================================================================

Smooth muscle

Longitudinal

Transverse

Smooth muscle composite

Positive stains
=========================================================================

● Trichrome stains smooth muscle cytoplasm red and collagen blue or green
● Actin, desmin and calponin stain smooth muscle, but are non-specific because they also stain myofibroblasts
● Smooth muscle myosin and h-caldesmon are more specific for smooth muscle versus myofibroblasts (Am J Dermatopathol 2006;28:105)



Smooth muscle

Angioleiomyoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 17 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Benign, painful, subcutaneous or deep dermal tumor of smooth muscle and vessels
● Part of morphologic spectrum with myopericytoma (Hum Pathol 2007;38:645) and myofibroma
● Arises from smooth muscle of blood vessels without elastic fibers

Terminology
=========================================================================

● Also called angiomyoma, vascular leiomyoma
● Do NOT diagnose as “superficial angiomyolipoma” even if it contains some fat

Epidemiology
=========================================================================

● Relatively common, usually females, ages 30-60 years

Clinical features
=========================================================================

● Solitary, slow growing nodule
● Often in soft tissue of lower limbs, but tumors in males are more common in upper extremity, head and neck (Laryngoscope 2004;114:661)
● Pain in 60% (Int J Clin Pract 2004;58:587), due to stretching of nerves in tumor or capsule or release of mediators from mast cells; pain may be exacerbated by wind, cold, pressure, menses
● Other painful nodules are glomus tumor, traumatic neuroma, eccrine spiradenoma and angiolipoma

Case reports
=========================================================================

● 38 year old man with auricular tumor (Turk Patoloji Derg 2011;27:268)
● 51 year old man with nasal turbinate mass (Case of the Week #138)
● 57 year old man with recurrent oral tumor (Contemp Clin Dent 2011;2:102)
● 58 year old woman with small intestinal tumor (World J Surg Oncol 2007;5:129)
● 61 year old woman with thigh tumor for 10 years and coexisting epithelioid granuloma (Case Rep Dermatol 2011;3:170)
● 62 year old woman with nasal septum tumor (Braz J Otorhinolaryngol 2010;76:675)
● 66 year old woman with posterior mediastinal tumor (Yonsei Med J 2008;49:666)

Treatment and prognosis
=========================================================================

● Simple excision; does not recur

Gross description
=========================================================================

● Firm, sharply circumscribed gray-white-brown nodules
● Usually 2 cm or less

Gross / clinical images
=========================================================================



Well dermacated tumors (left: small intestinal, right: posterior mediastinum)


Retromolar growth


Thigh nodule

Micro description
=========================================================================

● Well circumscribed fascicles of mature smooth muscle cells surrounding vascular lumina, lined by normal appearing endothelium but with no elastic lamina present
● Subtypes are solid (closely compacted smooth muscle bundles), venous (vessels have thick muscular walls that merge with smooth muscle bundles) and cavernous (dilated vascular channels with minimal smooth muscle that merges with smooth muscle bundles), but subtypes have no clinical significance (Cancer 1984;54:126)
● Venous type is most common in head and neck, usually males
● Solid type is most common in lower extremeties, usually females
● May have foci of cartilaginous or adipose metaplasia
● May have bizarre degenerative type cells similar to symplastic leiomyoma of uterus
● Rarely prominent calcification in acral sites (J Am Acad Dermatol 2008;59:1000)
● Rarely epithelioid cells (Am J Dermatopathol 1998;20:213) or epithelioid granulomas (Case Rep Dermatol 2011;3:170)
● No hemorrhage, no necrosis, no mitotic activity, no vasculitis, no fibromuscular dysplasia

Micro images
=========================================================================



Smooth muscle and vessels, often thick walled


Smooth muscle in vessel walls merge with smooth muscle of lesion


Closely compacted eosinophilic smooth muscle cells merge with blood vessels


Mediastinal tumor


Nasal cavity (left to right): submucosal tumor composed of abundant thick-walled blood vessels blending with proliferative smooth muscle tissue; focal fatty metaplasia; smooth muscle actin+


Nasal turbinate: H&E (3) and actin (2)


Oral cavity: retromolar mass


Skin tumor


Skin tumor-ear


Skin-thigh tumor


Small intestinal tumor

Cytology description
=========================================================================

● Moderate or sparse cellularity
● Usually uniform spindle cells mixed with smooth muscle cells and fragments of collagenous tissue in varying proportions
● Occasional macrophages, fat cells, ganglion-like cells (Diagn Cytopathol 2002;27:161)

Positive stains
=========================================================================

● Alpha smooth muscle actin, desmin, myosin, trichrome, HHF35, calponin, h-caldesmon
● Also vimentin, type IV collagen, S100 in small nerve fibers
● Variable PR in nasal cavity cases (Acta Otolaryngol 2002;122:408, Chin Med J (Engl) 2007;120:350)

Negative stains
=========================================================================

● HMB45, ER

Differential diagnosis
=========================================================================

● Angiomyolipoma - prominent adipose tissue component, HMB45+
Leiomyoma with bizarre nuclei: no prominent vascular component



Smooth muscle

EBV (Epstein-Barr virus) associated smooth muscle tumors (EBV-SMT)


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Not a WHO diagnosis

Epidemiology
=========================================================================

● Rare; occur in immunocompromised patients (post-transplant [kidney], AIDS, Arch Pathol Lab Med 1997;121:834)
● Adults, 60% male

Clinical features
=========================================================================

● EBV-SMT are histologically distinct from classic soft tissue smooth muscle tumors, are not readily evaluated by conventional histologic criteria; multifocal tumors are due to multiple infection events, not metastasis (Am J Surg Pathol 2006;30:75)
● AIDS patients have multifocal tumors in liver, brain, spinal cord and adrenal gland, with slow disease progression (Oncology 2008;74:167)
● Note: EBV is also associated with leiomyosarcoma in immunocompromised (Am J Surg Pathol 2000;24:614)
● EBV-SMTs have variable aggressiveness with tumor-related death occurring in 4 of 51 patients (Patholog Res Int 2011;2011:561548)

Case reports
=========================================================================

● 27 year old man with AIDS and tonsillar mass (Auris Nasus Larynx 2012;39:329)
● 34 year old man with AIDS and multicentric hepatic EBV associated smooth muscle tumors (Int J Clin Exp Pathol 2011;4:421)

Treatment and prognosis
=========================================================================

● Excision, possibly chemotherapy; also improving host immune status (Sarcoma 2008;2008:859407)
● Occasionally causes death

Micro description
=========================================================================

● Well differentiated smooth muscle tumors with primitive round cell areas and prominent intratumoral T cells
● No/mild atypia, no/rare mitotic figures, no pleomorphism
● May occasionally have features of high grade sarcoma

Micro images
=========================================================================



Liver tumor


Tumors post-liver transplant (N Engl J Med 1995;332:19)



Liver tumors in AIDS patient


EBV-SMTs with variable aggressiveness

Positive stains
=========================================================================

● Actin, EBER (in situ hybridization for EBV early RNAs)
● Often desmin

Negative stains
=========================================================================

● HMB45

Molecular / cytogenetics description
=========================================================================

● Multiple tumors in same patient are clonally distinct



Smooth muscle

Leiomyoma-Classic


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Leiomyoma: see also bizarre, cutaneous, epithelioid, genital, leiomyoma of deep soft tissue

Definition
=========================================================================

● Bland smooth muscle tumor without mitotic figures (eMedicine)

Terminology
=========================================================================

● Not a WHO diagnosis (cutaneous and pilar tumors are described in the Skin volume)
● Some tumors previously considered to be leiomyomas are actually GI stromal (GIST) tumors
● See also Colon-tumor, Esophagus, Uterus chapters

Epidemiology
=========================================================================

● Skin and subcutis; also deep soft tissue, uterus (most common neoplasm in women)
● Patients with multiple cutaneous leiomyomas may have autosomal dominant disorder (described under Cutaneous leiomyoma)

Case reports
=========================================================================

● 34 year old man with sickle cell thalassemia and ossified leiomyoma (J Cutan Pathol 2005;32:696)
● 59 year old woman with finger lesion (Chang Gung Med J 2004;27:134)

Gross images
=========================================================================



Myxoid subcutaneous tumor

Micro description
=========================================================================

● Bundles or fascicles of spindled cells with eosinophilic and possibly fibrillary cytoplasm
● Nuclei are blunt ended and elongated with fine chromatin, indistinct nucleolus and variable cytoplasmic vacuole at one end
● Minimal atypia
● Few mitotic figures
● No coagulative tumor necrosis

Micro images
=========================================================================



Bundles of elongate cells with eosinophilic cytoplasm and oblong nuclei

Oblong nuclei have rounded ends


Calcified leiomyoma

Positive stains
=========================================================================

● Desmin, alpha smooth muscle actin
● h-caldesmon, calponin, muscle specific actin, myosin
● ER and PR for uterine tumors

Negative stains
=========================================================================

● CD117, CD34, S100; low Ki-67 (<5%)

Differential diagnosis
=========================================================================

● Angiomyolipoma: usually prominent vascular and lipomatous component
Leiomyosarcoma: more cellular, infiltrative, pleomorphic; mitotic activity and coagulative tumor cell necrosis



Smooth muscle

Bizarre leiomyoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Leiomyoma: see also classic, bizarre, cutaneous, epithelioid, genital, leiomyoma of deep soft tissue

Terminology
=========================================================================

● Also called symplastic, atypical, apoplectic leiomyoma

Epidemiology
=========================================================================

● Usually found in uterus; also scrotum, skin (Am J Dermatopathol 2001;23:299)

Clinical features
=========================================================================

● May recur locally after excision (Ann Diagn Pathol 2008;12:328)

Case reports
=========================================================================

● 59 year old man with scrotal mass (Cases J 2008;1:381)
● 68 year old woman with thigh nodule (Dermatol Online J 2009;15:6)
● 69 year old man with scrotal mass (Arch Pathol Lab Med 2004;128:e37)
● 72 year old woman with nasal cavity mass (J Clin Pathol 2002;55:872)

Clinical images
=========================================================================


Scrotal mass

Thigh nodule

Micro description
=========================================================================

● Large, atypical nuclei in otherwise normal appearing leiomyoma
● No/rare mitotic figures
● Suggested classification for vulvar tumors is based on number of features below (0-1: leiomyoma, 2: atypical leiomyoma, 3-4: leiomyosarcoma)
  (a) 5+ cm in greatest dimension
  (b) infiltrative margins
  (c) 5+ mitotic figures per 10 HPF
  (d) moderate to severe cytologic atypia (Am J Surg Pathol 1996;20:779)

Micro images
=========================================================================



Smooth muscle cells with focal atypia


68 year old woman with thigh nodule (figures 2-5)


72 year old woman with nasal obstruction, rhinorrea, and epistaxis

Positive stains
=========================================================================

● Desmin, smooth muscle actin, muscle specific actin, vimentin (Mod Pathol 1998;11:282)

Negative stains
=========================================================================

● Keratin, GFAP



Smooth muscle

Cutaneous leiomyoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Leiomyoma: see also classic, bizarre, cutaneous, epithelioid, genital, leiomyoma of deep soft tissue

Definition
=========================================================================

● Arises from arrector pili muscles
● Superficial, small, multiple, painful

Terminology
=========================================================================

● Also called cutaneous piloleiomyoma

Clinical features
=========================================================================

● May be due to hereditary leiomyomatosis and renal cell cancer syndrome (J Urol 2007;177:2074); may be associated with germline mutations in the fumarate hydratase gene (Nat Genet 2002;30:406, Cancer Genet Cytogenet 2008;183:83)

Case reports
=========================================================================

● 51 year old woman with multiple cutaneous and uterine leiomyomatosis (Dermatol Online J 2005;11:21)
● 79 year old man with hereditary leiomyomatosis and renal cell carcinoma syndrome (Dermatol Online J 2008;14:16)

Treatment
=========================================================================

● Avoidance of cold
● Possibly nifedipine, nitroglycerine, phenoxybenzamine (block smooth muscle contraction, Dermatol Online J 2005;11:21)
● Possibly botulinum toxin-type A (Dermatology 2009;218:44)
● Possibly excision with dermal skin template for multiple tumors (J Cutan Med Surg 2009;13:102), carbon dioxide laser ablation

Clinical images
=========================================================================


Leg

Shoulder

Trunk

Micro images
=========================================================================


Various images

51 year old woman with painful papules of the shoulder
79 year old man with multiple nodular skin lesions of leg:

Intradermal nodular neoplasm with proliferated cellular elements having elongated blunt-end nuclei and fibrillar cytoplasm

Interlacing bundles with whorled appearance of uniform neoplastic cells

Uniform neoplastic cells with no mitotic figures

Trichrome staining showed proliferative smooth muscle cells (red) with collagen (blue)

Molecular description
=========================================================================

● Almost all patients with multiple skin leiomyomas have germline fumarate hydratase mutation (Arch Dermatol 2005;141:199)



Smooth muscle

Epithelioid leiomyoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Leiomyoma: see also classic, bizarre, cutaneous, epithelioid, genital, leiomyoma of deep soft tissue

Terminology
=========================================================================

● Called leiomyoblastoma in stomach

Case reports
=========================================================================

● 29 year old pregnant woman with myxoid epithelioid leiomyoma of vulva (Gynecol Oncol 2006;103:342)
● 40 year old woman with vaginal mass (The Internet Journal of Gynecology and Obstetrics)
● 42 year old woman with breast tumor with granular cell change (Hum Pathol 1993;24:1260)
● 46 year old woman with bladder tumor (Case Rep Urol 2012;2012:759150)
● 48 year old man with urethral tumor (Arch Pathol Lab Med 2000;124:302)
● 50 year old woman with tumor of buccal mucosa (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:670)
● Laryngeal tumor (Histopathology 1994;24:155)

