Primary Urinary Bladder Research Articles

Primary urinary bladder angiosarcoma with ascites

Non-urothelial tumors of the urinary bladder are rare. Sarcomas constitute less than 1% of all malignant neoplasms and angiosarcomas comprise 2% of all sarcomas [1]. We report a case of a 69-year old male with history of a low-grade prostatic adenocarcinoma for which he underwent external beam radiation therapy in 1/2010. He presented to the ER in 9/2015 with an abdominal distension and urinary retention and was found to have malignant ascites, hydronephrosis and a urinary bladder mass. Pathologic evaluation of the ascites and urinary bladder tumor revealed metastatic epithelioid angiosarcoma. Since the patient presented with an advanced stage inoperable disease, chemotherapy was initiated shortly thereafter. Unfortunately, the patient became septic and died 6weeks following the original diagnosis.

Bladder Adenocarcinoma: A Persisting Diagnostic Dilemma

Primary urinary Bladder Adenocarcinoma (PBA) is an uncommon neoplasm and can cause diagnostic difficulties due to histologic similarities with adenocarcinomas of adjacent structures like Gastrointestinal Tract (GIT) and prostate, since involvement of the bladder by metastasis or direct spread can occur. Seven cases of bladder adenocarcinomas were diagnosed during a period of four years in a tertiary care hospital. Patient's age ranged from 26-78 years with a male predilection. Three cases were signet ring type adenocarcinomas, two cases were subtyped as enteric variant, one as mucinous variant and one as adenocarcinoma Not Otherwise Specified (NOS) variant. One case showed urachal involvement. Common site of involvement was the base and posterior wall of the bladder. Three cases had prior history of GIT malignancy. No morphologic difference was identified to differentiate primary from secondary adenocarcinomas. Bladder adenocarcinoma is rare tumours. Primary and secondary adenocarcinomas cannot be distinguished from each other on morphologic grounds. Ancillary studies may have limited role in distinguishing between the two. Hence, clinical correlation has a major role in their evaluation.

The diagnostic role of vimentin in differentiation between muscularis propria and muscularis mucosa in urinary bladder carcinoma

Objective The aim of this study was to evaluate the diagnostic value of vimentin expression for differentiation between muscularis mucosa (MM) and muscularis propria (MP) in urinary bladder carcinoma cases. Background The single most important prognostic factor in urothelial carcinoma is the pathological stage, which includes the anatomic depth of invasion on which major therapeutic decisions are made. Correct assessment of invasion necessitates discrimination between MM and MP. Vimentin is the most widely distributed intermediate filament and is expressed in virtually all mesenchymal tissues. Materials and methods This study was carried out on 70 urinary bladder specimens, including 59 cases of primary urinary bladder carcinoma and 11 cystitis specimens. The specimens were submitted to vimentin immunostaining under the streptavidin–biotin amplified system. Results MM was identified histologically in 40 cases, whereas MP was morphologically designated in all cases (70 cases). Vimentin was negative in MP and showed positive expression in 32/40 (80%) cases of MM with a statistically significant difference (P = 0.000), 80% of sensitivity, and 100% of specificity. Conclusion Negative vimentin expression in MP could be a useful tool for identification of MP with 80% of sensitivity and 100% of specificity in urinary bladder carcinoma cases.

The Ewing's Sarcoma Family of Tumors of Urinary Bladder: A Case Report and Review of the Literature.

