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A difficult diagnosis of hepatocellular carcinoma recurrence after liver transplant
Accepted Manuscript Title: A difficult diagnosis of hepatocellular carcinoma recurrence after liver transplant Authors: Federica Invernizzi, Marco Maggioni, Laura Forzenigo, Maria Francesca Donato PII: DOI: Reference:
S1590-8658(17)30978-7 http://dx.doi.org/doi:10.1016/j.dld.2017.07.003 YDLD 3491
To appear in:
Digestive and Liver Disease
Please cite this article as: Invernizzi Federica, Maggioni Marco, Forzenigo Laura, Donato Maria Francesca.A difficult diagnosis of hepatocellular carcinoma recurrence after liver transplant.Digestive and Liver Disease http://dx.doi.org/10.1016/j.dld.2017.07.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
A difficult diagnosis of hepatocellular carcinoma recurrence after liver transplant Federica Invernizzi1, Marco Maggioni2, Laura Forzenigo3, Maria Francesca Donato1 1) Liver Transplant Hepatology Unit, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano 2) Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico 3) Division of Radiology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Corresponding Author: Maria Francesca Donato, MD Liver Transplant Hepatology Unit, Division of Gastroenterology and Hepatology Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico Via F. Sforza 35 – 20122 Milan ITALY Tel: +39-0255035432 Fax: +39-0250320410 email: [email protected]
A 61-year-old man received a liver transplant (LT) for multifocal hepatocellular carcinoma (HCC) and decompensated cirrhosis (HCC Milan In, Child B, MELD 20) on January 9, 2015. While on the waiting list, he received two courses of TACE bridging to transplant and underwent treatment with Sofosbuvir and Ribavirin to prevent graft HCV reinfection. At transplant, the patient’s serum alphafetoprotein (AFP) level was 22 ng/ml. He then received tacrolimus-based immunosuppression and was monitored by means of blood tests (including AFP), abdominal ultrasound (US) and total-body computed tomography (CT) every 6 months. During post-LT follow-up, the patient remained HCV-free with normal AFP levels
(2-5 ng/ml), normal liver graft function and negative imaging by US and total-body CT scan until February 2016. On May 2016, when he was completely asymptomatic, an isolated rise of his serum AFP level was detected (12 ng/ml), followed by a rising trend of AFP levels, which reached a value of 57 ng/ml on September 2016. At the time, a total-body CT scan, a bone scan and a Positron Emission Tomography were all negative for the presence of suspicious masses or increased focal metabolism. In December 2016, the patient’s AFP levels reached 110 ng/ml and an Abdominal Magnetic Resonance was performed showing a solid hyper-vascular mass located between the liver graft and the diaphragm, and infiltrating the inferior vena cava (Figure 1). When looking back at the explant pathology, we noticed that 5 HCC nodules had been detected (with sizes ranging from 0.5 to 3.2 cm) and the main nodule was poorly differentiated with an extracapsular infiltration plus vascular invasion (Figure 2), thus suggesting a high propensity to tumor recurrence. This case is interesting based on three main features of this transplanted patient that are mainly related to the biology of the transplanted HCC. Firstly, the significance of an upward trend of AFP levels, in absence of recurrent hepatitis C, strongly indicates the need for a more aggressive search of HCC recurrence after transplantation, as also shown in the setting of HBV-related HCC; secondly, the value of HCC histological features at explant pathology, in terms of grading and/or microvascular invasion, are useful for the prediction of post-transplant risk of HCC recurrence; and, finally, the importance of the role of abdominal MRI as a complementary imaging to a CT scan in the presence of difficult-to-diagnose and atypical locations of HCC recurrence [1,2]. Conflict of interest statement: MFD, FI, LVF, MM Nothing to disclose
References 1. Wong GLH, Chan HLY, Tse YK, Chan HY, Tse CH, Lo AOS, Wong VWS. On-treatment alpha-fetoprotein is a specific tumor marker for hepatocellular carcinoma in patients with chronic hepatitis B receiving entecavir. Hepatology 2014;59:986-995 2. Zhou L, Rui JA, Zhou WX, Wang SB, Chen SG, Qu Q. Edmondson-Steiner grade: A crucial predictor of recurrence and survival in hepatocellular carcinoma without microvascular invasion. Pathol Res Pract. 2017;213:824-830.
Legend to Figures Figure 1. T1/T2 weighted axial images of MR. Pre-contrast phases: panel A (T1). Postcontrast phases: liver mass (arterial, panel B; portal, panel C); caval invasion (arterial, panel D, portal panel E). Figure 2. Hepatocellular carcinoma with mixed trabecular/solid growth pattern, poorly differentiated, (panel A: H&E, 400x). Tumor infiltrates extra-parenchymal soft tissue (panel B: H&E, 200x); arrows identify foci of vascular invasion.
