Metastatic transitional cell carcinoma causing a unilateral pleural effusion: a case report

BACKGROUND: Transitional cell carcinoma (TCC) is a common neoplasm, but it is only rarely associated with serous effusions. The cytologic features of metastatic TCC in pleural effusions have been described only in occasional studies. One feature that raises the possibility of metastatic TCC in this setting is the presence of eosinophilic cytoplasmic inclusions (ECIs). CASE: Metastatic TCC was diagnosed in a pleural fluid from a 50-year-old man with a unilateral effusion. Two years previously he had been diagnosed with a poorly differentiated TCC of the urinary bladder (WHO grade 3, stage pT2 at least), and more recently he had also been diagnosed with an omental metastasis. Cytologic examination of the pleural fluid sample revealed numerous pleomorphic malignant cells, many of which were vacuolated. Numerous eosinophilic inclusions were identified within the malignant cells in the liquid based cytology (ThinPrep) preparation. Examination of the omental cake biopsy revealed similar appearances. CONCLUSION: ECIs within malignant pleural effusion fluid specimens should, if detected, raise the possibility of metastatic transitional cell carcinoma.     

Comparison of urine cytology between the ileal conduit and Indiana pouch

OBJECTIVE: To compare the cytomorphologic features of urine obtained from two different kinds of urinary diversions constructed after total bladder resection. STUDY DESIGN: The smears of urine from 11 ileal conduits and 6 Indiana pouches were evaluated. All patients underwent total bladder resection due to transitional cell carcinoma (TCC) or other kinds of cancer before urine diversion. RESULTS: The cytologic features of Indiana pouch urine include degenerated, small, round cells without columnar cells derived from intestinal epithelium. In ileal conduit urine, well-preserved columnar cells and degenerated, small, round cells were frequently observed. The columnar cells in ileal conduit urine exhibited cytologic features that should be distinguished from TCC cells. CONCLUSION: The method of reconstructing the urinary tract is important in urine cytology from urine diversions because the cytomorphologic features of urine are different between the two kinds of urinary diversions. Since columnar cells in ileal conduit urine might lead to misdiagnosis as TCC, special consideration is required to examine ileal conduit urine.     

Expression of cytokeratin 20 in urine cytology smears: a potential marker for the detection of urothelial carcinoma

BACKGROUND: Urine cytomorphology is one of the oldest methods for screening and monitoring patients with transitional cell carcinoma (TCC). Sensitivity of urine cytology is relatively low. Ancillary techniques on urine sample may increase the sensitivity. AIM: To explore the utility of cytokeratin 20 (CK20) immunostaining in identifying malignant cells in urine cytology smears. MATERIALS AND METHODS: Fourteen cases each of confirmed TCC and benign urinary cytology along with five cases of atypical cells in urine were immunostained with a monoclonal CK20 antibody. Of 14 cases of TCC, 12 showed strong positive staining with the antibody. All benign cases were negative except for a few cases in which the umbrella cells were weakly to moderately positive. In all five cases of atypical urine cytology the atypical cells stained positive with the antibody. These cases were later confirmed as TCC on histopathology of bladder wall biopsy. CONCLUSION: CK20 is an important biomarker that can be used to identify TCC in urine cytology smears. It is particularly useful in those cases where malignancy cannot be confirmed by morphology alone.     

Papillary clusters as a diagnostic pitfall in urinary cytology of pseudosarcomatous fibromyxoid tumor of the bladder. A case report

