Hepatocellular carcinoma arising within focal nodular hyperplasia.

To the Editor: There are extremely broad differential diagnoses for a patient presenting with a liver mass, which includes both benign and malignant lesions. Most liver lesions can be identified based on clinical scenario and radiologic studies. However, they frequently pose a challenge for many clinicians. Benign liver tumors compose 3 to 5 per cent of all liver tumors with hemangioma (55–60%) and focal nodular hyperplasia (FNH) (21–27%) being most common. Adenomas comprise between 8 per cent and 19 per cent of benign liver tumors and are sometimes difficult to differentiate from other benign lesions and well-differentiated hepatocellular carcinoma (HCC) radiographically. Like FNH, adenomas typically display early contrast enhancement followed by rapid washout on both MRI and CT. FNH will demonstrate a characteristic “central scar” in two-thirds of lesions.1 Even if the preoperative diagnosis is correct, some masses may contain more than one lesion. HCC arising within FNH is very rare with only a few cases reported.2, 3 Herein, we report a case of HCC arising within FNH. An 86-year-old otherwise healthy woman who presented with abdominal pain and increased hepatic transaminases was found to have a liver mass on computed tomography. An 8.4 × 9.1 cm heterogeneously enhancing mass was noted in the right lobe of the liver arising from segment 6 (Fig. 1). There was slightly more enhancement on the arterial phase, as compared with the venous phase and an area of central lucency. There was no evidence of cirrhosis and tumor markers, including alpha-fetoprotein and carbohydrate antigen 19–9, were undetectable. Given the uncertainty of the radiographic findings and her advanced age, liver biopsy was undertaken. Histologic findings were consistent with HCC and the patient was referred to our institution. The patient was taken to surgery and underwent an uneventful partial right hepatectomy. The surgical specimen consisted of a segment of liver that measured 8.5 × 7.1 × 4.6 cm with a nodular external surface. Cut sections showed a well-circumscribed, nonencapsulated lobulated solid mass that measured 8.5 × 5.5 × 4.8 cm, with a red-brown, focally hemorrhagic surface alternating with pale trabecular stellate areas (Fig. 2). The surrounding uninvolved liver parenchyma was bile stained and rubbery, noncirrhotic appearing. Fig. 1 Computed tomography scan demonstrating a large liver lesion in segment VI with diffuse early arterial enhancement. Fig. 2 Gross appearance of resected specimen demonstrating well circumscribed heterogeneous 8.5 × 5.5 × 4.8 cm mass and adjacent noncirrhotic liver. Microscopically, the majority of the mass showed the histologic picture of a focal nodular hyperplasia with numerous foci of hepatocytes with a pseudoglandular pattern and intact reticulin framework, which prompted further sampling. Additional sections revealed two nodules of hepatocytes with greater cytologic atypia, Mallory’s hyaline, thickened trabecula, and loss of reticulin framework diagnostic of hepatocellular carcinoma. No vascular involvement was seen and the margin of resection was negative. After a rapid recovery, the patient has been followed every 3 months and remains free of disease 1 year after resection. HCC is one of the most common solid malignant tumors with an incidence of approximately one million new patients/year. Its incidence increases with age. There are several risk factors for HCC, all of which lead to or are a marker of chronic hepatocellular injury. The prognosis for untreated HCC is poor, with a median survival between 6 and 20 months. The gold standard of treatment remains surgical resection or transplantation. Poon et al.4 demonstrated 5-year survival rates for all patients with HCC undergoing resection as high as 25 to 49 per cent. HCC arising in a patient with FNH is a rare occurrence. There are several documented cases of HCC and FNH within the same patient.2, 3 Langerher et al.3 presented a study that showed 2 of 77 patients undergoing resection of FNH were found to have concomitant HCC. Most of the cases documented are of the fibrolamellar hepatocellular carcinoma variant. FNH is a benign process, and it is believed that FNH has no malignant potential. One theory of the development of FNH is that it is a localized hyperplastic response of hepatocytes to congenital arteriovenous malformation.1 Only one previous case of HCC appearing to arise within a background of FNH has been reported.2 In that case, Chen et al.2 described a tumor in which FNH abutted and partially surrounded an HCC within the same resected specimen. Clonal analysis was performed of the cell types and determined that the inactivated alleles in the FNH and HCC were different. These results suggest that HCC was not a product of malignant transformation of FNH. In our case, gross and microscopic review showed well-differentiated HCC surrounded by a background of FNH. Although clonal analysis was not completed in our patient, the complete embedding of HCC within the background of FNH suggests the potential of malignant transformation. Differentiation between benign and malignant hepatic lesions can be quite difficult with imaging alone, especially when tumor types such as FNH and HCC can coexist such as in the case described above. As such, a high index of suspicion with aggressive surgical intervention should be entertained in patients with symptomatic hepatic lesions.