Nephrogenic Adenoma of the Prostatic Urethra Mimicking Prostatic and Bladder Carcinomas.

A nephrogenic adenoma is a benign lesion consisting of the proliferation of tubules and glands in the urinary tract. The lesion, thought to be originated from renal tubules, is commonly seen in the urinary bladder. Microscopically, nephrogenic adenoma is composed of a proliferation of small tubules and microcysts encircled by a narrow rim of basement membrane-like hyaline material. There are tubules and microcysts lined by atrophic to undulating hobnail-appearing epithelial cells with bland nuclei and pale eosinophilic to clear cytoplasm. Focal cellular atypia characterized by somewhat coarse chromatin and prominent nucleoli may be present. The stroma is edematous and reveals a granulation tissue-like appearance. By immunohistochemical staining, nephrogenic adenoma is positive for PAX-2, PAX-8, P504S (α-methylacyl-CoA racemase), pan cytokeratin AE1/AE3, CK7, CAM5.2, epithelial membrane antigen (EMA), CD10, and napsin A. Occasionally the lesions are incidentally encountered in the prostatic urethra, which may lead to a misdiagnosis as prostatic adenocarcinoma, clear cell adenocarcinoma or urothelial carcinoma of the urinary bladder. Herein we present a case of nephrogenic adenoma which has been incidentally found in a transurethral resection of a prostate specimen for the management of benign prostatic hypertrophy. The evaluation of morphology, immunohistochemistry, and differential diagnoses have also been discussed.

Clear cell renal cell carcinoma with BAP1 mutation: a report of two cases.

Clear cell renal cell carcinoma is the most common subtype of renal cell carcinomas (RCCs) and accounts for 60%-70% of all RCCs cases in adults. Aberrations in the von Hippel-Lindau (VHL) gene on chromosome 3p occurred in > 90% of clear cell RCCs. Other tumor suppressor genes located on chromosome 3p, such as BAP1, PBRM1, and SETD2, also contribute to tumorigenesis. Clear cell RCCs with both BAP1 and VHL mutations may display distinctive histopathological features. Here, we report two cases of clear cell RCCs with BAP1 mutation. One tumor had VHL, BAP-1, and RAF1 mutations and the tumor nests and alveoli of tumor cells were surrounded by proliferative vessels and the optically clear cytoplasm contained numerous eosinophilic granules and hyaline globules of varying sizes. The other tumor had BAP1 and ATM mutations, and demonstrated clear cells with numerous eosinophilic granules and other typical histopathological features of conventional clear cell RCC. Furthermore, many tumor nodules with dense peripheral lymphocytic infiltrates contained rhabdoid cells. Sarcomatoid cells were also observed. Both tumor cells showed high-grade nuclei. Clear cell RCCs with BAP1 mutation exhibit aggressive clinical behaviors.

The expression of YAP1 is increased in high-grade prostatic adenocarcinoma but is reduced in neuroendocrine prostate cancer.

BACKGROUND: After long-term androgen deprivation therapy, 25-30% prostate cancer (PCa) acquires an aggressive neuroendocrine (NE) phenotype. Dysregulation of YAP1, a key transcription coactivator of the Hippo pathway, has been related to cancer progression. However, its role in neuroendocrine prostate cancer (NEPC) has not been assessed. METHODS: Immunohistochemistry and bioinformatics analysis were conducted to evaluate YAP1 expression levels during PCa initiation and progression. RESULTS: YAP1 expression was present in the basal epithelial cells in benign prostatic tissues, lost in low-grade PCa, but elevated in high-grade prostate adenocarcinomas. Interestingly, the expression of YAP1 was reduced/lost in both human and mouse NEPC. CONCLUSIONS: The expression of YAP1 is elevated in high-grade prostate adenocarcinomas but lost in NEPC.

Renal cell carcinoma with leiomyomatous stroma: a review of an emerging entity distinct from clear cell conventional renal cell carcinoma.

