Melanotic neuroectodermal tumor of infancy is a very rare oral cavity

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

that is seen in patients usually at or around birth. It must be removed to be cured. Definitions: A rare, biphasic, neuroblastic, and

pigment A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at some stage in their use. Generally dyes are often organic compounds whereas pigments are often inorganic compo ...

epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

of craniofacial sites, usually involving the oral cavity or

gums The gums or gingiva (plural: ''gingivae'') consist of the mucosal tissue that lies over the mandible and maxilla inside the mouth. Gum health and disease can have an effect on general health. Structure The gums are part of the soft tissue linin ...

Signs and symptoms

Most patients present with a very rapidly growing mass that often gives a bluish appearance in the mouth. This is because the pigmentation in the cells appears blue through the overlying epithelium (mucosa). By imaging studies, there is usually a large expansive

radiolucent Radiodensity (or radiopacity) is opacity to the radio wave and X-ray portion of the electromagnetic spectrum: that is, the relative inability of those kinds of electromagnetic radiation to pass through a particular material. Radiolucency or hypod ...

(clear) mass without well defined borders.

Calcification Calcification is the accumulation of calcium salts in a body tissue. It normally occurs in the formation of bone, but calcium can be deposited abnormally in soft tissue,Miller, J. D. Cardiovascular calcification: Orbicular origins. ''Nature Mat ...

s within the mass may be seen. More than 70% involve the

maxilla The maxilla (plural: ''maxillae'' ) in vertebrates is the upper fixed (not fixed in Neopterygii) bone of the jaw formed from the fusion of two maxillary bones. In humans, the upper jaw includes the hard palate in the front of the mouth. The t ...

(usually maxillary anterior alveolar ridge), while the

mandible In anatomy, the mandible, lower jaw or jawbone is the largest, strongest and lowest bone in the human facial skeleton. It forms the lower jaw and holds the lower tooth, teeth in place. The mandible sits beneath the maxilla. It is the only movabl ...

and skull are affected less often. There is often an elevated vanilmandelic acid level.

Pathogenesis

It is considered to be a developmental anomaly, and thus is

congenital A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

in presentation. It is thought to be derived from neural crest, which is one of the embryologic tissue types. The reason for this postulation is based on the expression of

melanotransferrin Melanotransferrin is a protein that in humans is encoded by the ''MFI2'' gene. MFI2 has also recently been designated CD228 (cluster of differentiation 228). The protein encoded by this gene is a cell-surface glycoprotein found on melanoma cells. ...

(melanoma-specific peptide that may play role in iron metabolism).

Diagnosis

Macroscopic

Usually there is a smooth, firm mass, with mottled white-gray to blue-black cut surfaces. The overall size ranges from 1–10 cm with a mean size 3.5 cm.

Microscopic

The tumor is usually very well

circumscribed In geometry, the circumscribed circle or circumcircle of a polygon is a circle that passes through all the vertices of the polygon. The center of this circle is called the circumcenter and its radius is called the circumradius. Not every polyg ...

but not encapsulated. There are two cell types present (biphasic), arranged in alveolar or tubular configurations. There are centrally located, small, darkly staining cells comprising the majority of cells. These cells have a fibrillary cytoplasm surrounding round nuclei with coarse and heavy nuclear chromatin. These cells are surrounded by much larger polygonal cells that have open nuclear chromatin and abundant opaque cytoplasm that has granular melanin pigment. There is usually no hemorrhage, necrosis or increased mitoses.

Immunohistochemistry

The lesional cells will show cross reactivity with several different families of

immunohistochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...

markers (polyphenotypic), including neural, melanocytic, and epithelial. * Large tumor cells:

Keratin Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ho ...

vimentin Vimentin is a structural protein that in humans is encoded by the ''VIM'' gene. Its name comes from the Latin ''vimentum'' which refers to an array of flexible rods. Vimentin is a type III intermediate filament (IF) protein that is expressed ...

HMB-45 HMB-45 is a monoclonal antibody that reacts against an antigen present in melanocyte, melanocytic tumors such as melanomas, and stands for Human Melanoma Black. It is used in anatomic pathology as a marker for such tumors. The specific antigen reco ...

, NSE,

CD57 3-beta-glucuronosyltransferase 1 (B3GAT1) is an enzyme that in humans is encoded by the ''B3GAT1'' gene, whose enzymatic activity creates the CD57 epitope on other cell surface proteins. In immunology, the CD57 antigen (CD stands for cluster of di ...

* Small tumor cells:

Synaptophysin Synaptophysin, also known as the major synaptic vesicle protein p38, is a protein that in humans is encoded by the ''SYP'' gene. Genomics The gene is located on the short arm of X chromosome (Xp11.23-p11.22). It is 12,406 bases in length and ...

, GFAP, NSE, CD57 * There is usually a variable expression of EMA and S100 protein.

Differential diagnoses

It is important in this age group to exclude other tumors that can have a similar appearance, such as rhabdomyosarcoma, lymphoma, Ewing sarcoma (primitive neuroectodermal tumor), or even a melanoma (although they are very very rare in infants).

Management

Even though there is often a very dramatic and rapidly enlarging, destructive tumor, there is usually a benign clinical course after complete local excision (usually by partial maxillectomy) with clear or free surgical margins. In rare cases, chemotherapy may be used for recurrent or residual tumors. Overall, the outcome is good, although it is quite unpredictable, with about 30% of patients have a recurrence. In about 10% of cases, metastasis may be seen (lymph nodes, liver, bone and soft tissue).

Epidemiology

This tumor is extremely rare, with fewer than 500 cases reported world wide. More than 95% of patients are less than 1 year of age at presentation, with about 80% less than 6 months. Females are affected more often than males (2:1).

References

External links

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