Ossifying Fibroma of Maxilla in a Female Affected by Neurofibromatosis Type 1

Abstract

Ossifying fibroma is a benign fibro-osseous lesion found exclusively in jaws. It has a predilection for premolar–molar region in the mandible. The occurrence of OF as solitary lesions with no underlying disease is common in jaws. However its co-existence in patients with neurofibromatosis type 1 (NF1) has not been described in jaws. NF1, also known as von Recklinghausen’s disease or peripheral neurofibromatosis, is an autosomal dominant multisystem disorder that approximately affects 1 in 2500–3000 births. The common manifestations of this disease include Café-au-lait macules, skinfold freckling, cutaneous neurofibromas, blue-red and pseudoatrophic macules on skin, plexiform neurofibroma, scoliosis, optic glioma. So far only one case of ossifying fibroma (OF) in such patients has been reported in the skull but not in the maxillofacial region. We report a case of OF of the maxilla in a 45 year old female suffering from NF1. To the best of our knowledge this is the first case report where OF occurred in the maxilla in patient with NF1.

Introduction

Ossifying fibroma (OF) of jaw is defined as a demarcated and occasionally encapsulated lesion consisting of fibrous tissue containing variable amounts of mineralized material resembling bone and/or cementum [1]. Ossifying fibroma is a true neoplasm that tends to arise from the mesenchymal blast cells of the periodontal ligament [2]. The co-existence of ossifying fibroma with neurofibromatosis type 1 (NF1) in head and neck region has only been reported in calvarial bone [3]. We present a case of ossifying fibroma in maxilla in a 45 year old female suffering from NF1 that was successfully enucleated under general anaesthesia. To the best of our knowledge such co-existence of ossifying fibroma in patient with NF1 has never been reported before in literature.

Case Report

A 45 year old female presented to the department of Oral and Maxillofacial Surgery for evaluation of upper jaw swelling on left side. She was known to be affected by NF1. Her family history was unremarkable. The lesion was enlarging progressively but painless and had been present since 12 months. The clinical examination revealed a well defined, hard swelling, measuring approx 6 cm in diameter, with expansion of both buccal and palatal cortices, extending from the left maxillary canine to the third molar region on ipsilateral side. The overlying mucosa was normal in appearance and the lesion had displaced the teeth in vicinity (Fig. 1a). She had no history of previous trauma or infection in the oral cavity.

Fig. 1.

a Slow-growing tumour with overlying normal mucosa present over the left maxillary arch. b Orthopantomogram showing a circumscribed radiolucency in the left maxilla extending superiorly up to the floor of maxillary sinus

On physical examination the patient revealed to be in good health. She had multiple neurofibromas over the entire face (Fig. 2a) and on the palms and hands, multiple café-au-lait spots over her entire body (Fig. 2b) and axillary freckling bilaterally. An opthalmological examination revealed several bilateral lisch nodules on the iris; fundoscopy was normal. The panoramic radiograph of the jaws showed a circumscribed radiolucency in the left maxilla extending from second premolar to the mesial of left second molar (Fig. 1b). Superiorly, it had extended up to floor of maxillary sinus. An incisional biopsy was performed from the patient’s maxillary lesion. Histologic examination showed the features of a benign fibro-osseous lesion consistent with ossifying fibroma (Fig. 3a). Subsequently, the patient was operated for enucleation of the tumour along with extraction of first premolar, second premolar, second and third molars. Histopathologic examination of the excised tumour showed the features similar to those found on incisional biopsy examination (Fig. 3b). On microscopic examination, dense fibrocollagenous tissue was seen which at places appeared myxomatous and was accompanied by islands of lamellated bone with osteoblastic rimming. The stromal fibroblastic cells were cytologically bland with no features of atypia. Thus the diagnosis of OF was confirmed after excision of the lesion.

