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Breast malignant, males, children
Superpage - Other
Revised: 12 December 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Sarcoma
General
Reviewer: Monika Roychowdhury, M.D (see Reviewers
page)
Revised: 24 September 2012, last major update September 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Epidemiology
=========================================================================
● Rare, < 0.1% of breast malignancies
● Median age 45-55 years
● Sarcomas rarely occur post-radiation therapy for breast cancer (Cancer 2005;104:856)
● Most common subtype is angiosarcoma (40%)
Treatment and prognosis
=========================================================================
● Treatment is similar as other sarcomas - excision with negative margins (J Clin Oncol 2003;21:2583)
● Axillary dissection not indicated
● 5 year overall survival is 67% (83% for tumors <5 cm and 42% for tumors >5 cm (Am J Surg 2008;196:559, Br J Cancer 2004;91:237)
● Angiosarcoma has worst prognosis (Radiother Oncol 2007;85:355, J Clin Oncol 2003;21:2583)
Gross description
=========================================================================
● Median size 4 cm
Micro description
=========================================================================
● Low grade: 0-5 mitotic figures/10 HPF and low grade nuclei
● High grade: 5+ mitotic figures/HPF and marked nuclear atypia or 6+ mitotic figures/HPF and moderate nuclear atypia
Sarcoma
Angiosarcoma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers
page)
Revised: 29 September 2012, last major update September 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Tumor composed of malignant cells with endothelial features
Terminology
=========================================================================
● Also called lymphangiosarcoma, less preferred term is “malignant hemangioendothelioma”
Epidemiology
=========================================================================
● Rare, < 0.2% of primary breast tumors (Ann Diagn Pathol 2009;13:147), 3-9% of breast sarcomas
● (a) young women with no prior history
● (b) women 5-10 years post-radiation therapy for breast carcinoma (in skin or breast, (Cancer 2009;115:4055), or
● (c) skin of chronically edematous arm after axillary lymph node dissection (Stewart-Treves syndrome, incidence has decreased dramatically due to use of more conservative surgery, Am J Surg Pathol 1983;7:329)
● Note: post-radiation and post-axillary dissection cases have more prominent cutaneous involvement
Clinical features
=========================================================================
● Clinically forms bulky mass associated with bruise-like cutaneous changes
● Estimated incidence of 0.14% after breast conserving therapy (J Am Acad Dermatol 2006;54:499)
● Precursor lesion is “atypical vascular lesion”, which occurs after surgery and radiation of the breast (Am J Surg Pathol 2008;32:943)
● May resemble recurrent breast carcinoma clinically (Clin Breast Cancer 2008;8:94)
Xray
=========================================================================
● Solitary mass on mammography without calcifications or skin thickening, at site of prior surgical incision
Case reports
=========================================================================
● Tumor post-radiation therapy #1 (Arch Pathol Lab Med 2002;126:989), #2 (Univ Oklahoma), #3 (Int Semin Surg Oncol 2006;3:26), #4-low grade tumor (Hum Pathol 1992;23:710), #5 - bilateral tumor with Paget’s disease (Mod Pathol 1995;8:1)
● 26 year old woman with epithelioid angiosarcoma (Am J Surg Pathol 1997;21:599)
Treatment and prognosis
=========================================================================
● Treatment is complete excision
● Post-radiation cases have shorter latency period and no edema, compared to Stewart-Treves syndrome cases (Am J Surg Pathol 2004;28:781)
● Tumors have similar behavior with or without prior radiation therapy (Cancer 2005;104:2682)
● Median survival of 3-6 years (Am J Clin Oncol 2009;32:582)
● Often recurs locally
● Grading may not have prognostic significance (Am J Surg Pathol 2008;32:1896, but see Am J Surg Pathol 1983;7:53)
Clinical images
=========================================================================
Hemorrhagic lesion
Post-radiotherapy
Erythema and ulceration
51 year old woman with high grade tumor
Gross description
=========================================================================
● Soft, spongy, hemorrhagic
● May have blue nodules at site of prior scar
● Mean 5cm
● Usually poorly circumscribed
Gross images
=========================================================================
Well circumscribed mass (AFIP)
Infiltrative mass with hemorrhage
Intermediate grade tumor with hemorrhage
High grade tumor
Contributed by anonymous pathologist:
Mastectomy post radiation and chemotherapy for ductal carcinoma
Microscopic description
=========================================================================
● Anastomosing vascular channels lined by atypical endothelial cells with pleomorphic, hyperchromatic nuclei
● Infiltrative margins
● Microscopic heterogeneity common within same tumor, so sample thoroughly
● Variable mitotic activity
● Usually no fibrous septae, no epithelial component
● Post-radiation tumors are typically high grade
Grade I (well differentiated):
● Anastomosing vascular channels dissect interlobular stroma
● Vessels have wide lumina with red blood cells
● Endothelium lining vessels have prominent and hyperchromatic nuclei, may resemble benign vascular tumors
Grade II (moderately differentiated):
● 75% of tumor is well differentiated, but solid foci are also found (Am J Surg Pathol 1981;5:629)
Grade III (poorly differentiated):
● Interanastomosing vascular channels are intermingled with solid endothelial or spindled areas, with necrosis and mitotic figures
● At least 50% of tumor is composed of solid or spindled areas without vascular channels
Micro images
=========================================================================
Neoplastic vascular channels
Solid areas and neoplastic vascular channels
Markedly pleomorphic tumor cells, mitotic figures and apoptotic cells
Focal spindle cells
Various images
Fig 1: Infiltrating vascular lesion with spindle cell proliferation in dermis
Fig 2/3: Pleomorphic spindle cells with “blood lakes” and brisk mitotic activity
Low grade tumor recurring as high grade tumor
Low grade angiosarcoma:
Low grade angiosarcoma (contributed by anonymous pathologist)
Intermediate grade angiosarcoma:
Dilated vascular spaces contain endothelial cells and red blood cells
Focal solid neoplastic vascular proliferation in fat
Focal spindle cell and small vessel proliferation
Focal complex capillary and endothelial cell proliferation
Spindle cells and mitotic figure
High grade angiosarcoma:
Irregular spaces resemble adenocarcinoma
Anastomosing vascular channels
High grade tumor
Anastomosing vascular channels with spindle and papillary foci
Solid growth and hemorrhagic necrosis
Spindle cells with indistinct vascular spaces
Plump spindle cells with mitoses
Blood lakes (foci of hemorrhagic necrosis
Post-mastectomy (AFIP):
Atypical vascular proliferation in dermis and subcutis and changes of chronic lymphedema
Vascular channels in superficial dermis with endothelial atypia
Anastomosing vascular channels with papillary proliferation of atypical endothelial cells
Focal solid pattern of atypical endothelial cells
Post-radiotherapy:
Skin tumor
Stains:
H&E, Ki-67 and Skp2
Left: CD31; right: Factor VIII-related antigen
Cytology description
=========================================================================
● Moderate to highly cellular with variable cellular aggregates
● Cells are epithelioid and spindled
● May have subtle angioformative changes (Cancer 2005;105:145)
Positive stains
=========================================================================
● Vimentin, Factor VIII
● CD31 and CD34 (well differentiated areas)
● High Ki-67 (Arch Pathol Lab Med 2007;131:538)
● ER (variable)
Negative stains
=========================================================================
● Keratin
Electron microscopy description
=========================================================================
● Prominent pinocytic vesicles and cell-cell junctions
Differential diagnosis
=========================================================================
● Metaplastic carcinoma
● Acantholytic squamous cell carcinoma: has at least focal areas of squamous differentiation, keratin+, negative for vascular markers
● Hemangioma: well circumscribed, no atypia
● Atypical vascular lesions: more circumscribed, less atypia than low grade angiosarcoma
● Pseudoangiomatous stromal hyperplasia
Additional references
=========================================================================
Sarcoma
Leiomyosarcoma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers
page)
Revised: 14 October 2012, last major update October 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Malignant smooth muscle tumor
● Rare in breast as primary or metastases (< 1% of all breast tumors, ~25 cases reported in English literature (J Breast Cancer 2012;15:124)
Treatment
=========================================================================
● Excision with negative margin
● Radiation therapy suggested for large tumors with < 3 cm margin (Breast 2011;20:389)
Case reports
=========================================================================
● 18 year old woman (Breast 2011;20:389)
● 48 year old woman (J Breast Cancer 2012;15:124)
● 50 year old woman with 10 year history of cyclophosphamide for SLE (Cases J 2008 Nov 7;1(1):301)
● 52 year old woman (J Zheijiang Univ Sci B 2008;9:109)
● 53 year old man with leiomyosarcoma of nipple (Am J Surg Pathol 1978;2:299)
Clinical images
=========================================================================
Necrotic breast mass
Gross images
=========================================================================
Lobulated elastic tumor
Micro description
=========================================================================
● Intersecting fascicles of spindle cells with moderate eosinophilic cytoplasm, cigar shaped nuclei with blunt ends, moderate nuclear atypia, frequent mitotic figures
Micro images
=========================================================================
Dense cellularity and intersecting fascicles
48 year old woman
Tumor of nipple-areolar complex
Nuclear pleomorphism and mitotic activity (AFIP)
Cellular pleomorphic tumor
Cytology description
=========================================================================
● Large, dissociated round to spindle cells, medium to large, with abundant vacuolated cytoplasm with occasional intranuclear cytoplasmic invaginations; cells have pleomorphic nuclei, prominent nucleoli
● Also mitotic figures, osteoclast-like giant cells and stromal fragments (Diagn Cytopathol 2003;29:172, Acta Cytol 2008;52:485)
Cytology images
=========================================================================
Various images
Positive stains
=========================================================================
● Actin, desmin, vimentin
Negative stains
=========================================================================
● Keratin, S100, CD34
Molecular / cytogenetics
=========================================================================
● 10q-, 13q-
● Also 17p-, 1q+, 17p+ (Cancer Genet Cytogenet 2004;149:53)
Differential diagnosis
=========================================================================
● Metastatic tumor (Diagn Cytopathol 2007;35:508, Ir J Med Sci 2011;180:889)
Sarcoma
Liposarcoma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers
page)
Revised: 7 November 2012, last major update October 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Malignant tumor containing at least a few lipoblasts
Epidemiology
=========================================================================
● Rare, 100 cases reported through 2002
● 0.3% of all breast sarcomas, themselves only 1% of all breast malignancies
● Median age 47 years, range 19-76 years
Clinical
=========================================================================
● May be associated with radiation therapy
● Slow growing, painful breast mass, usually unilateral
● Axillary nodal metastases are rare, skin changes unusual
● Usually myxoid or pleomorphic subtype
Treatment and prognosis
=========================================================================
● Particularly aggressive when associated with pregnancy
● Death, when it occurs, is usually within 18 months of diagnosis
● Treatment is wide excision, axillary dissection not needed (Hum Pathol 1986;17:906)
Case reports
=========================================================================
● 19 year old woman with pleomorphic liposarcoma mimicking abscess (Breast J 2010;16:537)
● 25 year old woman with myxoid liposarcoma diagnosed as fibroadenoma on FNA (Diagn Cytopathol 2008;36:674)
● 42 year old woman (JBR-BTR 2010;93:299)
● 47 year old woman with primary pleomorphic liposarcoma (Indian J Pathol Microbiol 2011;54:124)
● 75 year old woman (Arch Pathol Lab Med 2001;125:1503)
Gross description
=========================================================================
