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Context.--Serosal involvement (pT4a category) and lymphovascular invasion have prognostic significance in colorectal carcinoma, but are subject to interobserver variation in assessment. Objectives.--To provide the first large-scale assessment of interobserver variability in pT4a category and lymphovascular invasion reporting in real-world practice and to explore the impact of information from guidelines on variability in reporting these features. Design.--Analysis of 1555 consecutive synoptic reports of colorectal carcinoma was performed using multivariate logistic regression. Interobserver variability before and after the presentation of guideline information was assessed using an image-based survey. Results.--Significant differences in the odds of reporting pT4a versus pT3 category, detecting lymphovascular invasion of any type, and detecting large vessel invasion were identified among hospital sites and for individual pathologists compared with the median pathologist at the same site. Consistent with these results, interobserver agreement was only moderate in the image-based survey regarding T4a staging and lymphovascular invasion (all κ ≤ 0.57). The provision of information from guidelines did not tend to increase interobserver agreement in the survey, though responses in favor of using an elastic stain increased following recommendations for their use. However, when observers were provided with elasticstained images, interobserver agreement remained only moderate (κ = 0.55). Conclusions.--Real-world reporting of pT4a category and lymphovascular invasion shows substantial variability at both local and regional levels. Our study underscores the need to address these features in quality initiatives, and provides a novel method through which existing synoptic data can be harnessed to monitor reporting patterns and provide individualized feedback. [ABSTRACT FROM AUTHOR]

Fibrolamellar carcinoma is a rare primary hepatocellular malignancy arising in noncirrhotic livers of young individuals. Patients commonly present with a large solitary liver mass and nonspecific symptoms. Characteristic histologic features include large polygonal cells with oncocytic cytoplasm and prominent nucleoli separated into trabeculae and cords by dense parallel bands of collagen. Important differential diagnoses include classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma, which may be distinguished by a judicious panel of immunohistochemical studies, including cytokeratin 7, CD68, and hepatocyte paraffin 1 (HepPar-1). In addition, fibrolamellar carcinomas are characterized by activation of protein kinase A. Prognosis of fibrolamellar carcinoma is similar to classical hepatocellular carcinoma occurring in the absence of liver cirrhosis and is strongly correlated with tumor resectability. Other treatment options include liver transplant, chemotherapy, and hepatic artery embolization. In this article, we review the clinical features, gross and microscopic pathology, molecular genetics, differential diagnosis, treatment, and prognosis of this rare and interesting tumor. [ABSTRACT FROM AUTHOR]

Context.—Colorectal cancer is a heterogeneous disease resulting from different molecular pathways of carcinogenesis. Recent data evaluating the histologic features and molecular basis of the serrated polyp-carcinoma pathway have significantly contributed to more comprehensive classifications of and treatment recommendations for these tumors. Objective.—To integrate the most recent molecular findings in the context of histologic classifications of serrated lesions and their implications in diagnostic pathology and colorectal cancer surveillance. Data Sources.—Published literature focused on serrated polyps and their association with colorectal cancer. Conclusions.—Three types of serrated polyps are currently recognized: hyperplastic polyps, sessile serrated adenomas/polyps, and traditional serrated adenomas. The BRAF V600E mutation is one of the most frequent molecular abnormalities identified in hyperplastic polyps and sessile serrated adenomas. In contrast, in traditional serrated adenomas, either BRAF V600E or KRAS mutations can be frequently identified. CpG methylation has emerged as a critical molecular mechanism in the sessile serrated pathway. CpG methylation of MLH1 often leads to reduced or lost expression in dysplastic foci and carcinomas arising in sessile serrated adenomas/polyps. [ABSTRACT FROM AUTHOR]

Context.--In advanced gastric, esophageal, and gastroesophageal junction adenocarcinomas (GE-GEJ-AC) that overexpress ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2), anti-HER2 monoclonal antibody therapy confers survival benefit. To select patients for treatment, HER2 expression and gene amplification are evaluated by immunohistochemistry (IHC) and in situ hybridization. Objective.--To determine whether GE-GEJ-AC tested for HER2 on biopsy specimens of a primary tumor show different IHC scores and/or HER2 amplification by in situ hybridization in matched resection specimens, potentially changing therapy eligibility. Design.--Immunohistochemistry and silver in situ hybridization were performed in biopsy and/or resection specimens from 100 patients. HER2 testing was performed in matched resection and biopsy specimens of 15 cases to determine whether GE-GEJ-AC with IHC scores of 0, 1+, and 2+ in biopsy and resection specimens had different IHC and silver in situ hybridization results. Results.--The IHC 3+ cases showed HER2 amplification in 4 of 5 cases (80%), and IHC scores of 0, 1+, and 2+ showed 3.5%, 14.3%, and 23.5% HER2 amplification by silver in situ hybridization. Among the 15 paired biopsy and resection specimens, 9 (60%) had at least pT2 stage GE-GEJ-AC with HER2 IHC scores of 0, 1+,or2+ in the biopsy, and 2 of those 9 cases (22%) had IHC 3+ and HER2 amplification by silver in situ hybridization on the resection specimen. Conclusions.--Our data suggest that HER2 testing should be repeated on resection specimens of GE-GEJ-AC with HER2 IHC scores of negative (0 and 1+) or equivocal (2+) and in situ hybridization amplification negative biopsy specimen results to evaluate for HER2 heterogeneity when patients are being considered for anti-HER2 therapy. [ABSTRACT FROM AUTHOR]

Fibrolamellar carcinoma is a rare primary hepatocellular malignancy arising in noncirrhotic livers of young individuals. Patients commonly present with a large solitary liver mass and nonspecific symptoms. Characteristic histologic features include large polygonal cells with oncocytic cytoplasm and prominent nucleoli separated into trabeculae and cords by dense parallel bands of collagen. Important differential diagnoses include classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma, which may be distinguished by a judicious panel of immunohistochemical studies, including cytokeratin 7, CD68, and hepatocyte paraffin 1 (HepPar-1). In addition, fibrolamellar carcinomas are characterized by activation of protein kinase A. Prognosis of fibrolamellar carcinoma is similar to classical hepatocellular carcinoma occurring in the absence of liver cirrhosis and is strongly correlated with tumor resectability. Other treatment options include liver transplant, chemotherapy, and hepatic artery embolization. In this article, we review the clinical features, gross and microscopic pathology, molecular genetics, differential diagnosis, treatment, and prognosis of this rare and interesting tumor.