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Soft Tissue

Superpage 3

Revised: 16 December 2014
Copyright: (c) 2001-2014, PathologyOutlines.com, Inc.

Fibrohistiocytic Tumors

Benign fibrous histiocytoma (superficial)


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

See also deep benign fibrous histiocytoma

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

● Storiform pattern of bland spindle cells and foamy histiocytes centered in dermis with possible extension to subcutis
● Variable hemosiderin, multinucleated giant cells, chronic inflammatory cells and pseudoepitheliomatous hyperplasia

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

● Also called dermatofibroma (particularly if sclerotic and hypocellular), dermal fibrous histiocytoma, sclerosing hemangioma, histiocytoma cutis
● Part of WHO classification for skin tumors, not soft tissue tumors
● See also Bone, Eye-Conjunctiva, Eye-Orbit and Heart chapters
● See also variants described separately - aneurysmal, angiomatoid, atypical, cellular, epithelioid, juvenile xanthogranuloma
● Other variants: lipidized, osteoclastic, myxoid, palisading, monster cell

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

● Very common benign, indolent tumor of adults, common site is legs of women 20-50 years old
● Slight female predominance
● May be associated with trauma
● Line of differentiation is uncertain
● Multiple lesions may be associated with immunosuppression (Int J Dermatol 2008;47:723)

Pathophysiology
=========================================================================

● Fibroblasts cause strong expression of keratin 19 by keratinocytes and production of a galectin1 rich extracellular matrix, which may account for pseudoepitheliomatous hyperplasia (J Dermatol Sci 2009;55:18)

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

● Excision; local recurrence is rare even with involved margins
● Rarely is locally aggressive or metastatic (more common for facial lesions, with extension into subcutis)

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

● Tan-brown (also pink-red, flesh colored, rarely blue), firm, mobile, painless papule < 2 cm in dermis
● Size varies slightly with time; rarely > 5 cm and plaque-like (Australas J Dermatol 2008;49:106) or pedunculated (Case Rep Dermatol 2011;3:32)
● Polypoid, flat, dome shaped or depressed
● May dimple upon lateral compression; may have overlying scaling

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



Inward dimpling due to tumor binding to subcutis (arrow); source: UAB


Dimpling when squeezed along its margins; source: UCSF


Polypoid nodule with slim pedicle

Dermoscopy description
=========================================================================

● Wide range of presentations (Arch Dermatol 2008;144:75)
● Pigment network (72%, 3% are atypical), white scar-like patch (57%), different vascular structures (50%), white network (18%)
● May resemble melanoma

Dermoscopy images
=========================================================================



Pseudonetwork present


Central white scar-like patch surrounded by a pigmented network and many brown globules


Different patterns


Various images

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



Various images

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

● Well defined but non-encapsulated
● Overlying epidermis shows pseudoepitheliomatous hyperplasia and hyperpigmentation of basal cell layer
● Grenz zone is usually present
● Storiform pattern of spindled and bland fibroblasts and histiocyte-like cells in mid-dermis and subcutaneous tissue with infiltrative margins but sparing epidermis
● Loose collagenous and rarely myxoid stroma
● Spindle cells have scant cytoplasm, thin elongated nuclei with pointed ends
● Nuclei almost touch each other, unlike smooth muscle lesions
● Also foamy histiocytes with variable hemosiderin (Case Rep Dermatol 2011;3:32), some multinucleated giant cells, branching vessels & chronic inflammatory cells; rarely is marked eosinophilic infiltrate (European Journal of Dermatology 2011;21:138)
● Often Touton giant cells (superficial and filled with hemosiderin), individual hyaline collagen bundles surrounded by tumor cells at periphery
● 2% have 4 or more mitotic figures/10 HPF, but still benign behavior (J Cutan Pathol 2008;35:839)
● See also variants described separately - aneurysmal, angiomatoid, atypical, cellular, epithelioid, juvenile xanthogranuloma
● Rare variants are balloon cell (Am J Dermatopathol 2007;29:197), clear cell, osteoclast like giant cells, signet ring (Am J Dermatopathol 2009;31:84)

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



Tumor is more basophilic than surrounding dermis


Basophilia is due to increased cellularity


Sharp border between tumor and subcutis


Tumor cells are composed of histiocyte-like cells and foam cells


Tumor cells are mostly fibrous in this focus


Fat may be entrapped at edge, but must differentiate from infiltration of DFSP


Randomly arranged foam cells, fibroblasts and histiocyte-like cells; foam cells are somewhat specific for this lesion


Foam cells vary from none (top), mixed (middle) to predominating (bottom)


Less common finding of predominately foam cells and cholesterol clefts


Epithelial hyperplasia-left side shows squamous / basaloid differentiation, right side shows follicular differentiation


Cellularity changes over time from subtle increase in fibroblasts (fig A) to cellular tumor (fig B/C) to sclerotic Lesion (fig D-right side)


Vulvar tumor has uniform spindle cells confined to dermis

       
Various images


H&E and D2-40

Other images: tumor with hyperplastic epithelium #1;   #2;   hyperplastic epidermis and sclerotic stroma #1;   #2;   #3;   foam cells with vacuolated cytoplasm;   fibroblastic cells with vacuolated cytoplasm in collagenous stroma;   spindle cell nodule;   paucicellular dermal tumor;   spindle cells in dense collagenous stroma

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

● Highly variable immunohistochemical profile
● Vimentin, Factor XIIIa, CD34 (only in cellular variant)
● Also tenascin at dermoepidermal junction (Hum Pathol 2001;32:50); variable calponin (65%), actin, desmin, myosin, D2-40 (Mod Pathol 2010;23:434)
● Early lesions are reactive for CD68 (Ann Dermatol 2010;22:333)

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

● CD68, CD34, BCL2, desmin
● Ki-67 < 10% (Arch Pathol Lab Med 2006;130:831)

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

● Often clonal

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

Atypical fibroxanthoma: characteristic gross appearance, storiform pattern not prominent, marked pleomorphism
Dermatofibrosarcoma protuberans: “tight” storiform pattern, infiltrative, more cellular, no foam cells, CD34+
Kaposi’s sarcoma: vascular tumor with red blood cell extravasation
Leiomyoma or leiomyosarcoma: confusion based primarily on variable staining of benign fibrous histiocytoma for muscle markers
Low grade myofibroblastic sarcoma: ill defined fascicles, diffusely infiltrative, desmin+
Malignant fibrous histiocytoma: infiltrative, marked pleomorphism and mitotic activity
Rosai-Dorman disease: CD68+ histiocytes, not storiform



Other tumors of skin

Deep benign fibrous histiocytoma


Reviewers: Christopher Hale, M.D., Vijay Shankar, M.D. (see Reviewers page)
Revised: 23 October 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

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

● Benign fibrous histiocytoma of subcutaneous tissue, deep soft tissue or parenchymal organs, with no dermal involvement (Am J Surg Pathol 1994;18:677, Am J Surg Pathol 1990;14:801, Stanford Medicine)
● Rare painless lesions, <1% of fibrohistiocytic tumors
● Usually adult males > 25 years (range 6-84 years)
● Usually extremities, head and neck, trunk; rarely in deep soft tissue of retroperitoneum, mediastinum or pelvis

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

● Excision
● May recur if incompletely excised, rare metastases (Am J Surg Pathol 2008;32:354)

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

● 25 year old woman with painful foot mass (Ann Dermatol 2011;23:S239)

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



Nodule in arch of foot

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

● Well circumscribed with pseudocapsule, typically 4 cm (range 0.5 to 25 cm), variable hemorrhage

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

● Prominent storiform pattern of uniform spindle cells with ill defined eosinophilic cytoplasm and bland, elongated or plump vesicular nuclei with no atypia
● Often hemangiopericytoma-like vasculature
● Scattered lymphocytes, either multinucleated giant cells, osteoclastic giant cells or foam cells in 59%
● Usually less than 5 mitotic figures/10 HPF
● Stroma is myxoid or hyaline
● Borders are non-infiltrative, with no trapping of fat cells
● Necrosis or angiolymphatic invasion are rare

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



Circumscribed tumor with no trapped fat


Cellular tumor


Tumor with more fibrous stroma


Foam cells help distinguish from DFSP


Focal storiform pattern and cellular uniformity

   
Hemangiopericytoma-like vascular pattern

   
Various images

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

● CD34 (40%), smooth muscle actin (38%)

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

● Keratin, EMA, desmin, S100

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

Dermatofibrosarcoma protuberans: not circumscribed, usually infiltrative borders, “tight” storiform pattern, uniform cellularity, usually no foam cells, not sclerotic, strongly CD34+, Factor XIIIa weak/negative (Semin Cutan Med Surg 1999;18:91, Am J Surg Pathol 1994;18:677)
Nodular fasciitis: loose collagenous stroma, myxoid, mixed inflammatory cells, thin walled blood vessels
Solitary fibrous tumor: patternless (not storiform), alternating hypo- and hypercellular areas, prominent collagen fibers, no histiocytes, strongly CD34+



Fibrohistiocytic tumors

Aneurysmal fibrous histiocytoma


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

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

● Rare variant with dermal spindle cells and lakes of blood, but no endothelium

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

● First described in 1981 (Cancer 1981;47:2053)
● Early lesion also called hemosiderin variant of fibrous histiocytoma
● Similar to sclerosing hemangioma variant of fibrous histiocytoma, which has more prominent capillaries, but differs from lung lesion called sclerosing hemangioma

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

● Usually extremities or trunk; often pigmented, rapid growth and pain (J Clin Pathol 1996;49:313)
● May have history of trauma (J Korean Med Sci 1989;4:159)

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

● 10 year old girl with leukemia (Pediatr Dermatol 2006;23:591)
● 38 year old man with abdominal lesion called hemosiderotic variant (Dermatology 2007;214:82)
● 48 year old woman with recurrent tumor (J Clin Pathol 2004;57:312)

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

● Excision
● Tends to recur if there is incomplete excision
● Rarely metastasizes

