Perinodular K19 Patterns Are Generic to Advanced Chronic Liver Disease, a Study of 176 Hepatocellular Nodules (HCN) in Explanted Livers
JKM Lennerz, N Vachharajani, WC Chapman, EM Brunt. Washington University St. Louis, St. Louis
Background: In fibrotic chronic HCV and NASH, the epithelial-stromal compartment (ESC) hosts ductular reaction (DR), inflammation and fibrosis. Highlighted by type 2 keratin 7, DR is a reported diagnostic aid: indicative of perinodular stromal invasion by hepatocellular carcinoma (HCC) when absent. Proposed stem cell niches in the ESC include epithelial cells that express type 1 keratin 19 (K19). Study of the perinodular ESC of HCN is limited.
Design: Thirty-five coded slides from 32 patients with HCC in cirrhotic explants for HCV, Alcohol, HBV, cryptogenic, NASH, autoimmune, primary sclerosing cholangitis and Alagille's syndrome were used to mark 176 distinct HCN by H&E (EMB) as: cirrhotic nodule (CN), dysplastic nodule (DN), or HCC. Independent blinded review (JKL) noted 3 perinodular patterns of K19: (A) absent; (B) fragmented and thin cores of ovoid cells but not tubular formations; (C) circumferential, complex ductular structures, often multilayered. This study used virtual microscopy and statistical testing included intraclass-correlation-coefficient ICC and chi-square.
Results: By H&E, HCN were 54 HCC, 45 DN and 71 CN; the K19 IHC patterns were 62A, 41B and 67C (Fig. 1). The remaining 6 were 5 nodule-in-nodule (NIN) and 1 CN with mixed features of DN; K19 patterns were A(5 NIN) and C(1) respectively. As anticipated, K19 pattern of some DNs overlapped; with CN (24%), and HCC (26%). The ICC for H&E vs. K19 was 0.878 (p<0.02) overall; the distinction of non-HCC vs. HCC was also 'almost perfect' and the negative predicitve value of pattern A was 94%.
Conclusions: The study indicates very robust correlation of K19 patterns in the perinodular ESC with various HCN, regardless of liver disease: concentric tubular structures in ESC of CN, fragmented, attenuated cords <5 cells of DN, and absent in perinodular ESC of HCC. Thus the compelling relationship of intra- and extranodular pathology suggests the ESC as important in progression of CN and DN to HCC, and opens new approaches in the understanding of HCN pathogenesis.
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 164, Tuesday Morning