Clinical and pathological characteristics of micropapillary transitional cell carcinoma: a highly aggressive variant

PURPOSE: We present preliminary clinical, histochemical and molecular findings for 5 patients with micropapillary transitional cell carcinoma of the bladder, a rare histological variant not widely recognized in the urological literature. MATERIALS AND METHODS: The 5 patients were prospectively identified. In 3 cases immunohistochemical staining for expression of CD31, p53, E-cadherin, and alpha, beta and gamma-catenin was performed on paraffin embedded tissue. Sequencing was used to identify point mutations in exons 5 to 9 of p53, and exons 1 and 2 of H-ras. RESULTS: Of the patients 2 died within 1 year of presentation to our institution with rapid local extension along the bladder serosal surface and ureteral sheaths. Another patient had progression to invasive disease within 22 months. In the 3 cases with immunohistochemical staining p53 was negative, despite positive staining of nonmicropapillary transitional cell carcinoma within the same specimen. Stains for the angiotrophic marker CD31 were negative. In all 3 cases normal membrane associated alpha, beta and gamma-catenin expression was present. Examination of p53 sequences revealed a single point mutation in exon 8 of 1 case. In 2 cases different mutations in exon 1 of H-ras were noted. CONCLUSIONS: Micropapillary transitional cell carcinoma is a rare and highly aggressive variant. Paradoxically, our study demonstrated no significant p53 abnormalities. The lacunar histological pattern did not appear to represent invasion of vascular spaces. Rather, these tumors seemed to have the ability to disrupt and replace the normal stromal matrix to achieve rapid nonendothelial extension. Thus, micropapillary histology may predict a lesser likelihood of surgical cure.     

Micropapillary urothelial carcinoma of the urinary bladder: A clinicopathological analysis of 24 cases

Objectives: To stratify patients with micropapillary urothelial carcinoma of the urinary bladder based on the percentage of micropapillary component and to correlate tumor volume with other clinicopathological features. Methods: Cases of micropapillary urothelial carcinoma of the urinary bladder from 2002 to 2009 were identified. Only patients with available follow‐up information were included in the analysis. Tumor volumes were stratified based on the percentage of micropapillary component (<50%, >50% and 100%). Results: Overall, 24 cases were analyzed. Mean patient age was 71 years (range 55–86 years), with a male to female ratio of 3:1. Six cases (6/24; 25%) were composed entirely of micropapillary component. A total of 12 cases (12/24; 50%) showed >50% micropapillary component. Six cases (6/24; 25%) showed <50% micropapillary component. A higher percentage of micropapillary urothelial carcinoma component was significantly associated with male sex, regional lymph node metastasis and pathological stage (P‐values = 0.0005, 0.01 and 0.03, respectively). The percentage of the micropapillary component was, however, unrelated to patients' survival. Conclusions: The present study confirms that micropapillary urothelial bladder carcinoma is typically aggressive and presents with advanced stage disease in most cases. A quantification of the micropapillary component is to be recommended. An accurate diagnosis of this entity in relatively small biopsies or transurethral resection of bladder tumor specimens is especially critical to define the best treatment plan.     

In situ adenocarcinoma of the bladder.

In situ adenocarcinoma of the bladder has not been well studied. Only one other case not associated with infiltrating adenocarcinoma has been reported in the literature. We identified 19 biopsies of in situ adenocarcinoma of the bladder without concurrent infiltrating adenocarcinoma or villous adenoma from the surgical pathology files of the Johns Hopkins Hospital between May 1984 and July 2000. The majority of patients (89%) were seen in consultation. The mean age at diagnosis was 70.4 years (range 48-88 years) and 79% were male. None of the patients developed a pure infiltrating adenocarcinoma; however, two patients had invasive urothelial carcinoma with focal glandular differentiation on prior or subsequent specimens. Two cases were pure in situ adenocarcinoma and 10 were seen with carcinoma in situ and/or papillary transitional cell cancer without invasion. Most patients (74%) had invasive carcinoma on either concurrent or subsequent specimens (five small cell and nine transitional cell [four micropapillary]). The majority (84%) of in situ adenocarcinomas were papillary, often seen in combination with either cribriform or flat architecture. In most cases the in situ adenocarcinoma was the predominant component when it was present with another in situ urothelial carcinoma. Seventy-nine percent of in situ adenocarcinomas showed >5 mitoses/10 HPF and 42% showed >10 mitoses/10 HPF. Moderate to severe nuclear pleomorphism was seen in 84% of cases. All cases showed apoptosis, and only one case showed focal necrosis. Seven patients were treated with cystectomy within 2-12 months. Of the other 12 patients, 10 were followed for a mean of 19.3 months (range 1-62 months). Ten (52%) patients were treated with bacille Calmette-Guérin, of whom four had no residual tumor on subsequent biopsy or cystectomy specimens. Three patients developed metastatic disease. In situ adenocarcinoma is a rare lesion that has a high incidence of association with small cell and micropapillary transitional cell carcinomas. When identified, in situ adenocarcinoma may indicate subsequent development of specific types of prognostically poor invasive carcinomas.     

