- Email: [email protected]
Brain metastases from hepatocellular carcinoma in two Caucasian Australian patients
Journal of Clinical Neuroscience 19 (2012) 1442–1445
Contents lists available at SciVerse ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case Reports
Brain metastases from hepatocellular carcinoma in two Caucasian Australian patients J. Shapey a,⇑, Y. Li a, M. Gonzales b, K. Drummond a,c a
Department of Neurosurgery, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia Department of Anatomical Pathology, The Royal Melbourne Hospital, Parkville, Victoria, Australia c Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia b
a r t i c l e
i n f o
Article history: Received 21 February 2012 Accepted 24 February 2012
Keywords: Brain metastasis Hepatocellular carcinoma Pathology
a b s t r a c t Hepatocellular carcinoma (HCC) is one of the world’s most common malignant cancers. Its incidence is particularly high in Asia and sub-Saharan Africa but, in recent years, significant increases in HCC have been observed in Australia and other Western countries. Therapeutic advances have contributed to improved survival rates in patients with HCC although intracranial metastases are extremely rare. Here we report the first two published Australian cases of brain metastases from HCC, both in Caucasian patients. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Hepatocellular carcinoma (HCC) is one of the world’s most common malignant cancers.1 Its incidence is particularly high in Asia and sub-Saharan Africa where hepatitis B and C infections are most prevalent, although in recent years significant increases in HCC have been observed in Australia and other Western countries.1 Recent therapeutic advances have contributed to improved survival rates in patients with HCC. Consequently, metastatic spread of HCC is no longer uncommon although intracranial metastases are rare.2,3 Here we report the first two published Australian cases of brain metastases from HCC, both in Caucasian patients.
2. Case reports 2.1. Patient 1 A 53-year-old right-handed Caucasian woman was admitted to hospital with a short history of increasing confusion, memory deficit and speech disturbance. She had a history of alcoholic liver disease and the previous year had been diagnosed with HCC during routine radiological investigation. Hepatitis serologies were negative. She was treated with transarterial chemoembolization (TACE) and no recurrence or metastatic spread had been detected on follow-up imaging. Her last alpha-fetoprotein (a-FP) level one year prior had also been normal. Past medical history included insulin-dependent diabetes and she was a heavy smoker. On examination, the patient was drowsy, confused and uncooperative. Limited neurological assessment elicited that her pupils ⇑ Corresponding author. Tel.: +61 3 93428218. E-mail address: [email protected] (J. Shapey).
were equal and reactive to light and she was spontaneously moving all limbs with no gross motor deficits. Laboratory investigations revealed a mild hyponatraemia (Na 130 mmol/L), anaemia (Hb 87 g/L), thrombocytopaenia (platelet count 131 109/L) and deranged liver function (alkaline phosphatase [ALP] 147 IU/L, gamma glutamyl transferase [GGT] 157 IU/L, albumin: 28 g/L). Her chest radiograph demonstrated a 5 cm 5 cm 7 cm left lower lobe mass and brain MRI with gadolinium contrast showed a large 2.5 cm 2.5 cm 3 cm heterogeneously enhancing mass within the left temporal lobe with areas of haemorrhage and central necrosis. There was also extensive surrounding vasogenic oedema causing 1 cm of uncal herniation (Fig. 1). She was commenced on phenytoin and high-dose dexamethasone and was subsequently transferred to our institution for consideration of surgery. Following transfusion of platelets and packed red blood cells, she underwent a frameless stereotactic craniotomy and gross macroscopic resection of the left temporal mass. Histology confirmed a poorly differentiated metastatic carcinoma staining positively for hepatocyte-paraffin 1 antigen, strongly suggestive of hepatocellular origin (Fig. 2). The patient remained confused postoperatively and was transferred to the referring hospital on the sixth postoperative day for further inpatient care. Unfortunately she died 18 days following her surgery. No adjuvant treatment was given. 2.2. Patient 2 A 77-year-old right-handed Caucasian man presented to a regional hospital with a three-week history of headache, right-sided weakness and right temporal visual field loss. Past history was notable for hypertension and heavy alcohol use. On examination, the patient was alert and oriented. Neurological assessment demonstrated a right temporal hemianopia and a right hemiparesis more pronounced in the lower limb, and general physical examina-
Case Reports / Journal of Clinical Neuroscience 19 (2012) 1442–1445
Fig. 1. Patient 1. Axial T1-weighted post-gadolinium MRI illustrating a heterogeneously enhancing mass in the anteroinferior temporal lobe.
