Recurrent melanotic neuroectodermal tumor of infancy: a proposal for treatment protocol with surgery and adjuvant chemotherapy Johannus Neven, MD, DMD, a Christine Hulsbergen–van der Kaa, MD, b Jacqueline Groot-Loonen, MD, PhD, c Peter C.M. de Wilde, DMD, PhD, d and Matthais A.W. Merkx, MD, DMD, PhD, e Nijmegen, The Netherlands RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE The case of a 4-month-old male infant treated with combined surgery and chemotherapy for an aggressive recurrent melanotic neuroectodermal tumor of infancy (MNTI) on the top of the alveolar process of the mandible with a long-term follow-up is presented. Initial treatment comprised conservative local excision and curettage of the mandible. After several local recurrences and because radical surgical excision would give gross functional and aesthetic mutilation, finally complete, long-lasting remission was achieved with adjuvant chemotherapy, according to a neuroblastoma protocol (10-year follow-up). The reason for this protocol was because molecular genetic studies of this tumor showed loss of heterozygosity of chromosome 1p and gain of chromosome 7q analogue to neuroblastomas. A combination of surgery and chemotherapy should be the preferred treatment in case of a recurrence MNTI because optimal functional and aesthetic outcome. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:493-6) Melanotic neuroectodermal tumor of infancy (MNTI) has been described as a rare benign pigmented lesion in the head and neck area of infants younger than 1 year of age (93%). The most commonly affected sites are the maxilla (68% to 80%), skull (10.8%), mandible (5.8%) and brain (4.3%). 1 The terms “retinal anlage tumor,” “melanotic progonoma,” and “melanotic ameloblas- toma” have also been applied to this tumor and reflect the uncertainty as to its histogenesis. 1 Biochemical, histochemical, ultrastructural, and immunophenotypic studies now support a neural crest origin. In an exten- sive systematic review of the literature, Kruse-Lösler et al. 1 evaluated clinical features, treatment alternatives, and follow-up protocol. 1 In the oral cavity, MNTI shows as a soft nontender, nonulcerated, rapidly growing pigmented (brown/red) swelling on the top of the alveolar crest. On a radio- graph, a local erosion of the alveolar process is seen. Therefore, these are generally depicted as benign le- sions. 1 After surgical removal, the primary mode of therapy, an overall recurrence rate of 20% is seen. Recurrences may be caused by incomplete removal of the primary lesion, dissemination of neoplastic cells during surgery, and multicentricity. Most recurrences occurred within the first or second month after primary surgical intervention because of incomplete (retrospec- tively) first resection. 1 A malignancy rate of 2% to 7% has been reported (in 2% of the cases malignancy is seen). 1 Microscopically, MNTIs are biphasic tumors with one cell population consisting of cuboidal epithelial cells with open vesicular nuclei clustered in alveolar or tubular patterns. These cells typically have abundant brown intracellular melanin granules. The second le- sional cell is a small, dark, round cell with a hyper- chromatic nucleus and minimal cytoplasma. It has the appearance of a neuroblast. The cells aggregate in loose nests or islands within the background fibrovascular tissue. Since this benign neoplasm was first described by Krompecher in 1918, slightly more than 365 cases have been reported in the world literature, with 93% of these occurring in the head and neck as mentioned before. 1-4 In the past 20 years, 17 recurrences and their treatment modality have been published in the international liter- ature. As extensive radical surgery and radiotherapy are very mutilating, there is a need for new treatment modalities to cure patients with extensive or recurrent a Oral and Maxillofacial Surgeon, Department of Oral and Maxillo- facial Surgery, Radboud University Nijmegen Medical Centre. b Clinical Pathologist, Institute of Pathology, Radboud University Nijmegen Medical Centre. c Associate Professor, Department of Pediatric Oncology, Radboud University Nijmegen Medical Centre. d Associate Professor, Institute of Pathology, Radboud University Nijmegen Medical Centre. e Professor, Department of Oral and Maxillofacial Surgery, Radboud University Nijmegen Medical Centre. Received for publication Oct 24, 2007; returned for revision Jan 23, 2008; accepted for publication Feb 1, 2008. 1079-2104/$ - see front matter © 2008 Mosby, Inc. All rights reserved. doi:10.1016/j.tripleo.2008.02.001 493