膀胱非尿路上皮性肿瘤的诊治(附46例报告)

目的:探讨膀胱非尿路上皮性肿瘤的诊断、治疗方法和预后。方法:回顾性分析2002年1月～2010年12月收治的46例膀胱非尿路上皮性肿瘤患者的临床资料:男34例,女12例。年龄30～82岁,平均61.3岁。术前辅助检查主要包括B超、盆腔CT、膀胱镜加病理活检以及131I-MIBG。42例行手术治疗,4例放弃手术。结果:46例术前或术后病理检查诊断为膀胱鳞状细胞癌19例,膀胱腺癌18例(单纯性非脐尿管腺癌8例,脐尿管腺癌5例,转移性腺癌5例),膀胱小细胞癌4例,膀胱嗜铬细胞瘤5例。术后40例随访12～72个月,膀胱嗜铬细胞瘤5例均健在,膀胱鳞癌及腺癌各2例随访至14～26个月仍存活,其余患者平均存活时间13.2个月。结论:膀胱非尿路上皮恶性肿瘤恶性程度高,确诊时大多已是晚期,预后差。膀胱根治性切除术是除转移性癌和小细胞癌外的膀胱非尿路上皮性恶性肿瘤的推荐手术方案,小细胞癌以化疗为主,转移性癌以改善尿路症状为主,良性嗜铬细胞瘤以膀胱部分切除为主。     

膀胱腺癌的诊断和治疗(附29例报告)

目的提高膀胱腺癌的诊断与治疗水平。方法29例中原发性膀胱腺癌18例，其中行全膀胱切除、尿流改道11例，膀胱部分切除7例；脐尿管腺癌9例，6例行扩大膀胱部分切除术，3例行全膀胱切除、尿流改道；印戒细胞癌2例，行全膀胱切除、尿流改道术。结果4例患者失访，25例患者随访时间为5个月一10年。生存1年者17例（64％），生存2年15例（60％），生存5年5例（20％），生存时间超过5年者均为早期患者。结论早期诊断、鉴别原发性膀胱腺癌与脐尿管腺癌、选择合适的手术方式是膀胱腺癌治疗的关键。     

Autoimplants in serous borderline tumors of the ovary: a clinicopathologic study of 30 cases of a process to be distinguished from serous adenocarcinoma

The clinical and pathologic features of serous borderline tumors (SBTs) with autoimplants (AIs) were studied with emphasis on their relation to survival, ovarian SBT with a micropapillary pattern, and their distinction from serous adenocarcinoma. The 30 patients ranged in age from 17 to 70 years (mean, 35.8 years). Two had stage I disease, 10 had stage II disease, and 18 had stage III disease. Twenty-five patients had bilateral ovarian tumors. In 28 cases, AIs were present on the surface of the neoplasm or between exophytic surface tumor papillae; in 2 cases, AIs were between papillae within intracystic tumor. The AIs consisted of single cells or glands and clusters of cells with mild to moderate nuclear atypia within a fibroblastic stroma; the stroma dominated over the epithelium in extent within the AI. In many cases, the epithelial cells in the AI had abundant eosinophilic cytoplasm. All but 2 of the patients had coexisting noninvasive peritoneal implants; 3 of them also had invasive peritoneal implants. Six of the SBTs had a micropapillary pattern; 3 of these were stage III and 3 stage II tumors. Clinical follow-up was available for 11 patients. Eight were alive and well after 4 to 7 years (mean, 5 years); 3 of these patients had stage II disease and 5 had stage III disease. Three were dead of disease after 7 to 12 years (mean, 9 years). Two patients who died of disease had stage III disease, and 1 of them had invasive implants. The third patient had stage II disease, invasive implants, and the tumor was of the micropapillary type. Our study indicates that the majority of patients with SBT with AI have stage II or III disease and abundant exophytic tumor. SBTs with AI had a micropapillary pattern in 20% of the cases. AIs do not appear to have an adverse impact on survival when controlled for peritoneal implant type and for this reason must be distinguished from true stromal invasion in serous carcinoma, a misdiagnosis sometimes made, or seriously entertained, initially in these cases. Features that favor AI over carcinoma arising in an SBT are 1) a location between tumor papillae or on the ovarian surface 2) a predominance of stroma over epithelial cells, and 3) the "borderline" cytologic appearance of epithelial cells.     

