Mahyar Kashan

Outcomes of reduction cystoplasty in men with impaired detrusor contractility.

OBJECTIVE To report surgical outcomes in patients with impaired detrusor contractility (IDC) treated with reduction cystoplasty (RC). METHODS This was a retrospective study of consecutive patients with IDC who underwent RC. IDC was defined as a bladder contractility index of <100 and/or a detrusor contraction of insufficient duration resulting in a postvoid residual volume (PVR) >600 mL. Bladder outlet obstruction was defined by a bladder outlet obstruction index (BOOI) >40. All patients had preoperative International Prostate Symptom Score, maximum uroflow (Qmax), PVR, bladder diary, videourodynamics, and cystoscopy. Patients with prostatic obstruction underwent synchronous open prostatectomy. Postoperative Qmax, PVR, need for clean intermittent catheterization (CIC), and Patient Global Impression of Improvement (PGII) score were obtained. Follow-up was at 3 months, 1 year, and yearly thereafter. RESULTS Eight men met inclusion criteria (mean age, 60; range, 43-75 years). Preoperatively, 3 of 8 patients (37.5%) had moderate-sized bladder diverticula, 4 of 8 (50%) had a bladder contractility index <100, and 6 of 8 (75%) had a BOOI <40. Two patients (25%) fulfilled criteria for bladder outlet obstruction (BOOI, 67 and 72). Three (37.5%) underwent synchronous bladder diverticulectomy, and 3 (37.5%) underwent suprapubic prostatectomy. All patients were available for follow-up at 1 year. Seven of 8 (88%) had a successful outcome (PGII ≤2). One patient was unchanged (PGII, 4) and still needed CIC. CONCLUSION All but 1 patient who met specific criteria for RC had excellent outcomes after surgery based on the PGII, PVR, Qmax, and need for CIC. RC is a viable option for properly selected patients with IDC.

PD46-04 ELOC-MUTATED RENAL CELL CARCINOMA: A DISTINCT CLINICAL ENTITY WITH UNCLEAR DISEASE COURSE

INTRODUCTION AND OBJECTIVES: Renal medullary carcinoma (RMC) is a rare renal neoplasm accounting for less than 1% of all renal cell carcinomas. RMC, which frequently occurs in young African Americans with sickle cell trait, is an aggressive and lethal cancer with a median overall survival of about 13 months. Recent studies identified the biallelic loss of SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex, as a characteristic feature of RMC tumors. Other reports suggest that the presence of vinculin-anaplastic lymphoma kinase (VCL-ALK) fusion without SMARCB1 loss may represent an RMC variant. We hypothesize that in addition to these alterations, novel driver mutations are present and may become potential targets for treatment. To test this hypothesis, we carried out whole exome sequencing of RMC tumor specimens. METHODS: Formalin fixed paraffin embedded (FFPE) RMC tumor and adjacent normal tissue specimens of 21 African American patients with sickle cell trait were obtained from the Joint Pathology Center. RNA and DNA were isolated using the Qiagen FFPE All Prep kit. Quantity and integrity of DNA samples were evaluated by Qubit fluorometer and Advanced Analytical Fragment Analyzer, respectively. Whole exome DNA libraries were prepared from sample using the Illumina TruSeq Exome kit. Paired end sequencing (2x75) were performed on the Illumina HiSeq3000 instrument. In parallel with genomic evaluations, known RMC associated molecular alterations, including SMARCB1, VHL, HIF2A, AURKA, and EZH2, were analyzed by immunohistochemistry (IHC). RESULTS: Somatic copy number alterations were estimated from the whole exome sequencing of seven tumor normal pairs. Recurrent amplifications of chromosome 7 and 8 and deletions on chromosome 15 were identified. Analysis of somatic sequence mutations detected recurrent non-silent mutations on NF2 and RBM47, and a canonical hotspot mutation (R132C) in IDH1. IHC results show the loss of SMARCB1 expression in all 21 cases assayed. Furthermore, the upregulation of EZH2 and AURKA, genes normally repressed by SMARCB1, were detected in 3 of 21 and 11 of 21 cases, respectively. Focal HIF2A staining was detected in 7 of 21 tumor cases. CONCLUSIONS: The discovery of recurrent somatic sequence mutations, gene amplifications and deletions reveals potential novel oncogenic drivers of RMC. Further validation of these genomic alterations may offer additional insight into the etiology of RMC and new options to manage the disease. The inactivation of SMARCB1 protein expression and upregulation of EZH2 and AURKA supports the evaluation of epigenetic modulating agents for treatment of RMC.

