Mandible / maxilla
Benign tumors / tumorlike conditions
Melanotic neuroectodermal tumor of infancy

Authors: Kelly Magliocca, M.D. and Anthony Martinez, M.D. (see Authors page)

Revised: 18 October 2017, last major update September 2017

Copyright: (c) 2004-2017, PathologyOutlines.com, Inc.

PubMed Search: Melanotic neuroectodermal tumor of infancy [title]

Cite this page: Magliocca, K. and Martinez, A. Melanotic neuroectodermal tumor of infancy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/mandiblemaxillaPigNEtumor.html. Accessed October 20th, 2017.
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
Terminology
  • Melanotic neuroectodermal tumor of infancy (MNTI)
  • Other synonyms the current WHO no longer recommends:
    • Melanotic progonoma
    • Retinal anlage tumor
Epidemiology
Sites
  • 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
    Diagnosis
    • Based on clinical, radiographic and pathologic features, but most important is biphasic components with histology
    Laboratory
    • 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
    Treatment
    • 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

    Images hosted on PathOut server, contributed by Dr. Karen Fritchie:

    H&E, 200x

    H&E, 400x

    AE1 / AE3, x100

    HMB45, 200x

    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 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 answer #1
    D. A is seen in Ewing sarcoma, C is seen in desmoplastic small round cell tumor, and D is seen in alveolar rhabdomyosarcoma