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



Exophytic lesion with slight scaling; irregular coloration mimics melanoma


Grayish brown atrophic shiny patch

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

● Blue, black or dark red cystic nodule
● Size varies from 0.5 to 4 cm
● Rarely presents as atrophic patch

Dermoscopy description
=========================================================================

● Multicomponent pattern with central blue/red homogeneous area, white structures, peripheral delicate pigment network and vascular structures (Br J Dermatol 2006;154:244); this pattern also present in some melanomas

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

● Storiform pattern of fibrohistiocytic cells (as in classic fibrous histiocytoma), but many cells are filled with hemosiderin
● Also large cystic spaces filled with blood, but without an endothelial lining
● Bizarre cells often present
● May have hemangiopericytoma-like pattern of cysts
● Periphery may have hyalinized collagen bundles surrounded by tumor cells (Histopathology 1995;26:323)
● Usually epidermal hyperplasia
● May have up to 10 MF/10 HPF

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



Non-endothelial lined clefts or lakes containing blood


Various images


Hemangiopericytoma-like pattern of cysts


Large irregularly shaped cysts resembling HPC


Large amounts of hemosiderin


Hemosiderin with marked sclerosis

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

● Vimentin, Factor XIIIa (in areas without hemosiderin, J Dermatol 2002;29:744)
● Variable NKI-C3 (60%), smooth muscle actin (45%)

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

● CD31, CD34 (confirms that cysts do not contain endothelium), Factor VIIIa, CD68
● Actin, desmin, cytokeratin, Ki67

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

● Hemosiderin containing histiocyte-like cells, fibroblast-like cells and intermediate cells
● No prominent proliferation of endothelial cells (Am J Dermatopathol 1995;17:179)

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

● Single case report of recurrent tumor with t(12;19) (Cancer Genet Cytogenet 2006;164:155)

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

Angiomatoid fibrous histiocytoma: thick pseudocapsule, marked chronic inflammatory infiltrate and cystic areas of hemorrhage
Spindle cell hemangioendothelioma: thick walled muscular blood vessels, organizing thrombi
Angiosarcoma: lined by endothelial cells, variable atypia (APMIS 2006;114:744)
Kaposi’s sarcoma: endothelial lined vessels are present (CD31+, CD34+), KSHV / HHV8+



Fibrohistiocytic tumors

Angiomatoid fibrous histiocytoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 27 October 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

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

● Uncommon variant with thick pseudocapsule, marked chronic inflammatory infiltrate and cystic areas of hemorrhage
● Also called fibrohistiocytic tumor of intermediate malignancy

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

● First described in 1979 (Cancer 1979;44:2147)
● Formerly called angiomatoid malignant fibrous histiocytoma
● May not actually be fibrohistiocytic - Rosai believes origin is vessel related myoid cells with inflammatory features

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

● Teens/young adults, often on extremities in areas of lymphoid tissue (popliteal fossa, decubital fossa) or neck
● Rare in elderly
● Often fever, malaise, anorexia, anemia, paraproteinemia
● Unusual sites: lung, mediastinum, ovary, retroperitoneum, vulva (Mod Pathol 2011;24:1560)

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

● 8 year old boy with pleomorphic scalp tumor with minimal angiomatoid or lymphoid features (J Cutan Pathol 2008;35:855)
● 23 year old woman with spontaneous perforation of hard palate (Oral Maxillofac Surg 2012;16:237)
● 25 year old man with t(12;22) and intracerebral primary (Am J Surg Pathol 2008;32:478)
● 25 year old man with axillary mass (Rare Tumors 2010;2:e20)
● 28 year old woman with leg tumor with cystic structures of sweat duct origin (Pathol Int 2007;57:513)
● 29 year old man with 7 cm swelling in ankle (Case of Week #239)

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

● Excision; may recur locally (10%), distant metastases are rare (1%, Hum Pathol 1999;30:1336)
● Radiotherapy if wide excision margins are not feasible

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



Axillary mass at surgery

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

● Circumscribed, multinodular or multicystic hemorrhagic mass
● Median 2 cm, usually subcutaneous

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

● Thick fibrous pseudocapsule surrounds nodules, sheets, short fascicles or whorls of monomorphic bland spindle to ovoid eosinophilic cells
● Often highly cellular with bland histiocytoid cells and hemorrhagic cyst-like spaces, large aggregates of chronic inflammatory cells at edge of tumor in lymphoid follicles
● May have moderate pleomorphism and mitotic activity
● Rare clear cells, rhabdomyoblast-like cells, myxoid change in stroma (Mod Pathol 2011;24:1560)

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



Resembles out of place lymph node


Chronic inflammatory cells and nodules of cells with round / oval nuclei surround hemorrhagic cystic spaces


Cells surrounding cystic spaces are uniform with round / oval nuclei


Some tumors have moderate pleomorphism


Various images


Mediastinal tumor


H&E and desmin

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

● Histiocyte-like cells in clusters or dispersed
● Eosinophilic mesenchymal fragments in bloody background with lymphocytes
● Tumor cells have moderate pleomorphism with abundant fragile cytoplasm and prominent nucleoli (Diagn Cytopathol 2005;33:116)

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

● Calponin, CD68
● Variable desmin (40-50%), EMA (40%), CD99 (45%), actin (14%)

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

● Factor VIII, CD34, CD31, S100, keratin

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

● Usually t(12;16)(q13;p11) creating ATF1-FUS fusion gene, t(12;22)(q13;q12) creating ATF1-EWSR1 gene, or t(2;22)(q33;q12) creating CREB1-EWSR1 gene (Mod Pathol 2010;23:93, Pathol Oncol Res 2012;18:545, Clin Cancer Res 2007;13:7322, Pediatr Dev Pathol 2009;12:143)
● Note: t(12:22)(q13:q12) also present in GI clear cell sarcoma (Am J Surg Pathol 2008;32:858)

Molecular / cytogenetics images
=========================================================================



FISH


t(12;16) karyotype


Diagram

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

Aneursymal variant of benign fibrous histiocytoma: no thick pseudocapsule, no inflammatory cells, no significant pleomorphism
Angiosarcoma: endothelial tufting present, CD31+, CD34+, desmin-

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

Arch Pathol Lab Med 2008;132:273, Atlas of Genetics and Cytogenetics, Stanford University



Fibrohistiocytic Tumors

Atypical fibrous histiocytoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 16 December 2014, last major update August 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

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

● Cellular, circumscribed dermal lesion of spindled fibroblasts, myofibroblasts, histiocyte-like cells and often giant cells
● Marked nuclear pleomorphism and mitotic figures (often atypical)
● No tumor cell necrosis
● No vascular invasion

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

● Rare variant of cutaneous fibrous histiocytoma
● Also called pseudosarcomatous fibrous histiocytoma or dermatofibroma with monster cells
● Part of WHO classification for skin tumors, not soft tissue tumors
● First described in 1983 (J Cutan Pathol 1983;10:327)

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

● Median age 38 years (range 5-90 years), no gender preference

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

● Solitary lesions usually arise on extremities or trunk (Am J Dermatopathol 1986;8:467)
● Also head and neck, vulva, rarely scrotum

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

● 25 year old woman with recurrent leg lesion (Eur J Dermatol 1998;8:122)
● 62 year old woman with leg lesion (Tokai J Exp Clin Med 2004;29:49)
● 64 year old woman with 3 cm back lesion (Am J Dermatopathol 2002;24:36)
● 79 year old woman with leg lesion (Am J Dermatopathol 1997;19:312)
● 90 year old man with scrotal lesion (Ann Diagn Pathol 2003;7:370)

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

● May be misdiagnosed as sarcoma (Histopathology 1990;17:167)
● Complete excision with negative margins
● Occasional local recurrence (14%) or distant metastasis (Am J Surg Pathol 2002;26:35)

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



Exophytic nodular lesion of abdominal wall

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

● Median 1.5 cm (0.4 to 8 cm), nodular or polypoid

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

● Involvement of dermis and superficial subcutaneous tissue by pleomorphic, plump, spindle or polyhedral cells with large hyperchromatic, irregular or bizarre nuclei
● Background of classic fibrous histiocytoma including epidermal hyperplasia, Grenz zone, spindle cells with storiform pattern and entrapped thick collagen bundles, especially at periphery
● Variable multinucleated giant cells, often with bizarre nuclei (“monster cells”, Am J Dermatopathol 1987;9:380) and foamy or hemosiderin-rich cytoplasm
● Mild to marked pleomorphism
● 0-15 mitotic figures/10 HPF, frequently atypical
● Necrosis occasionally present

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



Enlarged cells with hyperchromatic nuclei, but no / rare mitotic figures (source: AFIP Fascicle, 3rd series)

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

● Vimentin, Factor XIIIa, CD34 (occasionally)

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

● CD68, actin, desmin, CD10, S100, keratin (MNF116), EMA; < 1% positive for MIB1 (Am J Dermatopathol 2004;26:367)

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

Atypical fibroxanthoma: sun damaged areas of head and neck in elderly, presents as dome shaped or ulcerated nodule, tumor cells abut epidermis without a grenz zone; also marked actinic elastosis, no classic features of fibrous histiocytoma
Dermatofibrosarcoma protuberans: strongly positive for CD34, lacks pleomorphism
Nodular melanoma: S100+
Pleomorphic fibroma: hypocellular, no epidermal hyperplasia, no classic features of fibrous histiocytoma
MFH-pleomorphic or other pleomorphic sarcomas: infiltrative, marked atypia, brisk mitotic activity, necrosis; no classic features of fibrous histiocytoma
Spindle cell squamous cell carcinoma: cytoketatin positive



Fibrohistiocytic

Cellular fibrous histiocytoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 27 October 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

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

● More cellular than classic fibrous histiocytoma, elongated cells are arranged in storiform pattern or fascicles

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

● 5% of dermal fibrous histiocytomas
● Young or middle-aged adults, 60% men
● Extremities or head and neck are most common

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

● Excision
● 26% recur (Am J Surg Pathol 1994;18:668)
● Rare metastases (Am J Surg Pathol 1996;20:1361)

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

● Up to 2.5 cm, rarely can be giant and multinodular mimicking dermatofibrosarcoma protuberans

