Small Cell Carcinoma Of The Urinary Bladder Research Articles

Small cell carcinoma - Urinary bladder

Primary small-cell neuroendocrine carcinoma of the urinary bladder is a rare type of poorly differentiated and highly aggressive tumor. It accounts for <0.7% of all cancers arising from the bladder. Small-cell carcinoma of the urinary bladder is frequently found in conjunction with other histologic types such as urothelial carcinoma (transitional cell carcinoma [TCC]), squamous cell carcinoma, and adenocarcinoma. Although the tumor shares similar histological features like small-cell carcinoma originating from other sites of the body, its clinical picture is very similar to conventional TCC of the urinary bladder. Unknown etiology and pathogenesis makes its diagnosis and treatment difficult. Here, we report a case of small-cell carcinoma of the urinary bladder, its clinical presentation, pathological characteristics, behavior, management, and outcome.

Survival of Contemporary Patients With Non-metastatic Small-cell Carcinoma of Urinary Bladder, According to Alternative Treatment Modalities.

The objective of this study was to test the effect of chemotherapy and/or radical cystectomy (RC) and/or radiotherapy (RT) on survival of patients with non-metastatic small-cell carcinoma of the urinary bladder (SCCUB). Within the Surveillance, Epidemiology, and End Results registry (2001-2016), we identified patients with non-metastatic (T1-4, N0, M0) SCCUB. Treatment was defined as: chemotherapy alone, chemotherapy+ RC, and chemotherapy+ RT. Temporal trends, cumulative incidence plots, and multivariable competing risks regression models were used. Of 595 patients with SCCUB, 230 (38.5%), 159 (27%), and 206 (34.5%) were treated with chemotherapy alone, chemotherapy+ RC, and chemotherapy+ RT, respectively. The rates of chemotherapy+ RC increased (estimated annual percentage changes [EAPC],+5.9%; P= .002). Conversely, chemotherapy alone (EAPC,-1.7%; P= .1) and chemotherapy+ RT rates decreased (EAPC:-2.2%; P= .08). Overall, 5-year cancer-specific mortality (CSM) rates were 44%, 29%, and 40% for patients treated with chemotherapy alone, chemotherapy+ RC, and chemotherapy+ RT, respectively (P= .004). Relative to chemotherapy alone, patients treated with chemotherapy+ RC experienced lower CSM (hazard ratio, 0.5; P< .001). Conversely, patients treated with chemotherapy+ RT did not exhibit any CSM benefit (hazard ratio, 0.8; P= .2), when compared with chemotherapy alone. In contemporary patients with SCCUB with non-metastatic disease, the rates of chemotherapy+ RC are increasing. Conversely, the rates of combined chemotherapy with RT and chemotherapy alone are decreasing. These patterns of treatment are in agreement with better cancer control in patients with SCCUB. In consequence, until more robust data become available, the combination of chemotherapy and RC should represent the recommended treatment strategy.

Prognosis of early stage small cell bladder cancer is not always dismal

Background Small cell carcinoma of the urinary bladder (SCCB) is an extremely rare malignancy which is often associated with poor survival outcome. Literature reporting such disease is scarce. There is no standardised management. This retrospective audit examines a UK Cancer Centre’s SCCB management and survival outcomes.Methods Histopathology database at Nottingham University Hospitals, UK, was used to identify patients diagnosed with SCCB from January 2008 to January 2016.Results 27 patients had confirmed diagnosis of SCCB. Mean age at diagnosis was 68.7 (range 37–90). 30% of the cases had pure small cell histology, while the rest were mixed histological subtype. Of the 12 patients with early stage disease (stage I and II), three had radical cystectomy and chemotherapy, six had both radiotherapy and chemotherapy, two had either radiotherapy or chemotherapy alone, and one declined active treatment. Of the 12 patients with advanced disease (stage III and IV), four had chemotherapy alone, four had both radiotherapy and chemotherapy and four was for best supportive care. 13 out of 16 patients who had chemotherapy received combination of carboplatin and etoposide. Patients with advanced stage disease had medial survival of 9 months (95% CI 3.9 to 14.1 months). The median survival for patients with early disease was not reached. There is significant difference in survival between early and late stage disease (p value 0.008, Log rank test).Conclusions Our results demonstrated a reasonable survival outcome in early stage SCCB patients. Radical multimodality treatment options should not be precluded in patients with early stage SCCB.

