Micropapillary variant of transitional cell carcinoma of the ureter

Micropapillary variant of transitional cell carcinoma (TCC) is a rare entity, having a distinct micropapillary component mimicking papillary serous carcinoma of the ovary and has been reported exclusively in the urinary bladder. We experienced a case of micropapillary variant of TCC in the ureter. The tumor showed a predominant proportion of micropapillary component and accompanied a TCC in situ lesion and a high-grade TCC. A metastatic lesion in the regional lymph node also showed an entirely micropapillary pattern. Initially, our case was confused with adenocarcinoma, especially metastatic, because the micropapillary architecture resembled an abortive glandular structure and tumor cell nests were predominantly located in empty spaces mimicking vascular invasion. The patient died with peritoneal metastases 20 months after the initial diagnosis. We report the first case of a micropapillary variant of TCC occurring in the ureter.     

A micropapillary variant of transitional cell carcinoma arising in the ureter

A 79-year-old woman was evaluated for a ureteral stricture related to laser ablation of a tumor 6 months earlier at another institution. A ureteroscopic examination revealed an exophytic papillary tumor that was resected and examined histologically. The tumor was characterized by delicate papillae with thin stromal cores and numerous secondary micropapillae lined by small cuboidal to low columnar cells with uniform low-to-intermediate-grade nuclei, reminiscent of a serous borderline tumor of müllerian origin. The cell linings were 1 to 4 layers thick; mitotic figures were easily identified. The underlying stroma appeared edematous and contained scattered chronic inflammatory cells. No invasion was identified. After ascertaining that the patient had no known gynecologic neoplasm, the differential diagnoses considered included papillary nephrogenic adenoma, clear cell carcinoma, and the recently described entity of micropapillary transitional cell carcinoma. Because of the striking resemblance to serous carcinoma and the presence of significant mitotic activity, this case was felt to represent a case of micropapillary transitional cell carcinoma (World Health Organization grade 1 to 2) occurring in the ureter. To our knowledge, this tumor had some unique features (no areas of grade 3 nuclei or invasion) that have not been reported in tumors occurring in the urinary bladder. The transitional cell nature of the tumor cells was supported by the immunohistochemical staining pattern. The anatomic distribution of micropapillary transitional cell carcinoma is now expanded to include the ureter, and this tumor should be considered in the differential diagnosis for papillary lesions occurring in the ureter.     

Multicentric transitional cell carcinoma of the vagina and the ureter

Primary transitional cell carcinoma (TCC) of the vagina represents an extremely rare neoplasm and is associated with multicentric TCC of the urinary tract in all described cases. A case of multicentric TCC of the vagina and the left ureter in a 73-year-old woman is reported. Immunohistochemical analysis of cytokeratin expression was performed. Immunohistochemistry proved to play an important role in the differential diagnosis of vaginal TCC, supported the morphological diagnosis of TCC, and largely excluded the diagnosis of vaginal papillary carcinoma with transitional features as a morphological variant of squamous cell carcinoma. Subsequent urological examination revealed multicentric TCC of the left ureter. During the follow up, the metastases of the vaginal TCC into the regional inguinal lymph nodes were diagnosed, suggesting that indolent clinical course is not a rule in this type of tumor.     

A possible specific chromosome change in transitional cell carcinoma of the bladder

Chromosome changes were ascertained in nine tumor samples from seven untreated patients with transitional cell carcinoma of the urinary bladder. All tumors analyzed showed abnormal karyotypes. In one tumor, a single numerical abnormality (+7) was the sole detectable change. From 1 to 19 structurally abnormal chromosomes could be identified in the remaining 8 tumors. The same abnormality, an isochromosome of the short arm of chromosome #5, was found in five tumors from four patients. We have previously described the presence of this marker chromosome in three of nine cases of transitional cell carcinoma of the bladder. We therefore conclude that i(5p) constitutes the most consistent nonrandom chromosome abnormality in this malignancy. Other chromosomes most frequently involved in structural changes in the present series of tumors were chromosomes #1, #6, #11, and #13.     

