Solitary Neurofibroma of the Gingiva – A Case Report

INTRODUCTION

Neurofibromas are benign tumors of neural differentiation. They originate from sympathetic, peripheral or cranial nerves^1,2. They are non-encapsulated, engulf the nerve of  origin and have the potential for malignant transformation³ . Neurofibroma can occur as a solitary lesion or as a part of generalized syndrome of neurofibromatosis [Von Recklinghausen's disease of skin] or very rarely as multiple neurofibromas without Von Reckling Hausen's disease⁴ . 

Neurofibromas are derived from the cells that constitute the nerve sheath and are composed of neurites, Schwann cells and fibroblasts within a collagenous or myxoid matrix. The cell of origin though not definitely identified has been thought to arise from the perineural fibroblasts⁵ .

Solitary Neurofibromas(SN) though commonly found on the skin are uncommon in the oral ^cavity4 and only a few cases have been reported in the literature. The first description of solitary neurofibroma of the oral cavity was reported by Bruce in 1954⁶ . In the oral cavity, neurofibromas occur either intraosseous or extraosseous. The most common extraosseous sites are tongue, buccal mucosa, lips and gingiva^7,8 . Hence we present a rare case of solitary neurofibroma of gingiva in a 44 year old male patient, with a one year follow-up.

CASE REPORT

A 44 year old male patient was referred to the Department of Oral Medicine, Diagnosis and Radiology, Dayananda Sagar College of Dental Sciences and Hospital, Bangalore with a chief complaint of a painless growth on the left posterior mandibular gingiva. The growth started 3 years back and has slowly increased to the present size. His family history was non-contributory. Intra oral examination showed a solitary growth with respect to the left mandibular premolars involving the interdental and marginal gingiva of 34 and 35. The growth was present on both the buccal and lingual aspects, was ovoid in shape and measured about 3 cm X 2 cm and 2 cm X 1cm respectively. The lesion was firm in consistency, sessile and non-tender with normal overlying mucosa. Teeth associated with the growth showed heavy deposits of calculus (Fig 1). The regional lymph nodes were not palpable. Provisionally the case was diagnosed as irritational fibroma. Differential diagnosis of pyogenic granuloma, peripheral ossifying fibroma, peripheral odontogenic tumors, peripheral giant cell granuloma and neurofibroma were considered.

Intra-oral periapical radiographs were taken with respect to 34, 35 which showed interdental bone loss upto the middle third of the roots of 34 & 35 with cupping resorption of bone (Fig 2). Blood investigations were advised and found to be within normal limits. Excisional biopsy was done under local anesthesia. The complete lesion along with 1mm of normal tissue was excised. The excised tissue (Fig 3) was fixed in 10% formalin and sent for histopathological examination.

The Hematoxylin & Eosin (H&E)(Fig 4) stained biopsy section showed stratified squamous parakeratinized epithelium. Connective tissue showed proliferation of numerous spindle cells with thin wavy nuclei. Delicate inter-twining collagen fibres with fibroblasts were also seen. Blood vessels were prominent with few scattered lymphocytes within the connective tissue and the tumor was not encapsulated. Immunohistochemical staining for S-100 protein was positive and was diffuse, supporting an origin from nerve sheath element (Fig 5). Correlating history, clinical examination, histopathological and immunohistochemical examination, the case was diagnosed as Solitary neurofibroma of gingival w.r.t 34,35. The patient has been on regular follow up and has shown no recurrence or complication over the last one year.

DISCUSSION

Neurofibromas are slow growing benign nerve sheath tumors that are composed of variable mixture of Schwann cells, perineural like cells and fibroblasts immersed in a collagenous or myxoid matrix⁹ . Many different forms of neurofibromas have been described in literature. These include cutaneous neurofibroma (localized and diffuse), intra oral neurofibroma (localized and plexiform), massive soft tissue neurofibroma (diffuse and plexiform), visceral neurofibroma (solitary or multiple), sporadic or associated with Neurofibromatosis-I (Von Recklinghausen's disease)¹⁰ .

Neurofibromas are said to be indicative of Von Recklinghausen's disease, even though it may be the only manifestation of the disease. Neurofibromas usually associated with Von Recklinghausen's disease are generally encountered as multiple lesions and rarely occur as a solitary tumour⁵ .

