Melanotic Neuroectodermal Tumor of Infancy: Background, Pathophysiology, Epidemiology

Sections

Melanotic Neuroectodermal Tumor of Infancy

Sections Melanotic Neuroectodermal Tumor of Infancy
Overview
Presentation
DDx
Workup
Treatment
Media Gallery
References

Overview

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, 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.^[12]

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.^[13]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.^{[14, 15, 16]}However, only 9% of cases are seen in patients older than 12 months.^[17]

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.^[12]Unfortunately, reports have shown that recurrent tumors tend to behave more aggressively and involve other anatomic structures such as the orbit and skull base.^{[18, 19]}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.^[17]

Clinical Presentation

Chi A, Neville B, Damm D, Allen C. Melanotic Neuroectodermal Tumor of Infancy. Oral & Maxillofacial Pathology. 4th ed. St Louis, Mo: Saunders/Elsevier; 2016. 500-1.
Krompecher Z. Zur histogenese and morphologic den adamantinome und sonstiger kiefergeschwulste. Beitr Pathol Anat. 1918. 165-97.
Allen MS Jr, Harrison W, Jahrsdoerfer RA. "Retinal anlage" tumors. Melanotic progonoma, melanotic adamantinoma, pigmented epulis, melanotic neuroectodermal tumor of infancy, benign melanotic tumor of infancy. Am J Clin Pathol. 1969 Mar. 51(3):309-14. [Medline].
Kilmer JB. The pigmented ameloblastomas or "retinal anlage" tumors. Report of two cases. Laryngoscope. 1963 Oct. 73:1303-8. [Medline].
Lurie HI. Congential melanocarcinoma, melanotic adamantinoma, retinal anlage tumor, progonoma, and pigmented epulis of infancy. Summary and review of the literature and report of the first case in an adult. Cancer. 1961 Sep-Oct. 14:1090-108. [Medline].
Borello ED, Gorlin RJ. Melanotic neuroectodermal tumor of infancy--a neoplasm of neural crese origin. Report of a case associated with high urinary excretion of vanilmandelic acid. Cancer. 1966 Feb. 19(2):196-206. [Medline].
Cutler LS, Chaudhry AP, Topazian R. Melanotic neuroectodermal tumor of infancy: an ultrastructural study, literature review, and reevaluation. Cancer. 1981 Jul 15. 48(2):257-70. [Medline].
Pettinato G, Manivel JC, d'Amore ES, Jaszcz W, Gorlin RJ. Melanotic neuroectodermal tumor of infancy. A reexamination of a histogenetic problem based on immunohistochemical, flow cytometric, and ultrastructural study of 10 cases. Am J Surg Pathol. 1991 Mar. 15(3):233-45. [Medline].
Dehner LP, Sibley RK, Sauk JJ Jr, Vickers RA, Nesbit ME, Leonard AS, et al. Malignant melanotic neuroectodermal tumor of infancy: a clinical, pathologic, ultrastructural and tissue culture study. Cancer. 1979 Apr. 43(4):1389-410. [Medline].
Navas Palacios JJ. Malignant melanotic neuroectodermal tumor: light and electron microscopic study. Cancer. 1980 Aug 1. 46(3):529-36. [Medline].
Chaudhary A, Wakhlu A, Mittal N, Misra S, Mehrotra D, Wakhlu AK. Melanotic neuroectodermal tumor of infancy: 2 decades of clinical experience with 18 patients. J Oral Maxillofac Surg. 2009 Jan. 67(1):47-51. [Medline].
Rachidi S, Sood AJ, Patel KG, Nguyen SA, Hamilton H, Neville BW, et al. Melanotic Neuroectodermal Tumor of Infancy: A Systematic Review. J Oral Maxillofac Surg. 2015 Oct. 73 (10):1946-56. [Medline].
Agarwal P, Saxena S, Kumar S, Gupta R. Melanotic neuroectodermal tumor of infancy: Presentation of a case affecting the maxilla. J Oral Maxillofac Pathol. 2010 Jan. 14(1):29-32. [Medline]. [Full Text].
Gorhan C, Soto-Ares G, Ruchoux MM, Blond S, Pruvo JP. Melanotic neuroectodermal tumour of the pineal region. Neuroradiology. 2001 Nov. 43(11):944-7. [Medline].
Vajtai I, Suták I, Varga Z. Melanotic progonoma as a component of ovarian teratoma. Histopathology. 2000 Mar. 36(3):283-5. [Medline].
Schulz DM. A malignant, melanotic neoplasm of the uterus, resembling the retinal anlage tumors; report of a case. Am J Clin Pathol. 1957 Nov. 28(5):524-32. [Medline].