Small cell carcinoma of the urinary bladder, a single institution experience.

e16512Background: Small cell carcinoma of the urinary bladder (SCCB) is a rare but aggressive malignancy associated with poor prognosis. There is no established treatment guideline. It is typically...

A rare case of small cell carcinoma of urinary bladder in a bladder diverticulum: Case report and review of literature

Small cell carcinoma of the urinary bladder (SCCB) is a rare and aggressive non-urothelial tumour of the urinary bladder. It represents neuro endocrine type of malignancy, being diagnosed on histopathology and immuno histo chemistry. Bladder diverticulum tumours are rare and present with early lamina propria invasion. Furthermore, the risk of bladder perforation is high during resection due to the lack of muscle. Thus, these tumours have a risk of being under-staged and have a poor prognosis. Till now, very few cases have been reported of SCCB in bladder diverticulum. Multi-modality management in the form of combined chemotherapy and surgery is required for the optimal management. We report this rare case and review the literature for the management of SCCB in bladder diverticulum.

Small-cell Carcinomas of the Urinary Bladder and Prostate: TERT Promoter Mutation Status Differentiates Sites of Malignancy and Provides Evidence of Common Clonality Between Small-cell Carcinoma of the Urinary Bladder and Urothelial Carcinoma

BackgroundSmall-cell carcinoma (SCC) of the urinary bladder frequently appears alongside urothelial carcinoma, suggesting common clonality. TERT promoter mutations have been recently implicated in urothelial carcinogenesis. ObjectiveTo investigate the degree to which TERT promoter mutations are involved in SCC of the urinary bladder, the linked tumorigenesis between urothelial carcinoma and SCC of the urinary bladder, and the molecular distinctions between SCC of the urinary bladder and of the prostate. Design, setting, and participantsWe investigated TERT promoter mutations in 53 cases of SCC of the urinary bladder and in 26 cases of SCC of the prostate using laboratory-based studies of tissue samples and clinical data. Outcome measurements and statistical analysisWe measured the frequency of TERT promoter mutations in SCCs of the urinary bladder and prostate, and concordance of the mutation status between concurrent urinary bladder SCC and urothelial carcinoma. Results and limitationsTERT promoter mutations were detected in 29/53 (55%) cases of urinary bladder and 0/26 (0%) cases of prostate SCC. Of 25 cases with concurrent urinary bladder SCC and non–small-cell components, all cases harbored identical TERT promoter mutation status in both phenotypes. ConclusionsTERT promoter mutations are found in more than half of urinary bladder SCCs. Mutation status is also identical in urothelial carcinoma and SCC components of concomitant malignancies, providing evidence of a common clonality. TERT promoter mutation status can differentiate SCC of the urinary bladder from prostate SCC, suggesting potential diagnostic use. Patient summarySmall-cell carcinoma of the urinary bladder shares a common clonal origin with conventional urothelial carcinoma and may arise from a heterogeneous subclone. TERT promoter mutations may have utility as a differential biomarker for determining the primary site of a genitourinary small-cell carcinoma.

Prognostic significance of serum neuron-specific enolase in small cell carcinoma of the urinary bladder.

Small cell carcinoma of the urinary bladder (SCCB) is known for its aggressive clinical features and poor prognosis. No prognostic factor has been established so far. The aim of this study was to assess the significance of possible prognostic factors, including serum neuron-specific enolase (NSE), an established biomarker for small cell lung carcinoma. We retrospectively reviewed 31 patients with primary SCCB treated at our eight affiliate institutions between 2001 and 2014. The association of various clinicopathological factors at diagnosis, including the serum NSE value, with cancer-specific survival (CSS) was assessed. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. Nineteen (61.3%) died of SCCB during the follow-up, with a median survival time of 12.7months. Prognostic factors were analyzed for the 25 patients after excluding six with missing data. Univariate analysis demonstrated that stage (extensive disease) and serum NSE ≥25ng/ml were significantly associated with worse CSS. Multivariate analysis identified increased serum NSE value as a sole independent predictor of CSS (hazard ratio 18.52, p=0.0022). Serum NSE value at diagnosis was an independent prognostic factor for primary SCCB and may serve as a useful biomarker in the management of SCCB.

