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03 June 2024: Articles  Thailand

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

Unusual clinical course, Unusual setting of medical care

Jirapat Wonglhow ORCID logo1ABCDEF, Arunee Dechaphunkul1BE, Patrapim Sunpaweravong1BE, Chirawadee Sathitruangsak ORCID logo1BE, Suchaya Pajareeyaphan2BE, Panu Wetwittayakhlang ORCID logo3ACDEF*

DOI: 10.12659/AJCR.944002

Am J Case Rep 2024; 25:e944002

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Abstract

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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.

Keywords: Liver Neoplasms, Eye Neoplasms, Immunotherapy, Treatment Outcome

Introduction

Hepatocellular carcinoma (HCC), which is the most common liver cancer, was the sixth most frequently diagnosed cancer globally and the third leading cause of cancer-related deaths in 2020 [1]. More than 90% of HCC cases are related to chronic liver disease, with liver cirrhosis being the most potent risk factor [2]. Major contributors to the risk of HCC include chronic alcohol consumption, nonalcoholic steatohepatitis associated with diabetes or obesity, and hepatitis B (HBV) or C (HCV) infection [2]. HCC is aggressive, with 50% to 75% of patients developing metastases during the course of their disease [3,4], most commonly involving the lungs and lymph nodes [5]. The prognosis of HCC is determined by its stage and the severity of liver cirrhosis. Notably, advanced-stage HCC has an extremely poor prognosis, with a 5-year survival rate of only 7% [6].

Orbital metastasis, comprising 1% to 13% of all orbital tumors, is rare [7,8]. The most common primary cancers causing orbital metastasis include breast cancers (36%), malignant melanoma (10%), and prostate cancers (9%) [8–11]. Liver cancers, including HCC, account for only 3.4% of all orbital metastases [11]. Common clinical presentations of orbital metastases include proptosis (52%), diplopia (34%), impaired eye motility (29%), palpable masses (22%), orbital pain (19%), impaired vision (19%), and ptosis (16%) [11]. The median duration from the initial diagnosis of the primary tumor to the appearance of orbital metastases is approximately 12 months, thus highlighting the prolonged course of orbital spread [11].

Orbital metastases originating from HCC are exceptionally rare, with only a few cases with confirmed histopathology [12–14]. Unfortunately, the prognosis of HCC metastasized to the orbit remains unfavorable [9,15]. Data on the optimal treatment of HCC with orbital metastasis are lacking, and therapeutic options are still limited.

Herein, we present a case of a patient with pathologically confirmed HCC exhibiting initial clinical symptoms of uni-lateral proptosis and visual impairment. This case represents the first report of the use of combined dual immunotherapy of durvalumab and tremelimumab, which could be a potential effective treatment in advanced HCC with orbital metastasis. Furthermore, we provide a review of the existing literature on HCC with orbital metastasis.

Case Report

A 65-year-old man with underlying type 2 diabetes mellitus and essential hypertension presented to an ophthalmology clinic with right eye proptosis for 2 weeks. The patient had progressive, painless blurred vision in the right eye for 6 months before the onset of proptosis. Nonproliferative diabetic retinopathy was diagnosed, and he underwent laser therapy; however, his symptoms did not improve. The patient subsequently developed proptosis of the right eye, with intermittent pain for 2 weeks. The patient had no history of chronic liver disease or cancer. The patient had normal appetite and presented with no weight loss, abdominal pain, or jaundice.

Examination of the right eye revealed axial proptosis (Figure 1), visual acuity of 20/200, intraocular pressure (tension) of 29 mmHg, color test score of 0/17, Hertel exophthalmometer reading of 21 mm, a mildly injected conjunctiva, a pupil size of 3 mm (reactive to light), positive relative afferent pupillary defect, a normal fundus with a cup-to-disc ratio of 0.3, a sharp disc, and limited eye movement of 30% in all directions and 0% in the superior rectus muscle direction. The patient’s left eye was normal. Physical examination revealed a body temperature of 36.7°C, pulse rate of 67 beats per min, and blood pressure of 138/75 mmHg. No pale conjunctivae or anicteric sclerae were observed, and no palpable superficial lymph nodes were present. Abdominal examination revealed no hepatomegaly, with a liver span of 10 cm, or splenomegaly. No chronic liver stigmata or signs of portal hypertension were observed.

