A case of micropapillary bladder carcinoma

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

Vascular plexus is a differentation criterion for muscularis mucosa from muscularis propria in small biopsies and transurethral resection materials of urinary bladder?

Objective: Smooth muscle fibres are found within thesuperficial lamina propria of urinary bladder (Muscularis Mucosa). Thesemuscle fibres of muscularis mucosa should be distinguished from themuscularis propria in cases with urothelial carcinoma, because the depthof infiltration affects prognosis and therapy modalities. The aim of thepresent study was to evaluate whether the presence of vascular plexus isa criterion for muscularis mucosa and to distinguish it from muscularispropria in urinary bladder biopsies and transurethral resectionspecimens. Materials and methods: Hematoxylin-Eosin andMasson-Trichrome stained slides of 54 cases with urothelial carcinomawere reviewed. Results: In all cases (100%), thick walledvessels were observed within the lamina propria of urinary bladder.Smooth muscle layer of lamina propria was seen in 48 of 54 cases(88.8%), and these smooth muscle fibres were co-existed with thickwalled vessels. In invasive urothelial carcinoma; thin smooth musclefibres and thick walled vessels were seen within the lamina propria in22 of 24 cases (91.7%). There were two cases (8.3%)including only vessels in small biopsies of invasive urothelialcarcinoma cases. In cases with non-invasive urothelial carcinoma; musclefibres of muscularis mucosa and vessels were found within the laminapropia in 26 of 30 cases (86.7%). In this group, muscle fibreswere not detected in 4 cases (13.3%). Conclusion:Muscularis mucosa can be detected histologically in urinary bladderbiopsies and TUR materials. We emphasize that the presence of vascularnetwork is a useful criterion to determine muscularis mucosa of urinarybladder, even in the absence of muscle fibres.     

Behavior of urothelial carcinoma with respect to anatomical location

PURPOSE: Urothelial carcinoma is a disease of the entire urothelium. Recent molecular insights suggest that the biology of some upper urinary tract and bladder urothelial carcinoma differ. These differences may affect tumor phenotype. Observational studies conflict as to the significance of anatomical location on the behavior of urothelial carcinoma. We compared the biological outcome in a large series of urothelial carcinoma with respect to anatomical location. MATERIALS AND METHODS: We analyzed urothelial carcinoma in 425 patients treated at 4 centers according to stage and anatomical location, including the bladder in 275, the ureter in 67 and the renal pelvis in 79. Relapse surveillance was performed for a median of 46 months (range 2 to 216). A separate invasive bladder urothelial carcinoma population was also included to pathologically balance upper and lower tract urothelial carcinoma cases to allow behavioral comparisons. RESULTS: As a whole, upper urinary tract urothelial carcinoma is more invasive and worse differentiated than bladder cancer (chi-square test p<0.0001 and 0.015, respectively). In pathologically matched cohorts recurrence to less aggressive disease, progression to more advanced disease and death occurred in 37%, 40% and 44% of patients with bladder urothelial carcinoma, and in 41%, 44% and 43% of those with upper urinary tract urothelial carcinoma, respectively. Multivariate analysis revealed that tumor stage and grade (Cox p=0.0001 and 0.012, respectively) but not location were associated with behavior. CONCLUSIONS: Urothelial carcinoma behaves identically in the upper and lower urinary tracts when stage and grade are considered. The majority of tumors relapse within 5 years of excision. The current move to minimally invasive/nephron sparing techniques for urothelial carcinoma of the upper urinary tract appears safe. Care could be analogous to that for bladder urothelial carcinoma.     

