Sotos syndrome and hepatocellular carcinoma

Clinical History

A 42-year old woman with clinically diagnosed Sotos syndrome (overgrowth and mental retardation) was referred to our institution by her G.P. because of fatigue and weight loss. There was no history of alcohol /drug abuse. The only medication that our patient used was an oral contraceptive.

Imaging Findings

Ultrasonography showed a mass in the right side of the abdomen extending from the liver to the pelvis and several liver lesions with a “target phenomenon” (hyperechoic lesion with a hypo-echogenic peripheral rim) (Figure 1). CT scan of the chest and abdomen showed an enlarged liver containing multiple hypervascular masses of variable sizes. As the masses had arterial blood supply through the hepatic artery and venous drainage through the hepatic veins a hepatic origin was suspected (Figures 2 -7). A mosaic enhancement pattern is seen in the masses (Figure 3), as well as ‘wash-out’ in the venous phase (Figures 4 and 5), characteristic of hepatocellular carcinoma (HCC). A small amount of ascitic fluid was present. No pulmonary or skeletal metastases were seen. The differential diagnosis based on CT findings included HCC, multiple hepatic adenomas with possible malignant degeneration of one or multiple nodules, fibrolamellar carcinoma, sarcoma and metastases.

Discussion

Background
HCC represents 90% of primary malignant liver tumours. The incidence of liver cancer in the Netherlands was 2.0 (males) and 0.8 (females) per 100.000 person years in 2008. [1] Cirrhosis is the most important risk factor for HCC and can be caused by chronic viral hepatitis (hepatitis B or C), alcohol abuse, metabolic diseases such as haemochromatosis, and non-alcoholic fatty liver disease. One out of three patients with cirrhosis develops HCC during their lifetime. [1] Patients with Sotos syndrome, one of the overgrowth syndromes that involves macrocephaly, tall stature and mental retardation, have an increased risk of developing a malignancy as compared to healthy controls. The risk of malignant disease has been estimated as 1 per 41 below the age of 4 years. [2] An increased risk of e.g. neuroblastoma, acute lymphoblastic leukaemia, Wilms tumour, and small cell lung cancer has been described amongst other types of cancer. [2, 3] The occurrence of HCC in a 14-year old boy with Sotos syndrome has been described in a previous case-report. [4] We present another case of HCC in a young patient with Sotos syndrome.
In Sotos syndrome, the insulin-like growth factor axis may play an important role in the aetiology of overgrowth and malignancies. [5, 6] Moreover, the insulin-like growth factor axis has recently been shown to be an important pathway in the development and progression of HCC and as a potential therapeutic target. [7] The insulin-like growth factor pathway promotes cell proliferation, migration as well as transformation into malignant clone. This might be an explanation for the occurrence of HCC in a liver without underlying chronic liver disease or cirrhosis.

Outcome
A biopsy was performed, that showed well differentiated HCC and no characteristics of sarcoma. Due to the extensive disease and the mental retardation of the patient, no locoregional treatment or systemic therapy (the only option being sorafenib) was initiated.

Differential Diagnosis List

Final Diagnosis

HCC with extracapsular tumour load.

URL:	https://www.eurorad.org/case/10976
DOI:	10.1594/EURORAD/CASE.10976
ISSN:	1563-4086