Small cell carcinoma of the bladder in transplant recipients: a report of 2 cases

Small cell carcinoma (SCC) of the urinary bladder is a rare disease accounting for 0.5% to 0.7% of all primary bladder cancers. Transplant recipients are a special subset of patients with increased risk for various urologic malignancies, including transitional cell carcinoma of the bladder. However, to the best of our knowledge, a SCC of the urinary bladder has not been reported in transplant recipients. We report what we believe are the first 2 reported cases of transplant recipients with SCC of the bladder. Small cell carcinoma was diagnosed 5 years after transplantation in both patients and they died due to metastatic SCC. Our report emphasizes the highly aggressive nature of SCC and also the rapid progression seen in transplant recipients.

A Surveillance, Epidemiology, and End Results analysis of small cell carcinoma of the bladder

Small cell carcinoma of the urinary bladder (SCCB) is difficult to characterize and study because of its rarity. For the current study, a large population-based database was used to address ill-defined clinical parameters for this disease. The authors analyzed the incidence, sociodemographics, prognostic variables, and treatment trends of this cancer in the Surveillance, Epidemiology, and End Results (SEER) limited database (1991-2005). The SEER-Medicare database (1991-2005) was used to estimate chemotherapy use. There were 642 patients in the SEER limited dataset. From 1991 to 2005, the incidence of SCCB increased significantly from 0.05 to 0.14 cases per 100,000 population (P < .01; approximately 500 new cases of SCCB per year, representing 0.7% of all bladder malignancies). The median overall survival was 11 months. Elderly Caucasian men were the most commonly affected (ratio of Caucasians to non-Caucasians, 10:1; ratio of men to women, 3:1; median age, 73 years). Age, race, marital status, and TNM staging were identified as independent prognostic variables (P < .05). Patients who had stage IV disease without distant metastasis (ie, positive lymph node status) had overall and cancer-specific survival rates similar to those of patients who had stage I through III disease, but they had significantly better survival compared with patients who had distant metastasis (P < .0001). Transurethral resection of the bladder tumor became the most common surgical treatment (P < .0001), representing 55% of patients from 2001 to 2005. The receipt of radiation and chemotherapy did not change significantly during the study period. These comprehensive data delineated the patient population for this rare disease, described several independent prognostic variables, and demonstrated clear treatment trends for this disease. The results suggest that a simpler staging system (ie, limited stage vs extensive stage) may be appropriate for patients with SCCB.

Symptomatic brain metastases from small-cell carcinoma of the urinary bladder: The Netherlands Cancer Institute experience and literature review

BackgroundThe incidence of symptomatic brain metastases in small-cell carcinoma of the urinary bladder (SCBC) is unknown. This precludes advice about prophylactic cranial irradiation (PCI). Patients and methodsThe medical records of all patients with SCBC seen at The Netherlands Cancer Institute from 1993 to 2009 (n=51) were reviewed. Limited disease (LD) was defined as any pT, cN0–1, and cM0. Patients with LD were offered bladder-preserving treatment involving combined chemoradiotherapy. Patients with extensive disease (ED) were treated with palliative chemotherapy. PCI was not applied in any patient. ResultsAmong 39 patients with LD, median disease-specific survival was 35 months. Four developed symptomatic brain metastases after a median follow-up of 15 months (range 3–24) and were treated with whole-brain radiotherapy. No patient with ED developed symptomatic brain metastases during a median follow-up of 6 months. The reported incidence of brain metastases in SCBC in the literature ranges between 0% and 40%. On the basis of all reported series, the pooled estimate of the cumulative incidence of brain metastases is 10.5% (95% confidence interval 7.5% to 14.1%). ConclusionsThe incidence of symptomatic brain metastases from SCBC is significantly lower than that from small-cell lung cancer. Therefore, we do not routinely advise PCI in patients with SCBC.