Inverted papilloma of the bladder: A review and an analysis of the recent literature of 365 patients

ObjectivesUntil the 1970s, inverted urothelial papilloma (IUP) of the bladder was generally regarded as a benign neoplasm. However, in the 1980s, several reported cases suggested the malignant potential of these papillomas, including cases with features indicative of malignancy, recurrent cases, and cases of IUP synchronous or metachronous with transitional cell carcinoma. The aim of this systematic review and analysis of the literature since 1990 to date is to contribute to unresolved issues regarding the biological behavior and prognosis of these neoplasms to establish some key points in the clinical and surgical management of IUP.Materials and methodsDatabase searches yielded 109 references. Exclusion of irrelevant references left 10 references describing studies that fulfilled the predefined inclusion criteria.ResultsOne problem regarding these neoplasms is the difficulty of obtaining a correct histopathologic diagnosis. The main differential diagnosis is endophytic urothelial neoplasia, including papillary urothelial neoplasia of low malignant potential or urothelial carcinoma of low or high grade, while other considerably rare differential diagnoses include nephrogenic adenoma, paraganglioma, carcinoid tumor, cystitis cystica, cystitis glandularis, and Brunn's cell nests. The size of the lesions ranged from 1 to 50 mm (mean 12.8 mm). Most cases occurred in the fifth and sixth decade of life. The mean age of affected patients was 59.3 years (range 20–88 years). Analysis of the literature revealed a strong male predominance with a male/female ratio of 5.8:1. The most commonly reported sites of IUP were the bladder neck region and trigone. Of 285 cases included in 8 studies, 12 cases (4.2%) were multiple. Out of the total of 348 patients, 6 patients (1.72%) had a previous history of transitional cell carcinoma of the urinary bladder, 5 patients (1.43%) had synchronous transitional cell carcinoma of the urinary bladder, and 4 patients (1.15%) had subsequent transitional cell carcinoma of the urinary tract. The time before recurrence was <45 months (range 5–45 months, mean 27.7 months) after surgery.ConclusionsInverted papilloma could be considered a risk factor for transitional cell carcinoma, and it is clinically prudent to exclude transitional cell cancer when it is diagnosed. Follow-up is needed if the histologic diagnosis is definitive or doubtful. We recommend 4-monthly flexible cystoscopy for the first year and then every 6 months for the subsequent 3 years. Routine surveillance of the upper urinary tract in cases of inverted papilloma of the lower part of the urinary tract is not deemed necessary.     

Micropapillary carcinoma of the urinary bladder: a case report and review of the literature

Micropapillary carcinoma is an uncommon variant of urothelial carcinoma with high metastatic potential. The presence of micropapillary carcinoma component in bladder biopsies should alert urologists to its aggressive behaviour. We report the case of a 70-year-old man who presented with macroscopic hematuria lasting 2 weeks. Magnetic resonance imaging revealed a bladder tumour in the dome area extended to perivascular adipose. The transurethral biopsy showed a high-grade micropapillary carcinoma with muscle invasion. Radical cystectomy with lymph node dissection was then performed. The pathological examination revealed a high-grade purely micropapillary carcinoma invading the perivesical adipose. No tumour recurrence or metastasis were reported at the 6-month follow-up.     

Overexpression of p27kip1 in urinary bladder urothelial carcinoma

OBJECTIVES: Cyclins and cyclin-dependent kinase (CDK) complexes have important regulatory roles during cell cycle progression and can be used as prognostic markers in various kinds of malignant tumors. This study investigated the expression of proliferative cell nuclear antigen (PCNA), p53, Rb, p27(kip1), and cyclin D1 by immunostains in bladder tumors, especially urothelial papilloma, papillary urothelial neoplasm of low malignant potential, and low and high grade urothelial carcinoma, to see if their expression is associated with classification or grading of the urinary bladder urothelial carcinoma. METHOD: Nuclear expression of PCNA, p53, Rb, p27(kip1), and cyclin D1 was determined immunohistochemically in a series of 89 urinary bladder tumor specimens, including 13 papilloma, 15 urothelial neoplasm of low malignant potential, 17 low grade urothelial carcinoma, and 44 high grade urothelial carcinoma. The results of immunoreactivity were analyzed with respect to the associations with tumor grade. RESULTS: Eighty-two percent (38/45) of the p27(kip1) positive tumors were urothelial carcinoma, and the percentage of the p27(kip1) positivity was higher with increasing grade of the urothelial carcinoma (P = 0.011). A tendency of higher percentage of positive p53 immunoreactivity was noted in the urothelial carcinoma (P = 0.053). There was no significant difference in cyclinD1, Rb and PCNA expression between benign, low malignant potential and urothelial carcinoma. CONCLUSION: We first noted an overexpression of p27(kip1) in urinary bladder urothelial carcinoma. The result indicates that some urothelial carcinomas may tolerate this inhibitor of cell cycle progression.     

