title: Clear Cell Urothelial Carcinoma.
abstract: Clear cell urothelial carcinoma (CCUC) is a rare variant of urothelial carcinoma (UC) and its clinical significance has not been well elucidated. Consecutive cases of UC over a period of 5 years were reviewed. Histopathological tumor parameters, including the proportion of tumor cells with clear cell change, and patient outcomes were recorded. Expression of the following immunohistochemical markers was investigated: CK7, CK20, CK5, CD44, and PAX8. We also conducted a review of the literature for case reports/series of CCUC. Ten CCUCs were identified out of a total of 872 cases of UC. The clear cell component was characterized by prominent cytoplasmic membranes and voluminous clear cytoplasm, and accounted for 30% to 90% of the invasive tumor component. Of all the non-CCUC cases reviewed, at least 50% (noninvasive or invasive UC) showed focal areas of clear cell change that accounted for less than 5% of the neoplastic cells. Immunohistochemically, CCUC exhibited positive reactivity for CK5/CD44 (n = 9); CK20 (n = 5), PAX8 (very focal to extensive) (n = 6), and GATA3/CK7 (n = 10). Eight of 10 CCUC were of advanced clinical stage (pT3/pT4) and 6 of 10 experienced tumor recurrence and/or death due to disease. In conclusion, CCUC can be distinguished from non-CCUC by the extensive clear cell change in more than 30% of cells. This variant is associated with rapid progression to muscle invasion and metastasis, with an aggressive clinical course. Expression of CK5/CD44 may represent basal cell features in most CCUC cases, while PAX8 expression is suggestive of mesonephric derivation.
authors.affiliation: 1 The Ottawa Hospital, Ottawa, Ontario, Canada.|2 University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Kien T
authors.initials: KT
authors.lastname: Mai
authors.affiliation: 1 The Ottawa Hospital, Ottawa, Ontario, Canada.|2 University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Justin
authors.initials: J
authors.lastname: Bateman
authors.affiliation: 1 The Ottawa Hospital, Ottawa, Ontario, Canada.|2 University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Bojana
authors.initials: B
authors.lastname: Djordjevic
authors.affiliation: 1 The Ottawa Hospital, Ottawa, Ontario, Canada.|2 University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Flood
authors.affiliation: 1 The Ottawa Hospital, Ottawa, Ontario, Canada.|2 University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Belanger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: PAX8; carcinoma; clear; mesonephric; urothelial