Introduction: Besides more common sites such as lung or peritoneum, hepatocellular carcinoma (HCC) can metastatize to rare sites. We report herein a new metastatic site of HCC: the nail-bed. We also review other recently reported rare site HCC metastases (RSHM).
Case Report: A 66-year-old woman with a 12-year history of resected-stage IA HCC who later presented lung, spleen and brain metastases treated with surgery, systemic therapies (sorafenib, sunitinib, capecitabine) and radiotherapy. The patient was referred to us because of a painful and rapidly evolving mass in the nail-bed of the left thumb. Biopsy confirmed nail-bed HCC metastasis, and the finger was amputated. The patient died few weeks later.
Conclusion: This case was an opportunity for us to review RSHM. This type of metastasis seems to be an early event, in the context of advanced stage HCC with elevated protein induced by vitamin K absence-II (PIVKA II). The Lee nomogram is useful in detecting patients at high risk of developing RSHM. We would suggest insisting on systemic treatment in these metastatic patients although overall survival after RSHM diagnosis is poor.

Keywords: hepatocellular carcinoma, rare metastasis, surgery, PIVKA II, systemic treatment, nomogram

INTRODUCTION

The most frequent hepatocellular carcinoma (HCC) metastases sites are, in descending order, lung, peritoneum, bone, spleen, adrenal gland, brain, pleura and kidneys.¹ In addition, unusual locations for HCC metastasis have been reported. In this article, we report a case of HCC metastasis at a location not previously described, the nail-bed. We also aimed to answer the questions raised to us by this case by contrasting it with other rare site HCC metastases cases (RSHM) reported in the last decade.

CASE REPORT

A 66year-old woman was referred from our Medical Oncology department because of a painful subungual mass in the left thumb, which has been growing rapidly over the prior 4 months. On physical exam, an inflammatory mass with hemorrhagic suffusion and nail extrusion was observed (Figure 1).

The patient’s past medical history was relevant for a 10 cm HCC in the right hepatic lobe resected 12 years before. She had no history of transfusions or alcoholic abuse. All hepatitis viral serologies were negative. A pulmonary HCC metastasis was resected two years later. On the path exam, PD-L1 222C3 was negative and MLH1, MSH2, MSH6 and PMS2 were positive. One year later, an unresectable pulmonary local relapse was treated with sunitinib on first line and sorafenib on second line. She subsequently received capecitabine (1800 mg/12h) on progression, with a complete response. Four years later a solitary lung metastasis was resected and the patient received capecitabine as adjuvant therapy. One year later, spleen and brain metastasis were discovered. The patient was treated with regorafenib and whole-brain radiotherapy, with a partial response.

Given her history and the macroscopic appearance the subungual mass (Figure 2), a biopsy was taken after nail resection. Path exam reported HCC metastasis with tumor emboli. The thumb was amputated, and path exam confirmed the diagnosis of HCC metastasis in the nail-bed (Figures 3–5) with intact phalanx bone. The patient died 2 weeks later with seizures. Written informed consent was provided by the patient to have the case details and any accompanying images published. No institutional approval was required to publish the case details, although the Ethics Committee of our center was informed about this submission.

This case raised several questions: are RSHM observed in initially early-stage HCC cases (like the present one) or in the context of more advanced stage HCCs at presentation? Is PIVKA-II elevated in RSHM? What percentage of these cases have received systemic treatment? Is the interval between primary HCC diagnosis and RSHM long (as in our case) or short? Do RSHM appear in the setting of more common site metastasis? Is the Lee et al nomogram for prediction of extrahepatic HCC metastasis² useful in these cases? Is the overall survival after RSHM diagnosis always poor? In order to try to answer these questions, we analyzed the RSHM cases published in the last decade together with our case (Table 1).