Papillary Urothelial Carcinoma Research Articles

Low-Grade Papillary Urothelial Carcinoma of the Urinary Bladder: A Clinicopathologic Analysis of a Post–World Health Organization/International Society of Urological Pathology Classification Cohort From a Single Academic Center

Few large cohort studies have addressed outcome in patients with noninvasive low-grade papillary urothelial carcinoma (LG-UrCa) following implementation of the 2004 World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification. To evaluate our cohort of LG-UrCa cases classified according to 2004 WHO/ISUP to reassess outcome and interobserver agreement. Files were searched for all patients diagnosed with LG-UrCa between 1998 and 2008. All sections were reevaluated for accuracy of classification. A total of 112 cases initially diagnosed as LG-UrCa were identified. Of those, 8 of 55 cases (15%) initially diagnosed by nonurologic pathologists were reclassified as high-grade papillary urothelial carcinoma and were excluded. The mean length of follow-up was 40.1 months (range, 2-113 months). Tumor recurrence was encountered in 56 of 104 patients (53.8%), including 37 (35.6%) with LG-UrCa or lower-grade tumors and 19 (18.3%) with high-grade papillary urothelial carcinoma. Of the 19 patients demonstrating grade progression, 7 (37%) also developed stage progression (invasive carcinoma, n = 5; metastatic carcinoma, n = 2). Seven patients eventually underwent radical cystectomy. None of the 104 patients died of bladder cancer. The mean number of recurrence episodes was 3.11. The mean durations of time to first recurrence and time to grade progression were 13.9 months and 25.1 months, respectively. The mean size of initial tumors was 1.73 cm. There was no significant correlation between tumor size, patient age, sex, or smoking history and the likelihood for recurrence or grade progression. A significantly higher rate of recurrence was seen in patients with multiple tumors at initial diagnosis (P = .04). A tendency to underdiagnose high-grade papillary urothelial carcinoma continues to exist. More than half (53.8%) of patients with LG-UrCa developed recurrence, with an 18.3% incidence of grade progression and a 6.7% incidence of stage progression. Patients with multiple initial tumors had significantly higher risk of developing recurrence.

Low-grade papillary urothelial carcinoma of the urinary bladder: a clinicopathologic analysis of a post-world health organization/international society of urological pathology classification cohort from a single academic center

AJR Am J Roentgenol. 2010; 194: W316-22.Objective: The objective of our study was to determine the relationship between the apparent diffusion coef-ficient (ADC) value on diffusion-weighted imaging (DWI) and Gleason score of prostate cancer and percentage of tumor involvement on prostate core biopsy. Materials and Methods: We performed a retrospective study of 57 patients with biopsy-proven prostate cancer who underwent endorectal MRI with DWI between July 2007 and March 2008. Regions of interest (ROIs) were drawn on ADC maps at sites of visible tumor on DW images and ADC maps. A hierarchic mixed linear model was used to compare the ADC value of prostate cancer with the Gleason score and the percentage of tumor on core biopsy. Results: Eighty-one sites of biopsy-proven prostate cancer were visible on DW images and ADC maps. The least-squares mean ADC for disease with a Gleason score of 6 was 0.860 x 10(-3) mm(2)/s (standard error of the mean [SEM], 0.036); Gleason score of 7, 0.702 x 10(-3) mm(2)/s (SEM, 0.030); Gleason score of 8, 0.672 x 10(-3) mm(2)/s (SEM, 0.057); and Gleason score of 9, 0.686 x 10(-3) mm(2)/s (SEM, 0.067). Differ-ences between the mean ADC values for a prostate tumor with a Gleason score of 6 and one with a Gleason score of 7 (p = 0.0096) and for a prostate tumor with a Gleason score of 6 and one with a Gleason score of 8 (p = 0.0460) were significant. Comparison between the ADC and percentage of tumor on core biopsy showed a mean ADC decrease of 0.006 (range, 0.004-0.008 x 10(-3) mm(2)/s) for every 1% increase in tumor in the core biopsy specimen. Conclusion: DWI may help differentiate between low-risk (Gleason score, 6) and intermediate-risk (Gleason score, 7) prostate cancer and between low-risk (Gleason score, 6) and high-risk (Gleason score > 7) prostate cancer. There is an inverse relationship between the ADC and the percentage of tumor involvement on prostate core biopsies.