BACKGROUND: Pseudosarcomatous fibromyxoid tumor (PFT) of the urinary bladder is an uncommon benign lesion that can involve any site in the bladder. Cellular features of PFT of the bladder are exceedingly rare. We describe the urinary cytology in a PFT patient who displayed numerous papillary fragments that suggested a malignant tumor. CASE: A 52-year-old man was seen at the hospital for evaluation of gross hematuria. At cystoscopy, the urologist observed a 3-cm, smooth, polypoid and ulcerated mass extending from the trigone to the bladder neck. Urinary cytology showed many papillary clusters with irregular nuclear margins in the bloody cell background. No spindle cells were noted. Cytology was interpreted as papillary growth, factor transitional cell carcinoma, grade 2-3. A laparotomy with partial resection of the urinary bladder was carried out, and histologically the tumor was composed of spindle, stellate, fibroblastic cells embedded in myxoid stroma with little collagen. Immunohistochemical and ultrastructural studies revealed the fibroblastic nature of the lesion. The final diagnosis was PFT of the bladder on the basis of histologic examination of the resected material. CONCLUSION: Papillary fragments are a diagnostic pitfall in urinary cytology of PFT lesions.     

Prostaglandin E2 concentrations in naturally occurring canine cancer

The purpose of this study was to determine the PGE2 concentration in naturally-occurring cancer in pet dogs and in canine cancer cell lines in order to identify specific types of canine cancer with high PGE2 production which could serve as preclinical models to evaluate anticancer strategies targeting PGE2. PGE2 concentrations were measured by enzyme immunoassay in canine melanoma, soft tissue sarcoma, transitional cell carcinoma, osteosarcoma, and prostatic carcinoma cell lines; in 80 canine tumor tissue samples including oral melanoma (MEL), oral squamous cell carcinoma (SCC), transitional cell carcinoma of the urinary bladder (TCC), lymphoma (LSA), mammary carcinoma (MCA), osteosarcoma (OSA), prostatic carcinoma (PCA); and in corresponding normal organ tissues. High concentrations of PGE(2)(range 400-3300 pg/10(4)cells) were present in cell culture medium from the transitional cell carcinoma, prostatic carcinoma, and osteosarcoma cell lines. PGE2 concentrations in tumor tissues were elevated (tumor PGE2 concentration>mean+2X sd PGE(2)concentration of normal organ tissue) in 21/22 TCC, 5/6 PCA, 7/10 SCC, 5/10 MEL, 3/8 MCA, 4/15 OSA, and 0/9 LSA. Results of this study will help guide future investigations of anticancer therapies that target cyclooxygenase and PGE2.     

Paranuclear blue inclusions of small cell carcinoma of the stomach: report of a case with cytologic presentation in peritoneal washings

BACKGROUND: Primary gastric small cell carcinoma is a rare but important entity. We describe a case that we diagnosed by peritoneal washing cytology. CASE: A 70-year-old male presented with upper abdominal discomfort and underwent endoscopic evaluation. Gastric endoscopy revealed a diffuse, infiltrating tumor from the body to the antrum. Total gastrectomy with lymph node dissection and intraoperative peritoneal washing cytology were carried out. Peritoneal washing cytology showed the presence of many undifferentiated malignant small cells with a necrotic background. The tumor cells were small and round, with naked, hyperchromatic nuclei and finely granular chromatin. Some tumor cells contained paranuclear blue inclusions (PBls) in the cytoplasm. The tumor cells were positive for neuron-specific enolase and synaptophysin on immunocyto-chemistry. Carcinoembryonic antigen, alpha-fetoprotein (AFP) and leukocyte common antigen were negative. Pathologic diagnosis after the operation was moderately to poorly differentiated adenocarcinoma and small cell carcinoma containing AFP-positive cells. CONCLUSION: The prognosis of primary gastric small cell carcinoma is usually poor. Our patient died of multiple liver metastases and peritonitis carcinomatosa 69 days after surgery. When a gastric small cell carcinoma is suspected in peritoneal washings, immunocytochemical demonstration of neuroendocrine differentiation is required to arrive at the final diagnosis.     

