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Breast malignant, males, children

Carcinoma subtypes

Metaplastic carcinoma - general


Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 3 April 2014, last major update September 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

See also subtypes / variants: fibromatosis-like,, matrix producing, spindle cell

Definition
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● Heterogeneous group of neoplasms with predominant component other than epithelial / glandular

Terminology
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● Also called carcinosarcoma (if mesenchymal component is malignant), carcinoma with osteoclastic giant cells and carcinoma with osseous metaplasia
● “Metaplastic” due to the transformation of epithelial component into a non-glandular component, such as spindle cells, squamous cells or heterologous elements

Clinical features
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● Uncommon (< 5% of breast carcinomas)
● More aggressive than invasive ductal NOS due to larger tumor size, higher grade
● Metastases tend to be hematogenous and not nodal (Ann Surg Oncol 2007;14:166, Breast Cancer Res Treat 2007;101:349)
● Represents a type of basal-like carcinoma lacking epidermal growth factor receptor and KIT activating mutations, but exhibiting high epidermal growth factor receptor copy number, primarily via aneusomy (Mol Cancer Ther 2008;7:944)

Case reports
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● 35 year old woman BRCA1 carrier (Breast Cancer 2011;18:137)
● 37 year old woman with giant cystic tumor (Acta Cytol 2006;50:327)
● 49 year old woman with metaplastic carcinoma of abdominal wall muscle (Breast Cancer 2012 Mar 2 [Epub ahead of print])
● 52 year old woman with CD117+ tumor (The Internet Journal of Pathology 2009;8:2)
● 52 year old woman with ductal, squamous and cartilaginous components in tumor (Mod Pathol 2001;14:1183)
● 57 year old woman with abscess (Int Semin Surg Oncol 2006;3:23)
● 66 year old woman with circumscribed mass (Case of the Week #6)
● 77 year old woman with extensive osseous differentiation (Breast 2008;17:314)
● Bilateral tumors, each clonal but different clones (Hum Pathol 2002;33:677)
● With melanocytic differentiation (Mod Pathol 1997;10:592)

Treatment
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● Mastectomy or local excision

Gross description
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● Well-circumscribed
● Median 3-4 cm, range 1-21 cm
● Usually firm, nodular
● Squamous or chondroid areas are pearly white to gray glistening areas on cut surface

Gross images
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Bisected squamous tumor (arrows at tumor margin)


Carcinoma with osteoclast-like giant cells

Causing skin ulceration

Sharply circumscribed tumor


Micro description
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● Sarcomatous component resembles fibromatosis (see variant), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma or osteosarcoma (see variant), rhabdomyosarcoma, spindle cells (see variant), angiosarcoma or combination
● May need to look carefully for epithelial component (may be ductal carcinoma in situ or invasive ductal carcinoma), may have osteoclast-like giant cells (Hum Pathol 1990;21:142)
● Some classify as “with squamous metaplasia” or “with heterologous metaplasia”
● Recommended to test any keratin negative stromal tumor of the breast with myoepithelial markers before calling it a primary sarcoma (Am J Surg Pathol 2005;29:347)

Micro images
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Epithelioid and spindled areas

               
Various images

                
With osteoclast-like giant cells                        Various images

                    
Case of the Week #6                                            CK7                             S100


Glandular and squamous components


Squamous component


EGFR expression


Ductal, squamous and cartilaginous components

   
Invasion patterns: left-irregular; right-DFSP like

               
Fibrosarcoma-like pattern

           
Angiomatoid pattern                                                                         Keratin+

          
Osteosarcoma-like         Low-grade spindle cell metaplastic carcinoma arising within papilloma

   
Nodal metastases

       
Keratin+ cells                                            Epithelium is keratin+, stroma is keratin-

       
H&E, EGFR and         EGFR                          EGFR and HER2 overexpression
EGFR-CISH                                                   in spindle cell carcinoma

           
Malignant squamous component                                             Storiform squamous type


Various images

AFIP images:
                                                         
Well differentiated epidermoid carcinoma                 Adenocarcinoma with a tubular pattern
and poorly differentiated adenocarcinoma                in the metaplastic spindle cell component
merge with the spindle cell component

                                                         
Carcinomatous glands are surrounded by an           Transition from adenocarcinoma
undifferentiated round cell proliferation                     to spindle cell pattern
that merges with the spindle cells

                                                         
Poorly differentiated carcinoma with traces              Invasive adenocarcinoma at upper right, but most
of squamous metaplasia giving rise to the                tumor is solid pseudosarcomatous metaplastic
spindle cell component                                                elements with pale, serpiginous areas of necrosis

                                                         
Adenocarcinoma with transition to                             Recurrent metaplastic carcinoma 4 years
undifferentiated carcinoma, an intermediate             after mastectomy, tumor was initially
step in conversion to spindle cell metaplasia            interpreted as a radiation induced sarcoma

                                                             
Osteoclast-like giant cells in stroma                           Resembles giant cell tumor of bone
associated with the carcinoma component                due to osteoclast-like giant cells

Cytology description
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● Moderate / high cellularity (68%), necrosis (47%), cells are sarcomatoid, poorly differentiated carcinoma or squamous carcinoma
● Dual components usually not identified (J Clin Pathol 2007;60:529)
● Also clusters of carcinoma cells (Diagn Cytopathol 2006;34:772)

Virtual slides
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With myoepithelial and myxoid components

Positive stains
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● Vimentin in mesenchymal elements
● Keratin (broad spectrum or 34betaE12) in spindle or epithelial cells
● EGFR (76%, Breast Cancer Res 2005;7:R1028)
● Squamous components are p63+
● Non-squamous tumors express smooth muscle actin and p63 (nuclear staining, Am J Surg Pathol 2004;28:1506)
● Chondroid cells are S100+
● Also laminin 5 (Am J Surg Pathol 2008;32:345), CD10, CD29 and 14-3-3-sigma (Am J Surg Pathol 2005;29:347)
● Variably positive for CK5 and CK14 (Hum Pathol 2003;34:1009)

Negative stains
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● ER, PR, HER2 (Turk Patoloji Derg 2012;28:134) and mucin
● Often S100
● Mammaglobin (Am J Clin Pathol 2012;137:747)

Molecular description
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● Epithelial and sarcoma components originate from same clone
● Epidermal growth factor receptor overexpression in 2/3, 1/3 of these have EGFR gene amplification, but no activating EGFR mutations (J Pathol 2006;209:445)

Differential diagnosis
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Myoepithelial carcinoma: may have ducts with prominent myoepithelial cells at periphery, diffusely S100+
Myofibroblastic tumors
Phyllodes tumor
Primary breast sarcoma: no epithelial elements or keratin+ elements

Additional references
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Am J Surg Pathol 1998;22:188, Am J Surg Pathol 1987;11:918, Stanford University
J Clin Imaging Sci 2012;2:21, J BUON 2011;16:652, Tumori 2011;97:e1

End of Breast malignant, males, children > Carcinoma subtypes > Metaplastic carcinoma - general


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