Expression of Gap Junction Protein Connexin 43 in Bovine Urinary Bladder Tumours

The aetiopathogenesis of urinary bladder tumours in cattle involves prolonged ingestion of bracken fern and infection by bovine papillomavirus types 1 or 2 (BPV-1/2). The oncogenic activity of BPV is largely associated with the major oncoprotein E5. Gap junctions are the only communicating junctions found in animal tissues and are composed of proteins known as connexins. Alterations in connexin expression have been associated with oncogenesis. The present study investigated biochemically and immunohistochemically the expression of connexin 43 in samples of normal (n=2), dysplastic (n=3) and neoplastic (n=23) bovine urothelium. The tumours included 10 carcinomas in situ, five papillary urothelial carcinomas and eight invasive urothelial carcinomas. Normal and dysplastic urothelium had membrane expression of connexin 43, but this was reduced in samples of carcinoma in situ. Papillary urothelial carcinomas showed moderate cytoplasmic and membrane labelling, while invasive carcinoma showed loss of connexin 43 expression.

Feasible Method to Successfully Uncover a Urothelial Carcinoma in the Urinary Bladder on the FDG PET/CT Scan Masked by Physiological Urine Radioactivity

A 71-year-old man asked for a F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan for follow-up of the renal cell carcinoma of right kidney after nephrectomy 2 years ago. Except for normal radioactivity outside the urinary system, however, a CT abnormality in the urinary bladder was noted but its character of metabolic activity was interfered with by the abundant physiological urine FDG radioactivity. After a simple procedure with intravenous administration of diuretics and asking the patient to hold his urine, the lesion emerged as an area of focal intense radioactivity after the dilute effect of the urine. The subsequent histologic examination via the cystoscopic biopsy revealed papillary urothelial carcinoma.

The origins of urothelial carcinoma

It is now widely believed that there are two major pathways for urothelial carcinogenesis. One pathway usually involves mutation of FGF receptor 3 and gives rise to low-grade papillary tumors that frequently recur but seldom invade. By contrast, high-grade urothelial malignancies, including high-grade papillary urothelial carcinoma and urothelial carcinoma in situ (CIS) usually exhibit deletions or mutations of TP53. Urothelial CIS is the most likely precursor of high-grade invasive bladder cancer. It is a ‘flat lesion’ that may be relatively inconspicuous at cystoscopy, or even endoscopically undetectable. The clinical hazards associated with this elusive and biologically dangerous neoplasm have been increasingly well documented since the original studies by Melicow in 1952. Primary or secondary urothelial dysplasia is even more challenging to detect and diagnose than CIS. It is theorized that dysplasia may antedate the onset of CIS, but support for the putative progression of dysplasia to CIS is found in fewer than 20% of cases. Since many benign urothelial changes may resemble CIS at cystoscopy, in biopsies and even with molecular profiling, care must be exercised when making a diagnosis of CIS. For patients whose screening tests are worrisome for the presence of premalignant urothelial disease, newer bladder imaging modalities, including Raman spectral imaging and optical coherence tomography, may enable improved biopsy site selection. In this article, we discuss the above-noted topics, as well as other related issues, such as the possible role of papillary urothelial hyperplasia as a preneoplastic lesion and the roles of cancer stem cells and field cancerization in urothelial carcinogenesis.