tion elicited a palpable liver several centimetres below his right costal margin. He was initially treated as a presumed stroke and was given aspirin; however, a subsequent CT scan of the brain demonstrated a space-occupying mass in the left parietal–occipital region. He was thus transferred to our institution for consideration of surgery. Laboratory investigations revealed deranged liver function (ALP 145 IU/L, GGT 254 IU/L, alanine transaminase 62 IU/L, aspartate transaminase 62 IU/L, bilirubin 36 lmol/L, albumin 32 g/L) and thrombocytopenia (platelet count 79 109/L). His a-FP was mildly raised (11.5 lg/L [normal < 8.1 lg/L]) but hepatitis serologies were negative. Post-gadolinium MRI brain showed a 3.2 cm heterogeneously enhancing intra-axial mass in the left parietal–occipital region with areas of haemorrhage and central necrosis, associated with marked surrounding vasogenic oedema and effacement of the ipsilateral lateral ventricle (Fig. 3). A staging CT scan of his chest and abdomen showed two low-attenuation lesions within segment VII of the liver, which progressively enhanced and attenuated on dedicated triple-phase contrast CT scan, suggestive of HCC. He was commenced on phenytoin and high-dose dexamethasone, had supplemental platelets, and underwent a frameless stereotactic craniotomy and macroscopic gross resection of the left
1443
Fig. 3. Patient 2. Axial T2-fluid-attenuated inversion recovery MRI illustrating a heterogeneous mass in the left parieto-occipital region with marked surrounding oedema.
parietal–occipital mass. Histology confirmed a metastatic moderately differentiated adenocarcinoma, positively staining for hepatocyte antigen, alpha-1 antitrypsin and cytokeratin CAM 5.2, consistent with HCC (Fig. 4). Following surgery he was commenced on sorafenib but this was ceased due to a severe rash. He subsequently received a course of fractionated external beam radiotherapy and remains under close neurological and oncological follow-up.
3. Discussion Hepatocellular carcinoma is the fifth most common cause of cancer worldwide.4 In some Asian countries it is the leading cause of cancer-related death; however, significant percentage increases in HCC have been observed in many Western countries over the past two decades including the USA, Europe and Australia.1 In developed countries HCC usually arises in cirrhotic livers because of hepatitis C infection or excessive alcohol intake and many epidemiologists have attributed the increased incidence of HCC to the epidemic rise of hepatitis C infection seen in these parts of
Fig. 2. Patient 1. (a) Haematoxylin and eosin stained section of the surgical specimen showing diffuse sheets of atypical epithelioid cells and frequent mitotic figures (400) and (b) immunohistochemical staining for Hep-par showing strong staining in tumour cells typical of hepatocellular carcinoma (400).
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Case Reports / Journal of Clinical Neuroscience 19 (2012) 1442–1445
Fig. 4. Patient 2. (a) Haematoxylin and eosin stained section showing a trabecular arrangement of atypical epithelioid cells (400) and (b) immunohistochemical staining for Hep-par showing strong staining in tumour cells (400).
the world.5–7 In developing Asian countries HCC is frequently the long-term result of chronic viral infection (usually hepatitis B) and may not necessarily occur in cirrhotic livers (40% of cases in non-cirrhotic livers).8 HCC is three times more frequent in males than females and usually presents in the 6th and 7th decades of life; however, recent series from hepatitis B- and C-endemic areas in Asia found that the peak incidence of HCC was one to two decades earlier in these countries.1,3 The reported incidence of extrahepatic metastases in HCC varies significantly (13–64%)9–11 but in Western countries recurrent HCC is usually confined to the liver.12 Extrahepatic metastases most commonly occur in the lung, followed by regional lymph nodes, adrenal glands and bone.2,3,9,11,13 Brain metastases from HCC are rare (0.2–2.2%)2,9,14,15 but the true incidence of such metastases is likely to be significantly higher as most asymptomatic patients do not undergo routine brain imaging as part of their routine evaluation. Most of the literature on metastatic HCC originates from Asian countries but only a few cases of brain metastases in Caucasians have been reported.9,12,16–19 To our knowledge, these are the first two reported cases of hepatocellular brain metastases occurring in Caucasians outside Europe and the USA. The reported interval between an initial diagnosis of HCC and the discovery of brain metastasis ranges from two months to 54 months.10 More recent series from Korea and Taiwan reported a median interval of 18.2 months and 10.5 months respectively,2,3 although Chang et al. observed one patient who presented with a brain metastasis 17 years after initial diagnosis of HCC.3 Neurological symptoms may be the first presentation for some patients with metastatic HCC, although such presentations are not common. In a series by Choi et al., only 8% of patients with intracranial HCC metastasis had neurological symptoms as the first