Urinary thrombomodulin is down regulated in schistosomiasis associated bladder cancer

BackgroundThrombomodulin (TM) is a surface glycoprotein and expressed in many cancers. The aim of the present study was to detect the expression levels of TM in plasma and urine of bladder cancer patients and to compare these levels to the clinicopathological data of the patients as well as the ploidy status of their exfoliated urinary cells. We studied the levels of TM in plasma and urine samples of 57 bladder cancer patients and 10 controls using the (ELISA) assay and compared the results to the ploidy status of the cells taken from the patents urine samples as well as their clinicopathological profile.ResultsUrinary TM was significantly down regulated while plasma TM was significantly up regulated in bladder cancer patients. Plasma TM was significantly higher in SCC than TCC patients. The sensitivity and specificity of urinary TM were 90% and 86%, respectively. While the sensitivity and specificity of plasma TM were 76% and 80%, respectively.ConclusionUrinary TM is significantly down regulated, while plasma TM is significantly up regulated in bladder cancer as compared to the control group. Urinary TM has superior sensitivity and specificity over plasma TM. Urinary TM could be used as a predictive marker in bladder cancer. Further studies are needed to detect the prognosis significance of thrombomodulin in schistosomiasis associated bladder cancer.     

Subcutaneous metastasis from transitional cell carcinoma of the bladder diagnosed by fine needle aspiration biopsy. A case report

BACKGROUND: Metastasis of transitional cell carcinoma (TCC) of the bladder to the skin and subcutaneous tissue is an uncommon finding. CASE: A 58-year-old man with a known case of high grade TCC of the bladder, presented with a right paraspinal mass. Clinically an abscess was suspected. Fine needle aspiration (FNA) showed many clusters and isolated malignant cells in an inflammatory background. The smears were diagnosed as positive for malignancy. CONCLUSION: It is essential to differentiate tumors metastatic to the skin and subcutaneous tissue from inflammatory lesions. FNA helped with the diagnosis in this case and prevented unnecessary biopsy.     

Immunocytochemistry of collagenase expression in transitional cell carcinoma of the bladder

OBJECTIVE: To evaluate the usefulness of collagenase immunocytochemistry as well as its immunohistochemistry in assessing the correlation with prognostic factors in transitional cell carcinoma (TCC) of the urinary bladder. STUDY DESIGN: We investigated the expression of collagenase in catheterized urine and histologic specimens from 38 patients with TCC and 20 cases with benign lesions of the urinary tract. RESULTS: Thirteen (34.2%) and 17 (44.7%) patients with TCC showed positive expression of collagenase on cytologic and histologic specimens, respectively, whereas in no cases with benign lesions was such expression found (P < .01). Invasive and nonpapillary TCC had higher positive rates than noninvasive and papillary TCC. Grade 3 TCC was positive at a higher rate than was grade 2, whereas there were no positive cases with grade 1. Collagenase expression did not correlate significantly with stage. CONCLUSION: Collagenase expression in urinary TCC correlated well with tumor growth pattern, pathologic grade and invasiveness of the carcinoma; all are known to be prognostic factors. The application of collagenase immunostaining to urinary cytology is very useful for assessing prognosis in TCC.     

Metatarsal metastasis from transitional cell cancer of the urinary bladder

Urinary bladder cancers can be grouped into three general categories: superficial, invasive and metastatic. Approximately 90% of malignant tumors of the urinary bladder are of epithelial origin and the majority of them are transitional cell carcinomas (TCC). Metastatic spread of urinary bladder cancers usually includes regional lymph nodes, the lung, the liver and the bones. The presence of metastasis tends to correlate with muscular wall invasion as often demonstrated at the initial diagnosis; consequently clinical bladder cancer represents a late phase of the disease. Although skeletal metastases of bladder cancers are rather common, they have been rarely described to occur in distal bones. For that reason, we report metatarsal metastasis from transitional cell cancer of the urinary bladder in a 59-year-old woman.     

P63 immunoreactivity distinguishes upper urinary tract transitional-cell carcinoma and renal-cell carcinoma even in poorly differentiated tumors.

