The Role of Chemotherapy in Management of Inoperable, Metastatic and/or Recurrent Melanotic Neuroectodermal Tumor of Infancy-Own Experience and Systematic Review

Abstract

Melanotic Neuroectodermal Tumor of Infancy (MNTI) is a very rare pediatric neoplasm of neural crest origin. In most cases, it develops in infants as a localized tumor of the maxilla, and surgery is usually curative. In less than 10% of patients with inoperable, metastatic or persistently recurring MNTI, chemotherapy (CHT) may be considered; however, its role is still unclear. The aim of our study was to assess the efficacy of CHT in children with large, inoperable, metastatic and/or recurrent MNTI. Four such infants, treated with CHT in Polish and German centers of pediatric oncology, were presented. Additionally, a systematic literature search of the PubMed/MEDLINE, Scopus and Web of Science databases was performed, yielding 38 similar cases within the last 42 years. Neoadjuvant CHT, based mainly on the protocols for neuroblastoma, was often effective, allowing for complete delayed surgery in most cases. However, the role of adjuvant CHT in preventing recurrences after incomplete resection of MNTI remains unclear. Disseminated inoperable MNTI was almost universally associated with poor response to CHT and unfavorable outcome. Further investigations to elaborate standards of management in patients with inoperable, metastatic or persistently recurring MNTIs are necessary to improve outcomes.

Keywords: adjuvant; chemotherapy; inoperable; melanotic neuroectodermal tumor of infancy; metastatic; neoadjuvant; recurrent; systemic treatment.

Figure 1

Patient 1: an intraoral tumor originating from the right side of the maxilla at first admission to the clinic.

Figure 2

Patient 1: an axial T2-weighted MR scan shows well-defined pathological solid mass originating from the alveolar process of the right maxilla.

Figure 3

Patient 1: histopathological examination of MNTI. (A) Neoplastic tissue surrounding developing tooth with a root resorption (HE, 40×); (B) Tumor composed of small hyperchromatic and bigger epithelioid pale cells’ islands embedded in mesenchymal stroma (HE, 400×); (C) Nests of small neuroectodermal cells rimmed with brown melanocytic cells (HE, 400×); (D) Pan-cytokeratin expression in epithelial population (CKAE1.AE3, 400×); (E) Synaptophysin staining with different intensity (synaptophysin, 200×); (F) Melanocytic marker HMB-45 within the pigmented cells (HMB-45, 200×); (G) Proliferative index up to 15% (Ki-67, 200×); (H) SOX10 nuclear expression within the tumor (SOX10, 200×).

Figure 4

Patient 1: an axial T2-weighted MR scan shows recurrence of MNTI in the postoperative area.

Figure 5

Patient 3: a sagittal T1-weighted MR scan shows large, suboccipital, mainly extracranial pathological solid mass compressing the spinal cord (C1–C3).

Figure 6

Flowchart of the study selection process (according to PRISMA 2020 guidelines).