- Email: [email protected]
Solitary oral plexiform neurofibroma: Review of literature and report of a case
Oral Oncology 47 (2011) 449–451
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Review
Solitary oral plexiform neurofibroma: Review of literature and report of a case N.P. Zwane a, C.E.E. Noffke a,⇑, E.J. Raubenheimer b a b
Radiology Unit, School of Oral Health Sciences, Faculty of Health Sciences, Medunsa Campus, University of Limpopo, 0204, South Africa Pathology Unit, School of Oral Health Sciences, Faculty of Health Sciences, Medunsa Campus, University of Limpopo, 0204, South Africa
a r t i c l e
i n f o
Article history: Received 11 February 2011 Received in revised form 14 April 2011 Accepted 14 April 2011 Available online 14 May 2011
s u m m a r y Plexiform neurofibroma (PN) is a rare, benign tumor of nerve sheath origin, which frequently manifests as part of neurofibromatosis type 1. The article presents a case of solitary PN in a 4-year-old girl, which manifested as a double lip and without systemic or familial involvement. A review of the literature on solitary PN in the oral soft tissue demonstrates the scarcity of such cases. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Neoplasm Oral mucosa Neurofibroma von Recklinghausen’s disease
Introduction Plexiform neurofibroma (PN) is an unusual histological variant of neurofibroma (NF) and is described as a benign tumor of nerve sheath origin involving multiple nerve fascicles of the smaller branches of peripheral nerves.1,2 PN can be sporadic without systemic or familial involvement. More frequently, however, the condition is generalized as part of neurofibromatosis type 1 (NF1), the most common form of neurofibromatosis.3 The presence of PN is considered pathognomonic for NF1, which is also referred to as ‘‘von Recklinghausen’s disease of the skin’’.4 Although PN is a dermatologic disorder, it may rarely affect the oral cavity where it has been described in the tongue,5,6 oropharynx6 and cheek mucosa.7 Some cases in the head and neck region of children affected the major salivary glands.8–10 Like their skin counterpart, oral solitary PN are uncommon and those reported are most frequently associated with neurofibromatosis type 1. Solitary cases were described in the maxillary sinus, pterygopalatine fossa and the vestibular side of the mandible.11–13 The solitary plexiform neurofibroma probably represents the segmental form of NF1 due to a later somatic mutation.14 This article presents a case of a solitary PN which manifested as a double lower lip in a 4-year-old black girl. The case is unusual in that no clinical signs, features or family history of NF1 could be demonstrated. To our knowledge, only few cases of solitary PN
⇑ Corresponding author. Address: Radiology Unit, School of Oral Health Sciences, University of Limpopo, P.O. Box D17, Medunsa Campus, 0204, South Africa. Tel.: +27 (0)12 521 4902/3; fax: +27 (0)12 521 5901. E-mail address: [email protected] (C.E.E. Noffke). 1368-8375/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.oraloncology.2011.04.005
without a family history or clinical signs associated with NF1 have been described in the oral cavity.11–13,15–17
Case report A 4-year-old female patient presented in the MEDUNSA Oral Health Center with a complaint of a gradual painless swelling of long duration on the inside of the lower lip. Her medical- and dental history was uneventful and there was no facial asymmetry. Upon retraction of the lower lip excess mucosal tissue on the inside of the lip was noticed which presented as a fold of tissue in the vestibular sulcus measuring 2 cm and resembling a double lip (Fig. 1). The mucosa overlying the alveolar bone appeared normal with no ulcerations or mucosal discoloration. The teeth appeared to be healthy and with palpation the lesion was non-pulsating and had a rubbery consistency. Radiographs showed a mixed dentition with a normal eruption sequence and healthy bone. The clinical differential diagnosis included double lip caused by Ascher syndrome and neoplastic disease. The patient’s medical history was insignificant. The case presented initially as a double lower lip, a rare acquired or congenital oral anomaly18 characterized by a redundant fold of tissue on the mucosal side of the lip. Double lip is associated with Ascher syndrome, a congenital condition that presents with a triad of blepharochalasis (a redundancy of eyelid skin), nontoxic thyroid enlargement and double lip.18–20 Due to the absence of blepharochalasis and goiter enlargement, Ascher syndrome was excluded in the initial differential diagnosis. The patient’s medical history was insignificant. Trauma due to lip biting or other habits were excluded in the differential diagnosis as no ulceration or signs
450
N.P. Zwane et al. / Oral Oncology 47 (2011) 449–451
Figure 1 Extra mucosal fold with the appearance of a double lip in the anterior vestibular sulcus.