Gross images
=========================================================================



Bladder tumor

Micro description
=========================================================================

● Round or polygonal cells, distinct cell borders, eosinophilic cytoplasm
● May have areas of classic leiomyoma, so take more sections
● May have perinuclear halo
● May have vacuolated cytoplasm (artifact of fixation)

Micro images
=========================================================================


Urethral tumor

Uterus tumor
40 year old woman with a soft, non-tender mass in the anterior vaginal wall:

Vaginal tumor #1:

#2: smooth muscle actin+

Positive stains
=========================================================================

● Desmin, smooth muscle actin

Differential diagnosis
=========================================================================

PEComa: clear cells, often atypia and necrosis, HMB45+



Smooth muscle

Genital leiomyoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Leiomyoma: see also classic, bizarre, cutaneous, epithelioid, genital, leiomyoma of deep soft tissue

Definition
=========================================================================

● Solitary tumor, arises from smooth muscle (dartos) bundles in superficial subcutaneous tissue or related structures of genitalia (penis / scrotum, labia, anal skin) or areola / nipple
● Also known as dartotic leiomyoma

Case reports
=========================================================================

● 25 year old woman with large labial tumor (J Med Assoc Thai 2005;88:118)
● 47 year old man with scrotal tumor (The Internet Journal of Dermatology 2009 Volume 7 Number 1)
● 53 year old man with tumor of epididymis (Kaohsiung J Med Sci 2006;22:519)
● 61 year old man with nipple leiomyoma (Dermatol Online J 2005;11:20)
● Tumor of female nipple (Breast J 2006;12:377)

Clinical images
=========================================================================



Nipple tumor

Micro description
=========================================================================

● Classic features of leiomyoma, but may also be cellular, epithelioid or myxoid
● Suggested classification for vulvar tumors is based on number of features below (0-1: leiomyoma, 2: atypical leiomyoma, 3-4: leiomyosarcoma)
  (a) 5+ cm in greatest dimension
  (b) Infiltrative margins
  (c) 5+ mitotic figures per 10 hpf
  (d) Moderate to severe cytologic atypia (Am J Surg Pathol 1996;20:779)

Micro images
=========================================================================



Nipple tumor: H&E, desmin


Scrotal biopsy

Positive stains
=========================================================================

● Desmin, smooth muscle actin
● Male genital leiomyomas are AR+ (J Cutan Pathol 2007;34:946)



Smooth muscle

Leiomyoma of deep soft tissue


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Leiomyoma: see also classic, bizarre, cutaneous, epithelioid, genital, retroperitoneal leiomyoma

Definition
=========================================================================

● Very rare tumor of deep subcutis or skeletal muscle of extremities (Stanford University) or retroperitoneum (described below)
● By definition, is distinct from uterus

Epidemiology
=========================================================================

● Tumors of deep somatic soft tissue affect males and females equally (Am J Surg Pathol 2001;25:1134)
● Tumors of retroperitoneum (described below) almost always occur in women
● Can rarely occur in children

Case reports
=========================================================================

● 32 year old man with carpal tunnel syndrome due to atypical deep soft tissue leiomyoma (World J Surg Oncol 2007;5:92)

Treatment and prognosis
=========================================================================

● Excision; rarely recurs

Clinical images
=========================================================================


Hand mass: intraoperative and gross specimen

Gross description
=========================================================================

● Well circumscribed, gray-white
● Usually large at presentation, up to 15 cm
● May have myxoid change

Micro description
=========================================================================

● Fascicles of normal appearing smooth muscle with eosinophilic cytoplasm
● Nuclei are bland and uniform, blunt ended, cigar shaped
● May have dystrophic calcification, degenerative nuclear changes or necrobiotic nodules resembling giant rosettes
● Hyalinization and fatty differentiation can also be seen rarely
● No/minimal atypia
● No/rare mitotic figures (Am J Surg Pathol 1994;18:576); <1 per 50 HPF
● No necrosis

Cytology description
=========================================================================

● Hypocellular smears, with scattered clusters of spindle cells (Diagn Cytopathol 1997;16:326)
● Clustered cells have syncytial appearance
● Bland nuclei have spindled appearance with rounded ends, condensed chromatin
● Usually no necrosis or inflammation
● No mitotic figures

Positive stains
=========================================================================

● Actin, desmin, h-caldesmon
● ER and PR in retroperitoneal tumors

Negative stains
=========================================================================

● S100

Differential diagnosis
=========================================================================

Benign metastasizing leiomyoma: see Am J Surg Pathol 1998;22:897
Myolipoma: prominent fatty change


Retroperitoneal leiomyoma

Definition
=========================================================================

● Well differentiated smooth muscle tumor resembling uterine leiomyoma, with trabecular pattern and hyaline change

Epidemiology
=========================================================================

● Usually occurs in women, mean 45 years (range 25-79 years)
● 40% have history of uterine leiomyoma (J Minim Invasive Gynecol 2008;15:152)
● Rare local recurrence, no metastases (Am J Surg Pathol 2001;25:1355)
● 73% are located in pelvis

Case reports
=========================================================================

● 26 year old woman with pelvic retroperitoneal leiomyoma (Am J Surg 2010;199:e36)
● 42 year old woman with myxoid deep soft tissue leiomyoma with abundant intracellular corpora amylacea (Pathol Res Pract 2007;203:121)
● 42 year old woman with 3 isolated tumors and no uterine tumor (Arch Gynecol Obstet 2009;280:499)
● 46 year old nulligravid woman with lower abdominal and pelvic pain with bloating (J Med Case Rep 2011;5:578)
● 48 year old woman, gravida 2, with incidental pelvic mass and multiple lung nodules (Clin Exp Reprod Med 2011;38:174)
● 49 year old woman with lower extremity mass (Acta Chir Belg 2009;109:112)

Treatment and prognosis
=========================================================================

● Excision; rarely recur locally

Gross images
=========================================================================


Retroperitoneal leiomyoma

Pelvic mass and lung nodules

Micro description
=========================================================================

Leiomyoma:
● 4 cm or less
● Bland smooth muscle tumor
● No mitotic figures
● Very rare at this site

Smooth muscle tumor of uncertain malignant potential:
● Bland smooth muscle tumor
● Either 4 cm or less and 1-4 MF/10 HPF or 5 cm or more and no mitotic figures

Leiomyosarcoma:
● Pleomorphism
● Nuclear atypia or tumor cell necrosis

Micro images
=========================================================================


Classic features of leiomyoma

Retroperitoneal mass

Pelvic mass and lung nodules

Positive stains
=========================================================================

● Smooth muscle actin, desmin
● Trichrome stains smooth muscle red, collagen blue
● ER, PR in women (may arise from hormonally sensitive smooth muscle)

Differential diagnosis
=========================================================================

● GIST tumors: CD117+
Leiomyosarcoma: much more common; necrosis, mitotic figures, pleomorphism
Parasitic leiomyoma: clearly attached to non-retroperitoneal structures



Smooth muscle

Leiomyosarcoma-general


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Leiomyosarcoma: see also cutaneous, epithelioid, myxoid, pleomorphic, rhabdoid features

Definition
=========================================================================

● Smooth muscle tumor with atypia plus either mitotic activity, tumor cell necrosis or size > 10 cm
● 10% of adult soft tissue sarcomas
● Variants are described separately above

Epidemiology
=========================================================================

Skin/subcutis: see cutaneous variants above; better survival than retroperitoneal tumors
Retroperitoneum: third most common retroperitoneal sarcoma after liposarcoma and MFH; usually women, 5 year survival is only 29% (Stanford University)
Immunocompromised patients: associated with EBV in HIV patients; may be multifocal

Sites
=========================================================================

● Usually extremities
● Often arises from large vessels (Am J Surg Pathol 2002;26:14), most commonly inferior vena cava, saphenous vein, femoral vein, pulmonary artery, femoral artery
● Also occurs in retroperitoneum, superficial or deep soft tissues, rarely in bone, breast, colon, epididymis, mediastinum

Case reports
=========================================================================

● 8 year old girl with oral cavity tumor (J Cancer Res Ther 2012;8:282)
● 26 year old man with EBV+ tumor after heart transplantation (Am J Surg Pathol 2000;24:614)
● 54 year old man with tumor of inferior vena cava (Arch Pathol Lab Med 2003;127:e423)
● 58 year old man with mediastinal tumor (Korean J Thorac Cardiovasc Surg 2012;45:192)
● 69 year old man with tumor of internal jugular vein (World J Surg Oncol 2008;6:113)
● 70 year old man with 25 cm epididymis mass (Case Rep Urol 2012;2012:236320)

Treatment and prognosis
=========================================================================

● Excision with clear margins (enucleation is inadequate treatment)
● Often recurs locally or metastasizes
● Lung is common site of metastasis, lymph nodes are uncommon site
Poor prognostic factors: retroperitoneal, mesenteric or other deep location, size > 5 cm, age > 62 years, high grade, tumor disruption by prior incisional biopsy or incomplete excision (Cancer 2007;109:282), possibly nuclear c-myc expression (Mod Pathol 2009;22:1432)
● In extremities, poor prognostic factors are large size and high mitotic rate; best treatment is wide surgical excision plus adjuvant radiation therapy (Eur J Surg Oncol 2004;30:565)

Clinical images
=========================================================================


12 cm tibial tumor

Oral cavity tumor

Epididymis mass (25 cm)

Internal jugular vein

Gross description
=========================================================================

● Low grade tumors are hard masses and resemble leiomyomas, with white whorled cut surface
● High grade tumors are large, soft, often with necrosis, hemorrhage and cystic degeneration
● May project into lumen of major vessels or be intramural

Gross images
=========================================================================


Leg tumor #1

#2

Retroperitoneal tumor

Thigh tumor

Bone

Micro description
=========================================================================

● Fascicular growth pattern (bundles intersect at right angles)
● Tumor cells merge with blood vessel walls
● Palisading of spindle cells with eosinophilic fibrillary cytoplasm, focal granularity
● Nuclei are cigar-shaped and blunt-ended with variable atypia, often with cytoplasmic vacuoles at both ends of nuclei (unlike neural lesions)
● Mitotic figures are common
● May have hemangiopericytoma-like vasculature, nuclear palisading, myxoid change, osteoclast-like giant cells, some may show extensive pleomorphism mimicking MFH
● Often infiltrates into adjacent tissue
● See also variants above

Malignant criteria by site
=========================================================================

Soft tissue: 1-2 MF/10 HPF and deep
Skin/subcutaneous: 2 MF/10 HPF is definitive, 1 MF/10 HPF if consistent in all fields
Retroperitoneum: 5 MF/10 HPF is definitive, or 1-4 MF/10 HPF plus necrosis plus size > 7.5 cm
Vascular: 1-4 MF/10 HPF plus large size plus necrosis
● Diagnose as tumor of uncertain malignant potential (UMP) if mitotic figures are fewer than above or focal

Micro images
=========================================================================



Oral cavity tumor


Thigh tumor


Retroperitoneum smooth muscle morphology

Marked pleomorphism and no identifiable smooth muscle

Uncertain malignant potential: 8 cm retroperitoneal tumor with bland cells and < 1 MF/10 HPF

Malignant based on low power pleomorphism

Pleomorphism and smooth muscle differentiation are evident

Markedly pleomorphic, little evidence of smooth muscle differentiation

Multinucleated giant cells

Intravenous tumor

Internal jugular vein tumor

Inf vena cava tumor: cytology, H&E, smooth muscle actin

Tibial tumor

Mediastinal tumor

Epididymis tumor

Cytology description
=========================================================================

● Fascicles with an mixture of dispersed cells or stripped nuclei
● Most cells are spindled with elongated, blunt-ended, segmented or fusiform nuclei or round/polygonal with round or indented nuclei
● Also pleomorphic cells, occasionally intranuclear vacuoles, mitoses and osteoclast-like giant cells (Diagn Cytopathol 2006;34:597)

Positive stains
=========================================================================

● HHF35 (90%), alpha-smooth muscle actin (90%), vimentin, desmin (75%, Cancer 2009;115:4186)
● H-caldesmon (Am J Clin Pathol 2000;113:663)
● PTAH (stains myofibrils), keratin (30%), ER (usually in uterine and female retroperitoneal tumors), S100 (occasionally weak staining), EMA (may be focal), occasionally CD34

Negative stains
=========================================================================

● CD117

Electron microscopy description
=========================================================================

● Some smooth muscle features, including cytoplasmic filaments with focal densities (also present in myofibroblasts), pinocytotic vesicles, thick basal lamina

Molecular / cytogenetics description
=========================================================================

● Often complex karyotypes with no consistent aberrations

Differential diagnosis
=========================================================================

Dedifferentiated liposarcoma: usually trunk, better prognosis, well differentiated component present, MDM2 and CDK4 amplification (Am J Surg Pathol 2007;31:1557)
Leiomyoma: no/rare mitotic activity, no/minimal atypia, small size, no hemorrhage, no necrosis



Smooth muscle

Cutaneous leiomyosarcoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 22 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Leiomyosarcoma: see also general, epithelioid, myxoid, pleomorphic, rhabdoid features

Epidemiology
=========================================================================

● More common in men, almost always whites in US (Cancer 2008;113:616)
● Mean age 40-60 years; childhood tumors are rare

Clinical features
=========================================================================

● Either dermal, arising from arrectores pilorum muscle, or subcutaneous, arising from wall of vessel
● Cutaneous tumors are indolent; subcutaneous tumors may metastasize (Cancer 2007;109:282)
● Head and neck, extremities, scrotal

