CASE REPORTS Metastatic Hepatocellular Carcinoma Presenting as Epidural Hematoma: Case Report Jon I. McIver, M.D., Bernd W. Scheithauer, M.D., Charlotte H. Rydberg, M.D., John L.D. Atkinson, M.D. Departments of Neurologic Surgery (JIM, JLDA), Pathology (BWS), and Radiology (CHR), Mayo Clinic, Rochester, Minnesota OBJECTIVE AND IMPORTANCE: A case of acutely symptomatic epidural hematoma caused by metastatic hepatocellular carcinoma (HCC) to the cranium is reported. This is a rare case of metastatic HCC without known primary presenting as an epidural hematoma. CLINICAL PRESENTATION: The patient presented with an acute onset of headache, aphasia, and right hemiparesis 2 weeks after he experienced minor trauma to the cranium. An emergency computed tomographic scan of the head revealed the presence of a left parietal epidural hematoma. INTERVENTION: An emergency evacuation of the epidural hematoma was performed, and metastatic HCC was diagnosed. CONCLUSION: The patient’s neurological deficits were reversed with surgical intervention, and he is now undergoing palliative chemotherapy. This was the first clinical manifestation of HCC in this patient. This case reaffirms the neurosurgeon’s role in the complex, multidisciplinary care of patients with craniospinal metastasis. (Neurosurgery 49:447–449, 2001) Key words: Epidural hematoma, Hepatocellular carcinoma, Metastasis H epatocellular carcinoma (HCC) is the eighth most frequent cancer in the world (1). Far more prevalent in subSaharan Africa and Asia (1, 3, 9), it is much less common in the United States and Western Europe, where at autopsy it accounts for only 1 to 2% of malignant tumors (4). The disease most frequently occurs in the sixth or seventh decade of life, and from 30 to 70% of patients are found to have metastases at the time of death (9). Metastasis rarely affects the craniospinal axis. Although no treatment has yet been proved to increase survival in patients with unresectable lesions, earlier diagnosis may improve the chances of successful surgical resection of primary tumors (9). We report a case of cranial metastasis of HCC with epidural hematoma as the initial manifestation of the disease. right hemiparesis, and extensor plantar responses of the right foot were noted. The patient’s medical history was significant for hepatitis of unknown type. The patient also reported a 6-week history of mild right lateral hip pain and intermittent right leg numbness and tingling. An emergency computed tomographic scan of the patient’s head revealed a left parietal epidural hematoma and an associated lytic cranial lesion with both intracranial and extracranial components (Fig. 1). Compression of the adjacent parietal and posterior frontal lobes was also noted, as was minimal midline shift. A subsequent magnetic resonance imaging scan showed a 10 ⫻ 10 ⫻ 5.5-cm, permeative, lytic enhancing tumor, but no edema of the underlying compressed brain parenchyma was observed (Fig. 2). The patient was rushed to the operating room for a left frontoparietal craniotomy and epidural hematoma evacuation. The left parietal skin flap was reflected, and a grossly hemorrhagic, exophytic, extracalvarial tumor was exposed and easily removed from the subgaleal layer. The tumor was radically resected with surrounding normal bone via a generous left parietal craniectomy (Fig. 3). There was no gross dural invasion, and hemostasis was easily attained after tumor removal. Because of the large calvarial defect, a cranioplasty was performed with a CLINICAL PRESENTATION The patient was a 50-year-old, white, right-handed man. Two weeks before admission, he bumped the left side of his head and experienced swelling of the involved area. The interim history was remarkable only for persistence of the left parietal scalp swelling. On the morning of admission, the patient awoke with a severe left hemicranial headache and weakness in his right arm and right leg. A friend noticed that the patient had trouble walking and urged him to report to the hospital. At admission, physical examination revealed a soft, nontender, protuberant mass on the left scalp with intact overlying skin. The patient was oriented but had slurred speech and displayed phonetic errors. A right lower facial droop, FIGURE 1. Nonenhanced computed tomographic image demonstrating large left frontoparietal epidural hematoma with lytic cranial lesion and extracalvarial component. Neurosurgery, Vol. 49, No. 2, August 2001 447 448 McIver et al. FIGURE 2. A, noncontrast axial T1-weighted magnetic resonance image showing the solid tumor posteriorly and the acute hematoma