Figure 2 Micrograph showing the histological features of a plexiform neurofibroma. Note the swollen nerve bundles in a fibrous stroma (H & E stain, magnification 200).
of inflammation were present. The non-compressibility and normal mucosal colour excluded a diagnosis of a hemangioma which would have been a contra indication for a biopsy procedure. Microscopic examination of the biopsy established a diagnosis of plexiform neurofibroma (PN) (Fig. 2), and the patient was referred for surgical management.
two or more neurofibromas of any type or one PN, two or more Lisch nodules (brown spots on the iris), optic glioma, distinctive osseous bony dysplasia (such as sphenoid wing dysplasia or thinning of the long bone cortex) and involvement of a close family member with NF1 by these criteria.24,25 Oral lesions in NF1 patients are found in almost 72% of the cases21 but only a few cases have been described in detail in the literature.25–27 Typically, radiologic manifestations include enlargement of the mandibular foramen and/or canal, increased bone density, a deep coronoid notch, concavity of the medial surface of the ramus as well as multiple radiolucencies.27,28 PN is commonly diagnosed in children and rarely after adolescence.2,24 It can involve superficial tissue or deeper tissue and the most common site is the trunk (43%), head and neck area (42%) and limbs (15%).2 The tumor is described as gradually progressive, locally invasive and often disfiguring.24 Due to neurovascular involvement with nerve compression loss of function is possible. In general, PN causes diffuse nodular enlargement of a nerve and its branches by a proliferation of Schwann cells in the nerve sheath across the length of a nerve.1,24 This characteristic was absent in our case. These nodular masses are classically described as a ‘‘bag of worms’’ upon palpation.1,24 The formation of PNs in the connective tissue of the submucosa caused a soft tissue overgrowth which presented as a double lip in our case. Our case is unusual as its presentation was sporadic and without a family history. Although none of the abovementioned diagnostic features indicative of NF1 were present, follow up is indicated as some of these manifestations may develop in later life. Unilateral gingival enlargement associated with NF1 has been described in a patient with gingival neurofibroma in the attached gingiva of the lingual aspect of the lower central incisors.26 To our knowledge, only few other cases of isolated PN without a family history or clinical signs associated with NF1 have been described in the oral cavity.10,13,15–17,29 It is recorded that, contrary to sporadic localized PNs, those associated with NF1 tend to be larger, multiple and involve deep nerves.16,30 The PN’s associated with NF1 have the potential to undergo sarcomatous change towards neurofibrosarcoma, or malignant schwannoma, which are the main cause of death in this group of patients.2,4 The solitary type of PN, however rarely undergoes sarcomatous change and for this reason follow-up with the late development of features of NF1 is important.4 Solitary lesions should be treated with excision and recurrence is rare.4,31 Conclusion We present a case of solitary PN, which manifested as a double lip in a 4-year-old girl, and reviewed similar cases reported in the literature. Follow-up of patients with solitary PNs is advised in order to identify ancillary clinical features of NF1 that may become evident in later life. Conflicts of interest statement
Discussion Neurofibromatosis type 1 (NF1), is the most common form of neurofibromatosis and accounts for about 90% of all cases21 with a prevalence of 1 in 3000–3500 persons worldwide.21–23 The condition may be inherited as an autosomal dominant trait or, in rare cases, represents a sporadic localized mutation4 of the NF1 tumor suppressor gene which encodes the protein neurofibromin.22 The diagnosis of NF1 requires at least two of the following clinical criteria: six or more café au lait macules on the skin which present as brownish smooth-edged pigmentation and can be present at birth or during the first year of life, axillary or inguinal freckling,
None declared. References 1. Citak EC, Oguz A, Karadeniz C, Okur A. Management of plexiformneurofibroma with interferon alpha. Am J Pediatr Hematol Oncol 2008;25:673–8. 2. Geller M, Darrigo Junior LG, Filbo AB, Ribeiro MG. Plexiformneurofibroma in the ear canal of a patient with Type 1 neurofibromatosis. Braz J Otorhinolaryngol 2009;75(1):158. 3. Powell CA, Stanley CM, Bannister SR, McDonnel HT, Morits AJ, Deas DE. Palatal neurofibroma associated with localized periodontitis. J Periodontol 2006;77(2):310–5. 4. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 2nd ed. Philadelphia: WB Saunders Company; 2002.
