Rosai-Dorfman disease of the genito-urinary tract: analysis of six cases from the testis and kidney.

AIMS: Rosai-Dorfman disease (RDD) commonly occurs in lymph nodes, but it can also affect the genitourinary (GU) system. In a search of GU RDD, we identified three cases involving the testis and three the kidney. METHODS AND RESULTS: The mean age was 52.4 (35-76) years. Tumour sizes were 3.6 cm on average (1.5-4.3) for testicular cases and 15.5 cm for the renal case treated by nephrectomy. All renal cases showed typical morphology similar to nodal RDD with scattered foci of lymphocytic aggregation. In contrast, all three testicular cases had an evenly distributed lymphocyte and plasma cell infiltration with entrapment of Sertoli-only seminiferous tubules. In all six cases, immunohistochemistry (IHC) for S100 showed strong reactivity in the lesional histiocytes and highlighted the hallmark emperipolesis. One testicular case had pleural and pericardial effusions but resolved after removal of the RDD lesion. Another renal case subsequently involved bone and then lung over a 3-year period. CONCLUSIONS: RDD involving the GU system is rare with it most commonly involving the kidney followed by testis. Our three renal cases were similar in morphology to typical nodal RDD. The testicular cases had a somewhat different histological picture and needed IHC for S100 to verify the diagnosis.

Molecular basis of urinary bladder cancer.

Bladder cancer is a relatively common and potentially life-threatening neoplasm. The diagnosis of urothelial carcinoma usually entails a lifelong surveillance to detect recurrent disease. In recent years, significant progress has been made in understanding the molecular mechanisms of carcinogenesis in urinary bladder. An early step in the process of carcinoma development is establishment of a premalignant abnormal urothelial patch that may give rise to various types of urothelial carcinoma and may provide a fertile ground for development of multifocal synchronous and metachronous tumors. Two distinct molecular pathways are involved. Low-grade papillary carcinoma is associated with mutation in the FGFR3 or in some cases mutations in RAS genes. High-grade in situ/muscle-invasive carcinoma on the other hand is characterized by alteration of p53 and pRB. Loss of function of these key genes, which play a crucial role in the control of cell cycle, leads to accumulation of additional mutations and deletions of genes resulting in an aggressive phenotype. It is hoped that a thorough understanding of the molecular basis of urothelial cancer will facilitate early diagnosis and will lead to development of new modalities for the management and treatment of these carcinomas.

Tubulocystic renal cell carcinoma with poorly differentiated foci and loss of fumarate hydratase: A case report.

Tubulocystic renal cell carcinoma (RCC) is one of the newly recognized subtypes of RCC. It has a unique cystic morphology and indolent behavior. During the last decade, few studies have been published describing tubulocystic RCC with poorly differentiated foci. A subset of these cases are associated with loss of fumarate hydratase which is a characteristic feature of hereditary leiomyomatosis and renal cell carcinoma-associated RCC. However, these two entities represent two distinct subtypes of RCC in the recent WHO Classification of kidney tumors. Herein, we are describing a rare case of tubulocystic renal cell carcinoma with poorly differentiated foci and loss of fumarate hydratase.

The grasper-integrated disposable flexible cystoscope is comparable to the reusable, flexible cystoscope for the detection of bladder cancer.

Flexible cystoscopy under local anaesthesia is standard for the surveillance of bladder cancer. Frequently, several reusable cystoscopes fail to reprocess. With the new grasper incorporated single-use cystoscope for retrieval of ureteric stents, we explored the feasibility of using it off-label for diagnosis and the detection of bladder cancer. Consecutive diagnostic flexible cystoscopies between Mar 2016 and Nov 2018 were reviewed comparing the reusable versus the disposable cystoscopes. A total of 390 patients underwent 1211 cystoscopies. Median age was 61.5 years (SD 14.2, 18.8-91.4), males 331 (84.9%) and females 59 (15.1%). Indication for cystoscopy was prior malignancy in 1183 procedures (97.7%), haematuria 19 (1.6%) or bladder mass 7 (0.6%). There were 608 reusable and 603 disposable cystoscopies. There was no significant difference between groups at baseline in age, sex, BMI, smoking status, or prior tumor risk category. There was no significant difference in positive findings (123/608, 20.2% vs 111/603, 18.4%, p = 0.425) or cancer detection rates (95/608, 15.6% vs 88/603, 14.4%, p 0.574) among the two groups, respectively. We conclude that the disposable grasper integrated cystoscope is comparable to reusable cystoscope in the detection of bladder cancer.

