Genitourinary Future by Diverse Educational Means
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188A ANNUAL MEETING ABSTRACTS signifi cantly predict MSI-L from MSS. More importantly, in multivariate analysis, beta- at our institution as Gleason score 5+5=10), only 26 (41.3%) were diagnosed as the catenin, CK20 and Cdx2 were independent predictors of MSI-L and together strongly same by the outside pathologists. discriminating (AUC=0.82). These features could be combined into a single score and Conclusions: Gleason pattern 5 is commonly underdiagnosed by outside pathologists visualized as an algorithm for the prediction of MSI-L. The parameter estimates from compared to an expert GU pathologist. One explanation is a hesitancy of pathologists logistic regression analysis were used as weights for each marker then a total score and to render the worst grade pattern possible and its adverse implications on prognosis probability of MSI-L were obtained. and treatment. Another explanation is that some cases may have consisted of mostly Conclusions: These results suggest that in contrast to MSS, MSI-L cancers may pattern 4, less pattern 3 (or vice versa), and tertiary pattern 5. According to the ISUP not frequently arise through deregulation of WNT pathway signaling. In addition, a modifi ed grade, Gleason score on biopsy is derived by adding the most prevalent and simple combined score of beta-catenin, CK20 and Cdx2 may be useful as a predictive highest grade patterns as opposed to the most and 2nd most common patterns. Not using algorithm for the MSI-L status. the ISUP modifi ed grading system could have accounted for at most 36/146 (24.7%) of the cases where Gleason pattern 5 was not recorded by the outside pathologists. Recognition of undergrading pattern 5 is the fi rst step to improving its grading in the Genitourinary future by diverse educational means. 779 KRAS Mutation Is Present in a Small Subset of Primary Urinary 781 De-Differentiated Tubulocystic Carcinoma of the Kidney: A Series Bladder Adenocarcinomas of 3 Cases with FISH Analysis RE Alexander, A Lopez-Beltran, R Montironi, GT MacLennan, GR Chen, KM Post, SA T Al-Hussain, L Cheng, S Zhang, JI Epstein. The Johns Hopkins Hospital, Baltimore; Bilbo, JD Sen, K Meehan, A Cornwell, L Cheng. Indiana University School of Medicine, Indiana University School of Medicine, Indianapolis. Indianapolis, IN; Cordoba University, Cordoba, Spain; Polytechnic University of the Background: Tubulocystic renal cell carcinoma (RCC) is relatively rare and was fi rst Marche Region (Ancona), United Hospitals, Ancona, Italy; Case Western Reserve described as a low grade variant of collecting duct carcinoma. This variant was not University, Cleveland, OH; First Affi liated Hospital of Wenzhou Medical College, recognized in the 2004 WHO classifi cation and only received its current name in 2009 Wenzhou, China. in a series of 39 cases from 7 large institutions. It is low grade with only 2/17 cases Background: The realization that the presence of KRAS mutations is a near absolute with follow-up in this prior series developing metastases. Its relationship to collecting contraindication to the use of EGFR-targeted therapies in colonic adenocarcinoma duct carcinoma is controversial and recent studies have linked it with papillary RCC. and non-small cell lung carcinoma has signifi cantly altered the clinical management Only 1 case from 2011 describes a sarcomatoid tubulocystic RCC. of individual patients with these types of cancer. The aim of this study is to determine Design: 3 consult cases of de-differentiated tubulocystic RCC were identifi ed. FISH whether KRAS mutations occur in primary bladder adenocarcinoma and/or urothelial was performed on 2 cases with available material. carcinoma with glandular differentiation. Results: Two lesions measuring 9.5 cm. and 3.8 cm. were described as partly solid and Design: Twenty cases of primary bladder adenocarcinoma were identifi ed. Clinical cystic. One case was grossly a 14.0 cm cyst with a granular lining. Microscopically, all histories and hematoxylin and eosin slides of each case were reviewed to confi rm had classic areas of circumscribed tubulocystic RCC occupying 30%, 80%, and 90% of primary bladder origin. An additional 5 cases of urothelial carcinoma with signifi cant the tumor. 2 cases had small components of papillary RCC and 1 case a central large degree of glandular differentiation were included. DNA was extracted from formalin- cystic component. In 2 cases, a proliferation of small tubules infi ltrated away from the fi xed paraffi n embedded tissue, amplifi ed with Shifted Assay Termination (STA) main mass with typical features of collecting duct carcinoma. In the 3rd case, a focus of technology. The STA reaction recognizes wild type or mutant target sequences and sarcomatoid carcinoma was seen adjacent to the tubulocystic RCC. In 2 cases, tumor selectively extends detection primers with 1 to 20 labeled nucleotides. This extension invaded peri-renal tissue. The 3rd case was organ confi ned with vascular invasion. 