Dhall, Deepti

Abstract Objectives Fibronodular hepatocellular carcinoma (FN-HCC) is a newly described variant of hepatocellular carcinoma (HCC), with only 29 cases reported. Histologically, it is divided into multiple smaller, well-defined tumor nodules by extensive fibrosis. Its differential diagnosis includes other HCC variants characterized by fibrous stroma, such as fibrolamellar hepatocellular carcinoma and scirrhous hepatocellular carcinoma. Fibronodular hyperplasia may also be considered in the differential diagnosis. We are reporting 7 cases to help better understand this entity. Methods We retrospectively identified 7 cases of FN-HCC and analyzed the clinical and histologic features of each tumor, as well as disease progression and patient prognosis. Results The FN-HCC cases were diagnosed at a median age of 58 years (range, 40-75 years), with a male predilection (n = 6, 86%). Most patients were White (n = 6, 86%), and 1 was African American (n = 1, 14%). Tumors had a mean size of 3.15 cm (range, 1-9 cm) and were mainly located in the right lobe (n = 5, 71%). Background liver was cirrhotic in 6 cases (86%). Five patients were hepatitis C positive (71%). All tumors were surgically removed, with a free resection margin. Among 3 patients with evident vascular invasion, 1 had a positive lymph node. This patient had tumor metastasis 6 years later; otherwise, all patients were disease free on follow-up. Conclusions Our cohort was concordant with published data showing a male predilection, hepatitis C association, and good prognosis when the disease is discovered before metastasis and is surgically excised with negative margins. However, it contradicts the published literature that associates FN-HCC with the absence of advanced fibrosis/cirrhosis.

Abstract Objectives Nodular regenerative hyperplasia (NRH) is a rare vascular disorder of the liver. Clinically, patients present with portal hypertension with or without a cholestatic pattern of injury. Histologically, the liver parenchyma is composed of small nodules of hypertrophic hepatocytes surrounded by atrophic hepatocytes without significant fibrosis. Nodular regenerative hyperplasia is a difficult diagnosis on biopsy specimens, but biopsy remains the gold standard for diagnosis. In this retrospective review, cytokeratin 7 (CK7) immunohistochemistry (IHC) was used to aid in the diagnosis and further characterization of NRH and NRH-like changes. Methods The H&E-stained slides, reticulin, and CK IHC were reviewed for 22 cases. The percentage of hepatocytes staining for CK7 (0%-100%), the location of staining (centrilobular hepatic progenitor cells vs periportal/bile ductular reaction), and the pattern of staining distribution (patchy or diffuse) were recorded for comparison. Results Of the 22 cases, 9 were CK7 positive. Cases of NRH, however, expressed various degrees of CK7 positivity in centrilobular hepatic progenitor cells, unlike NRH-like changes, which were either CK7 negative or CK7 positive in periportal hepatocytes or in areas of bile ductular reaction. Conclusions In cases with the appropriate clinical history and histology, CK7 immunohistochemistry can be performed to distinguish nodular regenerative hyperplasia (primary) and NRH-like changes (secondary). In difficult cases, CK7 positivity in centrilobular hepatic progenitor cells can help confirm the diagnosis of NRH. These data support NRH as a true entity with a distinct pathophysiology from NRH-like changes.

Currently, there are no internationally accepted consensus guidelines for pathologic evaluation of posttherapy pancreatectomy specimens. The Neoadjuvant Therapy Working Group of Pancreatobiliary Pathology Society was formed in 2018 to review grossing protocols, literature, and major issues and to develop recommendations for pathologic evaluation of posttherapy pancreatectomy specimens. The working group generated the following recommendations: (1) Systematic and standardized grossing and sampling protocols should be adopted for pancreatectomy specimens for treated pancreatic ductal adenocarcinoma (PDAC). (2) Consecutive mapping sections along the largest gross tumor dimension are recommended to validate tumor size by histology as required by the College of American Pathologists (CAP) cancer protocol. (3) Tumor size of treated PDACs should be measured microscopically as the largest dimension of tumor outer limits that is bound by viable tumor cells, including intervening stroma. (4) The MD Anderson grading system for tumor response has a better correlation with prognosis and better interobserver concordance among pathologists than does the CAP system. (5) A case should not be classified as a complete response unless the entire pancreas, peripancreatic tissues, ampulla of Vater, common bile duct, and duodenum adjacent to the pancreas are submitted for microscopic examination. (6) Future studies on tumor response of lymph node metastases, molecular and/or immunohistochemical markers, as well as application of artificial intelligence in grading tumor response of treated PDAC are needed. In summary, systematic, standardized pathologic evaluation, accurate tumor size measurement, and reproducible tumor response grading to neoadjuvant therapy are needed for optimal patient care. The criteria and discussions provided here may provide guidance towards these goals.