Orbital Metastasis as the First Manifestation of Hepatocellular Carcinoma, and Its Effective Treatment with Combined Dual Immunotherapy: A Case Report and Review of the Literature

Abstract

BACKGROUND Orbital metastasis originating from hepatocellular carcinoma (HCC), particularly as an initial manifestation in patients without a known history of HCC, is rare. Few reports exist on the treatment of patients having HCC with orbital metastasis using targeted therapy or immunotherapy. CASE REPORT We report a case of advanced-stage HCC in a 65-year-old man who first presented with progressive, painless blurred vision and proptosis of the right eye for 2 weeks. The patient had no history of chronic liver disease or cancer. Computed tomography revealed an enhancing hyperdense extraconal mass in the right orbit; a biopsy revealed metastatic HCC. Abdominal CT, which was performed to investigate the primary cancer, revealed a 1.2×1.6-cm arterial-enhancing nodule with venous washout in hepatic segment 5, associated with liver cirrhosis. The patient's serum alpha-fetoprotein level was 70.27 ng/dL. Chest computed tomography revealed lung metastasis. Thus, first-line systemic therapy combining durvalumab and tremelimumab was initiated alongside palliative radiotherapy targeting the right orbit, which began 1 week after the first dose of dual immunotherapy. The patient had significant clinical improvement, reduced proptosis, and serum alpha-fetoprotein levels. CONCLUSIONS Although orbital metastasis is a rare manifestation of HCC, physicians should recognize and consider aggressive investigations for early diagnosis, especially in patients with existing risk factors for HCC. Dual immunotherapy with durvalumab and tremelimumab in combination with radiotherapy can be considered a potential treatment option for managing advanced HCC with orbital metastasis.

Figure 1.

Right eye proptosis. (A, B) Right eye proptosis after incisional biopsy of the extraconal mass in the right eye and temporary tarsorrhaphy before systemic therapy and palliative radiotherapy. (C, D) Right eye proptosis improved after the first cycle of the STRIDE regimen (durvalumab plus tremelimumab) and palliative radiotherapy in the right orbit. (E, F) Right eye proptosis continued to improve after the sixth cycle of durvalumab.

Figure 2.

Computed tomography of the orbit. Computed tomography of the orbit and brain revealed a well-defined, oval-shaped, homogeneously enhancing hyperdense extraconal mass in the superior aspect of the right orbit, including the superior orbital fissure. The mass was responsible for right proptosis and exerted pressure on the superior rectus muscle.

Figure 3.

Right orbital mass pathology. (A) Histological examination revealed a tumor showing a trabecular, pseudoglandular, and solid pattern. The cytological features included atypical hepatocytes with mild pleomorphic nuclei, high nucleus-to-cytoplasm ratio, irregular nuclear membrane, prominent nucleoli, eosinophilic cytoplasm, and few mitotic figures. (B) Immunohistochemistry staining is positive for glypican-3. (C) Immunohistochemistry staining is positive for hepar-1.

Figure 4.

Multiphasic computed tomography of liver. Computed tomography shows an arterial-enhancing nodule with venous washout in hepatic segment 5 (green arrow) measuring approximately 1.2×1.6 cm. This finding is consistent with typical hepatocellular carcinoma in early cirrhosis. (A) Plain phase. (B) Arterial phase. (C) Venous phase. (D) Delayed phase.