The solid papillary variant of
ductal carcinoma in situ is an uncommon entity, which usually presents in the seventh or eighth decade and may be associated with invasive
mucinous carcinoma. Solid papillary
ductal carcinoma in situ (SP-
DCIS) shares many morphological features with usual ductal
hyperplasia (UDH) involving a
papilloma: papillary architecture, solid growth, cellular streaming, and low-grade nuclear features. These similarities can make the distinction between these 2 entities challenging. Recent studies have demonstrated that immunohistochemical staining for
cytokeratin 5/6 can distinguish UDH from conventional forms of
ductal carcinoma in situ. Most of the epithelial cells of UDH express
cytokeratin 5/6, but the
tumor cells of
ductal carcinoma in situ do not. We tested the hypothesis that the results of staining for
cytokeratin 5/6 can distinguish UDH from the solid papillary variant of
ductal carcinoma in situ. Immunohistochemical staining of 14 cases of SP-
DCIS and 9 cases of UDH (4 involving
papillomas) was performed using
cytokeratin 5/6 antibody clone D5/16 B4. Strong cytoplasmic or membrane staining was considered positive. The hyperplastic cells in all cases of UDH showed strong staining for
cytokeratin 5/6. The percentage of positive cells ranged from 50% to 80%. None of the SP-
DCIS tumor cells stained for
cytokeratin 5/6; however, many cases did show staining of occasional entrapped, benign epithelial, and myoepithelial cells. We conclude that the absence of strong
cytokeratin 5/6 expression by SP-
DCIS distinguishes it from its morphological mimic, UDH. Pathologists must guard against misinterpreting SP-
DCIS as UDH in those cases in which the
carcinoma cells engulf
cytokeratin 5/6-expressing residual, native epithelial cells.