N.P. Zwane et al. / Oral Oncology 47 (2011) 449–451 5. Güneri EA, Akoglu E, Sütay S, Ceryan K, Sagol O, Pabuccuoglu U. Plexiformneurofibroma of the tongue: a case report of a child. Turk J Pediatr 2006;48(2):155–8. 6. Sharma SC, Srinivasan S. Isolated plexiformneurofibroma of tongue and oropharynx: a rare manifestation of von Recklinghausen’s disease. J Otolaryngol 1998;27(2):81–4. 7. Oliveira G, Luengo J, Sastre R, Seijas B, Cembranos JL. Plexiformneurofibroma of the cheek mucosa. A case report. Med Oral 2004;9(3):263–7. 8. Weitzner S. Plexiformneurofibroma of major salivary glands in children. Oral Surg 1986;50:53–7. 9. Almela CR, Faubel SM, Cueva RC, Conde PI. Intra-parotid facial plexiformneurofibroma. Review of the literature. An Otorrinolaringol Ibero Am 2001;28(4):363–70. 10. Souaid JP, Nguyen VH, Zeitouni AG, Manoukian J. Intraparotid facial nerve solitary plexiformneurofibroma: a first paediatric case report. Int J Pediatr Otorhinolaryngol 2003;67(10):1113–5. 11. Boedeker CC, Ridder GJ, Kayser G, Schipper J, Maier W. Solitary neurofibroma of the maxillary sinus and pterygopalatine fossa. Otolaryngol Head Neck Surg 2005;133(3):458–9. 12. Robitaille Y, Seemayer TA, El Deiry A. Peripheral nerve tumors involving paranasal sinuses: a case report and review of the literature. Cancer 1975;35(4):1254–8. 13. Alatli C, Oner B, Unür M, Erseven G. Solitary plexiformneurofibroma of the oral cavity. A case report. Int J Oral Maxillofac Surg 1996;25(5):379–80. 14. Ruggieri M, Huson SM. The clinical and diagnostic implications of mosaicism in the neurofibromatoses. Neurology 2001;56(11):1433–43. 15. Marocchio LS, Pereira MC, Soares CT, Oliveira D. Oral plexiformneurofibroma not associated with neurofibromatosis type 1: case report. J Oral Sci 2006;48(3):157–60. 16. Lin V, Daniel S, Forte V. Is a plexiformneurofibroma pathognomonic of neurofibromatosis type 1? Laryngoscope 2004;114(8):1410–4. 17. Tsutsumi T, Oku T, Komatsuzaki A. Solitary plexiformneurofibroma of the submandibular salivary gland. J Laryngol Otol 1996;110(12):1173–5. 18. Martins WD, Westphalen FH, Sandrin R, Campagnoli E. Congenital maxillary double lip: review of the literature and report of a case. J Can Dent Assoc 2004;70(7):466–8.
