Author: Indraneel Bhattacharyya, DDS, MSD; Chief Editor: William D James, MD more...
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1 Medscape Reference Reference News Reference Education MEDLINE Oral Neurofibroma Author: Indraneel Bhattacharyya, DDS, MSD; Chief Editor: William D James, MD more... Updated: Aug 1, 2011 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. Multiple neurofibromas have also been strongly associated with the polyglandular syndrome multiple endocrine neoplasia type 3 (MEN-3). [1] 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 [2, 3] formation. Soft tissue growths are noted when smaller peripheral nerves are involved. 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. Pagina 1 di 5
2 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. [4, 5] 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. [6] Epidemiology 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 months. Race No racial predilection is recognized for oral neurofibromas. Sex Pagina 2 di 5
3 No sexual predilection has been described for oral neurofibromas. Age The average age of patients presenting with solitary neurofibromas ranges from 10 months to 70 years, with an average of approximately 45 years; however, for intraoral neurofibromas associated with neurofibromatosis, the lesions may present at any age, with no specific bias. [7] Contributor Information and Disclosures Author Indraneel Bhattacharyya, DDS, MSD Associate Professor, Department of Oral and Maxillofacial Diagnostic Sciences, Director of Oral & 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 Association for Dental Research, American Dental Association, International Association for Dental Research, and International Association of Oral Pathologists Coauthor(s) 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 Specialty Editor Board 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: American Academy of Dermatology, American Society for Clinical Pharmacology and Therapeutics, Canadian Dermatology Association, Canadian Medical Association, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada David F Butler, MD 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: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa 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, and American Dental Association Glen H Crawford, MD Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy Pagina 3 di 5
4 of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons 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 and Society for Investigative Dermatology References 1. 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]. 2. 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): [Medline]. 3. 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]. 4. 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): [Medline]. 5. Vivek N, Manikandhan R, James PC, Rajeev R. Solitary intraosseous neurofibroma of mandible. Indian J Dent Res. Jul-Sep 2006;17(3): [Medline]. 6. 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): [Medline]. 7. 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: [Medline]. [Full Text]. 8. 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): [Medline]. 9. 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): [Medline]. 10. 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): [Medline]. 11. Geist JR, Gander DL, Stefanac SJ. Oral manifestations of neurofibromatosis types I and II. Oral Surg Oral Med Oral Pathol. Mar 1992;73(3): [Medline]. 12. Gutmann DH, Aylsworth A, Carey JC, et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. Jul ;278(1):51-7. [Medline]. 13. 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): [Medline]. 14. 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): [Medline]. 15. Powell CA, Stanley CM, Bannister SR, McDonnell HT, Moritz AJ, Deas DE. Palatal neurofibroma Pagina 4 di 5
5 associated with localized periodontitis. J Periodontol. Feb 2006;77(2): [Medline]. 16. Regezi JA, Sciubba JJ. Connective tissue lesions. In: Oral Pathology: Clinical Pathologic Correlations. 3 rd ed. Philadelphia, Pa: WB Saunders; 1999: Shapiro SD, Abramovitch K, Van Dis ML, et al. Neurofibromatosis: oral and radiographic manifestations. Oral Surg Oral Med Oral Pathol. Oct 1984;58(4): [Medline]. 18. Skouteris CA. Incidence of solitary intraosseous neurofibroma of the maxilla. J Oral Maxillofac Surg. Feb 1994;52(2): [Medline]. 19. 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): [Medline]. 20. 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]. Medscape Reference 2011 WebMD, LLC Pagina 5 di 5
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