The term melanocytoma was coined by Limas and Tio. Primary central nervous system (CNS) melanocytomas are rare, benign tumors of the leptomeningeal melanocytes. They comprise 1% of all melanomas. Their incidence is 1 in 20 million individuals. They are more commonly seen in the fifth decade and predominantly in females. Approximately two-thirds of melanocytomas are located intracranially and rest in the spinal cord. Their location in the spinal cord is usually intradural and extramedullary. According to the World Health Organization (WHO), they are primarily classified under the subgroup of primary melanocytic lesions. They are generally solitary and low-grade neoplasms. However, intermediate grade and high-grade melanocytomas are also described in the literature. High-grade melanocytomas have a higher prevalence of thromboembolic complications.
A 39-year-old male patient presented with complaints of holocranial headache and vomiting for 2 months. He developed acute onset of gait imbalance and left upper limb sensory symptoms of tingling and numbness for a week. He was fully conscious. His higher mental functions were normal. Motor examination revealed a normal tone without any power deficit. Tendon reflexes were preserved. However, the Tandem walking and Romberg test were positive. Magnetic resonance imaging (MRI) of the brain revealed about 2.9 cm × 2.6 cm × 2.3 cm sized extra-axial, well-defined, contrast-enhancing lesion [Figures 1c and 2b] at the foramen magnum posterior to the medulla with its broad base toward dura. The lesion appeared heterogeneously hyperintense on T1-weighted images [Figure 1a] and hypo to isointense on T2-weighted images [Figures 1b and 2a]. With a working diagnosis of meningioma, surgical intervention was planned. With the patient in a prone position under general anesthesia, a midline suboccipital craniectomy and C1 laminectomy was done. A dark tarry-colored lesion was encountered, adherent to the posterior fossa dura. There was no component of the tumor adherent to the medulla. After ensuring complete excision of the lesion, the dural was closed primarily.
Histopathological examination revealed a variably pigmented spindled and epithelioid neoplasm with prominent nucleoli, mitotic activity, and scattered melanophages, typical melanoma [Figure 3]. A thorough clinical and radiological search for the primary site was attempted, which was unremarkable. Hence, the final diagnosis was a primary melanocytic melanoma.
The initial postoperative course was uneventful. Postoperative computed tomography (CT) scan revealed complete excision of the lesion [Figure 4a and b]. However, the patient developed left subclavian vein thrombosis on the 7th postoperative day for which anti-thrombotic medication was started. However, on the 14th day of surgery, he succumbed to his illness due to pulmonary embolism.
Primary melanocytomas were initially referred to as melanotic schwannoma, melanotic meningioma, and melanoblastic meningioma when Limas and Tao introduced this term in 1972.[1,4] It is a slow-growing tumor, predominantly encountered in females. There is three histogenic hypothesis for primary cerebral melanomas– mesodermal theory, ectodermal theory, and neurogenic theory. The mesodermal theory states that mesoderm gives rise to pigment cells that migrate to the brain or the spinal cord via the pial vessels. The ectodermal theory states that some epithelial cells produce pigment. Therefore, they derived from the misplaced embryonic ectodermal cells. In contrast, the neurogenic theory states that they are derived from scattered melanocytes which are derived from the neural crest during early embryonic development. They are most frequently encountered in the recesses of the sulci at the base of the brain, brain stem, and upper part of the cervical spinal cord. The melanocytomas found intra-parenchymal in the brain or intramedullary in the spinal cord are thought to originate from the Virchow-Robin spaces.[4,8] As of now, no genetic variations leading to this condition are known.
The WHO classifies melanocytic tumors into diffuse and circumscribed verities. Diffuse meningeal melanocytic tumors include meningeal melanocytosis and meningeal melanomatosis, whereas circumscribed meningeal melanocytic tumors include meningeal melanocytoma and meningeal melanoma. These lesions are usually benign and low-grade with inconspicuous mitotic activity (<1 Mitosis/10 High Power Field (HPF), Mind Bomb 1 (MIB 1) <1%–2%). However, some of these lesions show increased mitotic activity and features of invasions. Such lesions are often labeled as having intermediate grades. Malignant melanomas are malignant, infiltrating neoplasms with cytological atypia, brisk mitotic activity, and necrosis. However, the appropriate descriptions and nosology along these lines are not very transparent because of the rarity of these cases.