Only 15 cases of Ewing's Sarcoma (EWS) family of tumors of urinary bladder have been documented in the literature to date. We presented here a 38 year-old female with primary urinary bladder EWS with no distant metastases. She had presented with macroscopic hematuria and had undergone transurethral resection of the tumor within the following week. Microscopic examination revealed a tumor diffusely infiltrating the lamina propria and muscularis propria under an intact urothelium, which was composed of small round blue cells with scant cytoplasm, monotonous round or oval nuclei, stippled chromatin and small nucleoli. Immunohistochemistry showed strong vimentin, synaptophysin and membranous CD99 expression by the tumor. Fluorescent in situ hybridization analysis displayed the EWSR1 rearrangement. Radical cystectomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy, extended lymph node dissection, and ileal conduit were performed. As adjuvant chemotherapy, she received vincristine, doxorubicin, cyclophosphamide and mesna, alternating with courses of etoposide, iphosphamide and mesna. She is alive and well with no evidence of disease 14 months after the surgery. Surgery supported with chemotherapy should be considered as an option, especially in advanced Ewing's sarcoma family of tumors of urinary bladder.

Diffuse large B-cell lymphoma of the urinary bladder with synchronous rectum invasion: A rare case report

Diffuse large B-cell lymphomas (DLBCLs) are a heterogeneous group of malignant neoplasms appeared in the lymphocyte cell lines, accounting for approximately 25-30% of lymphoma cases. The occurrence of primary urinary bladder or rectal lymphomas synchronously is uncommon, also first presenting sign of disseminated disease in bladder or rectum are considerably rare. Here, we report the first case of extensive DLBCL in bladder and rectum synchronously mimicking primary urinary bladder lymphoma in a 43-year-old male, relatively young patient.

Analysis of HER2 expression in primary urinary bladder carcinoma and corresponding metastases [1] (multiple letters)

Analysis of HER2 expression in primary urinary bladder carcinoma and corresponding metastases [1] (multiple letters)

EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides.

BackgroundThere is limited effect of tyrosine kinase inhibitors or “naked” antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder cancer and these methods are therefore not routinely used. Targeting radio-nuclides to the extracellular domain of the receptors is potentially a better possibility.MethodsEGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose.ResultsEGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients.ConclusionsAt least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.

A rare case report: atypical epithelioid leiomyosarcoma of urinary bladder

Background Benign and malignant mesenchymal tumours of the urinary bladder are rare. Non-epithelial tumours account for 1–2% of all primary urinary bladder neoplasms. Among them, leiomyosarcoma is the most common type, representing only 0.1% of bladder cancers. It has three distinct histological variants: the classical spindle cell subtype, the myxoid subtype and the rare epithelioid subtype.1 Case report A 54-year-old female became increasingly symptomatic with urge incontinence and gross haematuria associated with significant weight loss. Abdominal ultrasound showed a large mass in urinary bladder. Core biopsy and then radical cystectomy show sheets of atypical cells which are mostly epithelioid or polygonal in shape. The main differentials include epithelioid leiomyosarcoma, sarcomatoid carcinoma and other sarcomas. Immunostains for smooth muscle markers, calponin, h-caldesmon, SMA, cytokeratin stains, S100 stains, HMB45, c-kit and myoglobin stain were performed. Other immunomarkers of epithelioid tumours were also checked. Overall features are consistent with an epithelioid leiomyosarcoma with urinary bladder involvement. Discussion Epithelioid leiomyosarcoma is a very rare tumour of the urinary bladder. The use of immunohistochemical staining is of value in assisting diagnosis.

Malignant Perivascular Epithelioid Cell Neoplasm (PEComa) of the Urinary Bladder With TFE3 Gene Rearrangement