451
19. Kruk-Jeromin J, Pisera P. Diagnostic and treatment protocol of Ascher syndrome. Pol Przegl Chir 2006;78:1323–31. 20. Atzeni M, Ceratola E, Zaccheddu F, Manca A, Saba L, Ribuffo D. Surgical correction and MR imaging of double lip in Ascher syndrome: Record of a case and a review of the literature. Eur Rev Med Pharmacol Sci 2009;13(4):309–11. 21. Cunha KSG, Baroza EP, Dias EP, Oliveira FM. Neurofibromatosis type 1 with periodontal manifestation. A case report and literature review. Br Dent J 2004;196(8):457–60. 22. Staser K, Yang Feng-Chun, Clapp DW. Mast cells and the neurofibroma microenvironment. Blood 2010;116(2):157–64. 23. Staser JM, Yang F-C, Clapp DW. Plexiformneurofibroma genesis: questions of Nf1 gene dose and hyperactive mast cells. Curr Opin Hematol 2010;17:287–93. 24. Sehgal VN, Sharma S, Oberai R. Evaluation of plexiformneurofibroma in neurofibromatosis type 1 in 18 family members of 3 generations: ultrasonography and magnetic resonance imaging a diagnostic supplement. Int J Dermatol 2009;48:275–9. 25. Mulvihill JJ, Parry DM, Sherman JL, et al. NIH conference. Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis). An update. Ann Intern Med 1990;113(1):39–52. 26. Bekisz O, Darimont F, Rompen EH. Diffuse but unilateral gingival enlargement associated with von Recklinghausen neurofibromatosis: a case report. J Clin Periodontol 2000;27(5):361–5. 27. Kaplan I, Calderon S, Kaffe I. Radiological findings in jaws and skull of neurofibromatosis type 1 patients. Dentomaxillofac Radiol 1994;23(4): 216–20. 28. Hisatomi M, Asaumi J, Konouchi H, Yanagi Y, Kishi K. Bone deformity showing a deep coronoid notch of the mandible in a patient with neurofibromatosis type 1. Dentomaxillofac Radiol 2005;34(6):380–3. 29. Malcolm EK, Lopes MB. 35-year-old healthy man with enlarging right parotid mass. Brain Pathol 2002;12(4):515–21. 30. Friedman JM. Neurofibromatosis type 1: clinical manifestations and diagnostic criteria. J Child Neurol 2002;17(8):548–54. 31. Ferner RE, O’Doherty MJ. Neurofibroma and schwannoma. Curr Opin Neurol 2002;15(6):679–84.
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Review
Solitary oral plexiform neurofibroma: Review of literature and report of a case N.P. Zwane a, C.E.E. Noffke a,⇑, E.J. Raubenheimer b a b
Radiology Unit, School of Oral Health Sciences, Faculty of Health Sciences, Medunsa Campus, University of Limpopo, 0204, South Africa Pathology Unit, School of Oral Health Sciences, Faculty of Health Sciences, Medunsa Campus, University of Limpopo, 0204, South Africa
a r t i c l e
i n f o
Article history: Received 11 February 2011 Received in revised form 14 April 2011 Accepted 14 April 2011 Available online 14 May 2011
s u m m a r y Plexiform neurofibroma (PN) is a rare, benign tumor of nerve sheath origin, which frequently manifests as part of neurofibromatosis type 1. The article presents a case of solitary PN in a 4-year-old girl, which manifested as a double lip and without systemic or familial involvement. A review of the literature on solitary PN in the oral soft tissue demonstrates the scarcity of such cases. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Neoplasm Oral mucosa Neurofibroma von Recklinghausen’s disease
