title: Flat urothelial carcinoma in situ of the bladder with glandular differentiation.
abstract: We present the clinicopathologic and immunonohistochemical features of 25 cases of flat urothelial carcinoma in situ with glandular differentiation. Previously, cases on this category have been reported as in situ adenocarcinoma (a term not currently preferred). Fourteen of 25 cases had concurrent conventional urothelial carcinoma in situ. Five of the cases were primary carcinoma in situ with glandular differentiation; twenty cases of secondary carcinoma in situ with glandular differentiation were associated with urothelial carcinoma alone (n = 11) or with glandular differentiation (n = 7), discohesive (n = 1) or micropapillary carcinoma (n = 1). The individual tumor cells were columnar. The architectural pattern of the carcinoma in situ with glandular differentiation consisted of 1 or more papillary, flat or cribriform glandular patterns. Univariate statistical analysis showed no survival differences between urothelial carcinoma in situ with glandular differentiation and conventional urothelial carcinoma in situ (log-rank 0.810; P = .368). Carcinoma in situ with glandular differentiation showed high ki-67 index and p53 accumulation, high nuclear and cytoplasmic p16 expression and diffuse PTEN expression, a phenotype that also characterized concurrent conventional carcinoma in situ. MUC5A, MUC2, CK20, and c-erbB2 were positive in all 25 cases of urothelial carcinoma in situ with glandular differentiation, and CDX-2 was present in 19 cases; MUC1, CK7, or 34βE12 was focally present in 21, 19, and 18 cases, respectively. MUC1core was negative in all cases. We concluded that urothelial carcinoma in situ with glandular differentiation is a variant of carcinoma in situ that follows the natural history of conventional urothelial carcinoma in situ. The immunophenotype suggests urothelial origin with the expression of MUC5A and CDX2 as signature for glandular differentiation.
authors.affiliation: Unit of Anatomic Pathology, Department of Surgery, Faculty of Medicine Cordoba University, E-14004 Cordoba, Spain. em1lobea@uco.es
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Jimenez
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Carlo
authors.initials: C
authors.lastname: Patriarca
authors.forename: Ana
authors.initials: A
authors.lastname: Blanca
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Menendez
authors.forename: Ferran
authors.initials: F
authors.lastname: Algaba
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D000071616:CDX2 Transcription Factor; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000473:pathology*; D002454:Cell Differentiation; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000032:analysis; D001743:Urinary Bladder / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000473:pathology*; D019459:Urothelium / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C524678:MUC5AC protein, human; D055271:Mucin 5AC