Solitary abdominal wall metastasis from a urothelial carcinoma of the urinary bladder

Few cases of abdominal wall metastasis from a urothelial carcinoma were reported in the literature, and those were mostly attributed to iatrogenic implantation after laparoscopic surgery or a percutaneous nephrostomy. An 85-year-old man presented with an infraumbilical mass 6 months after transurethral resection of a bladder tumor (TURBt) for a T4 urinary bladder urothelial carcinoma. Abdominal sonography disclosed a 1.6 cm × 1.5 cm subcutaneous hypoechoic lesion. Wide excision of the mass was performed, and skin flaps were used for skin coverage. A combination of the patient's clinical history, tumor morphology, and immunostaining results were compatible with the pathologic characteristic of his previous bladder urothelial carcinoma. We present this rare case of solitary abdominal wall mass metastasis from a urothelial carcinoma of the urinary bladder.     

Epidemiology of urothelial carcinoma

The epithelium lining is defined as the mucosal surfaces of the renal collecting tubules, calyces and pelvis, as well as the ureter, bladder and urethra. The term “urothelium” is used to refer to these surfaces. Upper tract urothelial carcinoma is a rare subset of urothelial cancers with a poor prognosis. Urinary bladder cancer is the most common malignancy involving the urinary system. Upper tract urothelial carcinoma is more common in men than in women, with a male‐to‐female ratio of 2:1. The incidence of urinary bladder cancer is also higher in men. Cigarette smoking and occupational exposure are the main upper tract urothelial carcinoma and urinary bladder cancer risk factors, while other factors are more specific to the carcinogenesis of upper tract urothelial carcinoma (i.e. Balkan endemic nephropathy, Chinese herb nephropathy). In Egypt until recent years, urinary bladder cancer was the most frequently diagnosed cancer due to Schistosoma haematobium. Substantial knowledge exists regarding the causes of upper tract urothelial carcinoma and urinary bladder cancer, and epidemiological studies have identified various chemical carcinogens that are believed to be responsible for most cases of urothelial carcinoma. In the era of precision medicine, genetic effects might play a direct role in the initiation and progression of urothelial carcinoma.     

Serotonin used as prognostic marker of urological tumors

Introduction  In regard to therapy and prognosis of urological tumors, specific tumor markers are lacking especially in renal and urinary bladder carcinoma. Our study examines the relevance of serum serotonin levels to urinary bladder, prostate, renal, and testicular carcinoma when it comes to prognosis and occurrence of these oncological conditions. Materials and methods  Serotonin levels were obtained in 109 patients presenting with urothelial carcinoma to the urinary bladder, adenocarcinoma of the prostate and renal cell carcinoma, as well as presenting with seminomatous and non-seminomatous testicular tumors. All of these conditions varied in grades and metastases. Serum levels were drawn between 7 and 8 a.m. exclusively in order to avoid circadian changes. Results  Serotonin levels in urothelial carcinoma appeared within pathological range in correlation with tumor stage, life expectancy, and statistical significant with distant metastases. In prostate carcinoma, serotonin levels showed a tendency with organ exceeding growth, Grading/Gleason Score, PSA values >100 ng/ml, and the presence of distant metastases. In renal cell carcinoma, serotonin levels were decreased in patients with lymph node and distant metastases; there was no significant correlation with extent of infiltration. In regard to testicular carcinoma, decreased serotonin levels were merely noted in mixed tumors and the one extragonadal seminoma. Otherwise there was no correlation observed with stage and grade as well as with common tumor markers (AFP/βHCG). Conclusion  Serotonin levels are suitable for prognostic evaluation of urothelial carcinoma in the urinary bladder, adenocarcinoma of the prostate, and renal cell carcinoma, especially taking into account the lab cost of 25€ per test.     