MP39-02 COMPARATIVE GENOMIC PROFILING OF MATCHED PRIMARY AND METASTATIC TUMORS IN RENAL CELL CARCINOMA

were found to be significantly more common in those who had recurrence or died of their disease (24% vs. 4%; adjusted p1⁄40.02). Survival analysis showed patients with KDM5C having statistically significant inferior cancer-specific survival (adjusted p1⁄4<0.01) and a trend for inferior survival in those with SETD2 mutations (adjusted p1⁄40.11) (Figure 1). CONCLUSIONS: We identified mutations in SRMs that are associated with recurrence and lethality. The strongest association was seen with KDM5Cmutations. Use of these potential genomic biomarkers may improve risk stratification of patients with SRMs and for those who may be appropriate for AS. Prospective evaluation of these markers is needed.

MP67-14 CHARACTERIZATION OF RENAL CELL CARCINOMA IN PATIENTS WITH GASTROINTESTINAL STROMAL TUMORS COMPARED TO OTHER SOFT TISSUE SARCOMAS

patterns in renal cell carcinoma (RCC) in patients with end stage renal disease (ESRD), such as acquired cystic disease (ACD)-associated and clear cell papillary RCC. In this study, a central pathologist reanalyzed the pathological findings of RCC in patients with ESRD from multiple institutions, based on the new classification. METHODS: This study included 315 patients who underwent radical nephrectomy in 3 Japanese institutes from 1987 to 2015. A central pathologist reviewed sections from all patients according to the 2016 WHO classification. RESULTS: Based on the new classification, clear cell was diagnosed in 144 patients (46%), ACD-associated in 100 (31%), papillary in 41 (13%), chromophobe in 10 (3%), clear cell papillary in 3 (1%), MiT family translocation in 2 (1%), and unclassified in 15 (5%). We next compared clinicopathological findings of ACD-associated RCC with those of non-ACD-associated RCC. Multivariate analysis showed that independent prognostic clinical factors for occurrence of ACDassociated RCC were the presence of acquired cystic disease of the kidney (ACDK) (hazard ratio [HR]: 2 D710, p<0.01), age (HR: 0.97, p1⁄40.03), and duration of dialysis (HR: 1.06, p<0.01). We further compared pathological features in ACD-associated and other RCCs. ACD-associated included more Furman grade 3/4 (90 vs. 47%, p<0.01). In contrast, other unfavorable findings was less frequent in ACD-associated RCC, including the presence of sarcomatoid features (2 vs. 7%, p1⁄40.04), lymphovascular invasion (3 vs. 11%, p<0.01), and necrosis (7 vs. 13%, p1⁄40.18). CONCLUSIONS: ACD-associated RCC accounts for 31% of RCC in patients with ESRD, and prognostic clinical factors for occurrence include young age, long dialysis duration, and presence of ACDK. In addition, ACD-associated RCC showed higher Furman grade, but fewer cases with other unfavorable pathological features, suggesting the need for an independent nuclear grading system for ACD-associated RCC.

MP55-01 MIXED EPITHELIAL AND STROMAL TUMOR FAMILY: A SINGLE INSTITUTIONAL EXPERIENCE WITH THIS RARE RENAL ENTITY

INTRODUCTION AND OBJECTIVES: In 2016 the World Health Organization coined the term mixed epithelial and stromal tumor family (MESTF) to encompass adult cystic nephroma (ACN) within the classification of mixed epithelial and stromal tumors (MESTs) on the basis of overlapping clinical and pathologic profiles. MESTs have traditionally been regarded as benign, with only a few reports of malignant transformation or recurrence in the literature. Diagnosis requires histopathological evaluation, as radiologic imaging cannot accurately determine whether such tumors are benign or malignant. We aim to characterize our institutional experience with this rare neoplasm. METHODS: We identified all patients with a pathological diagnosis of MEST or ACN from our prospectively collected institutional database between Jan 1995 Dec 2015. Available imaging was rereviewed by a single expert radiologist (AH). Demographic, radiologic, and clinical characteristics were recorded. RESULTS: Data was available for 40 patients. The median age at diagnosis was 48.8 years (31.5-73.4). Thirty-seven (92.5%) patients were female and three (7.5%) were male. Imaging was available for rereview for 29 (72.5%) patients. The mean diameter of the tumor on preoperative imaging was 5.8 cm (1.9-16.1). Patients presenting with symptoms at diagnosis had a mean diameter of 7.4 cm (4-16.1). On imaging, 25 (86.2%) tumors where characterized as Bosniak 3 lesions and four (13.8%) were described as Bosniak 4 lesions. All patients underwent surgical resection, with partial nephrectomy performed in 72.5% of cases. Mean pathological tumor size was 5.9 cm (1.5-15). Median follow-up was 71.6 months (1-217). Two (4.9%) patients died from non-tumor related causes. At last follow-up, all patients showed no evidence of disease. CONCLUSIONS: MESTF are indolent tumors with a female predominance. They are usually detected incidentally as Bosniak 3 or 4 lesions. Partial nephrectomy should be performed whenever possible to resect the tumor and preserve renal function. Given the low likelihood of recurrence following excision, we believe that, once pathologically identified, patients have an excellent long-term prognosis and require minimal surveillance imaging on follow-up. Genomic characterization is currently underway. Source of Funding: Funded in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and the National Cancer Institute Training Grant T32 CA082088 (BM, MG)