● Median 8 cm, well circumscribed, gelatinous to firm with yellow/tan cut surface; larger tumors may be necrotic
Gross images
=========================================================================
Circumscribed tumors
Micro description
=========================================================================
● Similar to soft tissue tumors
● Depending on subtype: mixture of pleomorphic bizarre giant cells, myxoid stroma, mature adipose cells, inflammatory cells, lipoblasts (scalloped, irregular, hyperchromatic nuclei and sharply defined intracytoplasmic vacuoles containing lipid) and capillaries
● Margins are usually at least focally infiltrative
Micro images
=========================================================================
Myxoid liposarcoma
Well differentiated liposarcoma
Lipoblast with vacuolated cytoplasm
Well circumscribed tumor (AFIP)
Positive stains
=========================================================================
● S100 (lipoblasts)
Differential diagnosis
=========================================================================
● Adenolipoma: lipoma with eccrine sweat glands or other epithelial elements
● Angiolipoma: prominent capillaries with hyaline thrombi; no atypia, no lipoblasts
● Fibroadenoma with fat: no atypia, no lipoblasts
● Lipoma: no atypia, no lipoblasts
● Malignant phyllodes tumor with focal liposarcomatous differentiation: has distinctive phyllodes component
● Pleomorphic lipoma: prominent floret cells, no atypia, no lipoblasts
● Silicone implants: silicone is refractile, may have granulomas that resemble lipoblasts
Sarcoma
Low grade myofibroblastic sarcoma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers
page)
Revised: 7 November 2012, last major update November 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Rare malignant tumor of myofibroblasts (Am J Surg Pathol 1998;22:1228)
Terminology
=========================================================================
● Also called myofibrosarcoma
● Not part of WHO breast classification
Clinical features
=========================================================================
● Commonly recurs, only rarely metastasizes
Case reports
=========================================================================
● 55 year old woman with death due to metastatic tumor (Am J Surg Pathol 1997;21:489)
Gross description
=========================================================================
● Firm, pale, fibrous cut surface, ill defined margins
Micro description
=========================================================================
● Fascicles of spindle cells surrounded by dense collagen
● Cells have ill defined, pale, eosinophilic cytoplasm, fusiform and pleomorphic nuclei, numerous mitotic figures
● Also some giant cells
● Margins are infiltrative, often grossly (Pathol Res Pract 1999;195:1)
Micro images
=========================================================================
Fig 1A: fascicular growth
Fig 1B: alpha smooth muscle actin+, vimentin+ (insert)
Fig 1C: fibronectin+ matrix
Fig 1D: type IV collagen negative
Positive stains
=========================================================================
● At least one myogenic marker (desmin, alpha smooth muscle actin, muscle specific actin or calponin)
Negative stains
=========================================================================
● S100, EMA, h-caldesmon, ALK
Electron microscopy
=========================================================================
● Features of myofibroblasts: discontinuous basal lamina, abundant rough endoplasmic reticulum, intermediate filaments and myofilaments; indented and clefted nuclei
Electron microscopy images
=========================================================================
Fig 2A: arrows point to thin filaments at the cell surface suggestive of fibronexus junctions
Fig 2B: arrows point to fibronectin fibrils extending into the extracellular matrix
Molecular / cytogenetics description
=========================================================================
● Gains at 1p11-->p36.3 (66%), 12p12.2-->p13.2 (45%), 5p13.2-->p15.3 (31%), +22 (28%), loss at 15q25-->q26.2 (24%) (Am J Clin Pathol 2009;131:701)
Differential diagnosis
=========================================================================
● Fibromatosis / myofibromatosis: irregular, nonencapsulated proliferation of spindle cells forming interlacing fascicles with variable collagen deposition and cellularity; no/rare mitotic figures
● Fibrosarcoma: highly cellular fibroblastic proliferation in herringbone pattern
● Inflammatory myofibroblastic tumor: more heterogeneous, less cellular, less hyperchromasia, less infiltrative, ALK+ (Hum Pathol 2008;39:846)
● Leiomyosarcoma: alternating fascicular pattern, usually high grade
● Myofibroblastoma: may have some pleomorphism, but low mitotic activity
● Nodular fasciitis: not infiltrative, not deep, lacks chromosomal anomalies
● Solitary fibrous tumor: patternless architecture of hypo- and hypercellular areas separated by thick, hyalinized collagen with cracking artifact and hemangiopericytoma-like vessels
Sarcoma
Malignant Fibrous Histiocytoma (MFH)
Reviewer: Monika Roychowdhury, M.D. (see Reviewers
page)
Revised: 7 November 2012, last major update November 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Terminology
=========================================================================
● Not part of WHO breast classification
● Rare in breast or elsewhere under new WHO definition (see micro description)
Clinical features
=========================================================================
● Aggressive, with frequent distant metastases and death due to disease (Am J Surg Pathol 1992;16:667)
Case reports
=========================================================================
● 32 year old woman with recurrent primary MFH of breast (Acta Cytol 2010;54:985)
● 44 year old woman post-radiation therapy for invasive ductal carcinoma (Int Semin Surg Oncol;3:18)
● 46 year old woman post-radiation therapy for invasive ductal carcinoma (Cases J 2008 Nov 17;1(1):313)
Clinical images
=========================================================================
Cystic tumor with skin tethering
Gross images
=========================================================================
Tumor invades skin
Specimen includes ribs posteriorly
Micro description
=========================================================================
● High grade spindle cell tumor
● Excludes tumors with any recognizable line of differentiation other than fibroblasts or myofibroblasts
● May show various patterns such as storiform-pleomorphic, myxofibrosarcoma or giant cell type
● Entrapped breast ductal epithelium should not be misinterpreted as the epithelial component of a biphasic tumor
● A florid lymphoid response should not be confused with metaplastic carcinoma
Micro images
=========================================================================
Marked nuclear pleomorphism and giant cells
Tumor necrosis after neoadjuvant chemotherapy
Cytology description
=========================================================================
● May show cell clusters, fascicles, and dissociated cells displaying spindle cell morphology, marked pleomorphism, bizarre uninucleate/multinucleate giant cells, prominent mitotic activity
Cytology images
=========================================================================
stromal sarcoma with features of giant cell MFH
Positive stains
=========================================================================
● CD68 (71%), smooth muscle actin (36%), rare focal ER and PR (Ann Diagn Pathol 2011;15:407)
Negative stains
=========================================================================
● CD34, S100, desmin, keratins (CK7, CK20, CK5/6, CK18, Ann Diagn Pathol 2011;15:407)
Differential diagnosis
=========================================================================
● May resemble medullary carcinoma at FNA (Acta Cytol 2006;50:577)
Sarcoma
Malignant Peripheral Nerve Sheath Tumor (MPNST)
Reviewer: Monika Roychowdhury, M.D. (see Reviewers
page)
Revised: 7 November 2012, last major update November 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Very rare in breast
● Most cases are not associated with neurofibromatosis
Terminology
=========================================================================
● Not part of WHO breast classification
Case reports
=========================================================================
● 19 year old woman (J Med Assoc Thai 2006;89:377)
● 38 year old woman (World J Surg Oncol 2007;5:142)
● 56 year old woman with 30 cm tumor (Br J Radiol 2007;80:e44)
Gross images
=========================================================================
30 cm tumor
Micro images
=========================================================================
Alternating hyper and hypocellular areas with palisading spindle shaped cells and intervening myxoid areas; cells are S100+ (inset)
Hyperchromatic and pleomorphic wavy nuclei with mitoses
Sarcoma
Osteosarcoma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers
page)
Revised: 13 November 2012, last major update November 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Malignant tumor of osteoid producing spindle cells
Epidemiology
=========================================================================
● Rare
● Median age 64 years, range 27-89 years
Case reports
=========================================================================
● 16 year old girl (J Pediatr Hematol Oncol 2012;34:e261)
● 40 year old woman (World J Surg Oncol 2006;4:90)
● 49 year old woman (APMIS 2006;114:581)
● 59 year old woman (Pathol Int 2009;59:111)
● 88 and 96 year old women (Arch Pathol Lab Med 2007;131:792)
Treatment and prognosis
=========================================================================
● Total excision without axillary dissection (Am J Surg Pathol 1998;22:925)
● Local recurrence, metastases and death from disease are common
Gross description
=========================================================================
● Mean 5 cm (1-13 cm)
● 60% are grossly circumscribed
Gross images
=========================================================================
Large, relatively well-circumscribed, necrotic tumor with cartilaginous and calcified foci (after tissue sampling)
Well circumscribed tumor with large areas of ossification (asterisks) and cystic or necrotic zones (stars)
Micro description
=========================================================================
● Resembles skeletal osteosarcoma, with fibroblastic, osteoclastic or osteoblastic subtypes
● By definition has spindle cells and neoplastic osteoid or bone, lacks an epithelial component and does not originate in bone
● Usually at least focally infiltrative
Micro images
=========================================================================
Neoplastic bone and spindle cells
Pleomorphic high-grade sarcoma with malignant osteoid (stars) and multinucleated osteoclastic giant cells (arrows)
Negative stains
=========================================================================
● ER, PR, HER2 (Arch Pathol Lab Med 2006;130:691)
Differential diagnosis
=========================================================================
● Metaplastic carcinoma: has epithelial component
● Metastases: need clinical history (Australas Radiol 1999;43:108)
● Phyllodes tumor with osteosarcomatous differentiation: phyllodes component present (J Med Case Rep 2011;5:293)
Sarcoma
Rhabdomyosarcoma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers
page)
Revised: 15 November 2012, last major update November 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Malignant tumor with features of skeletal muscle differentiation
● Primary or secondary (Pediatr Hematol Oncol 1996;13:277)
Epidemiology
=========================================================================
● Very rare (Chin Med J (Engl) 2012;125:2618), usually teenager girls with alveolar subtype
Case reports
=========================================================================
● 13 year old girl (Surg Today 2007;37:38)
● 51 year old woman (Arch Pathol Lab Med 1998;122:747)
Gross description
=========================================================================
● Round or oval, well-demarcated but non-encapsulated masses
● Hard or soft; cut surface has homogeneous grayish yellow or white tissue with focal necrosis
Micro description
=========================================================================
● Primitive myoblasts and rhabdomyoblasts with cytoplasmic cross striations
● Usually alveolar subtype (Med Pediatr Oncol 1997;29:181)
● Poorly-differentiated small round or polygonal cells with sparse eosinophilic cytoplasm
● Nuclei are round/oval and densely stained
● Frequent mitotic figuresd
● “Racquet” and “strap” cells with peripherally placed nuclei are specific
Micro images
=========================================================================
Variable skeletal muscle differentiation
Positive stains
=========================================================================
● Vimentin, desmin, MyoD1, myogenin
Negative stains
=========================================================================
● Cytokeratin AE1/AE3
Differential diagnosis
=========================================================================
● Malignant phyllodes tumor: may have rhabdomyosarcomatous differentiation, but also has phyllodes component