22例晚期膀胱癌患者术中放疗随访报告

目的：对晚期膀胱癌术中放疗患者进行临床效果观察，并与传统的全膀胱切除术进行比较，以探索一种更合理、有效的治疗晚期膀胱癌的途径。方法：术中将肿瘤处理完毕后，根据肿瘤情况，用直线加速器给予一次性剂量照射，作长期随访报告。结果：术中放疗后，膀胱内肿瘤局部复发低，本组仅有4例膀胱内小肿瘤复发，经TURBT治疗后未再复发。22例具有全膀胱切除指征的患者均保留了膀胱正常排尿功能，患者生活质量提高，生存期明显延长。结论：对位于膀胱三角区周围浸润型多发性膀胱癌，尤其是膀胱腺癌、鳞癌，可采用电子直线加速器进行术中放疗，是一种理想的治疗方法。     

膀胱混合癌的临床特征

目的:探讨膀胱混合癌的临床特征。方法:回顾性分析1990年6月~2004年8月收治的16例膀胱混合癌患者的临床资料,对该病的临床表现,诊断和治疗以及预后情况进行讨论。结果:膀胱混合癌16例,占同期230例膀胱恶性肿瘤的6.9%,其中移行、鳞状细胞混合癌7例,移行、腺细胞混合癌4例,移行、鳞状、腺细胞混合癌3例,鳞状、腺细胞混合癌2例。多数患者以膀胱刺激症为主要临床表现,治疗以膀胱全切为主,术后1、3和5年的生存率分别为81.3%、56.3%和12.5%。结论:膀胱混合癌以膀胱刺激症状为主要临床表现,恶性程度高,早期诊断困难。根治性全膀胱切除术有助于提高生存率。     

A case of micropapillary bladder carcinoma

A case of urothelial carcinoma containing micropapillary variant in the urinary bladder is reported. The micropapillary bladder carcinoma isa rare variant of urothelial carcinoma and has an aggressive clinical course. A 45-year-old man complained of hematuria in October, 2009. He visited a hospital and was diagnosed with a bladder tumor. Transurethral resection of the bladder tumor was performed at the hospital. The transurethral resection demonstrated poorly differentiated adenocarcinoma invading the bladder muscle layer. Then he consulted our hospital. Our pathologist diagnosed the case as micropapillary variant of urothelial carcinoma in the urinary bladder. Accordingly, radical cystectomy and pelvic lymph nodes dissection were performed. After the operation, he received three courses of gemcitabine and cisplatin as adjuvant chemotherapy. The patient remains free of tumor recurrence and metastasis for 28 months after the cystectomy.     

Mediastinal Metastases in Bronchogenic Carcinoma: Influence of Postoperative Irradiation,Cell Type,and Location

A 17-year experience with 136 patients with bronchogenic carcinoma and mediastinal metastases is reported. Six died postoperatively. Postoperative mediastinal irradiation was given to 110 patients surviving curative resection who had evidence of tumor spreading to the mediastinal lymph nodes. The remaining 20 patients did not receive radiation therapy.Of the 136 patients, 29 (21.3%) lived 5 years free from disease and 9 survived 10 or more years. Of the 110 patients who survived operation and underwent irradiation, 29 (26.4%) survived 5 years. None of the 20 patients not receiving radiation therapy lived 5 years. Of the patients who underwent irradiation, 18 of the 50 patients with squamous cell carcinoma survived 5 years, while only 7 of 55 with adenocarcinoma survived 5 years.We do not believe that the discovery of mediastinal lymph node involvement in bronchogenic carcinoma is a contraindication to pulmonary resection. As in our previous reports, histological cell type has proved to be an important indicator of absolute survival. Patients with squamous cell carcinoma had an absolute 5-year survival of 33.9%, while the patients with adenocarcinoma had an absolute survival of 12.3%.The level of lymph node metastasis has an influence on prognosis as well. Patients with subcarinal lymph node metastases had a lower survival than patients with superior mediastinal involvement.     

