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Breast malignant, males, children

Carcinoma subtypes

Medullary carcinoma


Reviewer: Monika Roychowdhury, M.D., (see Reviewers page)
Revised: 16 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

General
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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 features
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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 (Hum Pathol 1988;19:1340, Int J Radiat Oncol Biol Phys 2005;62:1040)
● Better prognosis may be due to prominent inflammation (Eur J Cancer 2009;45:1780, Mod Pathol 2010;23:1357)

Case reports
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● 58 year old woman with synchronous bilateral medullary carcinoma (J Cancer Res Ther 2012;8:129)

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)


Various images

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
● Moderate/marked nuclear pleomorphism and nuclear irregularities, 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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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
● Mammaglobin-A (Am J Clin Pathol 2012;137:747)

Molecular / cytogenetic description
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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: not circumscribed and may not be syncytial
Collision tumor of invasive ductal NOS and MALT lymphoma: see Arch Pathol Lab Med 2004;128:99

Additional references
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Stanford University

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


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