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Summary Invasive plasmacytoid urothelial carcinomas (PUCs) are an uncommon aggressive variant, which often shows immunohistochemical loss of E-cadherin, underlying its distinct discohesive histology. The marker P120 (well described in breast pathology as being a diagnostic tool alongside E-cadherin for lobular neoplasia) has not been evaluated in PUCs. Biopsies, transurethral resections, and cystectomies of PUCs were collected, and whole-slide immunohistochemical analysis of E-cadherin and P120 was applied. A subset of cases were also tested for CDH1 mutation. PUC cases were stratified into morphologic categories of classic, pleomorphic, or desmoplastic. For E-cadherin, 24 of 33 (73%) cases showed an abnormal staining pattern, consisting of complete absence of staining (17/24; 71%) or cytoplasmic staining (7/24; 29%). For P120, 24 of 33 (73%) cases showed an abnormal staining pattern, consisting of loss of membranous staining with cytoplasmic reactivity. Only 2 cases showed a discordant E-cadherin/P120 immunoprofile (94% concordance). Significant staining differences among the 3 morphologic categories were not found. CDH1 mutation was found in 4 of 8 (50%) of cases, with 3 of 4 (75%) cases showing matched molecular/immunoprofile reactivity. No cases with CDH1 mutation showed discordant pattern E-cadherin/P120 immunoreactivity. Our rate of aberrant E-cadherin immunoreactivity in PUCs (73%) is similar to a meta-analysis of published cases (74%). We also report an identical rate of aberrant P120 immunoreactivity in PUCs (73%). While PUC remains a histologic diagnosis, in a subset of cases showing a less appreciated pattern (such as desmoplastic) or confounding cytoplasmic E-cadherin reactivity, the utility of paired P120 staining may be a useful diagnostic tool.

Renal oncocytoma and chromophobe renal cell carcinoma have been long recognized as distinct tumors; however, it remains unknown if uniform diagnostic criteria are used to distinguish these tumor types in practice. A survey was distributed to urologic pathologists regarding oncocytic tumors. Responses were received from 17 of 26 invitees. Histologically, more than 1 mitotic figure was regarded as most worrisome (n=10) or incompatible (n=6) with oncocytoma diagnosis. Interpretation of focal nuclear wrinkling, focal perinuclear clearing, and multinucleation depended on extent and did not necessarily exclude oncocytoma if minor. Staining techniques most commonly used included the following: cytokeratin 7 (94%), KIT (71%), vimentin (65%), colloidal iron (59%), CD10 (53%), and AMACR (41%). Rare cytokeratin 7-positive cells (≤5%) were regarded as most supportive of oncocytoma, although an extent excluding oncocytoma was not universal. Multiple chromosomal losses were most strongly supportive for chromophobe renal cell carcinoma diagnosis (65%). Less certainty was reported for chromosomal gain or a single loss. For tumors with mixed or inconclusive features, many participants use an intermediate diagnostic category (82%) that does not label the tumor as unequivocally benign or malignant, typically "oncocytic neoplasm" or "tumor" with comment. The term "hybrid tumor" was used variably in several scenarios. A slight majority (65%) report outright diagnosis of oncocytoma in needle biopsies. The morphologic, immunohistochemical, and genetic characteristics that define oncocytic renal tumors remain incompletely understood. Further studies correlating genetics, behavior, and histology are needed to define which tumors truly warrant classification as carcinomas for patient counseling and follow-up strategies.

Urethral carcinoma is a rare tumor with predominantly poor survival. Both the disease and its treatment can affect both sexual and urinary function. The natural history of urethral carcinoma varies, therefore the appropriate application of surgery, radiation, and chemotherapy remain unknown. Management of this disease remains driven by individual clinician experience and data derived from small case series. This article discusses the histology and anatomy of the male and female urethra, as well as their natural history. In addition, the epidemiology, clinical presentation, diagnosis, staging, treatment, and future directions of management of cancer arising in the urethra are addressed.