manifestation of their disease.2 Our first patient was found also to have a metastatic lung lesion at diagnosis and larger series have demonstrated a high rate of co-existing lung involvement in patients with brain metastases. Choi et al. reported that 81% of all patients with brain metastasis had other extra-cranial metastases at diagnosis, most commonly lung metastases (44 of 62 patients [69.4%]).2 Kim et al. reported that of nine patients with brain metastasis, six had lung involvement,14 and in another study, all five patients with brain metastasis also had lung involvement.20 The possibility of brain metastasis should therefore be considered in patients with lung metastasis. Patients with intracranial HCC metastasis may present with a variety of neurological symptoms. Symptoms may be caused by local mass effect resulting in focal neurological deficit, reduced conscious state or sometimes seizures; however, metastases of HCC are frequently associated with haemorrhage and may therefore
present abruptly, mimicking a stroke.14 Recent series noted haemorrhage rates of between 40% and 55%2,3,14 which is significantly higher than the previously quoted incidence of 1.3% to 6.1%.21 HCC is an inherently hypervascular tumour and most of these patients will also have a degree of coagulopathy due to liver cirrhosis, both of which predispose HCC metastases to haemorrhage. Other metastatic tumours commonly associated with haemorrhage include melanoma, renal cell carcinoma, choriocarcinoma, thyroid, breast and lung tumours.22 The prognosis of patients with HCC brain metastases is poor. Both the large Korean and Taiwanese studies had a low median survival: Choi et al. reported a median survival of 6.8 weeks2 and in the study by Chang et al. the median survival was one month, with the caveat that patients who received surgery and/or radiotherapy had a survival time of more than four months.3 Patient selection is of paramount importance when deciding on a management strategy for these patients. Serum a-FP is generally recognised as the most useful tumour marker reflecting tumour burden and low levels of a-FP are positively associated with longer survival.23 However, in most patients with HCC brain metastasis, treatment is palliative but multimodality approaches including surgery, radiosurgery and whole brain radiotherapy have been shown to improve survival in selected patients.24 Improved oncological management of HCC has lengthened patient survival and so it is likely that the number of patients presenting with symptomatic intracranial metastases will increase in the coming years. It is therefore important for clinicians, including those in areas where HCC is traditionally less prevalent, to have an awareness of the disease so that patients receive optimal management. References 1. El-Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol 2002;35:S72–78. 2. Choi HJ, Cho BC, Sohn JH, et al. Brain metastases from hepatocellular carcinoma: prognostic factors and outcome: brain metastasis from HCC. J Neurooncol 2009;91:307–13. 3. Chang L, Chen Y-L, Kao M-C. Intracranial metastasis of hepatocellular carcinoma: review of 45 cases. Surg Neurol 2004;62:172–7. 4. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907–17. 5. El-Serag HB, Davila JA, Petersen NJ, et al. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 2003;139:817–23. 6. Hassan MM, Frome A, Patt YZ, et al. Rising prevalence of hepatitis C virus infection among young patients recently diagnosed with hepatocellular carcinoma in the United states. J Clin Gastroenterol 2002;35:266–9. 7. Tsukuma H, Hiyama T, Tanaka S, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 1993;328:1797–801. 8. Zhou XD, Tang ZY, Yang BH, et al. Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma. Cancer 2001;91:1479–86.
Case Reports / Journal of Clinical Neuroscience 19 (2012) 1445–1447 9. Katyal S, Oliver III JH, Peterson MS, et al. Extrahepatic metastases of hepatocellular carnioma. Radiology 2000;216:698–702. 10. Tunc B, Filik L, Tezer-Filik I, et al. Brain metastasis of hepatocellular carcinoma: a case report and review of the literature. World J Gastroenterol 2004;10:1688–9. 11. Sithinamsuwan P, Piratvisuth T, Tanomkiat W, et al. Review of 336 patients with hepatocellular carcinoma at Songklanagarind Hospital. World J Gastroenterol 2000;6:339–43. 12. Seinfeld J, Wagner AS, Kleinschmidt-DeMasters BK. Brain metastases from hepatocellular carcinoma in US patients. J Neuro-Oncol 2006;76:93–8. 13. Lee YT, Geer AD. Primary liver cancer: pattern of metastasis. J Surg Oncol 1987;36:26–31. 14. Kim M, Na DL, Park SH, et al. Nervous system involvement by metastatic hepatocellular carcinoma. J Neruro-Oncol 1998;36:85–90. 15. Murakami K, Nawano S, Moriyama N, et al. Intracranial metastases of hepatoceullular carcinoma:CT and MRI. Neuroradiology 1996;38:S31–35. 16. Salvati M, Cimatti M, Frati A, et al. Brain metastases from hepatocellular carcinoma. A case report. J Neurosurg sci 2002;46:77–80. 17. Del Ben M, Caporale A, Feole K, et al. Intracranial haemorrhage due to brain metastases in an Italian HCV patient with hepatocellular carcinoma. J Exp Clin Cancer Res 2003;22:641–4.