anteriorly. The dark line (arrow) represents the displaced dura. B, postcontrast axial T1-weighted magnetic resonance image showing the enhancing epidural tumor posteriorly and extravasation of contrast into the anterior hematoma (arrow). C, coronal T1-weighted magnetic resonance image with contrast showing strongly enhancing transcalvarial metastasis. rigid titanium mesh plate without methylmethacrylate. Pathological findings confirmed a diagnosis of metastatic Grade 2 (on a 4-point scale) HCC. The patient’s neurological deficits quickly resolved. Later, an oncological evaluation was performed. The patient had chronic active hepatitis C and previously had been exposed to hepatitis B. A magnetic resonance imaging scan indicated hepatic cirrhosis and a solid 5.4 ⫻ 5.1-cm lesion in the right lobe of the liver. An 11 ⫻ 10-cm soft tissue mass centered within the right iliac bone was also detected. At the time of the most recent follow-up examination, the patient displayed no neurological deficits and was undergoing palliative chemotherapy. DISCUSSION The most common sites of metastasis of HCC are regional lymph nodes and the lung (3, 5). The incidence of osseous metastasis ranges from 2 to 16%, depending on the prevalence of the disease in the population (5, 7). The vertebrae, sternum, ribs, and long bones are sites (7, 9), although metastasis to the cranium is rare, with a reported incidence of 0.5 to 1.6% (3, 5, 6). Brain metastasis is also rare, with a similar incidence of 0.3 to 1.7% (3, 6). The higher incidence of HCC in Asia is linked to the increased prevalence of chronic hepatitis there. The role of hepatitis B or C virus as a direct carcinogen is unclear, but the latter is thought to increase the risk for HCC through the pathogenesis of cirrhosis (1). Headache, the presence of a painful mass, and neurological deficits were commonly reported symptoms of HCC cranial metastases in the series of Murakami et al. (5). These findings were present in five of the six cases reviewed. In the literature review of Friedman (3), three of five patients with HCC cranial metastases had limb weakness with an associated palpable scalp mass, and two patients had cranial nerve palsy. The Neurosurgery, Vol. 49, No. 2, August 2001 FIGURE 3. Intraoperative photograph demonstrating grossly hemorrhagic tumor (arrow). Bone flap with lytic lesion and adherent clot are visible above surgical bed. patient whom we assessed presented with a palpable, nontender scalp lesion, headache, and acute neurological deficit. These symptoms were the first overt clinical manifestations of HCC, as was the case in three of six patients reported by Murakami et al. (5). Only four cases of HCC associated with epidural hematoma have been reported (2, 6–8). All of these patients were Japanese, and in only one patient was the diagnosis of HCC not previously known. Our patient was a white man with symptomatic epidural hematoma after minor trauma, which led to a diagnosis of metastatic HCC. To our knowledge, this case is the first reported case of metastatic HCC without a known primary presenting as an epidural hematoma as well as the first report of an epidural hematoma due to metastatic HCC that occurred in a country other than Japan. HCC metastasizes by hematogenous and lymphatic routes (9). In HCC and other carcinomas, seeding of the brain, the meninges, or the cranium is usually in the distribution of the middle cerebral artery (9). In this patient, the tumor invaded the full thickness of the calvarium, but no gross invasion of the dura was observed. Epidural Metastatic Hepatocellular Carcinoma We did not obtain a biopsy of the dura, so microscopic dural invasion could not be excluded. Hemorrhage from the diploic marrow, emissary veins, or the tumor itself may have contributed to the epidural hematoma. Perhaps such hemorrhage was initiated 2 weeks earlier by the trivial cranial injury to the area. Such low-pressure bleeding alone would probably be insufficient to develop and expand the epidural space. As suggested by Nakao et al. (7), immediate dural stripping from the cranium at head injury probably produced an epidural space that served as a reservoir for blood. Although Nakao et al. did not think that progressive dural stripping occurred in their patient with a chronic epidural hematoma, the acute presentation of our patient suggests that it did. An acute epidural hemorrhage of this size would have been fatal, and the brain was without marked herniation or edema. It is also likely that tumor spread along the dura in our patient further developed the epidural component. Thus, both