|Year : 2014 | Volume
| Issue : 1 | Page : 77-81
Central neurofibroma: A rare pathology at a rare site
Ajas A Gogri1, Sonali G Kadam1, Hemant R Umarji1, Pravin R Shinde2
1 Departments of Oral Medicine, Diagnosis and Radiology, Government Dental College and Hospital, Mumbai, Maharashtra, India
2 Departments of Oral Pathology and Microbiology, Government Dental College and Hospital, Mumbai, Maharashtra, India
|Date of Submission||08-Jul-2014|
|Date of Acceptance||07-Aug-2014|
|Date of Web Publication||26-Sep-2014|
Ajas A Gogri
Departments of Oral Medicine, Diagnosis and Radiology, Government Dental College and Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Neurofibroma is a tumor of nerve tissue origin. It is an uncommon benign tumor of the oral cavity. It generally appears as a part of syndrome, neurofibromatosis type 1, i.e., Von Recklinghausen's disease of skin. Oral neurofibroma as a solitary lesion is very uncommon. Few sporadic cases have been reported on tongue and submandibular gland. On rare occasions, the tumor can arise centrally within bone. This article presents a case of variation in the observed characteristics of neurofibroma being present centrally within maxillary alveolus and with no relation to neurofibromatosis. A discussion of its clinical, radiological, and histological features and a review of the same are included.
Keywords: Central neurofibroma, neurofibromatosis, solitary neurofibroma, Von Recklinghausen′s disease
|How to cite this article:|
Gogri AA, Kadam SG, Umarji HR, Shinde PR. Central neurofibroma: A rare pathology at a rare site
. J Indian Acad Oral Med Radiol 2014;26:77-81
|How to cite this URL:|
Gogri AA, Kadam SG, Umarji HR, Shinde PR. Central neurofibroma: A rare pathology at a rare site
. J Indian Acad Oral Med Radiol [serial online] 2014 [cited 2020 Feb 28];26:77-81. Available from: http://www.jiaomr.in/text.asp?2014/26/1/77/141866
| Introduction|| |
Neurofibroma is an irregular benign tumor of peripheral nerve sheath. It is relatively circumscribed, but non-encapsulated, and rarely occurs as a solitary lesion. It mostly occurs as a part of generalized syndrome of neurofibromatosis (Von Recklinghausen's disease of the skin). , In a series studied by Preston and his associates between 1932 and 1952, they reported the occurrence of intraoral neurofibromas in 6% of patients.  Of a series of 19 cases of neurofibromatosis studied by Cherrick and Eversole, the occurrence of intraoral neurofibroma in association with Von Recklinghausen's disease was reported as 20% in year 1971.  In a study published in 1969, among 303 cases of benign nerve sheath tumors, Das Gupta et al. found approximately 9% occurrence in the oral cavity.  In 1980, Wright and Jackson reported 60% of neurofibromas to be associated with Von Recklinghausen's disease. 
Clinically, neurofibromas appear as soft and drooping doughy mass and are characterized by slow growth, lack of pain, and superficial location. The tongue and buccal mucosa are the most common intraoral sites, with 50% of cases occurring in the soft tissue of tongue.  Occurrence at other sites like palate, gingiva, and intraosseus variety in mandible has also been reported. , Although neurofibromas occur in cervicofacial region, solitary intraosseus neurofibroma is a rare benign tumor with very few cases reported in the literature. 
| Case Report|| |
A female patient aged 8 years had come to our institute with a chief complaint of an enlarging asymptomatic swelling in the anterior maxilla region since 3 months. Her past medical history was unremarkable. No history of similar swelling was seen in the first relatives of the patient. On general examination, the patient was having average physique and height.
On extraoral examination, a swelling was seen protruding from the anterior maxillary alveolar region, causing incompetency of lips [Figure 1]. Detailed examination of the patient revealed no evidence of any other pathology.
Intraorally, a well-defined, solitary, round to ovoid, sessile, nodular swelling was seen involving the maxillary anterior alveolus region, extending mesio-distally from the mesial surface of 53 to erupting 22 and antero-posteriorly from the labial vestibule to the midpalatal region. Obliteration of upper labial vestibule was seen due to the lesional mass. Surface of the lesion was covered with normal pink-colored mucosa, except in the labial region. The labial surface of the swelling exposed to the external environment, due to lip incompetency, showed evidence of chronic inflammation. This could be attributed to absence of protective influence of saliva (similar to gingival inflammation seen in mouth breathers). The mucosal margin around the area of inflammation was raised but not indurated. Vermillion border of the upper lip showed diffuse areas of inflammation probably related to incompetent lips. On palpation, the lesion was firm in consistency suggestive of fibrous nature of the swelling. It was non-tender on palpation except in areas of ulceration. The lesion was non-pulsatile and non-fluctuant [Figure 2].
