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Year : 2018  |  Volume : 6  |  Issue : 2  |  Page : 36-41

Use of advanced imaging in diagnosis of neurofibromatosis 1

1 Department of Oral Medicine and Radiology, Maulana Azad Institute of Dental Sciences, New Delhi, India
2 Department of Conservative Dentistry and Endodontics, Government Dental College, Bengaluru, Karnataka, India

Date of Web Publication13-Aug-2018

Correspondence Address:
Eiti Singh
Department of Oral Medicine and Radiology, Maulana Azad Institute of Dental Sciences, New Delhi - 110 002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jomr.jomr_15_18

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Neurofibromatosis (NF) is a Mendelian disorder which is carried as an autosomal dominant trait. Two genetically distinct subtypes have been recognized, NF type 1 (NF1) and NF2. NF1 patients present with cutaneous, ocular, musculoskeletal, cardiovascular, gastrointestinal, neurologic, and dental findings but chiefly characterized by neurofibromas of central and peripheral nervous systems. Approximately 75%–80% of NF1 patients present with oral and radiographic manifestations, while 80% present with facial plexiform neurofibroma. This article aims to present a case report of NF1 diagnosed with the help of higher imaging. NF1 in a pediatric patient was diagnosed with classic findings of plexiform neurofibroma and sphenoid dysplasia diagnosed on cone-beam computed tomography (CT) and contrast-enhanced CT. Development of malignancies such as malignant peripheral nerve sheath tumors, optic gliomas, and leukemias is a major risk factor of NF1. Therefore, the use of imaging for early diagnosis of NF1 is critical.

Keywords: Central nervous system, neurofibroma, neurofibromatosis type 1

How to cite this article:
Singh E, Singh K, Gupta S, Shailat M. Use of advanced imaging in diagnosis of neurofibromatosis 1. J Oral Maxillofac Radiol 2018;6:36-41

How to cite this URL:
Singh E, Singh K, Gupta S, Shailat M. Use of advanced imaging in diagnosis of neurofibromatosis 1. J Oral Maxillofac Radiol [serial online] 2018 [cited 2023 Mar 28];6:36-41. Available from: https://www.joomr.org/text.asp?2018/6/2/36/238930

  Introduction Top

Neurofibromatosis type 1 (NF1; OMIM 162200) presents with birth incidence and prevalence of 1 in 2500 and 4000, respectively.[1] Dominant loss-of-function mutations of neurofibromin 1 gene located on the long arm of chromosome 17 (17q11.2) encoding neurofibromin result in NF1. Multiple café-au-lait spots, axillary freckling, Lisch nodules, optic pathway gliomas, and peripheral nerve sheath tumors are the main clinical features of NF1.[1],[2],[3] NF1 patients should essentially undergo computed tomography (CT) and/or magnetic resonance imaging (MRI), ensuring timely detection of developing systemic lesions.[4],[5] This article presents a case report of plexiform neurofibroma with classical features, emphasizing on the use of higher imaging in diagnosis of NF1.

  Case Report Top

An 8-year-old female patient of Indian origin reported to the Outpatient Department at Maulana Azad Institute of Dental Sciences with the chief complaint of swelling on the right side of the palate. The swelling had been present for 2 years. There was no significant traumatic or dental history, as reported by the patient's guardian. The patient had a known complaint of seizure disorder (absence seizure), for which she was medicated with valproate (20 mg/kg/day) for 2 weeks. There was a history of previous episodes of seizures at 1 year of age, for which she took treatment for 6 months.

Electroencephalography, complete blood count, liver function test, kidney function test, orthopantomogram (OPG), and CT head were advised for the patient. Ultrasonographic (USG) cheek and fine-needle aspiration cytology from left palatal swelling were also advised. No other fresh complaints were made by the patient. There were no similar complaints in the younger sister who was 6 years old.