Recently, a small subgroup of PEComas has been recognized to harbor rearrangements involving TFE3, a gene also involved in rearrangements in translocation-associated renal cell carcinomas and alveolar soft part sarcomas. The few TFE3 rearrangement-associated PEComas reported have exhibited distinctive pathologic characteristics contrasting to PEComas in general, including predominantly epithelioid nested or alveolar morphology and underexpression of muscle markers by immunohistochemistry. In this study, we report the clinicopathologic, immunohistochemical, and molecular features of a primary urinary bladder PEComa diagnosed by transurethral resection in a 55-year-old woman that clinically mimicked urothelial carcinoma. Light microscopy demonstrated mixed spindle cell and epithelioid morphology with the epithelioid component preferentially associated with blood vessels. Immunohistochemistry revealed positive staining for HMB45, tyrosinase, MiTF, cathepsin K, smooth muscle actin, and TFE3 protein. Fluorescence in situ hybridization for the TFE3 gene revealed a split signal pattern, indicating TFE3 rearrangement. X chromosome inactivation analysis demonstrated a clonal pattern despite the heterogenous appearance of the tumor. Unfortunately, despite surgical resection and sarcoma-directed therapy, the patient died of metastatic disease 12 months after diagnosis. This report adds to the known data regarding urinary bladder PEComas and PEComas with TFE3 rearrangement, indicating that both can pursue an aggressive course. Although the few reported TFE3-rearranged PEComas have predominantly lacked a spindle cell component and expression of smooth muscle actin and MiTF by immunohistochemistry, the findings in this study indicate that these features are sometimes present in TFE3-rearranged PEComas.

Vinorelbine rescue therapy for dogs with primary urinary bladder carcinoma

The goal of this study was to evaluate the anti-tumour activity and toxicoses of vinorelbine as a palliative rescue therapy for dogs with primary urinary bladder carcinoma. Thirteen dogs refractory to prior chemotherapeutics and one dog naïve to chemotherapeutic treatment were enrolled. Vinorelbine (15 mg m(-2) IV) was administered intravenously along with concurrent oral anti-inflammatory drugs, if tolerated. A median of six doses of vinorelbine (range: 1-16) was administered. Two dogs (14%) had partial responses, and eight (57%) experienced stable disease. Subjective improvement in clinical signs was noted in 11 dogs (78%). Adverse events were mild and primarily haematological in nature. Median time to progression was 93 days (range: 20-239 days). Median survival time for all dogs was 187 days; median survival for 13 pre-treated dogs was 207 days. Vinorelbine may have utility in the management of canine primary urinary bladder carcinoma and should be evaluated in a prospective study.

Benzo[a]pyrene-mediated toxicity in primary pig bladder epithelial cells: A proteomic approach

The studies described in this paper deal with a sequence of cellular events induced by the environmental toxicant benzo[a]pyrene (B[a]P) that were investigated in primary urinary bladder epithelia cells (PUBEC) from pigs by using a proteomic approach. Two-dimensional (2DE) gel electrophoresis unveiled the differences in protein expression between cells exposed to 0.5 μM B[a]P for 24 h and control cells. Twenty-five differentially expressed proteins involved in DNA repair, mitochondrial dysfunction, and apoptosis were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). These findings were supported by the concentration-dependent increase in olive tail moments as determined by the comet assay and by a time-dependent increase in histone H2A.x (H2AX) phosphorylation upon B[a]P exposure. On the other hand, the expression of voltage-dependent anion channel 2 (VDAC2), cathepsin D (CTSD), heat shock protein 27 (HSP27), and heat shock protein 70 (HSP70) hinted to apoptosis occurring through the intrinsic apoptotic mitochondrial pathway. Taken together, these data suggest that B[a]P is capable of inducing DNA damage in urinary bladder epithelial cells at low concentrations during a short exposure period, thus eventually leading to cell death by apoptosis. Epidemiological studies have indicated PAHs as potential candidates for initiating bladder cancer development, although the precise risk is still unknown (Kaufman et al. (2009)). In recent years, the understanding of the metabolic capacity of urothelial cells has broadened continuously; i.e. a wide range of xenobiotic metabolizing cytochrome P450 enzymes (CYP) were detected in urothelial cells from humans and animals (Roos et al., 2006; Guhe et al., 1996), thus indicating that urothelial cells are not only passively exposed to reactive metabolites but also actively by intracellularly producing reactive intermediates that can induce cancer. Moreover, small quantities of non-metabolized B[a]P and its hydroxylated derivatives have been identified in blood and urine (Rossella et al. (2009)). Thus, it appears plausible that B[a]P, a highly lipophilic compound, is taken up by the urothelium and metabolically activated to carcinogenic intermediates in these cells. In our previous studies with primary uroepithelial cells isolated from freshly slaughtered pigs we demonstrated the ability of these cells for a strong uptake of B[a]P and its conversion to the oxidative metabolite (3-OH-B[a]P) (Verma et al. (2012)). The present study is a continuation of this previous work exhibiting the effects of B[a]P exposure on cellular functions of PUBEC. The results indicated caspase-dependent apoptosis induced by B[a]P due to DNA damage (possibly lethal double-strand breaks as indicated by H2AX phosphorylation). Taken together, these studies provide strong evidence for the ability of B[a]P to act as a bladder carcinogen.