Diagnosis and Classification of Flat, Papillary, and Invasive Urothelial Carcinoma: The WHO/ISUP Consensus

Diagnosis and Classification of Flat, Papillary, and Invasive Urothelial Carcinoma: The WHO/ISUP Consensus

Prognostic Significance of the 2004 WHO/ISUP Classification for Prediction of Recurrence, Progression, and Cancer-Specific Mortality of Non–Muscle-Invasive Urothelial Tumors of the Urinary Bladder

To verify prognostic significance of the 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading systems, we retrospectively studied the tumors of 1,515 patients who underwent transurethral resection of primary non-muscle-invasive urothelial tumors (pTa, 1,006 patients; pT1, 509 patients) confined to the bladder. Cases were classified according to the 2004 WHO/ISUP systems as 212 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP), 706 low-grade papillary urothelial carcinomas (LPUCs), and 597 high-grade papillary urothelial carcinomas (HPUCs). PUNLMP showed the statistically significantly lowest recurrence cumulative incidence compared with the other tumor types. There were significant differences and trends for higher progression and cancer-specific mortality cumulative incidence in the following order: PUNLMP, LPUC, pTa HPUC, and pT1 HPUC. No differences of progression and cancer-specific mortality cumulative incidence were found between pTa and pT1 LPUC. Our study validates the usefulness of the 2004 WHO/ISUP system to classify urothelial tumors into prognostically distinct categories that would contribute to the design of therapeutic and monitoring strategies for patients with non-muscle-invasive bladder urothelial tumors.

Evolution on experimental animal model for upper urothelium carcinogenesis

No optimal, well designed and reproducible animal model for upper urothelial carcinogenesis exists. This study characterized the histopathological features on top of immunolocalization of alpha-dystroglycans (alpha-DG) and matrix metalloproteinase (MMP-9) and cell turn-over in the upper urinary tract using a novel experimental model. Seventy-five female Fischer 344 rats were divided into three groups: the control group received a 0.30-ml dose of 0.9% physiological saline; the MNU group (chemical carcinogen N-methyl-N-nitrosourea) received 0.30 ml of MNU; and the MNU-citrate group received 0.30 ml of MNU plus sodium citrate, every one intravesically every other week for a total of 4 doses. After 15 weeks, bladder, ureters and renal pelvis were collected for morphological and molecular analysis. Associated management with MNU and sodium citrate was able to lead to 100% of both urinary bladder and upper urinary tract tumors, being the high-grade noninvasive papillary urothelial carcinoma the most frequent lesion. The upper urothelium showed reduced alpha-DG and increased MMP-9 and Ki-67 immunoreactivities in the MNU-citrate group in relation to the other groups. MNU group presented no upper urothelium tumor and 100% bladder tumor. This is a relevant evolution on experimental animal model for upper urinary tract carcinogenesis field. MMP-dependent disruption of the DG complex plays an important role in urothelial tumor carcinogenesis and showed the model applicability and significance. MNU-citrate model could contribute to a better understanding of human upper urothelial cancer development as well as to its local treatment strategies in a near future.