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

● Fascicular or storiform but no “tight” storiform pattern
● Cells are plumper than DFSP, with eosinophilic cytoplasm and tapering nuclei; may entrap dermal collagen
● Mean 3 mitotic figures/10 HPF but may be >10 MF/10 HPF
● Extension into subcutaneous fat in 1/3 cases
● At least focal inflammatory cells, foam cells or giant cells
● Epidermal changes in the form of hyperplasia in 58%, focal central necrosis in 12%

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



Left: storiform growth pattern; right: deep tumor extension


More cellular than classic fibrous histiocytoma


Elongated cells are arranged in fascicles or a storiform pattern


Tumor cells are more histiocyte-like and foam cells are present

● Other images: hyperplastic and acanthotic epithelium;   spindled tumor resembles a leiomyoma

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

● Vimentin, CD163, CD68 (83%, J Cutan Pathol 2006;33:353)
● CD63/NKI-C3 (50%), Factor XIIIa (48%), focal smooth muscle actin
● HMGA1, HMGA2, CD10, focally CD34+

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

● CD117 (J Cutan Pathol 2007;34:857), CD34, desmin, S100, keratin, HMB45

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

Dermatofibrosarcoma protuberans: tight storiform pattern, less polymorphic, cells more spindly than cellular fibrous histiocytoma, CD34+ (strong), Factor XIIIa negative
Leiomyosarcoma: smooth muscle morphology with cigar shaped nuclei, more pleomorphism, infiltrative dermal growth, muscle markers+



Fibrohistiocytic tumors

Epithelioid fibrous histiocytoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 27 October 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

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

● Variant with 50% or more of tumor cells having epithelioid morphology

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

● Mean/median age 40-42 years (Br J Dermatol 1989;120:185)
● No gender preference

Pathophysiology
=========================================================================

● May arise from dermal microvascular unit (J Cutan Pathol 2003;30:415)

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

● Uncommon, usually presents as small (0.5 to 2 cm), solitary, very rarely multiple, skin colored elevated nodules
● Usually seen on trunk and extremities, rarely in head and neck regions

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

● 20 year old man with multiple lesions (Am J Dermatopathol 2008;30:373)
● 60 year old man with scalp lesion (Case of the Week #116)
● Underlying a damaged artery (J Dermatol 2005;32:721)

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

● Excision, only rarely recurs (Histopathology 1994;24:123)

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

● Often exophytic with epidermal collarette
● Circumscribed with uniform, medium to large angulated epithelioid cells (50%+ of tumor cells) that are often perivascular
● Many binucleated cells are often seen
● May be cellular (Am J Surg Pathol 1994;18:583)
● Periphery shows typical features of dermatofibroma
● Minimal inflammation, no prominent giant cells

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



Histiocyte-like cells with abundant cytoplasm, no / rare spindle cells


Epithelioid cells in hyalinized stroma


60 year old man with scalp lesion


Left to right: above case is Vimentin+, Factor XIIIa+, CD68-, keratin-. Melan A-


Epithelioid fibrous histiocytoma

● Other images: epithelioid cells with vesicular nuclei

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


40 year old man with exophytic nodule on foot

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

● Factor XIIIa, vimentin
● EMA (64%, J Cutan Pathol 2011:38:697)
● CD163 (J Cutan Pathol 2009;36:859)
● Rarely D2-40, smooth muscle actin

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

● Keratin, S100, myogenic markers, CD68

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

Epithelioid sarcoma: deep seated, granuloma-type clusters with necrosis, more atypia, keratin+, CD163-
Granuloma: epithelioid histiocytes in well formed clusters, surrounded by lymphocytes
Histiocytic sarcoma: marked atypia and mitotic activity
Melanoma: tight clustering of atypical cells, S100+, HMB45+
Rosai-Dorfman disease: multiple skin lesions and adenopathy, histiocytes are S100+ and pleomorphic with emperipolesis, also prominent B cells and plasma cells
Solitary epithelioid histiocytoma: dense eosinophilic and glassy cytoplasm, often with spiked cytoplasmic extensions, variable nuclear grooves and multinucleated cells, frequent lymphocytes and neutrophils, CD68+, CD163+ (Am J Surg Pathol 2006;30:521)
Spitz nevus: nevoid type clusters in periphery with spindle cell component, S100+



Fibrohistiocytic tumors

Juvenile xanthogranuloma variant of fibrous histiocytoma


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 27 October 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

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

● Benign proliferative disorder of dendrocytes in skin, usually self-limited (Am J Surg Pathol 2003;27:579)

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

● Also called nevoxanthoendothelioma (eMedicine)
● See also topics in these chapters: Breast-nonmalignant, Eye-uvea and Liver-tumor

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

● Uncommon (< 0.5% of pediatric tumors in one study)
● Usually infants (median age 5 months) with a congenital mark, although 10-30% occur in adults
● Male/female = 1.4:1

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

● Skin of face or trunk, less commonly in subcutis, skeletal muscle, eye, peripheral nerve or testis
● Also liver, spleen, kidney; rarely intracranial (Am J Neuroradiol 2011;32:E132)
● 20% of patients have multiple lesions, usually males
● In neonates, rarely associated with giant cell hepatitis and tumor in liver and viscera, requiring chemotherapy

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

● 2 year old boy with multiple lichenoid papules (Pediatr Dermatol 2009;26:238)
● 20 year old woman with “extranumerary nipple” of breast (Case of Week #5)
● 49 year old woman with lingual lesion (J Med Case Rep 2011 Jan 24;5:30)

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

● Conservative excision (Am J Surg Pathol 2005;29:21)
● May spontaneously regress leaving depressed area of skin with variable hyperpigmentation
● Multisystemic disease requires Langerhans cell histiocytosis-type chemotherapy (Pediatr Blood Cancer 2008;51:130)
● Can be fatal if massive hepatic or CNS involvement

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

● Up to 2 cm, yellow-red or brown, papulonodular

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



Smooth domed papule


Nodule over dorsum of tongue


Well circumscribed yellow nodule

Other images: various images #1;   #2

Dermoscopy description
=========================================================================

● Orange-yellow setting sun appearance (Dermatology 2007;215:256)

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

● Dense dermal infiltrate of lymphocytes, histiocytes, Touton giant cells (usually), eosinophils and neutrophils, which may extend into subcutis
● 0-2 mitotic figures per 10 HPF, rarely numerous
Late - epidermis thins out, rete ridges become elongated
Deep lesions - more cellular and monotonous with fewer Touton cells, can have more mitosis

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



20 year old woman (Case of the Week #5)


48 year old woman


Touton type giant cells: ring (wreath) of nuclei surround foamy cytoplasm, with cytoplasm visible around nuclei


Langhans type giant cell (for comparison): nuclei form a horseshoe arrangement; may not be distinct from Touton type


Foreign body type giant cell (for comparison): nuclei have haphazard arrangement

Other images: foam cells, Touton giant cells and scattered lymphocytes #1;   #2

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

● Vague, granulomatous aggregates with monotonous CD68+ histiocytic cells (Acta Cytol 2007;51:473)

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

● Vimentin CD68, HAM56, Factor XIIIa; also NKI-C3/CD63 (60%), lysozyme, alpha-1–antichymotrypsin

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

● S100, CD1a, EMA, keratin, HMB45

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

● No Birbeck granules; may have cytoplasmic lipid

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

Langerhans cell histiocytosis: more common, tumor cells have coffee bean nuclei/nuclear grooves, no Touton giant cells, are S100+ and CD1a+ and negative for CD68, HAM56 and Factor XIIIa, have Birbeck granules by EM
Xanthoma: associated with hyperlipidemia, uniform collection of foam cells and variable Touton giant cells, but no other inflammatory cells
Spindle cell xanthogranuloma: storiform array of cells and Touton type giant cells



Fibrohistiocytic

Fibrohistiocytic tumors - general


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

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

● Tumors composed of cells with morphologic features of fibroblasts and histiocytes
● Cells are actually fibroblasts, myofibroblasts or primitive mesenchymal cells
● Cells are NOT histiocytes, but may exhibit phagocytic properties, including phagocytosis of neutrophils
● Tumor cells may express histiocytic markers CD68, alpha-1-antitrypsin or alpha-1-antichymotrypsin

Classification
=========================================================================

WHO Classification (2006) of fibrous, fibrohistiocytic and histiocytic tumours occurring in skin (superficial) and ICD-O codes:

      ● Dermatomyofibroma: 8824/0
      ● Infantile myofibromatosis: 8824/1
      ● Sclerotic fibroma: 8823/0
      ● Pleomorphic fibroma: 8832/0
      ● Giant cell fibroblastoma: 8834/1
      ● Dermatofibrosarcoma protuberans: 8832/3
      ● Dermatofibroma (fibrous histiocytoma): 8832/0

WHO classification (2002) of fibrohistiocytic tumors of soft tissue (deep) and ICD-0 codes:

Benign
      ● Giant cell tumour of tendon sheath: 9252/0
      ● Diffuse-type giant cell tumour: 9251/0
      ● Deep benign fibrous histiocytoma: 8830/0

Intermediate (rarely metastasizing)
      ● Plexiform fibrohistiocytic tumour: 8835/1
      ● Giant cell tumour of soft tissues: 9251/1

Malignant
      ● Pleomorphic ‘MFH’ / Undifferentiated pleomorphic sarcoma: 8830/3
      ● Giant cell ‘MFH’ / Undifferentiated pleomorphic sarcoma with giant cells: 8830/3
      ● Inflammatory ‘MFH’ / Undifferentiated pleomorphic sarcoma with prominent inflammation: 8830/3

● References: Fletcher: Pathology and Genetics of Tumours of Soft Tissue and Bone, FLetcher-Chapter 5 (PDF), Fletcher-Chapter 3 (PDF)



Other tumors of skin

Atypical fibroxanthoma (AFX)


Reviewers: Christopher Hale, M.D., Vijay Shankar, M.D. (see Reviewers page)
Revised: 26 October 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

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

● Dermal variant of MFH-pleomorphic with low-grade behavior
● Also called intermediate fibrous histiocytoma
● Part of WHO classification for skin tumors, not soft tissue tumors