输尿管癌中MMP-9、uPA的表达及与预后的关系

目的探讨基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)和尿激酶型纤溶酶原激活剂(urokinase plasminogen ac-tivator,uPA)在输尿管癌组织中的表达及其对患者预后的影响。方法应用免疫组化PV两步法检测51例手术切除的原发性输尿管癌组织中MMP-9和uPA蛋白的表达和临床病理因素及预后的关系。结果 (1)51例标本中MMP-9和uPA阳性率分别为60.8%(31/51)、64.7%(33/51)。(2)MMP-9、uPA蛋白过表达存在相关性(P=0.000,r=0.835)。(3)MMP-9和uPA的表达均与年龄(P均=0.000)、临床分期(P均=0.000)、组织学分级(P=0.001,P=0.00)及病理分级(P=0.014,P=0.042)明显相关。(4)Kaplan-Meier法描绘生存曲线分析表明,MMP-9蛋白阴性组患者中位生存时间(65.00个月)明显大于阳性组(50.00个月),差异有统计学意义(P=0.00);uPA蛋白阳性组患者中位生存时间(57.00个月)明显较阴性组(65个月)短,差异亦有统计学意义(P=0.000);MMP-9阴性/uPA阴性组患者(13例)中位生存时间(65.00个月)明显高于其他组,差异有统计学意义(Log-rank检验,χ2=25.464,P=0.000)。(5)Cox比例风险模型(χ2=236.769,P=0.000)多因素分析表明:临床分期(P=0.044)、组织学分级(P=0.000)、手术方式(P=0.001)及uPA过表达(P=0.016)为影响输尿管癌预后的独立因素。结论输尿管癌组织中存在MMP-9、uPA的高表达,且两者之间的表达强度具有等级相关性,其高表达提示患者预后不良。在细胞外基质和基膜的降解过程中MMP-9和uPA可能有协同作用,最终促进肿瘤的侵袭和转移,不利于预后。联合检测二者表达可作为预测输尿管癌发生转移的危险性及患者预后情况。     

Small cell carcinoma of the ureter with squamous cell and transitional cell carcinomatous components associated with ureteral stone.

We report a case of primary small cell carcinoma of the ureter with squamous cell and transitional cell carcinomatous components associated with ureteral stone, which is unique in that the patient has remained free of tumor recurrence for 36 months after the surgery without adjuvant chemotherapy or radiotherapy. A 60-yr-old man presented himself with a right flank pain. Computed tomography revealed an ill-defined mass and a stone in the lower one third of the right ureter, and hydronephroureterosis above the stone-impacted site. The patient underwent right nephroureterectomy and stone removal. Upon gross examination, a 3.8 x 1.8 x 1.2 cm white and partly yellow mass was noted in the anterior part of the ureter, resulting in indentation of the ureteral lumen on the posterior side. Light microscopic examination revealed that the mass was mainly composed of small cell carcinoma, and partly squamous cell and transitional cell carcinomatous components. The overlying ureteral mucosa and renal pelvis also contained multifocal dysplastic transitional epithelium and transitional cell carcinoma in situ. There was no vascular invasion, and the surgical margins were free of tumor. The small cell carcinomatous component was positive for chromogranin, neuron specific enolase, synaptophysin, and pancytokeratin but negative for high molecular-weight cytokeratin (K-903) by immunohistochemistry.     

Chromosome 3 allelic losses and microsatellite alterations in transitional cell carcinoma of the urinary bladder.

A deletion analysis of chromosome 3 was conducted in 72 cases of transitional cell carcinoma of the urinary bladder using seven microsatellites spanning the 3p arm and two additional microsatellites in 3q. Results showed that 19 of 72 (26.4%) cases had deletions in one or more 3p regions. Two regions of frequent deletion were identified: 3p12-14 and 3p21-23. Less frequent deletions at 3p24.2-25 were also observed. Deletions at 3p were weakly correlated with tumor grade, but strongly with pathological stage. Among 70 cases with histological grade available, 4 of 29 (13.8%) grade 1 and 2 tumors, and 15 of 41 (36.6%) grade 3 tumors showed allelic losses in one or more of the 3p regions studied (P = 0.055). Among 69 cases with pathological stage available, none of 27 superficial carcinomas (pTa, pTis, and pT1) showed 3p deletions, whereas 18 of 42 (42.9%) muscle invasive lesions (pT2, pT3, and pT4) displayed allelic losses at 3p (P < 0.001). In addition, 12 cases showed microsatellite instability, but there was no correlation between abnormalities and tumor grade or stage. No correlation was found between deletions at 3p21-23 and microsatellite instability. In conclusion, deletions at three discrete regions of 3p were identified in bladder carcinoma, suggesting the involvement of candidate tumor suppressor genes residing in these regions. Moreover, detection of allelic losses in these regions was associated with higher tumor grade and more advanced stage, suggesting their potential involvement in bladder tumor progression.     

