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PRIMARY CNS MELANOMA IN AN ALBINO: A RARE CASE REPORT

Primary intracranial melanoma is a rare and uncommon lesion. Association of primary CNS melanoma in an albino has not been reported in literature searched till now. We are presenting a rare case of primary CNS melanoma in a 52years old male with occulocutaneous albinism. The patient presented with repeated episodes of generalized headache, vomiting and ataxia for duration of 5months. MRI examination showed a tumor in the posterior fossa that was diagnosed as Ependymoma radiologically. Surgical treatment with total removal of tumor was done. Intraoperative squash cytology and frozen section followed by histopathology confirmed the diagnosis of Melanoma. A thorough investigation of the patient was performed including chest radiography, ocular examination, ultrasonography of abdomen and barium enema to rule out any other site of primary melanoma in the body. Thus a final diagnosis of primary CNS melanoma was given.

INTRODUCTION: Primary melanocytic tumours of CNS are rare and comprise 1% of all the tumours. [1] An estimated incidence of 0.9 per 10 million of these tumours has been reported from the literature. [2] Their spectrum varies from benign to malignant and includes leptomeningeal melanocytosis, melanocytoma to its overtly malignant counterpart melanoma. [1] The diagnosis of intracranial melanomas is often complicated and a differential diagnosis of other pigmented lesions like pigmented Meningioma, Schwannoma, Medulloblastoma, Choroid plexus papilloma, Astrocytoma and pituitary tumours should be considered. A diagnosis of primary CNS melanoma should be made after extensive exclusion of cutaneous or mucosal / retinal melanomas by clinical and radiological examination. [3] Herein, we present a rare case of Primary CNS melanoma in an albino patient who presented to Neurosurgery OPD with generalized headache.

CASE REPORT:
A 52years old albino male patient presented to Neurosurgery department with repeated episodes of generalized headaches, vomiting and ataxia for duration of 3-4 months. MRI of the patient was performed and a mass lesion with T2 hypointense hemosiderin rim involving the cerebellum off midline that involved mainly left cerebellar hemisphere and vermis was detected. The mass measured 5.0x4.4x4.5cms. approximately on radiological examination. Based on these findings a diagnosis of Ependymoma was given on radiology. (Fig. 1a) Intraoperative squash cytology and frozen section were performed. The intraoperative smears were highly cellular, composed of discohesive sheets of spindle to medium sized epithelioid like cells. These cells had prominent macronucleoli, intranuclear inclusions of cytoplasm and dense abundant eosinophillic cytoplasm. (Fig. 1b The tumour was resected in Toto and sent for histopathological examination. Grossly, excised tissue was a firm mass, dark brown to black in color measuring 5.5x5x4cms. (Fig. 2a) Microscopy revealed cellular malignant neoplasm showing sheets and loose nests of epithelioid like cells, ill defined fascicles of anaplastic spindle-shaped cells. These cells exhibited a moderate grade of cellular and nuclear pleomorphism, prominent macronucleoli and mitoses (>4/10 HPF). The cytoplasm showed abundant melanin pigment in the cytoplasm, which stained black with Masson Fontana. (Fig.  2b & c) Furthermore, Immunohistochemistry was performed employing S-100 and HMB-45 which exhibited strong and diffuse positive reaction. (Fig. 2d & e) Thus, a confirmed diagnosis of Malignant Melanoma was made. Extensive search of primary comprising dermatological evaluation, ophthalmologic evaluation, X-ray chest and USG abdomen showed no primary lesion elsewhere. Based on these findings a confirmed diagnosis of Primary CNS Melanoma was given.

DISCUSSION:
Albinism is an inborn error of metabolism that is genetically inherited and has an autosomal recessive (A-R) inheritance. It is due to deficiency of enzyme tyrosinase which is responsible for the hydroxylation of L-tyrosine to 3, 4, dihydroxyphenylalanine (DOPA) and its subsequent oxidation to dopaquinone. Subsequent polymerization of dopaquinone derivatives and its reaction with a specialized protein results in formation of melanoprotein in melanocytes. [4] Albinos although have melanocytes but they do not contain melanin. Melanin acts as a sunscreen protecting the skin from the damaging effects of ultraviolet radiations hence warrants protection against various skin cancers such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM). There have been sporadic occurrences of MM at different sites in albinos in literature such as metastatic malignant melanoma of the nasal cavity, choroidal malignant melanoma and primary malignant melanoma in lungs. [5,6] However, occurrence of Primary CNS melanoma in an albino patient has not yet been reported in literature searched.
Virchow first described the case of primary CNS melanoma in 1859, and labeled it diffuse Melanosarcoma. [7] Primary intracranial melanomas are exceptionally rare. Most of the cases of CNS melanin bearing tumours are metastatic melanomas constituting 3-16% of secondary neoplastic foci in CNS, melanotic neurocutaneous syndromes and primary leptomeningeal melanoma. [8,9] Primary melanocytic neoplasms arise from normally occurring leptomeningeal melanocytes which are derived from the neural crest during early embryonic development. [10] Normal rests of pigmented cells within the CNS include the medulla, pons, substantia nigra, locus cerulus and the leptomeninges over the convexities, basal region and upper cervical spinal cord. [1,11] They may arise either de novo or in a pre-existing neurocutaneous melanosis.
These neoplasms are divided into three main types including diffuse melanocytosis, melanocytoma and malignant melanoma. [1] From the histopathological point of view the principle differential is between melanocytoma and malignant melanoma. [1,12] Meningeal melanocytomas are histologically characterized as cellular lesions. They have variable amount of melanin pigment in the cytoplasm as intracellular granules. These lesions typically should not have nuclear pleomorphism, atypia or macronucleoli, necrosis and have very occasional mitotic figures (0-1/10 HPF). They usually have low MIB 1 staining (1-2%).
On the contrary, melanomas are more pleomorphic, have anaplastic nuclei with prominent macronucleoli. Mitosis is extensive (about 5-7/10 HPF) and MIB-1 labeling index (about 8.1%). A third subset of meningeal melanocytic tumours falls in the intermediate grade because they demonstrate intermediate histologic features. They have sheet like growth patterns, microscopic CNS invasion and occasional mitoses.MIB-1 staining ranges from 1%-4%. On Immunohistochemistry, all the three types are immunoreactive for HMB-45 and S-100protien and negative for EMA. [12] For the diagnosis of primary CNS melanoma, Hayward criteria should be fulfilled that includes absence of melanoma outside the CNS, absence of melanoma in other sites in CNS and histologic confirmation of melanoma. [13] Studies suggest that primary CNS melanomas grow slow and are less malignant than skin melanomas metastatic to CNS. [14] Other primary tumours of CNS with melanotic elements originate from non-melanoma cells of CNS. They acquire melanin and these lesions include Meningioma, Medulloblastoma, Astrocytoma, Melanotic Schwannoma, Pitutary tumours and Choroid plexus Papilloma. [14,15] In conclusion, primary CNS melanoma is rare and its occurrence in an albino is still rarer that has not yet been reported.