Molecular testing for the clinical diagnosis of fibrolamellar carcinoma.

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed to detect this fusion event and to examine its diagnostic performance in a large, multicenter, multinational study. Cases initially classified as fibrolamellar carcinoma based on histological features were reviewed from 124 patients. Upon central review, 104 of the 124 cases were classified histologically as typical of fibrolamellar carcinoma, 12 cases as 'possible fibrolamellar carcinoma' and 8 cases as 'unlikely to be fibrolamellar carcinoma'. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) typical fibrolamellar carcinomas, 9 of 12 'possible fibrolamellar carcinomas' and 0 of 8 cases 'unlikely to be fibrolamellar carcinomas'. Within the morphologically typical group of fibrolamellar carcinomas, two tumors with unusual FISH patterns were also identified. Both cases had the fusion gene DNAJB1-PRKACA, but one also had amplification of the fusion gene and one had heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. These findings demonstrate that FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more accurate when based on morphology plus confirmatory testing than when based on morphology alone

HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma

CONTEXT: ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA. OBJECTIVES: To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making. DESIGN: The College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology convened an expert panel to conduct a systematic review of the literature to develop an evidence-based guideline with recommendations for optimal HER2 testing in patients with GEA. RESULTS: The panel is proposing 11 recommendations with strong agreement from the open-comment participants. RECOMMENDATIONS: The panel recommends that tumor specimen(s) from all patients with advanced GEA, who are candidates for HER2-targeted therapy, should be assessed for HER2 status before the initiation of HER2-targeted therapy. Clinicians should offer combination chemotherapy and a HER2-targeted agent as initial therapy for all patients with HER2-positive advanced GEA. For pathologists, guidance is provided for morphologic selection of neoplastic tissue, testing algorithms, scoring methods, interpretation and reporting of results, and laboratory quality assurance. CONCLUSIONS: This guideline provides specific recommendations for assessment of HER2 in patients with advanced GEA while addressing pertinent technical issues and clinical implications of the results

Interobserver agreement of estimating the extent of intestinal metaplasia in patients with chronic atrophic gastritis

The extent of gastric intestinal metaplasia (GIM) can be used to determine the risk of gastric cancer. Eleven international gastrointestinal expert pathologists estimated the extent of GIM on haematoxylin and eosin (H&E)- and Alcian blue-Periodic acid Schiff (AB-PAS)-stained slides of 46 antrum biopsies in 5% increments. Interobserver agreement was tested with the intraclass correlation coefficient (ICC). Correlation between standard deviation and extent of GIM was evaluated with the Spearman correlation. The interobserver agreement was very good (ICC = 0.983, 95% confidence interval (CI) 0.975–0.990). The use of AB-PAS did not increase the agreement (ICC = 0.975, 95% CI 0.961–0.985). Cases with a higher amount of metaplastic epithelium demonstrated a higher standard deviation (rs = 0.644; p < 0.01), suggesting lower diagnostic accuracy in cases with extensive GIM. In conclusion, estimating the extent of GIM on H&E-stained slides in patients with chronic atrophic gastritis can be achieved satisfactorily with high interobserver agreement, at least among international expert gastrointestinal pathologists.Open access funding provided by Medical University of Graz.https://www.springer.com/journal/428am2023Anatomical Patholog

Consensus Recommendations for Histological Criteria of Autoimmune Hepatitis from the International AIH Pathology Group

Background & Aims Diagnostic histological criteria for autoimmune hepatitis (AIH) have not been clearly established. Previously published criteria focused mainly on chronic AIH, in which inflammatory changes mainly occur in portal/periportal regions and may not be applicable to acute presentation of AIH, in which inflammatory changes are typically predominantly lobular in location. International consensus criteria for the diagnosis and assessment of disease severity in both acute and chronic AIH are thus urgently needed. Methods Seventeen expert liver pathologists convened at an international workshop and subsequently used a modified Delphi panel approach to establish consensus criteria for the histopathological diagnosis of AIH. Results The consensus view is that liver biopsy should remain standard for diagnosing AIH. AIH is considered likely, if there is a predominantly portal lymphoplasmacytic hepatitis with more than mild interface activity and/or more than mild lobular hepatitis in the absence of histological features suggestive of another liver disease. AIH is also considered likely if there is predominantly lobular hepatitis with or without centrilobular necroinflammation and at least one of the following features: portal lymphoplasmacytic hepatitis, interface hepatitis or portal-based fibrosis, in the absence of histological features suggestive of another liver disease. Emperipolesis and hepatocellular rosettes are not regarded as being specific for AIH. Conclusions The criteria proposed in this consensus statement provide a uniform approach to the histological diagnosis of AIH, which is relevant for patients with an acute as well as a chronic presentation and to more accurately reflect the current understanding of liver pathology in AIH

A practical diagnostic approach to hepatic masses

The differential diagnosis of hepatic mass lesions is broad and arriving at the right diagnosis can be challenging, especially on needle biopsies. The differential diagnosis of liver tumors in children is different from adults and is beyond the scope of this review. In adults, the approach varies depending on the age, gender, and presence of background liver disease. The lesions can be divided broadly into primary and metastatic (secondary), and the primary lesions can be further divided into those of hepatocellular origin and nonhepatocellular origin. The first category consists of benign and malignant lesions arising from hepatocytes, while the second category includes biliary, mesenchymal, hematopoietic, and vascular tumors. Discussion of nonepithelial neoplasms is beyond the scope of this review. The hepatocytic lesions comprise dysplastic nodules, focal nodular hyperplasia, hepatic adenoma, and hepatocellular carcinoma, and the differential diagnosis can be challenging requiring clinicopathological correlation and application of immunohistochemical (IHC) markers. Liver is a common site for metastasis, sometimes presenting with an unknown primary site, and proper workup is the key to arriving at the correct diagnosis. The correct diagnosis in this setting requires a systematic approach with attention to histologic features, imaging findings, clinical presentation, and judicious use of IHC markers. The list of antibodies that can be used for this purpose keeps on growing continually. It is important for pathologists to be up to date with the sensitivity and specificity of these markers and their diagnostic role and clinical implications. The purpose of this review is to outline the differential diagnosis of hepatic masses in adults and discuss an algorithmic approach to make a right diagnosis

Pathologic assessment of endoscopic resection specimens with superficial carcinoma of the esophagus: current practice and practical issues.

Endoscopic resection (ER) has become the first-line therapy for early esophageal cancer and offers a treatment alternative to surgery, owing to less morbidity and better quality of life. ER techniques include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). EMR is faster, simpler, and cheaper than ESD, but limited by its ability to resect lesions larger than 1.5 centimeters. Piecemeal EMR has limitations, including a high local recurrence rate and a suboptimal specimen for an accurate pathologic assessment. ESD, on the other hand, allows en bloc resections with negative (R0) margins, irrespective of lesion size, providing an excellent pathologic specimen, however, is technically challenging with a higher risk of complications. The evaluation of ER specimens in pathology varies slightly from institution to institution. Our review summarizes the current practices and issues in the pathologic assessment of esophageal ER specimens, which highlights the necessity of a systematic approach and standardization of both macroscopic and microscopic evaluation. There is a need for a comprehensive and standardized pathology report that will allow for uniform terminology for endoscopists, surgeons, and pathologists, which, in turn, will result in better treatment guidance