eMedicine Specialties > Dermatology > Diseases of the Oral Mucosa
Oral Neurofibroma
Updated: Oct 7, 2009
Introduction
Background
Neurofibroma is an uncommon benign tumor of the oral cavity derived from the cells that constitute the nerve sheath. Neurofibroma is seen either as a solitary lesion or as part of the generalized syndrome of neurofibromatosis (usually neurofibromatosis type 1 [NF-1], also called von Recklinghausen disease of the skin). The solitary form does not differ from the disseminated form or the multiple form of the disease, except that systemic and hereditary factors present in the disseminated form are absent in the solitary type.
Oral cavity involvement by a solitary and peripheral plexiform neurofibroma in patients with no other signs of neurofibromatosis is uncommon. Sporadic cases have been reported in the submandibular gland, tongue, and on the periosteum at the mental foramen. This sporadic syndromic occurrence has also been seen in the cutaneous region, and several authors have suggested that these isolated neurofibromas may represent a hamartomatous growth.
The World Health Organization (WHO) has subdivided neurofibromas into 2 broad categories: dermal and plexiform. Dermal neurofibromas arise from a single peripheral nerve, while plexiform neurofibromas are associated with multiple nerve bundles. Other clinicopathologic subtypes include localized neurofibroma (sporadic neurofibroma), diffuse neurofibroma, plexiform neurofibroma, and epithelioid neurofibroma.
Localized or solitary neurofibroma is the most frequent manifestation and develops along a peripheral nerve as a focal mass with well-defined margins but not encapsulated. Localized or solitary neurofibroma is rare in infancy and typically appears in late childhood or during teenage years. The majority of isolated or solitary neurofibromas are sporadic, and a small minority may be associated with the NF-1 syndrome. Most of these arise in the third to fourth decades of life. Neurofibroma involving a major nerve, especially those encased in bone, such as the inferior alveolar nerve in the mandible, results in a fusiform expansion of the nerve canal—the so-called blunderbuss canal formation. Soft tissue growths are noted when smaller peripheral nerves are involved.1,2
Plexiform neurofibroma arises along peripheral nerves and tends to involve the smaller branches of the nerves, producing a poorly circumscribed and locally invasive tumor. Approximately 21% of patients with NF-I present with plexiform neurofibromas. These lesions can result in substantial morbidity, mainly due to their size and ability to cause disfigurement. Plexiform neurofibromas are considered to be pathognomonic of for NF-1. These lesions produce the classic "bag-of-worms" appearance. Occasionally, malignant transformation of plexiform neurofibroma is reported (<5%). This tumor is better designated as a malignant peripheral nerve sheath tumor (MPNST), which tends to exhibit a poor prognosis compared with nonsyndromic MPNSTs.
An uncommon variant of neurofibroma is the diffuse neurofibroma, which typically involves the skin and subcutaneous tissues, resulting in enlargement of affected tissues. Diffuse neurofibromas are most often seen in the head and neck region and may involve the oral cavity.3,4 These lesions are more common in adolescents or young adults. Malignant transformation of diffuse neurofibromas is rare, and rapid growth and careful microscopic examination of the biopsy sample is essential to rule out such a change. A minority of diffuse neurofibromas (<10%) are seen in the setting of NF-1.
Intrabony presentation of neurofibroma. Note the extensive bone destruction caused by the lesion.
Pathophysiology
The cell of origin for neurofibroma has not been definitively identified. Some believe it arises from the Schwann cell. Perineural fibroblasts are neuroectodermal tissue cells that synthesize collagen and create a network that envelops the individual axis cylinders of the nerves with their associated Schwann cells. Some investigators believe that perineural fibroblasts give rise to the neurofibroma.
