Breast – Malignant, Males, Children

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Breast-malignant, males, children

Apocrine carcinoma

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

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

Revised: 8 September 2009

Last major update: September 2009

Definition

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● >90% of tumor cells have cytologic or immunohistochemical features of apocrine cells

● Rare, 1-4% of all breast carcinomas

Case reports

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● 46 year old woman (Univ Pittsburgh Case #209)

● 71 year old woman with nipple (skin) tumor (Cases J 2008 Aug 12;1(1):88)

● 84 year old woman (Case of the Week #68)

Treatment and prognosis

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● Similar (Breast J 2008;14:164), or slightly better (Breast 2005;14:3) prognosis as invasive ductal carcinoma

Gross description

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● May be mural nodule within cyst

● Often multicentric (Breast Cancer Res Treat 2004;88:49)

Microscopic description / grading

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● Tumor cells have distinct cell margins, acidophilic cytoplasm with eosinophilic granules, central to eccentric vesicular nuclei with prominent nucleoli

● May have glandular differentiation with apocrine snouts

● Limit diagnosis to tumors with widespread apocrine change and obvious malignancy

● Type A cells: abundant granular and intensely eosinophilic cytoplasm, granules are PAS+ diastase resistant, nuclei vary from globoid with prominent nucleoli to hyperchromatic

● Type B cells: abundant cytoplasm with fine empty vacuoles, creating a foamy appearance resembling histiocytes, nuclei are similar to type A cells

Micro images

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Low power Cancerization of lobule

Case of the week images

Low power High power

Cells have abundant cytoplasm Cytoplasm is granular, nuclei

with distinct cell margins are round with prominent nucleoli

GCDFP-15 #1 #2 (most cells stain) bcl2 negative

AFIP Fascicle Third Series

Tumor with solid growth pattern Histiocytoid variant with isolated cells resembling

histiocytes in desmoplastic stroma, may be confused

with granular cell tumor

Other images: cells have abundant cytoplasm with distinct cell margins #1; #2; #3; cytoplasm is granular, nuclei are round with prominent nucleoli #1; #2; #3; #4; #5; with apocrine DCIS

Positive stains

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● Keratin, GCDFP-15 (76-100%), B72.3 (92%, APMIS 2006;114:712), PAS (granules)

● ER-beta (73%, Histopathology 2007;50:425), particularly ER-beta1 (APMIS 2008;116:923)

● Androgen receptor (54%)

● HER2 (33%), p53 (29-39%), Ki-67

● Note that GCDFP-15 and AR expression decrease in larger or node-positive tumors (Histopathology 2005;47:195)

Negative stains

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● ER-alpha (usually), PR (usually), bcl-2

Electron microscopy

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● Prominent mitochondria, some with abnormal cristae

● Large membrane bound vesicles with dense homogenous osmophilic cores

Electron microscopy images

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Cytoplasm is rich in organelles Electron dense granules, condensed,

at secretory pole of cell

AFIP Fascicle Third Series

Smooth and rough endoplasmic Cytokeratin filaments (arrow),

reticulum, dense nucleoli lipid droplets, mitochondria,

lysosomes

Cytoplasm contains numerous lysosomes, lipid droplets,

dilated mitochondria and vesicular endoplasmic reticulum

Molecular / cytogenetics

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● Form a distinct, even if heterogeneous, molecular subgroup of breast carcinomas that recapitulate the phenotype of apocrine sweat glands (Mol Oncol 2009 Feb 3 [Epub ahead of print])

● Abnormalities at 7q (codes for GCDFP-15 and prolactin-inducible protein)

● Also loss of heterozygosity for p53 gene, VHL (3p25) gene, NB gene (1p35-36), PKD1/TSC2 gene at 16p13 (Mod Path 1999;12:1083)

Differential diagnosis

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● Apocrine metaplasia - not infiltrative, no atypia

● Histiocytic proliferation

● Inflammation

● Granular cell tumors

Additional references

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● Pathol Res Pract 2008;204:367, Breast Cancer 2002;9:43, Stanford University

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

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