Renal Stromal Expression of Oestrogen and Progesterone Receptors in Chronic Pyelonephritis as Compared to Normal Kidneys.

OBJECTIVE:  To determine and compare the distribution of oestrogen and progesterone receptors (ER and PR) expression between normal kidneys and chronic pyelonephritis. STUDY DESIGN: Comparative-descriptive study. PLACE AND DURATION OF STUDY: King Faisal Specialist Hospital and Research Centre, and Alfaisal University, Riyadh, Saudi Arabia, between January 2017 and December 2018.  Methodology: Renal specimens, including 41 chronic pyelonephritis, and 21 healthy specimens were examined. ER/PR expression was determined immunohistochemically, termed focal if <50% of nuclei stained positively, and diffuse when >50%. The intensity of staining was labelled weak (pale), moderate or strong. RESULTS: Majority of samples showed presence of diffuse ER (82.9% diseased; 71.4% healthy) and focal PR (53.7% diseased; 76.2% healthy), mostly with strong intensity. ER and PR distribution whether focal or diffuse, correlated with each other in 41.9%. All proportions comparisons showed p values greater than 0.05. CONCLUSION: There was a trend of diffuse renal stromal expression of ER and PR in chronic pyelonephritis as compared to healthy specimens. However, the difference did not reach statistical significance. Key Words: Oestrogen receptor, Progesterone receptor, Chronic pyelonephritis, Renal cancer, Renal stroma.

Clinical significance of IgM deposition in pediatric minimal change disease.

BACKGROUND: Idiopathic nephrotic syndrome (INS) is a common pediatric disease. Minimal change disease (MCD) is the most common histopathological subtype and usually has good prognosis. However, in less common presentations, INS may have an unusual course that makes renal biopsy a necessity to identify its etiology. Immunoglobulin M (IgM) occasionally deposits in the mesangium and can be seen under immunofluorescence (IF). The role of IgM is controversial in MCD. It is likely associated with less favorable outcomes for MCD. This study aims to investigate the clinical significance of mesangial IgM deposits on the outcome of MCD in a pediatric population. METHODS: In this retrospective cohort study, we obtained native kidney biopsy samples from 192 children who were diagnosed with MCD from 2003 to 2014. The samples were divided into groups according to the histopathological deposition of IgM in biopsies under IF. The group for which biopsies showed IgM was labeled as IgM + IF (n = 77), and the group for which biopsies were without IgM was labeled as IgM-IF (n = 115). We reviewed hypertension, hematuria, and estimated glomerular filtration rate (eGFR) at the time of presentation to our institute; response to steroid therapy (remission, dependence, frequent relapses, and resistance) and response after adjuvant immunosuppressive therapy (complete remission, partial remission, frequent relapses, and no response) when indicated; development of chronic kidney disease (CKD) and end-stage renal disease during the course of the disease (ESRD). RESULTS: Our results showed that mesangial IgM deposition in MCD showed significant statistical association with hypertension at the time of presentation (P = .05). There was statistically significant association between the presence of IgM deposition and the development of steroid dependence (P = .05) and CKD during the course of the disease (P = .05). CONCLUSIONS: Our study showed that IgM deposition in MCD showed statistical association with hypertension by the time the patient presented to our institute, development of steroid dependence, and CKD. IgM may play a role in MCD. However, we recommend a prospective study to verify the role of IgM in MCD outcomes.