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18. Friedman HD. Hepatocellular carcinoma with central nervous system metastasis: a case report and literature review. Med Ped Oncol 1991;19: 139–44. 19. Brunner DR, Dunne MG, Rao KC, et al. Hepatoma presenting as a cerebellar metastasis. J Comput Tomogr 1982;6:65–8. 20. Natsuizaka M, Omura T, Akaike T, et al. Clincial features of hepatocellular carcinoma with extrahepatic metastases. J Gastroenterol Hepatol 2005;20:1781–7. 21. Kuga Y, Waga S, Itoh H. Intracranial haemorrhage due to brain metastasis from hepatocellular carcinoma. Neurol med Chir (Tokyo) 1990;30:768–71. 22. Davis JM, Zimmerman RA, Bilaniuk LT. Metastases to the central nervous system. Radiol Clin North Am 1982;20:417–35. 23. Nomura F, Ohnishi K, Tanabe Y. Clinical features and prognosis of hepatocellular carcinoma with reference to serum alpha-fetoprotein levels. Analysis of 606 patients. Cancer 1989;64:1700–7. 24. Richards GM, Khuntia D, Mehra MP. Therapeutic management of metastatic brain tumours. Crit Rev Oncol Hematol 2007;61:70–8.
doi:http://dx.doi.org10.1016/j.jocn.2012.02.009
Bilateral non-arteritic anterior ischemic optic neuropathy following second-trimester spontaneous abortion-related haemorrhage Zafer Onaran a, Funda Uysal Tan b,⇑, Pelin Yılmazbasß a, Yüksel Onaran c a b c
Department of Ophthalmology, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey Department of Neurology, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey Department of Gynaecology and Obstetrics, Faculty of Medicine, Fatih University, Ankara, Turkey
a r t i c l e
i n f o
Article history: Received 15 March 2011 Accepted 6 November 2011
Keywords: Abortion Bilateral Haemorrhage Non-arteritic anterior ischemic optic neuropathy
a b s t r a c t Bilateral anterior ischemic optic neuropathy is a rare complication of massive haemorrhage and related hypotension and anaemia in young individuals. We report a 34-year-old woman with bilateral non-arteritic ischemic optic neuropathy (NAION) after a massive spontaneous abortion-related haemorrhage who presented with sudden painless visual loss in her left eye. Visual acuity was 20/20 in the right eye with only hand motion discernible in the left eye. There was a left relative afferent papillary defect (RAPD). Fundus examination revealed bilateral swollen, hyperaemic optic discs and nerve fiber layer haemorrhages. Brain MRI and magnetic resonance venography were normal. The diagnosis of bilateral NAION was made and intravenous pulse corticosteroid therapy (1000 mg/day) was administered for three days. On the sixth day, optic disc oedema regressed bilaterally and on the third week, the visual acuity improved to 20/80 in the left eye. The visual field showed only a small spared area in the nasal region, and persistent RAPD was present. After two months, fundus examination showed a small and crowded optic disc on the right and a pale optic disc on the left. Severe acute haemorrhage is an important risk factor for NAION in healthy young individuals. In addition to correction of hypotension and anaemia, intravenous high dose corticosteroid might be beneficial for treatment. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Non-arteritic ischemic optic neuropathy (NAION) is an ischemic process of the anterior portion of the optic nerve characterized by sudden, painless visual loss. Typically, NAION affects the elderly and is associated with risk factors such as diabetes mellitus, systemic hypertension and optic disc morphology (small and crowded optic disc).1,2 However, in younger patients, NAION is usually related to massive blood loss with resultant hypotension, and it has been reported after several surgical procedures, including spinal and cardiac surgery but rarely after trauma or obstetric haemorrhage.2–6
⇑ Corresponding author. Address: Elçi Sokak 19/18, Y. Ayrancı 06550, Ankara, Turkey. Fax: +90 312 2026202. E-mail address: [email protected] (F.U. Tan).
