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Oral Neurofibroma Workup

  • Author: Indraneel Bhattacharyya, DDS, MSD; Chief Editor: William D James, MD  more...
Updated: Sep 04, 2015

Laboratory Studies

A definitive diagnosis of oral neurofibroma can only be rendered after an incisional biopsy or an excisional biopsy followed by histopathologic examination.


Imaging Studies

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)

Other Tests

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.


Histologic Findings

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.

Contributor Information and Disclosures

Indraneel Bhattacharyya, DDS, MSD Professor, Department of Oral and Maxillofacial Diagnostic Sciences, Director of Oral and Maxillofacial Pathology Residency Program, University of Florida College of Dentistry

Indraneel Bhattacharyya, DDS, MSD is a member of the following medical societies: American Academy of Oral and Maxillofacial Pathology, American Dental Association, International Association for Dental Research, International Association of Oral Pathologists, American Association for Dental Research

Disclosure: Nothing to disclose.


Donald Cohen, DMD, MS Professor of Oral and Maxillofacial Pathology, Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry

Donald Cohen, DMD, MS is a member of the following medical societies: American Academy of Oral and Maxillofacial Pathology

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Drore Eisen, MD, DDS Consulting Staff, Department of Dermatology, Dermatology Research Associates of Cincinnati

Drore Eisen, MD, DDS is a member of the following medical societies: American Academy of Dermatology, American Academy of Oral Medicine, American Dental Association

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Neil Shear, MD Professor and Chief of Dermatology, Professor of Medicine, Pediatrics and Pharmacology, University of Toronto Faculty of Medicine; Head of Dermatology, Sunnybrook Women's College Health Sciences Center and Women's College Hospital, Canada

Neil Shear, MD is a member of the following medical societies: Canadian Medical Association, Ontario Medical Association, Royal College of Physicians and Surgeons of Canada, Canadian Dermatology Association, American Academy of Dermatology, American Society for Clinical Pharmacology and Therapeutics

Disclosure: Nothing to disclose.

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Intrabony presentation of neurofibroma. Note the extensive bone destruction caused by the lesion.
Multiple neurofibromas on the tongue.
Solitary neurofibroma on the hard palate.
An 11-year-old girl with an asymptomatic raised lesion on the anterior mandibular gingiva.
Isolated palatal lesion in a 27-year-old African American woman.
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