AUTHOR COPY — NON COMMERCIAL USE ONLY ONLINE EXCLUSIVE Hashim, Rahmat, Abdul Aziz, Chandran
Metastatic hepatocellular carcinoma presenting as a sphenoid sinus mass and meningeal carcinomatosis Hilwati Hashim, MBBCh, MRad; Kartini Rahmat, MBBS, MRad; Yang Faridah Abdul Aziz, MBBS, MRad; Patricia Ann Chandran, MD, MPath
Abstract
We report the case of a 30-year-old woman who was referred to us for evaluation of a 2-week history of fever, headache, vomiting, bilateral ptosis, and blurred vision. Imaging obtained by the referring institution had identified a sphenoid sinus mass and diffuse meningeal infiltration, which was thought to represent an infective process. We subsequently identified the mass as a metastatic hepatocellular carcinoma (HCC). The patient was placed under palliative care, and she died 1 month later. Metastases to the sphenoid sinus from any primary source are very rare, and they are generally not considered in the radiologic differential diagnosis. HCC is known to metastasize to the lung, lymph nodes, and musculoskeletal system; again, reported cases of metastasis to the sphenoid sinus are rare. Indeed, our review of the English-language literature found only 6 previously reported cases of sinonasal metastasis of a primary HCC. A diagnosis of a sinonasal metastasis is more difficult in a patient who has no previous diagnosis of a primary malignancy. In presenting this case, our aim is to remind readers of this possibility. Introduction
Hepatocellular carcinoma (HCC) is the seventh most common cancer in the world, with 782,000 new cases diagnosed in 2012.1 HCC commonly metastasizes to
From the Medical Imaging Unit, Universiti Teknologi Mara Faculty of Medicine, Sungai Buloh, Malaysia (Dr. Hashim); and the Department of Biomedical Imaging (Dr. Rahmat and Prof. Abdul Aziz) and the Department of Pathology (Dr. Chandran), University of Malaya Faculty of Medicine, Kuala Lumpur, Malaysia. The case described in this article occurred at the University of Malaya. Corresponding author: Dr. Hilwati Hashim, Medical Imaging Unit, Universiti Teknologi Mara Faculty of Medicine, Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia. Email:
[email protected]
the lungs (34 to 70% of cases), regional lymph nodes (16 to 41%), and musculoskeletal system (1.6 to 16%).2,3 Sinonasal metastasis from a primary HCC is very rare, as our review of the English-language literature found only 6 previously reported cases.4-6 In this article, we describe a new case of sinonasal metastasis of an HCC. Case report
A 30-year-old woman presented to a private hospital with a 2-week history of fever, headache, vomiting, bilateral ptosis, and blurred vision. She claimed to have been otherwise well, and she had no known history of significant medical illness. Cranial magnetic resonance imaging (MRI) had detected a soft-tissue mass in the sphenoid sinus, with adjacent cavernous sinus enlargement and pachymeningeal enhancement (figure 1). The adjacent internal carotid arteries were normal. The pituitary gland, stalk, and optic chiasm were preserved. No focal enhancing brain parenchymal lesion was seen. In view of the patient’s age and presenting symptoms, a diagnosis of an infective process was made. She was referred to our hospital for further management. Apart from bilateral ptosis, our findings on the neurologic examination were normal. However, examination of the abdomen revealed hepatomegaly. No stigmata of chronic liver disease were noted. A blood investigation revealed a very high a-fetoprotein level (534,000 ng/ml) and positivity for hepatitis B infection. Other tumor markers were normal. The VDRL and retroviral disease screens were negative. Contrast-enhanced computed tomography (CT) of the abdomen and pelvis detected the presence of a large, heterogeneous, ill-defined mass that was occupying almost the entire right liver lobe, along with an area of central necrosis (figure 2, A and B). The mass mea-
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AUTHOR COPY — NON COMMERCIAL USE ONLY Metastatic hepatocellular carcinoma presenting as a sphenoid sinus mass and meningeal carcinomatosis