Here we report a patient with bilateral NAION after abortion that resulted in a unilateral visual impairment. To our knowledge, this is a unique case presented after spontaneous abortion.
2. Case report A 34-year-old woman was referred to our clinic three days after spontaneous abortion with visual loss in her left eye. She first complained about blurred vision two days after the abortion. Her medical history was unremarkable. She had four healthy children and no history of prior miscarriages. During her fifth pregnancy recurrent vaginal bleeding began during the fourth gestational week and complicated the pregnancy until a spontaneous abortion at the 20th week. Presumed uterine atony led to massive haemorrhage and her haemoglobin decreased from 9.5 g/dL to 6.4 g/dL.
Contents lists available at SciVerse ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case Reports
Brain metastases from hepatocellular carcinoma in two Caucasian Australian patients J. Shapey a,⇑, Y. Li a, M. Gonzales b, K. Drummond a,c a
Department of Neurosurgery, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia Department of Anatomical Pathology, The Royal Melbourne Hospital, Parkville, Victoria, Australia c Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia b
a r t i c l e
i n f o
Article history: Received 21 February 2012 Accepted 24 February 2012
Keywords: Brain metastasis Hepatocellular carcinoma Pathology
a b s t r a c t Hepatocellular carcinoma (HCC) is one of the world’s most common malignant cancers. Its incidence is particularly high in Asia and sub-Saharan Africa but, in recent years, significant increases in HCC have been observed in Australia and other Western countries. Therapeutic advances have contributed to improved survival rates in patients with HCC although intracranial metastases are extremely rare. Here we report the first two published Australian cases of brain metastases from HCC, both in Caucasian patients. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Hepatocellular carcinoma (HCC) is one of the world’s most common malignant cancers.1 Its incidence is particularly high in Asia and sub-Saharan Africa where hepatitis B and C infections are most prevalent, although in recent years significant increases in HCC have been observed in Australia and other Western countries.1 Recent therapeutic advances have contributed to improved survival rates in patients with HCC. Consequently, metastatic spread of HCC is no longer uncommon although intracranial metastases are rare.2,3 Here we report the first two published Australian cases of brain metastases from HCC, both in Caucasian patients.
2. Case reports 2.1. Patient 1 A 53-year-old right-handed Caucasian woman was admitted to hospital with a short history of increasing confusion, memory deficit and speech disturbance. She had a history of alcoholic liver disease and the previous year had been diagnosed with HCC during routine radiological investigation. Hepatitis serologies were negative. She was treated with transarterial chemoembolization (TACE) and no recurrence or metastatic spread had been detected on follow-up imaging. Her last alpha-fetoprotein (a-FP) level one year prior had also been normal. Past medical history included insulin-dependent diabetes and she was a heavy smoker. On examination, the patient was drowsy, confused and uncooperative. Limited neurological assessment elicited that her pupils ⇑ Corresponding author. Tel.: +61 3 93428218. E-mail address: [email protected] (J. Shapey).
were equal and reactive to light and she was spontaneously moving all limbs with no gross motor deficits. Laboratory investigations revealed a mild hyponatraemia (Na 130 mmol/L), anaemia (Hb 87 g/L), thrombocytopaenia (platelet count 131 109/L) and deranged liver function (alkaline phosphatase [ALP] 147 IU/L, gamma glutamyl transferase [GGT] 157 IU/L, albumin: 28 g/L). Her chest radiograph demonstrated a 5 cm 5 cm 7 cm left lower lobe mass and brain MRI with gadolinium contrast showed a large 2.5 cm 2.5 cm 3 cm heterogeneously enhancing mass within the left temporal lobe with areas of haemorrhage and central necrosis. There was also extensive surrounding vasogenic oedema causing 1 cm of uncal herniation (Fig. 1). She was commenced on phenytoin and high-dose dexamethasone and was subsequently transferred to our institution for consideration of surgery. Following transfusion of platelets and packed red blood cells, she underwent a frameless stereotactic craniotomy and gross macroscopic resection of the left temporal mass. Histology confirmed a poorly differentiated metastatic carcinoma staining positively for hepatocyte-paraffin 1 antigen, strongly suggestive of hepatocellular origin (Fig. 2). The patient remained confused postoperatively and was transferred to the referring hospital on the sixth postoperative day for further inpatient care. Unfortunately she died 18 days following her surgery. No adjuvant treatment was given. 2.2. Patient 2 A 77-year-old right-handed Caucasian man presented to a regional hospital with a three-week history of headache, right-sided weakness and right temporal visual field loss. Past history was notable for hypertension and heavy alcohol use. On examination, the patient was alert and oriented. Neurological assessment demonstrated a right temporal hemianopia and a right hemiparesis more pronounced in the lower limb, and general physical examina-
Case Reports / Journal of Clinical Neuroscience 19 (2012) 1442–1445
Fig. 1. Patient 1. Axial T1-weighted post-gadolinium MRI illustrating a heterogeneously enhancing mass in the anteroinferior temporal lobe.