posttraumatic hemorrhage and tumor mass probably precipitated the acute presentation. This patient’s presenting symptoms were attributable to the brain compression caused by the epidural hematoma. The 6-week history of intermittent right hip pain and leg discomfort can be attributed to the iliac lesion. As in our patient, metastases to the pelvic bones are usually large, lytic lesions (9). Although instances of cord compression as a result of metastatic HCC have been reported (9), no neurological findings suggested radiculomyelopathy in this patient. CONCLUSION HCC may be the primary or secondary cause of neurological impairment. Earlier detection and effective local treatment have improved the prognosis of patients with HCC and have increased the likelihood of detecting treatable metastases. The neurosurgeon contributes to the multidisciplinary care of patients with craniospinal metastasis as both technician and diagnostician, sometimes being the first to introduce the patient to the sphere of therapy. ACKNOWLEDGMENT We thank Dr. Michi Jougasaki for translation of the Japanese case reports. Received, November 9, 2000. Accepted, March 9, 2001. Reprint requests: Jon I. McIver, M.D., Department of Neurologic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Email: mciver.jon@mayo.edu REFERENCES 1. Carr BI, Flickinger JC, Lotze MT: Hepatobiliary cancers, in DeVita VT Jr, Rosenberg SA, Hellman S (eds): Cancer: Principles and Practice of Oncology. Philadelphia, Lippincott-Raven, 1997, ed 5, pp 1089–1090. 2. Endo M, Hamano M, Watanabe K, Wakai S: Combined chronic subdural and acute epidural hematoma secondary to metastatic hepatocellular cancer: Case report [in Japanese]. No Shinkei Geka 27:331–334, 1999. 3. Friedman HD: Hepatocellular carcinoma with central nervous system metastasis: A case report and literature review. Med Pediatr Oncol 19: 139–144, 1991. 4. Isselbacher KJ, Dienstag JL: Tumors of the liver and biliary tract, in Fauci AS, Braunwald, Isselbacher KJ, Wilson JD, Martin JB, Kasper D, Hauser SL, Longo DL (eds): Harrison’s Principles of Internal Medicine. New York, McGraw-Hill, 1997, ed 14, vol 1, pp 578–581. 5. 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COMMENTS McIver et al. report a case of hepatocellular carcinoma (HCC) metastasis to the cranium with the initial clinical presentation of epidural hematoma. Distant metastasis of HCC is uncommon, but metastasis to the cranium and its association with epidural hematoma has been reported. The interesting point about this case is the temporal relationship of a mi- Neurosurgery, Vol. 49, No. 2, August 2001 449 nor trauma to that region of the head and the onset of acute neurological symptoms. The authors offer an explanation for the cause of the hematoma by inferring that traumatic injury to the tumor resulted in a low-pressure bleed. They further elaborate that the growth of the tumor is responsible for progressive stripping of the dura. This event created an epidural space to potentiate the bleed. The authors do not address the fact that their patient has hepatitis and may have marginal coagulopathy. Furthermore, HCC is known for its vascularity, and if this tumor has already invaded both tables of the bone, then it is not surprising for it to bleed into the epidural space even after a trivial trauma. These comments do not, however, reduce the merit of the authors’ reiteration that isolated craniospinal metastasis can be the initial presentation of the systemic disease in more than 10% of all cancer patients. Undoubtedly, tissue diagnosis is an important component in the management of this and other, similar patients. Victor Tse John R. Adler, Jr. Stanford, California McIver et al. report an extremely rare instance of a transcranial metastasis from a HCC. Also rare is the initial presentation of the primary cancer as an epidural lesion. Although occasionally prostate carcinoma presents as an extradural metastasis appearing as a subdural hematoma, this epidural presentation of HCC is unique. I agree with the authors that an epidural hematoma of this size would be fatal if not for the epidural space previously having been expanded by the tumor. A slow ooze into this space would have the effect noted in the radiological images. Jack P. Rock Detroit, Michigan This case is indeed a very rare manifestation of a HCC. That the calvarial mass was the first indication of the presence of the disease is even more unusual. This case is well illustrated and provides a useful addition to the literature on differential diagnosis of calvarial masses. Raymond Sawaya Houston, Texas