Primary CNS melanoma in an albino: a rare case report.
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) Intracytoplasmic melanin could be identified easily. On Frozen section, sheets of malignant cells with eccentrically placed nuclei and punched out prominent nucleoli were seen. These cells displayed abundant eosinophillic cytoplasm and presence of fine to coarsely abundant brownish black pigment which bleached with potassium permanganate. (Fig. 1c & d) Many mitotic figures were noted. Thus, an intraoperative diagnosis of malignant melanoma of CNS was made.
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. 2 a) 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.  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.  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.  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.  From the histopathological point of view the principle differential is between melanocytoma and malignant melanoma^ 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. 
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.  Studies suggest that primary CNS melanomas grow slow and are less malignant than skin melanomas metastatic to CNS.  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.
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[2.] Schuster LM, Haliska F, Fraker D, Elenitias R. Skin: Malignant Melanoma In: Abeloff MD (ed) Clinical Oncology. New York: Churchill Livingstone, 2000: 1326-32.
[3.] Baena RR, Gaeliani P, Danova H. Primary solitary intracranial melanoma: Case report and review of literature. Surg Neurol 1992; 38: 26-37.
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[8.] Biernat w. Metastatic tumours of the Central Nervous System- a pathological approach. Folia Neuropathol 2009; 47: 228-33.
[9.] Kiel FW, Starr LB, Hansen JL. Primary melanoma of the spinal cord. J Neurosurg 1961; 18: 61629.
[10.] Aichner F, Schuler G. Primary leptomeningeal melanoma: diagnosis by ultrastructural cytology of cerebrospinal fluid and cranial computed tomography. Cancer 1982; 50: 1751-6.
[11.] Vanzieleghem BD, Lemmerling MM, Van Coster RN. Neurocutaneous melanosis presenting with intracranial amelanotic melanoma. AJNR AM J Neuroradiol 1999; 20: 457-60.
[12.] Brat DJ, Gianni C, Scheithauer BW et al.. Primary melanocytic neoplasms of the central nervous systems. Am J Surg Pathol 1999; 23: 745-54.
[13.] 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.
[14.] Jaiswal S, Agarwal V, Vij M, Sahu RN, Jaiswal AK, Behari S. Glioblastoma with melanocytic differentiation. Clin Neuropathol 2010; 29: 330-33.
[15.] Smith AB, Rushing EJ, Smirinio to populous JG. Pigmented lesions of the central nervous system: radiologic-pathologic correlation. Radiographies 2009; 29: 330-3.
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Kishore Sanjeev (1), Bhardwaj Aparna (2), Gupta Mohit (3), Seema Acharya (4), Kudesia Sandip (5)
(1.) Kishore Sanjeev
(2.) Bhardwaj Aparna
(3.) Gupta Mohit
(4.) Seema Acharya
(5.) Kudesia Sandip
PARTICULARS OF CONTRIBUTORS:
(1.) Professor, Department Pathology, SGRRIM & HS, Dehradun.
(2.) Associate Professor, Department of Pathology, SGRRIM & HS, Dehradun.
(3.) IIIrd Year Junior Resident, Department of Pathology, SGRRIM & HS, Dehradun.
(4.) Professor, Department of Pathology, SGRRIM & HS, Dehradun.
(5.) Professor & Head, Department of Pathology, SGRRIM & HS, Dehradun.
NAME ADDRESS EMAIL ID OF THE CORRESPONDING AUTHOR:
Dr. Aparna Bhardwaj, Department of Pathology, SGRRIM & HS, Dehradun, Uttrakhand, India.
Date of Submission: 12/06/2014.
Date of Peer Review: 13/06/2014.
Date of Acceptance: 27/06/2014.
Date of Publishing: 07/07/2014.
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|Title Annotation:||CASE REPORT|
|Author:||Sanjeev, Kishore; Aparna, Bhardwaj; Mohit, Gupta; Acharya, Seema; Sandip, Kudesia|
|Publication:||Journal of Evolution of Medical and Dental Sciences|
|Date:||Jul 7, 2014|
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