Typically in invasive papillary urothelial carcinoma both the overlying papillary and the invasive components are high grade. We describe a series of patients with invasive low-grade papillary urothelial carcinoma (LPUC) in which both the noninvasive and invasive components are low grade. A retrospective search from The Johns Hopkins Surgical Pathology Database and consult cases from one of the author's files from 1998 to 2011 found 54 cases of invasive LPUC, excluding the more common, unique, and already well-characterized nested variant of urothelial carcinoma. Slides were available for 41 cases and formed the basis of the current study. The mean patient age was 68.4 years, with a male predominance. The specimens consisted of 37 bladder biopsies, 1 renal pelvis biopsy, 1 cystoprostatectomy specimen, 1 nephrectomy specimen, and 1 nephroureterectomy specimen. In all cases, invasion was limited to the superficial lamina propria above the muscularis mucosae. None of the histologic features correlated with tumor recurrence. Follow-up information was available for 73% of cases, with an average time interval of 49 months. Recurrent tumor was identified in 10/29 (34%) cases; however, 34% of cases without recurrence had limited follow-up (<24 mo). Three patients showed progression in tumor grade, and 3 additional patients progressed in both grade and stage (60% stage/grade progression). Four patients developed recurrence with ureteral noninvasive LPUC (2 in the bladder and 2 in the ureter). All are alive without disease. As this lesion is being increasingly recognized, larger studies are needed to determine whether invasion arising in LPUC is a significant risk factor for future disease.
[Show abstract][Hide abstract] ABSTRACT: Sinulariolide, an isolated compound from the soft coral Sinularia flexibilis, possesses the anti-proliferative, anti-migratory and apoptosis-inducing activities against the TSGH bladder carcinoma cell. The anti-tumor effects of sinulariolide were determined by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell migration assay and flow cytometry, respectively. Sinulariolide inhibited the growth and migration of bladder carcinoma cells in a dose-dependent manner, as well as induced both early and late apoptosis as determined by the flow cytometer. Also, the sinulariolide-induced apoptosis is related to the mitochondrial-mediated apoptosis via caspase-dependent pathways, elucidated by the loss of mitochondrial membrane potential, release of cytochrome C, activation of caspase-3/-9, Bax and Bad, as well as suppression of Bcl-2/Bcl-xL/Mcl-1. Detection of the PARP-1 cleaved product suggested the partial involvement of caspase-independent pathways. Moreover, inhibition of p38MAPK activity leads to the rescue of the cell cytotoxicity of sinulariolide-treated TSGH cells, indicating that the p38MAPK pathway is also involved in the sinulariolide-induced cell apoptosis. Altogether, these results suggest that sinulariolide induces apoptosis against bladder cancer cells through mitochondrial-related and p38MAPK pathways.
[Show abstract][Hide abstract] ABSTRACT: We present the clinicopathological features of 56 cases of the nested variant of urothelial bladder carcinoma. This is an uncommon variant of bladder cancer, recognized by the current WHO classification of urologic tumors. The nested component represented 100 % of the tumor in 24 cases. The architectural pattern of the tumor varied from solid expansile to infiltrative nests characterized by deceptively bland histologic features resembling von Brunn nests. Typical features of high-grade conventional urothelial carcinoma were present in 32 cases. Most neoplastic cells had nuclei of low to intermediate nuclear grade with occasional nuclear enlargement, most frequently seen in deep areas of tumor. The nested component expressed cytokeratins 7, 20, CAM5.2, and high molecular weight (34ßE12), p63, Ki67, p53, p27, and GATA3. Tumor extension was T1 (n = 9), minimally T2 (n = 10), T2a (n = 1), T2b (n = 4), T3a (n = 8), T3b (n = 13), and T4a (n = 11). On follow-up, 36 of patients died of or were alive with disease from 2 to 80 months (mean 21 months). Four patients died of other causes. Eleven other patients remained disease free. Univariate survival analysis showed no differences for nested carcinoma compared with conventional urothelial carcinoma. As in conventional urothelial carcinoma, in nested carcinoma of the bladder pT category defined different survival groups. In summary, nested variant of urothelial bladder carcinoma is typically associated with advanced stage. In samples of limited volume, it may be misdiagnosed as proliferation of von Brunn nests or other nested-like bladder lesions, delaying definitive therapy.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 05/2014; 465(2). DOI:10.1007/s00428-014-1601-y · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nested/microcystic (NV/MV) urothelial carcinoma (UC) variants are associated with mild cytologic atypia and commonly present at high-stage disease. The histopathogenesis is investigated using urothelial basal cell markers. Archival 14 NV/MV and three inverted papilloma (IP) were immunostained for CD44, cytokeratin 5 (CK5), CK34bE12 and p63. Twenty consecutive cases of invasive high-grade UC including 14 superficial and 6 muscle-invasive UC cases were used as control. Immunostaining was scored as high for staining of full or more than 50% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity and negative reactivity. All 14 NV/MV, 3 IP and 6 control cases showed a high score of immunoreactivity for CK5, CD44, CK34bE12 and focally for p63. The remaining control cases showed a high score of immunoreactivity for CK34bE12, while negative or low for CK5, CD44 and p63. In conclusion, immunoreactivity CK5 and CD44 commonly immunostained NV/MV and some invasive high grade UC. Other basal cell markers (CK34bE12 and p63) appear to be non specific or non sensitive. NV and MV and some UC likely represent a subset of UC displaying immunohistochemical features of urothelial basal cells. They had tendency of endophytic growth and early invasion despite the innocuous cytologic appearance.
Pathology International 08/2014; 64(8):375-81. DOI:10.1111/pin.12187 · 1.69 Impact Factor
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