Significant activity of single agent vinorelbine against small-cell cancer of the bladder as second line chemotherapy: A case series and review of the literature

Small-cell carcinoma of the urinary bladder is an extremely uncommon form of urologic malignancy, accounting for less that 1% of new cases of bladder cancer. It is an aggressive malignancy which, like its pulmonary counterpart, tends to spread with distant metastases. This malignancy is generally chemotherapy and radiotherapy sensitive. Metastatic disease is typically treated with regimens active against small-cell carcinoma of the lung, such as cisplatin and etoposide. There are no data regarding second-line treatment of this cancer. We report our experience in 3 patients using the second generation vinca alkaloid, vinorelbine, in refractory metastatic small-cell carcinoma of the bladder. These 3 patients had extensive prior therapy but all 3 responded to weekly vinorelbine, with a complete response (CR) in 1, near CR in the second, and partial response in the third. Of note, the patient who sustained a CR has remained without disease and with excellent quality of life for nearly 4 years since starting vinorelbine. Indeed, the therapy was very well tolerated in all 3 patients with grade 2 cytopenia being the only toxicity. We conclude that vinorelbine is well tolerated and has activity in this case series in the second-line treatment of metastatic small-cell carcinoma of the bladder.

Small cell carcinoma of the urinary bladder.

Small cell carcinoma of the urinary bladder (SCCUB) is a rare and aggressive cancer of the bladder. SCCUB is part of neuroendocrine family of tumors that affect several organ systems including respiratory, gastrointestinal and male and female genitourinary tract. SCCUB affect males predominantly with common risk factors include smoking, bladder calculi, bladder manipulation, and chronic cystitis. Prognosis of SCCUB remains poor due to high metastatic potential and lack of symptoms in earlier stages of the disease. Pathogenesis of the disease is linked to loss of genetic material, hypermethylation of tumor suppressors and at times amplification of the chromosomal regions carrying oncogenes. Majority of cases are treated with local resection of the tumor with neoadjuvant or adjuvant platinum-based chemotherapy regimen. Radiation therapy is used as alternative to radical cystectomy or as palliative measure. This article provides epidemiology, molecular pathogenesis, histochemistry, and current management options for SCCUB. Furthermore we reviewed all recent studies involving advancement in targeted molecular therapy for neuroendocrine tumors.

Small cell carcinoma with skeletal muscle differentiation of urinary bladder

Reported herein is a case of small cell carcinoma (SCC) with skeletal muscle differentiation of urinary bladder in a 76-year-old woman presenting macrohematuria. Ultrasonography and CT detected a mass at the anterior wall of the urinary bladder, and total cystectomy followed. The tumor consisted of solid growth of small round cells with high nucleocytoplasmic ratio admixed with rhabdoid cells with eosinophilic cytoplasmic inclusions, invading the perivesical tissue. On immunohistochemistry the tumor cells were diffusely positive for neural markers and CD99, and sporadically for skeletal muscle markers. Fluorescence in situ hybridization showed no translocation of EWS. The patient died from massive recurrence in the pelvis 4 months after operation. This rare tumor indicates a potential of myoid differentiation in SCC of the urinary bladder and differential diagnosis from primitive neuroectodermal tumor is important because the treatment is different.

Small cell carcinoma of the urinary bladder: a 15‐year retrospective review of treatment and survival in the Anglian Cancer Network

To report the clinical experience and management of patients with small cell carcinoma (SCC) of the bladder, treated in the Anglia Cancer network from 1992 to 2007, and to review published studies, as SCC is a rare condition, accounting for <1% of all bladder tumours, and there is no established treatment strategy for managing these patients. We analysed retrospectively data from all patients diagnosed with SCC of the urinary bladder between 1992 and 2007, with an emphasis on stage, treatment and overall survival. Twenty patients were identified with primary bladder SCC (male: female ratio 3:1; mean age 68 years; mean follow-up 15.8 months). Nine patients (45%) had extensive-stage disease at diagnosis. Four patients received best supportive care, three had a radical cystectomy, one radical radiotherapy and six sequential chemo-radiotherapy. In all, 13 patients were treated with chemotherapy, with six receiving cyclophosphamide, doxorubicin and vincristine, three receiving carboplatin and etoposide, and the remainder receiving alternative platinum-based regimens. For 12 patients with assessable disease, six had a complete response, three a partial response and three had progressive disease after chemotherapy. No patient received prophylactic cranial irradiation (PCI). At the time of analysis, 14 (70%) patients had died, with one (5%) developing brain metastasis. The median survival was 33 months for patients receiving chemotherapy, vs 3 months with no chemotherapy. SCC of the bladder tends to occur in an older population, more commonly in men. It is an aggressive tumour with a propensity for early metastasis. The response rate to chemotherapy is high but the overall prognosis is poor. Brain secondaries are less common than for SCC of the lung and currently the role of PCI is unclear. As there is no standard of care for these patients, they are treated according to local protocols. Further efforts should be made to develop more effective treatments and the role of PCI should be assessed in the setting of a clinical trial, in conjunction with other extrapulmonary SCCs.