Adjuvant methotrexate,vinblastine, adriamycin,and cisplatin chemotherapy has potential to prevent recurrence of bladder tumors after surgical removal of upper urinary tract transitional cell carcinoma

Objectives: To evaluate the efficacy of adjuvant platinum based chemotherapy in upper urinary tract urothelial cancer following surgical resection in terms of survival benefit and inhibition of bladder cancer recurrence. Methods: Between April 1986 and August 2005, a total of 132 patients with a diagnosis of upper urinary tract urothelial cancer underwent radical nephroureterectomy with cuff of bladder at our department. A total of 46 patients (13 with pT2pN0M0 and 33 with pT3 pN0M0 transitional cell carcinoma without prior bladder cancer) were enrolled. Patients with locally advanced disease were divided into two groups: the adjuvant chemotherapy group (24 patients) who received adjuvant methotrexate, vinblastine, adriamycin, and cisplatin (M‐VAC) and the non‐adjuvant chemotherapy group who did not receive adjuvant M‐VAC (22 patients). Results: There were no statistically significant differences in patient characteristics or 10‐year survival between the two groups. The recurrence rate in the non‐adjuvant chemotherapy group was significantly higher than in the adjuvant chemotherapy group (log‐rank test, P < 0.0001). Only non‐adjuvant chemotherapy was a significant and independent risk factor (hazard ratio 6.97) for the development of intravesical recurrence (P < 0.01). Conclusion: Adjuvant M‐VAC is an important optional adjuvant therapy and can prevent recurrent bladder tumors following surgery for upper urinary tract transitional cell carcinoma. To determine whether adjuvant chemotherapy has further benefit, a randomized study would be needed.     

The fate of an unsatisfactory urine cytology test among patients with urothelial carcinoma

OBJECTIVE

To determine the outcome of patients with a urinary cytology test that is unsatisfactory (UUCyt) for evaluation (<50 urothelial cells) to guide the clinical decision‐making process, as currently there are no guidelines to aid in interpreting this result and directing further investigations.

PATIENTS AND METHODS

We retrospectively reviewed 142 patients, with 265 instances of UUCyt, in our bladder cancer database and by chart review. The cytology, cystoscopy and pathology results in the subsequent 12 months after a UUCyt result were reviewed, and the incidence of new and recurrent genitourinary tract cancers was calculated.

RESULTS

All patients had a previous history of, or developed, urothelial carcinoma during the follow‐up. There were 41 instances (16.3%) in which bladder cancer was evident at the time of the UUCyt and 29% of these tumours were high‐grade. There were another 44 instances (17.5%) in which new or recurrent bladder cancer developed in the subsequent year after a UUCyt test, and many (38.6%) of these tumours were high‐grade.

CONCLUSION

The incidence of urothelial carcinoma after a UUCyt was high (33.9%) with a substantial number of high‐grade (34%) tumours, implying that a UUCyt result cannot be interpreted as negative for malignancy. Therefore, in these cases, the urologist must depend on cystoscopy to make a diagnosis.     

Urothelial carcinoma with trophoblastic differentiation: Reappraisal of the clinical implication and immunohistochemically features

PurposeTo investigate the clinical implications of identifying urothelial carcinoma (UC) with trophoblastic differentiation (UCTD).Materials and MethodsA prospective cohort study was performed from 2010 to 2016 to examine the incidence of UCTD in urinary tract cancer and association with clinicopathological indicators and patient outcome.ResultsUCTD was detected in 47 of 859 (5.5%) cases of UC of the bladder and 65 of 635 (10.2%) cases in the upper urinary tract. UCTD of the bladder was significantly associated with non-papillary, multiple, larger size ( > 3 cm), muscle invasion, and nodal metastasis (P ≤ 0.0001, respectively). A higher risk of recurrence (P = 0.005), progression (P < 0.0001), and patient death (P < 0.0001) was observed for UCTD than those with traditional, high-grade UC of the bladder. Among four patterns of expression, focal expression of β-human chorionic gonadotropin was frequently detected in papillary tumor (P < 0.005) and UCs of smaller than 3 cm (P = 0.03). Significant indicators in predicting poor disease-specific overall survival in multivariate statistical model were tumor staging (P = 0.001), followed by non-focal β-hCG expression (P = 0.049).ConclusionUCTD is more often identified in the upper urinary tract than in the bladder. UCTD of the bladder was significantly associated with higher risk of recurrence, progression, and patient death. Expression of β-hCG in non-focal patterns predicts a worse prognosis for patients with UCTD and deserves an individualized treatment planning.     