Computed tomography (CT) of the orbit and brain was performed to investigate the etiology of the unilateral proptosis. CT revealed a 5.0×4.0-cm well-defined, oval-shaped, homogeneously enhancing hyperdense extraconal mass in the superior aspect of the right orbit, including the superior orbital fissure (Figure 2), which was responsible for proptosis of the right orbit and was exerting pressure on the superior rectus muscle. Additionally, bone remodeling was observed in the right sphenoid wing. Incisional biopsy of the extraconal mass in the right eye was subsequently performed, which revealed metastatic HCC (tissue immunohistochemistry was positive for AE1/AE3 [focal], CK7 [focal], glypican 3, and hepar 1, but negative for CK20) (Figure 3). The final diagnosis was consistent with metastatic HCC.

An additional multiphasic CT of the liver was performed to identify the primary cancer (Figure 4), revealing an arterial-enhancing nodule with venous washout in hepatic segment 5, measuring approximately 1.2 cm. This finding was consistent with typical HCC in cases of early cirrhosis. Furthermore, chest CT detected 2 enhanced right upper lung nodules, measuring 1.8 cm and 0.5 cm, along with a 0.6-cm subpleural nodule, indicative of potential lung metastases.

Further serological workup for the etiology of cirrhosis revealed a positive result for HCV antibodies, with an HCV ribonucleic acid (RNA) viral load of 431 171 IU/mL. Other viral serological test results were negative for HIV, hepatitis B surface antigen, and anti-hepatitis B core antibodies. Liver function test results revealed a total bilirubin level of 0.52 mg/dL, direct bilirubin of 1.65 mg/dL, aspartate transaminase of 64 U/L, alanine transaminase of 94 U/L, alkaline phosphatase of 104 U/L, total protein of 8.2 g/dL, and albumin of 3.8 g/dL. The patient’s serum alpha-fetoprotein (AFP) level was 70.27 ng/dL. The prothrombin time was 12.7 s, with an international normalized ratio of 1.17. Esophagogastroduodenoscopy revealed no esophageal or gastric varices. HCV treatment was initiated using sofosbuvir, velpatasvir, and ribavirin for 12 weeks.

HCC staging was categorized as Barcelona Clinic Liver Cancer (BCLC) classification C [16], considering the presence of extra-hepatic metastasis and HCV-related cirrhosis, according to the Child-Turcotte-Pugh A classification. First-line systemic therapy with durvalumab and tremelimumab was subsequently initiated following the “Single Tremelimumab Regular Interval Durvalumab” (STRIDE) regimen [17], with tremelimumab 300 mg as a single dose plus durvalumab 1500 mg every 4 weeks. The patient underwent palliative radiotherapy (RT), targeting the right orbit with high energy X-rays (photon beam) at a dose of 30 Gy in 10 fractions, beginning 1 week after the first dose of dual immunotherapy.

The patient reported significant improvement in pain, with reduced proptosis of the right eye (Figure 1) after RT and the first cycle of durvalumab plus tremelimumab. Stable disease was achieved according to evaluation using the Response Criteria in Solid Tumors (version 1.1), with a 3.75% decrease in the summation of sizes following the third cycle of durvalumab. The size of the orbital mass reduced to 4.6×1.1 cm, and the size of liver and lung lesions remained stable. Moreover, the serum AFP levels decreased from 70.27 to 13.5 ng/dL. The clinical conditions continually improved, with the right eye proptosis gradually decreasing to nearly normal size. After the sixth cycle of durvalumab, the size of the orbital mass continued to decrease to 4.5 cm ×0.9 cm, the size of liver and lung lesions remained stable, and serum AFP levels decreased to 6.90 ng/dL. Hence, this treatment regimen was proven effective for at least 6 cycles (6 months), with continued clinical response observed (Figure 1). The patient is currently still undergoing this treatment regimen, with the latest cycle administered in March 2024 being cycle 7 of durvalumab.

