Keywords
hepatocellular carcinoma - metastasis - orbital - palliation - radiotherapy
Introduction
Orbital metastases are relatively uncommon accounting for 1 to 13% of all orbital tumors and occur in 2 to 5% of cancer patients.[1]
[2]
[3]
[4] Hepatocellular carcinoma (HCC) is an aggressive malignancy, with 50 to 75% of patients developing metastases during the course of their disease.[5]
[6] The most common sites of metastasis are the regional lymph nodes and lungs. The less common sites of distant metastases include bone, brain, adrenal glands, and skin.[5]
[7]
[8]
The common malignancies metastasizing to the orbit are breast, lung, prostate, kidney, thyroid, and gastrointestinal.[1]
[9]
[10]
[11] Orbital metastasis from HCC is a rare presentation with only a handful of cases reported in the literature. Herein, we report a rare case of orbital metastasis as the initial clinical presentation in a patient with HCC with a brief review of the literature.
Case Report
A 66-year-old male patient presented with a history of protrusion of the eyeballs, double vision, and swelling over the left side of the head for 8 months. There was no history of jaundice, awareness of mass anywhere else in the body, loss of weight, and loss of appetite. On clinical examination, left eye proptosis with reduced visual acuity and conjunctival chemosis was present. A soft-tissue swelling measuring 4 cm × 4 cm was present in the left frontal region and orbit. Abdominal examination revealed hepatomegaly. The differential diagnosis at this stage included primary orbital neoplasm or metastatic tumor to the orbit. Baseline investigations including hemogram and kidney function tests were normal. Bilirubin was within normal limits, but liver enzymes were raised (aspartate transaminase: 87.3 U/L, alanine transaminase: 93.17 U/L, and alkaline phosphatase: 223 U/L). Serum α fetoprotein was found to be elevated (1000 ng/mL). Peripheral blood film examination did not show any abnormality. The patient tested positive for hepatitis C antibody. Magnetic resonance imaging (MRI) of the brain with orbit revealed a heterogeneous lesion in the left frontal lobe causing its destruction with intraorbital and intracranial extension ([Fig. 1]). Contrast-enhanced computed tomography of the chest was normal, and a triphasic scan of the abdomen showed multiple arterial hypervascular lesions in both lobes of the liver with washout in venous and delayed phases, suggestive of multifocal HCC. The largest lesion measured 2.5 cm × 3.2 cm in the right lobe of the liver ([Fig. 2]). Multiple, small, similar arterial hypervascular lesions were seen in both lobes of the liver. Ultrasound-guided fine-needle aspiration cytology from the liver was suggestive of HCC ([Fig. 3]). The patient was treated with palliative radiotherapy of 30 Gy in 10 fractions to the left eye. The patient was subsequently started on sorafenib. MRI of the brain including the orbit was done after 3 months of radiotherapy, which revealed a significant reduction in the size of the lesion. Four months later, the patient developed lung metastasis and left iliac bone metastasis. He was given palliative radiotherapy of 20 Gy in five fractions to the left iliac bone, following which he had significant pain relief. The patient was given the option of second-line treatment with immune checkpoint inhibitors or second-line tyrosine kinase inhibitors, but he refused due to cost issues. The patient received intravenous zoledronic acid for 3 months. The patient is alive with progressive disease and is on palliative care.
Fig. 1 Magnetic resonance imaging of the brain with orbit showing a heterogeneous lesion in the left frontal lobe causing its destruction with intraorbital and intracranial extensions.
Fig. 3 The tumor cells were highly pleomorphic with coarse chromatin, prominent nucleoli, and moderate amount of cytoplasm. These tumor cells showed prominent cytoplasmic and nuclear vacuoles, and some of them showed intracytoplasmic bile pigment and intranuclear inclusions.
Fig. 2 Contrast-enhanced computed tomography (CECT) showing a lesion in segment VI of the liver with small lesions in both lobes of the liver.
Discussion
Metastasis to the orbit is a rare presentation in HCC. Breast constitutes the most common primary site, with 28 to 70% of orbital metastasis.[11] The common presenting symptoms of orbital metastases include diminished vision, pain, proptosis, double vision, awareness of mass, and limitation of extraocular movements. The differential diagnosis includes vascular lesions; lymphoproliferative lesions; tumors of the lacrimal gland and optic nerve; and metastatic tumors from the breast, lung, prostate, thyroid, and orbital chloroma in patients with acute myeloid leukemia or chronic myeloid leukemia.
The presence of orbital metastasis in HCC predicts a poor prognosis. In a series of 100 patients by Lubin et al,[12] the breast was the most common site in 53% of the patients, followed by the prostate in 12% and lungs in 8%. The most common clinical findings were limited to ocular motility (54%), proptosis (50%), and palpable mass (43%). The mean survival time after the orbital diagnosis was 20 months. Patients with metastatic carcinoid tumors had the longest mean survival (60 months) and patients with breast cancer had the second-longest mean survival (22 months) after diagnosis of orbital metastasis. In a series of 93 patients of orbital metastasis by Magliozzi et al,[2] HCC was the primary site in only one patient. Orbital metastases occur unilaterally in more than 90% of the patients.[11] To the best of our knowledge, 33 cases have been reported in the literature including case reports and series.[2]
[5]
[6]
[6]
[7]
[8]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34] Most of the patients were in the sixth and seventh decades of life.
