Additional Morphological Features of Hepatocellular Carcinoma (HCC) Correlate with Disease Free Survival (DFS) but Are Not Independent Prognosticators: A Multivariate Survival Analysis
Vladislav Y Zakharov, Mark Orloff, Benedict J Maliakkal, Aram F Hezel, Gregory Connolly, Christa L Whitney-Miller. University of Rochester, Rochester, NY
Background: In addition to the routinely reported gross and microscopic morphological features of HCC, multiple other findings, such as histologically identifiable tumor capsule (TC), tumor capsule invasion (TCI), tumor infiltration by neutrophils (TIN), tumor infiltration by lymphocytes (TIL), apoptotic hepatocytes (AH), overall number of apoptotic cells (AC), intratumoral fibrosis (ITF), mitotic rate (MR) and gross tumor classification (GTC) have been described in literature as independent prognosticators of recurrence and metastasis after curative resection. We analyzed macro- and microscopic findings in HCC as prognostic factors of DFS after orthotopic liver transplantation.
Design: This study is a retrospective analysis of liver explant specimens with HCC and a corresponding chart review. 90 consecutive cases with a minimum 27-month follow up were identified in our departmental files from 2004-2009. The following histological features were evaluated on slide review: Edmondson-Steiner grade, margin status (MS), small vascular invasion (SVI), large vascular invasion (LVI), TCI, TIN, TIL, AH, AC, ITF and MR. The size of the largest nodule (SLN), number of nodules (NN), presence of satellite nodules (SN), necrosis or hemorrhage (NH), laterality, involvement of both lobes (BL) and GTC were recorded based on gross description and archive photos. The significance of individual parameters was established using Kaplan-Meier survival analysis (KMSA). As a second step, statistically significant findings were analyzed using a Cox regression multivariate survival analysis (CRMSA) model.
Results: The median age of patients was 57 years. Tumors ranged from grade 1 to 4, AJCC stage T1 – T4b. 20 patients (22%) had documented recurrence (either intra- or extra-hepatic) with 14.8 months of median disease free survival (DFS). Based on KMSA method, TCI, TIL, AH, MR, NN, SLN, HN, LVI, SVI, MS, BL and GTC were individually statistically significant. These values were subjected to CRMSA. Only size of the largest nodule, MS, LVI and number of nodules were identified as independent prognostic factors of DFS.
Conclusions: To our knowledge, this is the first multivariate survival analysis study which included routinely reported and additional morphological features of HCC. Multiple individual morphological features of HCC were shown to have significant correlation with clinical outcomes after liver resection. However, only features included in the current AJCC staging scheme had prognostic significance for DFS based on a CRMSA model.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 264, Monday Morning