908 EVALUATION OF ADEQUACY OF PATHOLOGIC SPECIMENS USING A NOVEL BACKLOADING URETEROSCOPIC BIOPSY FORCEPS

You have accessJournal of UrologyTechnology & Instruments: Robotics/Laparoscopy/Ureteroscopy II1 Apr 2010908 EVALUATION OF ADEQUACY OF PATHOLOGIC SPECIMENS USING A NOVEL BACKLOADING URETEROSCOPIC BIOPSY FORCEPS Shaun Wason, Alan Schned, John Seigne, and Vernon Pais Shaun WasonShaun Wason More articles by this author , Alan SchnedAlan Schned More articles by this author , John SeigneJohn Seigne More articles by this author , and Vernon PaisVernon Pais More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1664AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Quality of ureteroscopic biopsies may be limited by the small specimen size. Dictated by the working channel of the ureteroscope, biopsy forceps of 3fr have less than 1mm3 of biopsy head volume. Utilizing a backloading design, the BIGopsy™ ureteroscopic biopsy forceps has a biopsy head larger than the working channel of the ureteroscope. Recognizing that small biopsied tissue volume may preclude adequate pathologic evaluation, we sought to assess the adequacy of surgical specimens obtained utilizing the BIGopsy™ forceps. METHODS In accordance with our IRB, patients undergoing nephroureterectomy for suspected upper tract TCC were recruited. Surgical specimens, immediately after extirpation were examined. The most clinically suspicious region to gross examination was alternatively biopsied with a 3fr Piranha® followed by the BIGopsy™ biopsy forceps. These specimens were fixed, stained and evaluated by a single pathologist. Biopsy size and qualitative assessment of specimen adequacy were recorded. Pathologic diagnosis of the biopsy specimens were compared to the final pathologic diagnosis. RESULTS Three nephroureterectomy specimens were evaluated. A total of 6 biopsies were obtained from the Piranha® and 5 biopsies from the BIGopsy™. Biopsy size from the Piranha® ranged from 1 to 8mm2, while those from the BIGopsy™ ranged from 6 to 80mm2. Average biopsy size from the Piranha® was 3.5 +/- 2.8mm2 while the average biopsy size from the BIGopsy™ was 31.2 +/-34.6mm2. In 2 of 3 nephroureterectomy specimens, final diagnosis was high grade papillary urothelial carcinoma in accordance with both the Piranha® and BIGopsy™ specimens. In the third specimen, the final diagnosis was benign polypoid/papillary pyelitis consistent with only the BIGopsy™ specimen, while the Piranha® specimen was suspicious for a low grade papillary lesion. Subjectively, the BIGopsy™ specimens revealed less distortion and fragmentation and were easier to interpret by the pathologist. Smooth muscle was contained in 1 of 3 BIGopsy™ specimens and in none of the Piranha® specimens. CONCLUSIONS The BIGopsy™ backloading biopsy forceps allows removal of ureteral and renal pelvic tissue larger than the standard 3fr biopsy forceps. In all 3 cases, the diagnosis based upon the BIGopsy™ biopsy agreed with the final pathologic report, one of which was pathologically misassigned as malignant by the smaller 3fr Piranha® biopsy forceps specimen. Improved biopsy quality may translate into improved ability to diagnose ureteral and renal pelvic mucosal lesions endoscopically. Lebanon, NH© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e354-e355 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shaun Wason More articles by this author Alan Schned More articles by this author John Seigne More articles by this author Vernon Pais More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Robotic Distal Ureterectomy with Boari Flap Reconstruction for Distal Ureteral Urothelial Cancers: A Single Institutional Pilot Experience

Low-grade urothelial tumors of the distal ureter historically can be managed by open distal ureterectomy and ureteral reimplantation with or without bladder reconstruction. In recent years, the da Vinci surgical robotic system (DSRS) (Intuitive Surgical Inc., Sunnyvale, CA) has being increasingly used to perform complex urologic cancer surgeries. In this article, we report first on two consecutive patients undergoing robotic distal ureterectomy and Boari flap reconstruction (RDUBF) for distal ureteral cancer. Two consecutive patients underwent RDUBF, both with a diagnosis of low-grade papillary neoplasm of a distal ureter at our institution between August 2008 and November 2008. Perioperative parameters were prospectively collected and analyzed following institutional review board approval. Two patients, male and female (age, 70 and 71 years, respectively) were included in the study. In both the patients, RDUBF was completed transperitoneally without the need for open conversion. The operative time, estimated blood loss, time to hospital discharge, and time to stent removal for both patients were 270 and 220 minutes, 25 and 35 mL, and 2 days and 6 weeks, respectively. The percentage change in hematocrit following surgery was within 5% in all patients. There were no postoperative complications in both patients. Final pathology demonstrated low-grade carcinoma pT1NxMx and pTaNxMx papillary urothelial carcinoma with negative margins in both patients. A MAG3 (mercapto-acetyl-tri-glycine) renal scan at 3 months demonstrated prompt drainage in both patients. At a median follow-up of 6 months, the patients were alive with no signs of recurrent or metastatic disease on cystoscopic, cytologic, or radiologic follow-up. RDUBF reconstruction is technically feasible with using DSRS in select patients with distal ureteral cancer without disease recurrence in the short term. A larger cohort, with long-term follow-up, is necessary to validate our results.