Introduction Plexiform neurofibroma (PN) is an unusual histological variant of neurofibroma (NF) and is described as a benign tumor of nerve sheath origin involving multiple nerve fascicles of the smaller branches of peripheral nerves.1,2 PN can be sporadic without systemic or familial involvement. More frequently, however, the condition is generalized as part of neurofibromatosis type 1 (NF1), the most common form of neurofibromatosis.3 The presence of PN is considered pathognomonic for NF1, which is also referred to as ‘‘von Recklinghausen’s disease of the skin’’.4 Although PN is a dermatologic disorder, it may rarely affect the oral cavity where it has been described in the tongue,5,6 oropharynx6 and cheek mucosa.7 Some cases in the head and neck region of children affected the major salivary glands.8–10 Like their skin counterpart, oral solitary PN are uncommon and those reported are most frequently associated with neurofibromatosis type 1. Solitary cases were described in the maxillary sinus, pterygopalatine fossa and the vestibular side of the mandible.11–13 The solitary plexiform neurofibroma probably represents the segmental form of NF1 due to a later somatic mutation.14 This article presents a case of a solitary PN which manifested as a double lower lip in a 4-year-old black girl. The case is unusual in that no clinical signs, features or family history of NF1 could be demonstrated. To our knowledge, only few cases of solitary PN
⇑ Corresponding author. Address: Radiology Unit, School of Oral Health Sciences, University of Limpopo, P.O. Box D17, Medunsa Campus, 0204, South Africa. Tel.: +27 (0)12 521 4902/3; fax: +27 (0)12 521 5901. E-mail address: [email protected] (C.E.E. Noffke). 1368-8375/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.oraloncology.2011.04.005
without a family history or clinical signs associated with NF1 have been described in the oral cavity.11–13,15–17
Case report A 4-year-old female patient presented in the MEDUNSA Oral Health Center with a complaint of a gradual painless swelling of long duration on the inside of the lower lip. Her medical- and dental history was uneventful and there was no facial asymmetry. Upon retraction of the lower lip excess mucosal tissue on the inside of the lip was noticed which presented as a fold of tissue in the vestibular sulcus measuring 2 cm and resembling a double lip (Fig. 1). The mucosa overlying the alveolar bone appeared normal with no ulcerations or mucosal discoloration. The teeth appeared to be healthy and with palpation the lesion was non-pulsating and had a rubbery consistency. Radiographs showed a mixed dentition with a normal eruption sequence and healthy bone. The clinical differential diagnosis included double lip caused by Ascher syndrome and neoplastic disease. The patient’s medical history was insignificant. The case presented initially as a double lower lip, a rare acquired or congenital oral anomaly18 characterized by a redundant fold of tissue on the mucosal side of the lip. Double lip is associated with Ascher syndrome, a congenital condition that presents with a triad of blepharochalasis (a redundancy of eyelid skin), nontoxic thyroid enlargement and double lip.18–20 Due to the absence of blepharochalasis and goiter enlargement, Ascher syndrome was excluded in the initial differential diagnosis. The patient’s medical history was insignificant. Trauma due to lip biting or other habits were excluded in the differential diagnosis as no ulceration or signs
450
N.P. Zwane et al. / Oral Oncology 47 (2011) 449–451
Figure 1 Extra mucosal fold with the appearance of a double lip in the anterior vestibular sulcus.
Figure 2 Micrograph showing the histological features of a plexiform neurofibroma. Note the swollen nerve bundles in a fibrous stroma (H & E stain, magnification 200).
of inflammation were present. The non-compressibility and normal mucosal colour excluded a diagnosis of a hemangioma which would have been a contra indication for a biopsy procedure. Microscopic examination of the biopsy established a diagnosis of plexiform neurofibroma (PN) (Fig. 2), and the patient was referred for surgical management.
