Kirkpatrickfleming0093

Purpose Oral potentially malignant disorders (OPMDs) may have varying degrees of oral epithelial dysplasia (OED). Traditional grading schemes separate OED into three-tiers (mild, moderate, and severe). Alternatively, a binary grading system has been previously proposed that stratifies OED into low-risk and high-risk categories based on a quantitative threshold of dysplastic pathologic characteristics. This systematic review evaluates the predictive value of a binary OED grading system and examines agreement between pathologists. Methods This meta-analysis queried 4 databases (PubMed, Ovid-MEDLINE, Cochrane, and SCOPUS) and includes 4 studies evaluating binary OED grading systems. Meta-analysis of proportions and correlations was performed to pool malignant transformation rates (MTR), risk of malignant transformation between OED categories, and measures of interobserver agreement. Results Pooled analysis of 629 lesions from 4 different studies found a six-time increased odds of malignant transformation in high-risk lesions over low-risk lesions [odds ratio (OR) 6.14, 95% 1.18-15.38]. Reported ORs ranged from 2.8 to 22.4. DBZ The overall MTR was 26.8%, with the high-risk and low-risk lesions having MTRs of 57.9% (95% CI 0.386-0.723) and 12.7% (95% CI - 0.210 to 0.438), respectively. Pooled unweighted interobserver kappa values for the binary grading system and three-tiered system were 0.693 (95% CI 0.640-0.740) and 0.388 (95% CI 0.195-0.552), respectively. Conclusion Binary grading of OED into low-risk and high-risk categories may effectively determine malignant potential, with improved interobserver agreement over three-tiered grading. Improved grading schemes of OED may help guide management (watchful waiting vs. excision) of these OPMDs.Biliary tract carcinomas are divided into intrahepatic, perihilar, distal extrahepatic cholangiocarcinomas, and gallbladder adenocarcinomas. Therapies targeting ROS1, ALK, MET, and HER2 alterations are currently evaluated in clinical trials. We assessed ROS1 and ALK translocations/amplifications as well as MET and HER2 amplifications for each tumor subtype by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) in 73 intrahepatic, 40 perihilar bile duct, 36 distal extrahepatic cholangiocarcinomas, and 45 gallbladder adenocarcinomas (n = 194). By FISH, we detected targetable alterations in 5.2% of cases (n = 10) HER2 and MET amplifications were found in 4.1% (n = 8) and 1.0% (n = 2), respectively. The HER2-amplified cases were mostly gallbladder adenocarcinomas (n = 5). The MET- and HER2-amplified cases were all positive by IHC. Fourteen cases without MET amplification were positive by IHC, whereas HER2 over-expression was detected by IHC only in HER2-amplified cases. We detected no ALK or ROS1 translocation or amplification. Several alterations were consistent with aneuploidy 24 cases showed only one copy of ROS1 gene, 4 cases displayed a profile of chromosomal instability, and an over-representation of centromeric alpha-satellite sequences was found in five cases. We confirm a relatively high rate of HER2 amplifications in gallbladder adenocarcinomas and the efficacy of IHC to screen these cases. Our results also suggest the value of IHC to screen MET amplification. Contrary to initial publications, ROS1 rearrangements seem to be very rare in biliary tract adenocarcinomas. We confirm a relatively high frequency of aneuploidy and chromosomal instability and reveal the over-representation of centromeric alpha-satellite sequences in intrahepatic cholangiocarcinomas.The existence of a true mixed germ cell-sex cord stromal tumor (MGSCT) of the testis remains controversial. Based on our experience with rare testicular tumors in this spectrum, we sought to perform a detailed clinicopathologic and molecular study of MGCSCT. Eight cases of testicular MGSCT were morphologically reviewed, screened for chromosomal aberrations (using array comparative genomic hybridization (aCGH) and low pass genomic sequencing), and analyzed by next generation sequencing (The Illumina TruSight Tumor 170). Immunohistochemistry for OCT3/4, Nanog, SALL4, DMRT1, and inhibin was performed on the cohort. Clinical data and follow-up were assessed by medical record review. All patients were karyotypically normal men aged 27-74 years (median 41). All tumors had a similar biphasic morphology characterized by various proportions of the sex cord component resembling granulosa cell tumor of adult type and the germ cell component cytomorphologically akin to spermatocytic tumor. Germ cells were haphazardly scaby extensive aneuploidies including recurrent gains of chromosomes 9 and 20 and loss of chromosome 7. In summary, our data support that rare examples of true MGSCT of the testis do exist and they represent a distinct tumor entity with admixed adult-type granulosa cell tumor and spermatocytic tumor components.The presence of sarcomatoid or rhabdoid features (which are associated with advanced disease and poor prognosis) is rarely observed in the subtypes of renal cell carcinoma (RCC). The SWI/SNF chromatin-remodeling complex, which is composed of evolutionarily conserved core subunits including SMARCB1/INI1 (SMARCB1), SMARCA4/BRG1 (SMARCA4), SMARCC1/BAF155 (SMARCC1), and SMARCC2/BAF170 (SMARCC2), can be regarded as the prototype of an epigenetic regulator of gene expression that is involved in tumor suppression. We analyzed the histological, immunohistochemical, and clinicopathological status in 72 cases of RCC with sarcomatoid or rhabdoid features, focusing on the expression status of the subunits of SWI/SNF chromatin-remodeling complex proteins. Cases with lost or reduced expression were defined as showing aberrant expression. The frequency of aberrant SMARCA4 immunoexpression of a sarcomatoid or rhabdoid component in clear cell RCC (ccRCC) (47/50, 94%) was significantly higher than that in non-ccRCC (4/9, 44%) (p less then 0.001). In ccRCC without sarcomatoid or rhabdoid features, aberrant SMARCA4 immunoexpression was observed in 33 of 48 (67%) cases. Immunoreactivities for SMARCB1, SMARCA2, and SMARCC2 were retained in almost all subtypes of RCC. The patients with aberrant SMARCA4 expression in RCC with sarcomatoid or rhabdoid features achieved shorter progression-free survival compared with the patients with retained SMARCA4 expression (all subtypes of RCC, p = 0.0212; ccRCC, p = 0.0265). These results suggest that in ccRCC, aberrant SMARCA4 expression is one of the adverse prognostic factors or a high-grade malignant transforming factor. The evaluation of SMARCA4 immunoexpression may be a useful diagnostic tool to help distinguish ccRCC from non-ccRCC.