P63 is essential for the differentiation of normal urothelium and is also expressed in transitional cell carcinoma (TCC) of the bladder. We investigated p63 immunoreactivity in upper urinary tract TCC (n=53) and in renal-cell carcinoma (RCC; n=188) using a tissue microarray technique. P63 expression was detected in 51/53 (96.2%) TCCs, showing decreased expression in high-stage (pT1 and pT2 100%; pT3 90.9%) and poorly differentiated (G1 and G2 100%; G3 92%) tumors. All RCCs were negative for p63. P63 proved to be a helpful tool, even in poorly differentiated and undifferentiated renal malignancies, to distinguish TCC from RCC.     

The diagnostic accuracy of sputum and urine cytology

The diagnostic accuracies of sputum and urinary cytology were examined in series spanning more than 20 years. The sensitivity and respiratory tract cytology in 1,289 patients with subsequently proven lung cancer was 69% while that or urine cytology in 860 patients with urinary tract cancer was 77%. The specificities were 96% for lung cancer and 97% for urinary tract cancer. Neither procedure was widely used for routine screening, but diagnostic cytology played an important part in providing a definite morphologic diagnosis in many of these cases. Urinary cytology was also very effective in the follow-up of patients with treated bladder cancer because of its high sensitivity for detecting carcinoma in situ.     

Could nuclear matrix protein 22 (NMP22) play a role with urine cytology in screening for bladder cancer? – experience at Kuwait University

Objectives:  This prospective study was undertaken to evaluate nuclear matrix protein (NMP22) compared to urine cytology in the detection of bladder cancer and also to determine whether indexing suspicious cytology to NMP22 could enhance the clinical utility of cytology.
Methods:  Cytological findings of voided urine collected prior to a cystoscopic biopsy were correlated with urine NMP22 assay in 46 patients attending the urology clinic in Mubarak Al-Kabeer Hospital. The patients were clinically categorized into newly diagnosed cases of transitional cell carcinoma (TCC), recurrent TCC, TCC in remission and controls.
Results:  Using histological diagnosis as the gold standard the sensitivity and specificity of NMP22 were 78% and 43% respectively and of cases with malignant urine cytology were 30% and 87% respectively. If suspicious and malignant cytology were combined as positive results the sensitivity increased significantly to 87% while the specificity decreased but not significantly to 74%. Suspicious or malignant cytology enhanced by positive NMP22 gave a sensitivity of 70% and specificity of 87% neither of which was significantly different from cytology alone. There were three false positive cases on cytology and 13 false positive cases on NMP22 assay. There were three false negative cytology and five false negative NMP22 cases but only one was false negative for both, resulting in a high sensitivity (96%) but low specificity (30%) if either positive NMP22 or malignant or suspicious cytology was taken as a positive result.
Conclusion:  Combining NMP22 with malignant or suspicious cytological result improved sensitivity for the detection of bladder cancer but with a major decrease in specificity, suggesting a potential role in screening rather than diagnosis.     

Monoclonal antibodies to antigens associated with transitional cell carcinoma of the human urinary bladder

Summary Spleen cells from BALB/c mice immunized with cells derived from transitional cell carcinomas (TCC) of the human urinary bladder were fused with mouse myeloma Sp 2/0 Ag14 cells. Monoclonal antibodies from six established hybridomas were investigated for specificity in a cell ELISA and in indirect immunofluorescence against a large panel of fixed intact cells. Three of the antibodies reacted with half or more of the eight bladder tumors and with a few unrelated tumors. They did not react at all with malignant or normal cells of hematopoietic origin. A fourth antibody reacted with seven of eight bladder tumors. It also reacted weakly with a prostatic carcinoma, with five of six malignant or transformed B cell lines, and with a subpopulation of normal lymphocytes, but not with any of the other cells on the test panel. These four antibodies did not react with cells derived from normal urothelium. The results suggest that these antibodies might recognize cell-type-restricted antigens associated with malignancy. Another antibody reacted with almost all urothelium-derived cells. It also reacted with three of three melanomas but not with any other cells on the panel. The sixth antibody reacted with 32 of the 37 cells tested. The spectrum of reactivities displayed by the antibody suggested that it recognizes HLA antigens. Abbreviations used in this paper: TCC, transitional cell carcinoma of the urinary bladder; TAA, tumor-associated antigens; ELISA, enzyme-linked immunosorbent assay; NBCS, newborn calf serum; PBS, phosphate-buffered saline, pH 7.2; ALP, alkaline phosphatase; GDA, glutardialdehyde; BSA, bovine serum albumin; IF, indirect immunofluorescence; LCL, lymphoblastoid cell lines: B-lymphocytes transformed in vitro with Epstein-Barr virus     