Operative outcomes of robotic partial nephrectomy. A report of the first 101 cases from a single center in Saudi Arabia.

OBJECTIVES: To report robotic partial nephrectomy (RPN) outcomes from a single tertiary hospital in Saudi Arabia. Methods: We retrospectively reviewed consecutive cases of patients undergoing RPN at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of  Saudi Arabia, between January 2008 and January 2018. The study reports patient's demographics, tumor characteristics, operative details, and perioperative outcomes, using descriptive statistics of median and range values. Results: One hundred and one patients underwent RPN during the study period. Average tumor size was 3 (1.3-6.4) cm and average radius exophytic nearness anterior/posterior location (RENAL) score was 6 (4-10). Perioperative parameters were blood loss 200 (5-1500) ml and warm ischemia time 17 (8-40) minutes, excluding off-clamp surgery in 12 (11.9%); operative time was 166 (66-381) minutes. Conversion to open partial nephrectomy occurred in 9 (8.9%) patients, major complications in 3 (3%) patients, positive surgical margins in 5 (5%) patients, and the hospital stay was 4 (2-14) days. A total of 73 (73%) patients achieved a trifecta of freedom from any complication, negative surgical margins, and ischemia time ≤25 minutes. Study limitations included the retrospective design and small cohort size. Conclusions: The initial experience of robotic partial nephrectomy was associated with a surgical outcome comparable to that reported by higher-volume centers.

Chromophobe renal cell carcinoma occurring in the renal allograft of a transplant recipient presenting with weight loss.

The incidence of renal cell carcinomas (RCCs) in renal transplant recipients is reported as 1.1-1.5% in the native kidneys and 0.22-0.25% in the renal allograft. There are no data to support routine surveillance for tumors in transplant recipients. Most reported cases of RCCs occurring in renal allografts were incidental findings in asymptomatic patients. Herein, we report the second case of lone chromophobe RCC (ChRCC) of the renal allograft presenting with weight loss. Loss of weight is a presenting symptom in one-third of ChRCCs occurring in the native kidneys in the general population. Based on the age of the patient, R.E.N.A.L nephrometry score of the tumor and the lack of data on the prognosis of this histological subtype in a climate of long-term immunosuppression, we elected for radical nephrectomy. We suggest that RCCs should be considered in the differential diagnosis of a transplant recipient presenting with weight loss even in the absence of localizing symptoms or signs.

Tubulocystic carcinoma of the kidney with poorly differentiated foci: a series of 3 cases with fluorescence in situ hybridization analysis.

We identified 3 consult cases of tubulocystic renal cell carcinoma with poorly differentiated areas. Two lesions measuring 9.5 and 3.8 cm were described as partly solid and cystic. One case was grossly a 14.0-cm cyst with a granular lining. Microscopically, all had classic areas of circumscribed tubulocystic renal cell carcinoma occupying 30%, 80%, and 90% of the tumor; 2 cases had small components of papillary renal cell carcinoma, and 1 case had a central large cystic component. In 2 cases, proliferations of small tubules infiltrated away from the main mass with typical features of collecting duct carcinoma. In the third case, a focus of poorly differentiated carcinoma was seen adjacent to the tubulocystic renal cell carcinoma. In 2 cases, tumor invaded perirenal tissue. The third case was organ confined with vascular invasion. One patient died 9 months postoperatively with metastases to the abdominal wall and femur. The second case developed a recurrence in the renal bed 3 years postoperatively. The third patient was lost to follow-up. Fluorescence in situ hybridization studies results showed some features overlapping with papillary renal cell carcinoma in both the tubulocystic and collecting duct-like components and with 1 exception showed identical cytogenetic findings between the 2 components. Morphologically, in 2 cases, the collecting duct-like areas were also indistinguishable from collecting duct carcinoma suggesting a relationship between the 2 entities. This is the first series and only the second report of tubulocystic renal cell carcinoma with poorly differentiated components and documents the increased the risk of aggressive behavior above that of usual tubulocystic renal cell carcinoma.

