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Primary spinal melanoma with bilateral papilledema
Clinical Neurology and Neurosurgery 107 (2005) 525–527
Case report
Primary spinal melanoma with bilateral papilledema Gueorgui K. Kounina , Kiril V. Romanskya , Latchezar D. Traykovb,c,∗ , Penko M. Shotekovb , Detelina Z. Stoilovab a
Department of Neurosurgery, University Hospital Alexandrovska, Georgi Sofijski 1 Str., 1431 Sofia, Bulgaria Department of Neurology, University Hospital Alexandrovska, Georgi Sofijski 1 Str., 1431 Sofia, Bulgaria c Department of Neurology, University Hospital Henri Mondor, Mar´ echal de Tassigny 51 Av., 94010 Creteil Cedex, France
b
Received 23 June 2004; received in revised form 14 October 2004; accepted 25 October 2004
Abstract A case of primary leptomeningeal malignant melanoma localized in the cervical region in a 41-year-old woman is presented. The only clinical finding was intracranial hypertension with papilledema. A diagnosis of primary CNS melanoma was made after dermatological and ophthalmological consultations, ruled out a metastatic lesion. Primary leptomeningeal melanoma is an extremely rare spinal tumor. Its clinical presentation with signs of increased intracranial pressure but without cord symptoms is unusual. Clinical features of this case including the radiological and histologic findings are described. Diagnosis as well as management is discussed. © 2004 Elsevier B.V. All rights reserved. Keywords: Melanoma; Spinal; Tumor; Papilledema; Neurosurgery; Intracranial pressure
1. Introduction
2. Case report
Central nervous system primary malignant melanoma accounts for approximately 1% of all cases of melanoma. Localization in the spine is unusual and reports in the literature are relatively rare. Since the initial report in 1906, only 34 cases have been reported [1]. Intramedullary [2], leptomeningeal and dural origin [3] of primary malignant melanoma were demonstrated. A case of primary spinal leptomeningeal melanoma diagnosed by magnetic resonance imaging (MRI) and surgery and confirmed by the pathological examination as well as by dermatological opinion was analyzed. To the best of our knowledge no case of primary cervical extramedullary subdural melanoma presenting clinically with signs of elevated intracranial pressure and without cord symptoms has ever been published.
A 41-year-old female patient was admitted to our department with headache, intermittent nausea and vomiting. The symptoms had appeared 9 months prior to admission and progressively worsened since then. A brain computed tomographic (CT) scan without abnormalities was obtained 4 months prior to admission. On admission, the neurological examination revealed no deficits. Ophthalmoscopy showed bilateral papilledema with normal visual acuity. Goldmann visual field testing showed no field defects. Examination of the cerebrospinal fluid (CSF) revealed an elevated level of protein and red blood cells (RBCs): a total protein level of 0.74 g/l (normal values = 0.20–0.45 g/l), Cl = 122 mmol/l (mean normal value = 125 mmol/l), glucose = 3.1 mmol/l (normal value = 2.2–4.7 mmol/l), red blood cells = 431 mm−3 , white blood cells (WBCs) = 3 m−3 (lymphocytes = 80%). Malignant melanoma cells were not encountered. Under the basis of the commonly used three-tube method, we considered that the elevated level of RBCs in CSF was caused by a traumatic LP.
∗
Corresponding author. Tel.: +33 1 49 81 23 03; fax: +33 1 49 81 23 26. E-mail address: traykov [email protected] (L.D. Traykov).
0303-8467/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2004.10.013
526
G.K. Kounin et al. / Clinical Neurology and Neurosurgery 107 (2005) 525–527
Cranial and cervical MRI was done in one stage in this patient with progressive signs of unexplained intracranial hypertension and normal CT images. As a rule, patient with unexplained papilledema and/or communicating hydrocephalus as well as increased CSF protein should be examined for spinal tumor. MR venography was not done because we are not discussing venous thrombosis as a reason for papilledema. Cranial MRI does not show any abnormalities. Spinal MRI (Fig. 1) showed an intradural–extramedullary lesion at the C2–C4 levels. The tumor was located laterally displacing the spinal cord to the right. There was a broad base on the dura. No meningeal enhancement was seen following a gadolinium-based contrast agent injection. The mass appeared hyperintense on T1-weighted MR images and hypointense on T2-weighted images. Mild cord swelling adjacent to the tumor was also noted. There was moderate hydrocephalus without periventricular edema. The rapid evolution of ophthalmological findings–peripapillar hemorrhages, exudates and elevation of the optic disc required immediate surgery. During surgery, a soft, deep-black colored tumor, with a rich blood supply, which was causing lateral displacement of the cord, was found. The opening pressure was 12 cmH2 O (120 mmH2 O). The tumor had a plane of cleavage from adjacent medulla but there were some areas of tight adherence to the madre pia that required meticulous dissection in order to prevent damage of the lateral column of the cord. Inspection under highest magnification disclosed some places of pial invasion and minimal subpial penetration and infiltration. The tumor was totally excised. The tumor size was of 30–35 mm, there was no vascular invasion. No post-operative neurological deficit was detected. Frozen section revealed melanoma. Post-operative
Fig. 2. Post-operative sagittal MRI scan of the spine revealed a total tumor excision.