Clear cell renal cell carcinomas accounts for 65 to 75% of all malignant renal tumors. The International Society of Urological Pathology 2012 Vancouver Classification of renal neoplasia and the World Health Organization 2016 Classification of renal tumors have included renal cell carcinoma with leiomyomatous stroma in a category of emerging/provisional entities of renal cell carcinoma. Macroscopically, renal cell carcinomas with leiomyomatous stroma are well circumscribed tumors with a cut surface of gray-white fibrotic tissues. Microscopically, the tumors are composed of nodules and anastomosing tubules of renal cells with clear cytoplasms. The carcinoma cells are embedded in a cellular stroma composed of intertwining bundles of smooth muscle. Immunohistochemically, the neoplastic cells are typically positive for CK7 and CD10 immunomarkers. Biomarkers including CAIX, pankeratin, vimentin, and HIF1-alpha stain positively in many renal cell carcinomas with leiomymomatous stroma. Molecular genetic studies of this variant of tumor reveal no VHL mutation, trisomy 7 or trisomy 17. However, a TCEB1 mutation has been demonstrated in a subset of tumors and rare cases are reported from patients with a family history of tuberous sclerosis. The biological behavior of this variant of tumor is indolent and the prognosis is favorable.

Prostatic adenocarcinoma with novel NTRK3 gene fusion: a case report.

TMPRSS2-ERG gene fusion occurs in approximately 50% of prostatic adenocarcinoma and their expression is associated with aggressive phenotype, higher tumor stage, and tumor metastasis. A case of prostatic adenocarcinoma with IRF2BP2-NTRK1 translocation was previously reported. We report a prostatic adenocarcinoma with novel NTRK3 gene fusion that occurs in a 71-year-old male patient with aggressive histologic phenotype and multiple bony metastases. Prostatic biopsy revealed that there is a prostatic adenocarcinoma with a Gleason score of 9 (4+5), grade group 5, and multiple sites of perineural and ganglional invasion. Fluorescence in-situ hybridization (FISH) and next-generation sequencing were performed. FISH studies showed a breakage within the NTRK3 gene in prostatic adenocarcinoma cells. Next-generation sequencing confirmed that there is a PRPSAP1-NTRK3 translocation in the prostatic adenocarcinoma. In addition, ASXL1, KIF5B, MED12, PIK3CA mutations were found. NTRK alterations or dysregulation of PI3K signaling pathway were found in many types of cancers. TRK inhibitors including larotrectinib and entrectinib were approved by the US Food and Drug Administration for treating TRK fusion-positive malignant tumors and PI3K/AKT/mTOR pathway inhibitors were under clinical studies on various cancers including prostate cancer. In our current case, both NTRK3 and PIK3CA may serve as biomarkers for precision targeted therapy.

Challenges and potential solutions to meeting accrual goals in a Phase II chemoprevention trial for prostate cancer.

OBJECTIVE: The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer. METHODS: We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented. RESULTS: Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety-four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies. CONCLUSION: A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials.

Prostate Cancer Chemoprevention Targeting Men with High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Atypical Small Acinar Proliferation (ASAP): Model for Trial Design and Outcome Measures.

In spite of the large number of nutrient-derived agents demonstrating promise as potential chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving nutrient-derived agents to recommendation for clinical use include adopting a systematic, molecular-mechanism based approach and utilizing the same ethical and rigorous methods such as are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity as observed from epidemiological, in vitro and preclinical studies, phase I data of safety in suitable cohorts, duration of intervention based on time to progression of preneoplastic disease to cancer and the use of a valid panel of biomarkers representing the hypothesized carcinogenesis pathway for measuring efficacy must inform the design of phase II clinical trials. The goal of this paper is to provide a model for evaluating a well characterized agent- Polyphenon E- in a phase II clinical trial of prostate cancer chemoprevention.

Fate of the leftover bladder after supravesical urinary diversion for benign disease.

PURPOSE: We studied the fate of the leftover bladder in patients who underwent supravesical urinary diversion without cystectomy for benign pathology. MATERIALS AND METHODS: This retrospective study was performed in 9 males and 15 females with a median age of 59 years in whom supravesical urinary diversion was performed for various benign conditions from 1996 to 2004. These conditions were incontinence, acontractile bladder, radiation and/or hemorrhagic cystitis, and neuropathic bladder. Median followup was 48 months. RESULTS: Of the patients 13 (54%) experienced problems with the retained bladder, 2 (8%) presented with urethral bleeding, which resolved by conservative means, and 11 (46%) had infective complications, which resolved with expectant treatment in 3 (12%). However, 8 patients (33%) had frank pyocystis and 3 (12%) were treated with the Spence procedure, which alleviated symptoms in only 1. Six patients (25%) required cystectomy. CONCLUSIONS: In patients undergoing supravesical urinary diversion for benign disease in whom the bladder remains in situ the risks of complications related to the defunctionalized bladder are more than 50% and 25% of patients subsequently need cystectomy. These patients should be offered primary cystectomy at urinary diversion.