Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 27, 2015; 7(2): 276-284
Published online Feb 27, 2015. doi: 10.4254/wjh.v7.i2.276
Post-transplantation hepatocellular carcinoma recurrence: Patterns and relation between vascularity and differentiation degree
Annarita Pecchi, Giulia Besutti, Mario De Santis, Cinzia Del Giovane, Sofia Nosseir, Giuseppe Tarantino, Fabrizio Di Benedetto, Pietro Torricelli
Annarita Pecchi, Giulia Besutti, Mario De Santis, Pietro Torricelli, Dipartimento di Diagnostica per Immagini, Azienda Ospedaliero-Universitaria Policlinico di Modena, 41124 Modena, Italy
Cinzia Del Giovane, Unità di Statistica Medica, Dipartimento di Medicina Diagnostica, Clinica e Sanità Pubblica, Università di Modena e Reggio Emilia, 41124 Modena, Italy
Sofia Nosseir, Dipartimento dei Laboratori, Anatomia Patologica e Medicina Legale, Università degli studi di Modena e Reggio Emilia, 41124 Modena, Italy
Giuseppe Tarantino, Fabrizio Di Benedetto, Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa, Università di Modena e Reggio Emilia, 41124 Modena, Italy
Author contributions: Pecchi A, Besutti G, De Santis M and Torricelli P designed the study and reviewed imaging examinations; Nosseir S reviewed pathological reports; Del Giovane C carried out the statistical analysis; Tarantino G and Di Benedetto F provided all clinical information.
Ethics approval: This work has been carried out in accordance with the Declaration of Helsinki (2000) of the World Medical Association.
Informed consent: All patients gave their verbal consent to the use of their data for scientific purposes at the moment of their admission to the Transplantation Department.
Conflict-of-interest: All authors have no conflicts of interest to declare.
Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Annarita Pecchi, Dipartimento di Diagnostica per Immagini, Azienda Ospedaliero-Universitaria Policlinico di Modena, Via del Pozzo 71, 41124 Modena, Italy.
Telephone: +39-059-4225282 Fax: +39-059-4224290
Received: August 21, 2014
Peer-review started: August 23, 2014
First decision: November 14, 2014
Revised: December 16, 2014
Accepted: January 9, 2015
Article in press: Janurary 12, 2015
Published online: February 27, 2015

AIM: To evaluate the relationship between hepatocellular carcinoma (HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence.

METHODS: This retrospective study included 165 patients (143 men, 22 women; median age 56.8 years, range 28-70.4 years) transplanted for HCC who had a follow-up period longer than 2 mo. Pre-transplantation dynamic computed tomography or magnetic resonance examinations were retrospectively reviewed, classifying HCC imaging enhancement pattern into hypervascular and hypovascular based on presence of wash-in during arterial phase. All pathologic reports of the explanted livers were reviewed, collecting data about HCC differentiation degree. The association between imaging vascular pattern and pathological grade was estimated using the Fisher exact test. All follow-up clinical and imaging data were reviewed for evidence of recurrence. Recurrence rate was calculated and imaging features of recurrent tumor were collected, classifying early and late recurrences based on timing (< or ≥ 2 years after transplantation) and intrahepatic, extrahepatic and both intrahepatic and extrahepatic recurrences based on location. All intrahepatic recurrences were classified as hypervascular or hypovascular and the differentiation degree was collected where available. The presence of variations in imaging enhancement pattern and pathological grade between the primary tumor and the intrahepatic recurrence was evaluated and the association between imaging and histopatholgical variations was estimated by using the χ2 test.

RESULTS: Of the 163 patients with imaging evidence of viable tumor, 156 (95.7%) had hypervascular and 7 (4.3%) hypovascular HCC. Among the 125 patients with evidence of viable tumor in the explanted liver, 19 (15.2%) had grade 1, 56 (44.8%) grade 2, 40 (32%) grade 3 and 4 (3.2%) grade 4 HCC, while the differentiation degree was not assessable for 6 patients (4.8%). A significant association was found between imaging vascularity and pathological grade (P = 0.035). Post-transplantation recurrence rate was 14.55% (24/165). All recurrences occurred in patients who had a hypervascular primary tumor. Three patients (12.5%) experienced late recurrence; the location of the first recurrence was extrahepatic in 14 patients (58.3%), intrahepatic in 7 patients (29.2%) and both intrahepatic and extrahepatic in 3 patients (12.5%). Two patients had a variation in imaging characteristics between the primary HCC (hypervascular) and the intrahepatic recurrent HCC (hypovascular), while 1 patient had a variation of histopathological characteristics (from moderate to poor differentiation), however no association was found between imaging and histopathological variations.

CONCLUSION: A correlation was found between HCC grade and vascularity; some degree of variability may exist between the primary and the recurrence imaging/histopathological characteristics, apparently not correlated.

Keywords: Contrast media, Hepatocellular carcinoma, Liver transplantation, Cell differentiation, Recurrence

Core tip: During hepatocarcinogenesis, besides the differentiation loss, blood supply changes occur. Recently, a correlation between higher histopathological grades and hypervascular dynamic-imaging enhancement pattern has been demonstrated. Hepatocellular carcinoma recurrence after transplantation is relatively common, however the issue of possible variations in imaging and histopathology between the primary and the recurrent tumor, and particularly the relationship between enhancement and grade changes, has never been investigated. We demonstrated a correlation between vascularity and pathological grade in a large population of transplanted patients, and some degree of variability between the primary and the recurrent tumor vascularity was found, though not associated with histopathological changes.