MP55-08 DIAGNOSIS, MANAGEMENT, AND CLINICAL OUTCOMES OF CYSTIC RENAL CELL CARCINOMA

INTRODUCTION AND OBJECTIVES: Complex cystic masses pose a clinical challenge given lack of certainty for malignant potential. Cystic changes are common in renal cell carcinoma (RCC); however, there is limited data on cystic RCC (cRCC) specifically. The Bosniak classification system is used to categorize these lesions and help predict risk of malignancy. Current literature suggests that cRCC has a more favorable and benign course, but with no consensus on proper diagnosis and intervention. We aim to better categorize cRCC and the natural history of this disease. METHODS: We identified all patients with pathologically confirmed cRCC, multilocular cRCC, or RCC with cystic features between Jan 2000 Dec 2015 from our institutional database. Patients with follow-up of <1 year, previous history of RCC, familial syndromes, multifocal tumors, and lesions with >50% solid component on imaging were excluded from our analysis. Available imaging was re-reviewed by a single expert radiologist (AH). Radiological, clinical, and pathological characteristics were recorded. RESULTS: Of 128 patients identified for analysis, 76 (59.4%) were male and 52 (40.6%) were female. Median age at surgery was 54.4 years (17.3-78.4). Twenty (15.6%) patients had a family history of RCC. The majority of lesions were found incidentally on imaging (89.1%). Fourteen (10.9%) patients had local symptoms, with flank pain (8.6%) being the most common. Partial nephrectomy was performed on 116 (90.6%) patients and radical nephrectomy on 12 (9.4%); open technique was used in >80% of cases. Pathologic and imaging characteristics are shown in Table 1. On median follow-up of 66.1 months, there were no tumor recurrences or metastatic disease. A total of 5 (3.9%) patients died from other conditions. CONCLUSIONS: Diagnosis of cRCC should include cystic lesions with <50% solid component on imaging. Our data shows that cRCC includes a wide variety of tumors, most commonly with clear cell features. Most of these lesions are discovered incidentally on imaging as Bosniak grades 3 or 4 and are surgically resected. These patients uniformly do well with minimal risk of recurrence or metastasis on follow-up, thus, nephron sparing surgery is recommended. Given the indolent nature cRCC, enrollment of these patients into active surveillance protocols should be considered. Source of Funding: Funded in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and the National Cancer Institute Training Grant T32 CA082088 (BM, GM)

MP39-01 CHARACTERIZING RECURRENT AND LETHAL SMALL RENAL MASSES IN CLEAR CELL RENAL CELL CARCINOMA USING SOMATIC MUTATIONS

25.5% had Gleason 6, 25.5% had Gleason 7, and 9.0%, had Gleason 810 on final histopathology. Fusion Biopsy of PIRADSv2 3 lesions (n1⁄466) revealed no cancer in 65.2%, Gleason 6 in 15.2%, Gleason 7 in 19.7% and Gleason 8-10,in 0% of patients. Of 83 patients with clinically significant cancer, 26 (31.3%) would have been missed on standard biopsy and 12 (14.5%) would have been missed using fusion biopsy alone. Concordance between both biopsy modalities was 63.1%. CONCLUSIONS: mp-MRI targeted fusion biopsy improves the detection of clinically significant prostate cancer in select patients. However, our results demonstrate that a significant proportion of these cancers will not be detected by a targeted biopsy alone. Therefore, standard template biopsies should remain an integral component of any fusion biopsy program.

MP39-04 MOLECULAR AND CLINICAL CHARACTERIZATION OF RENAL CELL CARCINOMA WITH UNCLASSIFIED HISTOLOGY: NF2 LOSS PREDICTS WORST OUTCOMES

(28%) lung, 20 (21%) bone, 13 (14%) lymph node, 7 (7%) adrenal gland, 7 brain (7%), and 21 other sites (22%). The most common alterations were VHL (85%), PBRM1 (45%), SETD2 (37%), BAP1 (20%). When analyzing samples by site, metastases to pleura presented with enrichment in BAP1 mutations (P1⁄40.008), adrenal gland metastases had an enrichment in MED12mutations (P1⁄40.005), and NF2 alterations were found to be associated with bone metastases (P1⁄40.08). CONCLUSIONS: Our data suggest SM may be correlated with a site-specific pattern of metastatic spread. In our cohort, the presence of BAP1,MED12 and NF2mutations was associated with increased pleural, adrenal gland, and bone metastasis, respectively. The extent to which the identified molecular factors contribute to the development of these characteristics needs to be analyzed in further studies. Patterns of SM in ccRCC metastasis could result in the creation of gene signatures predicting metastasis.