进展期腹、盆腔脏器肿瘤侵犯膀胱21例诊治分析

目的探讨进展期腹、盆腔脏器肿瘤侵犯膀胱的临床特点及其诊断和处理。方法回顾性分析经临床和病理证实的21例进展期腹、盆腔脏器肿瘤侵犯膀胱的临床资料。结果本组原发癌占13例和复发癌8例。其中降、乙状结肠癌10例,直肠癌7例,卵巢癌2例,恶性子宫内膜异位症2例。临床表现主要为便血,血尿,腹痛,腹部肿块,肾积水。手术配合化疗15例(根治性手术9例,姑息性手术6例),放弃治疗6例。术后随访15例,随访3个月～5年,平均2.6年,无瘤生存6例,局部复发带瘤生存4例,死于癌症或晚期并发症11例。结论进展期腹、盆腔脏器肿瘤侵犯膀胱,主要依据临床表现、影像和窥镜等检查而诊断。处理取决于原发肿瘤的进展情况,对局部进展侵犯膀胱者,可以施行肿瘤扩大根治手术或姑息切除术,配合化疗等综合措施,近期效果良好,生活质量改善。     

膀胱非移行细胞肿瘤的诊断与治疗(附18例报告)

目的：提高膀胱非移行细胞肿瘤的诊治水平。方法：结合文献对收治的１８例膀胱非移行细胞肿瘤的诊断与治疗进行讨论。结果：１８例膀胱非移行细胞肿瘤占同期３５２例膀胱肿瘤的５．１％。其中良性非移行细胞肿瘤３例（１６．７％）,恶性非移行细胞肿瘤１５例（８３．３％）,后者以鳞癌、腺癌及其与移行细胞癌混合癌为主,占７３．３％,且临床分期Ｔ３期以上者亦占７３．３％。以血尿和膀胱刺激症状为主要临床表现。治疗以膀胱全切     

Invasive micropapillary salivary duct carcinoma: a distinct histologic variant with biologic significance

An invasive micropapillary component has been described in tumors of several organs and is nearly always associated with aggressive biologic behavior. We present 14 cases of salivary duct carcinoma (SDC) with an invasive micropapillary component (invasive micropapillary SDC) and compare the clinicopathologic findings of these cases with those of cases of conventional SDC. The mean age of the 14 patients (10 men, 4 women) was 65.8 years (range, 26-80 years). The mean size of the tumors was 2.4 cm (range, 1.3-5 cm). The parotid gland was involved in 12 patients and the submandibular gland in 2. Histologically, all tumors had an invasive micropapillary architecture admixed with features typical for SDC. Invasive micropapillary carcinoma was characterized by morula-like small cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells exhibited moderate- to high-grade nuclear features, conspicuous nucleoli, and eosinophilic cytoplasm. This component was distributed diffusely in 9 tumors and focally in 5. Angiolymphatic and perineural invasion was seen in all tumors. A residual pleomorphic adenoma was detected in four tumors. Of the 12 tumors examined, all were diffusely positive for cytokeratin 7 and epithelial membrane antigen (with a distinctive "inside-out" pattern) but negative for cytokeratin 20. Tumors were frequently immunoreactive for BRST-2 (gross cystic disease fluid protein-15) and androgen receptor protein. Aberrant expression of HER-2/neu or p53 was detected in seven tumors each. The mean Ki-67 labeling index was 33.1% (range, 6.3%-61.6%). All 14 patients with invasive micropapillary SDC had cervical or periglandular lymph node metastasis, and this value was significantly higher than for conventional SDCs. Local recurrence developed in 4 patients and distant metastatic disease in 9. Clinical follow-up (mean, 25.5 months) was available for 13 patients: 9 died of disease within 24 months after the diagnosis (mean, 17.6 months), 1 was alive with metastatic disease at 19 months, and 3 were free of disease. Overall survival of these patients with invasive micropapillary SDC was significantly shorter than that of patients with conventional SDC (n = 49) in our series (P = 0.031). Our results suggest that invasive micropapillary SDC is a distinct, aggressive variant of SDC, with a propensity for extensive lymph node metastasis and rapid disease progression.     

Tumors of the bladder in renal transplant patients: report of a case of adenocarcinoma and review of known cases.