Robotic Partial Cystectomy for Bladder Cancer: A Single-Institutional Pilot Study

Open partial cystectomy has been used as a curative option for select group of patients with bladder cancer. In recent years, the da Vinci Surgical Robotic System is being increasingly used to perform complex urologic cancer surgeries. We report first on a consecutive cohort of patients undergoing robotic partial cystectomy (RPC) for bladder cancer. Three consecutive patients underwent RPC, two with diagnosis of papillary neoplasm of bladder and one with urachal adenocarcinoma at our institution from July 2008 to January 2009. Perioperative parameters were prospectively collected and analyzed after Institutional Review Board approval. All three patients in the study were men with a median age of 50 years (range, 24-70 years). The RPC was completed transperitoneally in all three patients without the need for open conversion. The operative time, estimated blood loss, and time to hospital discharge for the three patients undergoing RPC were 185, 135, and 165 minutes; 25, 20, and 20 mL; and 5, 2, and 2 days, respectively. The percentage change in hematocrit after surgery was within 5% in all patients. There were no postoperative complications before discharge; however, one patient was readmitted and underwent small bowel resection secondary to bowel obstruction. Final pathology demonstrated high-grade carcinoma pT2bNxMx and pTaNxMx papillary urothelial carcinoma in two patients and invasive adenocarcinoma of the bladder pT3aNxMx in the remaining patient. The median follow-up was 6 months (range, 3-10 months). All three patients were alive with no signs of recurrent or metastatic disease on cystoscopic, cytological, or radiological follow-up. RPC is technically feasible using the da Vinci Surgical Robotic System in select patients with bladder cancer without disease recurrence in the short term. A larger cohort with long-term follow-up is necessary to validate our results.

Urine and bladder washing cytology for detection of urothelial carcinoma: standard test with new possibilities

BackgroundLight microscopic evaluation of cell morphology in preparations from urine or bladder washing containing exfoliated cells is a standard and primary method for the detection of bladder cancer and also malignancy from other parts of the urinary tract. The cytopathologic examination is a valuable method to detect an early recurrence of malignancy or new primary carcinoma during the follow-up of patients after the treatment of bladder cancer.ConclusionsCharacteristic cellular and nuclear signs of malignancy indicate invasive or in situ urothelial carcinoma or high-grade papillary urothelial carcinoma. However, low sensitivity of the method reflects the unreliable cytopathologic diagnosis of low-grade urothelial neoplasms as cellular and nuclear signs of malignancy in these neoplasms are poorly manifested. Many different markers were developed to improve the diagnosis of bladder carcinoma on urinary samples. UroVysion™ test is among the newest and most promising tests. By the method of in situ hybridization one can detect specific cytogenetic changes of urothelial carcinoma.

Urinary bladder carcinoma with triplicate differentiations into giant cell sarcomatoid carcinoma, squamous cell carcinoma, and papillary urothelial transitional cell carcinoma: a case report

The author reports a very rare and very unique urinary bladder carcinoma. This carcinoma occurred in a 68-year-old Japanese patient who underwent cystectomy for bladder tumor. The tumor was large polypoid and ulcerated one. Histologically, the tumor consisted of the following three elements: giant cell sarcomatoid carcinoma (70% in area), squamous cell carcinoma (20% in area), and papillary urothelial transitional cell carcinoma (10% in area). The former two elements were invasive into the peribladder fat tissue, while the latter one element invaded into the submucosa. There were gradual merges between the giant cell sarcomatoid element and squamous cell carcinoma element. Apparent transitions were not seen between the transitional cell carcinoma element and the giant cell sarcomatoid element or the squamous cell carcinoma element. Immunohistochemically, the giant cell sarcomatoid element was positive for various kinds of cytokeratins and vimentin while the squamous and transitional cell carcinoma elements were positive for various kinds of cytokeratins and negative for vimentin. The giant cell sarcomatoid element was free of other specific antigens. The author speculates that giant cell sarcomatoid carcinoma transdifferentiates into squamous cell carcinoma, and vice versa. The relationship between transitional cell carcinoma and the other two elements is unclear in the present case.

