Noninvasive Urothelial Carcinoma of the Bladder With Glandular Differentiation

ArticleinThe American journal of surgical pathology 33(8):1241-8 · June 2009with10 Reads
DOI: 10.1097/PAS.0b013e3181a1ff41 · Source: PubMed
Noninvasive urothelial carcinoma (UC) with glandular differentiation in the absence of infiltrating carcinoma is a rare entity that has not been well characterized. We retrieved 24 cases of noninvasive UC of the bladder with glandular differentiation on biopsy (n=20) or transurethral resection (n=4) without an associated invasive component. The cases were identified from the consult files of one of the authors between 1992 and 2008. Mean patient age at diagnosis was 70 years (range: 48 to 87 y) and 75% were male. Half of the cases were pure noninvasive UC with glandular differentiation; half were associated with either carcinoma in situ or high-grade noninvasive papillary carcinoma. The glandular component consisted of 1 or more patterns: papillary (46% of cases), glandular (42%), cribriform (33%), and flat (25%). Mitoses, apoptosis, and necrosis were identified in 83%, 67%, and 17% of the biopsies, respectively. One case was a recent diagnosis, and 5 patients either refused treatment or were lost to follow-up. Of the 18 patients with available follow-up information, 9 (50%) did not develop invasive carcinoma; the remaining 9 (50%) eventually developed an invasive bladder tumor. Of these, 2 were small cell carcinoma, 3 were poorly-differentiated UC (2 of these developed widespread metastases), and 4 were UC, not otherwise specified. In both instances of eventual small cell carcinoma, and in 2 of the 3 cases of poorly-differentiated UC, the initial biopsy consisted of pure noninvasive UC with glandular differentiation without carcinoma in situ or noninvasive papillary carcinoma. Of note, none of the patients in the study developed invasive adenocarcinoma.
    • "Likewise some adenocarcinomas originating in cystitis glandularis may be diagnosed in the preinvasive stage [24]. Adenocarcinomas should not be confused with urothelial carcinoma showing mucoid changes in the stroma [25], or benign glandular lesions that may present as exophytic polypoid tumors [26]. "
    [Show abstract] [Hide abstract] ABSTRACT: Bladder cancer is a common form of neoplasia which most often presents histologically as urothelial (transitional cell) carcinoma. In this article we review recent publications dealing with the less common variants of urothelial carcinoma such as tumours that show unusual forms of differentiation or the well know squamous, glandular, or sarcomatoid differentiation. Urothelial tumours may also show several distinct growth variants characterized by a nested, micropapillary, lymphoepithelioma-like, or plasmacytoid and giant cell growth pattern.The clinical course of bladder cancer varies depending on the histological type of neoplasia, grade and stage of the tumour. High-grade muscle-invasive urothelial cancers and tumours showing variant microscopic morphology have in general high mortality and poor prognosis.
    Full-text · Article · Sep 2011
    • "In the urinary bladder, the main differential diagnostic considerations of CISg include benign conditions such as intestinal metaplasia [1,10,12,24]. Some other lesions such as cystitis glandularis may pose differential diagnostic problems, and the recently described noninvasive urothelial carcinoma with glandular differentiation and urothelial carcinoma with villoglandular differentiation might enter the differential diagnosis of CISg; [3,13] likewise, as stated by Lim et al [13], CISg does not form filliform finger-like projections, which are seen in villous adenomas and in urothelial carcinoma with glandular or villoglandular differentiation. Rarely, urothelial CIS with gland-like lumina enters the differential diagnosis because they may have a prominent intracellular mucinous production, but these are not lined by columnar epithelium [2,10]. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Apr 2011
    • "After a median follow-up of 22 months, none developed recurrence or progression. The largest series of noninvasive UC with glandular differentiation was reported by Miller and Epstein.12 In that series, 7 patients were treated with BCG and follow-up was available in 6. "
    [Show abstract] [Hide abstract] ABSTRACT: Urothelial carcinomas have an established propensity for divergent differentiation. Most of these variant tumors are muscle invasive but not all. The response of non muscle invasive variant tumors to intravesical immunotherapy with BCG is not established in the literature, and is reported here. Between June 1995 and December 2007, 760 patients (mean age of 67.5 years) underwent transurethral resection of first time bladder tumors in our institution. Histologically variant tumors were found in 79 patients (10.4%). Of these 57 patients (72%) of them had muscle-invasive disease or extensive non-muscle invasive tumors and remaining 22 patients (28%) were treated with BCG immunotherapy. These included 7 patients with squamous differentiation, 4 with glandular, 6 with nested, 4 with micropapillary and 1 patient with sarcomatoid variant. The response of these patients to immunotherapy was compared with that of 144 patients having high-grade conventional urothelial carcinomas. Median follow-up was 46 months. The 2 and 5-year progression (muscle-invasion) free survival rates were 92% and 84.24% for patients with conventional carcinoma compared to 81.06% and 63.16% for patients with variant disease (P=0.02). The 2 and 5-year disease specific survival rates were 97% and 91.43% for patients with conventional carcinoma compared to 94.74 % and 82% for patients with variant disease (P=0.33). 5 patients (22.7%) of variant group and 13 patients (9.03%) of conventional group underwent cystectomy during follow-up (P=0.068). Patients with non-muscle invasive variants of bladder cancers can be managed with intravesical immunotherapy if tumor is not bulky (>4 cm). Although progression to muscle invasive disease is more common than in conventional group and occurs in about 40% of the patients, life expectancy is similar to patients with conventional high-grade urothelial carcinomas provided that follow-up is meticulous.
    Full-text · Article · Apr 2011
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