Kruse-Lösler B, Gaertner C, Bürger H, Seper L, Joos U, Kleinheinz J. Melanotic neuroectodermal tumor of infancy: systematic review of the literature and presentation of a case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Aug. 102(2):204-16. [Medline].
Neven J, Hulsbergen-van der Kaa C, Groot-Loonen J, de Wilde PC, Merkx MA. Recurrent melanotic neuroectodermal tumor of infancy: a proposal for treatment protocol with surgery and adjuvant chemotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Oct. 106(4):493-6. [Medline].
Davis JM, DeBenedictis M, Frank DK, Lessin ME. Melanotic neuroectodermal tumor of infancy: a wolf in sheep's clothing. Ann Otol Rhinol Laryngol. 2015 Feb. 124 (2):97-101. [Medline].
Madrid C, Aziza J, Hlali A, Bouferrache K, Abarca M. Melanotic neuroectodermal tumour of infancy: a case report and review of the aetiopathogenic hypotheses. Med Oral Patol Oral Cir Bucal. 2010 Sep 1. 15(5):e739-42. [Medline].
Lacy SR, Kuhar M. Melanotic neuroectodermal tumor of infancy presenting in the subcutaneous soft tissue of the thigh. Am J Dermatopathol. 2010 May. 32(3):282-6. [Medline].
Choi IS, Kook H, Han DK, Baek HJ, Jung ST, Lee JH, et al. Melanotic neuroectodermal tumor of infancy in the femur: a case report and review of the literature. J Pediatr Hematol Oncol. 2007 Dec. 29(12):854-7. [Medline].
Ma Y, Zheng J, Yang S, Zhu H, Dong K, Xiao X, et al. Melanotic neuroectodermal tumor of infancy in the soft tissue of the forearm: report of a case. Int J Clin Exp Pathol. 2015. 8 (10):13584-9. [Medline].
Barnes DJ, Hookway E, Athanasou N, Kashima T, Oppermann U, Hughes S, et al. A germline mutation of CDKN2A and a novel RPLP1-C19MC fusion detected in a rare melanotic neuroectodermal tumor of infancy: a case report. BMC Cancer. 2016 Aug 12. 16:629. [Medline].
Steinberg B, Shuler C, Wilson S. Melanotic neuroectodermal tumor of infancy: evidence for multicentricity. Oral Surg Oral Med Oral Pathol. 1988 Dec. 66(6):666-9. [Medline].
Pontius EE, Dziabis MD, Foster JA. Multicentric melano-ameloblastoma of the maxilla. Cancer. 1965 Mar. 18:381-7. [Medline].
Haque S, McCarville MB, Sebire N, McHugh K. Melanotic neuroectodermal tumour of infancy: CT and MR findings. Pediatr Radiol. 2012 Jun. 42(6):699-705. [Medline]. [Full Text].
Fowler DJ, Chisholm J, Roebuck D, Newman L, Malone M, Sebire NJ. Melanotic neuroectodermal tumor of infancy: clinical, radiological, and pathological features. Fetal Pediatr Pathol. 2006 Mar-Apr. 25(2):59-72. [Medline].
Atkinson GO Jr, Davis PC, Patrick LE, Winn KJ, Ball TI, Wyly JB. Melanotic neuroectodermal tumor of infancy. MR findings and a review of the literature. Pediatr Radiol. 1989. 20(1-2):20-2. [Medline].
Koob M, Fayard C, Pariente D, Adamsbaum C, Franchi-Abella S. Prenatal Diagnosis Of Orbital Melanotic Neuroectodermal Tumor Of Infancy. Ultrasound Obstet Gynecol. 2015 Jan 16. [Medline].
Koral K, Derinkuyu B, Timmons C, Schwartz-Dabney CL, Swift D. Melanotic neuroectodermal tumor of infancy: report of one calvarial lesion with T1 shortening and one maxillary lesion. Clin Imaging. 2010 Sep-Oct. 34(5):382-4. [Medline].
Kapadia SB, Frisman DM, Hitchcock CL, Ellis GL, Popek EJ. Melanotic neuroectodermal tumor of infancy. Clinicopathological, immunohistochemical, and flow cytometric study. Am J Surg Pathol. 1993 Jun. 17(6):566-73. [Medline].
Woo SB. Melanotic neuroectodermal tumor of infancy. In: Oral Pathology: A Comprehensive Atlas and Text. 1st ed. Philadelphia, Pa: Saunders/Elsevier; 2012. 207-09.
Dammann O, Hagel C, Allers B, et al. Malignant melanotic neuroectodermal tumor of infancy. Childs Nerv Syst. 1995 Mar. 11(3):186-8. [Medline].
Block JC, Waite DE, Dehner LP, Leonard AS, Ogle RG, Gatto DJ. Pigmented neuroectodermal tumor of infancy. An example of rarely expressed malignant behavior. Oral Surg Oral Med Oral Pathol. 1980 Apr. 49(4):279-85. [Medline].
Nicosia G, Spennato P, Aliberti F, Cascone D, Quaglietta L, Errico ME, et al. Giant melanotic neuroectodermal tumor of infancy (melanotic progonoma) of the head and neck: report of a malignant case. J Neurosurg Pediatr. 2017 Feb 24. 1-8. [Medline].
