Pre-Invasive Lesions of the Breast: WHO Update

Pre-Invasive Lesions of the Breast: WHO Update Atypical Ductal Hyperplasia Flat Epithelial Atypia Stuart J. Schnitt, M.D. Department of Pathology Beth...
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Pre-Invasive Lesions of the Breast: WHO Update Atypical Ductal Hyperplasia Flat Epithelial Atypia Stuart J. Schnitt, M.D. Department of Pathology Beth Israel Deaconess Medical Center and Harvard Medical School Boston, MA, USA

Intraductal Proliferative Lesions (Proliferative Lesions of Ductal Pattern) • Usual ductal hyperplasia • Atypical ductal hyperplasia • Ductal carcinoma in situ • (Ductal intraepithelial neoplasia)

Relative Risk of Breast Cancer According to Category of Intraductal Prolfierative Lesion

8-10

RR

3-5

1.5-2

UDH

ADH

DCIS

Assessment of Intraductal Proliferative Lesions • Architecture • Cytology • Extent

Architecture

THINK UDH

THINK ADH/DCIS Page and Anderson, 1987

Morphological Criteria for UDH WHO, 2012

Immunophenotype of UDH • Mixed population of cells that express low and high molecular weight cytokeratins (the latter often in a heterogeneous or mosaic pattern)

HMW-CK in UDH CK 5/6

UDH: “Triple Stain” LMW-CK red, HMW-CK brown cytop, Myoep cells brown nuclear

Immunophenotype of UDH • Mixed population of cells that express low and high molecular weight cytokeratins (the latter often in a heterogeneous or mosaic pattern) • Heterogeneous expression of ER

ER in UDH

Atypical Ductal Hyperplasia • Defined in terms of its resemblance to low grade DCIS • Diagnosis of ADH should not be made unless a diagnosis of low grade DCIS is being seriously considered • Florid examples of usual ductal hyperplasia (UDH) should not be categorized as ADH • If there is uncertainty as to whether to categorize a lesion as UDH or ADH, categorize it as UDH

Morphological Criteria for ADH WHO, 2012

LG-DCIS

LG-DCIS

ADH

Immunophenotype of ADH • Uniform population of cells that lack expression of high molecular weight cytokeratins

HMW-CK in Atypical Ductal Hyperplasia CK 5/6

Immunophenotype of ADH • Uniform population of cells that lack expression of high molecular weight cytokeratins • Strong, diffuse expression of ER

ER in ADH

• UDH • ADH

Heterogeneity Uniformity

ADH vs DCIS

ADH vs Low Grade DCIS of Limited Extent

Why Bother to Make This Distinction? ADH

LG-DCIS

Marker

Precursor

•Observation •Chemoprevention •(Bilateral mastectomy)

Complete local eradication

Extent Criteria to Distinguish ADH from Low Grade DCIS • Lesions that show partial involvement of spaces by cells similar to those of LG-DCIS are given the diagnosis of ADH

Extent Criteria to Distinguish ADH from Low Grade DCIS • Lesions that possess ALL of the qualitative features of LG-DCIS but are limited in extent are given the diagnosis of ADH: –1985, Page et al:

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