EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Hepatocellular carcinoma with prominent fatty change is rare, and to date only a few cases have been reported. In this article, we present a 57-year-old woman who underwent a liver transplant for hepatocellular carcinoma. Ten months after liver transplant, she presented with a persistent cough. Computed tomography of the chest was performed, revealing a solid lung mass that measured 1 × 0.9 cm in the right inferior lobe. Right inferior lobectomy was performed, and the final diagnosis was noted as hepatocellular carcinoma with prominent fatty change. Fatty change was extensive in the tumor; therefore, lipoid pneumonia was the first condition that was considered in the differential diagnosis during examination of the lobectomy material. For the differential diagnosis, the immunohistochemistry panel was studied to show the hepatocellular nature of the tumor. Although metastasis of hepatocellular carcinoma to the lungs is expected, hepatocellular carcinoma with prominent fatty change can cause diagnostic difficulties, such as lipoid pneumonia, especially in small lung biopsies.

Key words : Carcinoma, Hepatocellular, Lung, Metastasis

Hepatocellular carcinoma is the most common primary malignant tumor in the liver.^1-3 It is 3 times more common in men than in women. Several typical histologic patterns of hepatocellular carcinoma have been described by the World Health Organization; the most common is the trabecular pattern.^1-3 Acinar, solid, scirrhous, and clear cell patterns are the other frequent patterns of hepatocellular carcinoma.^1,2 Hepatocellular carcinoma with fatty change is extremely rare and can cause some diagnostic difficulties in metastatic lesions. We present a case of a lung metastasis of hepatocellular carcinoma with prominent fatty change 10 months after liver transplant.

We report a 57-year-old woman who received a right lateral segment liver transplant from her 25-year-old daughter. The patient was started on an immunosuppression regimen of tacrolimus and mycophenolate mofetil. The patient was reviewed because of elevated serum hepatitis B surface antigen for 17 years and because she had chronic liver disease symptoms for 2 years. Multiple liver masses had been recognized during follow-up and biopsy was performed on the lesions. The final diagnosis was reported as hepatocellular carcinoma. She underwent arterial chemoembolization twice for hepatocellular carcinoma, and then was referred to Başkent University for liver transplant. On histopathological examination of the native liver, hepatocellular carcinoma with necrosis due to chemoembolization and a background of cirrhosis were noted. The tumor was composed of atypical cells with a trabecular pattern (Figure 1A), and fatty change was seen around the tumor cells (Figure 1B). Lymphovascular invasion also was detected. After 10 months, the patient presented with a persistent cough. Computed tomography of the chest revealed a solid lung mass in the right inferior lobe and a right inferior lobectomy was performed. On intra-parenchymal macroscopy, a yellowish mass that was 1 × 0.9 × 0.8 cm was noted. Microscopically, the tumor was composed of cells that mimic normal hepatocytes, but a high degree of nuclear atypia and widespread fatty changes was remarkable (Figures 2A and 2B). Immunohistochemical analysis showed positive staining for pan cytokeratin and Hep par 1 antibody (Figure 2C) and negative staining for the CD68 histiocytic marker. Based on these features, the diagnosis was metastasis of hepatocellular carcinoma with fatty changes.

Hepatocellular carcinoma is one of the most common malignancies in the world.¹ The vast majority of hepatocellular carcinoma develop in cirrhotic livers. Hepatitis B and C, alcohol, metabolic disorders, drugs, and toxins also may increase the risk for hepatocellular carcinoma by causing cirrhosis.¹ Surgical resection is the mainstay for hepatocellular carcinoma treatment for patients without cirrhosis and no evidence of vascular invasion or extrahepatic disease.¹ Liver transplant is the best treatment for hepatocellular carcinoma in cirrhotic patients. Outcomes after liver transplant depend on hepatocellular carcinoma recurrence.^1,2 Hepato-cellular carcinoma shows both intrahepatic and extrahepatic metastasis.^2-4 Extrahepatic metastasis of hepatocellular carcinoma occurs in about 30% to 50% of patients, and it depends on hepatocellular carcinoma stages.¹ The most common metastatic sites are the lung and (less frequently) the lymph nodes and bones.^2-4 The tumor size is the most important prognostic factor for hepatocellular carcinoma recurrences.⁵

Several typical histologic patterns of hepato-cellular carcinoma have been described by the World Health Organization. The most common is the trabecular pattern, also known as the sinusoidal pattern.¹ The other patterns include acinar, solid, scirrhous, and clear cell pattern. Hepatocellular carcinoma with fatty change is extremely rare. There are only a few case reports in the literature.^6-8Although the cause of hepatocellular carcinoma with fatty change has not been well understood, it is also considered to be related to ischemia and metabolic disorders.^6,7 In some reports, this fatty metamorphosis was more frequent in small, well-differentiated hepatocellular carcinomas; however, with increased tumor diameter and increased histological grade, the fatty changes became infrequent.^6,7 The fatty component of these tumors also can be detected by imaging techniques, such as ultrasonography or computed tomography.⁸ In some reports, fatty changes in hepatocellular carcinoma are more frequent in Asian than in non-Asian populations.⁹

The pathological diagnosis of metastatic hepatocellular carcinoma in extrahepatic metastatic sites can be relatively easily in classic forms of HCC, but the metastasis of rare variants of hepatocellular carcinoma can cause some diagnostic difficulties. Lung metastasis of fatty hepatocellular carcinoma can be confused with lipoid pneumonia— especially in small biopsies—by making a similar histologic picture, particularly when no information is available about the primary tumor.

Lipoid pneumonia is an uncommon disease and results from the aspiration of oil products.¹⁰ The cases are usually classified into 1 of 2 groups: exogenous or endogenous, with the distinction depending on the source of the lipids and fat found in the lungs.^10,11 Whereas exogenous lipoid pneumonia may result from the aspiration of foods and lipids, endogenous lipoid pneumonia results from a malfunction of monocytes and macrophages, which leads to repeated infections and the storage of cholesterol caused by tissue destruction and impaired tissue repair.¹⁰ Endogenous lipoid pneumonia also can be associated with bronchiolitis obliterans, pneumonia, and malignancies.^10,11 Histologically, it is characterized by the presence of lipid-laden macrophages that fill and distend the alveoli and interstitium.^10,11 The lung parenchyma may be altered by numerous round to oval, large lipid vacuoles. These spaces are frequently surrounded by fibrosis and histiocytes.^10,11 Although lipoid pneumonia is rare in routine pathology practice, it must be taken into account in detecting lipid vacuoles in lung parenchyma.

In conclusion, hepatocellular carcinoma with prominent fatty change is rare and the histologic picture is different from standard hepatocellular carcinoma; therefore, it may cause diagnostic difficulties, especially in metastatic lesions. In metastasis to the lung, fat droplets in the tumor cell cytoplasm may confused with the accumulation of aspirated oils in lipoid pneumonia, especially in small-needle biopsies. We presented this case because of its rarity and the difficulties that we had in differential diagnosis.

Volume: 12 Issue: 1 March 2014 - Supplement - 1

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