E-cadherin expression in urothelial carcinoma in situ,superficial papillary transitional cell carcinoma,and invasive transitional cell carcinoma

Flat urothelial carcinoma in situ (CIS) is a precursor of invasive transitional cell carcinoma (TCC). High-grade TCCs frequently are accompanied by CIS in surrounding urothelium. In contrast, superficial, noninvasive papillary TCCs are often low grade and generally are unaccompanied by CIS. E-cadherin (E-CD) is a member of a family of transmembrane glycoproteins involved in intercellular adhesion. Loss or decreased expression of E-CD has been linked to the invasive phenotype of a wide variety of human neoplasms, including bladder tumors. The objective of this study was to compare the expression of E-CD in high-grade urothelial dysplasia (HD)/CIS, superficial papillary TCC, benign urothelium, and invasive TCC. Staining for E-CD was performed in formalin-fixed, paraffin-embedded sections using a Ventana NexES immunostainer (Tuscon, AZ). Percentage and intensity of cell membrane staining for E-CD was calculated for the 4 groups using the quantitative Automatic Cellular Imaging System (ChromaVision, San Juan Capistrano, CA). The results were as follows: The CIS group (n = 23) had percentage and intensity (92.8%, 120.0 U) of E-CD expression similar to the superficial noninvasive papillary TCC group (n = 16, 97.8%, 123.0 U) and the benign urothelium group (n = 17, 87.9%, 104.6 U), but it had statistically significant higher percentage and intensity than the invasive TCC group (n = 15, 45.4%, and 39.2 U, P <.05). Our data indicate that CIS and superficial, noninvasive papillary TCCs strongly express E-CD. In contrast, loss of E-CD expression is associated with the invasive TCC phenotype. Only when TCCs become invasive does E-CD expression decrease in directly proportion to the depth of invasion.     

Concurrent tubulovillous adenoma and transitional cell carcinoma associated with diffuse gastric and intestinal metaplasia of the defunctioned ureter

Villous adenoma is a common lesion of the gastrointestinal tract, but it is rare in the ureter. Thus, as far as we know, only one case limited to this location has been described. Intestinal metaplasia of the urothelium is not rare. However, only one case of gastric metaplasia with pseudopyloric glands has been described in the literature. We here report in detail on a tubulovillous adenoma of the ureter associated with diffuse gastric and intestinal metaplasia and a concurrent primary, solid, high grade transitional cell carcinoma, with extensive clear cell change, in a 56-year-old male patient. He had undergone a left nephrectomy for renal tuberculosis twenty years earlier, and the lesions developed in the ureteric stump. To the best of our knowledge, such a combination of lesions has not been reported previously either in the ureter or in the rest of the urinary tract. The coexistence of diverse lesions in our case might represent the pluripotentiality of the urothelium in association with chronic inflammation and neoplastic induction. The present report also emphasizes the metaplastic and malignant potential of a defunctioned urothelial structure. This case is of particular interest, because these coexistent lesions arose simultaneously with an anatomically separate adenocarcinoma of the rectum (Dukes' B). The patient died 76 days after admission. The dismal prognosis of our case was determined by the advanced anatomical stage and the histological high grade of the transitional cell carcinoma of the ureter.     

Trisomy 7 may be a primary change in noninvasive transitional cell carcinoma of the bladder

We describe two cases of transitional cell carcinoma of the bladder associated with trisomy 7. In one of them, trisomy 7 was the only chromosome abnormality observed. In the second case, trisomy 7 was found in 25 (80.6%) of the metaphases; in two of them this was the only anomaly, while in three metaphases trisomy 8 was also present, and in other two trisomy 10 was also observed. Our results suggest that trisomy 7 could be a primary change in TCC, and a review of the literature indicates that when it is present as the sole karyotypic abnormality is may be associated with a non-invasive behavior of the tumor.     

