Breast – Malignant, Males, Children

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Breast-malignant, males, children

Metaplastic carcinoma

Author: Nat Pernick, M.D, PathologyOutlines.com, Inc.

Reviewer: Daniel Visscher, M.D., University of Michigan Hospitals, February 2009 (see Reviewers page)

Revised: 28 September 2009

Last major update: September 2009

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, carcinoma with osseous metaplasia

● “Metaplastic” due to the transformation of epithelial component into a nonglandular component, such as spindle cells, squamous cells or heterologous elements.

Clinical

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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 EGFR and KIT activating mutations but exhibiting high EGFR copy number, primarily via aneusomy (Mol Cancer Ther 2008;7:944)

Case reports

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● 35 year old female BRCA1 carrier (Breast Cancer 2009 Apr 7 [Epub ahead of print])

● 37 year old woman with giant cystic tumor (Acta Cytol 2006;50:327)

● 52 year old woman with CD117+ tumor (The Internet Journal of Pathology 2009;8(2))

● 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)

● Bilateral tumors, each clonal but different clones (Hum Path 2002;33:677)

● Tumor with ductal, squamous and cartilaginous components (Mod Path 2001;14:1183)

● With melanocytic differentiation (Mod Path 1997;10:592)

Treatment and prognosis

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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 firm glistening areas on cut surface

Gross images

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Bisected squamous tumor Carcinoma with osteoclast-like giant cells

(arrows at tumor margin)

Other images: causing skin ulceration; sharply circumscribed tumor

Microscopic description / grading

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● Sarcomatous component resembles fibromatosis (see variant), fibrosarcoma, MFH, chondrosarcoma or osteosarcoma (see variant), rhabdomyosarcoma, spindle cells (see variant), angiosarcoma or combination

● May need to look carefully for epithelial component (may be DCIS or invasive ductal carcinoma), may have osteoclast-like giant cells (Hum Path 1990;21:1142)

● 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 (AJSP 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 images CK7 S100

Glandular component Glandular and squamous Sarcoma (left) and

Components carcinoma (right) areas

With squamous differentiation Ductal, squamous and cartilaginous components

Invasion patterns: DFSP-like Into fat

Irregular

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

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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Two tumors 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+

● Nonsquamous tumors express smooth muscle actin and p63 (nuclear staining, AJSP 2004;28:1506)

● Chondroid cells are S100+

● Also laminin 5 (AJSP 2008;32:345), CD10, CD29, 14-3-3-sigma (AJSP 2005;29:347)

● Variably positive for CK5 and CK14 (Hum Path 2003;34:1009)

Negative stains

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● ER, PR, HER2, mucin

● Often S100

Molecular / cytogenetics

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● Epithelial and sarcoma components originate from same clone

● EGFR 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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● AJSP 1998;22:188, AJSP 1987;11:918, Stanford University

End of Breast – Malignant, Males, Children > Metaplastic carcinoma

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