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Dermatology > DISEASES OF THE ORAL MUCOSA
Oral Neurofibroma
Article Last Updated: Aug 30, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 9  
Author: Indraneel Bhattacharyya, DDS, MSD, Assistant Professor, Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, Director of Oral Maxillofacial Pathology Residency Program, University of Florida, College of Dentistry
Indraneel Bhattacharyya is a member of the following medical societies: American Academy of Oral and Maxillofacial Pathology and American Dental Association
Coauthor(s):
Donald Cohen, DMD, MS, Professor of Oral and Maxillofacial Pathology, Department of Oral & Maxillofacial Surgery & Diagnostic Sciences, University of Florida College of Dentistry
Editors: Neil Shear, MD, Professor and Chief of Dermatology, Professor of Medicine, Pediatrics and Pharmacology, University of Toronto Medical School; Head of Dermatology, Sunnybrook Women's College Health Sciences Center, Canada; David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic; Drore Eisen, MD, DDS, Consulting Staff, Department of Dermatology, Dermatology Research Associates of Cincinnati; Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
Author and Editor Disclosure
Synonyms and related keywords:
neurofibromatosis, von Recklinghausen's disease of the skin, von Recklinghausen disease, fibroma molluscum
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.
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. Recently, 2 subsets have been defined: one is associated with the neurofibromatosis type 1 (NF1) gene, and the other is associated with the neurofibromatosis type 2 (NF2) gene.
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.
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 1-2).
- 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.
Lipomas
Neurilemoma
Other Problems to be Considered
Granular cell tumor
Fibroma
Scar tissue
Neurilemmoma (schwannoma)
Leiomyoma
Rhabdomyoma
Other benign mesenchymal entities
Diffuse neurofibroma (as sometimes seen with neurofibromatosis) may involve the tongue, resulting in macroglossia that may require differentiation from amyloidosis and lymphangioma.
Lab Studies
- A definitive diagnosis 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)
Histologic Findings
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.
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. 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.
Recently, 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.
Surgical Care
- Solitary oral neurofibromas are usually treated by surgical excision, depending on the extent and the site.
- However, for neurofibromas associated with neurofibromatosis, surgical removal is attempted only for functional or cosmetic reasons.
- Surgical removal may result in recurrence, and multiple recurrences have been associated with malignant transformation.
Consultations
Many authorities believe that any individual presenting with neurofibroma at an early age (<20 y) should be referred for genetic studies to rule out the possibility of neurofibromatosis. Consultation with a geneticist and a family physician may be critical in establishing a diagnosis of neurofibromatosis.
Further Outpatient Care
- Solitary neurofibromas are treated by surgical excision and exhibit very low recurrence. The patient should be instructed to report any new growth seen in the area or any abnormal sensations, such as tingling. These signs may signify a recurrence, and lesions may require repeat excision.
Deterrence/Prevention
- No special precaution is recommended for prevention of recurrence. Surgical excision is usually curative.
Complications
- A possible, although extremely rare, complication may be recurrence of the lesion.
- Other potential complications that may be seen are purely associated with surgical treatment and may include scarring and numbness.
Prognosis
- Usually, the prognosis for solitary neurofibroma is extremely good, with only rare instances of recurrence after resection; however, 5-15% exhibit malignant transformation of 1 or more lesions. This neurofibrosarcomatous change has an extremely poor prognosis, and distant metastasis is common. The average 5-year survival rate is only 15%.
| Media file 1:
Intrabony presentation of neurofibroma. Note the extensive bone destruction caused by the lesion. |
 |  View Full Size Image | |
Media type: X-RAY
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Oral Neurofibroma excerpt Article Last Updated: Aug 30, 2007
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