Ipsilateral synchronous renal cell carcinoma and transitional cell carcinoma.

The simultaneous occurrence of renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) in the same kidney is unusual. We report a 53-year-old man with ipsilateral synchronous renal adenocarcinoma and renal pelvic transitional cell carcinoma with severe hypercalcemia and a huge staghorn calculus in the opposite kidney. The patient was admitted to the hospital because of left flank pain and intermittent fever which he had had for 2 months. Computerized tomography revealed a huge stone in the right kidney and a mass in the upper pole with an irregular calcified pelvis in the left enlarged kidney. Left radical nephrectomy was done. A section of the specimen revealed a renal cell carcinoma located at the upper pole and a papillary transitional cell carcinoma arising from the renal pelvis. This is a rare case of combined renal malignancies.     

Cytologic features of metastatic transitional cell carcinoma

Cytologic preparations containing metastatic transitional cell carcinoma (MTCC) from 18 sites in 16 patients were renewed to determine characteristic morphologic features. The patient group included 13 males and 3 females with a mean age of 66 years. Primary TCC occurred in the bladder (14), kidney (1) and ureter (1); nearly all the primary tumors were poorly differentiated and most were invasive at the time of diagnosis. The cytologic specimens were derived from lymph nodes (6). liver (4). serous fluids (2), pelvic soft tissue (2), subcutaneous nodules (2), and lung (1). One patient presented with MTCC in Pap smears. Cytologically MTCC presented as loosely cohesive, moderate to markedly pleomorphic cells which occurred singly and in syncytial clusters. The malignant cells were usually large with abundant granular or fibrillar cytoplasm and the cell borders were generally distinct. Most nuclei were large and hyperchromatic with irregularly distributed granular chromatin and prominent nucleoli. The most distinctive features were the presence of spindled, pyramidal, and/or racquet-shaped malignant cells with eccentric nuclei and cytoplasmic features of both squamous and glandular differentiation including endoplasmic/ectoplasmic interfaces and intracytoplasmic vacuoles. Although clinical history is most useful in the diagnosis of MTCC, these morphologic features in cytologic preparations of malignant epithelial neoplasms may be helpful. In the absence of a known primary TCC. it is doubtful that a definite cytologic diagnosis could be made; however, the characteristic cell shapes and cytoplasmic features may be suggestive of MTCC.     

Spindle cell carcinoma progressed from transitional cell carcinoma of the urinary bladder

The author reports a very rare case of spindle cell carcinoma (SpCC) of the urinary bladder progressed from ordinary papillary transitional cell carcinoma (TCC). A 63-year-old man complained of hematuria. A transurethral endoscopic examination revealed a papillary tumor, and transuthetral resection of bladder tumor (TUR-BT) was performed and was diagnosed as ordinary papillary urothelial TCC. Since then, he was treated with TUR-BT eight times. Chemotherapy, radiation, radical cystectomy and lymph nodes dissection were performed 16 years after the first TUR-BT. However, he developed rectal mucosal metastasis. He is now alive 17 years after the first presentation. All the TUR-BT specimens were ordinary papillary TCCs without invasion (pTa). Immunohistochemically, the TUR-BT specimens were positive for pancytokeratin, high molecular weight cytokeratin (CK), CK 5/6, CK 7, CK 18, CK 19, CK 20, p53, p63, Ki-67 (10%), and negative for other antigens examined including vimentin. The cystectomy bladder specimens show broad ulcers and polypoid lesions, and malignant spindle cells (SpCC) invading into muscular layer were present. No TCC elements were recognized. The tumor cells were positive strongly for vimentin, and less strongly for pancytokeratin, high molecular weight cytokeratin, CK 5/6, CK 14, CK 18, p53, p63 and Ki-67 (95%), and negative for other antigens examined. The rectal metastatic lesion showed SpCC without TCC elements, and were strongly positive for vimentin, and weakly positive for pancytokeratin, S100 protein, p53, p63, Ki-67 (90%), neuron-specific enolase, CD56, KIT and PDGFRA. It was negative for other antigen examined. It is strongly suggested that the present SpCC were progressed from ordinary TCC.