MRI (Fig. 2) confirmed the completeness of tumor removal. In the post-operative period, papilledema persisted a week after the intervention, whereas the headache rapidly improved. The operative specimen was stained with haematoxylin and eosin (HES). Microscopic examination showed features of a malignant pigmented tumor. It demonstrated a highly cellular lesion, which was composed of large epitheloid or fusiform cells growing in loose nests or sheets. The cytoplasm was weakly eosinophilic. The nuclei had irregular contours with clearly defined nucleoli. Nuclear pleomorphism and mitoses were seen (mean = 6.2 per 10 HPFs). Nuclear anaplasia has a tendency to form clusters of cells resembling the structure of a nevus. A dense deposit of intracellular melanin was present. Positive immunohistochemical reactions for S100 protein and HMB45 were the strong arguments in favor of its melanocytic origin. After surgery, the patient underwent complete dermatological and ophthalmological assessment, which did not reveal any other foci of melanoma. Thus the diagnosis of primary spinal malignant melanoma was considered established. Early post-operative assessment, 3 months following surgery, showed disappearance of symptoms of elevated intracranial pressure and absence of papilledema and hydrocephalus.
3. Discussion
Fig. 1. Pre-operative sagittal T1-weighted MR image shows the spinal tumor at the C2–C4 levels, which has a high signal intensity relative to that of the cord.
Primary spinal melanomas arise from melanoblasts derived from the neural crest during early embryonic development and normally occurring in leptomeninges. The diagnosis of primary central nervous system melanoma was made according to criteria used by Hayward [4], an absence of melanoma outside of the CNS, an absence of this lesion in another area of the CNS and histological confirmation of melanoma. Pathological examination and immunohistochemistry as well as electron microscopy of the primary spinal melanoma are critical to diagnose and distinguish it from other pigmented tumors–spinal meningeal melanocytoma, pigmented meningioma or schwannoma. The differen-
G.K. Kounin et al. / Clinical Neurology and Neurosurgery 107 (2005) 525–527
tial diagnosis with well-differentiated spinal melanocytoma is important. In our case, the characteristic cytologic features of malignant melanoma were large, atypical tumor cells with irregular nuclei some bizarre and pleomorphic, high mitotic rate, necroses, infiltrative growth. In all published cases, the clinical presentation is nonspecific and consists predominantly of symptoms of progressive myelopathy. In the present case, the only findings were those of elevated intracranial pressure. A close relationship between papilledema, the high level of protein in the CSF and spinal tumors is well known [5]. However, increased intracranial pressure is very rare in spinal tumors locating in the thoracolumbar region and only occasionally observed in the cervical region. Spinal cord tumors can cause elevated intracranial pressure without causing any myelopathic manifestations, perhaps by obstructing cerebrospinal drainage [6]. In our case, the mechanical obstruction of CSF circulation along with increased level of CSF protein is assumed to be mainly responsible for symptoms. In conclusion, when a patient is discovered to have communicating hydrocephalus and/or papilledema and the finding of increased CSF protein then the possibility of a spinal tumor should be considered. This case, like those described by Zhang et al. [7] emphasizes that comprehensive spine imaging should be a part of the evaluation of a patient with papilledema who has normal brain imaging but abnormal spinal fluid constituents. MRI is the method of choice in the diagnosis of spinal tumors. This technique may be used to demonstrate the appearance of spinal malignant melanoma. According to most authors [2,8,9], the MR imaging pattern of spinal melanoma includes signal hyperintensity on T1-weighted images and signal iso- or hypointensity on T2-weighted images. The MRI signal of melanocytic tumors depends on the presence of melanin as well as acute or chronic intratumoral hemorrhages and fat deposits [1,8]. Our MRI findings are similar to the available descriptions. It has been suggested that primary spinal melanoma exhibits slow progression and the tumor is less aggressive than the more common melanoma of the skin with metastases to