S1590-8658(17)30978-7 http://dx.doi.org/doi:10.1016/j.dld.2017.07.003 YDLD 3491
To appear in:
Digestive and Liver Disease
Please cite this article as: Invernizzi Federica, Maggioni Marco, Forzenigo Laura, Donato Maria Francesca.A difficult diagnosis of hepatocellular carcinoma recurrence after liver transplant.Digestive and Liver Disease http://dx.doi.org/10.1016/j.dld.2017.07.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
A difficult diagnosis of hepatocellular carcinoma recurrence after liver transplant Federica Invernizzi1, Marco Maggioni2, Laura Forzenigo3, Maria Francesca Donato1 1) Liver Transplant Hepatology Unit, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano 2) Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico 3) Division of Radiology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Corresponding Author: Maria Francesca Donato, MD Liver Transplant Hepatology Unit, Division of Gastroenterology and Hepatology Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico Via F. Sforza 35 – 20122 Milan ITALY Tel: +39-0255035432 Fax: +39-0250320410 email: [email protected]
A 61-year-old man received a liver transplant (LT) for multifocal hepatocellular carcinoma (HCC) and decompensated cirrhosis (HCC Milan In, Child B, MELD 20) on January 9, 2015. While on the waiting list, he received two courses of TACE bridging to transplant and underwent treatment with Sofosbuvir and Ribavirin to prevent graft HCV reinfection. At transplant, the patient’s serum alphafetoprotein (AFP) level was 22 ng/ml. He then received tacrolimus-based immunosuppression and was monitored by means of blood tests (including AFP), abdominal ultrasound (US) and total-body computed tomography (CT) every 6 months. During post-LT follow-up, the patient remained HCV-free with normal AFP levels
(2-5 ng/ml), normal liver graft function and negative imaging by US and total-body CT scan until February 2016. On May 2016, when he was completely asymptomatic, an isolated rise of his serum AFP level was detected (12 ng/ml), followed by a rising trend of AFP levels, which reached a value of 57 ng/ml on September 2016. At the time, a total-body CT scan, a bone scan and a Positron Emission Tomography were all negative for the presence of suspicious masses or increased focal metabolism. In December 2016, the patient’s AFP levels reached 110 ng/ml and an Abdominal Magnetic Resonance was performed showing a solid hyper-vascular mass located between the liver graft and the diaphragm, and infiltrating the inferior vena cava (Figure 1). When looking back at the explant pathology, we noticed that 5 HCC nodules had been detected (with sizes ranging from 0.5 to 3.2 cm) and the main nodule was poorly differentiated with an extracapsular infiltration plus vascular invasion (Figure 2), thus suggesting a high propensity to tumor recurrence. This case is interesting based on three main features of this transplanted patient that are mainly related to the biology of the transplanted HCC. Firstly, the significance of an upward trend of AFP levels, in absence of recurrent hepatitis C, strongly indicates the need for a more aggressive search of HCC recurrence after transplantation, as also shown in the setting of HBV-related HCC; secondly, the value of HCC histological features at explant pathology, in terms of grading and/or microvascular invasion, are useful for the prediction of post-transplant risk of HCC recurrence; and, finally, the importance of the role of abdominal MRI as a complementary imaging to a CT scan in the presence of difficult-to-diagnose and atypical locations of HCC recurrence [1,2]. Conflict of interest statement: MFD, FI, LVF, MM Nothing to disclose
References 1. Wong GLH, Chan HLY, Tse YK, Chan HY, Tse CH, Lo AOS, Wong VWS. On-treatment alpha-fetoprotein is a specific tumor marker for hepatocellular carcinoma in patients with chronic hepatitis B receiving entecavir. Hepatology 2014;59:986-995 2. Zhou L, Rui JA, Zhou WX, Wang SB, Chen SG, Qu Q. Edmondson-Steiner grade: A crucial predictor of recurrence and survival in hepatocellular carcinoma without microvascular invasion. Pathol Res Pract. 2017;213:824-830.
Legend to Figures Figure 1. T1/T2 weighted axial images of MR. Pre-contrast phases: panel A (T1). Postcontrast phases: liver mass (arterial, panel B; portal, panel C); caval invasion (arterial, panel D, portal panel E). Figure 2. Hepatocellular carcinoma with mixed trabecular/solid growth pattern, poorly differentiated, (panel A: H&E, 400x). Tumor infiltrates extra-parenchymal soft tissue (panel B: H&E, 200x); arrows identify foci of vascular invasion.