sured approximately 12.6 × 10.0 × A B 16.0 cm. Several lung nodules were also seen, as well as lytic lesions in the thoracic and lumbar vertebrae (figure 2, C and D). A diagnosis of hepatoma with lung and bone metastases was made, and the patient underwent a liver biopsy followed by transsphenoidal surgical debulking of the sphenoid C D sinus mass. Histopathologic examination of the liver biopsy specimen (figure 3) and the sphenoid sinus (figure 4) both demonstrated small sheets of malignant polygonal tumor cells with large, round, moderately pleomorphic nuclei, prominent nucleoli, abundant eosinophilic cytoplasm, and indistinct Figure 1. A: Contrast-enhanced coronal MRI of the pituitary area shows the rim-enhancing cell borders. Mitoses were frequent, mass in the sphenoid sinus (arrow). B and C: Coronal (B) and sagittal (C) views show the and atypical mitotic figures were adjacent cavernous sinus enlargement (arrows). D: Sagittal view also shows the thickened seen. In both specimens, the tumor pachymeningeal enhancement (arrowheads). cells were positive for a-fetoprotein. These findings were consistent with moderately to poorly if it is left untreated, mean survival has been reported to be less than 1 year.3 differentiated HCC with sphenoid sinus metastasis. In a review of 148 patients with metastatic HCC, Katyal The patient was not a native of Malaysia, and she requested to be transferred to a hospital in her home et al found that the most common sites of spread were the country. While arrangements were A B being made, she was placed under palliative care. However, her condition deteriorated, and she died 1 month after admission. Discussion
HCC is the most common primary hepatic tumor, and it is among the most common malignancies in the world (5.6% of all malignancies).1 It is rare in the Western Hemisphere and more common in Asia and Africa; for example, its incidence in men is 9.3 cases per 100,000 population in North America and 31.9 cases per 100,000 in eastern Asia.1 The most common etiologies of HCC are cirrhosis and exposure to hepatitis B and hepatitis C. In areas of high prevalence, it is more common in men than in women: (5:1).7 It is an aggressive tumor, and
C
D
Figure 2. A and B: Contrast-enhanced coronal (A) and sagittal (B) CTs of the abdomen and pelvis show the large, heterogeneously enhancing mass occupying almost the entirety of the right lobe of the liver (black arrows) with an area of central necrosis (white arrows). C and D: Axial and sagittal views show the lung nodules (C) and the lytic lesions in the thoracic and lumbar vertebrae, with an associated L3 pathologic fracture (D).
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AUTHOR COPY — NON COMMERCIAL USE ONLY Hashim, Rahmat, Abdul Aziz, Chandran
A
B
Figure 3. Liver biopsy. A: Histopathologic analysis with hematoxylin and eosin staining (original magnification ×10) reveals an aggressive and highly malignant hepatocellular carcinoma. The large polygonal cells resemble hepatocytes, with enlarged, moderately to severely pleomorphic vesicular nuclei, some of which have prominent nucleoli. The cells have ample eosinophilic cytoplasm. Mitosis is brisk, and atypical mitotic figures are seen (arrow). B: Immunohistochemical staining with a-fetoprotein (×10) shows strong cytoplasmic positivity in the malignant cells.
lung (55% of cases), the abdominal lymph nodes (41%), and bone (28%).3 In all the cases of bone metastasis, the lesions were lytic; two-thirds of them involved the spine. No cases involving the sinuses or skull base were reported in that series. Hsieh et al reviewed the literature published from 1966 to 2005 and found 68 reported cases of skull metastasis from HCC.2 In that review, the authors described the metastases as either calvarial or skull base lesions. Huang et al retrospectively studied 17 cases of sinonaA
B
Figure 4. Sphenoid sinus biopsy. A: Hematoxylin and eosin staining (×10) shows malignant hepatocytes similar to those seen in figure 3, A. B: Immunohistochemistry with a-fetoprotein staining (×10) shows the same strong cytoplasmic positivity in the malignant cells that is seen in figure 3, B.