Orbital metastasis, as the initial manifestation of disease, was present in 22 out of 33 patients ([Table 1]). Our patient also presented with orbital metastasis as the initial presentation of the disease. A detailed history and thorough ophthalmic and general physical examination must be done in patients with orbital metastasis. Prompt referral to an oncologist is necessary for patients who present with orbital metastasis as the initial manifestation of the disease to rule out primary at the earliest. Radiological investigations such as computed tomography and MRI are the principal means of evaluating orbital lesions. The potential risks of performing a biopsy of an orbital mass such as visual loss, bleeding, and diplopia, should always be weighed against the potential benefits, evaluating whether the management options are going to change as a result of the biopsy.
Table 1
Cases of orbital metastasis in hepatocellular carcinoma reported in the literature
|
Author
|
Year
|
Number of cases
|
Age
|
Gender
|
Orbital metastasis as the first manifestation of disease
|
Outcome
|
|
Lubin et al[12]
|
1980
|
1
|
69
|
Male
|
Yes
|
Alive
|
|
Zubler et al[13]
|
1981
|
1
|
64
|
Male
|
Yes
|
Died after 3 months
|
|
Wakisaka et al[14]
|
1990
|
1
|
58
|
Male
|
Yes
|
Died after 11 months
|
|
Phanthumchinda and Hemachuda[15]
|
1992
|
1
|
29
|
Female
|
Yes
|
Not mentioned
|
|
Kami et al[16]
|
1994
|
1
|
60
|
Male
|
Yes
|
Died after 3 months
|
|
Tranfa et al[19]
|
1994
|
1
|
85
|
Male
|
Yes
|
Not mentioned
|
|
Schwab et al[20]
|
1994
|
1
|
19
|
Male
|
Yes
|
Died 1 month
|
|
Hosokawa et al[21]
|
1994
|
1
|
70
|
Male
|
No
|
Not mentioned
|
|
Loo et al[22]
|
1994
|
1
|
71
|
Female
|
Yes
|
Lost to follow-up after 3 months
|
|
Font et al[23]
|
1998
|
1
|
79
|
Female
|
Yes
|
Alive
|
|
Scolyer et al[24]
|
1999
|
1
|
78
|
Male
|
No
|
Not mentioned
|
|
Kim et al[7]
|
2000
|
1
|
56
|
Female
|
Yes
|
Died after 2 months
|
|
Chen et al[25]
|
2003
|
1
|
69
|
Male
|
Yes
|
Orbital mass regressed
|
|
Oida et al[26]
|
2006
|
1
|
72
|
Male
|
No
|
Died after 4 months
|
|
Machado-Netto et al[17]
|
2006
|
1
|
57
|
Male
|
Yes
|
Died after 15 months
|
|
Srinivasan and Krishnanand[5]
|
2007
|
1
|
76
|
Female
|
Yes
|
Not mentioned
|
|
Hirunwiwatkul et al[8]
|
2008
|
1
|
74
|
Female
|
Yes
|
Died after 2 months
|
|
Pitts et al[27]
|
2008
|
2
|
61
47
|
Female
Male
|
Yes
Yes
|
Both patients died with progressive disease
|
|
Fonseca Júnior et al[28]
|
2008
|
1
|
57
|
Male
|
Yes
|
Died after 15 months
|
|
Quick et al[6]
|
2009
|
1
|
52
|
Male
|
No
|
Alive 20 months
|
|
Kolarević et al[29]
|
2011
|
1
|
70
|
Male
|
No
|
Died after 6 months
|
|
Mustapha and Madachi[30]
|
2011
|
1
|
25
|
Male
|
No
|
Not mentioned
|
|
Guerriero et al[31]
|
2011
|
1
|
45
|
Male
|
No
|
Not mentioned
|
|
Eldesouky et al[18]
|
2014
|
6
|
Range 47–70 Mean age 60.2 years
|
Male
|
3 cases
|
Survival of five cases ranged between 8 and 13 months with a mean of 10.2 (±2.3) months. One patient was receiving treatment (diagnosed for 6 months)
|
|
Téllez-Villajos et al[32]
|
2015
|
1
|
70
|
Female
|
No
|
Alive at 4 months
|
|
Madabhavi et al[33]
|
2020
|
1
|
72
|
Male
|
Yes
|
Alive at 7 months with stable disease
|
|
Protopapa et al[34]
|
2020
|
1
|
53
|
Male
|
Yes
|
Discharged after radiotherapy with little improvement
|
The intent of treatment in patients presenting with orbital metastasis is palliative as such metastasis suggests a hematogenous spread of disease. The aim of the treatment is to maximize the quality of life of such patients and to preserve visual function if possible. Radiotherapy is the mainstay of treatment in such patients as it will cause shrinkage of the lesion, control of symptoms, and visual preservation. Surgical resection is appropriate only in selected patients.
Orbital metastasis in HCC is rare. A high index of suspicion is required as proptosis and diplopia were the first manifestations of disease in the index case. Clinicians should be aware of such presentations. Prognosis in such patients remains dismal. The treatment should focus on providing relief from symptoms of the illness. Radiotherapy plays an important role in downsizing the lesion and symptom control.
