Metastatic Hepatocellular Carcinoma In A Liver Transplant Patient Presenting As Cheek Nodules

A 40-year-old Chinese man with a history of hepatitis B, cirrhosis, and hepatocellular carcinoma (HCC), status post transcatheter arterial chemoembolization and orthotopic liver transplantation in 2007, presented to the oncology and dermatology clinics with three months of worsening mid-back pain and two enlarging facial nodules. Physical examination revealed two 1-cm firm pinkto-erythematous nodules without overlying scale or crust (Fig. 1). The lesions were non-tender to palpation. The remainder of the exam revealed a 1-cm firm nodule in the left axilla. A repeat check of his alpha-fetoprotein (AFP) level was 13,298 ng/ml, increased from 7752 ng/ml several months earlier. Follow-up computed tomography imaging showed a recurrent tumor in the 5th segment of the liver with metastases to the ribs, spine, and lung, confirmed by biopsy. Punch biopsy of the facial nodules revealed nodular aggregates of atypical epithelial cells in the dermis associated with an increased number of blood vessels (Fig. 2a). The cells contained enlarged, pleomorphic, hyperchromatic nuclei, some with large basophilic nucleoli and abundant amphophilic to pale-staining cytoplasm (Fig. 2b). There were several multinucleated cells as well as typical and atypical mitotic figures and individual cell necrosis, consistent with metastatic non-small cell carcinoma. Immunoperoxidase studies revealed only focal reactivity of the tumor cells for cytokeratins AE1 and AE3 and no reactivity with melan-A. The cells were also focally reactive for CAM 5.2, and ductal structures and canaliculi were reactive for epithelial antigen membrane (EMA), CD10 and, to a lesser degree, carcinoembryogenic antigen (CEA; Fig. 2c and d). Additionally, the cells were reactive for hepatocyte paraffin 1 antigen (Hep Par 1) and AFP, confirming the diagnosis of metastatic HCC. Radiation of the facial lesions was recommended.