527
the CNS [1,10]. Metastatic melanomas grow rapidly and usually lead to fatal outcome within 6 months. Although primary CNS melanomas are potentially malignant and prone to local recurrence or systemic spread, Larson et al. [10] concluded that the average survival after surgery and radiotherapy was 6 years and 7 months. Most authors agree that complete surgical excision whenever possible is the best treatment. The role and efficacy of radiotherapy [8] and chemotherapy [3] remain controversial. In our case, the patient did not receive any radiotherapy because surgical excision was apparently total but regular clinical and MRI follow up evaluation was advised. References [1] Magni C, Yapo P, Mocaer J, Ranjard L, Sonier CB, Cottier JP, et al. Primary intramedullary melanoma. J Neuroradiol 1996;23: 41–5. [2] Farrokh D, Fransen P, Faverly D. MR findings of a primary intramedullary malignant melanoma: case report and literature review. AJNR 2001;22:1864–6. [3] Narayan RK, Rosner MJ, Povlishock JT, Girevendulis A, Becker DP. Primary dural melanoma: a clinical and morphological study. Neurosurgery 1981;9:710–7. [4] Hayward RD. Malignant melanoma and the central nervous system. A guide for classification based on the clinical findings. J Neurol Neurosurg Psychiatry 1976;39:526–30. [5] Ridsdale L, Mosely I. Thoracolumbar intraspinal tumors presenting features of raised intracranial pressure. J Neurol Neurosurg Psychiatry 1978;41:737–45. [6] Costello F, Kardon RH, Wall M, Kirby P, Ryken T, Lee AG. Papilledema as the presenting manifestation of spinal schwannoma. J Neuroophthalmol 2002;22:199–203. [7] Zhang Y, Lao Y, Guo Y, Guo H. Bilateral papilloedema associated with lumbo-sacral intraspinal tumor. Chin Med J 2000;113: 201–5. [8] Francois P, Lioret E, Jan M. Primary spinal melanoma: case report. Br J Neurosurg 1998;12:179–82. [9] Yamasaki T, Kikuchi H, Yamashita J, Asato R, Fujita M. Primary spinal intramedullary malignant melanoma: case report. Neurosurgery 1989;25:117–21. [10] Larson T, Houser OW, Onofrio B, Piepgras D. Primary spinal melanoma. J Neurosurg 1987;66:47–9.
Case report
Primary spinal melanoma with bilateral papilledema Gueorgui K. Kounina , Kiril V. Romanskya , Latchezar D. Traykovb,c,∗ , Penko M. Shotekovb , Detelina Z. Stoilovab a
Department of Neurosurgery, University Hospital Alexandrovska, Georgi Sofijski 1 Str., 1431 Sofia, Bulgaria Department of Neurology, University Hospital Alexandrovska, Georgi Sofijski 1 Str., 1431 Sofia, Bulgaria c Department of Neurology, University Hospital Henri Mondor, Mar´ echal de Tassigny 51 Av., 94010 Creteil Cedex, France
b
Received 23 June 2004; received in revised form 14 October 2004; accepted 25 October 2004
Abstract A case of primary leptomeningeal malignant melanoma localized in the cervical region in a 41-year-old woman is presented. The only clinical finding was intracranial hypertension with papilledema. A diagnosis of primary CNS melanoma was made after dermatological and ophthalmological consultations, ruled out a metastatic lesion. Primary leptomeningeal melanoma is an extremely rare spinal tumor. Its clinical presentation with signs of increased intracranial pressure but without cord symptoms is unusual. Clinical features of this case including the radiological and histologic findings are described. Diagnosis as well as management is discussed. © 2004 Elsevier B.V. All rights reserved. Keywords: Melanoma; Spinal; Tumor; Papilledema; Neurosurgery; Intracranial pressure
1. Introduction
2. Case report
Central nervous system primary malignant melanoma accounts for approximately 1% of all cases of melanoma. Localization in the spine is unusual and reports in the literature are relatively rare. Since the initial report in 1906, only 34 cases have been reported [1]. Intramedullary [2], leptomeningeal and dural origin [3] of primary malignant melanoma were demonstrated. A case of primary spinal leptomeningeal melanoma diagnosed by magnetic resonance imaging (MRI) and surgery and confirmed by the pathological examination as well as by dermatological opinion was analyzed. To the best of our knowledge no case of primary cervical extramedullary subdural melanoma presenting clinically with signs of elevated intracranial pressure and without cord symptoms has ever been published.
