DOI: 10.33962/roneuro-2022-012 Primary intracranial malignant melanoma. A case report and review of literature Deepak Kumar Singh, Diwakar Shankar, Vipin Chand, Mohammad Kaif Romanian Neurosurgery (2022) XXXVI (1): pp. 70-72 DOI: 10.33962/roneuro-2022-012 www.journals.lapub.co.uk/index.php/roneurosurgery Primary intracranial malignant melanoma. A case report and review of literature Deepak Kumar Singh, Diwakar Shankar, Vipin Chand, Mohammad Kaif Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, INDIA ABSTRACT Primary Intracranial Malignant Melanoma (PIMM) is a very rare neoplasm and accounts for 1% of all melanomas and 0.1% of all intracranial tumours. It carries a poor prognosis with overall poor survival. Diagnosis on mere imaging findings of an intracranial melanoma is a daunting task. Multimodality treatment with surgery followed by chemotherapy and radiotherapy have proved to be effective in improving clinical outcome in these patients. INTRODUCTION Primary Intracranial Malignant Melanoma (PIMM) is a very rare neoplasm and accounts for 1% of all melanomas [5]. It accounts for 0.1% of all intracranial tumours [5]. PIMMs are derived from melanocytes that are normally present in the leptomeninges. It is more common in males and has a poor survival rate overall. Pathologically it is of two types, diffuse type which infiltrates pia-mater and the subarachnoid space (SAS); and the solitary type which is present as nodular mass. Treatment of choice is complete resection followed by radiotherapy and chemotherapy. We here present a case of PIMM in a 35-year-old male presenting with signs and symptoms of a left cerebellar hemisphere malignant melanoma with leptomeningeal spread. CASE DISCUSSION A 35-year-old male presented to our institute with a complaint of headache, decreased hearing in the left ear, difficulty in walking, and diminished vision bilaterally for the past 2 years. Non-contrast computer tomography (CT) head revealed a hyperdense lesion in the left cerebellar hemisphere with associated perilesional edema (Figure 1, A). Contrast-enhanced MRI brain revealed a 4.5cm x 5cm x 3.5cm homogenous mass lesion in the left cerebellar hemisphere which was hyperintense on T1 and hypointense on T2 with mass effect and perilesional edema (Figure 1, B, C, D). Radiographic features were suggestive of meningioma. No evidence of hemorrhage on the GRE sequence was seen. Keywords melanoma, primary intracranial malignant melanoma, PIMM, intracranial melanoma case report, intracranial melanoma literature review Corresponding author: Diwakar Shankar Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India dev123diwakar@gmail.com Copyright and usage. This is an Open Access article, distributed under the terms of the Creative Commons Attribution Non–Commercial No Derivatives License (https://creativecommons .org/licenses/by-nc-nd/4.0/) which permits non- commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of the Romanian Society of Neurosurgery must be obtained for commercial re-use or in order to create a derivative work. ISSN online 2344-4959 © Romanian Society of Neurosurgery First published March 2022 by London Academic Publishing www.lapub.co.uk http://www.lapub.co.uk/ 71 Primary intracranial malignant melanoma The patient was taken for surgery and complete excision was done through the left retro-mastoid suboccipital approach. Meningeal spread of the tumor was evident from the dark-colored dural after removal of the bone flap (Figure 2, A). Intraoperative observation revealed a firm, well-demarcated, highly vascular, dark brown, 5cm x 4cm sized lesion with dural attachment (Figure 2, B, C). Histopathological examination confirmed melanocytes on H and E stains. The tumor consisted of polygonal to spindle-shaped cells disposed of in sheets with abundant dark melanin pigment deposits in the cytoplasm. These cells stained positively with human melanin black-45 (HMB-45) antibody, S-100, and Melan A. It was reported as malignant melanoma. The patient was evaluated for the alternative site of melanoma but no such sites were found. The postoperative period was uneventful and the patient was discharged on the tenth postoperative day. Figure 1. Preoperative CT Non-contrast (CT) and Contrast- Enhanced MRI images. (A) CT images revealed a hyperdense lesion in the left cerebellar hemisphere with associated perilesional edema. (B) Axial view, contrast-enhanced T1WI MRI. (C) Sagittal view, contrast-enhanced T1WI MRI. (D) Coronal view, contrast-enhanced T1WI MRI. Contrast-enhanced MRI brain revealed a 4.5cm x 5cm x 3.5cm intra-axial heterogeneous mass lesion in the left cerebellar hemisphere which was hyperintense on T1 and hypointense on T2 with mass effect and perilesional edema. Figure 2. Intraoperative images showing gross total resection of the dark-colored lesion with leptomeningeal involvement and dural attachment. DISCUSSION Primary Intracranial Malignant Melanoma (PIMM) is a very rare neoplasm and accounts for 1% of all melanomas [5]. It accounts for 0.1% of all intracranial tumors [5]. PIMMs are derived from melanocytes that are normally present in the leptomeninges. It is more common in males and has a poor survival rate