To date, only two cases of skull metastasis (temporal bone in one case and parietal region after a trauma in other one) of hepatocellular carcinoma (HCC) after liver transplantation (LT) have been reported in the pertinent literature (1, 2). Herein, we described a patient presenting with frontal skull metastasis extending through the scalp as an initial manifestation of HCC recurrence 5 years after LT. A 70-year-old male patient received living donor LT in August 2006 for hepatitis B virus–related liver cirrhosis complicated by HCC. Investigations including thorax and cranial computed tomography (CT) and bone scintigraphy showed no extrahepatic metastasis. No vascular invasion was reported in explanted liver. The initial immunosuppression used was prednisolone and sirolimus. Tacrolimus and mycofenolate mofetil were then added due to clinical rejection in the first month after transplantation. Prednisolone, mycofenolate mofetil, and tacrolimus were ceased after 6 months, 2 years, and 3 years, respectively. The patient’s immunosuppression was maintained at sirolimus 2 mg daily. Lamivudine and short-term hepatitis B immunoglobulin were used for preventing recurrence of hepatitis B virus after LT. However, hepatitis B surface antigen positivity was detected in 2008 and tenofovir was added. Annual ultrasonographic investigation of the liver showed no HCC recurrence for the period until 2010. In July 2011, the patient noticed a 3-cm painless, firm, subcutaneous mass with skin ulceration in the frontal region of the skull (Fig. 1). Cranial CT scan demonstrated the presence of an osteolytic lesion in frontal bone without involvement of the dura mater. A wide local excision was performed and histopathologic analysis revealed the diagnosis of HCC. Moreover, toracoabdominal CT scan revealed the presence of simultaneous 2.5-cm mass in the transplanted liver, metastatic pulmonary micronodules in the right lung, metastatic multiple nodules in both adrenal glands, and bone metastases in the ribs, lumbar vertebrae, and pelvis. A diagnosis of metastatic hepatocellular cancer recurrence was done. His α-fetoprotein was found to be 3.59 ng/mL. Due to the lack of clinical, laboratory, and radiologic manifestations of recurrent cirrhosis, liver biopsy was not performed. Because the histopathologic findings of the skull mass were also relevant with the radiologic signs of metastatic HCC, systemic sorafenib therapy (400 mg, twice daily, orally) was initiated and external radiotherapy was administered for bone metastases. A CT scan obtained after 6 months of therapy showed progression of the mass in the liver to 3 cm in diameter, without regression of metastatic nodules in the lung and adrenal glands. Therefore, sorafenib was discontinued and no further treatment was considered because of multiple intractable metastatic lesions. His clinical course was marked by refractory gastrointestinal bleeding due to tumoral infiltration of gastroduodenal artery followed by death 11 months after initial diagnosis of HCC recurrence.FIGURE 1: A subcutaneous mass in the frontal region of the skull with a deep central ulcer.Treatment of HCC using hepatic resection and LT achieves the best outcome in well-selected candidates, but 10% to 30% of patients still experience tumor recurrence after LT even if the restrictive criteria are employed (3). The most frequent site of extrahepatic metastasis after LT is the lung followed by bone and others (lymph nodes and adrenal glands). Bone metastasis has been reported ranging from 6% to 33% (3), the most common sites are the vertebrae followed by pelvis and ribs (4). Considering the lack of signs of liver cirrhosis, bone and soft tissue involvement of HCC may suggest de novo HCC, which should be established by molecular techniques (5). Among the approximately 100 cases of HCC within more than 900 LTs performed in our center, this report represents the first case of frontal skull metastasis as an initial sign of HCC recurrence after LT. Ilker Turan 1,2 Suna Yapali1 Omer Ozutemiz1 Zeki Karasu1