Melanotic Neuroectodermal Tumor of Infancy Treatment & Management

Updated: Jun 19, 2018
  • Author: Leticia Ferreira, DDS, MS; Chief Editor: William D James, MD  more...
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Treatment

Surgical Care

The treatment of choice for melanotic neuroectodermal tumor of infancy (MNTI) is surgical excision, and it is usually curative. [11, 18, 44]  Existing teeth and developing teeth must be sacrificed when they lie within the lesion or near the borders of an MNTI. Some controversy still exists regarding the amount of adjacent bone that needs to be removed during the surgical procedure. Many clinicians advocate for a 5-mm margin of healthy tissue be included with the surgical specimen. [45, 46] Others advocate for only enucleation of the tumor followed by curettage of the bony cavity. [11, 47]

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Adjuvant and Neoadjuvant Therapies

Complete tumor removal of the melanotic neuroectodermal tumor of infancy (MNTI) may not be the goal when it may sacrifice vital structures such as the orbital or intracranial contents. In such cases, adjuvant chemotherapy may be beneficial. [48] Cases of primarily inoperable MNTIs have also been reported, for which chemotherapy was performed to reduce extension of the tumor mass before surgical treatment. [49, 50] Only rarely has radiotherapy been successfully used in combination with surgical treatment or in combination with chemotherapy and surgical treatment for MNTI. [51, 52]

Local recurrence is a possibility and has been documented to range from 10-60% of patients, depending on the study. Overall, recurrence has been reported to occur in 20% of cases. [18] The recurrent lesions, possibly secondary to inadequate excision or multicentricity, usually become apparent within the first year after surgery. In instances of inoperable recurrence or when clear margins are impossible to obtain, chemotherapy and/or radiation therapy have been used. [20, 51, 52, 53]

Neven et al in 2008 advocate for adjuvant chemotherapy in cases of multiple aggressive recurrences and/or inoperable tumors. [19] These authors followed a successful neuroblastoma chemotherapy protocol for a recurring aggressive MNTI, which, in molecular studies, showed 1p deletion and gain of chromosome 7q, analogous to a neuroblastoma. Hence, in cases in which chemotherapy is necessary, it appears that molecular studies of the resection specimen might be beneficial to identify which protocol will have the most successful results.

Interestingly, Davis et al in 2015 reported a unique mixed response of an aggressive recurrent tumor to neoadjuvant chemotherapy using agents known to be effective for neuroblastomalike tumors (vincristine and cyclophosphamide). [20] The postchemotherapy surgical specimen showed that the treatment resulted in complete obliteration of the neuroblastlike cells, but only a minimal effect in reducing the larger, polygonal cell population.

Gomes et al in 2015 found a BRAFV600E oncogenic mutation in one case of MNTI of the three studied. This might suggest that currently available BRAF-targeted therapies might be successful alternative treatments for aggressive MNTIs harboring the mutation. [54]

A 2016 study performed exhaustive genomic, transcriptomic, epigenetic, and pathological characterization of a MNTI involving the fibula of a 2-month-old baby girl. Whole-exome analysis of genomic DNA from both the tumor and blood indicated a heterozygous, unique-germline, loss-of-function mutation in CDKN2A (p16INK4A , D74A), as well as tumor-promoting somatic fusion genes and epigenetic deregulation. The study also found that a derived MNTI cell line was sensitive to inhibitors of lysine demethylase. [26]

Although MNTI is an aggressive benign tumor, malignant variants have been reported. Of reported cases, mostly of the brain and skull, 6.5% have exhibited malignant behavior. [18] Nevertheless, some authors believe the estimation of 6.5% is probably exaggerated in the literature because unusual malignant cases are more likely to be reported. [1, 22] Metastatic spread of MNTI occurs infrequently, in less than 5% of malignant cases. Management of these rare cases is different. Few, if any, parameters exist, either clinically or histologically, to predict the development of metastatic lesions. [34] In a few cases reported as malignant, the histologic features have taken on a neuroblastomalike appearance. [9, 37]

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Long-Term Monitoring

Address the documented 20% recurrence rate of melanotic neuroectodermal tumor of infancy (MNTI) in the postoperative care by monitoring the patient with physical and radiographic examination at monthly intervals for the first two postoperative years. Moreover, an estimated malignant transformation rate of 6.5% highlights the possibly serious nature of this tumor and the need for careful clinical evaluation and close follow-up of affected patients, especially for tumors located in the brain and skull.

Permanent reconstruction of the maxillary alveolus and missing dentition may have to be delayed until after growth is completed, often in the teenage years. In the interim, transitional removable partial dentures may be necessary. The skills of an orthodontist, prosthodontist, oral surgeon, and/or dentist may be required, based on the extent of the missing structures, to correct any functional and cosmetic deformity.

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