Fine needle aspiration of renal cortical lesions in adults

The role of fine needle aspiration (FNA) biopsy of renal cortical lesions was controversial in the past because the result of the FNA did not affect clinical management. All renal cortical lesions, except metastasis, were subject to surgical resection. However, with the advances in neoadjuvant targeted therapies, knowledge of the renal cortical tumor histological subtype is critical for tailoring clinical trials and follow-up strategies. At present, there are clinical trials involving the use of novel kinase inhibitors for conventional (clear cell) and papillary renal cell carcinoma. We studied 143 consecutive cases of renal cortical lesions, evaluated after radical or partial nephrectomies over a 2-year period. An air-dried smear and a Thinprep® slide were prepared in all cases. The slides were Diff-Quick and Papanicolaou stained, respectively. The cytology specimens were reviewed and the results were then compared with the histologic diagnosis. Cytology was highly accurate to diagnose conventional RCC, while the accuracy for papillary RCC, chromophobe RCC, and papillary urothelial carcinoma was much lower. Our results indicate that ancillary studies might have an important role in the subclassification of renal cortical neoplasms for targeted treatment.

CIS is a surrogate marker of genetic instability and field carcinogenesis in the urothelial mucosa

Objective To investigate whether carcinoma in situ (CIS) lesion could be considered a surrogate marker of urothelium genetic instability and field carcinogenesis or not, we evaluated DNA content, p53 overexpression, and proliferative index (Ki-67 expression) in primary tumor, in tumor-adjacent mucosa, and distant urothelial mucosa with and without presence of CIS. Patients and methods A retrospective study in radical cystectomy specimens from 49 patients was carried out. All the lesions present in each cystectomy specimen were studied, including the tumor area and the adjacent mucosa (AM). Whenever possible, the distant mucosa (DM) was also studied. When CIS was detected, this lesion and the surrounding normal mucosa were also studied. The 49 tumor areas included high grade papillary urothelial carcinoma (HGP) in 19 cases (38.8%) and invasive urothelial cell carcinomas in 30 cases (61.2%). The nuclear DNA content of cancer cells was evaluated using image cytometry allowing the determination of the DNA ploidy and 5cER parameters. The p53 and Ki-67 immunoexpression was evaluated by immunohistochemistry. Results CIS lesions were observed in the AM and DM of both tumor groups: 15.8% and 15.4% in AM and DM, for each one of them, in HGP group and 26.7% and 22.2% in AM and DM, for each one of them, in invasive tumors group. In CIS lesion aneuploid DNA content, p53 overexpression and high proliferative labeling index were observed. The so-called normal mucosa (AM and DM) with and without focus of CIS lesions were compared for genetic instability and molecular alterations profile. Statistical differences were observed between the normal mucosa with and without CIS: the so-called normal mucosa areas with focus of CIS revealed significantly higher frequencies of DNA content alterations, p53 overexpression, and higher proliferative index. These differences were significantly different in the invasive UCC group, but this profile it is also present in HPG group. Conclusion This study points out that CIS is a marker of genetic instability of the urothelium mucosa. The CIS surrounding morphologically normal urothelium showed a high frequency of abnormal DNA content, with high percentage of clear aneuploid cells (high 5cER), p53 mutated protein expression, and a proliferative status underlying a field carcinogenesis. These alterations in normal mucosa were not found when CIS was not present.