● Metaplastic carcinoma: has epithelial component
Sarcoma
Sarcoma NOS
Reviewer: Monika Roychowdhury, M.D., (see Reviewers
page)
Revised: 21 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
General
=========================================================================
● A diagnosis of exclusion
● Extensive tumor sampling and immunostaining are required before making this diagnosis
Terminology
=========================================================================
● Not part of WHO breast classification
Micro description
=========================================================================
● Spindle cells with markedly pleomorphic nuclei and abundant mitotic figures
(Am J Surg Pathol 2006;30:450)
● By definition, no evidence of carcinoma or a specific type of sarcomatous differentiation
Positive stains
=========================================================================
● CD10, vimentin
● EGFR (often)
Negative stains
=========================================================================
● Keratin, CD34, desmin, h-caldesmon
Differential diagnosis
=========================================================================
● Sarcomatoid metaplastic carcinoma: keratin+
● Stromal sarcoma: CD34+, no severe atypia
Sarcoma
Stromal sarcoma
Reviewer: Monika Roychowdhury, M.D., (see Reviewers
page)
Revised: 21 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
General
=========================================================================
● Rare lesion with sarcomatous stroma, benign ductal elements, no phyllodes architecture
(Am J Surg Pathol 2003;27:343)
Terminology
=========================================================================
● Also called periductal stromal sarcoma
Epidemiology
=========================================================================
● Mean age 55 years, range 37-89 years
Treatment and prognosis
=========================================================================
● Excision with negative margin
● May recur
Case reports
=========================================================================
● 14 year old boy (J Med Case Rep 2011;5:249)
● 29 year old woman (Surg Today 2011;41:1145)
● 47 year old woman with primary stromal sarcoma of the breast with MFH like features (Diagn Cytopathol 2011;39:223)
● 52 year old woman whose tumor had myxoid features (Pathol Int 2009;59:588)
● Tumor involving entire breast with axillary nodal metastases (Asian J Surg 2004;27:339)
● Two cases (Gan To Kagaku Ryoho 2011;38:2171)
Gross description
=========================================================================
● Mean 3 cm, solid, gray-white, homogenous
Micro description
=========================================================================
● Circumferential cuffs of predominantly uniform plump spindle cells with variable cellularity and atypia surrounding open tubules and ducts, but no phyllodes pattern
● May have multiple nodules separated by adipose tissue
● >3 stromal mitotic figures per 10 HPF
● Stromal infiltration into adjacent breast tissue
● May have osseous metaplasia or resemble fibrosarcoma
● Periductal stromal hyperplasia if no/minimal atypia and 0-2 stromal mitotic figures/10 HPF
Micro images
=========================================================================
14 year old boy
Positive stains
=========================================================================
● CD34
● Variable CD117
Negative stains
=========================================================================
● ER, PR, myoepithelial markers
Electron microscopy descriptions
=========================================================================
● Immature cells with abundant free ribosomes, profiles of rough ER, variable microfilaments
● Often prominent cell nesting and a variety of cell junctions, including desmosomes
(Cancer 1979;43:209)
Other malignancies
Lymphoma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 16 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Criteria for primary breast lymphoma: (a) sufficient tissue for diagnosis; (b) close interaction between lymphoma infiltrate and breast tissue; (c) no evidence of widespread lymphoma at time of diagnosis; (d) no prior diagnosis of nonbreast lymphoma (Cancer 1972;29:1705)
● Secondary breast lymphoma has similar incidence as primary breast lymphoma and is most common metastatic disease to breast
Epidemiology
=========================================================================
● Rare, < 1% of all breast malignancies are primary breast lymphoma
● Usually ages 30-35 years (diffuse large B cell) or 55-60 years (diffuse large B cell or MALT-type)
● Screening mammography may be increasing detection of low-grade lymphoma
● No association between implants and lymphoma (Plast Reconstr Surg 2009;123:790), but see anaplastic lymphoma below
Prognostic features
=========================================================================
● Low stage is favorable prognostic factor
● Unfavorable factors are young age and high stage (Leuk Lymphoma 2009;50:918)
● CNS is common site of relapse (BMC Cancer 2008;8:86)
Treatment
=========================================================================
● Radiation therapy, chemotherapy and Rituximab
● No advantage to mastectomy (Ann Surg 2007;245:784)
Gross description
=========================================================================
● Soft, gray-white
● 25% bilateral
● No skin retraction, no nipple discharge
Micro description
=========================================================================
● Varies by subtype - see lymphoma chapters for more detail
Cytology images
=========================================================================
Dyscohesive cells - subtype not specified
Positive stains
=========================================================================
● CD45, B or T cell markers
● Other markers vary by subtype
Negative stains
=========================================================================
● Keratin (may stain lymphoepithelial lesions)
Differential diagnosis
=========================================================================
● Lobular carcinoma: usually linear or targetoid patterns, keratin+ and CD45-
● Lymphoid hyperplasia: may resemble low grade B cell lymphomas
● Lymphocytic mastitis: may be difficult to differentiate on core biopsy (Breast Cancer 2009;16:141)
Additional references
=========================================================================
● Am J Surg Pathol 1993;17:574, Mod Pathol 2000;13:599 (T cell lymphomas), Am J Surg Pathol 1994;18:288, Arch Pathol Lab Med 1999;123:1208
Subtypes
=========================================================================
● 94% B cell and 4% T cell lymphomas in one study (Br J Radiol 2012;85:e195)
Anaplastic large cell lymphoma:
● Associated with implants, particularly if ALK negative: odds ratio is 18.2, although absolute risk is low (JAMA 2008;300:2030)
● Median age 52 years (Arch Pathol Lab Med 2009;133:1383)
● 33 year old woman with silicon implant and ALK negative tumor (Arch Pathol Lab Med 2003;127:e115)
● 92 year old woman with sarcomatoid variant (Arch Pathol Lab Med 2002;126:723)
Large cells with abundant cytoplasm Associated with silicon implant
ALK- cases Various images
Sarcomatoid variant TIA+ and ALK+
Burkitt’s lymphoma:
● In African patients, may present with massive bilateral breast involvement
● Patients may be pregnant or lactating
● Less common than other subtypes
● 12 year old girl in Africa with giant bilateral tumors (Arch Gynecol Obstet 2009;279:743)
Lymphocytic infiltrate Ki-67 staining is diffuse and strong
Large cells with deeply basophilic cytoplasm and multiple intracytoplasmic lipid vacuoles, high N/C ratio and hyperchromatic round nuclei
CLL / SLL:
Xray, H&E, CD5, CD20
Contributed by Dr. Julia Braza, Beth Israel Deaconness Medical Center, Boston, Massachusetts
Diffuse large B cell lymphoma:
● Most common subtype of primary breast lymphoma (Am J Hematol 2009;84:133, Cancer 2007;110:25)
● Typically poorer prognosis if high proliferative (Ki-67) activity and nongerminal center B cell phenotype (CD10-, MUM1+, Mod Pathol 2005;18:398); better prognosis if germinal center phenotype (Leuk Res 2008;32:1837)
● 40 year old woman with bilateral tumors, diagnosed by FNA (Arch Pathol Lab Med 2005;129:694)
● 55 year old woman whose tumor exhibited clear cell change (Case of the Week #217)
Rapidly growing mass
Large cells with 1 Diffuse proliferation of large centroblasts
or more nucleoli and starry sky macrophages
H&E and CD20 Weak BCL10+
Various images Mixed with MALT
Various images
Follicular lymphoma:
● Usually stage I (65%), but 20% are stage III/IV
● 56 year old woman a non-palpable BI-RADS 4B lesion without microcalcifications, diagnosed by biopsy (J Med Case Rep 2007;1:113)
Bulging and fleshy tumor
Follicular lymphoma BCL2+
Mantle cell lymphoma:
Various images
Marginal zone / MALT lymphoma:
● Usually stage I, 10% bilateral, survival > 90% at 5 years and no MALT1 gene rearrangement (Mod Pathol 2006;19:1402)
● Relatively indolent behavior compared to other sites (Ann Oncol 2009;20:1993)
● Bilateral MALT lymphoma (57 year old woman-World J Surg Oncol 2008;6:52, 64 year old woman-Arch Pathol Lab Med 2000;124:1233)
● 62 year old woman (Breast Care (Basel) 2011;6:391)
● 79 year old woman with collision tumor of invasive ductal NOS and MALT lymphoma (Arch Pathol Lab Med 2004;128:99)
● 87 year old woman with CD5+ marginal zone / MALT lymphoma (Arch Pathol Lab Med 2004;128:99)
H&E, CD20, BCL10
NK lymphoma, nasal type:
● 20 year old woman with post-transplant lymphoproliferative disorder (Mod Pathol 2004;17:125)
Lobular pattern of Tumor cells have abundant cytoplasm
infiltration and irregular nuclei
Pan-keratin immunostain high- TIA+ and CD56+
lights lymphoepithelial lesions
Peripheral T cell lymphoma:
● 37 year old woman with palpable breast mass (Case of the Week #192)
CD4+ large cell tumor Cells have clear cytoplasm and mitotic activity
CD8+ tumor
Other malignancies
Myeloid sarcoma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 17 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● See also leukemia-acute chapter
● Neoplasm of myeloid cells associated with acute myeloid leukemia (usually as relapse), myeloproliferative or myelodysplastic disorder
Terminology
=========================================================================
● Also called granulocytic sarcoma or chloroma
● Not part of WHO breast classification
Epidemiology
=========================================================================
● Uncommon (< 100 cases reported)
● Almost always women
● Median age 52 years, range 31-73 years
Clinical features
=========================================================================
● Rarely occurs as an isolated mass (Arch Pathol Lab Med 2005;129:32)
● Need immunostains to diagnose and to prevent misdiagnosis as lymphoma or sarcoma (Breast J 2004;10:48)
● In patients with leukemia, diagnosis is typically followed by bone marrow relapse after mean 7 months (range, 1-19 months) and poor outcome (Chin Med J (Engl) 2008;121:1854)
Case reports
=========================================================================
● 25 year old woman with AML without maturation (Coll Antropol 2010;34:641)
● 40 year old woman with synchronous granulocytic sarcoma of the breast and spine (Chin Med J (Engl) 2008;121:1854)
● Elderly woman with isolated breast myeloid metaplasia 16 years after initial diagnosis (Am J Surg Pathol 1980;4:281)
● Bilateral myeloid sarcoma of breast (J Clin Oncol 2012;30:e199)
● Other cases: Eur J Gynaecol Oncol 2011;32:435, Breast J 2004;10:48
Treatment
=========================================================================
● Systemic chemotherapy (similar to acute leukemia), possibly radiation therapy (Ann Hematol 2003;82:431)
Micro description
=========================================================================
● Well to poorly differentiated to blastic tumor of immature and mature granulocytes or monocytes
● Also immature eosinophilic precursors
● Usually preserves ductal and lobular structures
● No / minimal necrosis
● Dissection of collagen by tumor cells is common (Chin Med J (Engl) 2008;121:1854)
Micro images
=========================================================================
Various images
Myeloperoxidase+ and CD43+
Positive stains
=========================================================================
Varies by type of myeloid leukemia:
● Naphthol AS-D chloroacetate esterase, myeloperoxidase, lysozyme, CD43, CD68
● Variable CD117, CD45, TdT, CD79a and PAX5
Negative stains
=========================================================================
● CD3, CD20
Molecular description
=========================================================================
● May demonstrate mutations of primary hematopoietic neoplasm / leukemia (J Clin Pathol 2010;63:558)
Differential diagnosis
=========================================================================
● Small round cell tumors (in children)
● Lymphoma
● Lobular carcinoma
Other malignancies
Plasmacytoma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 17 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Neoplasm of plasma cells, either primary to breast or secondary (most cases) to a systemic process or another plasmacytoma
Terminology
