Mandible & maxilla

Other benign tumors / uncertain malignant potential tumors / tumor-like conditions

Melanotic neuroectodermal tumor of infancy

Last author update: 1 September 2017
Last staff update: 6 October 2022

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PubMed Search: Melanotic neuroectodermal tumor of infancy [title]

Kelly Magliocca, D.D.S., M.P.H.
Anthony Martinez, M.D.
Page views in 2022: 1,744
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Cite this page: Magliocca K, and Martinez A. Melanotic neuroectodermal tumor of infancy. website. Accessed September 21st, 2023.
Definition / general
  • A rare, locally aggressive biphasic tumor composed of a small round blue cell (neuroblast-like) component along with larger, melanin producing epithelioid cells
Essential features
  • A rapidly growing lesion in infants (usually in the first year of life) that can be associated with elevated VMA
  • Histologically is a biphasic tumor composed of a small round blue cell neuroblast-like component and larger, melanin producing epithelioid cells
  • Melanotic neuroectodermal tumor of infancy (MNTI)
  • Other synonyms the current WHO no longer recommends:
    • Melanotic progonoma
    • Retinal anlage tumor
  • Most cases occur in the craniofacial region, most commonly the maxilla ( > 60% of cases)
  • Testis and epididymis are most common sites outside head and neck
  • Rarely occurs in female reproductive tract
  • Etiology
    • Thought to be neural crest origin, based on:
      • Secretion of vanillylmandelic acid (VMA), characteristic of other neural crest tumors such as pheochromocytoma and neuroblastoma
      • VMA levels generally return to normal when excised
    Clinical features
    • Usually presents as a pigmented, rapidly expansile mass
    • Based on clinical, radiographic and pathologic features, but most important is biphasic components with histology
    • Can show elevated vanillylmandelic acid (VMA) levels
    Radiology images

    Images hosted on other servers:

    Presence of bone erosion

    Heterogenously enhancing soft tissue mass lesion

    Radiolucent expansile, solid lesion

    Prognostic factors
    Case reports
    • Complete local excision with clear margins
    • Adjuvant therapy for recurrent or residual tumor
    Clinical images

    Images hosted on other servers:

    Swelling on maxillary alveolus

    Upper vestibule, alveolar ridge and anterior hard palate

    Gross description
    • Lesions are usually gray to blue, firm and lobulated
    Gross images

    Images hosted on other servers:

    Excised tumor

    Microscopic (histologic) description
    • Biphasic population of cells composed of:
      • Nodules of round blue cells that are small and hyperchromatic with scant cytoplasm, often termed “neuroblastoma-like”
      • A second population of larger epithelioid cells arranged in cords and nests composed of abundant pale cytoplasm and round nuclei with vesicular chromatin
        • Within the cytoplasm is melanin pigment, although it can be focal and difficult to identify
    • The background consists of dense fibrosis creating the appearance of third component.
    Microscopic (histologic) images

    Contributed by Kelly Magliocca, D.D.S., M.P.H. and Karen Fritchie, M.D.
    Melanotic neuroectodermal tumor of infancy Melanotic neuroectodermal tumor of infancy Melanotic neuroectodermal tumor of infancy

    Melanotic neuroectodermal tumor of infancy

    AE1 / AE3

    AE1 / AE3



    Positive stains
    Negative stains
    Molecular / cytogenetics description
    Differential diagnosis
    • Ewing sarcoma
      • Only 2 - 10% develop in the head and neck
      • Small round blue cell tumor that grows in sheets and nests
        • Can have similar appearance to “neuroblast-like” component of MNTI, but lacks the epithelioid component
        • Should have rearrangements of EWSR1, unlike MNTI

    • Olfactory neuroblastoma
      • Most common during fifth and sixth decades
      • Typically involves the cribriform plate, nasal concha and septum
      • Also composed of small round blue cells
        • Can have Homer-Wright rosettes imparting biphasic morphology, but they are all the same population of cells
          • These will also stain with NSE and synaptophysin like the primitive component of MNTI
        • No epithelioid component with melanin pigment

    • Desmoplastic small round cell tumor
      • Rare, aggressive tumor, usually in abdomen of adolescents and young adults
        • More commonly affects men
      • Composed of nests of round blue cells with variable amounts of cytoplasm and hyperchromatic nuclei surrounded by desmoplastic stroma
      • Should not have the epithelioid component with melanin pigment
      • Also shows EWSR1 rearrangement as in Ewing sarcoma

    • Rhabdomyosarcoma
      • Individuals tend to be older at presentation than MNTI
      • More commonly involves sinonasal tract
      • Also composed of small primitive round blue cells but with scattered rhabdomyoblasts
      • Embryonal most common subtype in younger children
      • Should be positive for myogenic markers such as myogenin and myoD1
      • Should not have the epithelioid component with melanin pigment of MNTI

    • Lymphoma
      • Approximately 16% of NHLs involve the jawbones
        • 2/3 are diffuse large B cell lymphoma (DLBCL) which usually occur in an older age group
        • Main lymphoma mimics for MNTI are lymphoblastic lymphoma or Burkitt lymphoma, which feature monotonous, small to medium size round cells, without a biphasic component
        • Flow cytometry, immunohistochemistry (such as Tdt) and molecular studies would help classify and risk stratify the patient
    Board review style question #1
    What rearrangement has been described in melanotic neuroectodermal tumor of infancy?

    A. EWRS1-FLI1
    B. EWSR1-WT1
    C. PAX3-FOXO1
    D. RPLP1-C19MC
    Board review style answer #1
    D. RPLP1-C19MC has been described in one case of melanotic neuroectodermal tumor of infancy. EWRS1-FLI1 is seen in Ewing sarcoma, EWSR1-WT1 is seen in desmoplastic small round cell tumor and PAX3-FOXO1 is seen in alveolar rhabdomyosarcoma

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    Reference: Melanotic neuroectodermal tumor of infancy
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