Case reports
=========================================================================

● 57 year old man with hard, painless erythematous tumor of presternum (An Bras Dermatol 2011;86:999)
● 59 year old woman with leg tumor with osteoclast-like giant cells (J Med Case Rep 2007;1:180)
● 65 year old man with diffuse tumor of head and neck with desmoplasia (Australas J Dermatol 2006;47:291)
● 66 year old man with tumor arising in smallpox scar on shoulder (World J Surg Oncol 2012;10:148)
● 66 year old man with desmoplastic leiomyosarcoma of thigh (Dermatol Online J 2010;16:4)
● 67 year old woman with hip lesion (Univ Pittsburgh Case #107)
● 81 year old man with forehead mass (Am J Clin Dermatol 2008;9:185)
● 98 year old woman with facial lesion (The Internet Journal of Dermatology 2007 Volume 5 Number 1)
● Family with cutaneous leiomyosarcoma (not leiomyoma) and renal cell carcinoma, but no fumarate hydratase mutation (Int J Dermatol 2008;47:18)

Treatment
=========================================================================

● Complete excision with a narrow margin is acceptable for low-grade cutaneous tumors
● Wide excision with 2 cm lateral margin and one tissue barrier deep margin for low grade and early stage subcutaneous and soft tissue tumors
● Wide excision for high grade tumors (Plast Reconstr Surg 2005;116:8)
● Mohs surgery offers tissue sparing with comparable results (Dermatol Surg 2004;30:108)
● Tumors may recur and occasionally metastasize

Clinical images
=========================================================================



Left to right: presternum, shoulder, thigh

Micro description
=========================================================================

● Intersecting fascicles of brightly eosinophilic spindle cells with ovoid to cigar-shaped nuclei
● Pleomorphism and mitotic figures are common

Micro images
=========================================================================



Hip lesion


Leg tumor with osteoclast-like giant cells


Shoulder lesion (at smallpox scar)


Face #1

#2

#3-SMA

Dermal-based spindle cell tumor

Desmoplasia

Nuclear pleomorphism

Mitoses

Desmin+ tumor cells wrap around nerve

Presternum lesion

Positive stains
=========================================================================

● Smooth muscle actin, muscle-specific actin, vimentin, calponin
● Variable desmin, caldesmon, myosin and keratin (Am J Surg Pathol 1997;21:979)

Molecular description
=========================================================================

● No somatic mutations in fumarate hydratase gene in sporadic cases (Br J Cancer 2002;87:446)



Smooth muscle

Epithelioid leiomyosarcoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Leiomyosarcoma: see also general, cutaneous, myxoid, pleomorphic, rhabdoid features

General
=========================================================================

● Usually in uterus; rare in bone, soft tissue, skin or subcutis (Am J Surg Pathol 1994;18:232)
● In stomach is called leiomyoblastoma

Case reports
=========================================================================

● Infant with intraabdominal mass (Mod Pathol 2000;13:1156)
● 6 year old girl with mandibular tumor (Klin Padiatr 2005;217:291)
● 18 year old man with scrotal mass (Urol J 2004;1:215)
● 56 year old man with tumor of gastrocolic ligament (Acta Chir Belg 2003;103:105)
● 71 year old man with rectal tumor with osteoclast-like giant cells (Arch Pathol Lab Med 2000;124:438)
● 78 year old man with thigh tumor (Arch Pathol Lab Med 2002;126:468)

MRI images
=========================================================================



18 month old girl with intraabdominal mass

Gross images
=========================================================================



71 year old man with rectal tumor

Micro description
=========================================================================

● Round/polygonal cells with eosinophilic and vacuolated cytoplasm, vesicular nuclei
● Arranged in sheets with focal spindle cells

Micro images
=========================================================================



Various images


Bladder tumor: H&E and actin

Rectal tumor with osteoclast-like giant cells

Cytology description
=========================================================================

● Mononuclear, binucleated or multinucleated cells with eccentric nuclei and dense to vacuolar cytoplasm (Acta Cytol 1997;41:1801)
● Also highly cellular smears with many single polygonal cells having eccentric, malignant nuclei and a characteristic clear quality to the cytoplasm in Pap-stained material (Diagn Cytopathol 1994;11:321)

Positive stains
=========================================================================

● Alpha-smooth muscle actin, alpha-sarcomeric actin, vimentin
● Also CD99/MIC2
● Reticulin stain outlines individual tumor cells

Negative stains
=========================================================================

● CAM 5.2, EMA, CD34, CD45; usually desmin
● Factor VIII, glial fibrillary acidic protein, HMB45, S100, CD1a (Ann Diagn Pathol 2008;12:401)

Electron microscopy description
=========================================================================

● Abundant actin-type filaments in cytoplasm of some cells, glycogen

Electron microscopy images
=========================================================================



Intermediate filaments, thin filaments with subplasmalemmal dense bodies and glycogen

Differential diagnosis
=========================================================================

Epithelioid sarcoma
Melanoma: S100+, HMB45+
Metastatic carcinoma: clinical history, keratin+, no areas of classic leiomyosarcoma
Metastatic uterine tumor: clinical history



Smooth muscle

Myxoid leiomyosarcoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 17 November 2014, last major update November 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

Leiomyosarcoma: see also general, cutaneous, epithelioid, pleomorphic, rhabdoid features

Definition
=========================================================================

● Defined as 50%+ myxoid stroma

Epidemiology
=========================================================================

● Rare; 75% women, median age 58 years, range 22-84 years

Clinical features
=========================================================================

● Usually affects chest, female genitalia (particularly uterus), head and neck, limbs
● 40% recur, 15% metastasize, 17% have tumor related deaths (Am J Surg Pathol 2000;24:927)
● Recur and metastasize regardless of mitotic count (which is deceptively low due to hypocellularity, Histopathology 1985;9:159)

Case reports
=========================================================================

● 20 year old woman with cystic mass of uterus (Acta Cytol 2000;44:415)
● 54 year old woman with mass of uterus (J Korean Med Sci 1998;13:559)
● 64 year old woman with liver tumor (Korean J Intern Med 2002;17:278)
● 85 year old woman with a unilateral nonulcerating, painless vulvar mass (Gynecol Oncol 2005;96:548)

Gross description
=========================================================================

● Large gelatinous mass
● Well circumscribed
● May have cystic change, necrosis and hemorrhage

Micro description
=========================================================================

● Invasive and infiltrative
● Fascicular, reticular, microcystic or resembling myxofibrosarcoma
● Spindled cells with smooth muscle features surrounded by abundant basophilic (myxomatous) material composed of hyaluronic acid
● Tumor cells have moderate to marked atypia but variable tumor cell necrosis
● May have focal epithelioid cells
● Usually low grade
● Deceptively low mitotic rates are due to hypocellularity

Micro images
=========================================================================



Figure 9         Various images

Cytology description
=========================================================================

● Resembles low to intermediate grade myxofibrosarcoma; diffusely granular myxoid stroma is accompanied by randomly distributed spindled or ovoid tumor cells, either solitary or in large cohesive cellular clusters; nuclei are round to ovoid, moderately pleomorphic and contain small / inconspicuous nucleoli (Cancer 2000;90:167, Acta Cytol 2000;44:415)
● Peritoneal washing of disseminated uterine tumor: uniformly dispersed spindly to polygonal epithelioid tumor cells focally linked by background matrix; spindled tumor cells attach to and radiate from branching capillary structures; occasional scattered signet-ring cells; the background mucoid substance is more conspicuous in cell block (Diagn Cytopathol 2002;27:47)

Cytology images
=========================================================================



Figures 7-9

Positive stains
=========================================================================

● Smooth muscle actin
● High MIB-1 index although low mitotic count
● Desmin (50%), CAM5.2 (25%), EMA (15%)

Negative stains
=========================================================================

● S100, CD34

Differential diagnosis
=========================================================================

Inflammatory myofibroblastic tumor: no destruction of muscle fascicles at tumor-muscle interface, no nuclear pleomorphism, no tumor necrosis, ALK1+, h-caldesmon+ (Pathol Int 2006;56:625)
Myxofibrosarcoma: cells are myofibroblast or lipoblast-like, also typical MFH areas, curvilinear vessels (thick walled with broad arc) with condensation of cells around vessels, incomplete fibrous septa, myxoid stroma; no smooth muscle differentiation
Myxoid chondrosarcoma: malignant chondocytes present
Myxoid leiomyoma: not infiltrative; nuclei are small and bland, no mitotic activity
● Other myxoid tumors: low grade fibromyxoid sarcoma, myxofibrosarcoma, myxoid liposarcoma, cellular myxoma, myxoid peripheral nerve sheath tumor



Smooth muscle

Pleomorphic leiomyosarcoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Leiomyosarcoma: see also general, cutaneous, epithelioid, myxoid, rhabdoid features

Definition
=========================================================================

● Pleomorphic areas should be at least 2/3 of tumor

Epidemiology
=========================================================================

● 10% of all leiomyosarcomas
● Mean age 58 years, range 31-89 years

Clinical features
=========================================================================

● Usually extremities, also retroperitoneum/abdominal cavity, chest/abdominal wall, occasionally scalp
● May be more aggressive than ordinary leiomyosarcoma, as 65% die of disease

Case reports
=========================================================================

● 56 year old woman with pancreatic mass (J Int Med Res 2011;39:1555)
● 57 year old man with a mass in upper arm (Acta Cytol 2010;54:1013)
● 59 year old woman with adrenal tumor (Endocr Pathol 2005;16:75)
● 63 year old man with adrenal tumor (Arch Pathol Lab Med 2003;127:e32)
● 65 year old man with beta hcG producing retroperitoneal tumor (Sarcoma 2000;4:179)

Micro description
=========================================================================

● Focally fascicular with smooth muscle tumor cells
● Pleomorphic areas mimic MFH-pleomorphic
● Storiform pattern common
● Stromal hyalinization, chronic inflammatory infiltrate
● Usually high grade
● Occasionally rhabdoid features

Micro images
=========================================================================



Various images


Resembles MFH”

Abrupt transition from fascicular to pleomorphic areas

Positive stains
=========================================================================

● At least one smooth muscle marker (desmin, muscle-specific actin or alpha-smooth muscle actin) in the leiomyosarcomatous fascicular areas
● Also positive for collagen type IV around the individual tumor cells (Oncol Rep 1999;6:533)

Differential diagnosis
=========================================================================

Atypical fibroxanthoma: superficial skin lesion with no necrosis, no vascular invasion, no infiltrative margins
MFH-pleomorphic: negative for smooth muscle markers (i.e. no evidence of specific differentiation other than myofibroblasts / fibroblasts, Oncol Rep 1999;6:533, Am J Surg Pathol 2001;25:1030)
Myofibrosarcoma: low grade tumor overall, may have numerous thin walled capillaries, no prominent inflammation



Smooth muscle

Leiomyosarcoma with Rhabdoid features


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Leiomyosarcoma: see general, cutaneous, epithelioid, myxoid, pleomorphic

Definition
=========================================================================

● Diffuse proliferation of rhabdoid cells in otherwise identifiable leiomyosarcoma
● Tumors with scattered rhabdoid cells may be better classified as pleomorphic leiomyosarcoma
● Distinct from rhabdoid tumor of kidney

Epidemiology
=========================================================================

● Often infancy or childhood, in neck or paraspinal region (Pathol Int 2006;56:287); also adults

Case reports
=========================================================================

● 38 year old woman with leiomyosarcoma of broad ligament with osteoclast-like giant cells and rhabdoid cells (Int J Gynecol Pathol 2010;29:432)
● 56 year old woman with inguinal mass with epithelioid and rhabdoid features (Wien Klin Wochenschr 2007;119:557)

Treatment and prognosis
=========================================================================

● Presence of rhabdoid cells in a tumor, in general, is associated with aggressive behavior
● Poorer prognosis for external soft tissue (not intra-abdominal) cases, but not for retroperitoneal cases (Mod Pathol 2000;13:1211)

Gross description
=========================================================================

● 3-22 cm

Micro description
=========================================================================

● Rhabdoid cells are large and polygonal with eosinophilic cytoplasm, eosinophilic globular perinuclear inclusions, eccentric nuclei and prominent nucleoli

Micro images
=========================================================================



Thigh #1

Thigh #2

Thigh #3

Retroperitoneum

Thigh-stains

Positive stains
=========================================================================

● Rhabdoid cells: vimentin, desmin, low molecular weight cytokeratin in inclusion bodies, muscle actin in cytoplasm, INI1 in nucleus (Mod Pathol 2005;18:951)

Electron microscopy description
=========================================================================

● Paranuclear aggregates or whorls of intermediate filaments

Molecular description
=========================================================================

● Malignant rhabdoid tumors of various sites may have abnormalities in the long arm of chromosome 22 and alteration of the hSNF5/INI1 (SMARCB1) gene (Am J Surg Pathol 1999;23:249, Am J Hum Genet 1999;65:1342), also seen in epithelioid sarcoma (Am J Dermatopathol 2009;31:152)

Molecular images
=========================================================================



Normal 22q dosages

Differential diagnosis
=========================================================================

● Rhabdoid cells may also be present in synovial sarcoma and extraskeletal myxoid chondrosarcoma



Vascular tumors

Normal vessels


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Normal vessels contain endothelial cells facing lumen and pericytes, smooth muscle cells and glomus cells towards outside of vessel

Embryology
=========================================================================

● Development begins with formation of hemangioblasts, which organize in blood islands in yolk sac, and differentiate into hematopoietic and angioblastic cells
● Hematopoietic cells generate blood cells; angioblastic cells generate vascular endothelial cells (ECs)
● Notch signaling pathway helps determine arterial program of both endothelial and smooth muscle cells (Stem Cells Int 2012;2012:805602)
● See also Development 2011;138:4569, Int J Dev Biol 2011;55:419