A 41-year-old female patient was admitted to our department with headache, intermittent nausea and vomiting. The symptoms had appeared 9 months prior to admission and progressively worsened since then. A brain computed tomographic (CT) scan without abnormalities was obtained 4 months prior to admission. On admission, the neurological examination revealed no deficits. Ophthalmoscopy showed bilateral papilledema with normal visual acuity. Goldmann visual field testing showed no field defects. Examination of the cerebrospinal fluid (CSF) revealed an elevated level of protein and red blood cells (RBCs): a total protein level of 0.74 g/l (normal values = 0.20–0.45 g/l), Cl = 122 mmol/l (mean normal value = 125 mmol/l), glucose = 3.1 mmol/l (normal value = 2.2–4.7 mmol/l), red blood cells = 431 mm−3 , white blood cells (WBCs) = 3 m−3 (lymphocytes = 80%). Malignant melanoma cells were not encountered. Under the basis of the commonly used three-tube method, we considered that the elevated level of RBCs in CSF was caused by a traumatic LP.
∗
Corresponding author. Tel.: +33 1 49 81 23 03; fax: +33 1 49 81 23 26. E-mail address: traykov [email protected] (L.D. Traykov).
0303-8467/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2004.10.013
526
G.K. Kounin et al. / Clinical Neurology and Neurosurgery 107 (2005) 525–527
Cranial and cervical MRI was done in one stage in this patient with progressive signs of unexplained intracranial hypertension and normal CT images. As a rule, patient with unexplained papilledema and/or communicating hydrocephalus as well as increased CSF protein should be examined for spinal tumor. MR venography was not done because we are not discussing venous thrombosis as a reason for papilledema. Cranial MRI does not show any abnormalities. Spinal MRI (Fig. 1) showed an intradural–extramedullary lesion at the C2–C4 levels. The tumor was located laterally displacing the spinal cord to the right. There was a broad base on the dura. No meningeal enhancement was seen following a gadolinium-based contrast agent injection. The mass appeared hyperintense on T1-weighted MR images and hypointense on T2-weighted images. Mild cord swelling adjacent to the tumor was also noted. There was moderate hydrocephalus without periventricular edema. The rapid evolution of ophthalmological findings–peripapillar hemorrhages, exudates and elevation of the optic disc required immediate surgery. During surgery, a soft, deep-black colored tumor, with a rich blood supply, which was causing lateral displacement of the cord, was found. The opening pressure was 12 cmH2 O (120 mmH2 O). The tumor had a plane of cleavage from adjacent medulla but there were some areas of tight adherence to the madre pia that required meticulous dissection in order to prevent damage of the lateral column of the cord. Inspection under highest magnification disclosed some places of pial invasion and minimal subpial penetration and infiltration. The tumor was totally excised. The tumor size was of 30–35 mm, there was no vascular invasion. No post-operative neurological deficit was detected. Frozen section revealed melanoma. Post-operative
Fig. 2. Post-operative sagittal MRI scan of the spine revealed a total tumor excision.
MRI (Fig. 2) confirmed the completeness of tumor removal. In the post-operative period, papilledema persisted a week after the intervention, whereas the headache rapidly improved. The operative specimen was stained with haematoxylin and eosin (HES). Microscopic examination showed features of a malignant pigmented tumor. It demonstrated a highly cellular lesion, which was composed of large epitheloid or fusiform cells growing in loose nests or sheets. The cytoplasm was weakly eosinophilic. The nuclei had irregular contours with clearly defined nucleoli. Nuclear pleomorphism and mitoses were seen (mean = 6.2 per 10 HPFs). Nuclear anaplasia has a tendency to form clusters of cells resembling the structure of a nevus. A dense deposit of intracellular melanin was present. Positive immunohistochemical reactions for S100 protein and HMB45 were the strong arguments in favor of its melanocytic origin. After surgery, the patient underwent complete dermatological and ophthalmological assessment, which did not reveal any other foci of melanoma. Thus the diagnosis of primary spinal malignant melanoma was considered established. Early post-operative assessment, 3 months following surgery, showed disappearance of symptoms of elevated intracranial pressure and absence of papilledema and hydrocephalus.
3. Discussion
Fig. 1. Pre-operative sagittal T1-weighted MR image shows the spinal tumor at the C2–C4 levels, which has a high signal intensity relative to that of the cord.