N-Acetylation of p-Aminobenzoic Acid and p-Phenylenediamine in Primary Porcine Urinary Bladder Epithelial Cells and in the Human Urothelial Cell Line 5637

N-Acetyltransferases (NAT) are important enzymes in the metabolism of certain carcinogenic arylamines, as N-acetylation decreases or prevents their bioactivation via N-hydroxylation. To study such processes in the bladder, cell culture models may be used, but metabolic competence needs to be characterized. This study focused on the N-acetylation capacity of two urothelial cell systems, using p-aminobenzoic acid (PABA) and the hair dye precursor p-phenylenediamine (PPD), two well-known substrates of the enzyme NAT1. The constitutive NAT1 activity was investigated using primary cultures of porcine urinary bladder epithelial cells (PUBEC) and in the human urothelial cell line 5637 to assess their suitability for further in vitro studies on PABA and PPD-induced toxicity. N-Acetylation of PABA and PPD was determined by high-performance liquid chromatography (HPLC) analysis in cytosols of the two cell systems upon incubation with various substrate levels for up to 60 min. The primary PUBEC revealed higher N-acetylation rates (2.5-fold for PABA, 5-fold for PPD) compared to the 5637 cell line, based on both PABA conversion to its acetylated metabolite and formation of mono- and diacetylated PPD. The urothelial cell systems may thus be useful as a tool for further studies on the N-acetylation of aromatic amines via NAT1.

Effects of Cigarette Smoke Condensate on Primary Urothelial Cells in Vitro

Cigarette smoking is a risk factor for bladder cancer. Since urothelial cells express phase I and II enzymes these cells are able to metabolize precarcinogens into DNA reactive intermediates. Cigarette smoke is a complex mixture containing at least 80 known carcinogens. In this context especially aromatic amines and polycyclic aromatic hydrocarbons are discussed as being responsible for bladder-carcinogenicity. Cell cultures of primary porcine urinary bladder epithelial cells (PUBEC) have been useful models for studies on bladder-specific effects. These cells are metabolically competent and found to be a valuable tool for examining effects of cigarette smoke constituents. In the present study PUBEC were utilized to investigate the effects of the complex mixture cigarette smoke condensate total particulate matter (CSC TPM) with emphasis on induction of cytochrome P-450 1A1 (CYP1A1) and genotoxic effects. CYP1A1 induction was investigated by Western blot and flow cytometry. The most pronounced effects were found after 24 h of incubation with 1–10 μg/ml CSC TPM. Maximal induction was observed at 5 μg/ml by flow cytometry and at 10 μg/ml by Western blot analysis. Genotoxic effects were investigated by means of alkaline single-cell gel electrophoresis (“comet assay”) with and without the use of the DNA repair enzyme formamidopyrimidine-DNA glycosylase (Fpg) and the micronucleus (MN) test. A numerical concentration-dependent increase in Fpg-sensitive sites indicating oxidative DNA damage and a quantitative rise in MN formation were noted. The CSC utilized in this study contained low amounts of benzo[a]pyrene, 4-aminobiphenyl, and 2-naphthylamine. With regard to the observed CYP1A1 induction, these substances cannot explain the CYP1A1 inducing effect of CSC TPM. It is possible that other compounds within CSC TPM contribute to CYP1A1 induction in our cellular model.