Normal histology
=========================================================================

● Vascular layers are outer tunica adventitia, intermediate tunica media and inner tunica intima; thickness depends on size and type of vessel
● Tunica adventitia: longitudinally arranged collagen; layer is larger in veins than arteries
● Tunica media: concentrically arranged smooth muscle whose diameter is altered by autonomic control; smooth muscle may secrete collagen, elastic fibers, elastic lamellae and proteoglycans; larger diameter in arteries than veins of similar size
● Tunica intima: inner endothelium and variable outer subendothelial connective tissue
● Capillaries: no muscular layer or elastic lamella; endothelial layer is complete, with pericytes present but difficult to identify on H&E
● Glomus cells: (a) modified smooth muscle cell with indistinct borders, pale cytoplasm, uniform nuclei; surround arterial segment of glomeriform arteriovenous anastomosis, which is richly innervated by autonomic nervous system fibers; or (b) peripheral chemoreceptor in carotid body and aortic body that detects hypoxia (Novartis Found Symp 2006;272:54); large, epithelioid cells with abundant cytoplasm and membrane bound, electron dense granules; richly supplied with nerve endings, see diagram below
● Pericytes: relatively undifferentiated cell that regulates microvascular blood flow (Histol Histopathol 1991;6:269, Microvasc Res 2009;77:235)
● References: University of Ottawa, Southern Illinois University, Victoria College

Diagrams
=========================================================================


Glomus cell

Arterial wall
Pericyte and endothelial interactions

Pericyte and endothelial interactions

Aging related changes
=========================================================================

● Normal vascular structure changes during life, with progressive arterial stiffness
● Capillaries: basement membrane thickens with aging

Micro images
=========================================================================


Small arteries

Small arteries

Small artery and vein

Capillaries

Artery #1: H&E

#2: elastin

#3: trichrome

Arteriole

Venous wall


Pericytes


Artery wall: blue arrow is tunica intima; black bracket is tunica media; green bracket is tunica adventitia

Positive stains
=========================================================================

Vascular endothelium: CD34, CD31, Factor VIII related antigen, vimentin, Ulex europaeus I lectin (binds to alpha-L-fructose compounds), endothelin, von Willebrand factor; also FLI-1 (nuclear stain, Am J Surg Pathol 2001;25:1061)
Lymphatic endothelium: similar staining as vascular endothelial cells but also D2-40+, LYVE1+, and only weakly Factor VIII related antigen+
Pericytes: alpha smooth muscle actin, myosin, vimentin; also CD31
Smooth muscle cells: actin, desmin

Electron microscopy description
=========================================================================

Endothelial cells: cells are jointed by tight, adherans or gap junctions; numerous pinocytotic vesicles, cytoplasmic microfilaments, microvilli, continuous basal lamina and Weibel-Palade bodies (membrane bound organelle which contains von Willebrand factor)
Capillary endothelium: surrounded by basement membrane which contains pericytes, in contrast to lymphatic endothelium which contains little basement membrane

Electron microscopy images
=========================================================================


Brain capillary with endothelial cells and pericyte

Weibel-Palade bodies

Endothelial junctions

Endothelial tight junction

Pericytes

Pericytes


Normal / benign

Bacillary angiomatosis


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 25 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Opportunistic infection of immunocompromised, first described in AIDS, manifesting as vascular proliferations in bone, CNS, skin, other organs
● Rarely imunocompetent individuals (Indian J Dermatol Venereol Leprol 2010;76:682)
● Caused by infection with Bartonella species (gram negative rods), either Bartonella henselae (causes cat-scratch disease, reservoir in cats, vector is cat flea), B. quintana (cause of trench fever during WW I, reservoir in humans, vector is human body louse) or other species; transmitted via traumatic inoculation of skin
● Bacillary peliosis: related vascular lesion of liver and spleen

Case reports
=========================================================================

● 23 year old HIV+ woman with disseminated disease (Rev Soc Bras Med Trop 2011;44:641)
● 59 year old immunocompetent woman with no exposure to cats (Indian J Dermatol Venereol Leprol 2010;76:682)
● 66 year old woman with onset after chemotherapy for CLL (J Med Microbiol 2011;60:142)

Treatment
=========================================================================

● Erythromycin

Clinical images
=========================================================================

Skin: nodules with ulceration
Skin: erythematous nodular lesions
Skin: post CLL chemotherapy
Skin: at site of burn

Gross description
=========================================================================

● Moist, eruptive, cutaneous lesion

Micro description
=========================================================================

● Acute neutrophilic inflammation with vascular proliferation and prominent endothelial cells with nuclear atypia and mitotic figures
● Nuclear dust and granular material (bacteria) present
● Bacteria highlighted by silver stain

Micro images
=========================================================================

Dermal lobular vascular proliferation with swollen endothelial cells and bacteria (Warthin-Starry)
Warthin-Starry stain
Mixed inflammation, capillary proliferation

Differential diagnosis
=========================================================================

Angiosarcoma
Kaposi sarcoma
Pyogenic granuloma



Normal / benign

Glomus tumor


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 25 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also symplastic

General
=========================================================================

● Usually benign; excision curative
● Occurs in wide age range
● Subungual tumors are exquisitely painful due to abundant nerve fibers
● Arises from modified smooth muscle cells of glomus body, a specialized arteriovenous anastomosis involved in thermoregulation
● Usually under fingernails; also skin, flexor arm/knee, GI tract, rarely in head and neck
● All glomus tumors should have at least focal areas of typical glomus tumor, usually at periphery (Am J Surg Pathol 2001;25:1)

Glomangioma:
● Glomus tumors that resemble cavernous hemangiomas

Glomangiomatosis:
● Diffuse angiomatosis resembling angiomatosis with excess glomus cells
● Often associated with considerable fat and pain
● Probably represents vascular malformations

Glomangiomyoma:
● Combines features of glomus tumor and angioleiomyoma

Glomus tumor of uncertain malignant potential:
● High (5+/50 HPF) mitotic activity and superficial OR 2 cm+ only OR deep only

Glomangiosarcoma:
● Deep (to muscular fascia) and 2 cm or larger OR atypical mitotic figures OR moderate/high nuclear grade and 5+ MF/50 HPF
● 38% had metastases in one series, no metastases in symplastic, uncertain malignant potential, glomangiomatosis

Case reports
=========================================================================

● 24 year old man with glomus tumor of cheek (Case Report Med 2012;2012:307294)
● 44 year old man with painful lesion in plantar region (An Bras Dermatol 2011;86:1029)
● 47 year old man with glomangiosarcoma of shoulder (dermpathMD)
● 50 year old woman with primary glomus tumor of liver (Indian J Pathol Microbiol 2011;54:584)

Clinical images
=========================================================================


Thumb #1

#2

Index finger

Plantar nodule

Gross description
=========================================================================

● Less than 1 cm, rounded, red-blue, yellowish to tan red, firm
● Resembles fresh hemorrhage under the nail

Gross images
=========================================================================


Liver tumor

Micro description
=========================================================================

● Branching vascular channels separated by stroma containing glomus cells in nests, aggregates
● Glomus cells are arranged around vessels
● Have small, regular, round, indistinct nucleoli
● More infiltrative in children
● May have secondary myxoid change
● Very low mitotic activity

Micro images
=========================================================================


Index finger tumor


Thumb

Liver

Cheek is benign but invades vessel wall

Plantar nodule is SMA+

Glomangiosarcoma of shoulder

Cytology description
=========================================================================

● Cohesive clusters of uniform round cells with scanty cytoplasm
● Background of scattered amorphous magenta colored material, blood and occasional inflammatory cells (J Cytol 2010;27:104)

Cytology images
=========================================================================


Round to oval cells with homogenous granular chromatin

Positive stains
=========================================================================

● Smooth muscle actin, type 4 collagen, vimentin
● CD34 in 20% only
● Variable expression of h-caldesmon and calponin

Negative stains
=========================================================================

● Cytokeratin, desmin, S100, chromogranin

Electron microscopy description
=========================================================================

● Resemble smooth muscle cells


Symplastic glomus tumor

General
=========================================================================

● High nuclear grade but no mitotic figures or other features of malignancy; may be degenerative

Case reports
=========================================================================

● 78 year old male with nail deformity of indx finger (J Cutan Pathol 2009;36:1099)
● 81 year old man with mass in subcutis of great toe (Case of Week #238)

Micro images
=========================================================================



(a) multiple foci of glomus cells surrounding capillary-sized vessels in myxoid stroma with some nerve fibers and bone
(b) glomus cells show prominent cytological atypia with nuclear enlargement and pleomorphism, anisonucleosis, hyperchromasia, pseudoinclusions, bizarre nuclei, coarse chromatin, and irregular nuclear membrane


Images from Case of the Week #238:










CD34

Ki-67

Smooth muscle actin

Vimentin

Desmin


Benign vascular tumors

Hemangioma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 8 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See variants below: capillary, cavernous, intramuscular, large vessel, pyogenic granuloma

General
=========================================================================

● Common benign tumor, particularly in childhood; some may be hamartomas
● Usually superficial (head/neck), may occur internally (1/3 in liver), malignant transformation rare
● Usually localized, but may involve large segments of body (termed angiomatosis)
● Most pediatric angiomas are present at birth and expand with growth of child, may regress at puberty

Micro description
=========================================================================

● Increased number of vessels (normal/abnormal)
● Readily recognizable vascular structures with red blood cells or transudate
● Lined by monolayer of non-atypical endothelial cells


Capillary hemangioma

General
=========================================================================

● Blood vessels resemble capillaries
● Present in skin, subcutaneous tissue, mucous membranes of lips, mouth, internal viscera
● Strawberry type is seen in juveniles in 1/200 births, may be multiple, grow in first year, fade at ages 1-3, regress by age 7 in 75%

Micro description
=========================================================================

● Closely packed spindle cells with spaces containing little blood
● Lumens may be thrombosed or organized, hemosiderin present due to rupture
● Scant fibrous stroma

Micro images
=========================================================================



Thigh


VEGFR-3–negative tumor vessels and positive normal lymphatics (Mod Pathol 2000;13:180)


Cavernous hemangioma

General
=========================================================================

● In skin, called port-wine nevus or nevus flammeus
● Present at birth, grows slowly with patient; does not regress
● In deep locations may thrombose, ulcerate, become infected; associated with thrombocytopenia, intravascular coagulation
● Associated with von Hippel Lindau disease, which has cavernous hemangiomas in cerebellum, brain stem, eye grounds
Sinusoidal hemangiomas: cavernous hemangiomas with dilated, interconnected, thin-walled channels with occasional pseudopapillary projections

Gross description
=========================================================================

● 1-2 cm (larger than capillary), sharply defined

Micro description
=========================================================================

● Large cystically dilated vessels with thin walls
● Intravascular thrombosis or calcification is common

Micro images
=========================================================================



Various images


Intramuscular hemangioma

General
=========================================================================

● Resemble cavernous hemangiomas
● May resemble angiosarcoma due to high cellularity with mitotic figures, intraluminal papillary projections, plump endothelial cells, perineurial infiltration, but no atypia
● Also, angiosarcomas extremely uncommon in skeletal muscle

Micro images
=========================================================================



Various images


Large vessel hemangioma

General
=========================================================================

● Veins, arteries or a mixture
● May have abnormal vascular wall structure that defies classification
● Back, gluteal region, thigh; occasionally entire extremity
● Thrombosis and calcification common
Klippel-Trenaunay syndrome: varicose veins, dysplastic cutaneous hemangiomas and soft tissue and bone hypertrophy


Pyogenic granuloma

General
=========================================================================

● Also called lobular capillary hemangioma
● Rapidly growing, exophytic red nodule, attached by a stalk to skin or gingival mucosa
● Bleeds easily, ulcerates
● 1/3 due to trauma (1-2 cm after 1-2 weeks)
Pregnancy tumor: also called granuloma gravidarum, a pyogenic granuloma found in 1% of pregnant women, regresses after delivery

Micro images
=========================================================================



Polypoid red-brown mass

Micro description
=========================================================================

● Vessels, edema, acute and chronic inflammation
● Resembles granulation tissue



Benign vascular tumors

Microvenular hemangioma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Dermal proliferation of small, irregular branching capillaries and venules with inconspicuous lumina

Terminology
=========================================================================

● First described in 1989 as microcapillary angioma (Z Hautkr 1989;64:1071), and in 1991 with current terminology (J Cutan Pathol 1991;18:235)

Epidemiology
=========================================================================

● Rare, < 50 cases reported
● Young to middle aged adults

Sites
=========================================================================

● Often trunk or limbs

Etiology
=========================================================================

● May be form of acquired venous hemangioma
Microcapillary hemangioma: similar histology, but occurs in young women taking oral contraceptives or during pregnancy

Clinical features
=========================================================================

● Presents as slow growing, solitary, asymptomatic, purple-red papule or plaque, 0.5-2 cm, usually extremeties
● May mimic an inflammatory lesion (J Plast Reconstr Aesthet Surg 2009;62:e166)

Case reports
=========================================================================

● Boy with coexisting AML (Pediatr Dermatol 2003;20:266)
● 23 year old woman with slowly growing, solitary red plaque on back (Pathol Int 1998;48:237)
● 28 year old man with thigh nodule (Case of the Week #80)
● 40 year old woman (Dermatology 2003;206:161)
● 53 year old woman with numerous bilateral macules, patches, and plaques (Am J Dermatopathol 2013;35:98)
● 55 year old woman with POEMS syndrome and HHV8+ microvenular hemangioma (Arch Pathol Lab Med 2003;127:1034)