Adenocarcinoma with a neuroendocrine component arising in the urachus. A case report

The clinical, cytologic, histologic and ultrastructural findings in a mixed adenocarcinoma and neuroendocrine carcinoma of the urinary bladder urachus, an extremely rare tumor only recently described, are presented for a 31-year-old woman who died of widespread metastatic disease six months following the initial diagnosis and treatment. Cytologic study of voided urine and bladder washings disclosed the presence of malignant cells with the features of a small cell carcinoma; retrospectively, scarce adenocarcinoma cells were also identified in those specimens. Histologic study of resection specimens, including the use of special stains and electron microscopy, confirmed the presence of a small cell component, consistent with the poor prognosis in this case. Image analysis measurements of the malignant cells suggested a high proliferation rate.     

Primary malignant melanoma of the urinary bladder diagnosed by urine cytology: a case report

BACKGROUND: Primary melanoma of the urinary bladder is a rare neoplasm, and there have been no prior reports in which the initial diagnosis was made by urinary cytology. CASE: An 82-year-old woman presented with vaginal spotting, gross hematuria and dysuria. Voided urine cytology revealed malignant cells, several of which exhibited cytoplasmic melanin pigment and were accompanied by many macrophages also containing melanin. Cystoscopy revealed a darkly pigmented, polypoid mass at the bladder neck. Biopsy confirmed the diagnosis. CONCLUSION: Primary melanoma of the urinary bladder is rare. The diagnosis can be made on cytologic examination of voided urine if careful study of exfoliated malignant cells reveals cytoplasmic melanin pigment. Macrophages may also harbor melanin pigment, and their presence should alert the cytopathologist to search carefully for pigmented malignant cells. Clinical and radiologic studies are essential to rule out melanoma metastatic to the bladder.     

Plasmacytoma with involvement of the urinary bladder. Report of a case diagnosed by urine cytology

BACKGROUND: Plasmacytoma of the bladder is a rare but important entity. We report a case of plasmacytoma of the bladder that was diagnosed by urinary cytology. CASE: A 71-year-old male with a history of multiple myeloma presented in renal failure. Renal ultrasound revealed right-sided, moderate hydronephrosis with a 4 x 4-cm, posterolateral, obstructing mass. Magnetic resonance imaging demonstrated a bladder mass involving the bladder base, right lateral wall and dome with extension into the perivesical tissues on the right. The mass showed a moderate degree of enhancement following intravenous gadolinium administration. Urine cytology was performed to evaluate for bladder carcinoma or other malignancies besides plasmacytoma. The specimen was signed out as multiple myeloma of the bladder. Cystoscopy and biopsy were subsequently performed on the bladder mass. The diagnosis of plasmocytoma was made, confirming the urine cytology diagnosis. CONCLUSION: Urinary cytology can be a diagnostic tool for plasmocytoma involving the bladder.     

Sperm Associated Antigen 9 Plays an Important Role in Bladder Transitional Cell Carcinoma

Background

Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC) which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9) in bladder TCC.

Methodology and Findings

We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells) was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042) and low grade tumors (P = 0.002) suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G₀–G₁ arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro.

Conclusions

Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC.