Transurethral Resection Biopsy Research Articles

Unraveling the Mystery: Paraganglioma in the Urinary Bladder. A Case Report

The bladder paraganglioma, which makes up 0.06% of all bladder tumors, is a highly uncommon condition. A 30-year-old female patient who was diagnosed with bladder paragangliomas at our hospital. The study covers the patient's journey from the first clinical presentation to the follow-up after surgery, providing insight into this uncommon illness. Urinary bladder tumour shown on CT KUB. The case was established by a transurethral resection biopsy. In order to completely remove the tumour, the patient had a radical cystectomy along with a hysterectomy and a bilateral salpingo-oophorectomy. A tumour mostly seen in the detrusor muscle that is organised in zellbellen pattern and is bordered by pushing fibrovascular stroma. Upon CT follow-up at three and six months, the results were generally unremarkable in terms of margins, metastasis, and local recurrence. Urinary tract hyperplasia is the most typical sign in our instance of bladder paraganglioma, a very uncommon tumour. A tumour called a polypoid in the bladder's posterior wall suggests cancer. More investigation into this uncommon ailment is necessary, as surgical extraction is still the only treatment available to these people.

Expression of GATA3, p63, E-cadherin and Her2Neu Immunohistochemical Stains in Urothelial Carcinoma and their Relationship with Histological Grading and Prognosis- A Cross-sectional Study

Introduction: Urinary bladder cancer is the 10th most common cancer worldwide. Cystoscopy and biopsy/Transurethral Resection of Bladder Tumour (TURBT) are the best techniques for diagnosing and staging urinary bladder cancers. Urothelial Carcinomas (UC), particularly in transurethral resection biopsies, can pose diagnostic difficulties due to limited material. Immunohistochemistry (IHC) plays a valuable role in these settings, and many immunostains are being utilised for diagnostic evaluation. However, the relationship of these immunomarkers with histological grade and their prognostic utility has not been adequately explored. Aim: To analyse expression of Her2Neu, E-cadherin, p63, and GATA3 in UC and its relation with histological grading and prognosis. Materials and Methods: This was an observational crosssectional study conducted in the Pathology Department of IPGMER and SSKM Hospital, Kolkata, West Bengal, India over two years (November 2020-October 2022). Samples of 100 bladder carcinoma patients with predominant TURBT specimens were included in the study. The histopathological reports and tumour grading were done according to the World Health Organisation (WHO) classification of urinary bladder tumours. The Formalin Fixed Paraffin-embedded (FFPE) sections of the tumour blocks were subjected to IHC staining, and the results were interpreted accordingly. Statistical analysis was performed with the help of the Statistical Package for Social Sciences (SPSS), IBM (version 25.0). Unpaired t-test and Z-test (Standard Normal Deviate) were used to test the significant difference between two proportions. Results: The mean age of the study population was 59.69±14.53 years, and there was a male preponderance (male: female=3.54:1). Histopathological examination revealed 55% to be of low-grade morphology. Overall, 53% of cases were in T1 stage, and the rest were in T2 stage. On IHC analysis, E-cadherin showed a statistically significant decrease in intensity with increasing grade (p-value <0.001) and T stage of UC (p-value <0.001), but there was no statistically significant relationship between Her2Neu expression and tumour grade/ stage (p-value 0.5764 and 0.5663, respectively). A statistically significant relationship was observed between GATA3 and p63 scores with the grade and T stage of the tumour, i.e., GATA3 positivity increased with increasing grade and T stage of the tumour (p-value <0.001 in both), and there was a loss of p63 with advancing grade and stage of the tumour (p-value <0.001 in both). Conclusion: GATA3, p63, and E-cadherin can be used as prognostic markers in UCs. No significant relationship was found between Her2Neu expression and tumour grade in UC.

Predictors of Response Following Neoadjuvant Cisplatin-Based Chemotherapy for Muscle Invasive Urothelial Bladder Cancer Using Molecular Profile: A Prospective Clinical Study

ObjectivesTo predict response of patients with muscle invasive bladder cancer (MIBC) to neoadjuvant chemotherapy (NAC) through analysis of molecular profile assessed clinically (radiologically and by pathological examination of transurethral resection biopsy [TURBT] specimens) and definitively with histopathological examination after radical cystectomy (RC). MethodsIn a prospective study, tumor biopsies were obtained from patients with urothelial MIBC (T2-4a N0-2 M0) during TURBT. Patients were eligible for RC received 4 cycles of cisplatin-based NAC. DNA repair genes (BRACA1, ERCC1) & CTR gene m-RNA expression levels were assessed in resected tissue. The response to chemotherapy was assessed clinically (radiologically & TURBT) following NAC. Response was re-assessed for 64 patients who underwent RC and predictors of cancer-free survival (CFS) were calculated. Receiver operating characteristic (ROC) curve was used to delineate cutoff value copes with the best sensitivity and specificity for prediction of response to NAC. ResultsThe study included 104 patients, 42 (40.4%) responded well to NAC clinically. Out of 64 patients who underwent RC, 26 (40.6%) showed good response to NAC. CFS at 18 months for patients who underwent RC was 60%. Statistical analysis showed that molecular profile was an independent predictor of good response to NAC both clinically and pathologically and also predicted better CFS. ConclusionMolecular profile could play a decisive role in early detection of patients with MIBC who will get benefit from preoperative NAC.

GATA3 and CK5/6 Immunohistochemical Expression in Urothelial Carcinoma: Diagnostic, Biological and Prognostic Significance

Background: Urothelial carcinomas [UCs] can be diagnostically challenging, particularly transurethral bladder tumors resection biopsies with limited material. Immunohistochemistry is a valuable instrument for diagnosis when morphology alone is inadequate. GATA-binding protein 3 [GATA3] and cytokeratin 5/6 [CK 5/6] contributes to the growth of UC. However, their correlative expression in UC and prognostic value has not been sufficiently investigated. The aim of the work: The current study aimed to evaluate the utility of GATA3 expression in UC and correlate that with CK 5/6 expression to verify different subtypes of UC and assess their prognostic significance. Methodology: Here, we immunohistochemically stained GATA3 and CK 5/6 in 90 UCs samples by transurethral bladder tumor resection in a retrospective study, between May 2018 and February 2020. All were histopathologically evaluated and immunohistochemically stained for GATA3 and CK 5/6, and then correlated them with the clinicopathological parameters to investigate their clinical significance. Results: GATA3 expression was seen in 76 patients [84.44 %]. There was significant correlation between GATA3 expression with the tumor histological grade and degree muscle invasion. There was a weak or even negative expression in high‑grade, invasive than the low‑grade, non-invasive tumor [P= <0.001]. CK5/6 was positive and focally positive in 27.78% with a significant correlation of CK5/6 expression with tumor grade and muscularis propria invasion. On the other side, tumors with diffuse GATA3 expression had low CK5/6 expression. Conclusion: GATA3 and CK 5/6 should be used as sensitive and specific markers for UC. They can also be effectively used in the prediction of probable grade and tumor invasion in biopsied material with poor morphological characters; and thus, help in the future appropriate treatment.

Interpretation of Prostatic Biopsy at a tertiary care centre

Introduction: Worldwide prostatic carcinoma is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males. Prostate-specific antigen (PSA), digital rectal examination, and transrectal ultrasound are the tools most commonly used to screen for prostate cancer. Prostatic biopsy is most often preceded by abnormalities found on digital rectal examination (DRE) or serum prostate specific antigen (S.PSA) elevation. This study was planned to know proportion of malignant and benign lesions in histopathologic examination for prostatic lesions in patient who attend OPD/IPD and to analyze the usefulness of serum PSA & ultrasound examination by histopathological confirmation. Methods: Patients visited to urology department with urinary incontinence and other complaints were evaluated which includes clinical history, signs and symptoms. Rectal examination of patients was done. Serum PSA level and prostatic biopsy were sent of those who were suspected for prostatic disease. Prostate biopsy was obtained by using any one of the following method 1.Transurethral resection biopsy 2. Transrectal biopsy Trucut biopsy. Results: Out of 300 cases of prostatic biopsy 265 (88.33%) are benign and 35 (11.66%) cases are malignant lesions. Out of 300 cases, 191 (63.66%) are pure benign prostatic hyperplasia, 48(16%) are BPH with chronic prostatitis and 11(3.66%) are BPH with severe prostatitis. Out of 35 cases of prostatic carcinoma 33 (94.28%) cases are adenocarcinoma and 2 cases (5.71%) are transitional cell carcinoma. Out of 262 cases with clinically benign lesions, 258 cases proved benign histopathologically but 4 cases (1.52%) are diagnose malignant. 151 patients have S.PSA less than 4 ng/ml, out of 151, 149 turned to be benign on histopathological examination. 52 patient have S.PSA above 10 ng/ml, out of these 52 cases, 29 have malignancy in HPE examination. Out of 278 cases diagnosed as benign isoechoic by ultra sonography 262 cases have benign lesion on histologic diagnosis and 16 have malignant lesion. Out of 22 cases diagnosed as malignant (hypoechoic asymmetrical) by ultrasonographicaly 19 proved malignant histologically. Conclusion: The results of this study indicate that transrectal ultrasound, serum prostate specific antigen and digital rectal examination were good tool to differentiate between malignant and benign lesions of prostate. Proportion of malignancies are quiet significant in prostatic lesions and increased with age. Key words: Prostae, Malignancy, Biopsy, PSA, DRE

Leiomyoma of the Urinary Bladder: A Review and Update

Leiomyoma of the urinary bladder / leiomyoma of the ureter is a very rare benign tumour of smooth muscle origin which has been reported sporadically globally. Leiomyoma of the urinary bladder/ureter may be diagnosed incidentally during investigation of various conditions including infertility and hepatitis. Leiomyoma of the urinary bladder / ureter may manifest in female as well as in a male patient with non-specific symptoms including lower urinary tract symptoms / retention of urine, haematuria, loin pain/discomfort, urinary tract infections and cystitis. The general and systematic examinations may be normal but at times there may be a palpable mass within the area of the urinary bladder on bimanual examination but not always. There may occasionally be tenderness in the loin. The results of routine haematology and biochemistry blood tests would generally tend to be normal but there may be anaemia and impairment of renal function some cases of visible haematuria and obstruction of the ureter respectively. Ultrasound scan would tend to illustrate a well-circumscribed polypoidal soft tissue mass projecting into the urinary bladder or within the intramural area of the bladder. Intravenous urography would show a filling defect in the urinary bladder. CT and MRI scans of abdomen and pelvis with contrast would show a well-defined round mass in the area of the bladder which could be iso-tense to skeletal muscles on T1 and T2 weighted images and occasionally may show cystic areas of necrosis. Cystoscopy would show the lesion projecting into the urinary bladder at the specific area of the urinary bladder involved and at times the projecting lesion would be covered by normal looking urothelial mucosa and on other occasions when the lesion is large and in the area of a ureteric orifice the specific ureteric orifice would not be visualized. Diagnosis of leiomyoma of the urinary bladder / ureter would be confirmed upon histopathology and immunohistochemistry study features of trans urethral resection biopsies of the lesion which would tend to show smooth muscle spindled-cells with no evidence of atypia, or necrosis, or haemorrhage and associated with a low Ki67 index. Trans-urethral resection of the urinary bladder lesion tends to be undertaken for small to medium sized lesions with good outcome but this tends to be associated with about 18% recurrence rate that would require further resections or surgical excision to ensure complete removal of the lesion and no further recurrences. Surgical excision of the lesion including partial cystectomy, local excision / enucleation have been very effective for the treatment of larger leiomyomas with no reported recurrence so far; nevertheless, patients who undergo augmentation cystoplasty or total cystectomy and urinary diversion would need to cope with the functional problems related to the cystoplasty or urinary diversion. Differential diagnoses of leiomyoma of the urinary bladder / ureter include leiomyosarcoma, urothelial carcinoma and other malignant lesions affecting the urinary bladder. There is need for clinicians to explore minimal invasive surgery to treat patients who have leiomyoma of the bladder / ureter especially those who have multiple co-morbidities and the alterative management options that could be undertaken in multi-centre trials include: Cryotherapy, radiofrequency ablation, irreversible electroporation, high frequency ultrasound treatment and super-selective embolization of the arterial branch supplying the leiomyoma. Patients who develop ureteric obstructions would additionally require nephrostomy insertions or insertion of ureteric stents as a temporary measure to improve their renal functions.

Hsa-microRNA-101-3p expression in human urinary bladder cancer: Correlation with tumor pathology

IntroductionMicroRNAs (miRs) are a class of small, conserved, non-protein-coding RNAs that regulate gene expression by controlling translation of target messenger RNA. In cancer, miRs can act either as tumor suppressors or oncogenes. Reduced expression of hsa-miR-101-3p has been observed in different types of cancers, and was thus considered to be a tumor suppressor. In urinary bladder cancer (BC) cell lines, hsa-miR-101-3p was found to suppress cancer cells motility, however studies in human BC patients, correlating hsa-miR-101-3p expression to pathological findings are very limited. This study aims at assessing hsa-miR-101-3p expression in human BC in correlation to tumor pathology in transurethral resection biopsies. Material and methodsTransuretheral bladder tissue specimens were collected from 100 bladder cancer patients. Only bladder transitional cell carcinoma (BTCC) patients (n = 80) were considered. Total RNA was extracted and following reverse transcription, expression of hsa-miR-101-3p was assessed by quantitative real time PCR using Taqman assay. The fold change for hsa-miR-101-3p expression between malignant and surrounding non-malignant tissues was calculated using relative quantification method. Expression of hsa-miR-101-3p was correlated to tumor stage, grade, and lymphatic/ vascular involvement. ROC curve was done to calculate the discriminative ability of hsa-miR-101-3p expression between malignant and non-malignant tissues. ResultsHsa-miR-101-3p was significantly under-expressed in all malignant versus non-malignant tissue samples (median 13.6 (9.8–19.4) vs. median 10.9 (7.4–16.2), p < 0.001) respectively. Mann-Whitney test showed statistically significant hsa-miR-101-3p underexpression in high vs. low tumor grades (p < 0.001), and T2 vs. T1 tumor stages (p < 0.001). There was no significant association between hsa-miR-101-3p underexpression and lymphatic/vascular invasion. ROC curve demonstrated hsa-miR-101-3p to highly discriminate between malignant and non-malignant tissue (p < 0.001).At cut-off value >10.85, hsa-miR-101-3p showed sensitivity of 83% and specificity of 56%. ConclusionsHsa-miR-101-3p can highly discriminate between malignant and non-malignant samples in BTCC, and seems to associate with tumor progression and aggressiveness. It might be a promising diagnostic and perhaps prognostic marker for BTCC.

Diffusion weighted magnetic resonance imaging in bladder cancer, is it time to replace biopsy?

IntroductionTo assess if the apparent diffusion coefficient (ADC) value of magnetic resonance imaging (MRI) can discriminate between the cell type, histological grade and improve staging of urinary bladder cancer (BC).Material and methods102 patients with urinary bladder masses underwent MRI using a 1.5 T machine. T2 weighted and diffusion weighted imaging (DWI) using b values of 0, 150, 500 and 1000 s/mm2 were done. The ADC values of bladder masses were measured. These values were correlated with the histopathologic results. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of T2WI, DWI and T2WI plus DWI for detecting bladder lesions were evaluated.RESULTSThe cut-off ADC value for diagnosing malignant bladder wall pathologies was ≤1 x 10-3 mm2/s with 94.5% sensitivity and 87.5% specificity. The mean ADC value of different malignant cell types was statistically insignificant. A significant difference in ADC values was found between G1 and G3 (P = 0.000), G2 and G3 (P = 0.045) but not between G1 and G2 (p = 0.066). Staging accuracy for differentiation between invasive and non-invasive lesions was nearly the same for all MRI data sets. For differentiation between organ confined (pT1–pT2) and non-organ confined lesions (pT3–pT4), staging accuracy was better in T2WI plus DWI (83%) as compared to DWI alone (77%) or T2WI alone (75%).ConclusionsAdding DWI and the ADC value to T2WI improve the accuracy of MRI in BC detection and staging. However, at this time point, MRI cannot replace transurethral resection (TUR) biopsy or distinguish sharply between all different histologic grades and cell types.

Utility of Clinical Risk Stratification in the Selection of Muscle-Invasive Bladder Cancer Patients for Neoadjuvant Chemotherapy: A Retrospective Cohort Study.

Introduction: Level I evidence supports the use of cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer prior to radical cystectomy (RC). On average, 30–40% of patients achieve a complete pathologic response (i.e., stage pT0) after receiving NAC. Some centers risk-stratify patients, suggesting that there may be a higher-risk population that would derive the most benefit from NAC. Recently, a risk-stratification model developed at M.D. Anderson Cancer Center (MDACC) specified criteria for clinical staging and patient selection for NAC. We applied this model to our own RC patient cohort and evaluated our own experience with clinical risk stratification and the effect of NAC on post treatment risk categories.Methods: We retrospectively reviewed the charts of consecutive patients who underwent RC at two institutions between 2004 and 2014 and noted whether or not they received NAC. We determined the clinical stage by reviewing the exam under anesthesia, transurethral resection biopsy (TURBT) pathology, and preoperative imaging. Patients with cT2-T4a node-negative disease were included. Those with sarcomatoid features or adenocarcinoma were excluded. Patients were classified as high risk if they had tumor-associated hydronephrosis, clinical stage≥T3b-T4a disease, variant histology (i.e., micropapillary or small cell), or lymphovascular invasion (LVI), as specified by the MDACC model. Variables were examined for associations with cancer-specific survival (CSS), overall survival (OS), and risk-category reclassification.Results: We identified 166 patients with a median follow-up time of 22.2 months. In all, 117 patients (70.5%) did not receive NAC, 68 (58.1%) of whom we classified as high risk. Among patients not receiving NAC, CSS and OS were significantly decreased in high-risk patients (log-rank test p = 0.01 for both comparisons). The estimated age-adjusted hazard ratios of high-risk classification for cancer-specific and overall death were 3.2 (95% CI: 1.2 to 8.6) and 2.2 (95% CI: 1.1 to 4.4), respectively. On post-RC final pathology, 23 (46.9%) low-risk patients were up-classified to high risk and 17 (25.0%) high-risk patients were down-classified. Complete pathologic responses (pT0) were achieved in 7 (6.0%) patients and partial responses (pT1, pTa, pTis) were achieved in 28 (23.9%) patients. Of the 49 patients who did receive NAC, 43 (87.8%) received cisplatin-based and six (12.2%) received carboplatin-based regimens. Applying the MDACC model, we categorized 41 (83.7%) patients as high risk prior to NAC treatment. On final pathology, 3 (37.5%) low-risk patients were up-classified and 17 (41.5%) high-risk patients were down-classified. Complete pathologic responses (pT0) were seen in 13 (26.5%) patients and partial responses were seen in 10 (20.4%) patients. Although the utilization of NAC was not statistically significantly associated with CSS or OS (log-rank test p > 0.05 for both comparisons), it was associated with a 1.2 times increased odds (95% CI: 0.4 to 2.1) of post-RC reclassification from high to low risk on age-adjusted logistic regression.Conclusions: We found similar results using the clinical risk-stratification model in our cohort and showed that the high-risk category was associated with lower CSS and OS. NAC was associated with a higher probability of risk reclassification from high to low risk.

Transurethral biopsy of the prostatic urethra is associated with final apical margin status at radical cystoprostatectomy.

Biopsy of the prostatic urethra is an integral part of clinical staging in patients prior to radical cystoprostatectomy (RC) and urinary diversion. We examined whether preoperative transurethral resection (TUR) biopsy was associated with final apical urethral margin status and hypothesized that a negative biopsy could replace intraoperative frozen section for decision making regarding the feasibility of orthotopic neobladder reconstruction. TUR biopsy, frozen section, urethrectomy, and final apical urethral margin pathologic data were extracted from the charts of men who had undergone RC at the Houston Methodist Hospital between 1987 and 2013. TUR biopsies were performed at five and seven o'clock adjacent to the verumontanum. A positive biopsy was defined as the presence of in situ or invasive urothelial carcinoma. Clinical and perioperative variables were analyzed using descriptive and inferential statistics. We reviewed the medical records of 272 men. Preoperative TUR biopsies of the prostatic urethra were negative in 74% (200/272) and positive in 26% (72/272) of men. The overall incidence of apical urethral margin positivity on final pathology was 2.2% (six of 272). Four men underwent primary or secondary urethrectomy. TUR biopsy negative and positive predictive values for apical urethral margin positivity were 99.5% (95% confidence interval (CI): 97.2 to 99.9) and 6.9% (95% CI: 2.3 to 15.5), respectively. The incidence of a positive apical urethral margin was low in patients undergoing RC. A negative preoperative TUR biopsy of the prostatic urethra was reliably associated with a negative final margin, obviating the need for intraoperative frozen section. Furthermore, a positive biopsy was not reliably associated with final margin status. These data will aid in the counseling of patients regarding the feasibility of neobladder reconstruction.

Study of the reproducibility of the 2004 World Health Organization classification of urothelial neoplasms

The aim of the study was to evaluate urinary bladder biopsies showing papillary urothelial neoplastic lesions based on the 2004 WHO/ISUP classification of Urothelial Neoplasms of the Urinary Bladder, to assess the reproducibility of the bladder carcinoma grade. Fifty consecutive transurethral tumor resection biopsies were evaluated by four pathologists independently. The final diagnoses of each pathologist were subjected to statistical analysis to assess the degree of interobserver variability and reproducibility of this classification. Significant interobserver variation was found in the reporting of urothelial neoplasms. In 22 instances there was difference in opinion between PUNLMP and low-grade carcinoma, and in 59 instances between low and high grade carcinoma. The 4 observers never unanimously agreed on the diagnosis of PUNLMP.

Usefulness of Transurethral Biopsy for Staging the Prostatic Urethra before Radical Cystectomy

We determined the likelihood that transurethral resection biopsy of the prostatic urethra adjacent to the verumontanum would detect prostatic involvement of urothelial carcinoma in patients with bladder carcinoma. We compared precystectomy transurethral resection biopsy specimens of the prostatic urethra with those of the matched radical cystoprostatectomy in 272 patients with urothelial carcinoma of the bladder. All prostates were evaluated by whole mount step sections. Prostatic involvement by urothelial carcinoma was detected by transurethral resection biopsy or radical cystoprostatectomy in 101 patients (37.1%). Transurethral resection biopsy detected urothelial carcinoma in 72 cases with 71.3% sensitivity and 100% specificity. The overall accuracy of transurethral resection biopsy to detect urothelial carcinoma of the prostate was 89% (positive and negative predictive values 100% and 86%, respectively). Invasive prostatic urothelial carcinoma arising from the prostatic urethra was detected by transurethral resection biopsy in 21 of 26 patients (81%) while prostatic carcinoma in situ was detected in 39 of 52 (75%). Transurethral resection biopsy detected prostatic invasive urothelial carcinoma resulting from transmural invasion of a bladder tumor in 4 of 15 patients. Prostatic involvement by urothelial carcinoma of the bladder was found in 37.1% of patients. Transurethral resection biopsy missed most tumors resulting from transmural invasion of the bladder primary lesion. Carcinoma in situ and invasive urothelial carcinoma arising from the prostatic urethra were detected in most cases. Transurethral resection biopsy of the prostatic urethra can complement staging and support clinical decision making with respect to neoadjuvant chemotherapy and planning for an orthotopic neobladder.

A case of metastatic cancer with markedly elevated PSA level that was not detected by repeat prostate biopsy

BackgroundProstate-specific antigen (PSA) is a widely used specific tumor marker for prostate cancer. We experienced a case of metastatic prostate cancer that was difficult to detect by repeat prostate biopsy despite a markedly elevated serum PSA level.Case presentationA 64-year-old man was referred to our hospital with lumbar back pain and an elevated serum PSA level of 2036 ng/mL. Computed tomography, bone scintigraphy, and magnetic resonance imaging showed systemic lymph node and osteoblastic bone metastases. Digital rectal examination revealed a small, soft prostate without nodules. Ten-core transrectal prostate biopsy yielded negative results. Androgen deprivation therapy (ADT) was started because of the patient’s severe symptoms. Twelve-core repeat transrectal prostate biopsy performed 2 months later, and transurethral resection biopsy performed 5 months later, both yielded negative results. The patient refused further cancer screening because ADT effectively relieved his symptoms. His PSA level initially decreased to 4.8 ng/mL, but he developed castration-resistant prostate cancer 7 months after starting ADT. He died 21 months after the initial prostate biopsy from disseminated intravascular coagulation.ConclusionCUP remains a considerable challenge in clinical oncology. Biopsies of metastatic lesions and multimodal approaches were helpful in this case.

Plasmacytoid urothelial carcinoma of the urinary bladder – a review of the literature

Plasmacytoid urothelial carcinoma is a new variant of urothelial carcinomas that was added to the World Health Organization (WHO) classification list in 2004; therefore, in view of its rarity, most practitioners may not be familiar with its biological behaviour. Various internet databases were searched to identify cases of plasmacytoid urothelial carcinoma of the urinary bladder in order to document the presentation, investigation, management, treatment and outcome of the disease. In addition, the only reported case of plasmacytoid urothelial carcinoma of the ureter is included. Plasmacytoid urothelial carcinoma of the urinary bladder is a rare variant of urothelial carcinoma and fewer than 100 cases have been reported in the literature. It is an aggressive subtype of urothelial carcinoma with plasmacytoid features and the diagnostic features include mimicking haematolymphoid malignancy, a dyscohesive invasive pattern, eccentric nuclei, evidence of prominent eosinophilic cytoplasm (amphophilic cytoplasm may also be observed) and intracytoplasmic mucin-positive lumina may be present. Patients often present with plasmacytoid urothelial carcinoma at a late stage and exhibit peritoneal surface spread. Mucin stains may reveal intracytoplasmic lumina and plasmacytoid urothelial carcinomas tend to depict immunohistochemical staining characteristics such as keratin positivity [cytokeratin (CK)7 and, at times, CK20], CD138 positivity (many carcinomas, not only plasmacytoid urothelial carcinoma, stain positive for CD138), MUM1 and kappa/lambda light chain negativity, E-cadherin negativity (conventional and micropapillary types of urothelial carcinoma tend to stain positive for E-cadherin and signet-ring cell carcinomas of the bladder tend to stain negative). In the differential diagnosis of plasmacytoid urothelial carcinoma, plasmacytoma must be considered, and immunostaining characteristics can be helpful in the confirmation of the diagnosis in that p63-positive staining and strong keratin would indicate carcinoma. Kappa and lambda in situ hybridization or immunoperoxidase would identify most plasmacytomas. CD138 positivity is expressed by many carcinomas and is, therefore, not helpful, whereas MUM1 preferentially stains plasmacytoma. Plasmacytoid urothelial carcinoma of the urinary bladder has characteristic plasmacytoid morphological features and immunohistochemical staining is helpful in differentiating this tumour from other differential diagnoses. Plasmacytoid urothelial carcinomas are aggressive variants of urothelial carcinomas of the urinary bladder that have been associated with poor prognosis and death of patients following various treatment options including transurethral resection of bladder tumour and/or radical cystectomy, transurethral resection biopsy and/or cystectomy and/or chemotherapy, transurethral resection of bladder tumour, and chemotherapy and/or radiotherapy. Most patients do not survive post treatment; however, there are reports of survival following treatments that have included combination systemic chemotherapy.

1268 SIGNIFICANCE OF RANDOM BLADDER BIOPSIES IN PATIENTS UNDERGOING TRANSURETHRAL RESECTION OF NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Detection and Screening1 Apr 20121268 SIGNIFICANCE OF RANDOM BLADDER BIOPSIES IN PATIENTS UNDERGOING TRANSURETHRAL RESECTION OF NON-MUSCLE INVASIVE BLADDER CANCER Masafumi Kumano, Hideaki Miyake, and Masato Fujisawa Masafumi KumanoMasafumi Kumano Kobe, Japan More articles by this author , Hideaki MiyakeHideaki Miyake Kobe, Japan More articles by this author , and Masato FujisawaMasato Fujisawa Kobe, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1600AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Random bladder biopsies, taken from normal areas of urothelium, are widely performed to detect concomitant carcinoma in situ (CIS) in patients undergoing transurethral resection (TUR) of non-muscle invasive bladder cancer. However, there are few reports investigating the outcomes of random bladder biopsies based on the data from large series; thus, the significance of random biopsies remains controversial. The objective of this study was to retrospectively review the clinical outcomes of random bladder biopsies in patients with non-muscle invasive bladder cancer to identify predictive factors significantly associated with the findings of random biopsies. METHODS This study included a total of 451 consecutive patients with histopathologically confirmed non-muscle invasive bladder cancer who underwent TUR and random bladder biopsies. The random biopsies were taken from the seven different sites of normal-appearing urothelium, including right wall, left wall, trigone, dome, posterior wall, anterior wall and prostatic urethra. RESULTS Random biopsies were positive in 72 patients (16.0%), of whom 66 (91.7%) and 6 (8.3%) were diagnosed as Tis and Ta, respectively. The incidence of positive random biopsies was significantly associated with past history of upper urinary tract cancer, urinary cytology before TUR, number of tumors, pathological stage, tumor grade and presence of concomitant CIS. Univariate analysis identified past history of upper urinary tract cancer, urinary cytology before TUR and number of tumors as significant predictors of positive random biopsies, among which only urinary cytology before TUR appeared to be independently associated with positive random bladder biopsies on multivariate analysis. Furthermore, consideration of the preoperative finding of urinary cytology could diagnose concomitant malignant disease by random biopsies with 59.4% sensitivity, 88.8% specificity, 50.0% positive predictive value and 92.0% negative predictive value. CONCLUSIONS These findings suggest that the outcome of urinary cytology before TUR could be a useful predictor of positive biopsies in patients with non-muscle invasive bladder cancer. Accordingly, it would be important to further discuss the indication of random bladder biopsies in patients who were preoperatively diagnosed as negative in urinary cytology in order to avoid unnecessary biopsies. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e513 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Masafumi Kumano Kobe, Japan More articles by this author Hideaki Miyake Kobe, Japan More articles by this author Masato Fujisawa Kobe, Japan More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Transperineal template-guided prostate biopsy for patients with persistently elevated PSA and multiple prior negative biopsies

ObjectiveTo evaluate the use of transperineal template-guided prostate biopsy for patients with persistently elevated PSA despite multiple negative prior biopsies. Materials and methodsA retrospective review was performed of patients with at least two prior prostate biopsies who underwent transperineal template-guided biopsy. Electronic medical records were reviewed to obtain relevant clinical, laboratory, and pathologic data. ResultsA total of 34 patients underwent transperineal template-guided biopsy. Patients had a mean of 3.7 ± 1.6 (range 2–8) prior biopsies, including prior negative transurethral resection (TUR) biopsy in 6 (17.6%) patients. Prostate cancer was detected in 17 (50%) of the 34 patients. Of these, 14 (82.4%) patients had cancer in the anterior prostate, 9 (52.9%) patients had cancer in the apical prostate, and 16 (94.1%) patients had cancer in either the anterior or apical prostate. Gleason score was 3+3 in 9 (52.9%) patients and 3+4 or greater in 7 (47.1%) patients. The mean number of positive cores was 4.5 ± 3.0 (range 1–11). Of the 17 patients with a diagnosis of cancer, 7 underwent radical prostatectomy, 7 underwent radiation therapy, 1 elected active surveillance, and 1 was deciding between surgery and radiation therapy; 1 patient received palliative chemotherapy for synchronous metastatic pancreatic carcinoma. Patients in whom cancer was detected had significantly smaller prostate volume, higher PSA, higher PSA density, and greater PSA velocity. ConclusionsTransperineal template-guided prostate biopsy is an effective technique for detecting cancer in patients with persistently elevated PSA despite multiple negative biopsies. It improves sampling of the anterior and apical prostate, and should be included as part of the diagnostic algorithm to reduce extensive repeat biopsy.

Patterns of autophagy in urothelial cell carcinomas—the significance of “stone-like” structures (SLS) in transurethral resection biopsies

ObjectivesTo investigate the microtubule-associated protein LC3A, presumed to reflect autophagic activity, in urothelial cell carcinomas (UCC) for its relevance with muscle invasion in transurethral resection (TUR) biopsies. The LC3A antibody is specific for identifying the autophagy-related protein Atg8 and, hence, autophagy—a self-degradation mechanism by which cells recycle their own cytoplasmic constituents, providing with additional energy the rapidly proliferating cells. MethodsThe study comprised 210 TUR specimens of UCC of the urinary bladder: 70 low-grade non-muscle-invasive (NMI, group A), 70 high-grade NMI (group B), and 70 high-grade muscle invasive tumors (group C). These, together with 40 controls, were stained for Atg8/LC3 using an automated immunohistochemical technique. ResultsThe LC3A was detected as diffuse cytoplasmic staining, and as dense, spheroidal, “stone-like” structures (SLS) of variable size (1.2–12.0 μm in diameter), typically enclosed within cytoplasmic vacuoles. The LC3A reactivity, whether expressed in the form of SLS or as diffuse cytoplasmic staining, was higher in high-grade UCC than in low-grade disease and, more importantly, it was associated with muscle invasion. The median number of SLS per optical field, per section was 17.0, 19.0, and 37.0 for groups A, B, and C, respectively (A, B vs. C P < 178> 0.0001; A vs. B P = 0.27). The median SLS diameter was 4.9, 5.3, and 9.3 μm for groups A, B, and C respectively (A, B, vs. C P < 0.0001; A vs. B P = 0.03). ConclusionIt appears that the LC3A protein is closely connected with muscle invasion, but whether this finding is of clinical value in TUR specimens lacking muscularis propria remains to be proven.

Transurethral resection biopsy as part of a saturation biopsy protocol: A cohort study and review of the literature

ObjectiveTo evaluate the prostate cancer (CaP) detection rate and morbidity of performing a transurethral resection biopsy of the prostate (TURBP) at the same time as a saturation biopsy (SBx). PatientsA total of 102 men with previous negative transrectal ultrasound (TRUS) biopsies underwent a SBx under formal anaesthesia. Fifty-four [54 (52.9%)] had a combined SBx and TURBP (Group 1) and 48 (47.1%) had a SBx only (Group 2). ResultsThe CaP detection rate in Group 1 was 38.9% (21/54), which was significantly higher than the detection rate of 27.1% (13/48) in Group 2 (P = 0.005). CaP was detected via TURBP in 12 patients (22.2%) from Group 1, including 8 (14.8%) patients who had CaP solely in their TURBP chips. According to the D'Amico classification, 66.6% (14/21) of the cancers in Group 1 were intermediate (n = 4) or high risk (n = 10). Of the 8 ‘TURBP only’ cancers, 75% (6/8) were intermediate (n = 2) or high risk (n = 4). Seven of these eight patients went on to have a radical prostatectomy (RP) but only 2 (28.6%) were found to have a pure anterior/transition zone (TZ) tumor. The postoperative urinary retention and emergency admission rates for Groups 1 and 2 were 29.6% (16/54) vs. 16.6% (8/48) (P = 0.095) and 11.1% (6/54) vs. 5.5% (2/48) (n = 0.17). There was no difference in terms of hematuria (P = 0.54), urinary tract infection (UTI) (P = 0.22), or sepsis (P = 0.21), and patients in Group 1 spent an average of 0.5 days longer in hospital (1.9 vs. 1.4; P = 0.008). ConclusionsTURBP in association with SBx increases the detection of clinically important CaP. However, this does have to be balanced against the small increased incidence of urinary retention, emergency re-admission, and longer hospital stay.