Neurofibromatosis is a disease that includes two distinct variants that differ from each other, genetically, histologically and clinically, type I and type II. Neurofibromatosis type I often known as Von Recklinghausen's disease, is one of the most common autosomal dominant inherited disorders with an incidence of 1 in 3000. The neurofibromatosis-I gene is a large complex gene, the mutation of which gives rise to diverse manifestations in terms of gene organization and expression. The protein encoded by this gene (neurofibromin) is expressed in many different tissues and acts as a GTPase activator and its absence leads to severe developmental abnormalities³ .

Approximately 25% of all neurofibromas occur in the head and neck region^11,12 . By definition, solitary neurofibroma affects patients who do not have neurofibromatosis. They account for about 90% of all neurofibromas and affect men and woman equally. They most commonly appear during the third and fourth decades of life. The lesions are usually asymptomatic and are slow growing¹³ .

Oral neurofibromas, usually present as sub-mucosal non-tender, non-inflamed discrete masses that range from few millimeters to several centimeters. Common sites of the oral solitary neurofibromas include tongue 26%, buccal mucosa 8%, gingival 2%, alveolar ridge 2%, labial mucosa 8% and palate 8%. Nasopharynx, para nasal sinuses, larynx and floor of the mouth may also be involved. Tumors may also arise within the bone⁴ . Around 40 intraosseous solitary neurofibromas have been reported¹³ . Most of the intra-osseous varieties are present in the posterior mandible with only a few of the reported cases being in the maxilla. The lesions are described as pedunculated or sessile nodular growths. They are always slow-growing and painless. Pain and paraesthesia may be due to the nerve compression¹³ . Lesions affecting gingivo-dento alveolar complex can displace and cause the mobility of the erupted teeth, if they occur during the primary or mixed dentition stages. They may lead to the displacement or impaction of erupting permanent teeth. Radiographic features are seen mainly when it arises centrally with in the bone. Since the present case did not show any of the features of Neurofibromatosis-I, except the presence of intra oral lesion, the diagnosis of neurofibromatosis was excluded and diagnosis of solitary neurofibroma was made. During the excision of the lesion, tissues from marginal and attached gingival were included in the biopsy. The excised specimen appeared as a firm whitish mass with a shiny surface.

Histologically three different forms of solitary neurofibroma based on the content of cells, niticin and collagen have been described: The first form shows, interlacing bundles of elongated cells having wavy dark staining nuclei, cells are associated with wire like strands of collagen and small amounts of mucoid material. Second form shows, high cellularity and consists of Schwann cells set in a collagen matrix devoid of mucoid substance. The third form is very rare and these tumors are easily confused with myxomas. These hypocellular neoplastic types contain pools of acid mucoploysaccharides with widely placed Schwann cells⁴ . Histopathological examination in our case showed bundles of nerves arranged in fascicles with thin wavy nuclei. Delicate inter twining collagen fibres with fibroblasts were seen in the adjacent connective tissue with few scattered lymphocytes.

Solitary neurofibroma must be differentiated from a Schwannoma. A Schwannoma is encapsulated eccentric to the nerve and composed of Schwann cells. A neurofibroma on the other hand, incorporates the nerve and is composed of Schwann cells, perineural like cells, fibroblasts and transitional cells¹⁰ .

Nerve sheath cells of the peripheral nerves consist of Schwann cells, perineural cells and endoneural fibroblasts. These cells exhibit characteristic ultra-structural features and immunophenotypes. S-100 protein and EMA (epithelial membrane antigen) are known as specific markers for Schwann cells and perineural cells respectively¹⁴ . Neurofibroma is immune reactive for S-100 protein and this immunological marker was positive in our case also. The Schwann cells showed positivity for S-100 protein.

Surgical excision is the treatment of choice for solitary neurofibroma. Prognosis for solitary neurofibroma is good and recurrence is rare as compared to neurofibromatosis-I. In our case, there are no signs of recurrence till date since past one year¹⁵ .

Malignant transformation of neurofibromas into neurogenic sarcomas is seen in 5-15% of patients with neurofibromatosis-I. Solitary neurofibroma may be seen as an initial presentation of neurofibromatosis-I in young patients. So, every individual presenting with solitary neurofibroma below 20years of age should be referred for genetic studies to rule out the possibility of neurofibromatosis-I⁴.

Even though they are the rare lesions in the oral cavity, solitary neurofibromas must be considered in the list for differential diagnosis in cases of intra oral swellings and intra osseous lesions of the jaw.

ACKNOWLEDGEMENT

We would like to acknowledge the contributions made by the staff of Department of Oral Medicine, Diagnosis and Radiology, Department of Oral & Maxillofacial Surgery, Dayananda Sagar College of Dental Sciences and Hospital, Bangalore.