tion elicited a palpable liver several centimetres below his right costal margin. He was initially treated as a presumed stroke and was given aspirin; however, a subsequent CT scan of the brain demonstrated a space-occupying mass in the left parietal–occipital region. He was thus transferred to our institution for consideration of surgery. Laboratory investigations revealed deranged liver function (ALP 145 IU/L, GGT 254 IU/L, alanine transaminase 62 IU/L, aspartate transaminase 62 IU/L, bilirubin 36 lmol/L, albumin 32 g/L) and thrombocytopenia (platelet count 79 109/L). His a-FP was mildly raised (11.5 lg/L [normal < 8.1 lg/L]) but hepatitis serologies were negative. Post-gadolinium MRI brain showed a 3.2 cm heterogeneously enhancing intra-axial mass in the left parietal–occipital region with areas of haemorrhage and central necrosis, associated with marked surrounding vasogenic oedema and effacement of the ipsilateral lateral ventricle (Fig. 3). A staging CT scan of his chest and abdomen showed two low-attenuation lesions within segment VII of the liver, which progressively enhanced and attenuated on dedicated triple-phase contrast CT scan, suggestive of HCC. He was commenced on phenytoin and high-dose dexamethasone, had supplemental platelets, and underwent a frameless stereotactic craniotomy and macroscopic gross resection of the left
1443
Fig. 3. Patient 2. Axial T2-fluid-attenuated inversion recovery MRI illustrating a heterogeneous mass in the left parieto-occipital region with marked surrounding oedema.
parietal–occipital mass. Histology confirmed a metastatic moderately differentiated adenocarcinoma, positively staining for hepatocyte antigen, alpha-1 antitrypsin and cytokeratin CAM 5.2, consistent with HCC (Fig. 4). Following surgery he was commenced on sorafenib but this was ceased due to a severe rash. He subsequently received a course of fractionated external beam radiotherapy and remains under close neurological and oncological follow-up.
3. Discussion Hepatocellular carcinoma is the fifth most common cause of cancer worldwide.4 In some Asian countries it is the leading cause of cancer-related death; however, significant percentage increases in HCC have been observed in many Western countries over the past two decades including the USA, Europe and Australia.1 In developed countries HCC usually arises in cirrhotic livers because of hepatitis C infection or excessive alcohol intake and many epidemiologists have attributed the increased incidence of HCC to the epidemic rise of hepatitis C infection seen in these parts of
Fig. 2. Patient 1. (a) Haematoxylin and eosin stained section of the surgical specimen showing diffuse sheets of atypical epithelioid cells and frequent mitotic figures (400) and (b) immunohistochemical staining for Hep-par showing strong staining in tumour cells typical of hepatocellular carcinoma (400).
1444
Case Reports / Journal of Clinical Neuroscience 19 (2012) 1442–1445
Fig. 4. Patient 2. (a) Haematoxylin and eosin stained section showing a trabecular arrangement of atypical epithelioid cells (400) and (b) immunohistochemical staining for Hep-par showing strong staining in tumour cells (400).