The Expression of TTF-1 in Small Cell Carcinoma of Urinary Bladder

Small cell carcinoma (SMCC) of the urinary bladder is a rare tumor, accounting for less than 1% of all malignant neoplasms in the urinary bladder. Recently, thyroid transcription factor-1 (TTF-1), a putative marker for tumors originating from the lung and thyroid, was found to be expressed in SMCC of the urinary bladder, albeit in only a very small number of cases. Herein we report two additional cases of SMCC of the urinary bladder expressing TTF-1. The first patient was a 68-year-old white male with a 5-year history of a small focus of prostatic adenocarcinoma (biopsy proven) who was being treated with brachytherapy. He subsequently developed multiple large nodules at the base of the bladder, which by biopsy identified the presence of loosely cohesive small cells with minimal cytoplasm, coarsely and finely granular chromatin and indistinct nucleoli. Tumor cells were positive for TTF-1, CD56, chromogranin, synaptophysin and Cam 5.2, and negative for PSA. The location, morphological and immunochemical features of the tumor were diagnostic for SMCC of the urinary bladder. The second patient was a 76-year-old white female with a history of recurrent episodes of urinary tract infections. A biopsy showed a poorly differentiated carcinoma. The subsequent cystectomy revealed the presence of a 4.5 x 4.5 x 2.1 cm. tumor composed of a mixture of infiltrating high grade urothelial carcinoma and small cell carcinoma. The small cell component possessed similar morphological and immunohistochemical features as previously described in the first case, including positive expression for TTF-1. These two cases illustrate and concur with previous assertions that TTF-1 cannot be used to distinguish primary SMCC of the urinary bladder from metastatic SMCC of lung. [N A J Med Sci. 2009;2(3):94-96.]

Hypermethylation of tumor-suppressor gene CpG islands in small-cell carcinoma of the urinary bladder

Small-cell carcinoma of the urinary bladder (SCBC) is a rare tumor, which shows a common clonal origin with urothelial carcinoma. It bears a high metastatic potential, even when discovered in a localized state. Identifying the molecular underpinnings of this disease may elucidate useful clinical information regarding prevention, diagnosis, prognosis, treatment, and surveillance. As DNA methylation is widely recognized as having a pivotal role in the process of carcinogenesis, we analyzed the DNA methylation status of four frequently hypermethylated tumor suppressors in small-cell and transitional-cell carcinoma (TCC) arising concomitantly in 13 patients. Fourteen cases of pure TCC were also included in the analysis. We identified frequent methylation of RASSF1 and MGMT and infrequent methylation of MLH1 and DAPK1 in cases of concomitant TCC and SCBC. Similar rates of methylation were found in pure and concomitant histopathologies, with the exception of MGMT, which was much less frequently methylated in pure TCC. These findings suggest that SCBC and TCC have common origins, establish DNA methylation of some tumor suppressors as frequent occurrences in both histopathologies, and suggest that MGMT methylation may be an SCBC-specific epimutation.

Small-cell carcinoma of the urinary bladder: diagnosis and management

Small-cell carcinoma of the urinary bladder (SCCUB) accounts for less than 1% of all cancers arising in the urinary bladder. Current diagnosis and management of SCCUB are often patterned after small-cell lung cancer (SCLC). However, SCCUB therapy is different from that for SCLC. For example, many patients with SCCUB undergo local resection, which is rarely performed in SCLC. As in SCLC, platinum–etoposide combination chemotherapy is employed as the main systemic treatment option for SCCUB. Chemotherapy is usually combined with other therapeutic modalities, especially in patients whose disease is limited to the locoregional area. Owing to the rarity of this malignancy, no prospective study has been performed that establishes the efficacy and duration of chemotherapy or the relative efficacy of platinum–etoposide versus other chemotherapeutic regimens. This article provides a comprehensive review of the current status of SCCUB diagnosis and management, as well as some unique insights into this rare tumor.

