Malignant melanotic neuroectodermal tumor of infancy.A clinical, pathologic, ultrastructural and tissue culture study

The melanotic neuroectodermal tumor of infancy is an uncommon neoplasm typically of early childhood which has a predilection for the head and neck region, particularly the maxilla. Except for one previous example in the literature, this tumor has consistently behaved in a benign fashion. This study documents the clinical course and pathologic findings of a tumor which began in the maxilla of a 4-month-old boy, followed by a local recurrence, metastasis to a cervical lymph node and finally, widespread dissemination and death at 18 months, 24 months and 38 months, respectively. The tumor was initially composed of nests consisting of melanin-containing cells and small dark cells. An elevated vanillylmandelic acid level was recorded during the course of the disease. At autopsy, the tumor in lymph nodes, liver, bone and soft tissues had a monotonous pattern of small dark cells similar to a conventional neuroblastoma. Previous ultrastructural studies indicate that the melanotic neuroectodermal tumor of infancy is composed of melanocytes and neuroblast-like cells. Our case provided the unique opportunity to examine in sequence the ultrastructural and in vitro characteristics of a recurring and eventually metastasizing melanotic neuroectodermal tumor. Although the neuroblast-like cells were initially difficult to identify by electron microscopy, a melanin-producing cell line and a separate nonpigmented cell line were successfully isolated from various tumor explants. Various stages of melanosome development were identified in the pigmented cells from the local recurrences and in vitro. Dibutyryl cAMP accentuated the formation of pigment and dendritic development in the melanocytes and dendrites only in the small nonpigmented cells. Electron dense granules were observed in the cultured smaller cells and also in the lymph node and soft tissue metastases. Tyrosine hydroxylase activity was demonstrated in the neuroblast-like cells. In the final biopsy and autopsy material, only the neuroblast-like cells remained and the tumor resembled a conventional neuroblastoma.