=========================================================================
● Not part of WHO breast classification
Clinical features
=========================================================================
● Rare
● May progress to multiple myeloma after years of remission
● Frozen section diagnoses are often incorrect - resembles lobular or poorly differentiated tumor, but with a grossly well circumscribed appearance
Case reports
=========================================================================
● 27 year old woman with coexisting ductal carcinoma (World J Surg Oncol 2009;7:43)
● 37 year old woman with only breast involvement (Arch Pathol Lab Med 2001;125:1078)
● 70 year old woman with recurrence of mediastinal disease in bilateral breasts (World J Surg Oncol 2004;2:29)
● 78 year old man with breast and axillary nodal involvement (Clin Breast Cancer 2006;7:81)
● Patient with disease free survival of 9+ years (Arch Pathol Lab Med 1984;108:676)
Clinical images
=========================================================================
Well-defined mass with irregular borders
Micro description
=========================================================================
● Immature and mature plasma cells with nuclear pleomorphism
● Also binucleated and multinucleated forms, mitotic figures and necrosis
Micro images
=========================================================================
Plasma cells, some binucleated, Nuclear pleomorphism, binucleated and
surrounding benign lobules multinucleated plasma cells with enlarged nucleoli
Tumor in HIV+ man
Plasma cells (long arrows), Dense infiltrate of plasma cells
Russell bodies (short arrow) and lymphocytes (AFIP)
and lymphocytes
With ductal carcinoma Her-2 negtive
Plasma cells are IgA+ Monoclonal lambda staining
and kappa light chain+
Kappa staining Diffuse Ki-67 nuclear staining
Cytology description
=========================================================================
● Dispersed population of plasmacytoid cells at various stages of maturation (Acta Cytol 2003;47:1107)
● Mature plasma cells have an eccentric nucleus and abundant deep basophilic cytoplasm with a paranuclear halo
● Plasmablasts (immature plasma cells) have a prominent eccentric nucleus with a single large nucleolus and abundant deep basophilic cytoplasm with no paranuclear halo
● Also binucleate and multinucleate forms (Acta Cytol 1997;41:364)
Differential diagnosis
=========================================================================
● Plasma cell mastitis: no light chain restriction
● Melanoma
● MALT lymphoma
Other malignancies
Rosai-Dorfman disease
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 17 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Typically massive lymph node involvement that may also involve extranodal sites
● Associated with systemic symptoms (fever, leukocytosis, anemia)
Terminology
=========================================================================
● Not part of WHO breast classification
● Also called sinus histiocytosis with massive lymphadenopathy
Clinical features
=========================================================================
● Very rare in breast, < 25 cases reported
● May have disease confined to breast or disseminated disease
● Most common sites are skin, subcutis, upper respiratory tract, bone, eye, adnexae and CNS
● Usually resolves spontaneously, although systemic cases may cause death
Case reports
=========================================================================
● 35 year old man (Acta Cytol 2010;54:349)
● 43 year old woman with enlarging breast mass (Univ Pittsburgh Case #338)
● 50 year old woman with disease confined to breast mimicking cancer (Pathol Res Pract 2007;203:741)
● 65 year old woman with multiple breast nodules (Am J Surg Pathol 1999;23:359)
● 67 year old woman (Gac Med Mex 2010;146:212)
● 75 year old woman with 2 breast tumors (Ned Tijdschr Geneeskd 2011;155:A3176)
● Breast mass and axillary lymphadenopathy (Breast J 2011;17:516)
● Bilateral breast involvement by disseminated Rosai-Dorfman disease (Breast J 2011;17:309)
● Three patients with Rosai-Dorfman disease confined to breast (Ann Diagn Pathol 2010;14:81)
● With recurrence after excision (Am J Med Sci 2010;339:282)
Gross description
=========================================================================
● Circumscribed, often multinodular masses in breast stroma
● Dermis and subcutis uninvolved
Micro description
=========================================================================
● Large histiocytes with abundant pale eosinophilic cytoplasm, mildly atypical round vesicular nuclei (Am J Surg Pathol 1997;21:664)
● Lymphocytophagocytosis (emperipolesis) in background of mature lymphocytes and plasma cells
Micro images
=========================================================================
Lymphoplasmacytic infiltrate Histiocytes with emperipolesis (arrowhead) with
with histiocytes (fig 1) lymphocytes, plasma cells and fibrosis
AFIP images:
Erythrophagocytosis With marked sinusoidal edema
Emperipolesis CD68+ histiocytes (fig 2) Sinusoids distended by histiocytes
Cytology description
=========================================================================
● Large pale cells with enlarged irregular nuclei, lymphocytes and plasma cells, also fragments of fibrous tissue and calcific debris
● Only rare lymphophagocytosis (emperipolesis, Diagn Cytopathol 1999;21:287)
Positive stains
=========================================================================
● S100, CD68
Negative stains
=========================================================================
● CD1a
Differential diagnosis
=========================================================================
● Idiopathic granulomatous mastitis
● Tuberculosis or other infectious granulomas
● Langerhans’ cell histiocytosis
● Erdheim-Chester disease
● Benign fibrous histiocytoma
● Melanoma
Childhood tumors
Breast tumors in children - general
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 17 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
See also thelarche, pubertal macromastia, and other topics in Breast-nonmalignant chapter
Clinical features
=========================================================================
● Malignant disease is rare; most patients require only clinical examination and reassurance
● Fine needle aspiration or core biopsy is usually adequate (Eur J Pediatr Surg 2006;16:303, Acta Cytol 2008;52:681)
● Most common benign lesions are fibroadenoma, juvenile fibroadenoma and virginal hypertrophy (J Indian Med Assoc 2001;99:619)
● Masses may also be due to normal or abnormal breast development (physiological masses usually regress, Zhonghua Yi Xue Za Zhi 2008;88:2556), infection, trauma or cysts
Unilateral breast development:
● Common
● May resemble a mass
● May exist as long as 2 years before other breast becomes palpable
Fibrocystic disease:
● Rare
Carcinoma:
● Very rare
Childhood tumors
Juvenile fibroadenoma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Terminology
=========================================================================
● Also called giant fibroadenoma
● Not a distinct entity in WHO breast classification
Epidemiology
=========================================================================
● Usually adolescents, often African-American, often bilateral and with rapid growth to > 10 cm
Clinical features
=========================================================================
● May have atypical ductal hyperplasia suggestive of DCIS - low risk of carcinoma, but follow-up is recommended (Am J Surg Pathol 1987;11:184)
Prognostic features
=========================================================================
● Patients with multiple bilateral tumors should anticipate recurrence but not malignant change (Am J Surg Pathol 1985;9:730)
Case reports
=========================================================================
● 12 year old girl with Beckwith-Wiedemann syndrome and bilateral tumors (Ann Plast Surg 2010;64:803)
● 12 year old girl with bilateral giant tumors (Patholog Res Int 2011;2011:482046)
● 12 year old girl with bloody nipple discharge (Pediatr Neonatol 2010;51:190)
● 13 year old girl with hemihypertrophy and recurrent giant tumors (Breast Dis 2011;33:41)
● 13 year old girl with tumor exhibiting fibroadenomatoid hyperplasia (The Internet Journal of Surgery 2007;12:1)
● 15 year old girl with 3 kg tumor (J Pediatr Adolesc Gynecol 2009;22:e25)
Treatment
=========================================================================
● Excise but conserve as much breast tissue as possible (Breast J 2000;6:418)
Clinical images
=========================================================================
Various images
Gross images
=========================================================================
Various images
Bilateral giant juvenile fibroadenoma
Gray-white mass (fig 4)
Micro description
=========================================================================
● Stromal and epithelial hyperplasia, but no stromal atypia and no / rare stromal mitotic figures
● No periductal increase in cellularity, no stromal overgrowth, no cytologic atypia, mitotic rate < 3 / HPF (Stanford University)
Micro images
=========================================================================
Stromal and epithelial hyperplasia
Bilateral giant juvenile fibroadenoma
Cytology images
=========================================================================
Cluster of epithelial cells with Epithelial cells and stromal fragments
mild pleomorphism with few spindled cells
Branching sheets of epithelial cells with many bare nuclei and myxoid stromal fragments
Differential diagnosis
=========================================================================
● Phyllodes tumor: rare in young patients, leaf-like growth pattern
Childhood tumors
Juvenile papillomatosis (swiss cheese disease)
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Grossly distinct multinodular mass with clustering of cystic formations resembling swiss cheese, composed of epithelial proliferation and clustered cysts
● First described by Rosen in 1980 (Am J Surg Pathol 1980;4:3)
Terminology
=========================================================================
● Not part of WHO breast classification
Epidemiology
=========================================================================
● Mean age 19 years
● 2/3 are less than age 20 years
Clinical features
=========================================================================
● Resembles fibroadenoma clinically
● 10% develop breast carcinoma, higher risk if recurrent, bilateral disease and family history of breast cancer (Am J Clin Pathol 1990;93:599)
● 26-58% have positive family history of breast cancer (Cancer 1982;49:2591, Am J Clin Pathol 1986;86:745), 15% have bilateral disease
● May be associated with secretory carcinoma (Jpn J Clin Oncol 1985;15:457)
Case reports
=========================================================================
● Infant boy with Noonan syndrome and family history of breast cancer (Pediatr Blood Cancer 2005;45:991)
● 6 year old girl with coexisting secretory carcinoma (J Pediatr Surg 1987;22:637)
● 16 year old girl with ER-, PR+, HER2+ tumor and recurrences (Breast Cancer 1998;5:187)
● 17 year old boy (G Chir 2011;32:374)
Gross description
=========================================================================
● Localized multinodular mass with clustering of cystic formations resembling swiss cheese
Gross images
=========================================================================
Multiple cysts resembling swiss cheese
Micro description
=========================================================================
● Florid epithelial hyperplasia and papillomatosis, cysts with foamy histiocytes and sclerosing adenosis
● Variable apocrine metaplasia, atypia and necrosis
Micro images
=========================================================================
Various images
Clustered cysts Epithelial hyperplasia
AFIP images:
Multiple cystically dilated ducts Hyperplastic epithelium in dilated duct
Intraductal epithelial proliferation Apocrine metaplasia of hyperplastic
with necrosis intraductal epithelium
Hyperplastic epithelium and With sclerosing adenosis and apocrine
foam cells metaplasia adjacent to cystically dilated ducts
Multiple small intraductal papillomas #2-high power shows hyperplastic intraductal
in 15 year old girl epithelium, myoepithelial cells are associated with
the delicate fibrovascular stalks
Cytology description
=========================================================================
● Difficult to diagnose
● Cystic fluid, but mass persists after aspiration
● Sheets of hyperplastic breast epithelium with areas resembling fibroadenoma, macrophages and apocrine cells (Diagn Cytopathol 1993;9:457)
Additional references
=========================================================================
Childhood tumors
Breast cancer in children
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Clinical features
=========================================================================
● Rare; incidence of malignant pediatric breast tumors is 0.08 cases per 100K population
● Most common malignant breast lesions in children are metastases (Radiographics 2009;29:907)
