INTRODUCTION
Neurofibromatosis type 1 (NF1) is an autosomal dominant disease and the most common
type (96%) of neurofibromatosis. The other two types, neurofibromatosis type 2 (3%)
and schwannomatosis, are clinically distinct from NF1 and not discussed in this study1,2. NF1 is characterized by the presence of neurofibromas, skin and skeletal changes,
and involvement of multiple organs and systems.
Neurofibromas, benign tumors consisting of Schwann cells, fibroblasts, mast cells,
and perineural cells, may occur as solitary nodules or be associated with NF1, which
manifests as solitary, multiple, or diffuse nodules. Nodules, the most common manifestation
of NF1, occur in up to 60% of patients2. The prevalence of NF1 is similar between the sexes, and the disease may be cutaneous
or subcutaneous. The cutaneous form can be pedunculated, nodular, or flattened, and
the number of nodules increases until adulthood2. Subcutaneous neuromas may affect the deep tissues, including the periorbital region,
retroperitoneal space, gastrointestinal tract, and mediastinum2. Plexiform neuromas, the pathognomonic form of the disease2, consist of subcutaneous neurofibromas that grow in a single nerve as well as in
multiple fascicles and branches of a nerve or plexus.
Plexiform neuromas show a fascicular growth pattern ("bag of worms") and, in contrast
to the cutaneous form, have an increased risk of malignant degeneration2.
Neurofibrosarcomas, malignant tumors of the peripheral nerves, are rarer, representing
5-10% of soft tissue sarcomas, and primarily affect young adults3.
Epidemiology
The prevalence of NF1 worldwide is one case per 3,000 inhabitants, but it varies among
countries and regions, reaching a prevalence of one case per 960 inhabitants in Israel1. Regardless of the affected population, 50% of cases are due to family inheritance,
while the others are caused by a de novo mutation of the disease-causing gene.
The life expectancy of affected patients is reduced by 8-21 years, and the leading
cause of early death is the development of malignant tumors, which are more common
in affected patients than in the general population1.
Pathophysiology
NF1 is an autosomal dominant genetic disease with a 50% frequency of sporadic mutations1. It is caused by a mutation in the NF1 tumor suppressor gene located on chromosome
17q11.22 that expresses neurofibromin, a protein that negatively regulates RAS proto-oncogenes.
Neurofibromin inactivates RAS by binding to RAS-GTP. The absence of neurofibromin
activates RAS, which dysregulates cell growth and survival and leads to tumorigenesis
and other abnormalities, including pigmentary lesions, skin tumors, and bone changes1.
Clinical manifestations
Clinical manifestations are varied and may include dermal and plexiform neurofibromas,
neurofibrosarcomas, pigmentary abnormalities (the most common non-neoplastic manifestations
due to the common embryonic origin between melanocytes and Schwann cells), ophthalmic
changes such as Lisch nodules, glaucoma and glioma, bone dysplasia (resulting from
bone formation dysfunction due to osteoclast and osteoblast dysregulation), the involvement
of several organs, and behavioral alterations. Neurofibromas may appear on any peripheral
nerve; however, it is estimated that approximately 25% of symptomatic cases occur
in the head and neck4.
Plexiform neurofibromas involving the eyelid, eye socket, periorbital areas, and facial
structures may lead to visual loss in children at the age of visual maturity and occur
predominantly along the trigeminal nerve pathway5. Although most cases of blindness are secondary to optic nerve gliomas, periorbital
plexiform neurofibromas also cause vision loss secondary to amblyopia and glaucoma5.
Diagnosis and treatment
The diagnosis of NF1 is based on a thorough physical examination and family history
of neurofibromatosis. A genetic analysis may be useful for diagnostic confirmation
in challenging cases, including children younger than 6 years of age and patients
without a family history of NF1. The National Institutes of Health proposed diagnostic
criteria to improve early detection rates. Approximately 30% of patients with the
disease meet at least one of the criteria by 1 year of age, 97% of patients meet two
criteria by 8 years of age, and all patients meet all criteria by 20 years of age2,6.