sal metastases in Taiwan.8 They found that the primary tumor was located in the liver in 3 patients (18%). The most common sites of sinonasal metastasis were the maxillary sinus and the nasal cavity (42% each). The sphenoid sinuses were less commonly involved (5.9%). Bernstein et al9 and Friedmann and Osborn10 reviewed the world literature and reported on 82 and 31 cases of sinonasal metastatic tumors, respectively. The liver was not the primary site in any of these cases. The differences in the incidence of HCC metastatic to the sinonasal area reported by all these authors may be attributable to the geographical prevalence of HCC itself. Since chronic hepatitis B and hepatitis C, which play an important role in the development of HCC, are very prevalent in Asia, it is not surprising that the number of cases of primary HCC metastatic to the sinonasal area is higher in Asian countries. Among our patient’s presenting signs and symptoms were headache and blurred vision, which are signs of skull base involvement rather than of liver disease itself. Imaging and laboratory investigations of the abdomen were started only after hepatomegaly was detected during the physical examination. Our patient’s positive hepatitis B titer was also not detected until her referral to us. Since she was a foreigner in our country, it is possible that she had been having symptoms related to her hepatitis and hepatomegaly that had not been properly investigated before. It is unclear how HCC can metastasize to the sinonasal area. HCC is believed to spread through both hematogenous and lymphatic pathways.2,4 It is known to invade the local vascular networks by direct extension into the caval venous system (i.e., the hepatic vein and inferior vena cava). Once the tumor emboli enter the vascular system, they can flow through the pulmonary circulation and reach the sinonasal area through the arterial system of the head and neck.2,5,9 Another proposed hematogenous route is via the epidural venous plexus (Batson plexus), which is a network of valveless veins located in the epidural space of the spine.11 It is connected to the caval venous systems with rich venous intercommunications near the sinonasal area. An increase in intra-abdominal pressure may divert blood from the caval system into this valveless epidural system, thus providing a pathway for spread to the head and neck region.2,4,11 The lymphatic system provides another route of spread. Tumor emboli from the regional lymph nodes can flow into the thoracic duct. Via retrograde flow, they can reach the head and neck through intercostal,
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AUTHOR COPY — NON COMMERCIAL USE ONLY Metastatic hepatocellular carcinoma presenting as a sphenoid sinus mass and meningeal carcinomatosis
mediastinal, or supraclavicular lymph vessels.4 The treatment of HCC depends on tumor characteristics and the presence or absence of cirrhosis, comorbid diseases, and metastatic disease. Surgical resection and liver transplantation provide a chance of cure, but only for certain patients, depending on the size of their tumor and their liver function. Other treatment options for primary HCC include chemoembolization, ethanol ablation, radiofrequency ablation, cryoablation, and radiotherapy. Systemic chemotherapy may be used for advanced disease. Unfortunately, HCC is relatively chemotherapyresistant, and thus outcomes are usually unsatisfactory. In patients with bone metastasis, chemotherapy, surgery, and local ablation have been used as palliative measures to relieve pain and reduce the neurologic sequelae. Although the prognosis for patients with HCC and bone metastasis is not good, these treatments may improve the quality of their remaining life. The early diagnosis of a sphenoid sinus metastasis is difficult because the signs and symptoms are varied and nonspecific.3 A sphenoid sinus metastasis from any primary source is very rare and is generally not considered in the radiologic differential diagnosis. Diagnosis is even more difficult when the metastasis represents the initial manifestation of an undiagnosed malignancy. We present this case to remind readers of the possibility that a sphenoid sinus mass could represent a metastasis from an undetected primary. References
1. World Health Organization. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http:// globocan.iarc.fr. Accessed April 1. 2014. 2. Hsieh CT, Sun JM, Tsai WC, et al. Skull metastasis from hepatocellular carcinoma. Acta Neurochir (Wien) 2007;149(2):185-90. 3. Katyal S, Oliver JH III, Peterson MS, et al. Extrahepatic metastases of hepatocellular carcinoma, Radiology 2000;216(3):698-703. 4. Huang HH, Chang PH, Fang TJ. Sinonasal metastatic hepatocellular carcinoma. Am J Otolaryngol 2007;28(4):238-41. 5. Sim RS, Tan HK. A case of metastatic hepatocellular carcinoma of the sphenoid sinus. J Laryngol Otol 1994;108(6):503-4. 6. Tandon S, Nair A, Sawkar A, et al. Hepatocellular carcinoma presenting as an isolated sphenoid sinus lesion: A case report. Ear Nose Throat J 2012;91(1):E10-13. 7. Center MM, Jemal A. International trends in liver cancer incidence rates. Cancer Epidemiol Biomarkers Prev 2011;20(11):2362-8. 8. Huang HH, Fang TJ, Chang PH, Lee TJ. Sinonasal metastatic tumors in Taiwan. Chang Gung Med J 2008;31(5):457-62. 9. Bernstein JM, Montgomery WW, Balogh K Jr. Metastatic tumors to the maxilla, nose, and paranasal sinuses. Laryngoscope 1966;76(4): 621-50. 10. Friedmann I, Osborn DA. Metastatic tumors in the ear, nose and throat region. J Laryngol Otol 1965;79:576-91. 11. Nahum AM, Bailey BJ. Malignant tumors metastatic to the paranasal sinuses: Case report and review of the literature. Laryngoscope 1963; 73:942-53. COPYRIGHT 2014 BY VENDOME GROUP. UNAUTHORIZED REPRODUCTION OR DISTRIBUTION STRICTLY PROHIBITED Volume 93, Number 6 www.entjournal.com E23
