Oral Neurofibroma Workup
- Author: Indraneel Bhattacharyya, DDS, MSD; Chief Editor: William D James, MD more...
A definitive diagnosis of oral neurofibroma can only be rendered after an incisional biopsy or an excisional biopsy followed by histopathologic examination.
Magnetic resonance patterns for neurofibromas are characteristic. Patterns include the following:
Low-to-intermediate signal intensity on T1-weighted images
Enhancement of the solid component of the tumor after administration of contrast medium
Heterogeneity on T2-weighted images
Multiple target signs due to a central collagen area (some patients)
Cytogenetic testing for neurofibromatosis is discussed in detail in other articles (eg, Neurofibromatosis, Type 1, Neurofibromatosis, Neurofibromatosis). In short, unbalanced t(2;19) and unbalanced t(2;16) translocations have been identified.
The NF1 or neurofibromin 1 gene product has been identified and is located on the band 17q11.2. This gene product acts a negative regulator of the ras signal transduction pathway. More information on the gene and its products can be found on the public domain at Entrez Gene.
Macroscopically or grossly, neurofibromas appear to display a doughy consistency with a shiny, whitish surface.
Histopathologies of solitary and multiple neurofibromas are essentially identical. Neurofibromas contain spindle-shaped cells, with fusiform or wavy comma-shaped nuclei distributed on a background of delicate connective tissue matrix. This matrix is rich in mucopolysaccharides and is usually myxomatous. The lesion may be well circumscribed, or it may be diffuse with no apparent margins. Mast cells are usually scattered within the specimen.
In neurofibromatosis, a plexiform pattern may be predominant in which distorted masses of myxomatous peripheral nerve tissue still within the perineural sheath are scattered within a collagen-rich matrix. This histologic picture is considered to be virtually diagnostic of neurofibromatosis, even in the absence of other manifestations.
The histologic spectrum of neurofibromas includes interlacing bundles of cells with ovoid-to-spindle, often curved nuclei within a myxocollagenous background containing ropey collagen bundles. Plexiform neurofibroma, which is considered pathognomonic for neurofibromatosis type 1 (NF-1) exhibits multifocal, well-circumscribed, tortuous aggregates of neural tissue distributed in a myxoid matrix. Foci of possible nuclear atypia may be seen and should be carefully examined to rule out malignant transformation.
Diffuse neurofibroma presents with an ill-defined infiltration of neoplastic neural tissue into underlying connective tissue and consists of a matrix of fine fibrillary collagen with spindle-shaped or fusiform or rounded Schwann cells. Occasionally, clusters of Meissner body–like structures may be seen, which are helpful in the diagnosis. Diffuse neurofibromas occur more frequently than the plexiform type.
Immunohistochemistry is often used to aid in confirming the diagnosis made by using histologic findings. The lesional cells are uniformly positive for S-100 protein, signifying that they originate from neural crest–derived tissue. Immunopositivity for S-100 protein is seen in 85-100% of the cases. Antibodies to epithelial membrane antigen, CD57, and collagen IV are of secondary value and are used only when histologic differentiation with other neural tumors is difficult.
A rare variant of solitary neurofibroma with a large adipose tissue content has been reported. This lipomatous neurofibroma manifested as a solitary mucosal mass on the palatal gingiva. Based on limited biopsy material, it was initially diagnosed as a spindle cell lipoma; however, a subsequent review of the resected lesion revealed characteristic neurofibromatous areas, intricately admixed with mature adipose tissue. Immunohistochemically, many of the spindle cells were positive for common neural markers, with patchy staining for CD34 and epithelial membrane antigen. S-100 protein was also positive in adipocytes. Ultrastructural examination confirmed the diagnosis of neurofibroma.
Depprich R, Singh DD, Reinecke P, Kübler NR, Handschel J. Solitary submucous neurofibroma of the mandible: review of the literature and report of a rare case. Head Face Med. Nov/2009. 13;5:24.:24. [Medline]. [Full Text].
Marocchio LS, Oliveira DT, Pereira MC, Soares CT, Fleury RN. Sporadic and multiple neurofibromas in the head and neck region: a retrospective study of 33 years. Clin Oral Investig. 2007 Jun. 11(2):165-9. [Medline].
Johann AC, Caldeira PC, Souto GR, Freitas JB, Mesquita RA. Extra-osseous solitary hard palate neurofibroma. Braz J Otorhinolaryngol. 2008 Mar-Apr. 74(2):317. [Medline].
Shimoyama T, Kato T, Nasu D, Kaneko T, Horie N, Ide F. Solitary neurofibroma of the oral mucosa: a previously undescribed variant of neurofibroma. J Oral Sci. 2002 Mar. 44(1):59-63. [Medline].
Vivek N, Manikandhan R, James PC, Rajeev R. Solitary intraosseous neurofibroma of mandible. Indian J Dent Res. 2006 Jul-Sep. 17(3):135-8. [Medline].
De Raedt T, Maertens O, Chmara M, et al. Somatic loss of wild type NF1 allele in neurofibromas: Comparison of NF1 microdeletion and non-microdeletion patients. Genes Chromosomes Cancer. 2006 Oct. 45(10):893-904. [Medline].
Gomez-Oliveira G, Fernandez-Alba Luengo J. Martin-Sastre R, Patino-Seijas B, Lopez-Cedrun-Cembranos JL. Plexiform neurofibroma of the cheek mucosa. A case report. Med oral. May-Jul 2004. 9:263-7. [Medline]. [Full Text].