KRAS mutation is present in a small subset of primary urinary bladder adenocarcinomas

To determine whether KRAS mutations occur in primary bladder adenocarcinoma. Twenty-six cases of primary urinary bladder adenocarcinoma were analysed. DNA was extracted from formalin-fixed, paraffin-embedded tissue and amplified with shifted termination assay technology, which recognizes wild-type or mutant target sequences and selectively extends detection primers with labelled nucleotides. A mutation in KRAS was found in three (11.5%) of 26 primary bladder adenocarcinomas. Two of these three cases exhibited a G13D mutation, whereas the remaining case contained a mutation in G12V. None of the ten cases of urothelial carcinoma with glandular differentiation displayed KRAS mutation. Colonic adenocarcinoma contained a KRAS mutation in 18 (33%) of 55 cases. There was no distinct difference with regard to grade, stage or outcome according to the limited clinicopathological data available. However, the two youngest patients, aged 32 and 39 years, in our study group, with a mean population age of 61 years, were found to have mutations in KRAS. KRAS mutations are present in a small subset of primary urinary bladder adenocarcinomas. Future clinical trials for treatment of bladder adenocarcinoma, employing targeted therapies similar to those used for treatment of colon cancer, may also benefit from the predictive implications of KRAS mutational testing.

Exposure of primary porcine urothelial cells to benzo(a)pyrene: in vitro uptake, intracellular concentration, and biological response

More than 90% of all bladder cancers are transitional cell carcinomas arising from the cells lining the inside of the hollow organ (uroepithelium). Cell cultures from primary urinary bladder epithelial cells (PUBEC) of pigs were established to assess the uptake, intracellular concentration, and subcellular distribution of the environmental pollutant benzo(a)pyrene (BaP). During treatment of the cells with 0.5μM BaP for up to 24h, intracellular concentration of BaP increased without saturation but with marked differences between various PUBEC pools. Analysis of BaP uptake by laser scanning microscopy indicated that BaP is rapidly partitioned into the cell membrane, while only a slight but significant increase in BaP fluorescence intensity was observed in the cytosol and nucleus. Spectrofluorometric quantification of BaP in PUBEC using ex situ calibration revealed a strong accumulation of BaP, leading to intracellular concentrations ranging from 7.28 to 35.70μM in cells exposed to 0.5μM BaP and from 29.9 to 406.64μM in cells exposed to 10μM BaP. These results were confirmed by gas chromatographic mass spectrometric analysis. Apoptotic cell nuclei were assessed by TUNEL analysis to see whether BaP exposure at the given concentrations results in a toxic effect. While apoptotic cells were barely detectable in control epithelial cells, there was a marked elevation in apoptosis in the BaP-exposed cells. In conclusion, a comprehensive study on uptake and quantification of BaP in epithelial cells from pig bladder is reported for the first time. The study may be helpful in understanding the pattern of BaP uptake and distribution in bladder and its possible implication in bladder cancer development.

Absence of Urine Production Due to Renal Failure Enables Clear Visualization of Primary Urinary Bladder Carcinoma on 18F-FDG PET/CT

An 81-year-old man affected by renal failure, underwent 18F-FDG PET/CT for detecting primary lesion because of multiple lung nodules consistent with secondary lesions revealed by computed tomography without contrast. PET study documented high pathologic uptake at anterior and upper wall of urinary bladder, and a primary urinary bladder cancer was suspected. Biopsy confirmed the presence of a high-grade transitional cell carcinoma.