The cause of solitary neurofibroma is unknown. However, neurofibromatosis is inherited as an autosomal dominant trait with a high degree of penetrance but variable expressivity. As many as 50% of cases are reported to be the result of spontaneous mutation. Two subsets have been defined: one is associated with the NF-1 (NF1) gene, and the other is associated with the neurofibromatosis type 2 (NF2) gene.5
Frequency
United States
Little information is available regarding the relative frequency of solitary oral neurofibromas and oral manifestations of neurofibromatosis. A survey of series on oral neurofibromas has reported that approximately 20-60% of cases are associated with neurofibromatosis. Intraoral neurofibromas may be seen in as many as 25% of patients with neurofibromatosis. Another review of head and neck neurofibromas reported that approximately 25% of all neurofibromas are seen in the head and neck region and 6.5% occur in the oral cavity as solitary or multiple lesions associated with NF-1.
Although these lesions may be seen anywhere in the oral cavity, the most common location of this tumor is the tongue. They have also been described on the gingiva, palate, major salivary glands, and maxillary bones.
Mortality/Morbidity
Solitary neurofibromas have a good prognosis, with only rare instances of local recurrence after excision. However, in neurofibromatosis, a larger proportion of patients develop recurrence after excision, and multiple recurrences are associated with malignant transformation. Spontaneous malignant transformation of 1 or more lesions is also reported. The rate of transformation is estimated to be 5-15%. This neurofibrosarcomatous change has an extremely poor prognosis, and distant metastasis is common. The average 5-year survival rate is dismal and ranges around 10-15%. A study involving 66 cases of head and neck neurofibromas reported that no recurrence of the neurofibromas was detected after surgical removal in approximately 33% of the patients during follow-up ranging from 3-230 months.
Race
No racial predilection is recognized for oral neurofibromas.
Sex
No sexual predilection has been described for oral neurofibromas.
Age
The average age of patients presenting with solitary neurofibromas is approximately 45 years; however, for intraoral neurofibromas associated with neurofibromatosis, the lesions may present at any age, with no specific bias.
Clinical
History
- Patients usually present with an uninflamed, slowly enlarging, asymptomatic lesion that varies greatly in size from tiny nodules to large pendulous masses.
- The lesion is rarely painful; however, patients may experience pain if the lesion is secondarily traumatized due to its location, eg, on the tongue or on the hard palate.
Physical
- Presentation
- Oral neurofibromas usually present as submucosal, nontender, discrete masses that range in size from a few millimeters to several centimeters (see Media Files 2-3).
Multiple neurofibromas on the tongue.
Solitary neurofibroma on the hard palate.
- The tumors tend to grow slowly, and patients are usually asymptomatic.
- Manifestations of neurofibromatosis specific to the oral cavity include enlarged fungiform papillae on the dorsum of the tongue and diffuse enlargement of the gingiva.
- In patients with mandibular involvement, enlargement of the inferior alveolar canal in the mandible and a flaring of the inferior alveolar foramen (the so-called blunderbuss foramen) have been reported.
- Oral manifestations may be seen in as many as 70% of patients with neurofibromatosis. Involvement of the trigeminal nerve may cause facial pain or paresthesia. Neurofibromatosis of the skin may present as multiple nodules or as a single pendulous mass.
- In patients with neurofibromatosis, extensive destruction of alveolar bone, mimicking periodontal bone loss, has been reported. This may be confused with routine periodontitis or other systemic disease. Owing to the potential systemic and genetic implications, the diagnosis of oral neurofibroma requires referral to the appropriate medical specialist to rule out the association with neurofibromatosis.
- The tongue, the buccal mucosa, and the vestibular areas are the most common sites of presentation.
- Rare cases of diffuse unilateral enlargement of gingiva have been reported in association with neurofibromatosis. In a recent case report, an 8-year-old child presented with gingival enlargement around all teeth of the right side of both jaws. This may resemble drug-induced gingival enlargement or gingival fibromatosis.
- Occasional cases of neurofibroma located centrally within the jaw have been reported. These intraosseous lesions may exhibit large sizes with a considerable expansion potential (see Media File 2).