Molecular Genetic Evidence for a Common Clonal Origin of Urinary Bladder Small Cell Carcinoma and Coexisting Urothelial Carcinoma

In most cases, small-cell carcinoma of the urinary bladder is admixed with other histological types of bladder carcinoma. To understand the pathogenetic relationship between the two tumor types, we analyzed histologically distinct tumor cell populations from the same patient for loss of heterozygosity (LOH) and X chromosome inactivation (in female patients). We examined five polymorphic microsatellite markers located on chromosome 3p25-26 (D3S3050), chromosome 9p21 (IFNA and D9S171), chromosome 9q32-33 (D9S177), and chromosome 17p13 (TP53) in 20 patients with small-cell carcinoma of the urinary bladder and concurrent urothelial carcinoma. DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-assisted microdissection. A nearly identical pattern of allelic loss was observed in the two tumor types in all cases, with an overall frequency of allelic loss of 90% (18 of 20 cases). Three patients showed different allelic loss patterns in the two tumor types at a single locus; however, the LOH patterns at the remaining loci were identical. Similarly, the same pattern of nonrandom X chromosome inactivation was present in both carcinoma components in the four cases analyzed. Concordant genetic alterations and X chromosome inactivation between small-cell carcinoma and coexisting urothelial carcinoma suggest that both tumor components originate from the same cells in the urothelium.

Small-cell carcinoma of the urinary bladder: 10-year experience

Small-cell carcinoma of the urinary bladder is rarely encountered in clinical practice. We report on our clinical experience with affected patients presenting to our institution from 1986 to 1996. We retrospectively analysed 14 pathologically confirmed cases, specifically looking at stage, presenting features, treatment and overall survival. The median age at presentation was 74 years (range 54-91 years). Ten patients presented with stage III disease, and four patients with stage IV disease (1 = nodal, 3 = distant metastases). Four patients were treated with radical radiotherapy (one patient receiving neoadjuvant chemotherapy) and two underwent a radical cystoprostatectomy. Five patients received palliative bladder radiotherapy and three were too frail for treatment at presentation. The overall median survival was 5 months. Patients receiving radical treatment had a median overall survival of 21 months, with only one long-term survivor. This highly aggressive tumour tends to affect an elderly population who are generally frail and have significant comorbidity. Many are unfit for radical treatment. In patients with disease confined to the pelvis who are able to tolerate radical intervention, the results of local therapy alone are poor. It therefore remains incumbent on treating clinicians to explore means of improving these results. Initial chemotherapy analogous to small-cell lung cancer may offer a durable response with a better chance for long-term survival.

Small-cell carcinoma of the urinary bladder. A clinico-pathological study of ten cases.

Small-cell carcinoma (SCC) of the urinary bladder is an infrequent neoplasia accounting for 0.5% of all tumors located at this level. There is a predilection for males over females with a 4:1 proportion and a median age of 66 years. In most cases, the initial diagnosis is made at the metastatic or progressive stage of the disease. For this study, we collected ten cases of SCC of the urinary bladder, diagnosed over a period of 16 years, to describe the morphological and immunocytochemical characteristics of these infrequent neoplasia. In all cases, clinical data such as age at presentation, personal background, clinical symptoms, stage, treatment, clinical outcome and present status were available. Primary antibodies included chromogranin, neuron-specific enolase, synaptophysin, PGP 9.5, HNK-1, cytokeratin 34betaE12, cytokeratin 20, thyroid transcription factor-1 (TTF-1), c-erbB2 (CB-11), p53 (DO7), and Ki67 (MIB-1). In addition to the expression of neural/neuroendocrine markers, immunostaining for p53 and c-erbB2 was found in 80% and 50% of cases, respectively. In this paper, we confirm the aggressive course of the neoplastic disease. The expression of c-erbB2 in 50% of cases opens up hypothetical new possibilities for the use of immunotherapy in such cases.