Treatment
=========================================================================

● Excision is curative

Dermoscopic description
=========================================================================

● Multiple well-demarcated red globules; fine pigment network at periphery (Dermatology 2007;215:69)

Gross images
=========================================================================


Well defined, oval red lesion

Microscopic description
=========================================================================

● Dermal proliferation of small, irregular branching capillaries and venules with inconspicuous lumina
● Endothelial cells may be plump, but no atypia
● Stroma is collagenous
● Variable lymphocytes
● No fat invasion, although may grow along collagenous septa of subcutis
● No spindle cells

Micro images
=========================================================================



Case of the Week images


Dermal vascular proliferation


HHV8+ tumor

Positive stains
=========================================================================

Endothelial cells: CD34, CD31, Factor VIII related antigen, vWF, Ulex europaeus lectin
Pericytes: smooth muscle actin

Negative stains
=========================================================================

● Podoplanin (Pathol Res Pract 2008;204:817), HHV8

Differential diagnosis
=========================================================================

Acquired (tufted) angioma: multiple vascular lobules similar to pyogenic granuloma but more cellular, resembling cannonballs
Kaposi's sarcoma-patch stage: irregular vascular spaces are anastomosing but not collapsed, and are accompanied by atypical endothelial cells, eosinophilic hyaline globules, plasma cells and fascicles of spindle cells; may be irregular dissection of collagen bundles by vessels; spindle cells are HHV8+, patients are HIV+ (Am J Clin Pathol 2004;121:335)
Kaposiform hemangioendothelioma: also has slit-like lumina, but they are due to nodules and sheets of compact spindle cells; affects the skin or retroperitoneum of infants and children, may be associated with severe coagulopathy
● Sclerosing hemangioma
● Statis related change



Benign vascular tumors

Symplastic hemangioma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Hemangioma with bizarre stromal cells in fibrinous material around vessels

Epidemiology
=========================================================================

● Limited published reports

Etiology
=========================================================================

● Due to degenerative atypia of vascular smooth muscle and interstitial cells, similar to symplastic leiomyoma of uterus or ancient schwannoma

Treatment
=========================================================================

● Excision, does not recur or metastasize (Hautarzt 2000;51:327)

Micro description
=========================================================================

● Vascular lesion with thick walled and variably dilated vessels
● Degenerative atypia of vascular smooth muscle and interstitial cells within a pre-existing vascular lesion, with minimal endothelial cell atypia
● Atypical cells are spindled or epithelioid with variable hyperchromasia, nuclear enlargement, pleomorphism and multinucleation (J Cutan Pathol 2006;33:735)
● Perivascular hemorrhage, vascular thrombosis and focal papillary endothelial hyperplasia are common
● Stroma has hemosiderin and mononuclear inflammation
● May have fibrous tissue, stromal edema or fat cells within superficial dermis
● May have rare atypical mitotic figures or bizarre lipoblast-like stromal cells
● No endothelial cell multilayering
● No mitotic figures

Micro images
=========================================================================



Lower extremity

Virtual slides
=========================================================================



16 year old girl with calf lesion

Positive stains
=========================================================================

● Smooth muscle actin (pleomorphic cells)

Differential diagnosis
=========================================================================

Angiosarcoma: endothelial cells are atypical, there is frequent multilayering of cells and prominent mitotic activity
Pleomorphic hyalinizing angiectatic tumor: infiltrative lesion of superficial soft tissue of distal extremities; shows heavily hyalinized, fibrin containing vessels, spindled and pleomorphic stromal cells with frequent intranuclear inclusions



Benign vascular tumors

Intravascular papillary endothelial hyperplasia


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Reactive, not neoplastic, representing exuberant organization and recanalization of thrombus
● In normal vessels but also varices, hemorrhoids, pyogenic granulomas, hematomas, angiosarcomas

Terminology
=========================================================================

● Also known as Masson's tumor

Sites
=========================================================================

● Dermis and subcutis of head and neck, lip, tongue, buccal mucosa
● Also seen in heart, larynx and hypopharynx

Clinical features
=========================================================================

Pure type: within a dilated vascular space
Mixed type: with preexisting vascular disorder or in a hematoma
Extravascular form: rare and occurs in extravascular organizing hematoma

Case reports
=========================================================================

● 35 year old man with lesion of the paranasal sinus (Arch Pathol Lab Med 2000;124:1224)
● 39 year old man with painless enlargement of parotid gland (Indian J Pathol Microbiol 2011;54:226)
● 50 year old woman with small bowel lesion (Case Rep Gastroenterol 2010;4:124)
● 70 year old woman with mouth lesion (Case Rep Dermatol 2010;2:22)

Clinical description
=========================================================================

● Usually presents as a red blue nodue in skin

Clinical images
=========================================================================


Leg

Oral mucosa

Gross description
=========================================================================

● Small, firm, red-blue superficial masses in skin

Gross images
=========================================================================



Small bowel

Micro description
=========================================================================

● Intravascular lesion only, with papillary formations with hyaline or fibrous stalks, anastomosing vascular channels, plump endothelial cells; residual organizing thrombi
● No necrosis, no atypia, no atypical mitotic figures

Micro images
=========================================================================



Paranasal sinus lesion


Parotid gland lesion


Oral mucosa

Small bowel

Positive stains
=========================================================================

● Factor VIII, alpha smooth muscle adcin and CD34 in cells lining the papillae
● Occasionally podoplanin and CD105 (J Oral Sci 2011;53:475)

Differential diagnosis
=========================================================================

Angiosarcoma



Normal / benign

Myopericytoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 25 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called perivascular myoid tumor
● Usually adults, 60% male, median age 52 years, youngest case was age 10
● Affects skin (dermis or subcutis) or soft tissues of extremities, rarely head or trunk

Case reports
=========================================================================

● 32 year old woman with multiple lesions of face and parotid gland (Arch Plast Surg 2012;39:158)
● 45 year old woman with painless nodule on leg (Ann Dermatol 2011;23:201)
● 59 year old man with painless mass on nose (Acta Derm Venereol 2010;90:192)

Treatment
=========================================================================

● Excision; only rarely recurs

Gross / clinical images
=========================================================================


Multiple facial masses

Lower leg

Dorsal nose

Micro description
=========================================================================

● Thin walled vessels and concentric, perivascular arrangement of plump spindle to round myoxid cells
● May have hemangiopericytoma-like areas
● Occasional prominent atypia and mitotic activity
● Rarely infiltrative
● No giant cells (Am J Surg Pathol 2006;30:104)
● Rarely has lipomatous component (Cir Esp 2012;90:331)

Micro images
=========================================================================


Oval cells with eosinophilic cytoplasm

Well circumscribed spindle cell tumor

(a) Unencapsulated neoplasm in deep dermis extends into subcutis (arrows); (b) bland round-ovoid cells with concentric perivascular pattern and many thin-walled branching staghorn vessels

Lung tumor: 3A-SMA; 3B-vimentin, 3C-CD34

Positive stains
=========================================================================

● Alpha smooth muscle actin, h-caldesmon
● Rarely focal desmin

Differential diagnosis
=========================================================================

Angioleiomyoma
Myofibroma



Normal / benign

Vascular ectasias


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 26 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also hereditary hemorrhagic telangiectasia, nevus flammeus, port wine stain, spider telangiectasia, telangiectasias

General
=========================================================================

● Localized dilation of preformed vessels



Hereditary hemorrhagic telangiectasia

General
=========================================================================

● Also known as Osler-Rendu-Weber syndrome
● Autosomal dominant disorder in which localized capillary dilation causes arterial blood to be shunted directly into postcapillary venules from birth
● Dilated capillaries and veins are present over skin and mucous membranes of GI, GU, lips, oral cavity, respiratory
● May bleed into gut, nose, urine (Am Fam Physician 2010;82:785)
● Patients have mutations in two transforming growth factor-beta binding proteins including endoglin

Case reports
=========================================================================

● 73 year old woman with purpuric, punctuate, and tiny macules on fingertips and tongue (Ann Dermatol 2009;21:206)

Clinical images
=========================================================================


Fingertips, tongue, stomach

Nasal mucosa

Tongue

Micro images
=========================================================================


Dilated capillaries lined by flat endothelial cells


Nevus flammeus

General
=========================================================================

● Also known as salmon patch
● Ordinary birthmark, usually on head and neck, represents dilated dermal vessels
● Usually regress

Micro images
=========================================================================


Infant

Port-wine stain

General
=========================================================================

● Type of nevus flammeus
● May grow proportionately with the child and thicken the skin surface
● Those in distribution of trigeminal nerve are associated with Sturge-Weber syndrome (encephalotrigeminal angiomatosis), a rare congenital disorder with venous angiomatous masses in leptomeninges over cortex, ipsilateral port-wine nevi, mental retardation, seizures, hemiplegia, skull radiopacities
● Attributed to faulty development of mesodermal and ectodermal elements

Micro images
=========================================================================


Infant

Spider telangiectasia

General
=========================================================================

● Non-neoplastic vascular lesion, composed of radial, pulsatile array of dilated subcutaneous arteries or arterioles around a central core that blanches with pressure applied to its center
● Usually on face, neck, upper chest of pregnant women and patients with cirrhosis
● May be associated with hyperestrinism

Micro images
=========================================================================


Various images

Telangiectasias

General
=========================================================================

● Group of abnormally prominent capillaries, venules and arterioles that creates a small focal red lesion, usually in skin or mucous membranes
● Congenital anomalies or exaggerations of preexisting vessels
● Not true neoplasms



Low / intermediate grade vascular tumors

Giant cell angioblastoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare, congenital/neonatal soft-tissue tumor, infiltrative but slow growing; appears to be benign
● Hand, palate, scalp, rarely bone (Zhonghua Bing Li Xue Za Zhi 2010;39:752, Diagn Pathol 2012 Aug 29;7:113)

Treatment
=========================================================================

● Surgery, interferon-alpha

Clinical images
=========================================================================


Palate

Hand

Gross description
=========================================================================

● Ulcerated tumors infiltrating soft tissue and bone

Micro description
=========================================================================

● Solid, nodular, and plexiform proliferation of oval-spindle cells with striking concentric aggregation around small vascular channels
● Cells resemble undifferentiated mesenchymal cells, fibroblasts, myofibroblasts, pericytes
● Also large mononuclear and multinucleate giant cells with histiocytic features (Am J Surg Pathol 2001;25:185)

Micro images
=========================================================================


Femur

Stains

Positive stains
=========================================================================

● CD68 (large mononuclear and multinucleate giant cells)

Differential diagnosis
=========================================================================

Bacillary angiomatosis: positive special stains for organisms, patients usually immunosuppressed
Epithelioid hemangioendothelioma with osteoclast-like giant cells: Factor 8+ cells that don't resemble oval-spindle cells of giant cell angioblastoma, no concentric aggregation around vessels
Giant cell fibroblastoma: CD34+, molecular rearrangements of #17 and #22
Myopericytoma: older age group, no giant cells
Plexiform fibrohistiocytic tumor: children/young adults, no onion-skin layering of tumor cells around vessels



Low / intermediate grade vascular tumors

Hemangioendothelioma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 25 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See subtypes below: composite, epithelioid / histiocytic, endovascular papillary, kaposiform, polymorphous, retiform, spindle cell

General
=========================================================================

● Intermediate grade vascular tumor with variable histologic features and clinical behavior
● 40% recur, 20% metastasize, 15% die of tumors

Positive stains
=========================================================================

● FLI-1 (nuclear stain, Am J Surg Pathol 2001;25:1061)



Composite hemangioendothelioma

Definition
=========================================================================

● Mixtures of benign, low-grade malignant and malignant vascular components
● Predominant components resemble epithelioid and retiform hemangioendothelioma
● Very rare
● Usually women, median age 43 years, range 22-75 years
● Usually superficial dermis or subcutaneous, usually in hands or feet
● Recur locally, may metastasize, no deaths after median follow-up of 5 years
● Must sample extensively to obtain correct diagnosis

Case reports
=========================================================================

● 50 year old woman with dyspnea and cough (Tumori 2009;95:98)

Treatment
=========================================================================

● Excision, may recur locally, but no/rare metastases (Am J Surg Pathol 2007;31:1567)

Positive stains
=========================================================================

● CD31, CD34, Factor VIII

Additional references
=========================================================================

Am J Surg Pathol 2000;24:352


Epithelioid / histiocytic hemangioendothelioma

General
=========================================================================

● Intermediate grade vascular malignancies closely associated with or arising from a vein in 50% of cases
● Usually adults, 60% women
● Extremities (60%); also head and neck, mediastinum, trunk
● Unpredictable clinical course, but less aggressive than angiosarcoma
● 13% recur, 20-30% metastasize (lung, lymph nodes), 13% die of disease (Am J Surg Pathol 1997;21:363); for lung, mortality is 65%
● High risk (> 3 MF/50 HPF and size > 3 cm) have 5 year disease specific survival of 59% versus 100% for low risk (Am J Surg Pathol 2008;32:924)

Case reports
=========================================================================

● 16 year old girl with painful progressive swelling of lower limb (Indian J Dermatol 2012;57:53)
● 24 year old man with forearm mass (Diagn Pathol 2011;6:120)
● 27 year old woman with lower eyelid mass (Oman J Ophthalmol 2011;4:142)
● 42 year old woman with tumor of sphenoid bone (Neurol India 2012;60:344)
● 55 year old man with thigh mass (Case of the Week #77)

Treatment
=========================================================================

● Low grade tumors: wide local excision
● High grade tumors: radical local excision with possible neck dissection (head & neck tumors)

Clinical images
=========================================================================