A case is presented of adenocarcinoma of the bladder in a 36-year-old man who had undergone renal transplantation 4 years previously. Treatment was cystectomy and ileal loop diversion. A review of the known cases of bladder tumors obtained from the literature and from the Human Renal Transplant Registry is discussed. The 8 cases presented include 4 transitional cell carcinomas, 1 squamous cell carcinoma, 1 nephrogenic adenoma and 2 adenocarcinomas. The unusual occurrence of adenocarcinoma in young male subjects is noted.     

Micropapillary bladder cancer

A characteristic clinical course of a patient with micropapillary bladder cancer, a rare histological variant with high metastatic potential, is presented. An 80-year-old woman had locally advanced high-grade bladder cancer with a focal micropapillary variant identified which was treated with intra-arterial chemotherapy with radiation therapy. Standard follow-ups involving cystoscopy with cold-cup biopsies and computed tomography could not detail the bladder carcinoma; however, the patient died of carcinomatosis 20 months after treatment. At autopsy, carcinomas proliferated under benign mucosa and infiltrated diffusely in the retro peritoneum. This behavior differs from the normal pattern of invasive transitional cell carcinoma, which usually proliferates forming a mass lesion. Thus, it may be difficult to detect micropapillary bladder cancer by computed tomography which demonstrates only increased tissue density in retroperitoneal fascia; therefore, care should be taken in the follow-up of micropapillary bladder cancer.     

Clinical study of proton radiotherapy in urological cancers

Therapy with proton beam is superior to that with photon beam in concentrating the dose within a lesion. Fifteen patients with urinary malignant tumors were treated by proton irradiation during the period from June, 1985 to March, 1989 at Particle Radiation Medical Center, University of Tsukuba. Four patients were with renal cell carcinoma, five with prostatic cancer and six with bladder cancer. Treatment results were assessed by change in tumor size either three or six months after the irradiation. In all the four cases with renal cell carcinoma, the tumor sizes were found to be unchanged without any enlargement. Of the five cases with prostatic cancer, two showed that the treatment was effective and the tumor sizes in the other three cases were found to be unchanged. In three of the six cases with bladder cancer the tumors disappeared while the treatment was found effective in two other and it did not cause any enlargement of the tumor in the remaining one. Although local control of the tumor was successful in all the cases, one patient with prostatic cancer and three with bladder cancer died of cancer. Various side effects, such as radiation cystitis, were observed. This prospective therapy is expected to replace the conventional photon therapy. However, some improvement is needed to make full use of the advantageous properties in dose distribution. Combination therapy with other general therapy is required for some cases.     

Serous borderline tumors of the ovary: a long-term follow-up study of 137 cases,including 18 with a micropapillary pattern and 20 with microinvasion

The natural history of serous borderline tumors (SBTs) of the ovary varies considerably. A group of investigators have proposed that a small subset of SBTs with a micropapillary architecture and an allegedly higher incidence of invasive peritoneal implants should be designated "micropapillary serous carcinomas." Based on the overall favorable prognosis of the nonmicropapillary SBTs, these investigators have recommended abandoning the borderline category of serous tumors, restricting them to benign (benign and typical SBTs) and malignant types; other investigators, however, are in favor of retaining the original grouping, designating borderline tumors with a micropapillary pattern as such instead of designating them carcinomas. We have reviewed the clinicopathologic records of 137 patients with ovarian SBTs and obtained follow-up information on 106 of them ranging from 1 to 18 years (mean 7 years). Of the 21 patients with stage I tumors who had conservative surgical treatment, only two (9.5%) were subsequently found to have tumor in the contralateral ovary. Both were successfully managed by reoperation alone. Forty-five stage I patients had procedures that included bilateral oophorectomy, and two of them (4.4%) had a pelvic recurrence, which was fatal in one patient (whose tumor had been understaged) and occurred on multiple occasions in the other patient, finally transforming into invasive carcinoma; that patient survived. Of the 45 stage II-IV patients, only the six (13%) with invasive implants had an unfavorable outcome: three died of tumor (from 7 to 9.3 years), and the other three were alive with progressive disease from 5 to 10 years. Solid epithelial nests or small papillae surrounded by clefts and micropapillary architecture were found more often in invasive than in noninvasive implants. However, the only feature specifically associated with a poor outcome was obvious destructive invasion of the underlying tissue. Among the 137 SBTs, we identified 18 cases of serous borderline tumors with a micropapillary pattern (SBT-MP) (so-called "micropapillary carcinoma") and 20 cases of SBT with microinvasion (SBT-Minv) (three of which were also micropapillary). We compared the two groups of tumors with the remaining 102 cases of typical SBTs (which lacked micropapillary pattern and microinvasion). Of the 17 patients with SBT-MP and follow-up data, only the one patient with invasive implants had an unfavorable outcome; similarly, of the two patients with SBT-Minv and an unfavorable outcome, one had invasive implants and the other had been incompletely staged. SBTs have a very favorable prognosis, but complete surgical staging and prolonged follow-up are advised because pelvic recurrence and occasionally transformation to invasive carcinoma may occur. Designation of SBTs as "atypical proliferative tumors" is not recommended because it discourages complete surgical staging and follow-up. Advanced stage tumors with noninvasive implants are common, characteristically behave in a benign fashion, and can be safely treated conservatively. The rare SBTs associated with invasive implants are almost always fatal. SBT-MP and SBT-Minv are much closer in their biologic behavior to SBTs than to serous carcinomas. The micropapillary pattern alone does not imply an unfavorable prognosis; only micropapillary tumors associated with invasive implants behave aggressively.     

