Outline Intraductal proliferative lesions Usual ductal hyperplasia (UDH) Atypical ductal hyperplasia (ADH) Low grade DCIS Flat epithelial atypia (FEA) Clinical significance and management recommendations Not discussing: lobular neoplasia, intermediate and high grade lesions. Not much is helping us in this regard except we are seeing more of it due to increased resolution on mammos for calcs.

Intraductal proliferative lesions A group of cytologically and architecturally diverse proliferations originating in the TDLU. Increased risk for subsequent breast ca – but of vastly different magnitudes. ‘risk indicators’ VS ‘precursors’ Different genetics Different morphology: architecture, cytology, extent. This is about all they have in common.

UDH ADH DCIS INV CA CCL/FEA DIN terminology? UDH ADH HG DCIS LG DCIS Studies: IHC, gene-expression assays, CGH assays, LOH studies UDH shares few similarities with AHD, DCIS, CA (it has few and random chromosomal alterations) ADH shares many similarities with LG DCIS and CCL/FEA (the hallmark genetic alteration of low grade lesions is losses of chromosome 16q) LG DCIS and HG DCIS are genetically distinct FEA is a clonal lesion that is genetically similar to ADH, LG DCIS Thus, do FEA, ADH, and DCIS represent forms of intraepithelial neoplasia? LG DCIS INV CA

Genetics of intraductal proliferative lesions H CA Loss 16q FEA/CCL UDH ADH HG DCIS Studies: IHC, gene-expression assays, CGH assays, LOH studies UDH shares few similarities with AHD, DCIS, CA (it has few and random chromosomal alterations). Most represent ‘dead-end’ proliferations. ADH shares many similarities with LG DCIS and CCL/FEA (the hallmark genetic alteration of low grade lesions is losses of chromosome 16q) LG DCIS and HG DCIS are genetically distinct. DCIS and invasive carcinoma of similar grades share more genetic features than inv ca as a group. FEA is a clonal lesion that is genetically similar to ADH, LG DCIS. CCL (non atypical also show the same genetic changes but studies are limited. Most frequent is loss of 16q). Thus, do FEA, ADH, and DCIS represent forms of intraepithelial neoplasia? LG DCIS INV CA

Usual ductal hyperplasia Also known as epithelial hyperplasia of usual type Mild, moderate, florid – of no clinical significance* Architecture: solid, fenestrated, micropapillary (tapered), peripheral slit-like lumens, attenuated bridges Cytology: variable size and shape, overlapping, ill-defined cell borders, streaming of cells, necrosis is allowed. Occasional mitoses allowed. Compare to normal ducts for reference. *Some say that florid UDH has higher risk of breast ca.

CE 3887 UDH in complex sclerosing lesion.

36229 complex sclerosing lesion