After clinical examination, a provisional diagnosis of peripheral ossifying fibroma was made as it is a relatively common gingival growth, appearing as a nodular, sessile or pedunculated mass, the surface of which may be frequently but not always ulcerated. In this case, the lesion appeared as sessile gingival growth which was firm in consistency showing fibrous nature and with ulceration in the anterior part of the lesion.
The following differential diagnoses were considered:
- Giant cell lesion- As the lesion was anterior to 16 and 26 in a young patient, the possibility of giant cell lesion was considered.
- Irritation fibroma- It can appear as a sessile growth on gingiva and is associated with trauma or irritation of sharp edges. This lesion was a sessile growth on gingiva and irritation from lower anteriors could be appreciated.
- Metastatic carcinoma of gingiva- Evidence of uneven bony destruction was seen suggestive of metastatic carcinoma of gingiva, but the lesion also caused expansion of cortical plates. In addition, there was no history of any primary tumor elsewhere in the body. So, it was ruled out.
- Epulis- It is a pedunculated mass presenting as a peripheral growth. It was ruled out as the growth was sessile and appeared to show involvement of deeper tissues.
Patient was subjected to radiological examination. Orthopantomograph (OPG) revealed gross destruction of bone and displacement of floor of right maxillary sinus upward. Impaction of 13, 21, and 22 was also seen as they were obstructed in their eruption pathway due to the lesional mass [Figure 3].
|Figure 3: Panoramic view revealing displacement of right maxillary sinus upward|
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Cone beam computed tomography (CBCT) showed a radiolucent lesion extending from 21 to 55 and up to the inferior nasal cavity superiorly. Approximately it measured 27 mm × 20 mm × 32 mm antero-posteriorly, medio-laterally, and supero-inferiorly, and had caused expansion and thinning of buccal and palatal cortical plates. Margins of lesion were well-defined except at certain places where it was irregular with evidence of perforation in palatal as well as buccal cortex. The lesion was oval in shape and contained residual bony islands and trabeculae giving multilocular appearance [Figure 4]a-c. Giant cell lesion was ruled out as it shows wispy striae which were not seen in CBCT.
|Figure 4: (a) CBCT revealing the lesion causing bone destruction in axial plane. (b) CBCT revealing the lesion causing bone destruction in sagittal plane. (c) CBCT revealing the lesion causing bone destruction in coronal plane|
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The lesion had caused displacement of 11 postero-superiorly in lower nasal space area below the inferior nasal concha. Also, 12 was displaced posteriorly near 14; 13 was displaced bucally and superiorly due to the expanding lesion. The lesion had caused displacement of floor of the right side of the nasal cavity and right maxillary sinus upward. Inferior part of naso-palatine canal appeared to be involved by the lesion. Bilateral concha bullosa was also appreciated.
Patient was subjected to further investigation and an incisional biopsy was performed under local anesthesia. The biopsy revealed oral mucosa covered with parakeratinized stratified squamous epithelium with underlying dense connective tissue which was fibrocellular with myxoid appearance. The connective tissue showed pleomorphic fibroblast cells with intermingled nerve fibers. Cellular pleomorphism was seen in the form of tadpole, star-shaped, and spindle cells. Collagen fiber bundles were arranged in a wavy pattern throughout the stroma [Figure 5]a, b.
|Figure 5: (a) H&E stain showing neural tissue origin under low-power magnification. (b) H&E stain showing neural tissue origin under highpower magnification|
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Further special staining by Gros-Bielschowsky silver (GBS) stain showed uniform, sharp, and specific black staining of nerve fibers, in contrast to the fainter, grayish reticulin fibers and light-staining collagen fibers [Figure 6]. Immunohistochemical staining for the S-100 and smooth muscle actin (SMA) protein was performed and was found positive in 60% of the cells, confirming the neural origin of the tumor [Figure 7]. The histological diagnosis of neurofibroma was made, and correlating with the history and clinical features, a final diagnosis of solitary neurofibroma was made as no other features of neurofibromatosis were seen.
The lesion was completely excised after establishing the diagnosis.
| Discussion|| |
Neurofibromas are slowly growing benign tumors. The origin of neurofibroma has not been definitively identified, but it is believed to arise from perineural fibroblasts which are neuroectodermal in origin. 
Neurofibromatosis was first described in 1882 by Von Recklinghausen, and is a syndrome consisting of multiple neurofibromas affecting most areas of the body, café-au-lait spots (skin pigmentation), and bony changes such as macrocephaly, pseudoarthrosis mainly of tibia, cerebral kyphosis, and bowing.  Café-au-lait spots are light brown macules, 10-40 mm in diameter, and ovoid shaped, with poorly circumscribed borders. Generally appearing in childhood, they are seen in almost all patients.  To be diagnosed as having neurofibromatosis, a patient must have more than six café-au-lait spots greater than 1.5 cm, until proven otherwise.  This criterion was modified for children by Whitehouse as five or more spots greater than 0.5 cm.  Involvement of cardiovascular, gastrointestinal, and central nervous systems has been documented in the literature.
