Melanotic Neuroectodermal Tumor of Infancy

Definition

• Biphasic pigmented neoplasm arising from the neural crest, typically involving the head and neck region of children usually age 1 year or younger

Alternate/Historical Names

• Melanotic progonoma
• Retinal anlage tumor
• Pigmented epulis
• Melanotic epithelial odontoma, melanotic adamantinoma, pigmented teratoma
• Pigmented, atypical, retinal, melano-ameloblastoma

Diagnostic Criteria

• Biphasic proliferation lf small and large cells
  • Small neuroblastic cells resemble those of neuroblastoma
    • Small dense nuclei with scant cytoplasm
  • Large melanin pigmented epithelioid cells
    • Large vesicular nuclei with prominent nucleoli
• Cells are set in a dense collagenous stroma
  • Present as cords, poorly formed tubules, and clusters of cells
    • Clusters are frequently discohesive with an alveolar pattern
  • Large and small cells may be in adjacent discrete nodules or mixed
    • Large cells frequently form an outer layer surrounding small cells
• Tumor may be grossly circumscribed but is usually invasive
• Over 90% occur during the first year of life
  • May be present at birth
• Over 90% occur in bones of the head and neck (see Clinical at left)
  • Maxilla is most common site, followed by mandible and skull
  • Most common peripheral site is epididymis
• Over 90% are benign if entirely resected (see Clinical at left)

Florette K. Gray Hazard MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 2/5/11

Supplemental studies

Immunohistology

• Predominant reactivity from literature given above
  • Even for these markers there is considerable variability in reports
• Infrequent to rare positive cases are reported for the following:
  • S100, CD99, Desmin, Actin, Myogenin, Chromogranin, GFAP, EMA, Neurofilaments
• NB84 negative - both populations

Genetic Study

• There is no specific cytogenetic translocation
  • A wide range of chromosomal abnormalities may be identified

Differential Diagnosis

• While the morphology suggests many “small” round blue cell tumors, the clinical context of a maxillary tumor in a newborn or infant narrows the differential diagnosis to include rhabdomyosarcoma, neuroblastoma and lymphoma
  • In such cases, immunohistochemistry may be required

	Nblast	ALL	Ewing Sarc (PNET)	Rhabdo	MNTI	DSCT	Wilms Tumor
Synapto	pos	neg	neg	neg	pos	neg	neg
NB84	pos	neg	neg	neg	neg	neg	neg
CD45RB (LCA)	neg	pos	neg	neg	neg	neg	neg
CD99	neg	pos	pos	neg	rare	neg	neg
Myogenin	neg	neg	neg	pos	rare	neg	neg
MyoD1	neg	neg	neg	pos	neg	neg	neg
Keratin	neg	neg	rare	rare	pos	pos	neg
Desmin	neg	neg	neg	pos	rare	pos	neg
WT1(C)	neg	neg	neg	neg	neg	pos	pos
S100	neg	neg	rare	neg	rare	neg	neg
HMB45	neg	neg	neg	neg	pos	neg	neg

Nblast = Neuroblastoma; ALL = Precursor T Lymphoblastic Leukemia; Rhabdo = Rhabdomyosarcoma; MNTI = Melanotic Neuroectodermal Tumor of Infancy; DSCT = Desmoplastic Small (Round) Cell Tumor; Synapto = Synaptophysin

• Identification of melanin positive cells may raise the differential of melanoma or of teratoma with retina differentiation
  • Melanoma is rare in infants, lacks the bipasic pattern containing neuroblastic cells and usually arises in the sinonasal mucosal lining, not the bones
  • Teratoma contains other differentiated elements and occurs intracranially rather than in the bones or in the testis rather than the epididymis

Clinical

• Rapidly growing painless lesion
• Over 90% involve the bones of the head
  • Up to 80% arise in the maxilla and/or palate

Maxilla	80%
Skull	10%
Mandible	5%
Brain	4%
Other (epididymis, ovary, mediastinum, etc…)	< 1%

• Over 90% occur within the first year of life
• Classically regarded as benign but may recur and infrequently metastasize
• Local recurrence rate 10-36%
  • Often associated with incomplete surgical removal
• Metastasis rate 5- 7%
  • Usually liver, bone, lymph nodes, spinal cord or brain

Classification / Lists

Small round blue cell tumors

• Cellular myxoid liposarcoma
• Desmoplastic small cell tumor
• Melanotic neuroectodermal tumor of infancy
• Mesenchymal chondrosarcoma
• Nephroblastoma
• Neuroblastoma
• Peripheral primitive neuroectodermal tumor
• Poorly differentiated synovial sarcoma
• Precursor B lymphoblastic leukemia / lymphoma
• Precursor T lymphoblastic leukemia / lymphoma
• Rhabdomyosarcoma
• Small cell osteosarcoma

Bibliography

• Barrett AW, Morgan M, Ramsay AD, et al:: A Clinicopathologic and Immunohistochemical Analysis of Melanotic Neuroectodermal Tumor of Infancy. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology & Endodontics 2002;93(6):688-698.
• Chaudhary A, Wakhlu A, Mittal N, et al:: Melanotic Neuroectodermal Tumor of Infancy: 2 Decades of Clinical Experience with 18 Patients. Journal of Oral and Maxillofacial Surgery 2009;67(1):47-51.
• Dehner LP. Skeletal System. IN: Dehner LP, Husain AN, Stocker JT, (eds) Pediatric Pathology, Third edition, Lippincott Williams & Wilkins, Philadelphia, 2011, 1190-1270.
• Ellison DA, Adada B, Qualman SJ, et al:: Melanotic Neuroectodermal Tumor of Infancy: Report of a Case with Myogenic Differentiation. Pediatric and Developmental Pathology 2007;10(2):157-160.
• Fowler DJ, Chisholm J, Roebuck D, et al:: Melanotic Neuroectodermal Tumor of Infancy: Clinical, Radiological, and Pathological Features. Fetal & Pediatric Pathology 2006;25(2):59-72.
• Gonçalves CF, Costa NdL, Oliveira-Neto HH, et al:: Melanotic Neuroectodermal Tumor of Infancy: Report of 2 Cases. Journal of Oral and Maxillofacial Surgery 2010;68(9):2341-2346.
• Kruse-Lösler B, Gaertner C, Bürger H, et al:: Melanotic Neuroectodermal Tumor of Infancy: Systematic Review of the Literature and Presentation of a Case. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 2006;102(2):204-216.
• Metwaly H, Cheng J, Maruyama S, et al:: Establishment and Characterization of New Cell Lines Derived from Melanotic Neuroectodermal Tumor of Infancy Arising in the Mandible. Pathology International 2005;55(6):331-342.
• Pettinato G, Manivel JC, d'Amore ESG, et al:: Melanotic Neuroectodermal Tumor of Infancy: A Reexamination of a Histogenetic Problem Based on Immunohistochemical, Flow Cytometric, and Ultrastructural Study of 10 Cases. The American Journal of Surgical Pathology 1991;15(3):233-245.
• Selim H, Shaheen S, Barakat K, et al:: Melanotic Neuroectodermal Tumor of Infancy: Review of Literature and Case Report. Journal of Pediatric Surgery 2008;43E25-E29.