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

● Rapidly growing small dome-shaped or polypoid nodule on sun-damaged areas of head and neck of elderly (eMedicine-atypical fibroxanthoma)
● May present as bleeding ulcer < 2 cm
● Rarely presents as large mass in limb or trunk of younger individuals, or post radiation therapy
● May clinically resemble carcinoma
● Must exclude tumors with AFX-like patterns, other lines of differentiation, significant involvement of subcutis, necrosis, vascular invasion or infiltrative margins (Stanford Medicine)
● Poor prognostic indicators: history of immunosuppression, recurrence

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

● 21 year old woman with nasal nodule (Can J Plast Surg 2007;15:169)
● 63 year old man with metastatic tumor from eyebrow area to face (Arch Pathol Lab Med 2006;130:735)
● 81 year old man with widespread peritoneal metastases (Am J Surg Pathol 2006;30:1041)
● 81 year old woman with lower leg lesion (Dermatol Online J 2008;14:1)

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

● Local excision; Mohs micrographic surgery may be effective (Dermatol Surg 2009;35:765)
● Rarely recurs or metastasizes

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


       
Irregular polypoid tumors


21 year old woman with nasal nodule


Solitary dome shaped nodule

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

● Polypoid, ulcerated, usually small

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

● Well circumscribed, appears symmetric at scanning magnification
● Bizarre multinucleated tumor cells in hypercellular, spindly stroma with frequent mitotic figures, many atypical
● Also smaller fibroblastic, myofibroblastic and histiocyte-like cells with pleomorphism and angulated nuclei
● Histologically identical to MFH-pleomorphic but centered in dermis
● Background stroma appears inflammatory or reactive
● Pushes aside surrounding pilosebaceous units and eccrine glands
● Typically does not involve epidermis or subcutaneous tissue
● Lacks classic features of fibrous histiocytoma (entrapped hyalinized collagen bundles and epidermal hyperplasia)
● No grenz zone, no necrosis, no vascular invasion, no infiltrative margins

● Variants: angiomatoid, chondroid, clear cell (J Cutan Pathol 2006;33:343), granular cell (Am J Dermatopathol 2007;29:84), keloidal (J Cutan Pathol 2009;36:535), myxoid (J Cutan Pathol 2009;36:1177), osteoclastic, osteoid, pigmented (Actas Dermosifiliogr 2009;100:321)

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



Exophytic cellular nodule with ulceration


Fascicles of atypical spindle cells


Tumor is limited to dermis but otherwise resembles MFH-pleomorphic with marked cellularity,
prominent pleomorphism, mitotic figures and clumped chromatin



Marked cellularity and pleomorphism


Characteristic bizarre cells


Spindle variant has less pleomorphism


81 year old woman with lower leg lesion

       
Various images, contributed by Dr. Angel Fernandez-Florez, Hospital El Bierzo, Spain


Angiomatoid variant


Fig A: edge of lesion shows hyperchromatic cells next to elastotic dermis (arrow)
Fig B/C: atypical spindle cells and histiocytes, atypical mitotic figure (arrow)
Fig D: alpha-1-antichymotrypsin positive



Fig 1: eyebrow primary
Fig 2-4: facial metastasis (fig 4 is CD68)



Factor XIIIa


p53


CD68, contributed by Dr. Angel Fernandez-Florez, Hospital El Bierzo, Spain


CD10, contributed by Dr. Angel Fernandez-Florez, Hospital El Bierzo, Spain


AE1-AE3, contributed by Dr. Angel Fernandez-Florez, Hospital El Bierzo, Spain

Spindle and epithelioid cells with atypia

Ulcerated tumor #1, #2, #3, #4

Nodular spindle cell tumor #1, #2

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

● Vimentin, CD68, alpha-1-antitrypsin, alpha-1-antichymotrypsin, Factor XIIIa (focal)
● CD117 (Am J Dermatopathol 2008;30:34), CD99 (73%, Am J Clin Pathol 2002;117:126), CD10 (Australas J Dermatol 2005;46:235)
● D2-40 (50%, J Cutan Pathol 2011;38:631), calponin (30%, Virchows Arch 2002;440:404), desmin (30%), smooth muscle actin (30%)
● Procollagen-1, CD31 (5%), p75 (J Cutan Pathol 2011;38:631)

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

● Keratin (J Cutan Pathol 2010;37:301), EMA, S100 (although S100+ Langerhans cells may be present)
● HMB45 (rarely positive, J Cutan Pathol 2004;31:284), caldesmon, desmin

Electron Microscopic
=========================================================================

● Myofibroblasts, fibroblasts and primitive mesenchymal cells

Molecular
=========================================================================

● Diploid

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

● Squamous cell carcinoma-spindle cell type: deep extension, p63+ (J Cutan Pathol 2009;36:543)
● Desmoplastic melanoma: may have focal AFX-type features and stain negative for melanocytic markers ( Am J Dermatopathol 2007;29:551)
● Atypical fibrous histiocytoma
● Angiosarcoma-spindle cell variant



Fibrohistiocytic tumors

Giant cell tumor of soft tissue


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 27 October 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

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

● Soft tissue counterpart of giant cell tumor of bone (Mod Pathol 1999;12:894)
● Also called soft tissue giant cell tumor of low malignant potential (Stanford University)
● Prominent osteoclast-like giant cells and mononuclear cells, but at most mild atypia

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

● Rare, usually age 40+ years, rare in children
● Usually superficial soft tissue of extremities (70%); rarely breast, mediastinum, groin, surgical scars
● Presents as painless growing mass

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

● 40 year old woman with nodule on thigh (Dermatology Online J 2010;16:2)
● 53 year old man with a mediastinal mass (Rare Tumors 2009 Dec 28;1:e45)
● 54 year old man with tumor of finger (Dermatol Online J 2008;14:7)
● 60 year old woman with breast tumor and fatal outcome (Ann Diagn Pathol 2007;11:345)
● 73 year old man with metastatic tumor associated with post-transplant immunosuppression (Virchows Arch 2006;448:847)
● Two cases arising in surgical scars (Pathologe 2009;30:401)
● Tumor of 46 years duration (J Cutan Pathol 2009;36:20)

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

● Complete excision with negative margins
● Recurs in 12% (associated with incomplete excision)
● Rare metastases and death

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

● Up to 10 cm, usually dermis or subcutis, 30% are below superficial fascia
● Well circumscribed, nodular, fleshy, red-brown-gray, gritty at periphery due to calcification

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



54 year old man


Large, smooth, firm, erythematous nodule on thigh

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



Mediastinal mass

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

● Multinodular with fibrous tissue containing siderophages separating nodules
● Nodules contain round/oval mononuclear cells and multinucleated osteoclast-like giant cells with similar nuclei
● Mononuclear cells are epitheloid or spindled, with eosinophilic cytoplasm and central nuclei
● Stroma is vascularized; up to 30 mitotic figures/10 HPF
● Often metaplastic bone, blood lakes, vascular invasion
● Occasionally fascicular pattern with focal storiform arrangement of spindle cells
● No/rare atypia, pleomorphism or necrosis

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



Resembles giant cell tumor of bone, with osteoclast-like giant cells but at most mild pleomorphism


Chondroid pattern   Osteoid pattern


Mediastinal mass


Thigh tumor


Osteoclast–like giant cells are CD68+ (lesion of pinna)


Bone tumor (for comparison): Numerous osteoclast-like giant cells and surrounding mononuclear cells


Bone tumor (for comparison): Ki67 staining in mononuclear cells

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

● Numerous osteoclast-like giant cells and mononuclear cells with bland and vesicular nuclei
● Occasional/rare fragment of branching vasculature, mitotic figures (Acta Cytol 2003;47:1103)

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

● Vimentin, CD68 (strong in multinucleated giant cells), smooth muscle actin
● Also alkaline phosphatase, osteoprotegerin, RANKL, TRAIL and TRAP (Hum Pathol 2005;36:945)

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

● Usually no cytogenetic abnormalities
● Case report of telomeric association involving multiple chromosomes (Pediatr Dev Pathol 2005;8:718)

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

Giant cell tumor of tendon sheath-localized: near tendons, hyalinized stroma, foam cells and hemosiderin laded macrophages are common, metaplastic bone is uncommon
Plexiform fibrohistiocytic tumor: childhood tumor with plexiform growth pattern, complex tentacle like extensions
Malignant fibrous histiocytoma-giant cell type: infiltrative, moderate to severe atypia of non-giant cells, necrosis, atypical mitotic figures



Fibrohistiocytic tumors

Giant cell tumor of tendon sheath - diffuse type


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 27 October 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

See malignant tumors below

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

● Extra-articular, destructive villonodular hyperplasia with synovial mononuclear cells mixed with multinucleated giant cells, foam cells, siderophages and inflammatory cells
● Considered the soft tissue counterpart of pigmented villonodular synovitis - may represent extension of articular tumor since often occurs near a joint

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

● Also called tenosynovial giant cell tumor-diffuse type
● Called pigmented villonodular synovitis (PVNS) when occurs near a joint
● Note: terminology of giant cell tumors is inconsistent in literature

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

● Rare; less frequent than localized type
● Usually < age 40 years, with female predominance

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

● Develops in synovial lining of joints, tendon sheaths and bursae
● Usually knee (80%); also ankle, hip, shoulder, elbow, foot
● Almost always monoarticular, painful swelling
● May actually be hyperplastic, not neoplastic (Hum Pathol 2003;34:65)
● Occasionally invades underlying bone; may cause bone cyst formation, loss of bone and cartilage
● Locally aggressive; often recurs, but only rarely has malignant behavior (see below)

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

● 26 year old woman with tumor of subcutaneous thigh (Skeletal Radiol 2007;36:327)
● Arising in bursa of knee (Knee 2007;14:402)

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

● Excision; may recur if inadequate excision; radiation therapy for recurrences
● See below for cases with malignant behavior

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

● Brown-yellow spongy tissue, firm and nodular, often 5 cm or larger

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



Diffuse type of tenosynovial giant cell tumor consisting of mottled brown-yellow-red villonodular mass