脐尿管肿瘤16例临床分析

目的 揭示脐尿管肿瘤的临床特征,提高其诊治水平.方珐分析16例脐尿管肿瘤的临床资料.结果 男14例,女2例 平均年龄（52.0±4.5）岁.肉眼血尿11例,血尿伴尿频尿急5例,血尿时间中位数3.5个月.尿中有黏液者6例.肿瘤直径平均（6.0±1.2）cm,盆腔淋巴结转移4例.TNM分期：T2 2例,T3 10例,T4 4例.临床分级：G1 2例,G2 12例,G3 2例.均行扩大性膀胱部分切除术,术后病理诊断黏液性腺癌10例,混合癌3例,乳头状腺癌2例,小细胞型内分泌癌1例.术后IL-2治疗2例,羟基喜树碱膀胱灌注3例,M-VAC方案化疗1例.16例患者均获随访,随访3个月～11年,平均（28±3）个月.术后1年期生存率为50%（8/16）,5年期生存率为18.25%（3/16）.T2期患者的5年生存率明显高于T3、T4期患者.5例小于50岁的脐尿管癌患者均自青少年时期就开始大量吸烟.结论 血尿是脐尿管癌的最常见症状,扩大性膀胱切除术为标准手术方式,复发转移者应采取综合治疗.过早大量吸烟可能是脐尿管癌的一个危险因素.早诊、早治对脐尿管癌的长期存活有重要意义.     

Radical cystectomy for primary neuroendocrine tumors of the bladder: the university of southern california experience

PURPOSE: Primary neuroendocrine tumors of the bladder are rare and they include small and large cell variants. We reviewed our experience with treating these tumors with radical cystectomy to evaluate their histopathological characteristics and clinical outcomes. MATERIALS AND METHODS: From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer at our institution, of whom 25 (1.2%) had neuroendocrine tumors of the bladder, including small cell carcinoma in 20 and large cell carcinoma in 5. Pure neuroendocrine-type histology was identified in 16 cases, including 1 with small and large cell features, while the remaining 9 had mixed histology, that is transitional cell carcinoma in 8 and adenocarcinoma in 1. Multi-agent chemotherapy was administered to 14 patients. RESULTS: Median patient age was 68 years (range 40 to 82) and 19 patients were male (76%). A total of 19 patients (76%) had lymph node involvement, of whom 2 had small liver metastases found intraoperatively, while only 4 (16%) had organ confined tumors and 2 (8%) had extravesical, node negative disease. These tumors tended to have a flat, ulcerative gross appearance with lymphovascular invasion, carcinoma in situ and necrosis present microscopically. Median followup was 11.8 years (range 18 days to 15.1 years). Five-year overall and recurrence-free survival was 10% and 13%, respectively. There was no significant survival difference between small and large cell carcinoma. Mixed histologies tended to do better than pure neuroendocrine tumors, although this did not attain statistical significance (p = 0.064). Patients receiving multimodality therapy had significantly better overall (p = 0.051) and recurrence-free (p = 0.003) survival than those treated with cystectomy alone. CONCLUSIONS: Neuroendocrine tumors of the bladder usually present with advanced pathological stage and portend a poor prognosis. Adjuvant chemotherapy protocols may provide improved survival compared with cystectomy alone.