Fig. 2.

a Multiple neurofibromas over the face. b Multiple café-au-lait macules over the body

Fig. 3.

a Photomicrograph showing calcifications in the fibrocollagenous matrix (×40). b Photomicrograph showing islands of lamellated bone with osteoblastic rimming in fibrocollagenous matrix (×40)

Discussion

OF is benign fibro-osseous lesion and is a true neoplasm; it represents neoplastic process of bone forming tissues with membranous ossification and therefore it involves the maxillofacial bones exclusively [3, 4]. The original most widely used terminology to address this entity was cemento-ossifying fibroma [5]. It occurs between 2nd and 4th decade of life with female predilection. It occurs in tooth bearing areas of the jaws and most frequent location is mandibular premolar–molar region. Clinically, it appears as slow-growing, progressive, painless and expansile growth [4, 5]. It has a tendency to push the neighbouring tissues without destroying them. It is firm in consistency; firmness depends upon the degree of mineralization. It is covered with normal mucosa without associated lymphadenopathies [6]. It causes expansion of buccal and palatal cortices displacing the teeth in the vicinity inferiorly in maxilla and expands into the maxillary antrum [2]. Radiographically, in the initial stage OF typically appears as well circumscribed radiolucency. However with progression as more matrix gets calcified, it becomes radiopaque [2]. Histologically, a thin zone of fibrous tissue separates the lesion from the overlying cortical bone. The lesion is composed of cellular fibrous tissues that contain spindled fibroblasts and bone deposited in a variable pattern. Irregular trabeculae of woven bone rimmed by osteoblasts may be seen in the collagenous matrix [5]. The treatment of choice for OF is complete excision. There exists a cleavage surface between OF and the healthy bone that makes it accessible to enucleate the lesion and perform curettage of the residual cavity. The recurrence rate for OF after enucleation is 10–28% and after resection it is only 5%. For recurrent lesions enucleation or resection with or without reconstruction is the treatment of choice [4].

OF mostly occurs as sporadic lesion; however its co-existence has been described with various syndromes in the literature. Few of them to be mentioned are Sturge–Weber syndrome, Gnathodiaphyseal dysplasia, hyperparathyroidism, jaw tumour syndrome, Buschke–Ollendorff syndrome and Oculocerebrocutaneous syndrome, Encephalocraniocutaneous lipomatosis, and neurofibromatosis. Of all these syndromes more than half are neurocutaneous disorders [7]. So far only one case of OF associated with NF1 (a neurocutaneous disorder) has been reported in the literature that occurred in the skull [3]. The reason for the occurrence of OF in patients with neurocutaneous syndromes could be that OF in jaws arise from multipotent cells of periodontal membrane which are considered to be neural crest-derived cells [7].

NF1 is an autosomal dominant disease characterized by the development of multiple neurofibromas of the peripheral nerves. It has an estimated frequency of one per 2500–3000 births. NF1 is a result of mutation in NF1 gene located on chromosome 17q11.2 that encodes for the protein neurofibromin. Neurofibromin is a tumour suppressor that regulates guanosine triphosphatase activity and as such it serves as a regulator of signals for cell proliferation and differentiation. Neurofibromin is found primarily in neurons, glial and Schwann cells and in early developing melanocytes. Schwann cells in neurofibroma and melanocytes in café-au-lait macules have mutation in both the NF1 allels [8, 9]. The diagnostic criteria for NF1 is tabulated in Table 1 [10]. The clinical manifestations in NF1 include café-au-lait macules, skinfold freckling, generalized hyperpigmentation, neurofibromas, blue-red and pseudoatrophic macules, plexiform neurofibroma, juvenile xanthogranuloma, glomus tumour, melanoma, nevus anemicus, pruritis, scoliosis, dysplasia of long bone, Lisch nodules, optic glioma [8].

Table 1.

National Institute of Health Diagnostic Criteria for NF1 [10]

Two or more of the following features

Café-au-lait macules At least six macules of > 5 mm largest diameter in prepuberty individuals or > 15 mm in individuals past puberty

Skinfold freckling In axilla or groin

Neurofibromas Two or more neurofibromas of any type or ≥ 1 plexiform neurofibroma

Lisch nodules or iris hamartomas At least two

A distinctive osseous lesion

A first degree relative with NF1 diagnosed by using the above-listed criteria

In conclusion, the first report of a case of NF1 associated with OF of maxilla in a 45-year-old female is presented here. OF may be part of a wider phenotypic spectrum of the less common manifestations associated with NF1.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

Ethical approval has been obtained from the institutional ethical committee.

Informed Consent

A written informed consent has been obtained from the patient.