Urothelial carcinoma with villoglandular differentiation: a study of 14 cases

Tumors of the urinary bladder may have a variety of histological patterns. Tumors with either glandular or villous features, such as villous adenomas, in situ adenocarcinomas, invasive adenocarcinomas, and variants of urothelial carcinoma such as micropapillary carcinomas have been described. However, urothelial carcinomas with both villous and glandular features have not been well characterized. We identified 14 cases of urothelial carcinoma with villoglandular differentiation. These cases were defined as having villoglandular features if they contained superficial finger-like processes lined by epithelium having true glandular lumina. Mean patient age at presentation was 70 years (range: 46–84 years) with a male predominance (5:1). A total of 3 cases (21%) were non-invasive, five cases (36%) had lamina propria invasion, five cases (36%) had muscularis propria invasion and one case (7%) had extravesicular extension. A concurrent high-grade papillary urothelial carcinoma component was identified in 11 cases (79%), micropapillary component in 5 (36%) cases, in-situ urothelial carcinoma component in 3 cases (21%), plasmacytoid component in 3 cases (21%), invasive adenocarcinoma in 2 cases, sarcomatoid carcinoma component in one case (14%), and small-cell carcinoma component in 1 case (7%). Cystitis cystica et glandularis was present in 3 cases (21%). Angiolymphatic invasion was identified in 3 cases (21%). Histologically, the villoglandular components were composed of finger-like processes lined by glands intimately admixed with high-grade urothelial carcinoma. Many of the glands had cribriform features lined by non-mucin producing cuboidal to columnar cells. Urothelial carcinoma with villoglandular differentiation are high-grade tumors typically seen in elderly males, characterized by superficial filliform processes lined by glands intimately admixed with high-grade urothelial carcinoma (in situ or invasive) and other aggressive variants of urothelial carcinoma. These relatively rare tumors should be recognized as a variant of urothelial carcinoma.

Small Endoscopic Biopsies of the Ureter and Renal Pelvis

Technical advances in endoscopic equipment have led to increased ureteroscopic biopsies of the upper urinary tract, resulting in limited biopsy material. We retrospectively reviewed 76 consecutive mid-upper ureter and renal pelvis biopsies submitted for consultation from January 2004 to January 2009, where follow-up was obtainable. There were 49 (64.5%) males and 27 (35.5%) females. Thirty-nine (51.3%) of the biopsies were from the ureter with the remaining 37 (48.7%) from the renal pelvis. The mean age was 70 years for males and 71 for females (range: 24 to 89). At consultation, the most common diagnoses were benign urothelium (n=25, 32.9%); atypical (n=17, 22.4%); low-grade noninvasive papillary urothelial carcinoma (n=10, 13.2%); and high-grade noninvasive papillary urothelial carcinoma (n=8, 10.5%). In cases where a definitive diagnosis could not be reached on expert review, it was mainly because of the limited size of the biopsy, absence of papillary fronds, crush artifact, and distorted architecture. There were 7 major discrepancies between the outside and second opinion diagnosis, where all of the cases were initially diagnosed as an urothelial neoplasm, yet was non-neoplastic upon review. Strips of urothelium without well-developed fibrovascular cores, polypoid ureteritis/pyelitis, and reactive urothelium mimicked urothelial neoplasms. In 5 of these 7 cases, there was no gross lesion suspicious of a tumor present according to the urologist. Overall, 33 of the 44 (75%) cases with a mass noted by the urologist or by radiography was found to have a neoplasm at follow-up. Conversely, 24 of the 32 (75%) cases without a grossly suspected tumor had no neoplasm at follow-up. The association between the histologic presence of a neoplasm at follow-up and the presence of a clinically suspected tumor was highly significant (P<0.0001). Pathologists need to recognize that in almost 1 of the 4 renal pelvic/ureteral biopsies a definitive diagnosis cannot be made because of the inadequate tissue. Caution must be exercised in the evaluation of these limited specimens, especially in the absence of a clinically suspected tumor.

Synchronous squamous cell carcinoma of the kidney, squamous cell carcinoma of the ureter, and sarcomatoid carcinoma of the urinary bladder: A case report