On extraoral examination [Figure 1]a, a diffuse soft-tissue swelling measuring approximately 4 cm × 4 cm was present on the right side of the face. Superoinferiorly, it extended from the level of right lower eyelid to the level of right angle of mouth. Anterioposteriorly, it extended from right ala of nose to the level of lateral canthus of the right eye. Overlying surface was normal. No evidence of any scar or fistula was present.
Figure 1: (a) Extraoral view reveals a diffuse soft-tissue swelling measuring approximately 4 cm × 4 cm present on the right side of the face. (b) Intraoral view reveals a diffuse, soft and fluctuant swelling measuring approximately 4 cm × 4 cm present on the right side of the palate

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On intraoral examination [Figure 1]b, a diffuse, soft, fluctuant swelling measuring approximately 4 cm × 4 cm was present on the right side of the palate. Anteroposteriorly, it extended from the alveolar ridge with respect to 11 to the region of soft palate, and mesiodistally, it extended from approximately 1 cm lateral to the midpalatine raphe onto the buccal gingival with respect to maxillary deciduous molars on the right side. It was nontender on palpation. The overlying mucosa was lobulated and no secondary changes were evident. Permanent maxillary central incisors and maxillary right first molar were missing.

OPG revealed delayed eruption of 12, 22, 32, and 42. As seen in [Figure 2], an ill-defined mixed density lesion with the radiodensity similar to soft tissue was evident in the alveolar ridge with respect to developing tooth buds of 14, 15, and 16. The floor of the right maxillary sinus was not traceable. There was evidence of distalization of 16 and immature root apices. A well-defined pin-point-sized radiopaque lesion was seen in soft-tissue space inferior to the occlusal surface of 16.
Figure 2: Orthopantomogram reveals an ill-defined mixed density lesion with the radiodensity similar to soft tissue is evident in the alveolar ridge with respect to developing tooth buds of 14, 15, and 16

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Cone-beam CT (CBCT) scan of the maxilla [Figure 3]a revealed a soft-tissue swelling involving the right side of the face and hard palate partially covering the midpalatal aspect of the teeth 54, 55 caudally on the coronal section. Soft tissue extended superoposteriorly in the right infratemporal fossa with widening of the right pterygopalatine fossa and the sphenopalatine foramen. There was evidence of erosion of the greater and lesser wings and body of the sphenoid bone on the right side with widening of the optic canal and the middle cranial fossa as shown in [Figure 3]. Widening of the vidian canal on the right side was also noted. Findings were suggestive of an aggressive soft-tissue neoplasm, likely neurogenic in origin.
Figure 3: (a) CBCT reveals an evidence of erosion of the greater and lesser wings and body of the sphenoid bone on the right side (b) with widening of the optic canal (c) and the middle cranial fossa

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Three-dimensional reconstructed CBCT coronal image [Figure 3]b showed bare orbit with widened superior orbital fissure and dysplastic greater wing of sphenoid bone. Axial section [Figure 3]c revealed erosion with respect to right half of the palate.

Contrast-enhanced CT face [Figure 4] revealed sphenoid dysplasia, plexiform neurofibroma involving the palate and right inferior gingivobuccal sulcus, optic glioma/neuroma involving the optic canal. Possibility of pressure-induced blindness in the future could be excluded. Findings represented NF1. [Figure 4] shows multiple widened foramen.
Figure 4: Contrast-enhanced computed tomography reveals widened greater palatine foramen, foramen ovale, optic canal, pterygomaxillary fissure, and vidian canal

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The patient was taken up for optic evaluation to rule out optic glioma. USG for kidney, urinary bladder was advised along with genetic counseling of the mother for future pregnancies.

  Discussion Top

NF1 is also known as tumor predisposition syndrome as the patients are at an increased risk of developing both benign and malignant tumors.[6],[7] Neurocutaneous disorders are the group of heterogeneous genetic disorders which are characterized by the abnormalities of skin, brain, and other organ systems due to genetic mutations in cell growth regulating pathways. The typical neurocutaneous disorders are NF1, tuberous sclerosis, and  Sturge- Weber syndrome More Details More Details. The clinical presentation of NF1 is widely varied with the involvement of multiple organs [Table 1].[8]
Table 1: Clinical manifestations of neurofibromatosis 1

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Most of the clinical features are manifested at birth, while others appear during the later course of time. Neurofibromas are benign nerve sheath tumors arising from Schwann cells typically and constitute the important feature of NF1.[9] Neurofibromas are divided into four subtypes [Table 2].[10],[11]
Table 2: Types of neurofibromas

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Diagnostic criteria of neurofibromatosis type 1 (Stumpf et al.)[16],[17]

Two or more of the following criteria must be satisfied to establish the diagnosis [Table 3].
Table 3: Diagnostic Criteria of Neurofibromatosis Type 1 (Stumpf et al)[16],[17]