two or more neurofibromas of any type or one PN, two or more Lisch nodules (brown spots on the iris), optic glioma, distinctive osseous bony dysplasia (such as sphenoid wing dysplasia or thinning of the long bone cortex) and involvement of a close family member with NF1 by these criteria.24,25 Oral lesions in NF1 patients are found in almost 72% of the cases21 but only a few cases have been described in detail in the literature.25–27 Typically, radiologic manifestations include enlargement of the mandibular foramen and/or canal, increased bone density, a deep coronoid notch, concavity of the medial surface of the ramus as well as multiple radiolucencies.27,28 PN is commonly diagnosed in children and rarely after adolescence.2,24 It can involve superficial tissue or deeper tissue and the most common site is the trunk (43%), head and neck area (42%) and limbs (15%).2 The tumor is described as gradually progressive, locally invasive and often disfiguring.24 Due to neurovascular involvement with nerve compression loss of function is possible. In general, PN causes diffuse nodular enlargement of a nerve and its branches by a proliferation of Schwann cells in the nerve sheath across the length of a nerve.1,24 This characteristic was absent in our case. These nodular masses are classically described as a ‘‘bag of worms’’ upon palpation.1,24 The formation of PNs in the connective tissue of the submucosa caused a soft tissue overgrowth which presented as a double lip in our case. Our case is unusual as its presentation was sporadic and without a family history. Although none of the abovementioned diagnostic features indicative of NF1 were present, follow up is indicated as some of these manifestations may develop in later life. Unilateral gingival enlargement associated with NF1 has been described in a patient with gingival neurofibroma in the attached gingiva of the lingual aspect of the lower central incisors.26 To our knowledge, only few other cases of isolated PN without a family history or clinical signs associated with NF1 have been described in the oral cavity.10,13,15–17,29 It is recorded that, contrary to sporadic localized PNs, those associated with NF1 tend to be larger, multiple and involve deep nerves.16,30 The PN’s associated with NF1 have the potential to undergo sarcomatous change towards neurofibrosarcoma, or malignant schwannoma, which are the main cause of death in this group of patients.2,4 The solitary type of PN, however rarely undergoes sarcomatous change and for this reason follow-up with the late development of features of NF1 is important.4 Solitary lesions should be treated with excision and recurrence is rare.4,31 Conclusion We present a case of solitary PN, which manifested as a double lip in a 4-year-old girl, and reviewed similar cases reported in the literature. Follow-up of patients with solitary PNs is advised in order to identify ancillary clinical features of NF1 that may become evident in later life. Conflicts of interest statement
Discussion Neurofibromatosis type 1 (NF1), is the most common form of neurofibromatosis and accounts for about 90% of all cases21 with a prevalence of 1 in 3000–3500 persons worldwide.21–23 The condition may be inherited as an autosomal dominant trait or, in rare cases, represents a sporadic localized mutation4 of the NF1 tumor suppressor gene which encodes the protein neurofibromin.22 The diagnosis of NF1 requires at least two of the following clinical criteria: six or more café au lait macules on the skin which present as brownish smooth-edged pigmentation and can be present at birth or during the first year of life, axillary or inguinal freckling,
None declared. References 1. Citak EC, Oguz A, Karadeniz C, Okur A. Management of plexiformneurofibroma with interferon alpha. Am J Pediatr Hematol Oncol 2008;25:673–8. 2. Geller M, Darrigo Junior LG, Filbo AB, Ribeiro MG. Plexiformneurofibroma in the ear canal of a patient with Type 1 neurofibromatosis. Braz J Otorhinolaryngol 2009;75(1):158. 3. Powell CA, Stanley CM, Bannister SR, McDonnel HT, Morits AJ, Deas DE. Palatal neurofibroma associated with localized periodontitis. J Periodontol 2006;77(2):310–5. 4. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 2nd ed. Philadelphia: WB Saunders Company; 2002.