the world.5–7 In developing Asian countries HCC is frequently the long-term result of chronic viral infection (usually hepatitis B) and may not necessarily occur in cirrhotic livers (40% of cases in non-cirrhotic livers).8 HCC is three times more frequent in males than females and usually presents in the 6th and 7th decades of life; however, recent series from hepatitis B- and C-endemic areas in Asia found that the peak incidence of HCC was one to two decades earlier in these countries.1,3 The reported incidence of extrahepatic metastases in HCC varies significantly (13–64%)9–11 but in Western countries recurrent HCC is usually confined to the liver.12 Extrahepatic metastases most commonly occur in the lung, followed by regional lymph nodes, adrenal glands and bone.2,3,9,11,13 Brain metastases from HCC are rare (0.2–2.2%)2,9,14,15 but the true incidence of such metastases is likely to be significantly higher as most asymptomatic patients do not undergo routine brain imaging as part of their routine evaluation. Most of the literature on metastatic HCC originates from Asian countries but only a few cases of brain metastases in Caucasians have been reported.9,12,16–19 To our knowledge, these are the first two reported cases of hepatocellular brain metastases occurring in Caucasians outside Europe and the USA. The reported interval between an initial diagnosis of HCC and the discovery of brain metastasis ranges from two months to 54 months.10 More recent series from Korea and Taiwan reported a median interval of 18.2 months and 10.5 months respectively,2,3 although Chang et al. observed one patient who presented with a brain metastasis 17 years after initial diagnosis of HCC.3 Neurological symptoms may be the first presentation for some patients with metastatic HCC, although such presentations are not common. In a series by Choi et al., only 8% of patients with intracranial HCC metastasis had neurological symptoms as the first manifestation of their disease.2 Our first patient was found also to have a metastatic lung lesion at diagnosis and larger series have demonstrated a high rate of co-existing lung involvement in patients with brain metastases. Choi et al. reported that 81% of all patients with brain metastasis had other extra-cranial metastases at diagnosis, most commonly lung metastases (44 of 62 patients [69.4%]).2 Kim et al. reported that of nine patients with brain metastasis, six had lung involvement,14 and in another study, all five patients with brain metastasis also had lung involvement.20 The possibility of brain metastasis should therefore be considered in patients with lung metastasis. Patients with intracranial HCC metastasis may present with a variety of neurological symptoms. Symptoms may be caused by local mass effect resulting in focal neurological deficit, reduced conscious state or sometimes seizures; however, metastases of HCC are frequently associated with haemorrhage and may therefore
present abruptly, mimicking a stroke.14 Recent series noted haemorrhage rates of between 40% and 55%2,3,14 which is significantly higher than the previously quoted incidence of 1.3% to 6.1%.21 HCC is an inherently hypervascular tumour and most of these patients will also have a degree of coagulopathy due to liver cirrhosis, both of which predispose HCC metastases to haemorrhage. Other metastatic tumours commonly associated with haemorrhage include melanoma, renal cell carcinoma, choriocarcinoma, thyroid, breast and lung tumours.22 The prognosis of patients with HCC brain metastases is poor. Both the large Korean and Taiwanese studies had a low median survival: Choi et al. reported a median survival of 6.8 weeks2 and in the study by Chang et al. the median survival was one month, with the caveat that patients who received surgery and/or radiotherapy had a survival time of more than four months.3 Patient selection is of paramount importance when deciding on a management strategy for these patients. Serum a-FP is generally recognised as the most useful tumour marker reflecting tumour burden and low levels of a-FP are positively associated with longer survival.23 However, in most patients with HCC brain metastasis, treatment is palliative but multimodality approaches including surgery, radiosurgery and whole brain radiotherapy have been shown to improve survival in selected patients.24 Improved oncological management of HCC has lengthened patient survival and so it is likely that the number of patients presenting with symptomatic intracranial metastases will increase in the coming years. It is therefore important for clinicians, including those in areas where HCC is traditionally less prevalent, to have an awareness of the disease so that patients receive optimal management. References 1. El-Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol 2002;35:S72–78. 2. Choi HJ, Cho BC, Sohn JH, et al. Brain metastases from hepatocellular carcinoma: prognostic factors and outcome: brain metastasis from HCC. J Neurooncol 2009;91:307–13. 3. Chang L, Chen Y-L, Kao M-C. Intracranial metastasis of hepatocellular carcinoma: review of 45 cases. Surg Neurol 2004;62:172–7. 4. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907–17. 5. El-Serag HB, Davila JA, Petersen NJ, et al. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 2003;139:817–23. 6. Hassan MM, Frome A, Patt YZ, et al. Rising prevalence of hepatitis C virus infection among young patients recently diagnosed with hepatocellular carcinoma in the United states. J Clin Gastroenterol 2002;35:266–9. 7. Tsukuma H, Hiyama T, Tanaka S, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 1993;328:1797–801. 8. Zhou XD, Tang ZY, Yang BH, et al. Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma. Cancer 2001;91:1479–86.