Throughout the treatment, the patient experienced only 1 adverse effect – alopecia areata grade 1, which developed after 2 cycles of durvalumab. However, this adverse effect was fully resolved with 4 monthly steroid intralesional injections administered by a dermatologist.

Discussion

Orbital metastasis is a rare presentation of HCC, particularly as the first presentation of symptoms. Metastasis can also occur in individuals with no history of primary cancer. Typical symptoms include diplopia, ocular pain, vision loss, globe displacement, and palpable orbital mass. Irregular and contrast-enhancing lesions in the anterior orbit, affecting the bones and extraocular muscles, are commonly observed upon CT or magnetic resonance imaging [11,18]. Orbital metastases are predominantly unilateral (92%), with only 8% of patients demonstrating bilateral lesions [11].

Orbital metastasis can be categorized into 4 groups, based on its characteristic features [19]: infiltrative, marked by restricted motility and sometimes enophthalmos; mass effect, resulting in proptosis and/or globe displacement; inflammatory, with features such as pain, chemosis, and erythema; and functional, in which the cranial nerve endings are disproportionately affected by the degree of orbital involvement. Infiltrative lesions are the most common; however, mixed presentations can also occur. Our patient displayed all these features, including a mass effect causing proptosis, infiltrative signs resulting in motility restrictions, inflammatory symptoms causing pain, and a positive relative afferent pupillary defect, due to cranial nerve involvement.

The mechanism by which metastases reach the orbit is debatable. A hematogenous route, which has been reported for primary neoplasms in the abdomen, can also be applicable to HCC, leading to metastasis to other organs. Tumor cells can travel through the vena cava and bypass pulmonary filters to reach the heart and eventually spread to the orbital region through the arterial systemic circulation [20,21]. However, tumor cells reach the head and neck by bypassing the lungs, possibly through the vertebral venous plexus of Batson in most cases [21,22]. Another potential mechanism involves infiltration of the orbital bone, followed by invasion of other orbital structures, including soft tissues [21]. In the present case, chest CT revealed multiple lung nodules that were suspected to be lung metastases; thus, a hematogenous route may have contributed to these metastases.

We performed a systematic search in PubMed, Medline, and Scopus for reports of HCC with orbital metastasis published until January 15, 2024. The terms “hepatocellular carcinoma”, “metastasis”, “orbit”, and “eye” were used for searching case reports and case series. A total of 45 cases of patients with HCC and orbital metastases have been reported in the literature. The patient details are summarized in Table 1. Most of these patients were men (77.8%), with a median age of 60 years (range, 54–70 years). The leading causes of cirrhosis in these patients were HCV infection (40.0%), HBV infection (26.7%), and alcohol consumption (13.3%). Remarkably, 66.7% of these patients had no history of cancer before orbital metastasis presentation. In cases in which HCC had already been diagnosed, the median time from the initial HCC diagnosis to the development of orbital metastasis was 13 months. Approximately 60% of patients exhibited orbital metastasis without other extrahepatic metastases.