Hemosiderin pigment on surface


Knee synovectomy shows diffuse involvement with villous areas and a few nodules; flat shiny surface is normal synovium


Multinodular red-brown tumor (Univ Alabama)


White gray cartilage (arrow) and brown villous tissue

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

● Diffuse expansive sheets of cells with infiltrative borders and variable cellularity; tumor margins are more cellular
● Also hyperplastic synovium with papillary projections composed of foamy histiocytes and hemosiderin containing macrophages
● Large clefts, pseudoglandular or alveolar spaces lined by synovial cells, osteoclast-like multinucleated (10-70 nuclei) giant cells, epithelioid cells
● Abundant collagen may be present, but lymphocytes and plasma cells are sparse
● Also giant hemosiderotic granules (2-3x diameter of RBC), giant siderophages (Pathologe 2005;26:96)
● May have 5+ mitotic figures/10 HPF, rarely chondroid metaplasia (Mod Pathol 2007;20:545)
● Malignant if nodular and solid invasive growth plus large cells with large nuclei, prominent nucleoli, necrotic areas and atypical mitotic figures (see below)

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



Multiple synovial lined clefts and hemosiderin deposits in the subsynovial layer


Low power: sheets of small histiocytes, hyalinization and giant cells; high power: abundant hemosiderin pigment is seen


Villi have cellular cores, variable width and shape


Villi lined by synovial cells and histiocytes; giant cells and lymphocytes are also present


Various images


Papillary tumor


Multinucleated giant cells, synovial cells, fibroblasts and inflammatory cells


CD68+, S100+ cells in chondroid areas

Other images: shoulder tumor #1; #2; #3; #4; #5; histiocytes and giant cells in dense connective tissue stroma #1; #2; iron deposits (Prussian blue stain); foam cells

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

● Round, spindled and multinucleated cells without atypia
● Round cells have minimal cytoplasm and eccentric nuclei, occasional cytoplasmic hemosiderin, no mitotic figures

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



Various images

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

● CD68 (stromal and giant cells, Hum Pathol 2003;34:65)
● Also CD31 (75%), calretinin (63%, Pathologe 2005;26:96), desmin (35-40%), CD14
● HAM56, CD45, and lysozyme (Arkh Patol 2010;72:34)

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

● S100 (but chondroid areas are S100+), CD45/LCA, EMA, keratin, HMB45, CD34, smooth muscle actin

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

● Features of histiocytes and fibroblasts (Ultrastruct Pathol 2002;26:15)

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

● Clonal with neoplastic and reactive features
● Neoplastic due to CSF1 overexpression (Am J Surg Pathol 2007;31:970) or 1p13 (CSF1) rearrangements, often with COL6A3 at 2q35 (Proc Natl Acad Sci USA 2006;103:690)
● Also reactive features (Hum Pathol 2003;34:65)
● Translocations, t(2;3) and der(8) t(8;12) (Ultrastruct Pathol 2002;26:15)
● Some show trisomy of chromosome 5 & 7

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

● Hemosiderotic synovitis: associated with hemophilia and intraarticular bleeding, no mononuclear or giant cell nodular proliferation, hemosiderin primarily in synovial lining cells

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

eMedicine #1, #2, Am Fam Physician 1999;60:1404


Malignant giant cell tumor of tendon sheath-diffuse type

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

● Rare tumor with coexisting or prior benign giant cell tumor plus sarcomatous areas
● Not a WHO diagnosis

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

● Mean 61 years, no gender preference
● Usually extra-articular, near large joints or extremities
● Most common location is knee joint
● Often metastasizes or recurs, but variable outcome (Am J Surg Pathol 2008;32:587, Zhonghua Wai Ke Za Zhi 2008;46:1645)

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

● 72 year old woman with hip tumor (Jpn J Clin Oncol 1993;23:317)

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

● Mean 9 cm

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

● Benign areas with gradual or abrupt change to frank sarcoma containing pleomorphic, spindle or enlarged oval cells resembling MFH, fibrosarcoma, myxosarcoma or giant cell tumor with large nuclei and prominent nucleoli (Am J Surg Pathol 1997;21:153)
● Also necrosis and atypical mitotic figures
● Higher Ki 67 index

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



Various images

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

● Malignant cases may have trisomy 5 and 7 (Arch Pathol Lab Med 2000;124:1636)
● Deregulated CFS1 overexpression is frequent
● Cyclin A mRNA is up-regulated
● Aberrations of cyclin A, p53, 15q (Clin Cancer Res 2008;14:6023)



Fibrohistiocytic tumors

Giant cell tumor of tendon sheath - localized type


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 28 October 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

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

● Circumscribed proliferation of synovial like mononuclear cells with osteoclast-like giant cells, foam cells, siderophages and inflammatory cells, usually in digits

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

● Also called fibrous histiocytoma of tendon sheath, tenosynovial giant cell tumor-localized type, localized nodular tenosynovitis
● Family of lesions arising from joint synovium, bursae and tendon sheath; giant cell tumor of bone, giant cell tumor of tendon sheath and pigmented villonodular synovitis may have common cell lineage (Ultrastruct Pathol 2006;30:151)
● See also Joints chapter (fibrous histiocytoma of tendon sheath)

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

● Common, usually ages 30-50 years, 2/3 female, primarily affects the fingers
● #2 most common tumor of hand after ganglion cyst
● Rare in children, in whom recurrence is uncommon (J Pediatr Orthop 2007;27:67)

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

● Slow growing, painless mass, 2–5 cm

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

● 9 year old girl with finger nodule (Dermatology Online Journal 2011;17:9)
● 9 year old boy with giant cell tumour with cutaneous satellites near surgical scar following excision of primary lesion (Case Rep Dermatol 2011;3:118)
● 22 year old man with acutely painful finger (AJR Am J Roentgenol 2007;188:S13)
● 29 year old woman and 30 year old man with ankle masses (J Med Case Rep 2009 Dec 15;3:9331)
● 37 year old woman with tumor intertwined with ulnar nerve (Eplasty 2009;9:e8)

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

● Excision, 4-30% recur (treat with reexcision)

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



9 year old girl with nodule in the right index finger


Tumors at surgery

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

● Localized tumors up to 4 cm in small joints (larger elsewhere), circumscribed, lobulated, white-gray-brown (yellow-orange-red color due to xanthoma cells and hemosiderin)
● May have shallow grooves along deep surface due to underlying tendons

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



Well circumscribed masses

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

● Well circumscribed, lobulated, partially encapsulated
● Variable proportions of mononuclear cells (small, round to spindled, with pale cytoplasm and round or grooved nuclei), osteoclast-like giant cells with 3-50 nuclei, foam cells, siderophages, epithelioid cells with glassy cytoplasm and round vesicular nuclei
● Varying amounts of dense collagenous stroma
● Up to 20 mitotic figures/10 HPF
● Stroma is hyalinized
● Cartilaginous metaplasia rarely seen

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



Ankle lesion


9 year old boy with hand lesion

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



Giant cell tumor of tendon sheath

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

● High cellularity, polymorphic population of mononuclear histiocyte-like cells, hemosiderin laden macrophages, foamy macrophages and a few multinucleated giant cells (Acta Cytol 2008;52:152, Diagn Cytopathol 2004;30:14)
● Stromal cells are dispersed, polygonal to spindle shaped, with intranuclear cytoplasmic inclusions and occasional nuclear grooves and convolutions (Diagn Cytopathol 2003;29:105)

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



Scattered groups of mononuclear cells with occasional osteoclast-like giant cells

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

Mononuclear cells - CD68, variable muscle specific actin and desmin
Osteoclast-like giant cells - CD68, CD45 (Mod Pathol 1995;8:155), TRAP

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

● Histiocyte-like cells, fibroblast-like cells, multinucleated giant cells, foam cells

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

● Near diploid or pseudodiploid, often t(1;2) (Fetal Pediatr Pathol 2004;23:171)

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

eMedicine, Stanford University



Fibrohistiocytic tumors

Malignant fibrous histiocytoma of soft tissue - giant cell type


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 28 October 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

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

● Diagnosis of exclusion - an undifferentiated pleomorphic sarcoma with prominent osteoclast-like giant cells

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

● Also called malignant giant cell tumor of soft parts, malignant osteoclastoma, giant cell sarcoma

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

● 3-15% of malignant fibrous histiocytomas
● Number of cases is declining as specific sarcoma types are identified
● Rare in children

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

● Extremities and trunk
● Osteoclast-like cells have functional features of osteoclasts (J Pathol 1989;159:53)

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

● 5 year old boy with retroperitoneal tumor (Turk J Pediatr 2007;49:307)
● 53 year old male with laryngeal tumor (Rom J Morphol Embryol 2010;51:359)
● 59 year old male with vocal cord lesion on the vocal cord (Rom J Morphol Embryol 2009;50:481)
● Disseminated tumor (Indian J Pathol Microbiol 2007;50:795)

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

● Hemorrhagic and necrotic

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



Left atrial tumor at autopsy

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

● Resembles pleomorphic malignant fibrous histiocytoma, with addition of evenly dispersed osteoclast-like giant cells with 20-100 uniform nuclei that are small and round/oval, accompanied by smaller stromal cells with similar nuclei
● 2-3 MF/10 HPF
● May have angiolymphatic invasion
● Rarely small foci of neoplastic bone or cartilage (some designate these tumors as osteosarcoma or chondrosarcoma)
● No xanthoma cells or siderophages, no necrosis

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



Osteoclast-like giant cells with uniform nuclei in a pleomorphic MFH


Tumor cells may form neoplastic bone and osteoid


Similar lesion in prostate


Left atrial tumor at autopsy (H&E and vimentin)

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

● Hypercellular smear with cohesive, branching clusters of spindle cells with ovoid, focally hyperchromatic nuclei and inconspicuous nucleoli
● Also interspersed osteoclast-like giant cells, some associated with clusters of spindle cells
● Hemorrhagic background with cellular debris and occasional spindle cells and lymphocytes (Acta Cytol 2003;47:673)