Forearm

Lower eyelid

Gross description
=========================================================================

● Variable size, up to 18 cm

Micro description
=========================================================================

● Cords or small nests of round endothelial cells with abundant eosinophilic cytoplasm
● Tumors arising from vessels extend outward from the lumen towards soft tissue
● Tumor cells often have intracytoplasmic vacuoles representing small vascular lumina, which may resemble mucin
● Nuclei are round and may be indented
● Usually minimal mitotic activity, atypia or necrosis, but 25% of cases exhibit frank malignant features of prominent nuclear pleomorphism, mitotic activity, focal spindling or necrosis
● Stroma may be scanty or myxoid
● May have peripheral inflammatory infiltrate with germinal centers and eosinophils, multi-nucleated giant cells

Micro images
=========================================================================

Forearm mass
Spine
Lower eyelid
Sphenoid bone
Case of the Week #77: thigh tumor - H&E and CD31

Cytology description
=========================================================================

● Clusters of polygonal cells with moderate nuclear atypia (J Cytol 2012;29:89)

Cytology images
=========================================================================



Polygonal cells with moderate atypia

Positive stains
=========================================================================

● Vimentin, CD31, von Willebrand factor, keratin (30%, focal), reticulin (nests and cords of cells are invested by a reticulin sheath)

Molecular / cytogenetics description
=========================================================================

● Occasional tumors may demonstrate t(1;3)(p36.3;q25, Am J Surg Pathol 2001;25:684)

Differential diagnosis
=========================================================================

Epithelioid angiosarcoma: irregular sinusoidal vascular channels, solid sheets of cells with marked atypia and prominent mitotic activity, necrosis
Epithelioid sarcoma: distal extremities of young adults, tumor cells merge with collagenous stroma, keratin+ (strong), CD31-
Melanoma: S100+, HMB45+, CD31-
Metastatic carcinoma: more marked atypia, mitotic activity, usually not angiocentric, keratin+, CD31-


Endovascular papillary hemangioendothelioma

General
=========================================================================

● Also known as Dabska's tumor
● Very rare tumor of children in skin or soft tissue
● Good prognosis, with only rare nodal metastases

Case reports
=========================================================================

● 10 month old boy with pain and tender scrotal swelling (Diagn Pathol 2006;1:12)

Gross images
=========================================================================



Testicular tumor

Micro description
=========================================================================

● Papillary tufts lined by plump endothelial cells (epithelioid- or histiocytic-like) within dilated vascular lumina
● May have glomeruloid appearance

Micro images
=========================================================================


Testicular tumor

VEGFR3+

Positive stains
=========================================================================

● Vascular endothelial growth factor receptor 3 (Mod Pathol 2000;13:180), FLI1 (Am J Surg Pathol 2001;25:1061)


Kaposiform hemangioendothelioma

General
=========================================================================

● Rare, locally aggressive; tumor of infants and children; affects skin (75%), retroperitoneum (18%), bone
● Death due to extensive disease and severe coagulopathy (Kasabach-Merritt syndrome), although no metastatic potential (Mod Pathol 2001;14:1087)
● Usually initial tumor is cutaneous

Case reports
=========================================================================

● 2 year old boy with tonsillar mass (World J Surg Oncol 2011;9:57)

Clinical images
=========================================================================



2 year old boy with tonsillar mass

Micro description
=========================================================================

● Infiltrating nodules and sheets of compact spindle cells with slit-like lumina

Micro images
=========================================================================

Glomeruloid nests of spindled and epithelioid cells
"Cannon ball" appearance
Slit-like lumens
VEGFR3+
Various images
Tonsillar mass

Positive stains
=========================================================================

● Vascular endothelial growth factor receptor-3 (Mod Pathol 2000;13:180)

Differential diagnosis
=========================================================================

Kaposi's sarcoma


Polymorphous hemangioendothelioma

General
=========================================================================

● <10 cases reported
● Lymph nodes and soft tissue
● Recurs locally, rare metastases

Micro description
=========================================================================

● Combinations of solid, primitive vascular and angiomatous patterns
● Uniform cytologic features
● No epithelioid, spindle cell or angiosarcoma-like areas

Micro images
=========================================================================



Patterns in same tumor
Left: kaposiform pattern with extravasated red blood cells and blood cells within neolumina; mild atypia, no mitotic activity
Middle: epithelioid (lower right) and spindle patterns (upper left) with intracytoplasmic vacuoles containing erythrocytes
Right: CD34+



Typical mixed solid and angiomatous features


Retiform hemangioendothelioma

General
=========================================================================

● Low grade variant of angiosarcoma
● Usually distal extremities of young individuals
● Weiss and Goldblum use term “hobnail hemangioendothelioma” for retiform and Dabska-type tumors, which they believe to be closely related
● Rarely multiple (Am J Dermatopathol 1996;18:606)
● 2/3 recur, particularly without wide local excision; low rate of metastases, no tumor related deaths

Case reports
=========================================================================

● 20 year old man with mass in middle phalynx of finger (Arch Plast Surg 2012;39:80)
● 37 year old man with skin lesion on back (Case of the Week #107)
● 44 year old man with thigh mass (Sarcoma 2010;2010 pii: 756246)
● 61 year old woman with painful lesion on scalp (Int J Clin Exp Pathol 2010;3:528)

Treatment
=========================================================================

● Wide local excision

Clinical images
=========================================================================

Finger
Scalp

Gross description
=========================================================================

● Lesion of reticular dermis and subcutaneous tissue

Micro description
=========================================================================

● Retiform (net-like, similar to rete testis) pattern of blood vessels that disperse through reticular dermis and subcutis
● Vessels lined by monomorphic hobnail endothelial cells with scant cytoplasm and rounded, naked-type nuclei
● Often prominent lymphocytic infiltrate
● No epithelioid areas or cytoplasmic vacuoles (Am J Surg Pathol 1994;18:115)

Micro images
=========================================================================

Finger
Scalp


Case of Week #107: H&E and CD31

Positive stains
=========================================================================

Endothelial cells: CD34 (strong), CD31, vWF

Negative stains
=========================================================================

Endothelial cells: keratin

Differential diagnosis
=========================================================================

Angiosarcoma: may focally have low grade features, but also exhibits areas of marked atypia and pleomorphism; also dissects between individual collagen bundles and has mitotic activity
Hobnail hemangioma: smaller, more superficial and more localized, with papillary dermal vessels that disappear into reticular dermis


Spindle cell hemangioendothelioma

General
=========================================================================

● Any age, usually males, usually distal extremities
● Low grade lesion which recurs commonly and may be multicentric, but only one reported metastases after repeated recurrence and radiation therapy
● May be a hamartoma due to aberrations in local blood blow; perhaps should be called spindle cell hemangioma
● Associated with Mafucci's syndrome

Case reports
=========================================================================

● 67 year old woman with swelling in temporal region (Case Rep Surg 2011;2011:481654)

Clinical images
=========================================================================


Intramuscular tumor of temporal region

Gross description
=========================================================================

● Dermal or subcutaneous tumor

Micro description
=========================================================================

● Cavernous hemangioma and Kaposi sarcoma like features
● Cavernous spaces with solid areas composed predominantly of bland spindle cells, with a minor component of epithelioid, often vacuolated, endothelial cells, usually associated with irregular fascicles of smooth muscle fibers and adjacent malformed vessels

Micro images
=========================================================================



Intramuscular tumor of temporal region


Various images

Positive stains
=========================================================================

● Endothelial markers



Low / intermediate grade vascular tumors

Kaposi sarcoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 24 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See subtypes below: AIDS-associated, chronic, lymphadenopathic, transplant-associated

General
=========================================================================

● Vascular proliferative disorder mediated by inflammatory cytokines and angiogenic growth factors in patients with HHV8 / Kaposi sarcoma associated herpesvirus infection, influenced by immune status
● May originate from cell type capable of undergoing lymphatic differentiation based on D2-40 staining, a lymphatic specific marker (Mod Pathol 2002;15:434)
● Usually limited to skin; may involve mucus membranes, visceral organs, lymph nodes
● HHV8 also positive in multicentric Castleman’s disease, primary effusion lymphoma, some multiple myeloma

Micro images
=========================================================================


VEGFR3+ (fig C/D)

D2-40+

Positive stains
=========================================================================

● FLI-1 (nuclear stain, Am J Surg Pathol 2001;25:1061), vascular endothelial growth factor receptor-3 (● Mod Pathol 2000;13:180), D2-40, other vascular markers

Differential diagnosis
=========================================================================

Angiosarcoma: may have Kaposi-like features but is HHV8 negative (Arch Pathol Lab Med 2002;126:191)
Kaposiform hemangioendothelioma: may have Kaposi-like features but is HHV8 negative


AIDS associated (epidemic)

General
=========================================================================

● Historically, 40% of homosexual men with AIDS got Kaposi vs. 5% of others with AIDS
● Incidence of Kaposi has been decreasing over time (Arch Pathol Lab Med 2002;126:182)
● Early involvement of lymph nodes and gut and wide dissemination
● Usually not a direct cause of death, although 1/3 develop lymphoma or another second malignancy

Terminology
=========================================================================

Macule / patch:
● Pink-purple macules of lower extremity or feet
● Superficial or mid-dermal proliferation of collagen-dissecting jagged capillary vessels with inconspicuous spindle cell component
● May be confluence of vessels

Plaque:
● Dermal, dilated, jagged vascular channels that dissect collagen fibers and contain isolated or small groups of spindle cells
● Red blood cell extravasation prominent
● Also hemosiderin laden macrophages, pink hyaline globules

Nodule / tumor:
● More distinctly neoplastic, most of lesion composed of spindle cells with intersecting fascicle like pattern in a background of inflammatory cells and red blood cells
● Small vessels and slitlike spaces with hyaline droplets and rows of red blood cells
● Mitotic figures common
● May involve lymph nodes and viscera (African and AIDS variants)

Clinical images
=========================================================================


Rapidly growing nodule

Various images

Gross description
=========================================================================

Indolent disease has 3 stages:
● Early - macule/patch
● Intermediate - plaque
● Late - nodule/tumor

Micro description
=========================================================================

● Dilated irregular blood vessels in background of lymphocytes, plasma cells, macrophages
● Resembles granulation tissue
● Disease spreads proximally, converts to raised

Micro images
=========================================================================



Various stains

Positive stains
=========================================================================

● Smooth muscle actin, D2-40 (Mod Pathol 2002;15:434), other vascular markers

Negative stains
=========================================================================

● Factor 8

Molecular / cytogenetics description
=========================================================================

● Detect HHV8 by PCR or in-situ hybridization


Chronic / classic

General
=========================================================================

● Classic type seen in Europeans
● Described by Kaposi in 1872
● 90% occur in older men from Eastern Europe, often Ashkenazic Jews; rare in US
● Associated with second malignant tumor or altered immune state, but not with HIV
● Multiple red-purple skin plaques or nodules in distal lower extremity, slowing increasing in size and spreading proximally
● Locally persistent with remission and relapses, but usually stay localized to skin

Case reports
=========================================================================

● 11 year old boy with maculopapular and nodular lesions on dorsum of hands and feet (Indian J Dermatol Venereol Leprol 2011;77:730)
● 74 year old man with multiple, small, violaceous papules and nodules on trunk and extremities (J Dermatol Case Rep 2012;6:52)
● 82 year old man with painful purple lesions on palms that worsened with cold (Dermatol Online J 2011;17:16)
● 86 year old Mediterranean man with asymptomatic lesions on legs (CMAJ 2011;183:E1040)

Clinical images
=========================================================================

11 year old boy
74 year old man
82 year old man
86 year old man

Micro images
=========================================================================


Various images

11 year old boy

74 year old man

Figure 3a

Figure 3b

Figure 3c

Figure 3d
Dermis is packed by fusiform cellular proliferation with some hyaline globules (Fig 3a and 3c), with areas of irregular cleft-like vascular channels lined by plump, slightly atypical and hyperchromatic endothelial cells (Fig 3b). Cells were HHV8+ (Fig 3d)


Lymphadenopathic

General
=========================================================================

● Also known as African endemic
● Occurs in young Bantu children in South Africa (same population gets Burkitt lymphoma)
● Presents with localized or systemic lymphadenopathy
● Extremely aggressive disease; rarely is restricted just to lymph nodes; skin involvement is unusual


Transplant-associated

General
=========================================================================

● Occurs months to years after high-dose immunosuppressive therapy; 0.2-1.0% of kidney transplants
● Skin or metastatic lesions present
● Skin lesions may regress if immunosuppression is stopped
● Usually fatal if spreads to viscera

Case reports
=========================================================================

● 38 year old woman with purple lesion on leg (Saudi J Kidney Dis Transpl 2010;21:306)
● 40 year old man with severe hoarseness due to laryngeal involvement (Iran J Kidney Dis 2012;6:222)
● 49 year old man with ureteric lesion (Exp Clin Transplant 2012;10:70)

Micro images
=========================================================================



49 year old man with ureteric lesion




High grade vascular lesions
Angiosarcoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 14 May 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Sites
=========================================================================

Breast:
Extremities:
Kidney:
Liver:
Lung:
Skin:
Spleen:
Other sites:
Case reports
=========================================================================
Treatment
=========================================================================
Clinical images
=========================================================================
Elbow
Foot
69 year old man with raised lesion on nose
Nose
Gross description
=========================================================================
Gross images
=========================================================================
Ovary
Spleen
Thyroid
Micro description
=========================================================================
Micro images
=========================================================================
Breast
Lung: metastatic tumor
Lung: metastatic tumor
Nose
Ovary
Site unknown
Skin (image on right is epithelioid)
Spleen
Thyroid gland