Treatment strategies for HCC are based on BCLC staging and vary according to the patient’s Eastern Cooperative Oncology Group status, liver function, and HCC characteristics (tumor size and metastasis) [16]. In cases of advanced-stage HCC, for which surgical resection and local therapies, such as radiofrequency ablation or transarterial chemoembolization, are not viable treatment options, systemic targeted therapy and immune checkpoint inhibitors are considered the treatments of choice. These treatments have demonstrated significant improvements in overall survival rates [17,23,24]. According to the most recent National Comprehensive Cancer Network guidelines [25], the recommended initial treatment involves a combination of atezolizumab and bevacizumab or tremelimumab and durvalumab for advanced-stage HCC. Both regimens are category 1 recommendations, demonstrating superior overall survival than that of sorafenib. However, there have been no direct comparisons between these regimens. The decision to use a specific regimen depends on contraindications. Patients with uncontrolled hypertension, recent bleeding or thrombosis, untreated varices, or proteinuria should avoid bevacizumab. Otherwise, patients can consider both regimens based on availability and affordability. Other treatment options include sorafenib, lenvatinib, or durvalumab administration.

If immunotherapy is contraindicated, targeted therapy, for example, tyrosine kinase inhibitor therapy with sorafenib and lenvatinib, should be considered. However, at our center, reimbursement is not available for either atezolizumab plus bevacizumab or tremelimumab plus durvalumab. Fortunately, at the time of diagnosis, the Thai Society of Clinical Oncology had an early access program for tremelimumab and durvalumab.

Consequently, our patient was among the patients with advanced HCC in Thailand who received this regimen donated by the Thai Society of Clinical Oncology.

Durvalumab and tremelimumab are monoclonal antibodies used in cancer immunotherapy. While durvalumab specifically targets and blocks programmed death-ligand 1 (PD-L1) [26], tremelimumab targets and inhibits cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) [27]. PD-L1 is expressed on the surface of some cancer cells. Upon interaction with immune cell receptors, it suppresses the immune response, allowing cancer cells to evade immune system attacks. By blocking the interaction between PD-L1 and its receptor, durvalumab helps unleash the immune system, allowing it to recognize and attack cancer cells. CTLA-4, which is expressed on the surface of T cells, plays an important role in downregulating the immune response. By blocking CTLA-4, tremelimumab enhances the antitumor immune response, allowing T cells to attack cancer cells effectively. Combinations of CTLA-4 and PD-L1 inhibitors have demonstrated additive antitumor activities, associated with complementary immunostimulatory effects [28].

In the HIMALAYA trial [17], dual immunotherapy (tremelimumab plus durvalumab) and single immunotherapy (durvalumab) were compared separately to targeted therapy (sorafenib). Direct comparisons between dual and single immunotherapy were not made. Dual immunotherapy demonstrated significantly improved overall survival (median overall survival 16.4 vs 13.8 months; hazard ratio 0.78 [0.65–0.92]), while single immunotherapy was non-inferior but not superior to sorafenib (median overall survival 16.6 vs 13.8 months; hazard ratio 0.86 [0.73–1.03]). This indirectly suggests that dual immunotherapy may be more effective in terms of overall survival.

However, dual immunotherapy is associated with a higher rate of immune-related adverse events (irAEs), including hypothyroidism, hyperthyroidism, hepatitis, and colitis, although these are mostly mild. Therefore, single immunotherapy should be considered in settings in which anti-angiogenesis drugs are not eligible and tremelimumab is unavailable, not approved for use, or unaffordable. Safety concerns are also important, as dual immunotherapy can increase the rate of irAEs. However, despite the higher rate, most irAEs were mild.

In real-world clinical practice, the affordability of both immunotherapies and targeted therapies remains challenging. Orbital RT can be performed to reduce tumor size and alleviate symptoms [12,13,29–31] in cases in which surgery is contraindicated. Surgical debulking is effective in reducing tumor mass-related symptoms [20,21,29,32]; however, it could result in serious complications, including permanent visual deficits.

Dataon the optimal treatment of HCC with orbital metastasis are lacking, and therapeutic options are limited. To the best of our knowledge, only 5 patients among the 45 reported patients with advanced HCC and orbital metastasis underwent standard systemic therapy [4,12,13,33,34]. Among them, 1 patient received atezolizumab plus bevacizumab (survival of only 6 months) [13], whereas 4 received sorafenib (survival not reported). RT to the orbit was an adjunctive treatment administered to approximately one-third of the reported patients. One reported case showed complete response of the orbital lesion to RT [4]. However, the prognosis for these patients remains poor.