● Of primary breast malignancies, carcinomas represent 55% (usually ductal) and sarcomas represent 45% (85% of these are malignant phyllodes tumors, J Surg Res 2008;147:182)
● 7% of childhood carcinoma patients present with metastatic disease compared to 0% of sarcoma patients
● 5/10 year survival is 63%/54% for carcinoma, 90%/90% for sarcomas
Case reports
=========================================================================
● 13 year old boy with secretory breast cancer (Breast Cancer Res Treat 2012;133:813)
Gross images
=========================================================================
Maligant phyllodes tumor
Male tumors
General breast disease in males
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 8 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
See also gynecomastia, papilloma, myofibroblastoma, carcinoma, metastases
Clinical features
=========================================================================
● Rare - usually fibrocystic disease, fibroadenoma, phyllodes tumor (Mod Pathol 1992;5:114) or pseudoangiomatous stromal hyperplasia
Case reports
=========================================================================
● 23 year old man with synovial cyst post-surgery (Ann Diagn Pathol 2005;9:219)
● 48 year old man with neurofibroma (World J Surg Oncol 2007;5:23)
● 49 year old man with solitary fibrous tumor (World J Surg Oncol 2008;6:16)
● 49 and 50 year old men with granular cell tumor (J Ultrasound Med 2011;30:1295)
● 66 year old man with fibroadenomas with digital fibroma-like inclusions (Arch Pathol Lab Med 2007;131:1126)
● 75 year old man with pleomorphic hyalinizing angiectatic tumor (Pathol Res Pract 2009;205:69)
● 76 year old man with undifferentiated pleomorphic sarcoma (J Breast Cancer 2011;14:241)
● Factitious disease due to injection of liquid plastic (Int J Dermatol 2001;40:743)
● Granular cell tumor of nipple (Acta Chir Belg 2008;108:112)
● Sclerosing adenosis at autopsy in man with pulmonary small cell carcinoma (Hum Pathol 1986;17:861)
Micro images
=========================================================================
Fibroadenomas
Granular cell tumor
Epithelial inclusion cyst Neurofibroma Solitary fibrous tumor Undifferentiated pleomorphic sarcoma
Male tumors
Gynecomastia in males
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 8 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Enlargement of male breast due to hypertrophy and hyperplasia of glands and stroma
● Multifactorial etiology: physiological (puberty or aging), endocrine tumors, endocrine dysfunctions, non-endocrine diseases, drug induced, idiopathic
Clinical features
=========================================================================
● Most common lesion of male breast
● Usually bilateral, but may be more distinct in one breast
● Caused by increase in estrogen to androgen ratio (Sao Paulo Med J 2012;130:187)
● Occurs at birth, puberty or associated with Kleinfelter’s syndrome, functioning testicular tumors (Leydig, Sertoli), lung tumors, cirrhosis (hyperestrinism), neurofibromatosis (Plast Reconstr Surg 2008;121:34e alcohol, anabolic steroids, other drugs (digitalis, dilantin, highly active antiretroviral therapy for HIV, isoniazid-J Bras Pneumol 2008;34:978, methotrexate-Mod Rheumatol 2007;17:511, spironolactone-CMAJ 2007;176:620, lavender and tea tree oils-N Engl J Med 2007;356:479)
Prognostic features
=========================================================================
● May recur
Case reports
=========================================================================
● 69 year old man with fibroadenomatoid nodules associated with spironolactone (Am J Surg Pathol 1990;14:774)
Treatment
=========================================================================
● Observation / reassurance (often reversible, eMedicine), tamoxifen (Rev Med Chil 2007;135:1558), surgery with liposuction (Plast Reconstr Surg 2008;121:740) or endoscopic subcutaneous mastectomy (Surg Laparosc Endosc Percutan Tech 2009;19:e85)
● Folate for methotrexate associated disease (Rheumatol Int 2010;30:1371)
Clinical images
=========================================================================
Grades I-IV
Spironolactone induced
Gross description
=========================================================================
● Button or disk-like subareolar enlargement
● Oval, elastic and with well-circumscribed borders
● Unilateral (more common) or bilateral
● Firm, gray-white cut surface
Micro description
=========================================================================
● Proliferation of ducts without lobules
● Dense, periductal stromal fibrosis or edema with micropapillary hyperplasia and mild lymphocytic infiltrate
● Epithelium may be surrounded by prominent swollen stroma giving “halo” effect
● Over time, less hyperplasia and more stromal fibrosis
● May have pseudoangiomatous stromal hyperplasia, focal squamous metaplasia (Arch Pathol Lab Med 1986;110:971)
Micro images
=========================================================================
Gynecomastia
Periductal stromal edema
Solid form with microlumina, different
with mild epithelial hyperplasia
cell types in central and peripheral duct
Post-estrogen treatment for With atypical duct hyperplasia
prostatic carcinoma
Fig 1: dense fibrous stroma Micropapillary pattern of slender strands
and dilated ductules without lobules of cells with hyperchromatic nuclei (AFIP)
Virtual slides
=========================================================================
Gynecomastia
Cytology images
=========================================================================
Clusters of bland, cohesive epithelial cells
Positive stains
=========================================================================
● ER and PR are associated with Kleinfelter’s syndrome
● PSA is associated with antiandrogen therapy (but PSAP negative)
Electron microscopy description
=========================================================================
● Proliferation of epithelial and myoepithelial cells, intracytoplasmic lumina and squamous metaplasia
● Stroma shows fibroblasts, myofibroblasts and some pericytes (Arch Pathol Lab Med 1979;103:624)
Male tumors
Myofibroblastoma of breast
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 8 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Rare benign spindle cell tumor of mammary stroma composed of myofibroblasts
● First described in 1987 (Am J Surg Pathol 1987;11:493)
Terminology
=========================================================================
● Also called benign stromal spindle cell tumor with predominant myofibroblastic differentiation
Epidemiology
=========================================================================
● Although initially considered male predominant, now equal gender frequency (older men and post-menopausal women, Mod Pathol 1996;9:786)
● Incidence appears to be increasing, but probably an artifact of mammographic screening (Arch Pathol Lab Med 2008;132:1813)
Etiology
=========================================================================
● May derive from CD34+ vimentin+ fibroblasts of mammary stroma capable of multidirectional differentiation (Histopathology 2003;42:233)
● Probably related to spindle cell lipoma and solitary fibrous tumor (Virchows Arch 2002;440:249, Am J Surg Pathol 2001;25:1022, Breast J 2008;14:287)
Clinical features
=========================================================================
● Solitary, slow growing nodule
● Benign behavior
Case reports
=========================================================================
● 10 month old boy (Fetal Pediatr Pathol 2012;31:164)
● 25 year old man with bilateral gynecomastia (Int J Surg Pathol 2001;9:331)
● 40 year old woman (Indian J Pathol Microbiol 2008;51:395)
● 59 year old woman (University of Pittsburgh, Case #249)
● 65 year old man with 15 cm rapidly growing tumor (J Med Case Rep 2008;2:157)
● 72 year old man (Arch Pathol Lab Med 2003;127:e415)
● 73 year old man with cellular tumor (Am J Mens Health 2012;6:344)
● 83 year old man with 10 cm tumor (Am J Surg Pathol 1994;18:1170)
● Post-radiation tumor (Breast J 1999;5:136)
Treatment
=========================================================================
● Excision is curative
Clinical images
=========================================================================
15 cm tumor
Gross description
=========================================================================
● Well-circumscribed nodule or multilobar mass
● Bulging, gray-pink and 1-4 cm
● Resembles fibroadenoma
Gross images
=========================================================================
Firm, circumscribed, tan-gray lobulated nodule
Micro description
=========================================================================
● Well-circumscribed
● Uniform, bland spindle cells haphazardly arranged in fascicles with pushing borders, separated by broad bands of hyalinized collagen (Stanford University)
● Spindle cells have abundant eosinophilic cytoplasm, round / oval nucleus with 1-2 small nucleoli
● May have mild nuclear pleomorphism
● Prominent mast cells
● Variants include cellular, collagenized, epithelioid (Am J Surg Pathol 2009;33:1085), fatty (J Clin Pathol 2001;54:568) and infiltrative (no atypia or mitotic activity)
● May have histiocytoid cells, prominent vessels, focal cartilaginous differentiation (Virchows Arch 1999;434:547), smooth muscle and multinucleated floret-like giant cells
● No / rare mitotic activity
● Usually no entrapment of ducts or lobules
● Usually no necrosis
Micro images
=========================================================================
Epithelioid type
Well circumscribed Spindle cells and hyalinized collagen
Fascicles of spindle cells separated by dense collagen
Classic type
Cellular variant
Other variants
Predominantly fatty variant
CD34+
H&E, CD34, SMA
Fig 1: sharply circumscribed tumor with fibrous pseudocapsule
fig 2: bland spindle cells in collagenous or myxoid stroma
fig 3A: CD34+; fig 3B: bcl2+; fig 4: desmin+ (focal)
Cytology description
=========================================================================
● May appear malignant
● Cohesive and single spindle cells without atypia
● Scant cytoplasm and oval nuclei with fine granular chromatin, occasional nuclear grooves and small nucleoli (Diagn Cytopathol 2004;30:406)
● Tumor cells may be intimately associated with extracellular matrix material
● Also mast cells, hyaline bands between tumor cells (Diagn Cytopathol 2002;26:290)
● May have features of solitary fibrous tumor or pleomorphic lipoma (Pathol Res Pract 1999;195:257)
Cytology images
=========================================================================
Fig 2: loose groups of cells with abundant eosinophilic granular cytoplasm and bland nuclei
Positive stains
=========================================================================
● ER, PR (Histopathology 2000;36:515), vimentin and CD34 (often)
● bcl2
● Variable desmin, caldesmon and androgen receptors (Hum Pathol 1998;29:347)
Negative stains
=========================================================================
● S100, cytokeratin
● Ki-67 (or low)
Molecular description
=========================================================================
● 13q-, 16q- (similar to spindle cell lipoma, J Pathol 2000;191:282)
Electron microscopy description
=========================================================================
● Features of smooth muscle and myofibroblasts: rough endoplasmic reticulum, bundles of myofilaments with focal densities, intermediate filaments and attachment plaques (Ultrastruct Pathol 1999;23:249, Pathol Res Pract 1999;195:1)
Differential diagnosis
=========================================================================
● Fibromatosis: not circumscribed, more diffuse fibrosis and no thick bands of collagen
● Nodular fasciitis: more infiltrative, mucoid stroma
● Low grade myofibroblastic sarcoma: marked cellular pleomorphism, infiltrating margins and high mitotic rate
● Myoepithelioma: S100+, keratin+
Male tumors
Male papilloma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Usually presents with bloody nipple discharge
Terminology
=========================================================================
● Classified in WHO breast classification as central, peripheral or atypical papilloma (PubCan)
Case reports
=========================================================================
● 14 year old boy with enlarging breast mass (J Pediatr Surg 2011;46:e33)
● 57 year old man with intracystic papilloma associated with phenothiazine (Breast Cancer 2006;13:84)
Micro description
=========================================================================
● Identical to papillomas in women: multiple papillae in complex arborizing pattern with well-developed vascular connective tissue core surrounded by epithelial and myoepithelial cells; benign nuclei, frequentapocrine metaplasia, inflammationIdentical to papillomas in women
Micro images
=========================================================================
Various images
AFIP images:
Complex intraductal papilloma
Papillary tumor with fibrovascular core
Electron microscopy description
=========================================================================
● Epithelial cells, myoepithelial cells and intermediate cells with intranuclear helioid inclusions
● Squamous metaplasia (Ultrastruct Pathol 1994;18:601)
Male tumors
