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Breast malignant, males, children

Carcinoma subtypes

Basal-like invasive ductal carcinoma


Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 2 April 2014, last major update March 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

Definition
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● Not rigidly defined, usually positive for CK5/6, CK14 or CK17, and triple negative (ER-, PR-, HER2-), often positive for EGFR
● Original definition based on gene expression profile (Nature 2000;406:747, Proc Natl Acad Sci USA 2001;98:10869)
● Generally considered to not be comparable to triple negative tumors by immunostains (Clin Cancer Res 2008;14:1368, Med Mol Morphol 2009;42:128) but see Breast Cancer Res 2007;9:R65
● Classification of particular tumors may vary based on which classification system is used (Hum Pathol 2008;39:506)
● Tumors are clinically heterogeneous

Terminology
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● Not in WHO breast classification
● “Basal like” because tumors have high expression of genes characteristic of basal epithelial cells of normal mammary gland, including CK 5/6, CK14, CK15 and CK17

Epidemiology
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● 15% of all invasive ductal carcinoma NOS (Breast Cancer 2010;17:118), higher percentage (26-30%) of CNS metastases or primaries that metastasize to CNS (Mod Pathol 2007;20:864); higher percentage (34%) in Africa (APMIS 2007;115:1391)
● Basal-like expression also present in 17% of infiltrating lobular carcinoma based on CK5/6 expression, these cases are more likely to be ER- (Hum Pathol 2008;39:331)
● Associated with younger age, African-American women, high grade tumors, metaplastic subtype (Mol Cancer Ther 2008;7:944), medullary subtype (Breast Cancer Res 2007;9:R24), high stage, angiolymphatic invasion, BRCA1 (Oncogene 2006;25:5846)
● Not a common subtype in men (Breast Cancer Res 2009;11:R28)

Clinical description
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● Of academic interest, not currently used clinically (Arch Pathol Lab Med 2009;133:860); may not be a distinct clinical entity (Pathobiology 2008;75:119, J Biophotonics 2012 Jan 9 [Epub ahead of print])
● Associated with epithelial-mesenchymal transition, defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype (Cancer Res 2008;68:989)
● Poorer survival if express CK 17 or CK 5/6 (Am J Pathol 2002;161:1991), CK 5/6 or EGFR (BMC Cancer 2007;7:134), HER2+ (not common, Hum Pathol 2008;39:167)

Micro description
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● High grade or metaplastic morphology, may have medullary features (Am J Surg Pathol 2007;31:501)
● Also geographic necrosis, pushing borders, stromal lymphocytic response, increased mitotic count
● Subtypes include pure (negative for S100 and actin) or myoepithelial (S100+ or actin+, Mod Pathol 2007;20:1200)
● Includes secretory breast carcinomas with ETV6-NTRK3 fusion gene (Mod Pathol 2009;22:291)
Core biopsy: solid growth pattern, high nuclear grade, marked lymphocytic infiltrate and geographic necrosis are helpful features, also immunostains (Appl Immunohistochem Mol Morphol 2008;16:411)

Micro images
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Various images


H&E and CK14


p16+

           
Various immunostains


Sheet-like growth and high Ki-67 index


Tumor without sheet-like growth but with high Ki-67 index

Contributed by Dr. Semir Vranic, Sarajevo:

H&E


Central necrosis


40x


Inflammatory response, periphery


ER negative


CK 5/6


CK7


CK14


S100

Basoluminal variant:

CK 5/14 (Fig B/C)


CK 5/14 and K1-67

Normal breast:

CAM 5.2 (CK 8/18) stains luminal
epithelium, CK17 stains basal cells



CK5 and CK14

Virtual slides
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Tumor

Positive stains
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● Usually CK5 or CK5/6 (CK5 more sensitive, Am J Clin Pathol 2008;130:724), CK14 or CK17
● Ki-67 (high labeling index)
● Often EGFR, IGF-IR or c-kit/CD117
● CD109 (60%, Pathol Int 2008;58:288), laminin 5 (96%, Am J Surg Pathol 2008;32:345), vimentin (55-90%), p16 (Am J Surg Pathol 2009;33:163)
● Note: basoluminal variant may be HER2+ and only partially positive for CK5/14 (Clin Cancer Res 2006;12:4185)

Negative stains
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● ER, PR and HER2 (triple negative)

Molecular description
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● p53 mutations (Cancer Res 2009;69:663)

End of Breast malignant, males, children > Carcinoma subtypes > Basal-like invasive ductal carcinoma


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