Gleason pattern 5 is frequently underdiagnosed on prostate needle-core biopsy.

OBJECTIVE: To assess underdiagnosing Gleason pattern 5 on needle biopsy and discuss the potential consequences for patient management. MATERIAL AND METHODS: We retrieved 300 consecutive prostate biopsy cases from the consultation files at The Johns Hopkins Hospital (JHH) from 2009-2010 in which we identified Gleason pattern 5. All of these cases were diagnosed by one of the authors and all were sent in as a final diagnosis for which the outside pathologist was not requesting consultation because of difficulty with the diagnosis. The Gleason grades assigned to these cases at our institution were compared with the grade rendered by the submitting pathologists from the outside institution. RESULTS: In 146 (48.7%) of the cases, Gleason pattern 5 was not identified by the outside pathologists. Of the 146 cases, the outside Gleason score was ≤7 in 61 (20.3%) and 4+4=8 in 85 (28.4%). Even when the tumor was diagnosed at JHH as Gleason score 5+5=10, only 26 (41.3%) were diagnosed as the same by the outside pathologists; Gleason score 9 was graded in 27 (42.8%). CONCLUSION: Considering the important prognostic and therapeutic implication of misdiagnosing Gleason pattern 5, efforts should be made by the pathology community to acknowledge this as a problem and improve on individual pathologists' accuracy by diverse medical education programs. In addition, urologists should not hesitate in sending biopsies with high-grade prostate cancer for expert genitourinary pathology second opinions.

Initial high-grade prostatic intraepithelial neoplasia with carcinoma on subsequent prostate needle biopsy: findings at radical prostatectomy.

There are only a few small studies on men with an initial biopsy showing high-grade prostatic intraepithelial neoplasia (HGPIN) who later have cancer on repeat biopsy and then undergo radical prostatectomy. It is unknown whether this scenario impacts the prognosis of subsequent radical prostatectomy. We compared radical prostatectomy findings in 45 men with an initial diagnosis of HGPIN who subsequently were diagnosed with cancer with 18,494 men diagnosed with cancer who lacked an earlier diagnosis of HGPIN. All cases were retrieved from our institution between 1993 and 2008. The mean patient age was 60.2 years, and the mean serum prostate-specific antigen value was 9.0 ng/mL. For the 45 men with an initial HGPIN diagnosis, 21 of 45 (46.7%) men were found to have cancer within 6 months and 29 of 45 (64.4%) within 1 year after the diagnosis of HGPIN. Cancer involved a single core in 32 of 45 (71.1%) cases, and the maximum tumor volume was ≤5% in 57.8% of the 45 cases. Men with initial HGPIN had 84.4% organ-confined cancer, whereas cases without HGPIN had 65.4% organ-confined cancer (P=0.007) at radical prostatectomy. For the RPs performed in men with an earlier diagnosis of HGPIN followed by cancer on biopsy, the mean and median tumor volumes were 0.3 cm³ and 0.12 cm³ (0.003 cm³ to 1.46 cm³). Favorable pathologic stage was maintained even when we restricted the analysis to men with only Gleason score 6 cancer on biopsy. In men with Gleason score 6 cancer on biopsy, men with an initial diagnosis of HGPIN had 88.9% organ confined versus 73.2% for men with no earlier biopsy diagnosis of HGPIN, (P=0.03). At radical prostatectomy, although men with an earlier HGPIN diagnosis had less adverse findings in terms of Gleason score, surgical margin involvement, seminal vesicle involvement, and lymph node metastasis, the differences did not reach statistical significance. This was possibly due to the relatively small number of positive events in the men with no earlier HGPIN and due to the relatively small number of cases with earlier HGPIN. Prostatic adenocarcinomas discovered after an initial HGPIN diagnosis on biopsy are more likely to be organ confined, yet of similar grade, compared with cases diagnosed as cancer on the first biopsy. These findings likely reflect cancers associated with HGPIN, in which the cancers were missed on the initial biopsy as a result of smaller size.