Conclusions

This is the first report on the use of combined dual immuno-therapy with durvalumab and tremelimumab, along with targeted orbital RT, for the treatment of advanced-stage HCC in a patient with orbital metastasis. Herein, we reported a case of therapeutic success with clinical improvement. However, cases reporting long-term therapeutic responses and survival outcomes are still warranted to address the efficacy of these new therapies, and further prospective studies should be explored. We also highlighted orbital metastasis as a rare presentation of HCC that initially manifested as unilateral proptosis, a condition that physicians may not typically consider related to HCC, especially in the absence of underlying chronic liver disease.

Figures

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 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. 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 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. 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 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. 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.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.

References:

1.. Sung H, Ferlay J, Siegel RL, Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries: Cancer J Clin, 2021; 71; 209-49

2.. Llovet JM, Kelley RK, Villanueva A, Hepatocellular carcinoma: Nat Rev Dis Primers, 2021; 7; 6

3.. Srinivasan R, Krishnanand G, Cytologic diagnosis of metastatic hepatocellular carcinoma presenting as an orbital mass. A case report: Acta Cytol, 2007; 51; 83-85

4.. Quick AM, Bloomston M, Kim EY, Complete response to radiation therapy of orbital metastasisfrom hepatocellular carcinoma: World J Gastroenterol, 2009; 15; 6000-3

5.. Katyal S, Oliver JH, Peterson MS, Extrahepatic metastases of hepato-cellular carcinoma: Radiology, 2000; 216; 698-703

6.. Sayiner M, Golabi P, Younossi ZM, Disease burden of hepatocellular carcinoma: A global perspective: Dig Dis Sci, 2019; 64; 910-17

7.. Bonavolontà G, Strianese D, Grassi P, An Analysis of 2,480 space-occupying lesions of the orbit from 1976 to 2011: Ophthalmic Plast Reconstr Surg, 2013; 29; 79-86

8.. Magliozzi P, Strianese D, Bonavolontà P, Orbital metastases in Italy: Int J Ophthalmol, 2015; 8; 1018-23

9.. Valenzuela AA, Archibald CW, Fleming B, Orbital metastasis: Clinical features, management and outcome: Orbit, 2009; 28; 153-59

10.. Eldesouky MA, Elbakary MA, Clinical and imaging characteristics of orbital metastatic lesions among Egyptian patients: Clin Ophthalmol, 2015; 9; 1683-87

11.. Palmisciano P, Ferini G, Ogasawara C, Orbital metastases: A systematic review of clinical characteristics, management strategies, and treatment outcomes: Cancers, 2021; 14; 94

12.. Rana S, Khosla D, Periasamy K, Orbital metastasis as initial clinical presentation in a patient of hepatocellular carcinoma – a rare case with review of literature: Indian J Med Paediatr Oncol, 2021; 42; 385-89

13.. Mani I, Gkeka D, Athanasaki F, Metastasis of hepatocellular carcinoma in the orbit as first manifestation of extrahepatic spread – a case report and review of the literature: IJCIMR, 2023; 4; 1151

14.. Myint KT, Thant KK, Thazin M, Bilateral orbital metastasis as an initial presentation of hepatocellular carcinoma: Asian J Ophthalmol, 2020; 17; 302-10

15.. Gupta R, Honavar SG, Vemuganti GK, Orbital metastasis from hepatocellular carcinoma: Surv Ophthalmol, 2005; 50; 485-89

16.. Reig M, Forner A, Rimola J, BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update: J Hepatol, 2022; 76(3); 681-93

17.. Abou-Alfa GK, Lau G, Kudo M, Tremelimumab plus Durvalumab in unresectable hepatocellular carcinoma: NEJM Evid, 2022; 1; EVIDoa2100070

