Stromal lymphoid response status in micropapillary urothelial carcinomas diagnosed in bladder transurethral resections and its comparison with conventional urothelial carcinomas

Objective: Micropapillary urothelial carcinoma is an aggressive variant of urothelial carcinoma. Evidence suggests that the relationship between the tumor and inflammatory cells is important in tumor progression and the treatment response. We evaluated the stromal lymphoid response in micropapillary urothelial carcinomas and compared it with conventional urothelial carcinomas. Material and Method: Among bladder transurethral resection materials diagnosed as 'invasive urothelial carcinoma' between January 2010-March 2017, cases with at least 5% micropapillary urothdial carcinoma were evaluated for age, gender, grade, stage, micropapillary urothelial carcinoma percentage, presence/percentage of accompanying conventional urothelial carcinoma/urothelial carcinoma variants, in situ urothelial carcinoma/micropapillary urothelial carcinoma, lymphovascular invasion, necrosis, and stromal lymphoid response. Stromal lymphoid response was scored as 0-1-2-3. All parameters were evaluated in 50 pure conventional urothelial carcinomas. Results: Among 47 micropapillary urothelial carcinomas, 41 were male. The mean age was 69 years. pT1/pT2 was 23/24. Six cases were pure MPUC. Lymphovascular invasion was present in 8, necrosis in 9 cases. Stromal lymphoid response was present and scored as 1-2-3 in 32 micropapillary urothelial carcinomas (68.1%) and 48 conventional urothelial carcinomas (96%). Micropapillary urothelial carcinomas had significantly higher lymphovascular invasion and pT2 rates and lower stromal lymphoid response. Conclusion: Low stromal lymphoid response in micropapillary urothelial carcinomas can be responsible for the poor clinical outcome and impaired response to treatment of these tumors. This is the first study in the English literature to demonstrate a lower stromal lymphoid response rate in micropapillary urothelial carcinomas compared to conventional urothelial carcinomas

An epidemiologic study on urothelial carcinomas of bladder

Objectives: In this study, the epidemiological analysis of the bladder cancers was performed accompanied by the known environmental factors.Materials and methods: In this retrospective study, pathology archival materials of 420 patients (350 men (83.4%) and 70 women (16.6%)), consisting of bladder by transurethral resection, cystectomy and cystoprostatectomy specimens, histopathologically diagnosed as urothelial carcinoma and papillary urothelial neoplasia with low malignant potential, were included. For bladder carcinomas, the parameters such as tumor types, age, sex, and invasiveness of tumor were evaluated and analyzed.Results: In the study, it was found that 24.7% of papillary urothelial neoplasia with low malignant potential, 46.1% of low-grade urothelial carcinoma, and 29.0% of high grade urothelial carcinoma. The rate of bladder urothelial carcinomas was 5 times greater in men than in women. In addition, the high-grade papillary urothelial carcinoma was seen more frequently in men than in women (31.2% and 23.1% respectively), while low-grade papillary urothelial carcinoma was seen more frequently in women than in men (32.9% and 18.5% respectively) (p<0.05).Conclusion: The bladder urothelial carcinoma was more common in men than women, and high-grade urothelial carcinoma invading the lamina propria and the muscularis propria also found in a higher ratio in male. Further clinical and experimental studies are needed to explore the cause of high frequency of high-grade types in male gender

Lipid-Rich Variant of Urothelial Carcinoma Presenting as the Dominant Morphology in a Recurrent Tumor After Local Therapy

Objective: Rare co-existance of disease or pathology Background: The lipid-rich variant is a rare and aggressive type of urothelial carcinoma (UCa), with less than 40 cases reported in the literature. This variant usually presents as an advanced-stage primary tumor. Case Report: We report the case of a 61-year-old man with previous history of T1 high-grade conventional urothelial carcinoma treated with local therapy. The patient later presented with a new 6.5-cm exophytic bladder mass. Histopathological examination revealed a T2 urothelial carcinoma of the lipid-rich variant. Retrospective review of the previous biopsies confirmed conventional high-grade urothelial car0cinoma, but scattered rare individual or small clusters of cells that resemble the lipid-rich variant urothelial carcinoma were also noted. Conclusions: The findings in this case suggest that the differential sensitivity of conventional urothelial carcinoma to local therapy may have allowed the lipid-rich variant to predominate in the recurrence. Pathologists should be aware of the lipid-rich variant of urothelial carcinoma. The prognostic significance of rare lipoblast-like cells among predominantly conventional urothelial carcinoma may requires further study