Causes
The cause of these lesions is unknown; however, neurofibromatosis syndrome or the disseminated form is inherited as an autosomal dominant trait and may present with a variety of lesions, including a highly variable number of neurofibromas.
More on Oral Neurofibroma |
 Overview: Oral Neurofibroma |
| Differential Diagnoses & Workup: Oral Neurofibroma |
| Treatment & Medication: Oral Neurofibroma |
| Follow-up: Oral Neurofibroma |
| Multimedia: Oral Neurofibroma |
| References |
| Next Page » |
References
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. Jun 2007;11(2):165-9. [Medline].
Johann AC, Caldeira PC, Souto GR, Freitas JB, Mesquita RA. Extra-osseous solitary hard palate neurofibroma. Braz J Otorhinolaryngol. Mar-Apr 2008;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. Mar 2002;44(1):59-63. [Medline].
Vivek N, Manikandhan R, James PC, Rajeev R. Solitary intraosseous neurofibroma of mandible. Indian J Dent Res. Jul-Sep 2006;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. Oct 2006;45(10):893-904. [Medline].
Allen CM, Miloro M. Gingival lesion of recent onset in a patient with neurofibromatosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Dec 1997;84(6):595-7. [Medline].
Bekisz O, Darimont F, Rompen EH. Diffuse but unilateral gingival enlargement associated with von Recklinghausen neurofibromatosis: a case report. J Clin Periodontol. May 2000;27(5):361-5. [Medline].
Chrysomali E, Papanicolaou SI, Dekker NP, Regezi JA. Benign neural tumors of the oral cavity: a comparative immunohistochemical study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Oct 1997;84(4):381-90. [Medline].
Geist JR, Gander DL, Stefanac SJ. Oral manifestations of neurofibromatosis types I and II. Oral Surg Oral Med Oral Pathol. Mar 1992;73(3):376-82. [Medline].
Gutmann DH, Aylsworth A, Carey JC, et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. Jul 2 1997;278(1):51-7. [Medline].
Marocchio LS, Pereira MC, Soares CT, Oliveira DT. Oral plexiform neurofibroma not associated with neurofibromatosis type I: case report. J Oral Sci. Sep 2006;48(3):157-60. [Medline].
Neville BW, Hann J, Narang R, Garen P. Oral neurofibrosarcoma associated with neurofibromatosis type I. Oral Surg Oral Med Oral Pathol. Oct 1991;72(4):456-61. [Medline].
Powell CA, Stanley CM, Bannister SR, McDonnell HT, Moritz AJ, Deas DE. Palatal neurofibroma associated with localized periodontitis. J Periodontol. Feb 2006;77(2):310-5. [Medline].
Regezi JA, Sciubba JJ. Connective tissue lesions. In: Oral Pathology: Clinical Pathologic Correlations. 3rd ed. Philadelphia, Pa: WB Saunders; 1999:204-8.
Shapiro SD, Abramovitch K, Van Dis ML, et al. Neurofibromatosis: oral and radiographic manifestations. Oral Surg Oral Med Oral Pathol. Oct 1984;58(4):493-8. [Medline].
Skouteris CA. Incidence of solitary intraosseous neurofibroma of the maxilla. J Oral Maxillofac Surg. Feb 1994;52(2):205-6. [Medline].
Wright BA, Jackson D. Neural tumors of the oral cavity. A review of the spectrum of benign and malignant oral tumors of the oral cavity and jaws. Oral Surg Oral Med Oral Pathol. Jun 1980;49(6):509-22. [Medline].
Zachariades N, Mezitis M, Vairaktaris E, et al. Benign neurogenic tumors of the oral cavity. Int J Oral Maxillofac Surg. Feb 1987;16(1):70-6. [Medline].
Further Reading
Keywords
oral neurofibroma, neurofibroma, neurofibromatosis, von Recklinghausen's disease of the skin, von Recklinghausen disease, fibroma molluscum