Diagnostic criteria for NF1:
Two or more of the following features: at least six café-au-lait spots (>5 mm in diameter
in prepubertal children and >15 mm in postpubertal children); freckles in the axillary
or inguinal region; optical glioma; at least two Lisch nodules (iris hamartomas);
at least two neurofibromas of any type or one plexiform neurofibroma; a single bone
lesion; and a first-degree relative with NF12,5 (Figure 1).
Figure 1 - Non-neoplastic lesions caused by neurofibromatosis type 1 (NF1). A. Café-au-lait spots;
B. Freckles in skin folds; C. Lisch nodules; D. Tibial pseudarthrosis and fracture
in an affected child. Source: J.L. Anderson and D.H. Gutmann5.
Figure 1 - Non-neoplastic lesions caused by neurofibromatosis type 1 (NF1). A. Café-au-lait spots;
B. Freckles in skin folds; C. Lisch nodules; D. Tibial pseudarthrosis and fracture
in an affected child. Source: J.L. Anderson and D.H. Gutmann5.
The differential diagnosis includes Legius syndrome, skin hyperpigmentation, and tumors
misdiagnosed as neurofibromas such as lipomas1.
NF1 is progressive throughout life; nonetheless, its severity may vary significantly
among affected patients.
NF1 has no definitive treatment, and its management is usually based on clinical follow-up
and symptomatic treatment of systemic manifestations. Children who receive the early
diagnosis should undergo immediate and long-term follow-up by a multidisciplinary
team, including ophthalmological and dermatological consultations and routine blood
pressure measurements considering the occurrence of renal artery vasculopathy7,8.
Dermal neurofibromas usually cause itching, pain, bleeding, and aesthetic problems.
Their management includes the surgical removal of larger lesions, laser ablation of
smaller lesions, use of emollients, and psychological support1,5.
All NF1 patients who wish to have children should be referred for genetic follow-up.
Women should be advised of potential risks during pregnancy, including hypertension
and increases in neurofibroma number and size7.
OBJECTIVE
This study aimed to describe a case of a 1-year-old child with infraorbital nerve
neurofibroma manifesting as an expansive and deforming mass in the right hemiface
treated surgically with the facial approach to enable adequate tumor exposure and
possible preservation of the facial tissues and aesthetics.
CASE REPORT
T.J.R.R., a male patient aged 1 year and 11 months, was followed up at the Dermatology
Department for café-au-lait spots on the body surface and at the Ophthalmology Department
for iris hamartomas (Linch nodules), both of which are clinical manifestations of
NF12. The patient was referred to the plastic surgery service for the assessment of an
expansive and fibrotic lesion in the right maxilla, facial deformity including widening
and lifting of the right nasal wing, and deformity in the ipsilateral lower eyelid.
No visual, neurological, or neuromotor developmental delays were noted.
Computed tomography examination revealed a mass in the right maxillary sinus, involvement
of the infraorbital nerve, and enlargement of the infraorbital foramen, possibly without
bone involvement (Figure 2). An incisional biopsy identified the mass as a neuroma.
Figure 2 - Magnetic resonance image showing an infraorbital lesion and widening of the infraorbital
foramen.
Figure 2 - Magnetic resonance image showing an infraorbital lesion and widening of the infraorbital
foramen.
The patient underwent complete resection of the mass by an open approach with access
through a Weber-Ferguson incision. A retrograde resection (from bone to skin) was
performed to preserve as much soft tissue as possible (Figures 3A, 3B). The origin of the infraorbital nerve and the surrounding mass and tissues were
resected, and a flap and the superficial fat layer were preserved to cover the defect.
There was no apparent bone involvement (Figures 4A, 4B).
Figure 3 - A. (Left): facial access showing a mass on the right face. B. (Right): resected mass showing the infraorbital foramen.
Figure 3 - A. (Left): facial access showing a mass on the right face. B. (Right): resected mass showing the infraorbital foramen.
