Melanotic Neuroectodermal
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| Blue-black mass being removed from within the anterior maxillary alveolus. | ||
Quick Review for Patients
| The melanotic neuroectodermal tumor of infancy is a rare neoplasm of neural crest origin that usually occurs in infants under 1 year of age. Most lesions occur within the marrow spaces of the anterior maxilla but some have been outside the jaws, especially in the skull and brain. It appears as a somewhat irregular radiolucency, perhaps multilocular but usually unilocular. The tumor is benign but may grow very rapidly and may invade bone marrow, very rare examples of malignant transformation have been reported. Treatment is surgical removal, somewhat more aggressive than the typical "conservative" removal. One case in 8 recurs with this treatment. |
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The rare oral melanotic neuroectodermal tumor of infancy (pigmented epulis of infancy) is a congenital neoplasm of unclear histogenesis which was first described by Krompecher in 1918. Thus far, approximately 200 cases have been reported. Referred to additionally as retinal anlage tumor, melanotic progonoma, pigmented ameloblastoma, melanotic adamantinoma, and congenital melanocarcinoma, it is considered to arise from neural crest cells, the cells which are embryologically responsible for much of the development of the maxillofacial region. Extraoral examples have been reported from the mediastinum, brain, anterior fontanelle, epididymis, and soft tissues of the arm (Table 1). Malignant variants represent less than 5% of reported cases.
Clinical Features
More than
90% of cases of neuroectodermal tumor of infancy present during the first
year of life, and 4 of 5 occur in or on the anterior maxillary alveolus (Figure
1). Occasional cases are congenital, and males and
females are equally affected. The lesion appears as a sessile or slightly
pedunculated, lobulated, firm mass which typically has a deep blue or black
surface discoloration. The tumor is usually 2-4 cm. in diameter at diagnosis
and radiographs often reveal a destructive, poorly demarcated radiolucency
of the underlying bone, perhaps with a faint "sunburst" appearance from mild
calcification along vessels radiating from the center of the tumor (Figure
2). The lesion often grows very rapidly but the surface
mucosa does not become ulcerated and the lesion remains asymptomatic. High levels of urinary
vanilmandelic acid (VMA) are sometimes found, but this is not as common a
feature as it is in other neural crest tumors, such as pheochromocytoma,
ganglioneuroblastoma, neuroblastoma and
retinoblastoma. The presence or absence of
elevated VMA does not correlate with malignant or aggressive biological
behavior, it merely indicates the presence of a tumor.
Pathology and Differential Diagnosis
The tumor in gross cross-section has a whitish, gray or blue-black appearance, depending on the amount of melanin present (Figure 3). There is a biphasic microscopic pattern with one cell population consisting of cuboidal epithelioid cells with open, vesicular nuclei clustered in alveolar or tubular patterns (Figure 4). These cells typically have abundant brown intracellular melanin granules. Ultrastructural studies have shown the lesional cells to have features of epithelial and melanocytic cells, bounded by basal laminae and interdigitating with adjacent cells, with desmosomal attachments. Melanosomes are present in the cytoplasm and the cells are immunoreactive for cytokeratin and melanoma-associated antigen (HMB-45). Some lesional cells react for neuron specific enolase (NSE), synaptophysin and Leu-7 as well.
The second lesional cell is a small dark round cell with a hyperchromatic nucleus and minimal cytoplasm, it has the appearance of a neuroblast. The cells aggregate in loose nests or islands within the background fibrovascular stroma (Figure 5). The neuroblastic cells are often surrounded by the larger pigmented cells and may be associated with neurofibrillar material resembling glial tissue. This second cell type contains few organelles but demonstrates intracytoplasmic neurofilamentous material, elongated cell processes, and dense core vesicles under electron microscopic examination. Mitoses are rarely seen and the tumor cells extend to the overlying mucosa.
Many of the tumors show pseudoencapsulation, perhaps with reactive bone formation at the lesional periphery. Developing tooth buds are typically included in the specimen, tempting the pathologist to presume an odontogenic origin or diagnosis for the lesion.
There appear to be no microscopic parameters
able to distinguish the benign from the malignant neuroectodermal tumors
of infancy, unless lesional cells are obviously dysplastic or demonstrate
abundant or abnormal mitoses.
Treatment and Prognosis
Because
of its locally aggressive behavior, the melanotic neuroectodermal tumor of
infancy is treated by wide surgical excision. When
bone is involved, a 0.5 mm. margin of radiographically normal bone should
also be removed. Elevated VMA levels usually return to normal once the tumor
is resected. Recurrence occurs in 15% of treated cases, and 50% of cases
treated without wide resection, hence, careful follow-up is important. Malignant
variants of this tumor must, of course, be treated more radically, usually
by excisional surgery with a wider margin of normal surrounding
tissue.
References (Chronologic Order)
Note: General references can be found by clicking on that topic to the left.
Krompecher E. Zur Histogenese und Morphologie der Adamantinome und sonstiger Kiefergeschwuelste. Beitr Pathol Anat 1918; 64:169-197.
Borello ED, Gorlin RJ. Melanotic neuroectodermal tumor of infancy: a neoplasm of neural crest origin. Cancer 1966; 19:196-203.
Nikai H, Ijuhin N, Yamasaki A, et al. Ultrastructural evidence for neural crest origin of the melanotic neuroectodermal tumor of infancy. J oral Pathol 1977; 6:221-232.
Dehner LP, Sibley RK, Sauk JJ, et al. Malignant melanotic neuroectodermal tumor of infancy: a clinical, pathologic, ultrastructural, and tissue culture study. Cancer 1979; 43:1389-1410.
Mosby EL, Lowe MW, Cobb CM, Ennis RL. Melanotic neuroectodermal tumor of infancy: review of the literature and report of a case. J Oral Maxillofac Surg 1992; 50:886-894.
Kapadia SB, Frisman DM, Hitchcock CL, et al. Melanotic neuroectodermal tumor of infancy - clinicopathological, immunohistochemical, and flow cytometric study. Am J Surg Pathol 1993; 17:566-573.
Nelson ZL, Newman L, Loukota RA, Williams DM. Melanotic neuroectodermal tumor of infancy - an immunohistochemical and ultrastructural study. Brit J Oral Maxillofac Surg 1995; 33:375-380.
Batsakis JG, Mackay B, Elnaggar AK. Ewing sarcoma and peripheral primitive neuroectodermal tumor - an interim report. Ann Otol Rhinol Laryngol 1996; 105:838-843.
Kim YG, Oh JH, Lee SC, Ryu DM. Melanotic neuroectodermal tumor of infancy. J Oral Maxillofac Surg 1996; 54:517-520.
Bouckaert MMR, Raubenheimer EJ. Gigantiform melanotic neuroectodermal tumor of infancy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998; 86:569-572.
Hoshina Y, Hamamoto Y, Suzuki I, et al. Melanotic neuroectodermal tumor of
infancy in the mandible. Report of a case. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 2000; 89:594-599.
Table 1:
Location of melanotic neuroectodermal tumors, as reported in the literature,
1990-1997. Modified from Yukiko et al., 2000.
Location
Number
of
lesions reported
Maxilla
19
Skull
8
Epididymis
7
Brain
3
Mandible
2
Retina
1
Meninx
1
Transverse sinus
1
Total
42