N.P. Zwane et al. / Oral Oncology 47 (2011) 449–451 5. Güneri EA, Akoglu E, Sütay S, Ceryan K, Sagol O, Pabuccuoglu U. Plexiformneurofibroma of the tongue: a case report of a child. Turk J Pediatr 2006;48(2):155–8. 6. Sharma SC, Srinivasan S. Isolated plexiformneurofibroma of tongue and oropharynx: a rare manifestation of von Recklinghausen’s disease. J Otolaryngol 1998;27(2):81–4. 7. Oliveira G, Luengo J, Sastre R, Seijas B, Cembranos JL. Plexiformneurofibroma of the cheek mucosa. A case report. Med Oral 2004;9(3):263–7. 8. Weitzner S. Plexiformneurofibroma of major salivary glands in children. Oral Surg 1986;50:53–7. 9. Almela CR, Faubel SM, Cueva RC, Conde PI. Intra-parotid facial plexiformneurofibroma. Review of the literature. An Otorrinolaringol Ibero Am 2001;28(4):363–70. 10. Souaid JP, Nguyen VH, Zeitouni AG, Manoukian J. Intraparotid facial nerve solitary plexiformneurofibroma: a first paediatric case report. Int J Pediatr Otorhinolaryngol 2003;67(10):1113–5. 11. Boedeker CC, Ridder GJ, Kayser G, Schipper J, Maier W. Solitary neurofibroma of the maxillary sinus and pterygopalatine fossa. Otolaryngol Head Neck Surg 2005;133(3):458–9. 12. Robitaille Y, Seemayer TA, El Deiry A. Peripheral nerve tumors involving paranasal sinuses: a case report and review of the literature. Cancer 1975;35(4):1254–8. 13. Alatli C, Oner B, Unür M, Erseven G. Solitary plexiformneurofibroma of the oral cavity. A case report. Int J Oral Maxillofac Surg 1996;25(5):379–80. 14. Ruggieri M, Huson SM. The clinical and diagnostic implications of mosaicism in the neurofibromatoses. Neurology 2001;56(11):1433–43. 15. Marocchio LS, Pereira MC, Soares CT, Oliveira D. Oral plexiformneurofibroma not associated with neurofibromatosis type 1: case report. J Oral Sci 2006;48(3):157–60. 16. Lin V, Daniel S, Forte V. Is a plexiformneurofibroma pathognomonic of neurofibromatosis type 1? Laryngoscope 2004;114(8):1410–4. 17. Tsutsumi T, Oku T, Komatsuzaki A. Solitary plexiformneurofibroma of the submandibular salivary gland. J Laryngol Otol 1996;110(12):1173–5. 18. Martins WD, Westphalen FH, Sandrin R, Campagnoli E. Congenital maxillary double lip: review of the literature and report of a case. J Can Dent Assoc 2004;70(7):466–8.
451
19. Kruk-Jeromin J, Pisera P. Diagnostic and treatment protocol of Ascher syndrome. Pol Przegl Chir 2006;78:1323–31. 20. Atzeni M, Ceratola E, Zaccheddu F, Manca A, Saba L, Ribuffo D. Surgical correction and MR imaging of double lip in Ascher syndrome: Record of a case and a review of the literature. Eur Rev Med Pharmacol Sci 2009;13(4):309–11. 21. Cunha KSG, Baroza EP, Dias EP, Oliveira FM. Neurofibromatosis type 1 with periodontal manifestation. A case report and literature review. Br Dent J 2004;196(8):457–60. 22. Staser K, Yang Feng-Chun, Clapp DW. Mast cells and the neurofibroma microenvironment. Blood 2010;116(2):157–64. 23. Staser JM, Yang F-C, Clapp DW. Plexiformneurofibroma genesis: questions of Nf1 gene dose and hyperactive mast cells. Curr Opin Hematol 2010;17:287–93. 24. Sehgal VN, Sharma S, Oberai R. Evaluation of plexiformneurofibroma in neurofibromatosis type 1 in 18 family members of 3 generations: ultrasonography and magnetic resonance imaging a diagnostic supplement. Int J Dermatol 2009;48:275–9. 25. Mulvihill JJ, Parry DM, Sherman JL, et al. NIH conference. Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis). An update. Ann Intern Med 1990;113(1):39–52. 26. Bekisz O, Darimont F, Rompen EH. Diffuse but unilateral gingival enlargement associated with von Recklinghausen neurofibromatosis: a case report. J Clin Periodontol 2000;27(5):361–5. 27. Kaplan I, Calderon S, Kaffe I. Radiological findings in jaws and skull of neurofibromatosis type 1 patients. Dentomaxillofac Radiol 1994;23(4): 216–20. 28. Hisatomi M, Asaumi J, Konouchi H, Yanagi Y, Kishi K. Bone deformity showing a deep coronoid notch of the mandible in a patient with neurofibromatosis type 1. Dentomaxillofac Radiol 2005;34(6):380–3. 29. Malcolm EK, Lopes MB. 35-year-old healthy man with enlarging right parotid mass. Brain Pathol 2002;12(4):515–21. 30. Friedman JM. Neurofibromatosis type 1: clinical manifestations and diagnostic criteria. J Child Neurol 2002;17(8):548–54. 31. Ferner RE, O’Doherty MJ. Neurofibroma and schwannoma. Curr Opin Neurol 2002;15(6):679–84.