Urothelial bladder carcinoma metastasizing to the eye: a systematic review and case report

The eye is a rare site for disseminated malignancies; nevertheless, several tumors may metastasize to ocular structures. Few cases of urothelial and bladder cancer with eye involvement have been described in the literature thus far. The rarity of metastatic ocular localization implies an accurate differential diagnosis among the possible primary tumor sites. However, a specific diagnostic algorithm is not currently available, nor a defined therapeutic approach. Eye metastases are associated with advanced disease and poor prognosis. Physicians should be made aware of the possibility of eye involvement in patients with a past medical history of urothelial bladder cancer associated with ocular symptoms. The present case reports discusses the first documented case, to the best of our knowledge, of an urothelial bladder cancer metastasizing to the retro bulbar region that infiltrates the lacrimal gland. Furthermore, the report provides a systematic qualitative review of the current literature on eye metastases from urothelial bladder cancer using the Preferred Reporting Items for Systematic Reviews and Meta Analyses

Durvalumab: an investigational anti-PD-L1 monoclonal antibody for the treatment of urothelial carcinoma.

Our expanding knowledge of immunotherapy for solid tumors has led to an explosion of clinical trials aimed at urothelial carcinoma. The primary strategy is centered on unleashing the immune system by releasing the inhibitory signals propagated by programmed cell death-1 (PD-1) and its ligand programmed cell death ligand-1 (PD-L1). Many antibody constructs have been developed to block these interactions and are used in clinical trials. The Food and Drug Administration has already approved a number of checkpoint inhibitors such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibodies including ipilimumab; anti-PD-1 monoclonal antibodies including nivolumab and pembrolizumab; anti-PD-L1 antibodies including atezolizumab, avelumab, and durvalumab. One of the latest inhibitors is durvalumab, which is a high-affinity human immunoglobulin G1 kappa monoclonal antibody and blocks the interaction of PD-L1 with PD-1 and CD80. Currently, there are a number of ongoing trials in advanced urothelial carcinoma both using durvalumab monotherapy and in combination with other targeted therapies. In addition, durvalumab is being investigated in the non-muscle-invasive urothelial carcinoma, which is centered around intravenous formulations. These exciting developments have added a significant number of therapies in a previously limited treatment landscape

Functional Genomics Profiling of Bladder Urothelial Carcinoma MicroRNAome as a Potential Biomarker.

Though bladder urothelial carcinoma is the most common form of bladder cancer, advances in its diagnosis and treatment have been modest in the past few decades. To evaluate miRNAs as putative disease markers for bladder urothelial carcinoma, this study develops a process to identify dysregulated miRNAs in cancer patients and potentially stratify patients based on the association of their microRNAome phenotype to genomic alterations. Using RNA sequencing data for 409 patients from the Cancer Genome Atlas, we examined miRNA differential expression between cancer and normal tissues and associated differentially expressed miRNAs with patient survival and clinical variables. We then correlated miRNA expressions with genomic alterations using the Wilcoxon test and REVEALER. We found a panel of six miRNAs dysregulated in bladder cancer and exhibited correlations to patient survival. We also performed differential expression analysis and clinical variable correlations to identify miRNAs associated with tobacco smoking, the most important risk factor for bladder cancer. Two miRNAs, miR-323a and miR-431, were differentially expressed in smoking patients compared to nonsmoking patients and were associated with primary tumor size. Functional studies of these miRNAs and the genomic features we identified for potential stratification may reveal underlying mechanisms of bladder cancer carcinogenesis and further diagnosis and treatment methods for urothelial bladder carcinoma

Unusual manifestations of secondary urothelial carcinoma

AbstractHigh-grade papillary urothelial carcinoma regularly invades the bladder wall, adjacent prostate, seminal vesicles, ureters, vagina, rectum, retroperitoneum, and regional lymph nodes. In advanced stages, it may disseminate to the liver, lungs, and bone marrow. On rare occasions, unusual metastatic foci like skin have been reported. The incidence of urothelial carcinoma has increased with associated rise in variants of urothelial carcinoma and unusual metastatic foci. It is imperative that urologists and pathologists are aware of the unusual variants and unusual metastatic locations to expedite the diagnostic process. Hereby we report an unusual case of secondary involvement of spinal nerve by conventional urothelial carcinoma. Also a second case of rhabdoid variant of urothelial carcinoma showing synchronous involvement of bladder and subcutaneous tissue of upper extremity is presented