Primary spinal melanomas arise from melanoblasts derived from the neural crest during early embryonic development and normally occurring in leptomeninges. The diagnosis of primary central nervous system melanoma was made according to criteria used by Hayward [4], an absence of melanoma outside of the CNS, an absence of this lesion in another area of the CNS and histological confirmation of melanoma. Pathological examination and immunohistochemistry as well as electron microscopy of the primary spinal melanoma are critical to diagnose and distinguish it from other pigmented tumors–spinal meningeal melanocytoma, pigmented meningioma or schwannoma. The differen-
G.K. Kounin et al. / Clinical Neurology and Neurosurgery 107 (2005) 525–527
tial diagnosis with well-differentiated spinal melanocytoma is important. In our case, the characteristic cytologic features of malignant melanoma were large, atypical tumor cells with irregular nuclei some bizarre and pleomorphic, high mitotic rate, necroses, infiltrative growth. In all published cases, the clinical presentation is nonspecific and consists predominantly of symptoms of progressive myelopathy. In the present case, the only findings were those of elevated intracranial pressure. A close relationship between papilledema, the high level of protein in the CSF and spinal tumors is well known [5]. However, increased intracranial pressure is very rare in spinal tumors locating in the thoracolumbar region and only occasionally observed in the cervical region. Spinal cord tumors can cause elevated intracranial pressure without causing any myelopathic manifestations, perhaps by obstructing cerebrospinal drainage [6]. In our case, the mechanical obstruction of CSF circulation along with increased level of CSF protein is assumed to be mainly responsible for symptoms. In conclusion, when a patient is discovered to have communicating hydrocephalus and/or papilledema and the finding of increased CSF protein then the possibility of a spinal tumor should be considered. This case, like those described by Zhang et al. [7] emphasizes that comprehensive spine imaging should be a part of the evaluation of a patient with papilledema who has normal brain imaging but abnormal spinal fluid constituents. MRI is the method of choice in the diagnosis of spinal tumors. This technique may be used to demonstrate the appearance of spinal malignant melanoma. According to most authors [2,8,9], the MR imaging pattern of spinal melanoma includes signal hyperintensity on T1-weighted images and signal iso- or hypointensity on T2-weighted images. The MRI signal of melanocytic tumors depends on the presence of melanin as well as acute or chronic intratumoral hemorrhages and fat deposits [1,8]. Our MRI findings are similar to the available descriptions. It has been suggested that primary spinal melanoma exhibits slow progression and the tumor is less aggressive than the more common melanoma of the skin with metastases to
527
the CNS [1,10]. Metastatic melanomas grow rapidly and usually lead to fatal outcome within 6 months. Although primary CNS melanomas are potentially malignant and prone to local recurrence or systemic spread, Larson et al. [10] concluded that the average survival after surgery and radiotherapy was 6 years and 7 months. Most authors agree that complete surgical excision whenever possible is the best treatment. The role and efficacy of radiotherapy [8] and chemotherapy [3] remain controversial. In our case, the patient did not receive any radiotherapy because surgical excision was apparently total but regular clinical and MRI follow up evaluation was advised. References [1] Magni C, Yapo P, Mocaer J, Ranjard L, Sonier CB, Cottier JP, et al. Primary intramedullary melanoma. J Neuroradiol 1996;23: 41–5. [2] Farrokh D, Fransen P, Faverly D. MR findings of a primary intramedullary malignant melanoma: case report and literature review. AJNR 2001;22:1864–6. [3] Narayan RK, Rosner MJ, Povlishock JT, Girevendulis A, Becker DP. Primary dural melanoma: a clinical and morphological study. Neurosurgery 1981;9:710–7. [4] Hayward RD. Malignant melanoma and the central nervous system. A guide for classification based on the clinical findings. J Neurol Neurosurg Psychiatry 1976;39:526–30. [5] Ridsdale L, Mosely I. Thoracolumbar intraspinal tumors presenting features of raised intracranial pressure. J Neurol Neurosurg Psychiatry 1978;41:737–45. [6] Costello F, Kardon RH, Wall M, Kirby P, Ryken T, Lee AG. Papilledema as the presenting manifestation of spinal schwannoma. J Neuroophthalmol 2002;22:199–203. [7] Zhang Y, Lao Y, Guo Y, Guo H. Bilateral papilloedema associated with lumbo-sacral intraspinal tumor. Chin Med J 2000;113: 201–5. [8] Francois P, Lioret E, Jan M. Primary spinal melanoma: case report. Br J Neurosurg 1998;12:179–82. [9] Yamasaki T, Kikuchi H, Yamashita J, Asato R, Fujita M. Primary spinal intramedullary malignant melanoma: case report. Neurosurgery 1989;25:117–21. [10] Larson T, Houser OW, Onofrio B, Piepgras D. Primary spinal melanoma. J Neurosurg 1987;66:47–9.