Breast malignant, males, children

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Breast malignant, males, children

Carcinoma subtypes

Medullary carcinoma

Reviewer: Daniel Visscher, M.D., University of Michigan Hospitals, February 2009 (see Reviewers page)
Revised: 15 March 2011, last major update September 2009
Copyright: (c) 2001-2011, PathologyOutlines.com, Inc.

Definition
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● Well circumscribed, composed of poorly differentiated cells in syncytia or large sheets, with prominent lymphoplasmacytic infiltrate, scant fibrous stroma, no glandular structures, minimal DCIS
● Considered a type of basal-like carcinoma (Breast Cancer Res 2007;9:R24, Am J Surg Pathol 2007;31:501)
● “Medulla” refers to soft structure of marrow (tumors are often soft)

Clinical
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● Uncommon, <1% of invasive breast carcinomas
● Usually < 50 years old, often < 35 years old, common in Japanese, associated with BRCA1 mutations
● More activated cytotoxic lymphocytes than poorly differentiated ductal carcinomas (Mod Pathol 1999;12:1050, Mod Pathol 2008;21:1101)

Treatment and prognosis
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● Slightly better prognosis than invasive ductal carcinoma NOS, even though high grade, aneuploid, ER/PR negative, p53 positive and high proliferation rates (Int J Radiat Oncol Biol Phys 2005;62:1040)
● Better prognosis may be due to prominent inflammation (Eur J Cancer 2009;45:1780)

Gross description
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● Well circumscribed, often large, resembles fibroadenoma but without whorls
● Soft, fleshy, tan-gray
● No desmoplasia; easy to cut, large areas of necrosis and hemorrhage

Gross images
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Sharply defined margin with internal nodularity and bosselated surface (AFIP)

Gray-fleshy tumor

Well circumscribed 7 cm tumor

Atypical medullary carcinoma: primary and nodal metastases #1, #2

Other images:
Gray-fleshy tumor; Tan-pink tumor with circumscribed margin; Tumor with extensive hemorrhage

Micro description
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● (1) Indistinct cell borders (syncytial growth) making up 75%+ of tumor with large pleomorphic tumor cells containing large nuclei, prominent nucleoli, numerous mitotic figures; peripheral cells are more eosinophilic
● (2) Prominent lymphoplasmacytic infiltrate at periphery composed of T cells and IgA plasma cells
● (3) Pushing borders / well circumscribed

● Classify as medullary carcinoma if tumor has above three features
● Classify as atypical medullary carcinoma (or infiltrating ductal carcinoma) if tumor has only 2 of 3 features listed above (atypical medullary carcinoma has similar prognosis as ductal carcinoma NOS)

Other features:
● Sparse stroma
● Variable spindle cell or squamous metaplasia, occasional bizarre tumor giant cells and extensive necrosis
● No/minimal glandular differentiation, no intraductal growth or DCIS, no mucin, no calcification

Micro images
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High grade tumor cells with syncytial pattern of cells

More distinct cell borders

Clusters of sheets of syncytial cells with prominent lymphoplasmacytic infiltrate

Various images Lymphocytes in micropapillary and medullary carcinomas

Tumor cells have syncytial pattern and high grade nuclei,
necrosis at upper left, lymphoplasmacytic infiltrate at lower right (AFIP)

A lobule with in situ carcinoma in some lobular units;
thick basement membranes, are nonspecific feature (AFIP)

Focal areas of squamous metaplasia with keratin pearls
Note solid growth pattern with distinct cell membranes (not syncytia) in areas of squamous metaplasia (AFIP)


ER neg                      p63                            p53


HER2 staining (usually is negative, in this case, is focally 3+ [see image on right])

Other images: High grade syncytial pattern #1; #2

Atypical medullary carcinoma

Tumor invades fat and is not well circumscribed (AFIP)

Medullary features include poorly differentiated nuclei,
syncytial growth, lymphoplasmacytic infiltrate (AFIP)

Other images: Atypical medullary carcinoma because no lymphoplasmacytic infiltrate

Cytology description
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● Cellular smears
● Tumor cells in loosely cohesive sheets and single cells
● Have moderate/marked nuclear pleomorphism and nuclear irregularities, are mixed with mononuclear inflammation (Diagn Cytopathol 2007;35:408, Acta Cytol 2009;53:165)

Cytology images
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Fig D: FNA shows syncytium of cells with vesicular nuclei and prominent nucleoli in lymphocytic background

Other images: Atypical medullary carcinoma #1; #2

Virtual slides
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Medullary carcinoma; Atypical medullary carcinoma

Videos
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● Medullary carcinoma

Positive stains
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● CK5/6 (94%), p53 (77%); high Ki-67 index
● Also HLA-DR, S100

Negative stains
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● ER, PR, HER2 (Arch Pathol Lab Med 2003;127:1458),
● EBV

Molecular / cytogenetics
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● Microsatellite instability is uncommon, in contrast to medullary colonic tumors (Am J Clin Pathol 2001;115:823)
● Similar genetic alterations as basal-like carcinomas
● Usually aneuploid
● Associated with BRCA1 mutations

Molecular images
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FISH and IHC show HER2 amplification in high grade invasive ductal carcinoma
(figures A/B), but not in medullary carcinoma (figures C/D)

CISH - heterogeneous expression of HER2

Differential diagnosis
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● Undifferentiated ductal carcinoma - lacks prominent lymphoplasmacytic infiltrate; has infiltrative borders
● Lymphoepithelioma-like carcinoma - has infiltrative borders
● Lymph node in axillary tail - metastatic tumor is not circumscribed and may not be syncytial
● Collision tumor of invasive ductal NOS and MALT lymphoma (Arch Pathol Lab Med 2004;128:99)

Additional references
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● Hum Pathol 1988;19:1340, Stanford University

End of Breast malignant, males, children > Carcinoma subtypes > Medullary carcinoma

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