The author presents a unique case of a synchronous triple carcinoma of kidney, ureter, and urinary bladder. A 73-year-old man was admitted to our hospital because of hematuria and lumbago. Endoscopy and imaging modalities revealed a bladder tumor, a left ureter tumor, and a left kidney tumor. No other tumors were found in the body by imaging modalities. Cystectomy and left nephroureterectomy were performed. The bladder tumor was a large polypoid tumor consisting of pleomorphic sarcomatoid carcinoma (80%) and high-grade papillary urothelial carcinoma (20%), both invading the deep muscle layer. There were gradual merges between the two. The sarcomatous component was composed of malignant spindle, polygonal, and giant cells. Lymphovascular permeation was pronounced. Immunohistochemically, the sarcomatous element was positive for vimentin and various types of cytokeratins (CK), while the urothelial carcinoma element was positive for various types of CK and negative for vimentin. The ureter tumor was small and obstructed the ureter lumen. It was a pure squamous cell carcinoma without a urothelial component. The ureter tumor invaded the adventitia. A mild degree of lymphovascular invasion was recognized. Immunohistochemically, the tumor cells were positive for various types of CK but negative for vimentin. In the kidney, almost the entire kidney parenchyma was replaced by a tumor. The renal pelvis was broadly erosive but was free of apparent tumors. Histologically, the renal tumor was a pure squamous cell carcinoma without a urothelial component. Broad necrosis was present, and lymphovascular permeation was pronounced. The renal pelvis and calices were devoid of apparent tumor cells, but renal squamous cell carcinoma was present just beneath the pelvis and calices. Immunohistochemically, the kidney tumor was positive for various types of CK and negative for vimentin.

226 Genomic alterations in urothelial carcinoma subgroups

Papillary urothelial neoplasms of the urinary bladder comprise a heterogeneous spectrum of ‘continuous’ lesions in which the assessment of an accurate histological grade and tumour stage is mandatory for the clinical management of patients. The 1998 World Health Organization/International Society of Urologic Pathologists (WHO/ISUP) consensus classification and the 1999 WHO classification proposed new malignancy grading schemes, mainly based on morphometric studies for the replacement of the 1973 WHO grading system. In accordance with these novel grading systems, two major categories of papillary urothelial neoplasms were distinguished: low-grade and high-grade papillary urothelial neoplasms. Concerning the specific subgroup of low-grade tumours, two other entities were defined: papillary urothelial neoplasms of low malignant potential (PUNLMP) and low-grade papillary urothelial carcinomas (LGPUC). In long-term follow-up programmes, PUNLMP have demonstrated low recurrence rates and minimal risk for tumour progression in comparison with LGPUC. However, grade assessment is a subjective decision and, on occasion, the use of reproducible criteria by urological pathologists is difficult due to tumour heterogeneity and to the existence of a variable number of cases situated between consecutive groups. As a result, to determine a better correlation with clinicopathological patient outcome, other predictive markers are being investigated. Among these, the prognostic significance of classical clinicopathological, morphometric, cytometric, immunohistochemical and molecular markers have been widely reported. This review summarizes the prognostic importance of all these markers in the prediction of tumour recurrences and progression in low-grade papillary urothelial bladder neoplasms.

Combined Thermo-Chemotherapy for Recurrent Bladder Cancer After Bacillus Calmette-Guerin

Despite an initial adequate response many patients with nonmuscle invasive urothelial cell carcinoma of the bladder eventually have recurrence after intravesical bacillus Calmette-Guerin treatments. We evaluated the efficacy of combined bladder wall hyperthermia and intravesical mitomycin C instillation (thermo-chemotherapy) in cases of recurrence after bacillus Calmette-Guerin. A total of 111 patients with recurrent papillary nonmuscle invasive urothelial cell carcinoma of the bladder after previous bacillus Calmette-Guerin treatment underwent complete bladder tumor resection and were referred for prophylactic adjuvant treatment with thermo-chemotherapy. Treatment was received on an outpatient basis weekly for 6 weeks, followed by 6 maintenance sessions at 4 to 6-week intervals. Each treatment included 2, 30-minute cycles of 20 mg mitomycin C and bladder wall hyperthermia to 42C +/- 2C. Cystoscopy and urine cytology were performed after the completion of induction treatment and every 3 months thereafter. The Kaplan-Meier estimated disease-free survival rate was 85% and 56% after 1 and 2 years, respectively. No maintenance treatment was associated with decreased efficacy, that is the recurrence rate was 61% at 2 years vs 39% in those with maintenance treatments (p = 0.01). The progression rate was 3%. Thermo-chemotherapy may be effective for papillary nonmuscle invasive urothelial cell carcinoma of the bladder that recurs after BCG treatment without increasing the risk of tumor progression. Maintenance therapy is important and improves the outcome.