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


Multinucleated osteoclastic-type giant cells

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

● Vimentin, CD68, S100 (variable) , SMA (variable)

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

Extraskeletal osteosarcoma: prominent malignant osteoid
Giant cell tumor of soft tissue: no pleomorphic MFH features
Leiomyosarcoma: smooth muscle morphology and immunostains; no prominent osteoclastic giant cells
Melanoma: giant cells, if present, are typically not osteoclast-like; positive for melanocytic markers
Osteoclast-rich carcinoma: malignant epithelial component
MFH-pleomorphic: no osteoclast-like cells with uniform nuclei



Fibrohistiocytic tumors

Malignant fibrous histiocytoma of soft tissue - inflammatory


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 28 October 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

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

● Neoplastic histiocyte-like cells mixed with, and often obscured by neutrophils and other inflammatory cells

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

● Most of these tumors are probably dedifferentiated liposarcoma (J Pathol 2004;203:822, see also Pathol Int 1997;47:642) or leiomyosarcoma
● Diagnosis of exclusion; recommended to take many sections and use immunohistochemistry to rule out mimics

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

● Very rare, usually age 40+ years, often retroperitoneal
● May be associated with fever, leukocytosis (leukemoid reaction) and eosinophilia
● May occur in skin with predominance of lymphocytes (Am J Dermatopathol 2002;24:251)
● Very aggressive with poorest prognosis of all MFH types (2/3 die of disease, 1/4 have distant metastases) although these studies probably included other morphologically similar disorders

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

● 4 year old boy with chest wall swelling (Fetal Pediatr Pathol 2004;23:319)
● 45 year old woman with kidney tumor (Pathol Res Pract 2008;204:857)
● 46 year old man with tumor originating in thymus (Ann Thorac Surg 2010;89:2003)
● 63 year old man with abdominal tumor (Case of the Week #144)
● 65 year old woman with lumbar abscess (Case Rep Oncol 2011;4:343)

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

● 8-10 cm, yellow due to xanthoma cells; firm, lobulated

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

● Commonly has storiform pattern, background of inflammatory cells (histiocyte-like, xanthoma, neutrophils, lymphocytes, eosinophils, plasma cells) which may obscure tumor cells
● Tumor cytoplasm may contain phagocytized neutrophils; nuclei are large and vesicular with prominent nucleoli
● May have bizarre giant cells or atypical mitotic figures but no necrosis

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



Acute inflammatory cells and large histiocyte-like cells


Large histiocyte-like cells with prominent nucleoli resembling lymphoma or carcinoma, with variable fibroblasts


Numerous histiocyte-like cells resembling lymphoma


Associated with orthopedic implant




Case of week #144 - abdominal tumor


H&E, CD68, vimentin

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

● Neutrophilic infiltrate in and around tumor cells, which show prominent neutrophilic phagocytosis (Fetal Pediatr Pathol 2004;23:319)

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

● MDM2, CDK4 (these cases may actually be dedifferentiated liposarcoma), a1-antitrypsin
● Alpha 1 antitrypsin (Ann Thorac Surg 2010;89:2003)

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

● 12q13-15 amplification or gain (these cases may actually be dedifferentiated liposarcoma)

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

Myxoid or dedifferentiated liposarcoma: may need to submit additional sections of normal appearing fat to identify, perform MDM2 or CDK4 or obtain cytogenetics)
Hodgkin lymphoma or anaplastic lymphoma (Mod Pathol 1997;10:438)
Inflammatory myofibroblastic tumor
Melanoma
● Metastatic renal or adrenal carcinoma
Osteosarcoma-irradiated: malignant osteoid present
● Reactive abscess-like lesion
Xanthogranulomatous pyelonephritis : no malignant component, only reactive (Int J Urol 2006;13:1000)



Fibrohistiocytic tumors

Malignant Fibrous Histiocytoma (MFH) of soft tissue - pleomorphic


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

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

● Pleomorphic sarcoma composed of fibroblasts, myofibroblasts and histiocyte-like cells
● Diagnosis of exclusion; must sample generously and search for other components to rule out a dedifferentiated tumor or evidence of specific differentiation other than fibroblasts or myofibroblasts

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

● Also called pleomorphic undifferentiated sarcoma
● See also Bone, Eye-conjunctiva and Heart-tumor chapters
● First described in 1964 (Cancer 1964;17:1445)
Pleomorphic: variation in cytoplasmic and nuclear size throughout the tumor, not just “funny looking cells”

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

● Historically considered the most common adult soft tissue sarcoma
● Usually older adults (age 50+ years) with slight male predominance; more common in lower extremities, rarely retroperitoneum, head and neck, breast
● Large and deep-seated with progressive enlargement
● Sarcomas adjacent to orthopedic implants or post-radiation are usually osteosarcoma or MFH (Mod Pathol 2001;14:969)

Xray images
=========================================================================



Tumor surrounds intramedullary nail

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

● 60 year old male with liver tumor (Hepatobiliary Pancreat Dis Int 2009;8:541)
● 63 year old man with concurrent scrotal Fournier’s gangrene (Appl Immunohistochem Mol Morphol 2010;18:473)
● 76 year old man with a breast tumor (J Breast Cancer 2011;14:241)

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

● Wide local excision is occasionally curative in extremities; adjuvant or neoadjuvant radiation and chemotherapy often used
● Recurs locally, may metastasize to lungs or regional lymph nodes
● Almost never presents as metastasis with unknown small primary
● 5 year survival is 50-60% for all high grade pleomorphic sarcomas, better for some subtypes (dedifferentiated liposarcoma)
● Call “borderline” if features are between fibrous histiocytoma and MFH, and treat with wide local excision
● Good prognostic factors: superficial, small size, low grade
● When occurs in skin, is difficult to differentiate from atypical fibroxanthoma or DFSP

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

● Large, may appear circumscribed (but is not); subcutaneous lesions are usually 5 cm or less, retroperitoneal lesions may be 20 cm
● Cut surface is fibrous or fleshy with hemorrhage, necrosis or myxoid change

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



Implant related MFH is tan and fleshy and surrounds femur


Shoulder tumor


Sternal mass

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

● Storiform pattern (cells emanate from a central focus), irregular fascicles, variable cellularity
● Pleomorphic and bizarre tumor cells with foamy cytoplasm and marked atypia, in background of inflamed collagenous stroma
● May represent end stage of various sarcomas with common morphologic features of pleomorphism and storiform growth pattern
● Multinucleated giant cells may be seen; if prominent, classify as MFH-giant cell
● Numerous mitotic figures, including atypical forms
● Rarely metaplastic (not neoplastic) bone or cartilage

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



Striking low power appearance due to cellularity, whorled pattern, marked pleomorphism with bizarre nuclei


Characteristic giant cells with bizarre nuclei


Mixture of fibroblasts and histiocyte-like cells including multinucleated forms


Vague storiform pattern is often present, at least focally


Tumor cells have abundant eosinophilic cytoplasm and bizarre nuclei, and resemble a muscle tumor


Strap like cells resemble rhabdomyoblasts


Numerous mitotic figures, some bizarre forms


Frequent tumor cell necrosis, not seen in benign fibrous histiocytoma


Various images


Breast mass (recurrent)




Hard palate tumor (H&E, vimentin, CD68)

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

● Single cells to large storiform fragments
● Cells are spindled, plasmacytoid and pleomorphic (often multinucleated), all with malignant nuclear morphology (Cancer 1997;81:228)

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


Various images

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

● Note: positive stains are usually not helpful for diagnosis
● Vimentin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, Factor XIIIa, CD68 (may be due to lysosomal granules in non-histiocytic cells); also CD10, CD34, CD99 (35%, J Cutan Pathol 2006;33:24) very rarely aberrant expression of Melan A (J Cutan Pathol 2011;38:954)

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

● Keratin (usually), melanocytic markers, CD45, S100, muscle markers

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

● No features of a specific lineage
● Relatively undifferentiated fibroblastic, myofibroblastic or primitive mesenchymal cells, some with phagocytic properties

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



Tumor cell has fibroblastic features

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

● Highly complex karyotype, usually triploid or tetraploid
● Gene expression profiles may be somewhat similar to other sarcomas (Mod Pathol 2007;20:749)
● Frequent alterations in G1/S checkpoint genes (Genes Chromosomes Cancer 2011;50:291)

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

Anaplastic large cell lymphoma: CD30+
Atypical fibroxanthoma: cutaneous, small and superficial
Leiomyosarcoma, pleomorphic: smooth muscle differentiation
Leprosy, histiocytoid: prominent histiocytes but no prominent atypia or atypical mitotic figures, special stains may reveal mycobacteria
Liposarcoma, pleomorphic: lipoblasts, often S100+ or smooth muscle actin+
MFH-giant cell: numerous osteoclast-like giant cells
MFH-inflammatory: marked inflammatory cells
Myxofibrosarcoma: 10%+ myxoid foci
Renal cell carcinoma, metastatic: keratin+
Rhabdomyosarcoma, pleomorphic: evidence of skeletal muscle differentiation

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

J Exp Clin Cancer Res 2010;29:153, Expert Rev Anticancer Ther 2009;9:1135



Fibrohistiocytic tumors

Pleomorphic hyalinizing angiectatic tumor


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 28 October 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

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

● Rare tumor (< 50 cases reported) of subcutis, with ectatic blood filled vessels surrounded by hyalinized stroma and pleomorphic spindle cells, no mitotic activity (Stanford University)

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

● Part of WHO classification for skin tumors and soft tissue tumors
● First described in 1996 (Am J Surg Pathol 1996;20:21)

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

● Low grade malignancy of adults (median age 51 years), often in extremities or trunk
● May be derived from stromal fibroblasts or primitive undifferentiated mesenchyme

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

● 55 year old male with a left forearm mass (UPOJ 2010;20:121))
● 76 year old woman with sarcomatous component (Pathol Int 2007;57:281)
● 77 year old woman (West Indian Med J 2007;56:544)
● 83 year old woman with thigh tumor (Pathol Int 2002;52:664)