Cytology images
=========================================================================
Kidney
Positive stains
=========================================================================
Molecular / cytogenetics description
=========================================================================
Differential diagnosis
=========================================================================


High grade vascular lesions
Intimal sarcoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 19 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Case reports
=========================================================================
Gross images
=========================================================================
80 year old man with multiple splenic infarcts
Left two images are from abdominal aorta
Micro description
=========================================================================
Micro images
=========================================================================
80 year old man with multiple splenic infarcts
Causing aortic rupture
Case reports
=========================================================================


Lymphangioma - general


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 17 November 2014, last major update November 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

See also subtypes: cystic, lymphangiomatosis, lymphangiomatous papules/plaques post-radiation

Definition
=========================================================================

● May represent malformations due to failure of lymphatics to communicate with venous system
● Most described cases are cystic / cavernous
● Skin tumors are called lymphangioma circumscriptum

Clinical features
=========================================================================

● Benign
● See also discussion in these chapters: bone, breast, kidney tumor, lymph nodes, mediastinum, skin-nonmelanocytic tumors, skin-nontumor, spleen

Case reports
=========================================================================

● 13 year old girl with isolated laryngeal lymphangioma (Indian J Otolaryngol Head Neck Surg 2011;63:90)
● 35 year old pregnant woman with large cystic tumor in fetal chest (Ultrasound Obstet Gynecol 2008;31:697)
● 58 year old man with conjunctival lymphangioma (Case Rep Ophthalmol Med 2012;2012:836573)
● Secondary lymphangiomas of vulva (Indian J Dermatol 2012;57:149)

Treatment
=========================================================================

● Excision if possible (Lymphology 2006;39:147); also sclerotherapy or observation
● Recurrence is minimized by complete excision (Mayo Clin Proc 2006;81:1197)
● Intralesional bleomycin therapy may be an effective alternative to surgery (J Maxillofac Oral Surg 2011;10:152)

Clinical images
=========================================================================


Conjunctiva

Larynx

Micro description
=========================================================================

● Large lymphatic channels in loose connective tissue stroma
● Focally disorganized smooth muscle in wall of larger channels
● Peripheral lymphoid aggregates
● Often increased mast cells (Mod Pathol 1999;12:569)

Micro images
=========================================================================


Conjunctiva

Foot

Larynx

Pleura

Retroperitoneum

Vulva

Positive stains
=========================================================================

● CD31, CD34, D2-40 (Pediatr Dev Pathol 2005;8:181); patchy Factor VIII (Am J Clin Pathol 1981;75:167)
● Also CK7 (Hum Pathol 2000;31:1062)

Negative stains
=========================================================================

● Ki-67 (or low, Arch Pathol Lab Med 1997;121:1055)

Electron microscopy description
=========================================================================

● Poorly developed and discontinuous basal lamina; presence of anchoring fibrils (Arch Pathol Lab Med 1980;104:316)

Additional references
=========================================================================

Wikipedia, eMedicine

End of Soft tissue tumors > Lymphangioma - general



Lymphangioma

Cystic / cavernous lymphangioma (cystic hygroma)


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 26 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Large, irregular vascular spaces (similar to cavernous hemangioma, may resemble cysts) lined by flattened, bland epithelial cells
● Cystic and cavernous lymphangiomas are usually considered the same entity (eMedicine)

Clinical features
=========================================================================

● In children, usually in neck or axilla; may extend into mediastinum
● Large mediastinal lesions may compress lungs, heart and nerves, but most lesions are asymptomatic and found on Xray
● Rarely occur in lymph nodes (Am J Surg Pathol 1992;16:335)

Case reports
=========================================================================

● 1 year old boy with giant mesenteric tumor (Can J Surg 2009;52:E42)
● 3 year old boy with scrotal tumor with hemorrhage (Afr J Paediatr Surg 2009;6:110)
● 4 year old girl with 30 cm omental tumor (BMC Surg 2006 Dec 27;6:18)
● 7 year old boy with thigh tumor (Indian J Surg 2010;72:417)
● 12 year old girl with giant cystic lymphangioma of mesentery (Pan Afr Med J 2012;12:7)
● 12 year old girl with giant cystic lymphangioma of small bowel mesentery (Pan Afr Med J 2011;9:46)
● 25 year old woman with huge cystic lymphangioma mimicking ovarian malignancy (Turk J Gastroenterol 2011;22:344)
● 34 year old woman with cystic pancreatic lymphangioma (Rare Tumors 2012;4:e27)
● 38 year old woman with breast tumor (World J Surg Oncol 2007;5:69)
● 46 year old man with 44 cm abdominal mass (Arch Pathol Lab Med 2000;124:1723)
● 50 year old man with mediastinal tumor (J Bras Pneumol 2008;34:982)
● 70 year old woman with 19 kg tumor of broad ligament (J Med Case Rep 2008;2:310)

Treatment and prognosis
=========================================================================

● Complete surgical excision is recommended to prevent recurrence
● May cause fetal death due to hydrops
● Intra-uterine sclerosing agents may reduce respiratory and feeding problems associated with fetal neck tumors (Fetal Diagn Ther 2009;26:102)
● Rarely may spontaneously regress

Clinical images
=========================================================================



Omentum: 30 cm tumor in 4 year old girl


Scrotal tumor with hemorrhage in 3 year old boy


Abdominal cyst: 25 cm

Broad ligament: 19 kg tumor in 70 year old woman

Mesentery: 1 year old boy


Mesenteric tumors


Thigh tumor

Mesenteric tumor: 12 year old girl

Gross description
=========================================================================

● May be massive
● Gray-white, edematous appearing
● Variable sized cystic cavities with serous type fluid and smooth inner lining

Micro description
=========================================================================

● Large, irregular vascular spaces lined by flattened, bland epithelial cells with fibroblastic or collagenous stroma
● Stroma may contain lymphocytes
● Abdominal tumors may have marked inflammatory changes that obscure their lymphatic origin (Hum Pathol 2005;36:426)
● Rarely has papillary endothelial proliferation (Arch Pathol Lab Med 1979;103:306)
● No specialized epithelium, no cholesterol granulomas
● Not encapsulated, so removal can be difficult

Micro images
=========================================================================


Omentum

Pancreas

Abdominal mass

Mediastinal tumor

Mesenteric tumor

Adrenal gland: H&E and CD31

Broad ligament: H&E and D2-40

Breast tumor

Factor VIII

AFIP Third Series


Orbital tumor has large dilated lymphatics, some with blood

Numerous lymphatics, some with blood; lymphocytes between lymphatics

Videos
=========================================================================



Neck tumor

Molecular / cytogenetics description
=========================================================================

● Associated with Turner’s syndrome (Hum Pathol 1984;15:61) or other chromosomal abnormalities



Lymphangioma

Lymphangiomatous papules / plaques, post-radiation


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 26 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Due to obstruction/destruction of lymphatic drainage, often post-radiation therapy (Histopathology 1999;35:319) or idiopathic in elderly

Terminology
=========================================================================

● In breast, often called lymphangioma circumscriptum, although the classic lesion of lymphangioma circumscriptum appears at birth or in the early years, and most breast cases are actually post-surgery or radiation therapy within the field of radiation (Am J Clin Pathol 1994;102:757)

Epidemiology
=========================================================================

● In women, age 33-72 years
● Arises 3-20 years after radiation therapy for breast (93%) or ovarian (7%) carcinoma
● Associated with pain, chronic drainage, cellulitis (South Med J 1999;92:69)

Clinical features
=========================================================================

● Multiple papules, small vesicles or erythematous plaques in irradiated field
● Usually benign behavior (Cancer 2007;109:1584, Am J Surg Pathol 2005;29:983), but vascular type may progress to angiosarcoma (Am J Surg Pathol 2008;32:943)

Case reports
=========================================================================

● 39 year old woman with enlarging erythema and blisters on axilla (Indian J Dermatol Venereol Leprol 2012;78:121)
● 40 year old woman with multiple vesicles (The Internet Journal of Dermatology 2006;3(2))
● 48 year old woman with acquired progressive lymphangioma of skin following radiotherapy for breast carcinoma (J Cutan Pathol 1995;22:164)
● 50 year old woman with inguinal papules post radiotherapy for uterine rhabdomyosarcoma (Acta Dermatovenerol Alp Panonica Adriat 2009;18:24)
● 68 year old woman with multiple small vesicular lesions on breast (Dermatol Online J 2004;10:9)
● 72 year old woman with lesions associated with ovarian fibroma (J Am Acad Dermatol 2007;56:S41)
● Asymptomatic vesicular eruption on the chest (Arch Dermatol 2011;147:1443)

Treatment
=========================================================================

● Cryosurgery, electrocautery or laser therapy to vaporize surface lymphatics (Dermatol Surg 1998;24:893); frequently recurs and causes substantial morbidity so must monitor for recurrence

Clinical images
=========================================================================


3Axilla and shoulder lesions

Breast: multiple small vesicles

Breast: multiple vesicles of lymphangioma circumscriptum

Chest: asymptomatic vesicular eruption

Scrotum: vesicular rash

Gross description
=========================================================================

● One or more circumscribed papules, small vesicles or erythematous plaques, usually in irradiated field, median 0.5 cm
● Frequently multiple synchronous lesions with discoloration

Micro description
=========================================================================

● Irregular dilated vascular spaces with branching and anastomosing pattern in superficial and deep dermis
● Thin walls, lymphatic appearance
● Vascular channels lined by single discontinuous layer of endothelial cells with numerous small stromal papillary formations and flattened nuclei; also lined by endothelial cells projecting into lumina (lymphatic counterpart of intravascular papillary endothelial hyperplasia / Masson’s tumor)
● May have poorly circumscribed and focally infiltrating irregular jagged vascular spaces involving the entire dermis, lined by inconspicuous endothelial cells, dissecting collagen bundles of the dermis, and mimicking Kaposi's sarcoma (Am J Surg Pathol 2002;26:328)
● No necrosis, no mitotic figures, no blood lakes

Lymphatic type: predominantly thin walled, variably anastomosing lymphatics primarily in superficial dermis
Vascular type: predominantly small, irregularly dispersed, capillary type vessels, invested by pericytes, often blood filled, in superficial or deep dermis; associated with extravasated red blood cells or hemosiderin, minor lymphatic type component

Micro images
=========================================================================


Figures 1 and 2: benign lymphangio- endothelioma- like lesions

Figures 3 and 4: superficial lymphangioma- like patterns

Figure 5: mixed histologic patterns

Figure 6 and 7: nuclear hyperchromasia and prominent papillary projections

Figure 8: D2-40+ lymphangioma-like lesion

Breast: ectatic lymphatic spaces in papillary dermis

Chest: asymptomatic vesicular eruption #1

#2

Positive stains
=========================================================================

● CD31; D2-40 (40%)

Negative stains
=========================================================================

● CD34 (or focally positive), smooth muscle actin (no peripheral ring of stain characteristic of pericytes)
● Ki-67

Electron microscopy description
=========================================================================

● Endothelial cells have cytoplasmic microfilaments and pinocytotic vesicles; intermediate junctions are present between adjacent cells (Jpn J Clin Oncol 1991;21:129)

Differential diagnosis
=========================================================================

Angiosarcoma-well differentiated: may be part of morphologic continuum with atypical vascular lesions (J Am Acad Dermatol 2007;57:126)
● Hobnail hemangioma
Kaposi sarcoma: lymphangioma-like variant is HHV8+, not related to radiation therapy
Lymphangioendothelioma



Lymphangioma

Lymphangiomatosis


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 26 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Diffuse / multicentric lymphangiomas, often in thoracic cavity, also bone, extremities, soft tissue, viscera
● See also Lung tumor chapter

Clinical features
=========================================================================

● Rare, idiopathic, occurs mostly in children
● Cases with visceral involvement are often fatal (Am J Surg Pathol 1993;17:329), but cases involving limbs have good prognosis (Am J Surg Pathol 1995;19:125)
● Associated with kaposiform hemangioendothelioma (Am J Surg Pathol 1993;17:321), bony lytic lesions and chylothorax (J Pediatr Hematol Oncol 2008;30:66), total cavo-pulmonary connection for complex congenital heart disease (Pediatr Cardiol 2008;29:771)

Diffuse retroperitoneal cystic abdominal lymphangiomatosis: attributed to congenital malformation of lymphatic ducts; distribution often corresponds to primitive fetal lymphatic sacs; either capillary, cavernous or cystic; may have multisystem involvement involving bone, brain, extremities, liver, pancreas, soft tissue, spleen (Acta Cytol 2009;53:191)
Gorham’s disease: diffuse lymphangiomatosis also involving bony tissue

Case reports
=========================================================================

● 15 year old girl with perinephric lymphangiomatosis (Indian J Radiol Imaging 2010;20:224)
● 25 year old woman, with acute presentation of colonic lymphangiomatosis (Int J Surg Case Rep 2012;3:158)
● 25 year old woman with colonic lymphangiomatosis mimicking acute appendicitis (Indian J Cancer 2011;48:139)
● 33 year old woman with fatal case (Am J Med Sci 2008;336:445)
● 39 year old healthy man with recurrent, complicated scrotal lymphangiomatosis (Can Urol Assoc J 2012;6:E11)
● 71 year old man with mesenteric lymphangiomatosis (World J Gastroenterol 2009;15:3947)

Treatment
=========================================================================

● Excision if symptomatic

Clinical images
=========================================================================


Colonic

Scrotal

Gross images
=========================================================================


Colon

Omentum

Spleen

Micro description
=========================================================================

● Increase in size and number of thin walled channels
● Lymphatic spaces are interconnecting and dilated, lined by a single attenuated layer of endothelial cells involving the dermis, subcutis, and occasionally underlying fascia and skeletal muscle

