Background

Melanotic neuroectodermal tumor of infancy (MNTI) is a relatively uncommon osteolytic-pigmented neoplasm that primarily affects the jaws of newborn infants.^[1]The lesion has had an interesting history since its initial description by Krompecher in 1918 as a congenital melanocarcinoma.^[2]

For the next 5 decades, the lesion was reported under a variety of different names as succeeding authors attempted to identify the cell of origin. Some of the terms applied to this lesion included pigmented ameloblastoma, retinal anlage tumor, melanotic progonoma, melanotic adamantinoma, and pigmented epulis of infancy.^{[3, 4, 5]}These terms reflected theories of suspected origin from the odontogenic apparatus, the pigmented anlage of the retina, or the sensory neuroectodermal tissues.

In 1966, Borello and Gorlin reported a case with high urinary excretion of vanillylmandelic acid (VMA), suggesting a neural crest origin, and they proposed the term melanotic neuroectodermal tumor of infancy.^[6]Since then, numerous histochemical, immunohistochemical, electron microscopic, and tissue culture studies have supported the neural crest origin and confirmed the preferred term of melanotic neuroectodermal tumor of infancy.^{[7, 8, 9, 10]}

Pathophysiology

Several patients with melanotic neuroectodermal tumor of infancy (MNTI) have demonstrated a high urinary excretion of VMA.^{[6, 11]}This finding adds credence to a neural crest origin because elevated VMA has been reported in neuroblastoma, ganglioneuroblastoma, pheochromocytoma,^[12]and other neural crest tumors. However, the presence of elevated urinary VMA is not diagnostic for MNTI.

Frequency

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm and approximately 485 cases have been reported in the literature to date worldwide.

Sex

Melanotic neuroectodermal tumor of infancy (MNTI) has a slight male predilection, with a male-to-female ratio of 1.3:1.^[13]

Age

Most patients, by some estimates more than 90%, present with the tumor in the first year of life, usually from age 1-6 months, with a peak between the second and sixth month of life.^[14]A few cases of melanotic neuroectodermal tumor of infancy (MNTI) have been reported in adults, notably, a 23-year-old man, a 39-year-old woman, and a 67-year-old woman.^{[15, 16, 17]}However, only 9% of cases are seen in patients older than 12 months.^[18]

Prognosis

Most melanotic neuroectodermal tumors of infancy (MNTIs) are benign and effectively managed by aggressive surgical excision. Reconstruction may be challenging. In a systematic review, a recurrence rate of 20% was found, with the highest relative risk for recidivation being found in the mandible and skull (33.3% and 31.8%, respectively). Most recurrences appear to occur within 4 weeks after the operation. A comprehensive systematic review of 472 cases of MNTI found that age at diagnosis is an important prognostic indicator in these tumors. Infants diagnosed within the first 2 months of birth have a shorter disease-free survival period and the recurrence tends to occur within only 6 months from treatment, while patients older then 4.5 months have minimal risk of recurrence.^[13]Unfortunately, reports have shown that recurrent tumors tend to behave more aggressively and involve other anatomic structures such as the orbit and skull base.^{[19, 20]}Additionally, a malignancy rate of 6.5% has been reported for these tumors, with most malignant cases occurring in the skull and brain. Only very few tumors produce metastases and death.^[18]

Clinical Presentation

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Media Gallery

Melanotic neuroectodermal tumor of infancy presents as a rapidly growing bluish mass on the anterior aspect of the maxilla.
Axial CT, bone window, noncontrasted scan demonstrates expansile lytic lesion of the left maxilla producing displacement of dental follicles.
The biphasic population of cells demonstrates alveolar structures lined by cuboidal epithelioid cells demonstrating granules of dark-brown melanin pigment. The second cell type is neuroblastic in appearance and consists of small, round, hyperchromatic cells.

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Author

Leticia Ferreira, DDS, MS Associate Professor, Department of Diagnostic Sciences, University of the Pacific, Arthur A Dugoni School of Dentistry

Leticia Ferreira, DDS, MS is a member of the following medical societies: American Academy of Oral and Maxillofacial Pathology, American Academy of Oral Medicine, American Association of Women Dentists, American Dental Association, American Dental Education Association, California Dental Association, San Francisco Dental Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Drore Eisen, MD, DDS Consulting Staff, Dermatology of Southwest Ohio

Drore Eisen, MD, DDS is a member of the following medical societies: American Academy of Dermatology, American Academy of Oral Medicine, American Dental Association

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Mark G Lebwohl, MD Chairman, Department of Dermatology, Mount Sinai School of Medicine

Mark G Lebwohl, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Received none from Amgen for consultant & investigator; Received none from Novartis for consultant & investigator; Received none from Pfizer for consultant & investigator; Received none from Celgene Corporation for consultant & investigator; Received none from Clinuvel for consultant & investigator; Received none from Eli Lilly & Co. for consultant & investigator; Received none from Janssen Ortho Biotech for consultant & investigator; Received none from LEO Pharmaceuticals for consultant & inves.

Acknowledgements

James Burns, DDS, PhD, MEd Chairman, Professor, Department of Oral and Maxillofacial Pathology, Assistant Dean, Clinical Education, Virginia Commonwealth University School of Dentistry

James Burns is a member of the following medical societies: American Academy of Oral and Maxillofacial Pathology, American Association for Cancer Education, American Dental Association, and International Association of Oral Pathologists

Disclosure: Nothing to disclose.

William M Carpenter, DDS, MS Professor, Chairman, Department of Pathology and Medicine, University of the Pacific, Arthur A Dugoni School of Dentistry

William M Carpenter, DDS, MS is a member of the following medical societies: American Academy of Oral and Maxillofacial Pathology and American Academy of Oral Medicine

Disclosure: Nothing to disclose.

Robert Strauss, DDS Associate Professor, Department of Oral and Maxillofacial Surgery, Virginia Commonwealth University School of Dentistry

Robert Strauss is a member of the following medical societies: American Association of Oral and Maxillofacial Surgeons and American Dental Association

Disclosure: Nothing to disclose.