Male breast carcinoma - general
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Epidemiology
=========================================================================
● Very rare
● Have higher risk for second primary (breast, stomach and melanoma, Breast Cancer Res 2007;9:R10)
● In US, males have 1% the rate of breast carcinoma of women; 1000-1500 new cases per year in US
● Mean age 60 years at diagnosis
● Histology similar to women, mostly ductal and most ER+
● Incidence may be increasing in US, Canada and UK (World J Surg Oncol 2008;6:58)
Risk factors
=========================================================================
● Breast carcinoma in first degree relatives
● BRCA2 > BRCA1 mutation carriers (J Natl Cancer Inst 2007;99:1811, Ann Saudi Med 2009;29:288)
● Older age
● Infertility
● Obesity
● Ionizing radiation
● Klinefelter’s syndrome (50x risk)
● Estrogen treatment for prostate carcinoma or cirrhosis
Clinical features
=========================================================================
● Typically firm, painless mass in subareolar breast or upper, outer quadrant
● Nipple discharge in men is strongly suggestive
● Often presents at high stage since minimal breast substance (Saudi Med J 2009;30:1060)
● Axillary nodes in 50% at presentation
● Luminal A and B subtypes are most common (Breast Cancer Res 2009;11:R28)
Prognostic factors
=========================================================================
● Male patients with early stage disease may have poorer prognosis than similar stage female patients (Cancer 2007;109:1471)
● HER2+ patients have poorer survival stage by stage (Mod Pathol 2002;15:853, Am J Surg Pathol 2006;30:1292)
● Nodal metastases are an important, negative prognostic factor (Cancer Radiother 2009;13:103)
● Treatment is similar for men and women (US National Cancer Institute)
Case reports
=========================================================================
● 47 year old man with bilateral breast cancer and hypogonadism (World J Surg Oncol 2007;5:60)
● 54 year old man with synchronous bilateral male breast cancer (J Breast Cancer 2012;15:248)
● 59 year old man with pure mucinous carcinoma (Breast Cancer 2012;19:365)
● 75 year old man with intracystic papillary carcinoma (Arch Pathol Lab Med 1985;109:858)
● 76 year old man with oncocytic carcinoma (Arch Pathol Lab Med 1989;113:1396)
● 82 year old man with in situ and invasive lobular carcinoma (Hum Pathol 1989;20:1220)
● Tubulolobular carcinoma (Am J Surg Pathol 2005;29:980)
Treatment
=========================================================================
Similar to female breast cancer treatment:
● Surgery
● Sentinel node biopsy (J Am Coll Surg 2008;206:616)
● Radiation therapy
● Tamoxifen (Breast 2007;16 Suppl 2:S147)
● Adjuvant systemic therapy (Cancer 2005;104:2359)
Gross images
=========================================================================
Intracystic papillary carcinoma
Micro description
=========================================================================
● Similar to female tumors
● Invasive ductal carcinoma is most common, papillary is #2 (Virchows Arch 2006;449:507); invasive lobular / LCIS is rare
Micro images
=========================================================================
DCIS-various DCIS and invasive carcinoma
Infiltrating ductal carcinoma
Androgen receptor+ PSA+ Invasive ductal carcinoma (A),
solid papillary carcinoma (B)
Intracystic papillary DCIS
Nodal metastases HER2+ p53+
Moderately differentiated ductal carcinoma
ER+ PR+ HER2 negative
Luminal B tumor Various subtypes Intracystic papillary carcinoma
Invasive lobular carcinoma
AFIP images:
DCIS-solid type after estrogen for prostate cancer
Invasive carcinoma with cribriform pattern
Intracystic papillary carcinoma Cystic papillary carcinoma with invasion
Cytology description
=========================================================================
● Reliable but underutilized (Acta Cytol 2009;53:369)
Papillary tumors:
● Papillary clusters of epithelial cells with variable fibrovascular cores
● Also single epithelial cells with high N/C ratio and eccentric nuclei, hemosiderin-laden macrophages (Cancer 2006;108:222)
Cytology images
=========================================================================
Poorly cohesive groups of large, pleomorphic cells with
increased N/C ratios, irregular membranes and macronucleoli
Loosely cohesive malignant cells
Positive stains
=========================================================================
● ER (95%), PR (70%) and androgen receptors (Eur J Surg Oncol 2006;32:44)
● Ki-67 (20-40%)
Negative stains
=========================================================================
● p53, HER2 (usually, Arch Pathol Lab Med 2003;127:36)
Differential diagnosis
=========================================================================
● Gynecomastia with chemoradiation induced atypia (Arch Pathol Lab Med 2002;126:613, micro image)
Additional references
=========================================================================
Male tumors
Metastases to male breast
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Clinical features
=========================================================================
● 2% of all nonhematologic breast malignancies
● Most common primary is melanoma; also prostate (Urology 1978;11:641), colon, lung and bladder (Virchows Arch 2006;449:507)
● Prostate metastases are often bilateral, usually after estrogen therapy in background of gynecomastia; PSA+, PAP+ (note that the normal male breast and gynecomastia may be PSA+ but PAP-, Breast Cancer Res 2004;6:R18, Hum Pathol 1991;22:242)
● Need strong index of suspicious to diagnose, may need immunostains to distinguish primary and metastatic disease
Radiology
=========================================================================
● Single, round, discrete lesions without spiculation (Acta Cytol 2002;46:377)
Case reports
=========================================================================
Primaries from:
● Bladder (Br J Radiol 2000;73:1326)
● Lung (Australas Radiol 1998;42:16, South Med J 2007;100:850)
● Prostate (Hinyokika Kiyo 1999;45:269, Arch Pathol Lab Med 2001;125:1101)
● Skin eccrine adenocarcinoma (J Cutan Pathol 2007;34:934)
Micro description
=========================================================================
● Usually no DCIS or elastosis (J Clin Pathol 2007;60:1333)
Micro images
=========================================================================
Prostatic carcinoma metastases to male papillary breast cancer
Prostate primary
Miscellaneous
Treatment effect - chemotherapy
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Clinical features
=========================================================================
● With post-chemotherapy specimens, sample extensively before concluding “no invasive carcinoma” (Hum Pathol 2004;35:781)
● May have disseminated apoptotic or non-apoptotic tumor cells in bone marrow (Breast Cancer Res 2006;8:R60)
● Histologic changes do not correlate with clinical or pathologic response to chemotherapy (J Surg Oncol 2002;80:4), although tumor cell necrosis may have some predictive value (Am J Surg Pathol 2005;29:354)
Case reports
=========================================================================
● 46 year old woman with xanthomatous pseudotumor after preoperative chemotherapy for invasive ductal carcinoma (Arch Pathol Lab Med 2003;127:739)
Micro description
=========================================================================
● Smaller tumor size, reduced cellularity, generally same morphology and tumor markers (may change rarely)
● Extensive cytoplasmic vacuolization causing tumor cells to resemble histiocytes
● Also tumor necrosis, atrophy and marked nuclear atypia (enlarged, bizarre shapes) in a background of chronic inflammation with hemosiderin laden macrophages and fibrosis; similar changes in lymph nodes (Histopathology 1996;29:63, Pathol Res Pract 1997;193:187)
● May show distortion of glandular architecture, eosinophilic change, decreased mitotic activity (Arch Pathol Lab Med 2009;133:633)
Micro images
=========================================================================
Residual tumor cells have bizarre shapes with enlarged hyperchromatic nuclei and cytoplasmic vacuoles
Various images
Post-chemotherapy specimen has only scattered tumor cells in collagenous stroma (AFIP)
Post-chemotherapy fibrosis scar and foamy histiocytes foamy histiocytes and lymphocytes
Additional references
=========================================================================
● Ann Surg Oncol 2003;10:734, Breast 2001;10:492, Arch Pathol Lab Med 2009;133:633
Miscellaneous
Treatment effect - cryoprobe
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Clinical features
=========================================================================
● Cryoprobe: uses cryotherapy to makes nonpalpable carcinomas well-defined and palpable by creating an ice ball, leading to removal of less tissue (Am J Surg 2006;192:462)
● Alters tumor morphology making it difficult to grade tumor, distinguish DCIS and invasive tumor, and identify angiolymphatic invasion or mitotic figures (Am J Clin Pathol 2007;128:239)
● Alternative to excision of fibroadenomas (Radiology 2005;234:63)
● Normal breast parenchyma in cryozone shows dense fibrosis, fat necrosis, xanthogranulomatous reaction, endovascular fibrosis and hemorrhage (Cryobiology 2007;55:44)
● Causes reduction in ER/PR receptors, but does not affect Ki-67 staining or margin evaluation
Micro images
=========================================================================
Post-cryoprobe ablation shows coagulative Residual invasive ductal carcinoma
necrosis and amorphous eosinophilic staining
Cryoprobe related artifact (fig B) Cellular shrinkage, smudgy nuclei
compared to core biopsy (fig A) and prominent retraction artifact
Acellular central hyaline background
without residual fibroadenoma
Miscellaneous
Treatment effect - hormonal therapy
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 14 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Micro description
=========================================================================
● Causes stromal fibrosis and elastosis (Br J Cancer 1979;39:536), hyalinization and degenerative changes in tumor cells with cytoplasmic vacuoles, nuclear aberrations and necrosis
● Letrozole, an aromatase inhibitor (Wikipedia), produces central scarring (Histopathology 2007;51:219)
Miscellaneous
Treatment effect - radiation therapy
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
See also atypical or benign vascular proliferations post-radiation of breast
Case reports
=========================================================================
● 57 year old woman with radiation induced morphea (J Med Case Rep 2008;2:136)
Micro description
=========================================================================
● Giant tumor cells with bizarre nuclear changes (J Clin Pathol 1990;43:152), naked nuclei and abnormal mitotic figures
● Extensive tumor necrosis demarcated by thick fibrous walls
● Changes in non-neoplastic breast include atypia, lobular sclerosis and atrophy (may distort lobular architecture and obscure myoepithelial cells, Hum Pathol 1984;15:545), intimal thickening in small muscular arteries (Radiother Oncol 2009;92:477) and fat necrosis, but usually no mitotic activity or loss of polarity
● Changes do not regress over time (Am J Surg Pathol 2004;28:47)
Micro images
=========================================================================
Fibrotic stroma, DCIS and atrophic glands Atypical stromal cells, lymphocytic infiltrate
and increased collagen bundles
Large stromal fibroblasts may Thickened basement membranes
also occur In NON-irradiated tissue
Atypical stromal fibroblasts LCIS unchanged by radiation compared
to atrophic normal glands
Atypia in normal duct Atypia within normal lobule
Fat necrosis post-iridium implant Vessel shows reduplicated elastic lamina
and intimal thickening (elastin stain)
Collagenization of intralobular stroma and glandular atrophy (AFIP)
Radiation induced epithelial atypia #2 #3
Virtual slides
=========================================================================
Post-therapy
Differential diagnosis
=========================================================================
● Pleomorphic lobular carcinoma
Miscellaneous
Frozen sections
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
See also sentinel lymph nodes
Uses by pathologists
=========================================================================
● Historically used for primary diagnosis, not anymore (Pathologica 2011;103:325)
● Now used to evaluate margins at lumpectomy and reduce need for subsequent surgery (Ann Surg Oncol 2007;14:2953, J Am Coll Surg 2005;201:194, Scand J Surg 2009;98:34)
● Diagnosis of non-core specimens, although limitations include artifacts, sampling or interpretation errors, and in situ carcinoma only; recommended to use FNA, core biopsy or imaging as preoperative diagnostic tools (Tumori 1999;85:15)
● Frozen sections for ultrasound guided core needle biopsies may reduce patient stress waiting for paraffin results (BMC Cancer 2009;9:341)
Questions to ask prior to frozen section or intraoperative assessment (if any answer is no, don’t do frozen section):
● Is tumor > 1.0 cm?