Axillary freckles, iris hamartomas, schwannomas of nervous system, etc. are minor criteria in diagnosing neurofibromatosis.  Axillary and/or inguinal freckling can be seen in 90% of cases. Characteristic ophthalmic feature of neurofibromatosis type 1 (NF1) is the pigmented hamartomas of iris, also called as Lisch nodules. 
NF1 is genetically different from type 2 and is the most common autosomal dominant inherited disorder with an incidence of 1 in 3000.  NF1 gene is a large complex gene mutation which leads to absence of neurofibromin protein encoded by this gene and severe developmental abnormalities, as neurofibromin acts as GTPase activator in many tissues. 
Clinically, neurofibromas can occur as a subcutaneous tumor variety or a plexiform variety. Subcutaneous variety is also called as localized neurofibroma as it develops at peripheral nerve endings. It generally appears in late childhood or early adolescence and accounts for 95% of cases. It causes much disfigurement, but little or no clinical symptoms. Plexiform variety develops in deeper areas of the body near the nerve roots and accounts for 5% of cases. It generally appears within the first 2 years of life. Potential for malignant transformation into malignant peripheral nerve sheath tumors (MPNSTs) is high in plexiform neurofibromas. 
Neurofibromas generally occur as multiple lesions usually in association with NF1 and rarely as a solitary tumor as in our case. As there was no history of occurrence of such lesion in the family, this is a case of sporadic variety. Majority of the intraosseus cases of neurofibroma have been reported in the posterior mandible and a few in the maxilla. , The predisposition of its occurrence mostly in mandible is due to thick nerve bundles of inferior alveolar nerve. , Female to male ratio of 2:1 is noted.  It is generally seen in the third decade of life; however, its occurrence between 10 months and 70 years of age has been reported.  This case shows the involvement of maxilla in a female patient.
In a case reported by Dalili et al. in 2012, there was concurrent involvement of mandible, maxilla, and orbit. Radiographically, in the maxilla, the lesion showed bone destruction, multiple impacted maxillary molars, and displacement of the walls of right maxillary sinus into antral cavity.  Similar presentation was seen in our case which showed extensive bone destruction and displacement of the floor of nasal cavity along with maxillary sinus walls. In the mandible, neurofibroma may show features such as enlargement of foramen and inferior alveolar canal, deep sigmoid notch, deformity of condyle, unerupted teeth, and a cyst-like lesion. 
Another report of solitary neurofibroma was reported in year 2008 by Narwal et al. in a 5-month-old child, which involved maxillary alveolus.  It extended from the right maxillary alveolus region up to the right lateral surface of nose, measuring 2 cm × 1 cm radiographically. Our case showed similar presentation along with sinus displacement.
Recently, a case of neurofibroma of palate was reported in 2014 by Sreenivasa et al. and surprisingly, no bony involvement was seen on panoramic and PA skull view.  Although intraosseus neurofibromas are slowly growing benign tumors causing less destruction of surrounding bone, in our case, it showed rapid growth over a period of 3 months, with large destruction of bone in the maxilla.
Histologically, solitary neurofibromas are similar to the lesions seen in neurofibromatosis.  These tumors are not encapsulated and comprise a mixture of Schwann cells, perineural cells, and endoneural fibroblasts. , Neurofibromas show haphazard arrangement of nerve fibers on a background of irregularly distributed collagen matrix, with a few areas showing spindle cells and mucinous stroma.  Mast cells are frequently present with hyaline changes in older lesions. The lesional cells are uniformly positive for S-100 protein, signifying their origin from neural crest-derived tissue. 
The gold standard treatment of solitary neurofibroma is complete surgical excision and the same was done in this case.  Radiotherapy as an alternative to surgery is not sufficient, but it may retard growth and shrink the size of the tumor.  Small and accessible lesions of neurofibroma show excellent results when treated with diode lasers. 
Neurofibrosarcomas can develop in about 5-16% of all patients with multiple neurofibromas associated with neurofibromatosis.  Increased incidence of pheochromocytoma is also seen. Malignant potential of solitary neurofibroma is not known, but is considered to be negligible. Once malignancy develops in any of the lesions of neurofibromatosis, the prognosis becomes poor. 
| Conclusion|| |
Intraoral neurofibroma is an uncommon pathology and its occurrence within jaws is very rare, seen mostly in mandible. So, this case of solitary neurofibroma in maxilla is a rare pathology at a rare site.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]