Breast – Malignant, Males, Children - Basal-like invasive ductal carcinoma

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Breast-malignant, males, children

Basal-like invasive ductal carcinoma

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

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

Revised: 13 September 2009

Last major update: September 2009

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 Path 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 2009 May 23 [Epub ahead of print]), higher percentage (26-30%) of CNS metastases or primaries that metastasize to CNS (Mod Path 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 Path 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

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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)

● 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 Path 2008;39:167)

Microscopic description

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● High grade or metaplastic morphology, may have medullary features (AJSP 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 Path 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 Tumor without sheet-like growth

higk Ki-67 index but with high Ki-67 index

Basoluminal variant

CK 5/14 (Fig B/C) CK 5/14 and K1-67

Normal breast:

CAM 5.2 (CK 8/18) stains luminal CK5 and CK14

epithelium, CK17 stains basal cells

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%, AJSP 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

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

End of Breast – Malignant, Males, Children > Basal-like invasive ductal carcinoma

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