Rictor-dependent AKT activation and inhibition of urothelial carcinoma by rapamycin

ObjectiveWe previously reported a very high cumulative incidence of urothelial carcinoma in Taiwanese kidney transplant recipients. Rapamycin, the inhibitor of mTOR Complex 1, provides alternative immunosuppressive therapy after kidney transplantation with less neoplastic potential. We examined the in vivo and in vitro effects of rapamycin on urothelial carcinoma.Materials and methodsThe rat model of urothelial carcinoma was induced by 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in Fischer F344 rats. The anti-tumor effect of rapamycin was assessed grossly, microscopically, and by Western blot analysis. The mechanism of rapamycin's attenuation of urothelial carcinoma was also evaluated by T24 cells.ResultsRapamycin significantly reduced urinary bladder tumor growth in the rat model of 0.05% BBN-induced urothelial carcinoma (P < 0.001). The blood trough levels of rapamycin were correlated with the occurrence of urothelial carcinoma. In vitro, rapamycin also inhibited the cell proliferation, migration, and invasion, as well as the protein expression of vascular endothelial growth factor-A of T24 urothelial carcinoma cells, whereas rapamycin did not induce significant apoptosis in T24 cells. Rapamycin decreased the expression of phospho-mTOR, phospho-S6K, cyclin D1, and VEGF-A. Rapamycin also activated AKT in T24 cells in the rat model of urothelial carcinoma. The rapamycin-associated activation of AKT was inhibited by rictor siRNA, but not raptor siRNA.ConclusionsThis study provides in vitro and in vivo evidence that rapamycin may inhibit the development of urothelial carcinoma. The present findings also suggest rictor-dependent AKT activation as a consequence of mTORC1 inhibition.     

Variant histologies in bladder cancer: Does the centre have an impact in detection accuracy?

ObjectiveTo compare the accuracy in detecting variant histologies (VH) at transurethral resection of bladder (TURB) and radical cystectomy (RC) specimen among tertiary referral centres, in order to investigate potential reasons of discrepancies from the pathological point of view.Patients and MethodsClinical and histopathological data of TURB specimen and subsequent cystectomy specimen of 3,445 RC candidate patients have been retrospectively collected from 24 tertiary referral centres between 1980 and 2021. VH considered in the analysis were pure squamous cell carcinoma, urothelial carcinoma with squamous differentiation, pure adenocarcinoma, urothelial carcinoma with glandular differentiation, micropapillary bladder cancer (BCa), neuroendocrine BCa, and other variants. The degree of agreement between TURB and RC concerning the identification of VH was expressed as concordance, classified according to Cohen's kappa coefficient.ResultsA VH was reported in 17% of TURB specimens, 45% of which were not confirmed in RC. The lowest concordance rate was reported for micropapillary BCa with 11 out of 18 (61%) centres reporting no agreement, whereas neuroendocrine BCa achieved the highest concordance rate with only 3 centres (17%) reporting no agreement. Our results shows that even among centres with the advantage of a referent uropathologist the micropapillary variant is characterized by scarce accuracy between TURB and RC. Differences in TURB specimen acquisition by the urologist and in sampling methods among different centres are the main limitations of the study.ConclusionsAccuracy of TURB in detecting VH is poor for certain VH, in particular for micropapillary BCa, with evident variation among centres. Novel diagnostic tools are required to better identify these VH and drive patients toward a personalized treatment.     

Oncological outcomes of concomitant carcinoma in situ at radical cystectomy in pure urothelial bladder cancer and in histological variants.