18.. Char DH, Miller T, Kroll S, Orbital metastases: Diagnosis and course: Br J Ophthalmol, 1997; 81; 386-90

19.. Goldberg RA, Rootman J, Clinical characteristics of metastatic orbital tumors: Ophthalmology, 1990; 97; 620-24

20.. Baldovin M, Saratziotis A, Zanotti C, Emanuelli E, Orbital metastasis from hepatocellular carcinoma revealed by sudden exophthalmos: BMJ Case Rep, 2021; 14; e242136

21.. Oida Y, Ohtani Y, Dowaki S, Hepatocellular carcinoma metastatic to the orbit: A case report: Tokai J Exp Clin Med, 2006; 31; 7-10

22.. Batson OV, The function of the vertebral veins and their role in the spread of metastases: Ann Surg, 1940; 112; 138-49

23.. Finn RS, Qin S, Ikeda M, Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: N Engl J Med, 2020; 382; 1894-905

24.. Llovet JM, Ricci S, Mazzaferro V, Sorafenib in advanced hepatocellular carcinoma: N Engl J Med, 2008; 359; 378-90

25.. , Hepatobiliary cancers (Version 1.2023) [cited 2023 Aug 1]; Available from: https://www.nccn.org/professionals/physician_gls/pdf/hcc.pdf

26.. Stewart R, Morrow M, Hammond SA, Identification and characterization of MEDI4736, an antagonistic anti-PD-L1 monoclonal antibody: Cancer Immunol Res, 2015; 3; 1052-62

27.. France NL, Blair HA, Tremelimumab: A review in advanced or unresectable hepatocellular carcinoma: Target Oncol, 2024; 19; 115-23

28.. Kudo M, Scientific rationale for combination immunotherapy of hepato-cellular carcinoma with anti-PD-1/PD-L1 and anti-CTLA-4 antibodies: Liver Cancer, 2019; 8; 413-26

29.. Geske MJ, Bloomer MM, Kersten RC, Vagefi MR, Diagnostic approaches to metastatic hepatocellular carcinoma of the orbit: Ophthalmic Plast Reconstr Surg, 2017; 33; S129-31

30.. Protopapa MN, Lagadinou M, Papagiannis T, Hepatocellular carcinoma: An uncommon metastasis in the orbit: Case Rep Oncol Med, 2020; 2020; 7526042

31.. Pitts J, Chang CH, Mavrikakis I, Shaikh A, Rootman J, Hepatocellular carcinoma presenting as orbital bone metastasis: Ophthalmic Plast Reconstr Surg, 2008; 24; 477-79

32.. Chen CY, Zhong JH, Liu JL, Retrobulbar metastasis and intracranial invasion from postoperative hepatocellular carcinoma: A case report and review of the literature: Oncol Lett, 2015; 9; 721-26

33.. Sochat MM, Piao J, Poddar N, Hepatocellular carcinoma with orbital metastasis: A unique multidisciplinary case report: J Gastrointest Canc, 2019; 50; 978-82

34.. Madabhavi I, Ks S, Dharmarajan Lethika R, Intraconal metastasis leading to diagnosis of hepatocellular carcinoma: Middle East J Dig Dis, 2020; 12; 48-51

35.. Lubin JR, Grove AS, Zakov ZN, Albert DM, Hepatoma metastatic to the orbit: Am J Ophthalmol, 1980; 89; 268-73

36.. Zubler MA, Rivera R, Lane M, Hepatoma presenting as a retro-orbital metastasis: Cancer, 1981; 48; 1883-85

37.. Wakisaka S, Tashiro M, Nakano S, Intracranial and orbital metastasis of hepatocellular carcinoma: Report of two cases: Neurosurgery, 1990; 26; 863-66

38.. Phanthumchinda K, Hemachuda T, Superior orbital fissure syndrome as a presenting symptom in hepatocellular carcinoma: J Med Assoc Thai, 1992; 75; 62-65