● Will there be adequate essential diagnostic material after frozen section?
● Will additional material be sent after a biopsy is evaluated?
● Will diagnosis have immediate and relevant impact on operative management of patient?
● Note: some specimens may not be diagnostic at frozen section, including adenosquamous carcinoma-low grade (Histopathology 2006;49:603)
Gross images
=========================================================================
Tumor with positive margins (Fig 1A/1B)
Micro images
=========================================================================
Infiltrating ductal carcinoma (Fig 1A/1B)
Additional references
=========================================================================
● Arch Pathol Lab Med 2005;129:1565, Ann Surg Oncol 2012;19:3236
Miscellaneous
Grossing (histologic sampling) of breast lesions
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● For grossly benign biopsies, focus on fibrous tissue, since unlikely to detect carcinoma or atypia exclusively in unremarkable adipose tissue (Am J Surg Pathol 1989;13:505)
● Clinical outcomes of positive shaved and inked margins may differ (Cancer 1997;79:1568)
● Grossly negative margins may be histologically positive in up to 25% of specimens (Am Surg 2005;71:22)
Grossing the biopsy or excision of a palpable breast mass
=========================================================================
● Measure and (optionally) weigh specimen
● Take radiograph, if indicated
● Blot dry, ink margins and blot dry again
● If multiple orientations obtained, may want to ink in multiple colors to identify tumor proximity to specific margins
● Example: superior margin-blue, inferior margin-green, anterior margin-yellow, posterior margin-black, section and submit from medial to lateral
● Palpate specimen for masses and correlate with radiograph
● Section specimen as thin as possible (3-4 mm slices, may need to fix first)
● May want to photograph / make drawing and indicate where sections came from
● Describe: tumor (size in three dimensions, color, distance from margins, consistency, necrosis), fibrosis, cysts (number, size, content) and calcifications, if margins are submitted as shaved or perpendicular
● Submit entire specimen, if possible, in 3-5 sections; otherwise, at least 3 sections of tumor or 1 section per cm of tumor diameter (whichever is more), any suspicious areas and surgical margins; include center and periphery of tumor and adjacent tissue, areas of mammographic abnormality; Rosai suggests at least 2/3 of nonadipose breast tissue
● Note: resection by surgeon of 4-5 additional tumor cavity margins during breast conserving surgery for early stage invasive breast cancer is recommended (Ann Surg Oncol 2010;17:228)
Grossing re-excision for residual disease
=========================================================================
● Either submit entire specimen or submit 2 blocks per cm if grossly benign, remaining tissue if carcinoma identified (Am J Surg Pathol 1999;23:316)
Grossing a needle localization specimen
=========================================================================
● Review radiograph to confirm that calcified areas have been excised
● Measure and (optional) weigh specimen
● Blot dry, ink margins and blot dry again
● If multiple orientations obtained, may want to ink in multiple colors to identify tumor proximity to specific margins
● Example: superior margin-blue, inferior margin-green, anterior margin-yellow, posterior margin-black, section and submit from medial to lateral
● Palpate specimen for masses and correlate with radiograph
● May want to photograph / make drawing and indicate where sections came from
● Section specimen as thin as possible (3-4 mm slices, may need to fix first)
● Some recommend radiographs of sections to confirm that the calcified areas are being submitted
● Describe: tumor (size in three dimensions, color, distance from margins, consistency, necrosis), fibrosis, cysts (number, size, content) and calcifications, if margins are submitted as shaved or perpendicular
● Submit entire specimen, if possible, in 3-5 sections; otherwise, at least 3 sections of tumor or 1 section per cm of tumor diameter (whichever is more), any suspicious areas and surgical margins; include center and periphery of tumor and adjacent tissue, areas of mammographic abnormality; Rosai suggests at least 2/3 of nonadipose breast tissue
● Make sure to submit area of specimen containing radiographic microcalcifications; if carcinoma or atypical hyperplasia is found, submit additional sections (Am J Surg Pathol 1990;14:578)
Grossing a mastectomy specimen
=========================================================================
● Radical mastectomy: rare procedure currently; removal of entire breast, underlying and adjacent adipose tissue, pectoralis major and minor muscles and axillary contents en bloc
● Supraradical mastectomy: not performed today, radical mastectomy, chest wall, various ribs, sternum, internal mammary vessels and nodes, variable pleura
● Modified radical mastectomy: common, preserves pectoralis muscles, some skin is preserved (but nipple, areola and surrounding areas are excised), some lymph nodes containing fat from lower axilla
● Simple mastectomy: most / all mammary tissue, nipple and variable adjacent skin
● Subcutaneous mastectomy: most of mammary tissue, no skin or nipple and variable axillary tail
● Quadrantectomy: one of four anatomic breast quadrants, usually with axillary content
● Tylectomy / lumpectomy / excisional biopsy: removal of mass and variable amount of adjacent breast tissue
● Cavity margin sampling: surgeon biopsies entire wall of residual cavity created by prior procedure; results supercede lumpectomy margins, which are often falsely positive (i.e. positive when cavity margin is negative, Am J Surg Pathol 2005;29:1625)
● Measure and weigh specimen
● Ink margins (deep, superior, inferior, lateral, medial) - can use different colors to establish tumor distance to margins microscopically
● Palpate specimen for masses and correlate with radiograph (if present)
● Orient by using axillary fat as lateral
● If possible, separate axillary nodes into level I (low - inferior to lower border of pectoralis minor muscle in radical mastectomy specimens), level II (middle - between upper and lower borders of pectoralis minor muscle) and level III (high - superior to upper border of pectoralis minor muscle)
● If pectoralis minor muscle not present, separate lymph nodes into upper and lower half
● Should be 20 lymph nodes in usual radical mastectomy
● Recommended to fix overnight with Carnoy’s solution to clear the fat (although this is not often done)
● Section nipple and areola
● Divide breast into quadrants (with marker or mentally)
● Section entire breast into 2 cm thick slices, examine for tumor or suspicious areas
● May want to photograph / make drawing and indicate where sections came from
● Describe: specimen, tumor (size in three dimensions, color, distance from margins, consistency, necrosis), fibrosis, cysts (number, size, content), calcifications, gross abnormalities of skin, nipple, scar, biopsy site / cavity and lymph node findings, if margins are submitted as shaved or perpendicular
● Sections: nipple (perpendicular cuts to maximize cross sectional area), scar, tumor (at least 3 sections or 1 per cm of diameter, whichever is greater, include center and periphery of tumor and adjacent tissue), other gross lesions, areas of mammographic abnormality, closest tumor margin, other margins, representative sections of nonadipose tissue from each quadrant (upper-outer, lower-outer, upper-inner, lower-inner, Breast J 2003;9:307) and all lymph nodes (separate into upper and lower half or levels (for radical mastectomy), recommended to submit entire node unless grossly involved by tumor, Mod Pathol 1999;12:781)
Grossing a microdochectomy specimen
=========================================================================
● Definition: removal of diseased duct system to investigate nipple discharge
● Surgeon marks apex of specimen with suture and leaves probe in affected duct
● Duct may also be wire marked (BMC Cancer 2009;9:151)
● Dissect by making serial slices across duct lumen (or can open duct with fine scissors)
● Should report whether cause for nipple discharge was demonstrated
● Additional references: Breast 2008;17:309, BMC Cancer 2006;6:164
Microdochectomy images
=========================================================================
Insertion of ductoscope Selective lactiferous duct sample
Protocols
=========================================================================
● CAP protocol for excision of DCIS (Arch Pathol Lab Med 2009;133:15)
● CAP protocol for excision of breast cancer (Arch Pathol Lab Med 2000;124:1026)
● CAP protocol: updated regularly - visit http://www.cap.org, then type cancer protocols and checklists into search box
● RCPA, Drexel University
Additional references
=========================================================================
● Ann Diagn Pathol 2011;15:291
Miscellaneous
Features to report for breast carcinoma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Editor’s note
Required features to report
=========================================================================
● Specimen type / procedure
● Lymph node sampling (specify)
● Specimen size (third dimension is not required)
● Laterality (if known)
● Tumor site (if known)
● Invasive tumor size (at least one dimension is required)
● Invasive tumor histologic type
● Invasive tumor grade (Nottingham modification of Bloom-Richardson), including tubule formation, nuclear pleomorphism and mitotic activity (should grade lobular carcinoma and colloid carcinoma, don’t need to grade medullary carcinoma)
● Note: if another grading system is used, must still specify mitotic count
● TNM staging
● Number of lymph nodes examined, number involved by tumor, maximal metastasis size and presence of extracapsular spread
● Margins (distance of invasive and in-situ tumor from closest margin, specify margin)
Optional features to report, but recommended
=========================================================================
● Angiolymphatic invasion (note: tumor in dermal lymphatics may be due to benign mechanical transport, Hum Pathol 2005;36:310)
● Perineural invasion
● Involvement of nipple, skin (epidermis or dermis) and chest wall
● Multifocality
● Presence of microcalcifications and correlation with mammography
● Correlation of other findings with mammography
● Extent of margin involvement (if positive)
● DCIS (particularly if no invasive carcinoma present): size, morphologic type (architectural pattern), nuclear grade (high, intermediate, low), presence of comedocarcinoma (necrosis) and % of carcinoma represented by DCIS (25% or more is “extensive”); also margin involvement (focal or diffuse and distance to margin), presence of microcalcifications (within DCIS or elsewhere) and correlate with mammographic findings
● For invasive carcinoma: % of cells staining for ER and PR and intensity of staining (weak, moderate, strong)
● For invasive carcinoma: HER2 staining (0/negative, 1+/weak, 2+/partial circumferential staining and 3+/strong circumferential staining visible at low power)
● Fibrocystic disease
● Presence of ADH, ALH or LCIS
Optional features to report
=========================================================================
● Fibrotic focus
● Presence of extensive tumor necrosis
● Host lymphocytic response (Am J Surg Pathol 2003;27:194)
Quality of reporting
=========================================================================
● Improved in Australia after guidelines were issued; synoptic reports are more complete (Pathology 2009;41:361)
Templates
=========================================================================
Micro images
=========================================================================
AFIP images:
DCIS close to inked margin DCIS with a positive margin
DCIS at (or a basement membrane away from) the inked margin
Additional references
=========================================================================
● Arch Pathol Lab Med 2000;124:1026, Association of Directors of Anatomic and Surgical Pathology (2004), Arch Pathol Lab Med 2009;133:15
Miscellaneous
Staging of breast carcinoma
Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.