overall [4]. In humans, melanocytes are found in skin, mucous membrane, uvea, etc. There are many theories for the origin of primary intracranial melanomas. The endodermal theory states that some aberrant embryonic ectodermal cells in the central nervous system produce melanin pigment. The neurogenic theory states that the neural crest gives rise to pigment cells. Neural crest later develops into mesodermal and neural elements. The mesodermal theory proposes that the mesodermal pigment cells reach the central nervous system through pial vessels. Hayward proposed a few features of a primary intracranial melanoma[3]. He suggested that for a PIMM, there should be no malignant melanoma outside the CNS, evidence of leptomeningeal involvement, hydrocephalus, intramedullary spinal lesions, tumor located in the pituitary, or pineal region, and a single intracerebral lesion. Gibson et al divided intracranial melanomas into 72 Deepak Kumar Singh, Diwakar Shankar, Vipin Chand, Mohammad Kaif two pathological types [1]. The diffuse type which infiltrates pia-mater and the subarachnoid space (SAS); and the solitary (discrete) type which is present as nodular mass. The diffuse type was more prevalent in younger patients (mean age 26-years). It presented with clinical features of intracranial hypertension, cranial nerve deficit, or meningism. Solitary type is more common in adults (mean age 44-years). Most of the solitary tumors are supratentorial. Leptomeningeal involvement is frequently seen in solitary melanoma. Our patient has a solitary lesion. Symptoms included headache, vomiting (especially due to raised intracranial pressure), hydrocephalus (43%), focal neurological deficit (due to mass effect, 35%), and convulsion or subarachnoid hemorrhage (16%). Headache and focal neurological deficit were present in our case. Intracranial hypertension and hydrocephalus are more commonly seen in diffuse types. The presence of congenital melanocytic nevus increases the risk of malignant melanoma. 25% of patients with primary intracranial melanomas have congenital nevus. This was not the case with our patient. Extracranial metastasis of PIMM is rare. It is difficult to differentiate primary central nervous system (CNS) melanomas from metastatic melanomas based on imaging alone. Melanin cells in cerebrospinal fluid (CSF) analysis helps in the diagnosis. 86-97% melanocyte tumors are positive for HMB-45 Antigen. Other commonly used tumor markers are S100 and Melan A. All three were positive in our patient. Treatment of choice for the intraparenchymal melanocytic tumor is complete resection and postoperative chemoradiotherapy. Survival in adults can be up to 17 years and 8 months in pediatric patients[2]. Mean survival was found to be better (19.6 months) in patients in whom complete resection was done as compared with those where partial resection was done (9.3 months). Also, the prognosis of secondary melanoma was poorer than PIMM. There is 95% mortality in secondary intracranial melanomas. Initially, radiotherapy (RT) was not offered to patients of PIMM as melanomas were radioresistant tumors but recent studies showed that it was effective in controlling tumor growth. Stereotactic Radiosurgery (SRS) along with whole-brain radiotherapy (WBRT) has been shown to reduce recurrence and improve survival. A high dose of 5000 centigray as SRS in small lesions (size less than 3cm) gave better tumor control in almost 80% of cases. Hydrocephalus caused by the leptomeningeal spread of the disease has been shown to respond well to WBRT. Dacarbazine is commonly used in the treatment of PIMMs after surgery or radiotherapy. It has 16- 20% effectiveness. Other agents are temozolomide and Dimethyl-triazeno-imidazole-carboxamide which is common in use. Despite optimum treatment, median survival is less than a year. The leptomeningeal spread has a median survival of 10 weeks. CONCLUSION Primary Intracranial Malignant Melanoma (PIMM) is a very rare neoplasm and accounts for 1% of all melanomas and 0.1% of all intracranial tumors. It carries a poor prognosis with overall poor survival. Diagnosis on mere imaging findings of an intracranial melanoma is a daunting task. It is best diagnosed intraoperatively due to its characteristic appearance as well as during preoperative clinical examination. Postoperative chemoradiotherapy plays an important role in preventing recurrence as well as improving overall survival. Collaboration of large-scale data from many such small case series from centers all over the world can confirm findings suggested in this paper and formulate guidelines to improve clinical outcomes. REFERENCES 1. Gibson JB, Burrows D, Weir WP: Primary melanoma of the meninges. J Pathol Bacteriol 74:419–438, 1957. 2. Greco Crasto S, Soffietti R, Bradac GB, et al. Primitive cerebral melanoma: case report and review of the literature. Surg Neurol 2001;55:163–8. 3. 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. 4. Ma Y, Gui Q, Lang S. Intracranial malignant melanoma: a report of 7 cases. Oncol Lett 2015;10:2171–5. 5. Sloan AE, Nock CJ, Einstein DB. Diagnosis and treatment of melanoma brain metastasis: a literature review. Cancer Control. 2009;16:248e255.