IntroductionThe presence of carcinoma in situ at transurethral resection is known to increase the risk of recurrence and progression to invasive disease. However, the evidence regarding the prognostic role of concomitant carcinoma in situ after radical cystectomy due to bladder cancer is controversial. Moreover, concomitant carcinoma in situ was found to be significantly associated with bladder histological variants. The aim of our study is to evaluate whether the presence of concomitant carcinoma in situ at radical cystectomy, impacts on recurrence and survival outcomes in pure urothelial bladder cancer, compared to histological variants.MethodsWe evaluated 410 consecutive patients diagnosed with non-metastatic bladder cancer and treated with radical cystectomy at a single tertiary referral centre between January 2009 and May 2019. Patients were stratified according to the presence of carcinoma in situ. The Kaplan-Meier method was used to compare recurrence free, cancer specific and overall survival in pure urothelial and histological variants. Cox proportional hazards regression analyses model was used to predict recurrence, cancer specific and overall mortality in pure urothelial and histological variants bladder cancer, according to pathological stage.ResultsMedian age was 71 years. 340 patients (82%) were male. At a median follow-up of 32 months, disease recurrence, cancer specific mortality and overall mortality were, 37% (155 patients), 32.9% (135 patients) and 46.6% (191 patients), respectively. Concomitant and pure carcinoma in situ were found in 39% and 19% of radical cystectomy specimens, respectively. Concomitant carcinoma in situ was more frequent in patients with histological variants (50.9%) compared to pure urothelial bladder cancer (35.4%) (P-value <.001) and was associated with worst pathological features (lymphovascular invasion, lymph node involvement and non-organ confined disease).Recurrence free survival at Kaplan-Meyer analyses was significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001), similarly for patients without carcinoma in situ compared with those with concomitant Cis (P =.02) at radical cystectomy. Cancer specific and overall survival were significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001). Conversely no significant difference was found between patients without carcinoma in situ and with concomitant carcinoma in situ (P>0.1) at radical cystectomyMoreover, concomitant carcinoma in situ at radical cystectomy in histological variants is associated with higher free recurrence rate compared to the other groups. At multivariate Cox proportional hazards regression analyses the presence of carcinoma in situ at radical cystectomy was not associated with any survival effect or recurrence (all P > .05) in the overall population and when patients are stratified according to histology. However, concomitant carcinoma in situ represents an independent predictor of recurrence in the subgroup of patients with organ confined disease in case of urothelial bladder cancer and histological variants.ConclusionConcomitant carcinoma in situ should be considered a proxy of aggressiveness in bladder cancer after radical cystectomy. Based on its prognostic implications, concomitant carcinoma in situ should be considered for strict follow-up in patients with organ confined disease which may deserve adjuvant treatment both in pure urothelial bladder cancer and histological variants.     

MICROPAPILLARY BLADDER CARCINOMA: A CLINICOPATHOLOGICAL STUDY OF 20 CASES

PURPOSE: Micropapillary bladder carcinoma is rare, with only 18 cases reported to date. We report 20 additional cases with long-term followup. MATERIALS AND METHODS: A total of 680 patients with an initial diagnosis of bladder carcinoma in western Sweden in 1987 and 1989 were prospectively registered. The clinical records of all 816 patients with bladder cancer treated at Sahlgrenska University Hospital with external beam irradiation between 1962 and 1989 were reviewed. The histopathological material was reviewed and immuno-histochemical analyses were performed on 20 cases identified with micropapillary bladder carcinoma. RESULTS: The incidence of micropapillary bladder carcinoma was 0.7%. Mean patient age at diagnosis was 69 years (range 45 to 82) and the male-to-female ratio was 2.3:1. All but 5 patients had stage T3a disease or higher. There was no difference in stage or prognosis between the 5 prospectively identified patients and those treated with external beam irradiation. Only 2 patients had micropapillary bladder carcinoma as the only pattern, while 1 had 10% and the remainder had 20 to 95% micropapillary bladder carcinoma. Transitional cell carcinoma was noted in 17 patients and 5 had areas of gland forming adenocarcinoma. Carcinoma in situ was noted in 13 patients and 15 had lymphatic invasion. Only 5 patients survived 5 years, 1 of whom died of bladder cancer after 7 years. Radiation and chemotherapy did not seem to be effective. CONCLUSIONS: The light microscopic appearance, which is strikingly similar to ovarian papillary serous carcinoma, and immunohistochemical staining pattern lend some support to the theory that micropapillary bladder carcinoma is a variant of adenocarcinoma. Since even the focal presence of micropapillary bladder carcinoma is associated with a poor prognosis, recognition of this entity is important. Due to its rarity, the optimal treatment of micropapillary bladder carcinoma needs to be determined in a multicenter study.     

