Melanotic progonoma, also known as melanotic neuroectodermal tumor of infancy or retinal anlage tumor, is a rare tumor of neuroectodermal origin usually arising in the first year of life. It is described most often in the head and neck area especially the maxilla. Melanotic progonoma has also been reported in the skull, mandible (as in our case) and rarer sites such as the male or female genital tract (1-4).

Although generally thought to arise from the neural crest, the histogenesis of this tumor is not certain; other theories are that this tumor arises from odontogenic or germ cell origin. Neural crest origin, however, is supported by ultrastructural, histochemical and biochemical studies relating to the secretion of catecholamine-like hormones3. Vanillyl mandelic acid (VMA) and homovanillic acid (HVA) levels can be measured in the serum and urine, and are useful for clinical diagnosis and monitoring (1, 2, 4).

A melanotic progonoma presents as a discolored, firm and painless mass usually with no ulceration of overlying skin. The discoloration is due to melanin pigment within the tumor cells. X-ray reveals a well-demarcated osteolytic lesion while CT scan and MRI show a hypodense lesion (4, 5). This tumor is considered benign but can be fast growing and locally aggressive as this case study indicated. Dissemination via cerebrospinal fluid, lymph node metastases and recurrence after surgery have been occasionally described (6-8). In general, isolated tumors with benign behavior are managed with surgical excision alone. However, for tumors which are locally aggressive, those which have spread or are in sites which require delicate neurosurgical techniques, neoadjuvant chemo- and radiotherapy is often required (1). The tumor has been noted to behave more aggressively when the neuroblastic component predominates (1). The patient in our case, unfortunately, was lost to follow up, so the disease progression is unknown.

On gross examination, melanotic progonoma is firm and well-circumscribed, and often lobulated. The cut surface may be dark due to melanin pigment. The histology recapitulates the cytologic findings in that a biphasic cell population is noted usually within a fibrous stroma. The larger cells are found in alveolar or tubular formation around aggregates of the small neuroblastic-like cells. Necrosis and mitotic figures are rarely observed (5, 8-10). At the resection margins, nests of tumor cells can be found between bony trabeculae (4).

Immunohistochemistry is a useful ancillary investigation in this regard. The large epithelioid cells are positive for cytokeratins, HMB45 and EMA but negative for S100, GFAP, AFP and Melan A. The neuroblastic cells show positivity for CD57, NSE, and variable positivity for S100, CD99 and synaptophysin (1-4, 9). Ultrastructurally, the larger cells demonstrate melanosomes and the smaller cells, dense neurosecretory granules. The molecular profile of melanotic progonoma is not well understood and the role of the BRAF V600E transversion mutation is suspected to play a role due to the similarities of this tumor to melanoma (1). This mutation warrants further research as it is a potential target for personalized treatment.