DIAGNOSIS: MALIGNANT MELANOTIC NEUROECTODERMAL TUMOR OF INFANCY
The melanotic neuroectodermal tumor of infancy (MNTI) is a rare, usually benign pigmented lesion that characteristically involves the maxilla (70%), and less frequently other sites such as skull (10%), mandible (6%) and brain (1-4%). On rare occasions, the neoplasm has been found in the skin, epididymis, uterus, ovary and mediastinum (3). In approximately 6-9% the tumour could be multifocal (3). MNTI was first described by Krompecher in 1918 as a congenital "melanocarcinoma". Since then, other synonyms such as a melanotic epithelial odontoma, retinal anlage tumour and melanotic progonoma were also used. However, the modern terminology is restricted to "melanotic neuroectodermal tumor of infancy". Due to usually extra-axial location of MNTI, the present WHO classification of the brain tumors does not incorporates this neoplasm. Despite of some morphological similarities to the melanotic medulloblastoma (6), MNTI is considered an unrelated, benign tumor entity that can be easily distinguished from medulloblastomas on the basis of immunoreactivity for EMA, HMB-45 and cytokeratins. These immunohistochemical properties of MNTI, separate this entity also from other pigmented neuroectodermal tumors, such as melanotic Schwannoma, melanocytoma or pineal gland neoplasm (6). Electron microscopic studies consistently show the presence of pigmented epithelial cells with abundant premelanosomes and melanin granules, non-melanotic neuroblastic cells, and poorly differentiated anaplastic cell component (3). Molecular studies revealed strong expression of melanotransferrin within the tumor and provided proof for origin of neoplasm from the neural crest precursors (4). Borello and Gorlin reported increased 3-methoxy-4-hydroxy melanic acid (VMA) in urine supporting this hypothesis (1). On the basis of immunohistochemical studies, it has been suggested the MNTI recapitulates retina at fifth week of gestation (5). Review of the previously reported MNTI, indicates that approximately 3% of cases can behave in a malignant fashion (3). The malignant variant of MNTI is an aggressive neoplasm that more often spreads by local extension rather than metastases. This tendency to a local recurrence rather to dissemination in CSF or extracranial sites, further distinguishes this tumor from medulloblastoma. Recurrence rate remains approximately 15% and metastases to the lymph nodes, liver and bone have been described on a few occasions. Increased signal intensity on T1 and decreased signal on T2 weighted images may suggest the presence of melanin content on MRI, and guide to a correct diagnosis on radiological studies. The malignant variant of MNTI almost invariably has a poor prognosis. Only in two cases (2,6), disappearance of metastases was observed after the treatment with Cyclophosphamide and Carboplatin. However, the extent of the disease in our patient reached the point beyond any justification for an aggressive therapy, and she died two months after the last surgery, approximately eight months from the onset of the disease.
Contributed by MERDAS AL- OTAIBI, MD, B. LACH, MD, PhD, FRCPC and E. Al SHAIL, MD