1 is repeated 20 times to enrich the mutation signal. The enriched mutation signals are patient died 9 months post-operatively with metastases to the abdominal wall and femur. then detected by capillary electrophoresis fragment analysis. The PCR amplifi cation The 2nd case developed metastases to retroperitoneal nodes 3 years post-operatively. products were analyzed on an ABI-3130XL analyzer with GeneMapper® software The 3rd patient was lost to follow-up. (Applied Biosystems® Inc., Foster City, CA). Analysis included 6 different mutations Tumor Pattern Chromosome 7 Chromosome 17 Chromosome Y on codon 12 (G12C, G12V, G12S, G12D, G12R, G12A) and codon 13 (G13C, G13V, Case 1. Tubulocystic Disomy Trisomy Loss G13S, G13D, G13R, G13A) along with negative and positive controls. 55 cases of Case 1. De-differentiated Disomy Trisomy Disomy Case 2. Tubulocystic Disomy Trisomy Disomy colonic adenocarcinomas were also analyzed. Case 2. De-differentiated Disomy Trisomy Disomy Results: Two of twenty (10%) cases of primary urinary bladder adenocarcinoma were Conclusions: This is the fi rst series and only the 2nd report of de-differentiated found to contain a KRAS mutation. Both cases exhibited G13D mutations on codon 13. tubulocystic RCC. FISH results showed some features that are seen with papillary RCC None of the 5 cases of urothelial carcinoma with glandular differentiation displayed in both the tubulocystic and dedifferentiated components and with one exception showed KRAS mutation. Eighteen (33%) of 55 cases of colonic adenocarcinoma contained a identical cytogenetic fi ndings between the 2 components. Morphologically, in 2 cases KRAS mutation. the de-differentiated areas were also indistinguishable from collecting duct carcinoma Conclusions: KRAS mutations are present in a small subset of primary urinary bladder suggesting a relationship between the 2 entities. De-differentiated tubulocystic RCC adenocarcinomas, suggesting a possible role in tumorigenesis. KRAS mutations do not increases the risk of aggressive behavior above that of usual tubulocystic RCC. provide a means of distinguishing between primary urinary bladder adenocarcinoma and primary colonic adenocarcinoma. 782 Virtual Karyotype of Renal Carcinoid Tumors by SNP Microarrays RW Allan, JA Jeung, D Cao, AV Parwani, LD Truong, FA Monzon. University of 780 Gleason Pattern 5 Is Frequently Underdiagnosed on Prostate Florida College of Medicine, Gainesville, FL; Washington University School of Needle Core Biopsy Medicine, St. Louis, MO; University of Pittsburgh School of Medicine, Pittsburgh, PA; T Al-Hussain, MS Nagar, JI Epstein. The Johns Hopkins Hospital, Baltimore. The Methodist Hospital Research Institute, Weill Cornell Medical College of Cornell Background: The current study assesses underdiagnosing Gleason pattern 5 on biopsy University, Houston, TX. and discuss the potential consequences for patient management. Background: Renal carcinoid tumors (RCT) are rare neoplasms. Unlike carcinoid Design: We retrieved 300 consecutive prostate biopsy cases from our consultation fi les tumors at other anatomic site, scarce data are available on the genetic changes in from 2009-2010 in which we identifi ed Gleason pattern 5. All cases were diagnosed RCT. We sought to determine if there were characteristic chromosomal copy number by one expert GU pathologist, and were sent in as a fi nal diagnosis, where the outside changes in RCT using SNP arrays on archival formalin-fi xed paraffi n embedded pathologist was not requesting consultation as a result of diffi culty with the diagnosis. (FFPE) tissue blocks. Cases typically were sent for consultation at the request of the patient or the outside Design: We obtained demographic, clinicopathologic information and archival FFPE treating physician. tissue blocks from 5 patients with RCT from multiple institutions. DNA from the FFPE Results: Table compares Gleason grades rendered upon expert review (EXP) compared tissue blocks was analyzed with 250K Nsp SNP microarrays (Affymetrix, Santa Clara, to those at the outside institutions (OS). CA). Virtual karyotypes were obtained detailing the genomic imbalances and loss of OS 3+3=6OS3+4=7 OS4+3=7 OS3+5=8 OS5+3=8 OS4+4=8 heterozygosity (LOH). EXP3+5=8 2 (6.5%) 15 (48.4%) 1 (3.2%) 10 (32.2%) 0 1 (3.2%) EXP5+3=8 0 0 4 (44.5%) 0 3 (33.3% 1 (11.1%) Results: The average age was 56 years (Male:Female 2:3). Tumors invaded perinephric EXP4+5=9 1 (0.8%) 11 (8.8%) 21 (16.8%) 3 (2.4%) 1 (0.8%) 51 (40.8%) adipose tissue (n= 5), lymph nodes (n=3) or presented with metastatic disease (n=2, EXP5+4=9 0 1 (1.4%) 5 (7.0%) 2 (2.8%) 1 (1.4%) 24 (33.3%) both liver). Three renal carcinoid tumors showed no chromosomal abnormalities EXP5+5=10 0001 (1.6%) 1 (1.6%) 8 (12.7%) (NCA). One tumor showed focal deletions in 3q [-3q(q21.31-q26.32]. One tumor, an atypical carcinoid, showed multiple chromosomal abnormalities including loss of 3p OS4+5=9 OS5+4=9 OS5+5=10 Total and other chromosomal losses [-1(p31.1-p31.1), -1(p22.3-p11.2), -3(p26.3-q11.2), EXP3+5=8 2 (6.5%) 0 0 31 (100%) -10(q21.2-q26.3), -10(q21.1-q21.1), -11(q14.3-q23.3), -13, -16(q13-q24.3)].