39.. Tranfa F, Cennamo G, Rosa N, An unusual orbital lesion: Hepatoma metastatic to the orbit: Ophthalmologica, 1994; 208; 329-32

40.. Schwab L, Doshi H, Shields JA, Hepatocellular carcinoma metastatic to the orbit in an African patient: Ophthalmic Surg, 1994; 25; 105-6

41.. Loo KT, Tsui WM, Chung KH, Hepatocellular carcinoma metastasizing to the brain and orbit: report of three cases: Pathology, 1994; 26; 119-22

42.. Font RL, Maturi RK, Small RG, Garcia-Rojas M, Hepatocellular carcinoma metastatic to the orbit: Arch Ophthalmol, 1998; 116; 942-45

43.. Scolyer RA, Painter DM, Harper CG, Lee CS, Hepatocellular carcinoma metastasizing to the orbit diagnosed by fine needle aspiration cytology: Pathology, 1999; 31; 350-53

44.. Filippini DM, Di Federico A, Lenzi B, Critical diagnostic delay associated with unusual presentation of hepatocellular carcinoma (HCC) with orbital metastases: A case report: Ann Palliat Med, 2021; 10; 8474-78

45.. Kim IT, Na SC, Jung BY, Hepatocellular carcinoma metastatic to the orbit: Korean J Ophthalmol, 2000; 14; 97-102

46.. Machado-Netto MC, Lacerda ECA, Massive orbital metastasis of hepatocellular carcinoma: Clinics, 2006; 61; 359-62

47.. Hirunwiwatkul P, Tirakunwichcha S, Meesuaypong P, Shuangshoti S, Orbital metastasis of hepatocellular carcinoma: J Neuroophthalmol, 2008; 28; 47-50

48.. da Fonseca Júnior NL, Frizon L, Case report: Arq Bras Oftalmol, 2008; 71; 865-67

49.. Kolarević D, Tomasević Z, Boricić I, Metastasis of hepatocellular carcinoma presented as a tumor of the maxillary sinus and retrobulbar tumor: Vojnosanit Pregl, 2011; 68; 359-62

50.. Mustapha SK, Madachi DA, Orbital metastasis of hepatocellular carcinoma: A case report: West Afr J Med, 2011; 30; 305-7

51.. Guerriero S, Infante G, Giancipoli E, Hepatocellular carcinoma metastasis to the orbit in a coinfected HIV+ HBV+ patient previously treated with orthotopic liver transplantation: A case report: Case Rep Ophthalmol Med, 2011; 2011; 549270

52.. Jiang H, Wang Z, Xian J, Ai L, Bilateral multiple extraocular muscle metastasis from hepatocellular carcinoma: Acta Radiol Short Rep, 2012; 1; arsr.2011.110002

53.. Piccirillo M, Granata V, Albino V, Can hepatocellular carcinoma (HCC) produce unconventional metastases? Four cases of extrahepatic HCC: Tumori, 2013; 99; e19-23

54.. Eldesouky MA, Elbakary MA, Shalaby OE, Shareef MM, Orbital metastasis from hepatocellular carcinoma: Report of 6 cases: Ophthalmic Plast Reconstr Surg, 2014; 30; e78-82

55.. Téllez-Villajos L, Maroto-Castellanos M, Lledó-Navarro JL, Orbital metastasis from hepatocellular carcinoma: Rev Esp Enferm Dig, 2015; 107; 231

56.. Abdul Kader N, Abraham RM, Sathi PP, Unusual metastases of hepatocellular carcinoma: 2 cases: OGH Reports, 2018; 7; 109-10

57.. Salem G, Adhikari LJ, Hepatitis C, and cannot see!: Gastroenterology, 2019; 156; 1257-58

Figures

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.

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Am J Case Rep In Press; DOI: 10.12659/AJCR.943144  

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923