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

● Wide local excision, but 20% recur, rarely as sarcoma

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

● Unencapsulated with infiltrative margins
● Atypical spindle cells that contain hemosiderin and resemble MFH-pleomorphic and schwannoma, have intranuclear and cytoplasmic inclusions
● Also large ectatic spaces with blood and fibrin and perivascular hyalinization
● Abundant mast cells, occasional fat
Hemosiderotic fibrohistiocytic lipomatous lesion/tumor may be precursor lesion (Am J Surg Pathol 2004;28:1417, but see Orthopedics 2010;33:516)
● No/rare mitotic figures

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



Various images

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



Pleomorphic hyalinizing angiectatic tumor

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

● Both bland and larger pleomorphic cells, hyalinized vessels (Diagn Cytopathol 2011;39:214)

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

● CD34 (strong, Arch Pathol Lab Med 2000;124:423), vimentin, VEGF, CD99, Factor XIIIa (focal)

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

● S100, CD31; Ki-67 < 2% (Chin Med J (Engl) 2007;120:876)

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



Cytoplasmic granular deposits consistent with hemosiderin and wavy intermediate filaments consistent with vimentin

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

● Case report of 2 unbalanced translocations involving chromosomes 1 and 3 and chromosomes 1 and 10, with a karyotype of 45,XX,der(1)t(1;3)(p31;q12),-3,der(10)t(1;10)(p31;q25)[11]/46,XX[4 (Hum Pathol 2012;43:121)

Molecular / cytogenetic images
=========================================================================



Unbalanced translocations involving chromosomes 1 and 3 and chromosomes 1 and 10

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

Schwannoma: not infiltrative, no atypia, strongly S100+
Primary cutaneous myxofibrosarcoma: see Am J Dermatopathol 2005;27:322



Fibrohistiocytic tumors

Plexiform fibrohistiocytic tumor


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

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

● Dermal or subcutaneous, plexiform or multinodular proliferation of fibrohistiocytic cells and osteoclast-like giant cells with chronic inflammatory infiltrate

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

● First described in 1988 (Am J Surg Pathol 1988;12:818)
● Also called plexiform fibrous histiocytoma
● May have common histogenesis with cellular neurothekeoma (Am J Surg Pathol 2009;33:905)

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

● Usually children and young adults, 80% female

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

● Small, slow growing dermal or subcutaneous mass, upper extremity (65%) or lower extremity (27%), rarely head and neck (Dermatol Sinica 2010;28:117 (pdf))

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

● 3 year old child whose tumor lacked osteoclast-like giant cells (Am J Dermatopathol 2002;24:399)
● 5 year old boy with bilateral thigh tumors (J Chinese Oncol Soc 2009;25:153)
● 6 year old boy with small perioral tumor (Eur J Dermatol 2004;14:118)
● 17 year old girl with nasal tumor and nodal metastasis (Dermatol Sinica 2010;28:117)
● 21 year old woman with mass on back (Indian J Pathol Microbiol 2008;51:245)
● 24 year old woman with supraclavicular myxoid tumor without giant cells (Arch Pathol Lab Med 2004;128:931)
● 29 year old woman with occipital mass (Case of the Week #180)
● 39 year old woman with recurrent tumor (Univ Pittsburgh Case #316)

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

● Low grade malignant behavior
● After excision, recurs locally, rarely has nodal or pulmonary metastases (Am J Surg Pathol 1999;23:662)

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

● Multinodular, poorly circumscribed, firm, dermal or subcutaneous, 3 cm or less

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

● Deep dermal or subcutaneous tumor with ray like extension into skeletal muscle or adipose tissue
● Overlying epidermis and dermis are usually normal
● Plexiform or multinodular proliferation of fibrohistiocytic cells with minimal atypia plus osteoclast-like giant cells and chronic inflammatory infiltrate
● Nodules or clusters are interconnected in characteristic plexiform arrangement
● Prominent dilated vessels; more sclerotic than MFH
● Often hemorrhage and hemosiderin
● Vascular invasion in 10-20%
● Usually 0-2 MF/10 HPF, no necrosis
● Subtypes are fibrohistiocytic (histiocyte-like cells and giant cells), fibroblastic (fibroblast-like cells) and mixed

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



Subcutaneous proliferation of bland fibrous tissue which radiates outward from center of lesion


Most tumors have nodules of histiocyte-like cells and giant cells, also fibrous tissue and hemorrhage


Histiocyte-like cells have pale staining cytoplasm; giant cells are also present


Nodules may be composed of cells with elongated nuclei


Tumor with nodules and fibrous tissue


Fibrous tissue may resemble desmoid fibromatosis


Axillary lymph node has multiple plexiform nodules within and outside the node


Nodules are composed of plump cells and multi-nucleated giant cells


Various images




Case of Week #180: H&E, bottom row - CD68 and smooth muscle actin


12 year old girl with upper arm lesion

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



Plexiform fibrohistiocytic tumor

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

● Plump fibroblastic cells and histiocyte-like cells within a finely granular myxoid background
● Also osteoclast-like giant cells (Acta Cytol 1999;43:867)

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



Various images

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

● Vimentin, CD68 (giant cells and mononuclear histiocyte-like cells), smooth muscle actin (fibroblast-like cells, Histopathology 1991;19:503)
● Rarely alpha-1-antitrypsin and alpha-1-antichymotrypsin

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

● S100, keratin, CD45, Factor VIII, desmin

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

● Resembles myofibroblasts, fibroblasts and undifferentiated cells

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

Benign fibrous histiocytoma: older patients, prominent foam cells, no plexiform extensions of fibrous tissue, no nodules of histiocyte-like cells, no multinucleated giant cells
Cellular neurothekeoma: uniform population of epithelioid cells, no distinct nodules of histiocytoid cells or osteoclast-like giant cells (Am J Surg Pathol 2007;31:329), podoplanin+ (Am J Dermatopathol 2009;31:137)
Fibromatosis: centered in muscle, diffusely infiltrative, no nodules
Fibrous hamartoma of infancy: immature cells present, also myxoid stroma
Giant cell tumor of soft tissue: infiltrative nodules of mixed giant cells and spindle cells, frequent mitotic figures
Neurofibroma: no distinct nodules, S100+

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

Ann Diagn Pathol 2007;11:313, Arch Pathol Lab Med 2007;131:1135, Stanford University



Mesenchymal tumors
Mesenchymal hamartoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 10 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Case reports
=========================================================================
Micro images
=========================================================================
Malar mass


Mesenchymal tumors
Mesenchymoma

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: benign, malignant

Definition
=========================================================================
AFIP Third Fascicle and WHO dislike this terminology, and recommend:
  1. Describing as mixed mesenchymal neoplasm and specifying the components or
  2. Classifying based on predominant mode of differentiation and mentioning the other component(s)


Benign mesenchymoma
Definition
=========================================================================
Case reports
=========================================================================
Micro images
=========================================================================
Stomach tumor
Dense fibrous tissue, woven bone and cartilage like areas
Loose vascular mesenchyme, smooth muscle and fat
Fibrous, mature fat, and muscle tissue


Malignant mesenchymoma
Definition
=========================================================================
Sites
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Gross images
=========================================================================
Deep gluteal muscles
Rectus femoris muscle
Micro images
=========================================================================
Pleural tumor
Deep gluteal tissues
Rectus femoris muscle
Anterior thigh muscles
Uterus
Deep tissues in lateral neck
Leg
Liver
Retroperitoneum
Spindle cell component
Chondrosarcoma region
Area of bone formation


Mesenchymal tumors
Phosphaturic mesenchymal 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.

Definition
=========================================================================
Epidemiology
=========================================================================
Laboratory
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Clinical images
=========================================================================
Tumor of ethmoid sinus
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Tumor of craniofacial sinuses
Dentin matrix protein 1
Tumor of ethmoid sinus
Mandible tumor
Positive stains
=========================================================================
Differential diagnosis
=========================================================================


Neurofibroma - general

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 4 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Case reports
=========================================================================
Subtypes
=========================================================================
Clinical images
=========================================================================
Mouth
Skin
Gross description
=========================================================================
Gross images
=========================================================================
Scrotal tumor
Micro description
=========================================================================
Micro images
=========================================================================
Various images
Abdomen
Mouth

Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis (myxoid areas)
=========================================================================


Neurofibroma
Pacinian neurofibroma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 4 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================
Terminology
=========================================================================
Epidemiology
=========================================================================
Sites
=========================================================================
Etiology
=========================================================================
Case reports
=========================================================================
Diagrams
=========================================================================
Normal Pacinian corpuscle
Pacinian corpuscle labeled at bottom
Clinical images
=========================================================================
Forearm
Gingival lesion with smooth surface
Micro description
=========================================================================
Micro images
=========================================================================
Above row: normal Pacinian corpuscles; below row: pacinian neurofibroma
Elliptical or spindle-shaped nuclei
Pacinian corpuscle-like formations
Cells with concentric lamellar arrangement
Structures similar to Vater-Pacini corpuscles
S100+
A: mucinous nature is evident; B: tumor contains nerve fibers and delicate spindle cells focally arranged in parallel configurations similar to Pacinian corpuscles (C)
Source: AFIP Fascicle, 3rd series
Differential diagnosis
=========================================================================


Neurofibroma
Pigmented neurofibroma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 16 December 2014, last major update November 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

Definition
=========================================================================
Sites
=========================================================================
Clinical features
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Clinical images
=========================================================================
Above eyelid
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Above eyelid
Dermal spindle cell tumor
Loosely arranged tumor cells; pigment in inset
in NF1
S100+
MelanA +
Positive stains
=========================================================================
Negative stains
=========================================================================
Differential diagnosis
=========================================================================


Neurofibroma
Plexiform neurofibroma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 5 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================
Sites
=========================================================================
Clinical features
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Clinical images
=========================================================================
12 year old boy with swelling of the face and café-au-lait macules
Large mass on back - pre and post op
19 year old man with enlarging gluteal mass and café-au-lait patches
Neck tumor
Arm
Hand
Leg tumors
Gross description
=========================================================================
Gross images
=========================================================================
Brachial plexus
Micro description
=========================================================================
Micro images
=========================================================================
Facial swelling
Submandibular mass
Larynx
Plexiform features
Bladder tumor
Unknown sites
Tongue lesion - Contributed by Dr. R.F. Chinoy, Prince Aly Khan Hospital, India