Micro images
=========================================================================


Colon: dilated lymphatic channels

colon

colon

lung: H&E and CD31

mesenteric

spleen

Positive stains
=========================================================================

● CD31, Factor VIII, D2-40



Lymphangioma

Lymphangioendothelioma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 26 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Proliferation of D2-40+ endothelial cells
● Uncommon benign vascular lesion that may mimic well differentiated angiosarcoma or patch-stage Kaposi's sarcoma (Am J Surg Pathol 2000;24:1047)

Terminology
=========================================================================

● Also called acquired progressive lymphangioma

Epidemiology
=========================================================================

● Rare
● No gender preference, median age 54 years, range 17-90 years
● Usually not associated with other vascular anomalies or HIV infection

Clinical description
=========================================================================

● Solitary red or bruise-like slow growing plaque present for median 5.5 years
● Often in head and neck, but variable sites
● May resemble actinic keratosis (Cutis 2001;67:29)

Case reports
=========================================================================

● 26 year old woman with two year history of thigh lesion (Univ Pittsburgh Case #134)
● 32 year old man with a lesion in the hypogastric lesion (Actas Dermosifiliogr 2010;101:792)
● 75 year old man with giant lesion (J Cutan Pathol 2012;39:950)

Treatment and prognosis
=========================================================================

● Benign
● Occasional local recurrence

Clinical images
=========================================================================


Arm

Erythematous nodule

Hypogastrium (lower abdomen)

Thigh

Toe

Gross description
=========================================================================

● Median 1.5 cm, range 0.3 cm to 10 cm

Micro description
=========================================================================

● Delicate, thin-walled, endothelium-lined dilated vascular spaces involving the superficial dermis
● Intravascular papillary stromal projections resembles papillary endothelial hyperplasia
● Deeper portion of lesions have vascular space collapse and dissect collagen bundles, mimicking patch-stage Kaposi's sarcoma
● Preexisting vessels and adnexal structures of the dermis also appear dissected by newly formed vascular channels
● Smooth muscle often focally present around vascular spaces
● Endothelial cells may hobnail, may form morula resembling giant cells
● Crowding of endothelial cells present, but no endothelial atypia
● Vascular spaces lack erythrocytes and hemosiderin deposits
● No mitotic figures

Micro images
=========================================================================


Hypogastrium

Thigh

Toe

Lymphatic endothelium is podoplanin+

Site unspecified

Positive stains
=========================================================================

● CD31, CD34, Factor VIII, podoplanin, smooth muscle actin

Negative stains
=========================================================================

● HHV8

Differential diagnosis
=========================================================================

Atypical or benign vascular proliferations of breast: history of radiation therapy
Kaposi sarcoma: patch stage usually has widespread multiple lesions in HIV+ patients or extensive lesion of lower extremities in elderly patients of Jewish or Mediterranean origin; usually lymphoplasmacytic infiltrate, with inflammatory cells aggregating around vessels, commonly extravasated red blood cells, often other forms of Kaposi’s sarcoma present
Lymphangioma circumscriptum
Angiosarcoma-well differentiated: elderly patients, red-blue plaques or nodules, more endothelial atypia, multilayering and micropapillary tufting, often epithelioid or spindle cell component, inflammatory response common (Am J Dermatopathol 2000;22:151)

Additional references
=========================================================================

eMedicine



Lymphangioma

Lymphangiomyoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 25 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Benign, most commonly in women, very rarely males
● Formerly known as lymphangiopericytoma
● Localized form present in mediastinum and retroperitoneum, associated with thoracic duct, causes chylothorax, chylous ascities, chyluria, rarely chylopericardium (Korean J Thorac Cardiovasc Surg 2011;44:377)
● Rarely found in kidney as a multiloculated mass (AJR Am J Roentgenol 1989;152:307)
● Diffuse form is lymphangioleiomyomatosis

Case reports
=========================================================================

● 26 year old woman with painless shoulder mass (Acta Orthop Belg 2008;74:114)

Treatment
=========================================================================

● Progesterone, oophorectomy

Micro description
=========================================================================

● Proliferation of intermingled blood vessels and smooth muscle
● Tumor cells plumper and paler than leiomyoma

Micro images
=========================================================================



Slit-like vascular spaces and lymphoid tissue

Positive stains
=========================================================================

● Actin, desmin, HMB45

Differential diagnosis
=========================================================================

Angioleiomyoma



Lymphangioma

Lymphangiosarcoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 25 February 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Typically ~10 years post-axillary nodal dissection or radiation therapy for breast cancer with long-standing massive lymphedema
● Also after chronic lymphedema of lower leg
● 5 year survival < 10%

Case reports
=========================================================================

● 42 year old man with lymphangiosarcoma of pubic region arising in congenital non-hereditary lymphedema (Eur J Dermatol 1998;8:511)
● 74 year old woman with arm tumor 16 years after mastectomy (Cases J 2009 Sep 1;2:6887)
● 90 year old man with fatal lymphangiosarcoma on neck (Acta Derm Venereol 2009;89:318)

Clinical images
=========================================================================


Neck plaque

Arm

Arm

Gross description
=========================================================================

● Blue/purple papules in edematous skin, often multiple

Micro description
=========================================================================

● Angiosarcoma-like areas and endothelium-lined spaces without red blood cells
● Early: resembles benign collection of vessels, call "atypical vascular proliferation"
● Later: freely anastomosing vascular channels lined by atypical endothelial cells, often with solid areas resembling breast carcinoma
● Increased cellularity and pleomorphism with increased mitotic activity

Micro images
=========================================================================


Spindle cell proliferation with occasional intracytoplasmic vascular lumina

Atypical mitotic figures

CD31+

Various images


Thin walled vascular channels lined by endothelial cells are CD31+

Positive stains
=========================================================================

● D2-40

Differential diagnosis
=========================================================================

Angiosarcoma



Other tumors
Alveolar soft part sarcoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 10 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Clinical images
=========================================================================
Orbital tumor
Tongue
Nose and thigh
Gross description
=========================================================================
Gross images
=========================================================================
Deep soft tissue
Micro description
=========================================================================
Micro images
=========================================================================
Various images
Tongue
Lobular structure
Thigh mass
Tongue tumor
Case of the Week #222:
MyoD1
PAS-D
TFE3
Vimentin
Cytology description
=========================================================================
Cytology images
=========================================================================
Figures 1-6
Metastatic renal cell carcinoma
Positive stains
=========================================================================
Electron microscopy description
=========================================================================
Molecular description
=========================================================================


Other tumors
Clear cell sarcoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 10 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Clinical images
=========================================================================
Arm
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Various images
Arm
Foot tumor
Lower leg tumor
Spindled and epithelioid cells
Microphthalmia transcription factor
Cytology description
=========================================================================
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Molecular / cytogenetics description
=========================================================================
Molecular / cytogenetics images
=========================================================================
FISH
Differential diagnosis
=========================================================================


Other tumors
Desmoplastic small round cell tumor

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 10 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Case reports
=========================================================================
Gross / clinical images
=========================================================================
Greater omentum
Pancreas
Site unknown
Stomach
Micro description
=========================================================================
Micro images
=========================================================================
Abdominal tumor
Lung tumor
Pancreas
Stomach
Various images of unknown origin
Positive stains
=========================================================================
Molecular / cytogenetics description
=========================================================================


Other tumors
Epithelioid sarcoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 10 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See subtypes below: cutaneous, proximal type

General
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Clinical images
=========================================================================
Foot
Micro description
=========================================================================
Micro images
=========================================================================
Site unknown
Forearm
Cyclin D1+
keratin+, IN1-
Rhabdoid cells
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Molecular / cytogenetics description
=========================================================================
Differential diagnosis
=========================================================================


Cutaneous
General
=========================================================================
Clinical images
=========================================================================
Foot
Hand
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
4A-vimentin, 4B-EMA
Forearm
Positive stains
=========================================================================
Negative stains
=========================================================================
Differential diagnosis
=========================================================================


Proximal type
General
=========================================================================
Case reports
=========================================================================
Gross images
=========================================================================

Pubic tumor with ill defined multinodular masses
Micro description
=========================================================================
Micro images
=========================================================================
Perineal soft tissue mass
Chest wall
Back
Perineum
Keratin, CD34, neurofilament and p53
Case of the Week #69:
Large areas of necrosis
Infiltrative margins
Granuloma-like areas
Rhabdoid-like cells
EMA
CD34
PLAP negative
Positive stains
=========================================================================
Negative stains
=========================================================================
Differential diagnosis
=========================================================================


Other tumors
Granular cell tumor

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 10 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Gross / clinical images
=========================================================================
Chest wall
Tongue nodule
Forearm
Micro description
=========================================================================
Micro images
=========================================================================
Various images
Erythematous lesion on forearm
Orbit
Chest wall
Tongue nodule
Scrotum
Cytology images
=========================================================================
Forearm
Positive stains
=========================================================================
Electron microscopy description
=========================================================================


Other tumors
Metastases to soft tissue

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 11 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================


Other tumors
Myoepithelial carcinoma of soft tissue

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 11 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================
Epidemiology
=========================================================================
Sites
=========================================================================
Case reports
=========================================================================
Treatment and prognosis
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Various images
p63
Positive stains
=========================================================================
Molecular / cytogenetics description
=========================================================================
Molecular / cytogenetics images
=========================================================================
FISH
Differential diagnosis
=========================================================================


Other tumors
Myospherulosis

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 11 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================
History / etiology
=========================================================================
Etiology
=========================================================================
Clinical features
=========================================================================
Case reports
=========================================================================
Treatment and prognosis
=========================================================================
Gross description
=========================================================================
Gross / clinical images
=========================================================================
Buttock tumor
Large gluteal mass
Micro description
=========================================================================
Micro images
=========================================================================
Gluteal mass
Case of the Week #173:
Buttock tumor
Negative stains
=========================================================================


Other tumors
Myxoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 13 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See subtypes below: cardiac, Carney complex, fibromyxoma, intramuscular, jaw, Mazabraud syndrome, superficial acral fibromyxoma

General
=========================================================================
Sites
=========================================================================
Clinical description
=========================================================================
Diagnosis
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Periocular
Mandibular
Maxillary
Site unknown
Cytology description
=========================================================================
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Electron microscopy images
=========================================================================
Conjunctival myxoma: cell has infolding of nuclear membrane, forming membrane bound vacuoles (v);
nuclei has 2 nucleoli; prominent rough endoplasmic reticulum is in lower left; inset-membranous vacuole
Molecular / cytogenetics description
=========================================================================
Differential diagnosis
=========================================================================


Cardiac myxoma

See also Heart tumor chapter

General
=========================================================================
Case reports
=========================================================================
Gross / clinical images
=========================================================================
Atrial myxoma
Mitral valve mxyoma
Atrial myxoma
Micro images
=========================================================================
Myxomatous stroma
Anterior mitral valve leaflet
Myxomatous embolus


Carney complex associated
General
=========================================================================
Case reports
=========================================================================
Gross / clinical images
=========================================================================
Roof of atrium
Cardiac myxoma


Fibromyxomas
General
=========================================================================


Intramuscular myxoma
General
=========================================================================
Case reports
=========================================================================
Gross images
=========================================================================
Intramuscular myxoma
Gluteal tumor
Micro description
=========================================================================
Micro images
=========================================================================
Cellular tumor
Intramuscular tumors
Molecular / cytogenetics description
=========================================================================
Differential diagnosis
=========================================================================


Jaw myxomas
General
=========================================================================
Gross images
=========================================================================
Jaw tumor
Micro images
=========================================================================
Bland stellate cells in myxoid stroma


Mazabraud syndrome associated
General
=========================================================================
Case reports
=========================================================================
Micro images
=========================================================================
Femur and tibia


Superficial acral fibromyxoma
General
=========================================================================
Case reports
=========================================================================
Gross / clinical images
=========================================================================
Index finger
Micro images
=========================================================================
Index finger
Lobular spindle cell tumor with fascicular growth pattern, moderately cellular, fills dermis
Spindle and stellate cells arranged in loose storiform pattern embedded in myxocollagenous stroma
CD10 staining in neoplastic cells



Other tumors
Rhabdoid tumor

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 11 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Vulvar tumor (loss of INI1, ER+)
Lung tumor
Cytology images
=========================================================================
Abdominal mass
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Molecular / cytogenetics description
=========================================================================


Other tumors
Sinus histiocytosis with massive lymphadenopathy

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 11 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Case reports
=========================================================================
Gross images
=========================================================================
Thigh lesion
Micro description
=========================================================================
Micro images
=========================================================================
Cervical lymph node
Extranodal:
Subcutaneous right thigh
CD68
S100
Cytology images
=========================================================================
Cervical lymph node
Positive stains
=========================================================================
Differential diagnosis
=========================================================================


Other tumors
Synovial sarcoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 11 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See subtype below: calcifying

General
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Gross description
=========================================================================
Gross / clinical images
=========================================================================
14 cm mediastinal mass
Buttock mass
Mandibular region
Micro description
=========================================================================
Micro images
=========================================================================
Low power
High power
Cytokeratin
Vimentin
Forearm lesion
Biphasic vs monophasic
Hand between 2nd and 3rd metacarpus
Supraareolar region of breast
Mandibular region
Buttock mass
Various images
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Molecular / cytogenetics description
=========================================================================
Molecular / cytogenetics images
=========================================================================

SYT-SSX, SYT-SSX1, and SYT-SSX2
Differential diagnosis
=========================================================================


Calcifying synovial sarcoma
General
=========================================================================
Prognostic factors
=========================================================================


Other tumors
Teratoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 11 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

End of Soft Tissue > Superpage 4


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