The presentation of the patients usually varies with the location of the lesion. Patients with a lesion in the cerebellopontine Angle cistern or the posterior fossa present with single or multiple cranial nerve involvement and cerebellar features like axial or appendicular ataxia and central vertigo. Patients with intra-cranial melanomas typically present with headaches, seizures, hemiparesis, or ocular symptoms. Spinal cord melanomas present with varying power deficits with or without bowel bladder involvement. Melanoma has typical MRI findings. They are dense, extra-axial lesions in the posterior fossa or upper cervical spinal cord, typically hyperintense on T1-weighted images, typical shortening of T1 and T2 due to the presence of melanin, hypointense on T2-weighted images, hyperintense on Fluid attenuated inversion recovery images, and enhances homogenously postgadolinium contrast administration. They show dural attachment. The location in the spinal cord is usually intradural extramedullary. Intramedullary melanomas lack characteristic imaging features.[13,14] The most common differentials are schwannoma, medulloblastoma, neurofibroma, meningioma, and astrocytoma. Apart from imaging, a thorough clinical examination is warranted to rule out any cutaneous or mucosal melanomas as much intracranial mass lesion may be the sequelae of metastatic melanoma.
The mainstay of treatment for CNS melanocytoma is gross total surgical excision or maximum possible safe resection followed by postoperative radiotherapy and chemotherapy. A complete resection carries a better prognosis as higher relapse rates are seen after incomplete resection. Primary high-dose radiotherapy is effective in long-term control of the neoplasm in patients where no resection or incomplete resection is done. This fact is reiterated in the study by Rades etal. where patients who received radiotherapy despite complete or incomplete excision had a survival rate of 100% at 5 years. In contrast, it was only 46% without radiotherapy. Chemotherapeutic agents like dacarbazine are also being increasingly used for their management. Specific immunotherapies like high doses of interferon (IFN) β or IFN α-2b are being evaluated to prevent local recurrence.
Postoperatively, full-body positron emission tomography CT is warranted to rule out any primary. The tumor tissue should be subjected to detailed histopathological examination and immunohistochemistry (IHC) assessment. Spindle-shaped cells with oval nuclei, small nucleoli, and varying amounts of melanin are usually found. The number of mitotic activity and MIB index should be obtained. To firmly establish melanocytic differentiation and to distinguish from other standard spindle-shaped cells, immunohistochemical analysis is a must. IHC markers S100, Human Melanoma Black (HMB)-45, and Melan-A are specific for Melanocytes. In comparison to metastatic disease, the clinical outcome of primary CNS melanoma is better due to the possibility of long-term tumor control. However, owing to their high rate of misdiagnosis, malignant melanomas present poor prognoses.
Furthermore, one of the rare complications of high-grade melanoma is the thromboembolic phenomenon. This inadvertent complication can be catastrophic for the patient. Although rare, with its incidence of <1%, it can lead to patients’ sudden death, which warrants one to be cautious. The probable mechanism includes increased production of procoagulants like tissue factor and cancer procoagulant, increased fibrinolytic activity, endothelial damage by tumor cells, and monocyte macrophage-mediated overexpression tumor factor which in turn acts as a procoagulant. It is well known that leptomeningeal metastasis is often associated with immunogenic response resulting in rising in Ig M, IL-6, and other cytokines. Other factors include increased coagulability because of chemotherapeutic agents like dacarbazine. Hence, a high degree of suspicion on the slightest deterioration of the general condition and prompt action is required when such a complication is encountered. Adequate radiological imaging and commencement of anti-coagulants and an attempt to prevent pulmonary embolism should be made.
Malignant melanoma can present with brain metastasis without any evidence of primary. Poor prognosis is often associated with the disease due to the hypercoagulable status caused by the tumor. It should be considered in the differential diagnosis of extra-axial posterior fossa mass lesion. The surgical procedure remains the mainstay of the treatment, not only diagnostic but therapeutics also. Gross total or maximum possible safe resection, followed by adjuvant radiotherapy and chemotherapy, forms the cornerstone of their management.
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