Barrett AW, Morgan M, Ramsay AD, Farthing PM, Newman L, Speight PM. A clinicopathologic and immunohistochemical analysis of melanotic neuroectodermal tumor of infancy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002 Jun. 93(6):688-98. [Medline].
Nelson ZL, Newman L, Loukota RA, Williams DM. Melanotic neuroectodermal tumour of infancy: an immunohistochemical and ultrastructural study. Br J Oral Maxillofac Surg. 1995 Dec. 33(6):375-80. [Medline].
de Souza PE, Merly F, Maia DM, Castro WH, Gomez RS. Cell cycle-associated proteins in melanotic neuroectodermal tumor of infancy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999 Oct. 88(4):466-8. [Medline].
Nitta T, Endo T, Tsunoda A, Kadota Y, Matsumoto T, Sato K. Melanotic neuroectodermal tumor of infancy: a molecular approach to diagnosis. Case report. J Neurosurg. 1995 Jul. 83(1):145-8. [Medline].
Khoddami M, Squire J, Zielenska M, Thorner P. Melanotic neuroectodermal tumor of infancy: a molecular genetic study. Pediatr Dev Pathol. 1998 Jul-Aug. 1(4):295-9. [Medline].
Dashti SR, Cohen ML, Cohen AR. Role of radical surgery for intracranial melanotic neuroectodermal tumor of infancy: case report. Neurosurgery. 1999 Jul. 45(1):175-8. [Medline].
Béogo R, Nikiéma Z, Traoré SS, Bouletreau P. Maxillary melanotic neuroectodermal tumor of infancy management: is conservative surgery the best approach?. J Craniofac Surg. 2013 Jul. 24(4):e338-40. [Medline].
Rustagi A, Roychoudhury A, Karak AK. Melanotic neuroectodermal tumor of infancy of the maxilla: a case report with review of literature. J Oral Maxillofac Surg. 2011 Apr. 69(4):1120-4. [Medline].
Franchi G, Sleilati F, Soupre V, Boudjemaa S, Josset P, Diner PA, et al. Melanotic neuroectodermal tumour of infancy involving the orbit and maxilla: surgical management and follow-up strategy. Br J Plast Surg. 2002 Sep. 55(6):526-9. [Medline].
Pierre-Kahn A, Cinalli G, Lellouch-Tubiana A, Villarejo FJ, Sainte-Rose C, Pfister A, et al. Melanotic neuroectodermal tumor of the skull and meninges in infancy. Pediatr Neurosurg. 1992. 18(1):6-15. [Medline].
Hoshina Y, Hamamoto Y, Suzuki I, Nakajima T, Ida-Yonemochi H, Saku T. Melanotic neuroectodermal tumor of infancy in the mandible: report of a case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 May. 89(5):594-9. [Medline].
Mirich DR, Blaser SI, Harwood-Nash DC, Armstrong DC, Becker LE, Posnick JC. Melanotic neuroectodermal tumor of infancy: clinical, radiologic, and pathologic findings in five cases. AJNR Am J Neuroradiol. 1991 Jul-Aug. 12(4):689-97. [Medline].
Klimek L, Klein HM, Schneider W, Mösges R, Schmelzer B, Voy ED. Stereolithographic modelling for reconstructive head surgery. Acta Otorhinolaryngol Belg. 1993. 47(3):329-34. [Medline].
Woessmann W, Neugebauer M, Gossen R, et al. Successful chemotherapy for melanotic neuroectodermal tumor of infancy in a baby. Med Pediatr Oncol. 2003 Mar. 40(3):198-9. [Medline].
Gomes CC, Diniz MG, de Menezes GH, Castro WH, Gomez RS. BRAFV600E Mutation in Melanotic Neuroectodermal Tumor of Infancy: Toward Personalized Medicine?. Pediatrics. 2015 Jul. 136 (1):e267-9. [Medline].

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.

of 3

Author

Leticia Ferreira, DDS, MS Assistant Professor of Pathology and Medicine, Department of Dental Practice, 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: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Naked Biome<br/>Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>StatPearls; Editor.

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.

Sections Melanotic Neuroectodermal Tumor of Infancy
Overview
Presentation
DDx
Workup
Treatment
Media Gallery
References

Melanotic Neuroectodermal Tumor of Infancy

Background

Pathophysiology

Epidemiology

Frequency

Sex

Age

Prognosis

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Melanotic Neuroectodermal Tumor of Infancy

Background

Pathophysiology

Epidemiology

Frequency

Sex

Age

Prognosis

References

Tables

Contributor Information and Disclosures

What would you like to print?

Find Us On

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Medscape Consult

Tools

Most Popular Articles