Final Diagnosis -- Melanocytoma

FINAL DIAGNOSIS

Melanocytoma.

Molecular testing did not identify a BRAF codon 600 mutation or an NRAS codon 61 mutation.

DISCUSSION

Melanotic lesions of the central nervous system may be primary or metastatic. Primary melanotic neoplasms of the CNS arise from melanocytes of the cranial or spinal leptomeninges and can be solitary, diffuse, benign or malignant¹. This group includes diffuse melanocytosis and melanomatosis, melanocytoma, and primary malignant melanoma.

Diffuse melanocytosis and melanomatosis can be benign or malignant and is associated with neurocutaneous melanosis, a rare phakomatosis affecting primarily infants and characterized by numerous congenital cutaneous nevi. Neurologic symptoms develop due to hydrocephalus and compression. Neuropsychiatric symptoms, bowel and bladder dysfunction, and sensory and motor problems are often present. Malignant transformation can occur, and patients with both benign and malignant neoplasms have a poor prognosis¹.

The main differential diagnosis of a solitary primary melanotic neoplasm of the CNS is meningeal melanocytoma and primary malignant melanoma1. The histologic differentiation of these lesions can sometimes be challenging and presents a potential diagnostic pitfall in surgical neuropathology². Metastatic melanoma to the CNS is considerably more common than primary melanotic lesions and must also be included in the differential.

Meningeal melanocytomas are essentially benign lesions, although several cases of local recurrence and malignant transformation have been reported^3,4,9. Melanocytomas commonly present as a slow-growing intradural, extramedullary mass in the cervical or thoracic spine¹. Melanocytomas may also be intracranial^4,5. The peak incidence is in the fifth decade of life (reported range 9 to 73 years) and females are affected slightly more than males¹. Several cases in the literature describe an association of intracranial meningeal melanocytoma with nevus of Ota, an ipsilateral cutaneous pigmented lesion thought to develop from migration arrest of melanoblasts in the dermis⁶.

Melanocytomas are typically homogeneous lesions on MRI, hyperintense on T1-weighted images and hypointense on T2-weighted images⁵. On histologic examination, tumor cells are typically epithelioid with round nuclei and prominent nucleoli. Intracytoplasmic melanin pigment granules can usually be identified in both tumor cells and in macrophages present at the periphery of the tumor. The tumor cells can be arranged in whorls or sheets or have storiform or vasocentric patterns. Mitoses are infrequent (on average, less than 1 per 10 HPF, Ki67 <5%) and atypical mitoses are not present1. Well-differentiated melanocytomas typically do not invade surrounding tissues. The tumor cells are typically strongly positive for HMB-45 and Melan A (MART-1) and variably positive for S100 and vimentin^5,7. Melanocytomas are negative for EMA and Leu-75 helping to distinguish them from pigmented meningiomas. Complete resection is important to prevent tumor recurrence and localized radiation therapy has been shown to decrease the recurrence rate in cases of incomplete resection¹⁰.

The important diagnostic distinction to be made is primary or secondary malignant melanoma, which can present similarly but has a much poorer prognosis⁸. Cases have been reported in patients ranging from 15-71 years in age, with a peak in the fifth decade¹. Malignant melanoma can be histologically similar to melanocytoma, but usually has greater cellularity, atypia, pleomorphism and mitoses. Tumor cells may be round, epithelioid, or spindled with irregularly contoured nuclear membranes, mitotic figures, and prominent eosinophilic nucleoli. Melanoma cells are typically arranged in sheets or clusters and may infiltrate the meninges. Coagulative necrosis and hemorrhage are common. BRAF, NRAS and KIT mutations are common in melanoma and rare or absent in the small sample of melanocytomas characterized thus far, possibly due to a lack of sun/ultraviolet exposure⁵.

REFERENCES

1. Brat DJ and Perry A. Melanotic lesions. WHO Classification of Tumours of the Central Nervous System, 4th ed. Lyon: IARC, 2007.
2. O'Brien et al. Meningeal melanocytoma. An uncommon diagnostic pitfall in surgical neuropathology. Arch Path Lab Med. (1995) 119: 542-546.
3. Wang et al. Malignant transformation of spinal meningeal melanocytoma. Case report and review of the literature. J Neurosurg Spine (2007) 6: 451-454.
4. Wang et al. Malignant transformation of intracranial meningeal melanocytoma. Case report and review of the literature. (2011) 31: 414-420.
5. Wang et al. Melanocytomas of the Central Nervous System: a clinicopathological and molecular study. Eur J Clin Invest. 43 (2013), 8: 809-815.
6. Peircecchi-Marti et al. Intracranial meningeal melanocytoma associated with ipsilateral nevus of Ota. Case report. J Neurosurg. (2002) 96: 619-623.
7. Liubinas et al. Primary melanocytic neoplasms of the central nervous system. Journal of Clinical Neuroscience. (2010) 17: 1227-1232.
8. MacFarlane et al. Primary melanoma of the dura mater. Br J Neurosurg (1989) 3: 235-238.
9. Gempt et al. Black brain: transformation of a melanocytoma with diffuse melanocytosis into a primary cerebral melanoma. J Neurooncol (2011) 102: 323-328.
10. Rades et al. Therapy of meningeal melanocytoma. (2004) 100: 2442-7.

Contributed by Diana Thomas, MD, PhD and Clayton Wiley, MD, PhD