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Hepatocellular carcinoma occurring after successful treatment of childhood cancer with high dose chemotherapy and radiation
  1. T F Greten1,
  2. M P Manns1,
  3. I Reinisch2,
  4. P Kaatsch2
  1. 1Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Germany
  2. 2German Childhood Cancer Registry, Institute for Medical Biometrics, Epidemiology and Informatics, University of Mainz, Germany
  1. Correspondence to:
    Dr T F Greten
    Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg Str 1, 30625 Hannover, Germany;

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Hepatocellular carcinoma (HCC) is one of the world’s most common malignancies and accounts for more than 90% of all primary liver cancers. A number of different risk factors have been identified for the development of HCC.1 Hepatitis B carrier state, environmental toxins, chronic hepatitis C virus infection, hereditary haemochromatosis, and liver cirrhosis of almost any cause are well known risk factors for HCC. In addition, environmental toxins such as aflatoxins and contaminated drinking water may contribute to the pathogenesis of HCC, especially in Asia and underdeveloped countries. Finally, a number of HCC cases have occurred after the use of thorotrast for diagnostic procedures, and survivors of the atomic bomb of Hiroshima were also at higher risk for HCC development,2 indicating that radiation might also induce the development of HCC. Herein we describe a rare case of HCC occurring in a patient 17 years after successful treatment of peripheral neuroectodermal tumour (PNET)

A 32 year old female presented with pain in the right upper quadrant of her abdomen. Seventeen years prior to presentation in our hospital this patient was treated for a PNET with a combination of high dose chemotherapy (vincristine, adriablastin, ifosfamide, and actinomycin D) and surgical removal of the 10×5 cm tumour from her right chest followed by combined radiation (60 Gy) and chemotherapy. There were no signs of any recurrence of the tumour observed on her last check up 12 month earlier. Physical examination of the patient in our clinic showed typical signs of late radiation damage (erythema of the skin and an underdeveloped right breast) (fig 1). A firm 3–5 cm mass was palpable at the lower edge of the liver. Laboratory tests showed elevated α-fetoprotein (41881 μg/l). Hepatitis serology was negative and there was no evidence of any other liver disease. Magnetic resonance imaging revealed multiple intrahepatic masses up to 6.5 cm. A biopsy from the hepatic tumour was taken and confirmed the clinical diagnosis of HCC. The patient died three months after the diagnosis was made.

Figure 1

 Thorax and upper abdomen of the patient, 17 years after radiation with 60 Gy and removal of the peripheral neuroectodermal tumour.

To the best of our knowledge, secondary HCC following high dose chemotherapy has never been described and therefore we searched the German Childhood Cancer registry,3 which started to register all cases of malignancies in children (<15 years) in 1980. This database also collects data from secondary malignancies following chemotherapy. In this database we were able to detect a total of four more cases of secondary HCC, which are summarised in table 1. Interestingly one patient was hepatitis B surface antigen positive.

Table 1

 Details of five cases of secondary hepatocellular carcinoma

Radiotherapy has been shown to be associated with an increased risk of solid tumours 10–15 years after treatment and later.4 There is one report in the literature of a radiation induced hepatoma in a patient with a non-malignant hepatic haemangioma,5 which occurred 20 years after radiation of the liver with 28.5 Gy. To date, the molecular mechanism of hepatocarcinogenesis is not completely understood. The main causative agents—hepatitis B virus, hepatitis C virus, and aflatoxin B1—have been identified, which together are responsible for approximately 80% of all HCC in humans. This series of cases clearly supports the notion that secondary HCC can follow not only radiation therapy of children but also high dose chemotherapy, and may prompt careful follow up examinations of the liver in patients with a possible risk for the development of HCC.



  • Conflict of interest: None declared.