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There was the presence of plexiform neurofibroma of palate in the present case and hence has been kept under vigilant follow-up to rule out any malignant transformation. Malignant peripheral nerve sheath tumors (MPNSTs) are highly malignant, aggressively metastatic tumors with an overall poor prognosis, early oncological resection being the only curative option.[9],[18] There is cumulative 10% increased risk of developing MPNST in NF1 as compared to 0.1% in normal population.[9],[12],[19] Since MPNST has the poor prognosis, so early detection is very vital. The plexiform neurofibroma on palate in the present case did not show any features of malignant transformation at 2 years of follow-up.

Molecular basis of neurofibromatosis type 1

Although NF1 shows autosomal dominant type of inheritance, 50% of affected cases occur through de novo mutation.[8] Germline mutation in NF1 tumor suppressor gene is the underlying cause for NF. Normally, NF1 tumor suppressor gene codes for a neurofibromin protein which controls expression of Ras-proto-oncogene, thereby controlling excessive cellular proliferation.[11],[12],[20] Other functions of protein neurofibromin are tabulated in [Table 4].[11],[12]
Table 4: Normal functions of neurofibromin in an individual

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In mutated NF1 gene, Ras-proto-oncogene regulation is lost, causing loss of regulation of cellular growth. This results in manifestations due to multisystem involvement and increased predisposition to benign and malignant nerve sheath tumors.[9],[21]

Role of imaging for neurofibromatosis type 1-associated tumors

As discussed earlier. NF 1 is associated with increased risk of benign and MPNSTs, which may exhibit a destructive growth pattern and may be associated with poor prognosis. Therefore, early diagnosis is crucial to reduce associated morbidity and mortality. Early diagnosis is very crucial to reduce associated morbidity and mortality. Accurate and precise location of the tumor with the help of reliable imaging modalities aids in appropriate treatment planning, avoiding complications as well as therapy monitoring.

Magnetic resonance imaging in neurofibromatosis type 1-associated tumors

MRI allows the assessment of location, extent, and character of the soft-tissue tumors in NF1, owing to the high soft-tissue contrast.[8] Therefore, MRI for the whole body is advised to evaluate the patient's risk status for developing MPNST and also the evaluation of existing plexiform neurofibromas. Neurofibromas are best seen on T2-weighted imaging sequences.[8]

Along with anatomical MRI sequences, quantitative MRI imaging techniques such as diffusion-weighted imaging and dynamic contrast-enhanced-MRI are used for the assessment of tumor perfusion and nerve sheath tumor characterization.[8],[22] Detection of change in appearance of plexiform neurofibromas is made on serial MRI examinations, thereby increasing chances of identifying malignant transformation at an early stage.[23]

Computed tomography in neurofibromatosis type 1-associated tumors

Due to the presence of increased fraction of lipid content and accumulation of interstitial fluid, CT reveals low-density signal for neurofibromas.[24] Due to the variation in intercellular structure and density, contrast CT provides inhomogeneous contrast enhancement for nerve sheath tumors.[25] CT should be used in conjunction with MRI or positron emission tomography (PET) for determining the exact tumor location, staging, and imaging of subcranial tumors.[8]

Positron emission tomography/computed tomography in neurofibromatosis type 1-associated tumors

18F-fluorodeoxyglucose (18F-FDG) PET/CT permits high sensitivity (100%) and specificity (77%–95%) toward the detection of potential malignant transformation of a peripheral nerve sheath tumor.[8] PET/CT is of better use for detecting metastasis involving the bones and the lungs. However, it is not used extensively for cutaneous, subcutaneous, and spinal neurofibromas due to reduced uptake of 18F-FDG in these tissues.[8]

  Conclusion Top

NF1 shows a major risk factor for development of malignant tumors, particularly MPNST.[26] Dentists and physicians should be aware of the oral manifestations of pediatric NF1 patients and perform a careful examination to investigate these alterations. Long-term follow-up monitoring for oral manifestations is needed. Further, follow-up monitoring of plexiform neurofibromas is important due to the potential for malignant transformation, occurring in up to 5% of patients.[27] Pain and rapid growth may indicate malignancy and warrant further diagnostic investigation, such as MRI and PET/CT.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4]

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