Positive stains
=========================================================================
Differential diagnosis
=========================================================================


Neurofibroma
Neurofibromatosis type 1

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 5 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Clinical features
=========================================================================
Clinical images
=========================================================================
Lisch nodule
Cafe au lait spots
Differential diagnosis
=========================================================================


Neurofibroma
Neurofibromatosis type 2

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 5 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Additional references
=========================================================================


Peripheral nerve tumors
Nerve - normal

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 6 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

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


Peripheral nerve tumors
Myxopapillary ependymoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 6 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Gross images
=========================================================================
Two ovoid mass
Micro description
=========================================================================
Micro images
=========================================================================
Epithelioid cells with some cytoplasmic clearing
Cribriform pattern
Solid sheets and cords
L: S100; R: GFAP
L: AE1AE3; R: CAM5.2
Columnar cells
Radial processes
Positive stains
=========================================================================
Differential diagnosis
=========================================================================


Peripheral nerve tumors
Nerve sheath myxoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 6 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Case reports
=========================================================================
Clinical images
=========================================================================
Tender, solitary firm papule
Micro images
=========================================================================
Lower leg lesion
Gingival lesion is well demarcated
Thick, short collagen bundles and focal myxoid areas
S100
NSE
Positive stains
=========================================================================

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


Peripheral nerve tumors
Neuroma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 7 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See subtypes below: amputation/traumatic, granular cell traumatic, Morton, palisaded encapsulated

General
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Post-mastectomy
Positive stains
=========================================================================


Amputation / traumatic neuroma
General
=========================================================================
Case reports
=========================================================================
Micro images
=========================================================================
After neck surgery
L: S100, R: EMA


Granular cell traumatic neuroma
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Large granular cells in dense collagenous stroma
Positive stains (granular cells)
=========================================================================


Morton neuroma
General
=========================================================================
Diagram
=========================================================================
Metatarsal heads, intermetatarsal ligament, neuroma

Gross description
=========================================================================
Gross images
=========================================================================
Neuroma, fibrofatty tissue

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


Palisaded encapsulated neuroma
General
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Various images



Peripheral nerve tumors
Neurothekeoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 7 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Sites
=========================================================================
Clinical features
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Clinical images
=========================================================================
Thumb nodule
Lower back
Lower eyelid
Micro description
=========================================================================
Micro images
=========================================================================
Left thumb nodule of 5 month old boy
Lower eyelid of elderly man
Lobular proliferation with myxoid stroma
Mucin deposits (Alcian blue)
S100

Positive stains
=========================================================================
Negative stains
=========================================================================
Differential diagnosis
=========================================================================


Peripheral nerve tumors
Perineurioma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 7 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See subtypes below: reticular, sclerosing

General
=========================================================================
Case reports
=========================================================================
Clinical images
=========================================================================
Endobronchial nodule
Finger
Mouth
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Median nerve
Retroperitoneum
Site unknown
Endobronchial nodule in 53 year old woman
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Molecular description
=========================================================================


Reticular variant
General
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Stomach tumor
Positive stains
=========================================================================
Negative stains
=========================================================================
Differential diagnosis
=========================================================================


Sclerosing perineurioma
General
=========================================================================
Case reports
=========================================================================
Clinical images
=========================================================================
Palmar region
Micro images
=========================================================================
Various images
Buccal mucosa of 17 year old boy

Left palmar region of 16 year old girl


Peripheral nerve tumors
Pigmented neuroectodermal tumor of infancy

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 7 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================
Terminology
=========================================================================
Clinical features
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Clinical images
=========================================================================
Maxilla
Anterior region of maxilla
2 month old boy with maxillary tumor
Gross images
=========================================================================
Maxilla
Micro description
=========================================================================
Micro images
=========================================================================
Case of Week #165
Maxillary tumor #1
#2
Various stains of mandible lesion
Anterior region of maxilla
6 month old female infant with expansile growth of maxilla
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis
=========================================================================


Peripheral nerve tumors
Schwannoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 7 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See subtypes below: ancient, angiosarcoma-arising in, cellular, epithelioid malignant change, microcystic-reticular variant, pigmented, plexiform, psammomatous melanotic

General
=========================================================================
Clinical features
=========================================================================
Malignant transformation
=========================================================================
Treatment
=========================================================================
Gross description
=========================================================================
Gross images
=========================================================================
Well circumscribed
Micro description
=========================================================================
Micro images
=========================================================================
Various images
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Differential diagnosis (palisading patterns)
=========================================================================


Angiosarcoma in schwannoma
General
=========================================================================
Case reports
=========================================================================
Virtual slides
=========================================================================

Epithelioid angiosarcoma arising in a schwannoma
Differential diagnosis
=========================================================================


Ancient schwannoma
General
=========================================================================
Case reports
=========================================================================
Micro images
=========================================================================
Large, hyperchromatic, multilobated nuclei
Various images
Hypopharyngeal tumour
Thigh mass mimicking malignancy
Abdominal wall mass


Cellular schwannoma
General
=========================================================================
Case reports
=========================================================================
Micro images
=========================================================================
Site unknown
Nasal cavity
Bipolar spindle cells
S100 positive


Epithelioid malignant change
General
=========================================================================


Microcystic-reticular variant
General
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Various images from GI tract
Colon
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy images
=========================================================================
Irregular cell borders, elongated nuclei


Pigmented schwannoma
General
=========================================================================
Case reports
=========================================================================
Gross / clinical images
=========================================================================
Omental tumor
Micro images
=========================================================================
Omental tumor
Positive stains
=========================================================================
Negative stains
=========================================================================


Plexiform schwannoma
General
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Plexiform architecture
Nuclear palisading
Cellular areas
S100
Various images
Positive stains
=========================================================================
Differential diagnosis
=========================================================================


Psammomatous melanotic schwannoma
General
=========================================================================
Micro images
=========================================================================
Various images


Peripheral nerve tumors
Lymphoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 7 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

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


Peripheral nerve tumors
Malignant peripheral nerve sheath tumor (MPNST)

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

See subtypes below: epithelioid, malignant triton

General
=========================================================================
Case reports
=========================================================================
Clinical images
=========================================================================
Greater omentum
Gross description
=========================================================================
Gross images
=========================================================================
Large, yellow-tan
Firm, grey-white
Micro description
=========================================================================
Micro images
=========================================================================
Various images
Various images
Epithelioid cells
Plexiform
Various stains
Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Molecular / cytogenetics description
=========================================================================
Differential diagnosis
=========================================================================


Epithelioid MPNST
General
=========================================================================
Case reports
=========================================================================
Clinical images
=========================================================================
Foot #1
#2
Micro images
=========================================================================
Site unspecified: Fig 2 & 3a
Foot
Positive stains
=========================================================================
Negative stains
=========================================================================
Differential diagnosis
=========================================================================


Malignant triton tumor (MTT)
General
=========================================================================
Diagnostic criteria of Woodruff (Cancer 1973;32:426):
  1. Tumor arises along a peripheral nerve, in a ganglioneuroma, in NF1 patient, or is a metastasis from such a tumor
  2. Tumor has characteristics of Schwann cell tumor
  3. Rhabdomyoblasts arise from body of tumor
Case reports
=========================================================================
Gross images
=========================================================================
Buttock mass
Micro images
=========================================================================
Retroperitoneal tumor
Rhabdomyoblastic differentiation
Cerebellopontine angle


Perivascular epithelioid cell family of tumors (PEComas) of soft tissue
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.

See subtype below: sclerosing PEComa

Definition
=========================================================================
Epidemiology
=========================================================================
Prognostic factors
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Gross images
=========================================================================
Uterus: polypoid gray-white mass
Uterus: polypoid mass
Micro description
=========================================================================
Micro images
=========================================================================


Bladder:
Epithelioid cells with abundant eosinophilic cytoplasm
MelanA+
Smooth muscle actin+

Cervix:
Mass with central circular core
Infiltrative border
Spindled to epithelioid areas
Degenerative atypia
Pecomatosis
Ovarian hila
HMB45+

Head and neck:
Nasal PEComa
Larynx

Kidney:       Prostate:     Site unknown:
Figure 2b: MelanA+ tumor
Epithelioid cells are HMB45+
Spindle cells

Uterus:
Tumor, lung metastases, HMB45+
Malignant epithelioid cells
Actin+ (red) and HMB45+ (brown)
HMB45+ recurrent tumor

Unspecified:
Malignant tumor

Positive stains
=========================================================================
Negative stains
=========================================================================
Electron microscopy description
=========================================================================
Molecular / cytogenetics description
=========================================================================
Differential diagnosis
=========================================================================


Sclerosing PEComa
Definition
=========================================================================
Case reports
=========================================================================
Treatment
=========================================================================
Gross description
=========================================================================
Gross images
=========================================================================
Well-circumscribed, encapsulated tumor
Micro description
=========================================================================
Micro images
=========================================================================
Nests of clear cells in sclerotic stroma
Various stains
Positive stains
=========================================================================
Negative stains
=========================================================================


Perivascular epithelioid cell family of tumors (PEComas) of soft tissue
PEComa - abdominopelvic sarcoma

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 9 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Case reports
=========================================================================
Micro description
=========================================================================
Micro images
=========================================================================
Large neoplastic cells
Abundant cytoplasm
Nodal metastasis
Virtual slides
=========================================================================
Large renal tumor
Positive stains
=========================================================================
Negative stains
=========================================================================


Perivascular epithelioid cell family of tumors (PEComas) of soft tissue
PEComa - falciform ligament / ligamentum teres

Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 9 March 2013, last major update November 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================
Epidemiology
=========================================================================
Case reports
=========================================================================
Gross description
=========================================================================
Micro description
=========================================================================
Positive stains
=========================================================================
Negative stains
=========================================================================
Differential diagnosis
=========================================================================

End of Soft Tissue > Superpage 3


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