Case Reports / Journal of Clinical Neuroscience 19 (2012) 1445–1447 9. Katyal S, Oliver III JH, Peterson MS, et al. Extrahepatic metastases of hepatocellular carnioma. Radiology 2000;216:698–702. 10. Tunc B, Filik L, Tezer-Filik I, et al. Brain metastasis of hepatocellular carcinoma: a case report and review of the literature. World J Gastroenterol 2004;10:1688–9. 11. Sithinamsuwan P, Piratvisuth T, Tanomkiat W, et al. Review of 336 patients with hepatocellular carcinoma at Songklanagarind Hospital. World J Gastroenterol 2000;6:339–43. 12. Seinfeld J, Wagner AS, Kleinschmidt-DeMasters BK. Brain metastases from hepatocellular carcinoma in US patients. J Neuro-Oncol 2006;76:93–8. 13. Lee YT, Geer AD. Primary liver cancer: pattern of metastasis. J Surg Oncol 1987;36:26–31. 14. Kim M, Na DL, Park SH, et al. Nervous system involvement by metastatic hepatocellular carcinoma. J Neruro-Oncol 1998;36:85–90. 15. Murakami K, Nawano S, Moriyama N, et al. Intracranial metastases of hepatoceullular carcinoma:CT and MRI. Neuroradiology 1996;38:S31–35. 16. Salvati M, Cimatti M, Frati A, et al. Brain metastases from hepatocellular carcinoma. A case report. J Neurosurg sci 2002;46:77–80. 17. Del Ben M, Caporale A, Feole K, et al. Intracranial haemorrhage due to brain metastases in an Italian HCV patient with hepatocellular carcinoma. J Exp Clin Cancer Res 2003;22:641–4.
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doi:http://dx.doi.org10.1016/j.jocn.2012.02.009
Bilateral non-arteritic anterior ischemic optic neuropathy following second-trimester spontaneous abortion-related haemorrhage Zafer Onaran a, Funda Uysal Tan b,⇑, Pelin Yılmazbasß a, Yüksel Onaran c a b c
Department of Ophthalmology, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey Department of Neurology, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey Department of Gynaecology and Obstetrics, Faculty of Medicine, Fatih University, Ankara, Turkey
a r t i c l e
i n f o
Article history: Received 15 March 2011 Accepted 6 November 2011
Keywords: Abortion Bilateral Haemorrhage Non-arteritic anterior ischemic optic neuropathy
a b s t r a c t Bilateral anterior ischemic optic neuropathy is a rare complication of massive haemorrhage and related hypotension and anaemia in young individuals. We report a 34-year-old woman with bilateral non-arteritic ischemic optic neuropathy (NAION) after a massive spontaneous abortion-related haemorrhage who presented with sudden painless visual loss in her left eye. Visual acuity was 20/20 in the right eye with only hand motion discernible in the left eye. There was a left relative afferent papillary defect (RAPD). Fundus examination revealed bilateral swollen, hyperaemic optic discs and nerve fiber layer haemorrhages. Brain MRI and magnetic resonance venography were normal. The diagnosis of bilateral NAION was made and intravenous pulse corticosteroid therapy (1000 mg/day) was administered for three days. On the sixth day, optic disc oedema regressed bilaterally and on the third week, the visual acuity improved to 20/80 in the left eye. The visual field showed only a small spared area in the nasal region, and persistent RAPD was present. After two months, fundus examination showed a small and crowded optic disc on the right and a pale optic disc on the left. Severe acute haemorrhage is an important risk factor for NAION in healthy young individuals. In addition to correction of hypotension and anaemia, intravenous high dose corticosteroid might be beneficial for treatment. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Non-arteritic ischemic optic neuropathy (NAION) is an ischemic process of the anterior portion of the optic nerve characterized by sudden, painless visual loss. Typically, NAION affects the elderly and is associated with risk factors such as diabetes mellitus, systemic hypertension and optic disc morphology (small and crowded optic disc).1,2 However, in younger patients, NAION is usually related to massive blood loss with resultant hypotension, and it has been reported after several surgical procedures, including spinal and cardiac surgery but rarely after trauma or obstetric haemorrhage.2–6
⇑ Corresponding author. Address: Elçi Sokak 19/18, Y. Ayrancı 06550, Ankara, Turkey. Fax: +90 312 2026202. E-mail address: [email protected] (F.U. Tan).
Here we report a patient with bilateral NAION after abortion that resulted in a unilateral visual impairment. To our knowledge, this is a unique case presented after spontaneous abortion.
2. Case report A 34-year-old woman was referred to our clinic three days after spontaneous abortion with visual loss in her left eye. She first complained about blurred vision two days after the abortion. Her medical history was unremarkable. She had four healthy children and no history of prior miscarriages. During her fifth pregnancy recurrent vaginal bleeding began during the fourth gestational week and complicated the pregnancy until a spontaneous abortion at the 20th week. Presumed uterine atony led to massive haemorrhage and her haemoglobin decreased from 9.5 g/dL to 6.4 g/dL.