Figures 4 - A and 4B. Surgical site after resection (left) and surgical planes (right).
Figures 4 - A and 4B. Surgical site after resection (left) and surgical planes (right).
Histopathological examination of the surgical specimen indicated the presence of a
neurofibroma surrounded by fibrotic tissue without involvement of the infraorbital
foramen despite its widening.
The patient developed mild edema in the immediate postoperative period without complications
associated with the surgical procedure. During the 3-year postoperative period, the
affected hemiface had mild insensitivity to touch at the infraorbital nerve (which
was difficult to measure because of the patient's age) without other sequelae or signs
of relapse. The aesthetic results were good, with improved position of the nasal wing
without pathological scarring or scar retraction.
DISCUSSION
Surgical treatment of neurofibromas associated with NF1 can be challenging for the
plastic surgeon, especially those located on the face since they may cause skin deformities
and sensory and motor sequelae due to peripheral nerve involvement. Moreover, affected
children experience incomplete growth and development of the bones and soft tissues,
demanding less aggressive resections.
The infraorbital nerve is the end of the maxillary branch of the trigeminal nerve
(fifth cranial nerve), which emerges from the infraorbital foramen approximately 1
cm below the inferior orbital margin and is responsible for skin sensitivity in the
medial portion of the cheek, part of the nose, lower eyelid, and upper lip9.
The Weber-Ferguson incision can be used to reach tumors in the maxilla and lower orbit
and provides adequate access to these regions. Access may begin in the vermilion of
the upper lip following the philtrumor in the wing of the nose following the lateral
part of the nasal dorsum and continuing to the lower eyelid, 3-4 mm below the ciliary
margin. After a full-length incision is made, the flap is retracted after sub- or
supraperiosteal dissection, depending on the surgical objective and tumor invasiveness10 (Figures 5A, 5B).
Figures 5 - A and 5B. Access through a Weber-Ferguson incision resulting in adequate exposure of the maxilla
and infraorbital foramen. Source: AO Surgery Reference.
Figures 5 - A and 5B. Access through a Weber-Ferguson incision resulting in adequate exposure of the maxilla
and infraorbital foramen. Source: AO Surgery Reference.
This type of incision allowed adequate tumor visualization. We began retrograde subperiosteal
resection of the skin to preserve the unaffected soft tissues. This approach allowed
resection of the entire tumor and preservation of a flap suitable for covering the
defect without apparent deformities. Other possible incisions would be direct access
to the tumor, intraoral incision in the vestibular gingival sulcus, or lateral access
to the tumor.
Incisions in the skin over the lesions may result in unnecessary skin resections and
visible scars and deformities. An intraoral incision, despite ensuring optimal bone
exposure, does not provide adequate retraction of soft tissues. Lateral incisions
are adequate in extensive dissections of the parotid and facial nerve branches to
gain adequate tumor access.
CONCLUSION
The surgical approach through a Weber-Ferguson incision improved access to tumors
in the infraorbital nerve with adequate exposure of the lesion, preservation of the
soft tissues, and good aesthetic results, minimizing sequelae.
COLLABORATIONS
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MVCG
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Analysis and/or data interpretation, Conception and design study, Investigation, Writing
- Original Draft Preparation, Writing - Review & Editing
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SMC
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Supervision
|
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LCJ
|
Investigation, Writing - Review & Editing
|
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KRO
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Supervision
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PP
|
Original Draft Preparation
|
|
CMV
|
Visualization
|
|
ASM
|
Visualization & Review
|
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1. Hospital Felício Rocho, Barro Preto, Belo Horizonte, MG, Brazil.
Corresponding author: Marcus Vinícius Capanema Gonçalves Alameda Oscar niemeyer, 1100, 1501C, Vila da Serra, Nova Lima, MG, Brazil. Zip code:
34006-065. E-mail: marcusvic1@hotmail.com
Article received: January 5, 2019.
Article accepted: July 8, 2019.
Conflicts of interest: none.