Primary Signet-Ring Carcinoma in the Bladder Presenting as a Hypervascular Luminal Polypoid Mass

Primary signet-ring carcinoma is a very aggressive and rare variant of a primary urinary bladder cancer, accounting for less than 1% of cases. We reported on a 76-yearold patient with primary signet-ring carcinoma who occurred metastatic lymphadenopathy with extranodal invasion causing intraluminal tumor thrombi in the adjacent vein, and pulmonary metastasis over the course of three months. We demonstrated the computed tomography findings of primary signet-ring carcinoma of the bladder and correlated the imaging findings with the pathologic features. We reviewed the distinguishing imaging findings of the primary signet-ring carcinoma compared with urothelial cell carcinoma, the most common subtype of the bladder cancer. Index terms

Pseudosarcomatous Myofibroblastic Tumour of the Urinary Bladder: A Case Report

A pseudosarcomatous myofibroblastic proliferation is an unusual and a rare benign lesion which arises from the bladder submucosal stroma and is easily mistaken for a malignant neoplasm, clinically, radiologically and histologically. By definition, the tumour is composed of a dominant spindle cell proliferation with a variable inflammatory component. These spindle cells are now known to be myofibroblasts and this is the reason for the current designation for this disease. The term 'inflammatory' may not be applicable to all the tumours, since some investigators have demonstrated the presence of chromosomal abnormalities and have documented cases which showed recurrence, thus supporting the theory that at least some of these tumours were true neoplasms.Non-epithelial tumours account for 2-5% of all the primary urinary bladder neoplasms, with the most common types being rhabdomyosarcoma in patients under the age of 10 years and leiomyosarcoma in adults. A pseudosarcomatous myofibroblastic tumour is a nonepithelial lesion that follows a benign indolent course and a conservative management has been reported as the treatment of choice. Herein, we are reporting a case of a pseudosarcomatous myofibroblastic tumour which was mistaken for a sarcoma clinically and radiologically and which was proved as a pseudosarcomatous inflammatory myofibroblastic tumour by histopathology and immunohistochemistry.

Papillary urothelial neoplasm of low malignant potential of the urinary bladder: clinicopathologic and outcome analysis from a single academic center

Few long-term single-center studies have addressed the outcome of patients with papillary urothelial neoplasms of low malignant potential. Our study evaluates the behavior of these tumors occurring as primary urinary bladder lesions. For this purpose, 34 primary in-house cases diagnosed and treated between 1998 and 2008 were identified from our medical records. Upon review, 3 cases were upgraded to noninvasive low-grade urothelial carcinomas and excluded from further evaluation. During follow-up (range, 3-108 months; mean, 42 months), 13 patients developed recurrences; and 9 patients progressed to a noninvasive higher grade lesion (8 to low-grade and 1 to high-grade urothelial carcinomas). None of our patients developed stage progression (>pTa) or died of bladder cancer. Size of the primary tumor was associated with the risk of recurrence (P = .043), whereas the number of episodes of recurrence was associated with the likelihood of grade progression (P = .034). In conclusion, recurrences were observed in 42% of all our patients, with a grade progression rate of 29%. None of our patients developed invasive carcinoma or died as a consequence of their disease. Considering the low but definitive risk of recurrence and grade progression, appropriate clinical follow-up of patients with primary papillary urothelial neoplasm of low malignant potential is warranted.

Primary Adenocarcinoma of the Urinary Bladder

Primary adenocarcinomas of the urinary bladder are uncommon, and the molecular pathways are currently not well defined. In this study, we assessed the association between biologic markers and clinicopathologic characteristics in a cohort of 21 patients with primary urinary bladder adenocarcinoma. Immunohistochemical staining for cell cycle-specific markers, including p53, p21, p27, Ki-67, and cyclin E, were performed on sections of a tissue microarray construct. The tumors were high grade in 12 (57%) and pT2 or higher in 18 (86%); lymph nodes were involved in 6 cases (29%); and there was pathologic evidence of schistosomiasis in 14 (67%). The best prognostic combination of markers was combined alterations in p27 and Ki-67 and was associated with stage (P = .012), grade (P = .005), DNA ploidy (P = .005), and lymph node involvement (P = .04). Stage, lymph node involvement, combined alterations of p27 and Ki-67, and combined alterations of all 5 biomarkers were associated with increased probability of disease recurrence and cancer-specific mortality (P < .05).