Transurethral resection of the bladder tumour (TURBT) for non‐muscle invasive bladder cancer: Basic skills

Transurethral resection of the bladder tumour (TURBT) is the standard surgical procedure for non-muscle invasive bladder cancer. We believe that all urologists should be trained in this procedure. This DVD provides an overview of TURBT with particular focus on basic skills, including basic surgical techniques such as the obturator nerve block. Important basic surgical skills required for complete TURBT in non-muscle invasive bladder cancer are: (i) resection of all visible tumors; (ii) resection of apparently normal mucosa on the border of the tumor; (iii) resection of the muscle layer at the base of the tumor until normal muscle fibers are visible; (iv) in applicable cases, random biopsy of apparently normal urothelium of the bladder wall and transurethral resection (TUR) biopsy of both sides of the prostatic urethra; and (v) when possible, after these procedures are completed, a different operating surgeon should inspect the bladder lumen to confirm that there are no remaining tumors. In particular, sampling resection should be implemented in apparently normal mucosa for approximately 1 cm around the tumor, and at the base of the tumor down to the superficial muscle layer. Resected specimens should be examined histopathologically in order to confirm the absence of malignant findings. Fundamental procedures for TURBT include both one-stage and two-stage resection. One-stage resection is used for relatively small tumors and involves a single procedure with simultaneous resection of both the tumor and the tissue at the tumor base down to the superficial muscle layer. In the two-stage resection, the first resection exposes the lower level of the mucosa and the second resection removes that lower mucosal layer in order to sample the superficial muscle layer for cancer staging. At the start of the resection, the loop is electrified before it makes contact with the mucosa. Delicate movements of the sheath should be used, along with delicate movement of the loop itself to adjust the depth of resection. The illustration of surgical techniques shows not only the basic techniques but also some points for caution during the resection. For actual resection, it is important to fully understand the properties of the tumor and to combine these techniques appropriately for each individual resection procedure. When resecting multiple tumors, the same basic resection techniques used for single tumors should be applied, and repeated as necessary. (This is a translated section of a video article originally published in Japanese as a DVD in the Audio-Visual Journal Vol.14 No.1. 2008 by The Japanese Urological Association.).

Phosphorylated H2AX in Noninvasive Low Grade Urothelial Carcinoma of the Bladder: Correlation With Tumor Recurrence

Histone modifications have been linked to DNA replication, transcription and repair. The phosphorylation of histone H2AX at serine 139 (gamma-H2AX) is associated with DNA breaks. gamma-H2AX has been shown to be expressed in bladder urothelial carcinoma. To our knowledge studies of the relationship of gamma-H2AX expression and the clinical outcome of urothelial carcinoma are lacking. Hence, we evaluated the rate of H2AX phosphorylation in low grade bladder urothelial carcinoma and assessed its potential role for predicting recurrence and/or progression. Immunohistochemical expression of gamma-H2AX using a polyclonal antibody was retrospectively assessed in 2 groups of patients from The Johns Hopkins Hospital with low grade bladder urothelial carcinoma. Group 1 consisted of transurethral resection biopsies from 18 patients from 2004 to 2006 that were retrieved from our surgical pathology files. Group 2 consisted of 42 archival transurethral biopsies obtained between 1971 and 1995 with longer followup that were used to construct a tissue microarray. On univariate analysis recurrence in the entire cohort was more likely to develop in gamma-H2AX negative than in gamma-H2AX positive cases (24 of 32 or 81% vs 13 of 28 or 46%). The difference in recurrence was statistically significant (p = 0.02). The same was true in group 2 (16 of 21 cases or 76% vs 9 of 21 or 43%, p = 0.02). Female gender and intravesical therapy were also associated with a higher recurrence rate in our cohort. A higher progression rate was noted in group 2 patients and in the entire cohort in association with negative gamma-H2AX staining. However, the difference in progression between gamma-H2AX negative and positive tumors was not statistically significant. On multivariate analysis only patient gender and prior intravesical treatment remained predictive of recurrence (p <0.03). Our data suggest that epigenetic alterations may have an important role in the mechanism of bladder tumor recurrence. Analysis in a larger cohort is needed to further assess our current preliminary findings of the role of gamma-H2AX expression for predicting outcome in low grade urothelial carcinoma cases.