Definition
=========================================================================
● T and M (not N) are similar for clinical and pathologic staging
● Numerous changes were made in AJCC 7th edition - AJCC Cancer Staging Manual (7th ed)
Primary tumor (T)
=========================================================================
● Same definitions for clinical and pathologic classification, although T1 subclassification requires more than clinical examination
● TX: primary tumor cannot be assessed (includes cases with tumor present at margin by macroscopic examination, because total extent of tumor cannot be assessed)
● T0: no evidence of primary tumor
● Tis: carcinoma in situ
● Tis (DCIS): ductal carcinoma in situ
● Tis (LCIS): lobular carcinoma in situ
● Tis (Paget’s): Paget’s disease of the nipple NOT associated with invasive carcinoma or carcinoma in situ (DCIS or LCIS) in the underlying breast parenchyma; carcinomas in the breast parenchyma associated with Paget’s disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget’s disease should still be noted
● T1: tumor 2 cm (20 mm) or less in greatest dimension
● T1mic: tumor 1 mm or less in greatest dimension (if multiple foci of microinvasion, use largest focus and add a comment, don’t add sizes of individual foci)
● T1a: tumor more than 1 mm, but 5 mm or less in greatest dimension
● T1b: tumor more than 5 mm, but 10 mm (1 cm) or less in greatest dimension
● T1c: tumor more than 1 cm, up to 2 cm in greatest dimension
● T2: tumor more than 2 cm, up to 5 cm in greatest dimension
● T3: tumor more than 5 cm in greatest dimension
● T4: tumor of any size with direct extension to chest wall or skin as described below (invasion of dermis alone does not qualify as T4)
●T4a: extension to chest wall, not including only pectoralis muscle adherence / invasion
●T4b: ulceration or ipsilateral satellite nodules or edema (including peau d’orange) of the skin, which do not meet the criteria for inflammatory carcinoma
●T4c: both T4a and T4b
●T4d: inflammatory carcinoma (clinical diagnosis characterized by diffuse erythema and edema [peau d’orange] involving a third or more of the skin of the breast; skin changes are due to lymphedema caused by tumor emboli within dermal lymphatics, which may not be obvious in a small skin biopsy; however, tissue diagnosis is necessary to demonstrate an invasive carcinoma in the underlying breast parenchyma or at least in the dermal lymphatics; note that either tumor emboli in dermal lymphatics or locally advanced breast cancers directly invading the dermis or ulcerating the skin, without the clinical skin changes described above, do NOT qualify as inflammatory carcinoma; dimpling of the skin, nipple retraction or any other skin changes except those described under T4b and T4d may occur in T1-3 without changing the classification
Notes:
● Measure invasive component only, not DCIS
● T classification traditionally assumes there was no prior treatment; can stage after preoperative (neoadjuvant, primary) chemotherapy, but should indicate that prior treatment was received (J Natl Cancer Inst 2005;97:1137)
● pT classification requires pathologic examination of a primary carcinoma with no gross tumor at resection margins (but can classify if only microscopic tumor is present at resection margin)
● If tumor size is slightly less than or greater than a cutoff for a given T classification, it is recommended that the size be rounded to the millimeter reading that is closest to the cutoff
● Can attempt to reconstruct original tumor size if multiple biopsies / excisions; due to difficulties in adding sizes from two resections, may want to report “at least pT_, a more accurate estimate may be based on imaging studies”
● If there are multiple simultaneous, macroscopically measurable, ipsilateral invasive tumors, use largest size, don’t sum sizes (but add a comment)
● If there are multiple invasive carcinomas, the size, grade, histologic type and results of ER, PgR and HER2 should pertain to largest invasive carcinoma; if smaller invasive carcinomas differ in any of these features, include this information in “Comments”
● Tumor in pectoralis muscle should be measured with the breast tumor to determine the tumor size and T category
● Simultaneous bilateral breast carcinomas are staged as separate primaries in separate organs
● Gross measurement is recommended (either fresh or fixed); however if significant in situ disease is present or invasive tumor extends microscopically beyond the grossly measured mass, then microscopic measurements may be more accurate; using microscopic measurements only is discouraged because processing artifact may cause significant tissue expansion or shrinkage (Hum Pathol 2005;36:756)
● If a prior biopsy showed a larger area of invasion than excisional specimen, use dimension of invasive carcinoma in the prior specimen for T classification
● If patient received prior treatment and no invasive carcinoma is present in current specimen, classified as Tis if residual DCIS and T0 if there is no remaining carcinoma (but add comment)
● Grade corresponds to largest area of invasion; if there are smaller foci of invasion of a different grade, include this information under “Additional Pathologic Findings”
● Margin status is “positive” if there is ink on carcinoma (ie, the distance is 0 mm); if the margin is not positive, then a distance from the margin may be listed; distances can be specific measurements or expressed as greater than or less than a measurement
Regional lymph nodes (pN)
=========================================================================
● Note: IHC means immunohistochemistry, ITC means individual tumor cells
● pNX: regional lymph nodes cannot be assessed (e.g., previously removed or not removed for pathologic study)
● pN0: no regional lymph node metastasis identified histologically
● pN0 (i-): no regional lymph node metastases histologically, negative IHC
● pN0 (i+): malignant cells in regional lymph node(s) no greater than 0.2 mm (detected by H&E or IHC including ITC)
● pN0 (mol-): no regional lymph node metastases histologically, negative molecular findings (RT-PCR)
● pN0 (mol+): positive molecular findings (RT-PCR), but no regional lymph node metastases detected by histology or IHC
● pN1: micrometastases; or metastasis in 1-3 axillary lymph nodes; OR in internal mammary nodes with metastases detected by sentinel lymph node biopsy, but not clinically detected apparent
● pN1mi: micrometastasis (greater than 0.2 mm or more than 200 cells, but none greater than 2.0 mm)
● pN1a: metastasis in 1-3 axillary lymph nodes, at least one metastasis greater than 2.0 mm
● pN1b: metastasis in internal mammary nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy, but not clinically detected
● pN1c: metastasis in 1-3 axillary lymph nodes and in internal mammary nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy, but not clinically detected
● pN2: metastasis in 4-9 axillary lymph nodes; or in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastasis
● pN2a: metastasis in 4-9 axillary lymph nodes (at least one tumor deposit larger than 2.0 mm)
● pN2b: metastasis in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases
● pN3: metastasis in 10 or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or in clinically detected ipsilateral internal mammary lymph nodes in the presence of one or more positive level I or II axillary lymph nodes; or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy, but not clinically detected; or in ipsilateral supraclavicular lymph nodes
● pN3a: metastasis in 10 or more axillary lymph nodes (at least one tumor deposit greater than 2.0 mm); or metastasis to the infraclavicular (level III axillary) lymph nodes
● pN3b: metastases in clinically detected ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in 4 or more axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy, but not clinically detected
● pN3c: metastasis in ipsilateral supraclavicular lymph nodes
Notes:
● Requires resection and examination of at least the low axillary lymph nodes (level I)
● “i” stands for isolated tumor cells (ITC); “i+” means small clusters of tumor cells detected by H&E or IHC that are 0.2 mm or less (Am J Surg Pathol 2005;29:136) or fewer than 200 cells in a single histologic cross-section); isolated tumor cells are not counted as a positive node below
● In practice, the distinction between ITC and micrometastases is often difficult and without prognostic significance (Cancer 2008;112:1672)
● Classification based solely on sentinel lymph node biopsy, without subsequent axillary lymph node dissection, is designated (sn) for “sentinel node”, for example: pN0(sn)
● “Clinically detected” is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination and having characteristics highly suspicious for malignancy, or a presumed pathologic macrometastasis based on fine needle aspiration biopsy with cytologic examination
● Tumor in axillary fat without evidence of residual lymph node tissue is classified as a positive axillary lymph node
● Lymph node ratio (LNR, the ratio of positive over excised lymph nodes) is suggested as an alternative to pN staging (J Clin Oncol 2009;27:1062)
Diagrams
=========================================================================
Various possible difficulties
Additional references
=========================================================================
● Cancer 2003;98:2740, CA Cancer J Clin 2006;56:37, Cancer 2005;103:1319 (problems with assessing ITCs)
Distant Metastasis (M)
=========================================================================
● M0: no clinical or radiographic evidence of distant metastases; includes M0(i+)
● cM0(i+): no clinical or radiographic evidence of distant metastases, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow or other nonregional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastases
● M1: distant detectable metastases as determined by classic clinical and radiographic means or histologically proven larger than 0.2 mm
Stage grouping
=========================================================================
● Stage 0: Tis N0 M0
● Stage IA: T1 N0 M0
● Stage IB: T0-1 N1mi M0
● Stage IIA: T0-1 N1 M0 or T2 N0 M0
● Stage IIB: T2 N1 M0 or T3 N0 M0
● Stage IIIA: T0-2 N2 M0 or T3 N1-2 M0
● Stage IIIB: T4 N0-2 M0
● Stage IIIC: Any T N3 M0
● Stage IV: Any T Any N M1
Notes:
● Stage designation may be changed post-surgery if (a) imaging studies within 4 months of diagnosis reveal the presence of distant metastases, (b) there has been no disease progression and (c) no preoperative therapy was given
● T1 includes T1mi
● T0 and T1 tumors with nodal micrometastases only are excluded from Stage IIA and are classified as Stage IB
● The designation pM0 is not valid; any M0 should be clinical
Additional references
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● Arch Pathol Lab Med 2006;130:287, National Cancer Institute (USA), Updated CAP staging
End of Breast malignant, males, children > Superpage > Other
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