Invasive micropapillary carcinoma of the urinary bladder: An immunohistochemical study of neoplastic and stromal cells

A 66-year-old man complained of hematuria. A cystoscopy revealed a non-papillary tumor and radical cystectomy was performed. Macroscopically, an ulcerative lesion was observed. Microscopically, the neoplasm showed a mixture of urothelial carcinoma, squamous cell carcinoma and micropapillary carcinoma. Immunohistochemically, micropapillary carcinoma cells were positive for cytokeratins 7 and 20, carcinoembryonic antigen and CA125. Additionally, myofibroblasts were distributed in a chicken-wire pattern in the stroma of micropapillary carcinoma. Subsequently, the patient died of carcinoma 1 year after the onset of symptoms. Our results support the previous hypothesis that bladder micropapillary carcinoma runs an aggressive clinical course and suggest that micropapillary carcinoma may show the glandular differentiation of urothelial carcinoma and show the stromal reaction by myofibroblasts resembling that of carcinoma in other anatomic sites.     

In situ adenocarcinoma of the bladder.

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

Bacillus Calmette-Guérin Failure in Patients with Non–Muscle-invasive Urothelial Carcinoma of the Bladder May Be Due to the Urologist's Failure to Detect Urothelial Carcinoma of the Upper Urinary Tract and Urethra

BackgroundVarious reasons exist for so-called bacillus Calmette-Guérin (BCG) failure in patients with non–muscle-invasive urothelial bladder carcinoma (NMIBC).ObjectiveTo explore whether urothelial carcinoma of the upper urinary tract (UUT) and/or prostatic urethra may be a cause for BCG failure.Design, setting, and participantsRetrospective analysis of 110 patients with high-risk NMIBC repeatedly treated with intravesical BCG, diagnosed with disease recurrence, and followed for a median time of 9.1 yr.InterventionTwo or more intravesical BCG induction courses without maintenance.Outcome measurements and statistical analysisPrimary outcome was pattern of disease recurrence (BCG failure) within the urinary tract categorised into UUT and/or urethral carcinoma (with or without intravesical recurrence), and intravesical recurrence alone. Secondary outcome was survival. Predictors of UUT and/or urethral carcinoma and the effect of pattern of disease recurrence on cancer-specific survival were assessed with multivariable Cox regression analysis adjusting for multiple clinical and tumour characteristics.Results and limitationsOf the 110 patients, 57 (52%) had UUT and/or urethral carcinoma (with or without intravesical recurrence), and 53 (48%) had intravesical recurrence alone. In patients with UUT and/or urethral carcinoma, bladder carcinoma in situ (Tis) before the first and second BCG course was present in 42 of 57 (74%) and 47 of 57 (82%) patients, respectively. On multivariable analysis, bladder Tis before the first and/or second BCG course was the only independent predictor of UUT and/or urethral carcinoma. Of the 110 patients, 69 (63%) were alive at last follow-up visit, 18 (16%) had died due to metastatic urothelial carcinoma, and 23 (21%) had died of other causes. Pattern of disease recurrence within the urinary tract was not an independent predictor of cancer-specific survival. Main study limitations were retrospective design and limited power for survival analysis.ConclusionsIn our patients with high-risk NMIBC failing after two or more courses of intravesical BCG, UUT and/or urethral carcinoma was detected in >50% of the cases during follow-up. The vast majority of these patients had bladder Tis before the first and/or second BCG course. In patients experiencing the so-called BCG failure, a diagnostic work-up of UUT and prostatic urethra should always be performed to exclude urothelial carcinoma before additional intravesical therapy or even a radical cystectomy is considered.