Otolaryngologic Manifestations of Neurofibromatosis
Judith J. Owens, MD
August 6, 1992

In 1882, in a presentation to Rudolf Virchow, Friedrich von Recklinghausen reviewed three cases from the literature and added two of his own of what is now known as neurofibromatosis type 1 or classic von Recklinghausen's disease (VRD). It is now established that there are several types of neurofibromatosis. Most important is neurofibromatosis type 1 (NF1) and central neurofibromatosis also known as neurofibromatosis type 2 (NF2). A familial syndrome of cafe-au-lait spots not associated with neurofibromas occurs, and a rare type of neurofibromatosis involving an isolated body segment has been reported.

The diagnosis of NF1 requires that two or more of the following be present: 1) at least five cafe-au-lait macules greater than 5 mm; 2) two or more neurofibromas or one plexiform neurofibroma; 3) axillary or inguinal freckling; 4) sphenoid wing dysplasia or congenital bowing or thinning of long bone cortex; 5) bilateral optic gliomas; 6) two Leisch nodules; or, 7) a first degree relative with VRD. The diagnostic criteria of NF2 is fulfilled by the presence of bilateral internal auditory canal (IAC) masses or a first degree relative with NF2 and a single IAC mass, a plexiform neurofibroma, meningioma, glioma, neurofibroma, intracranial or spinal tumor.

Neurofibromas and schwannomas are separate pathologic entities. Neurofibromas are usually multiple, are not encapsulated and the axons seem to be incorporated into the tumor. Neurofibromas may be solitary or plexiform. The plexiform tumor is a poorly circumscribed tumor that forms cords along the segments and branches of nerves. They frequently involve a nerve plexus such as the cervical or lumbar plexus. Schwannomas are usually solitary and encapsulated. The neurites do not transverse the tumor; the tumor pushes the axons aside and is attached to, or even surrounds, the nerve. Antoni A or B pattern can often be identified within a schwannoma. Neurofibromas are characteristic of NF1 and schwannomas are the IAC tumors found in NF2.

Manifestations of both NF1 and NF2 are of otolaryngologic interest. Bilateral vestibular schwannomas characteristic of NF2 pose management dilemmas to the neuro-otologist interested in conserving the patient's hearing for as long as possible. Conductive hearing loss has been reported in a patient with a neurofibroma "seedling" in the perilymphatic space impinging on the stapes footplate. Within the oral cavity the tongue is a site of predilection and unilateral macroglossia is a characteristic finding. These lesions are subject to chronic trauma, and may interfere with speech and mastication. Excision is not always straight-forward as these lesions frequently infiltrate deeply into the neck. The peripharyngeal space is not a site of predilection but cranial nerves IX, X, XI and XII, as well as autonomic nerves can be involved at this location. Schwannomas are more common than neurofibromas in the peripharyngeal space. The nasal cavity and paranasal sinuses are an unusual site of neurofibromas. Epistaxis and nasal obstruction were the presenting complaints of the few cases reported in this location. Ophthalmic findings are common. Leisch nodules are seldom absent in individuals with NF1. Optic gliomas threaten vision in these patients and many authors recommend orbital CT scans in the initial evaluation of newly diagnosed NF1 patients. Periorbital neurofibromas of the skin may interfere with vision and pose difficult and recurring cosmetic challenges.

Neurogenic tumors including neurofibromas of the larynx are uncommon. Some of these have been associated with VRD but the majority of reports do not mention associated features of VRD. The cases of laryngeal plexiform neurofibromas are less common than solitary neurofibromas and some reports do not identify whether or not the neurofibromas are of the plexiform variety. Plexiform neurofibroma exists with and without associated VRD. Extensive involvement of many structures with these tumors is the usual situation. Nearly all of the solitary tumors are supraglottic with a predilection for the aryepiglottic fold or false vocal cord. Based on this anatomic association, Nanson has speculated that they most commonly arise from the superior laryngeal nerve and its terminal ramifications. Schwannomas and neurofibromas have been reported to arise throughout the larynx, involving the false vocal cord, epiglottis, and subglottis. Management of these tumors may be as simple as endoscopic removal or may involve extensive radical surgery to restore function. Plexiform tumors infiltrate widely and complete removal is usually not a realistic goal.

The management of these patients is highly individualized. The variable but always progressive nature of this disease necessitates a cautious, conservative approach whenever possible.

Case Presentation

A 13-year-old Hispanic female with von Recklinghausen's disease presented shortly after birth. She had respiratory difficulties and examination revealed a soft tissue mass in the postcricoid region. Over the following 2 years there was minimal improvement in her inspiratory stridor. Direct laryngoscopy revealed marked enlargement of the previously diagnosed soft tissue mass that now involved the entire postcricoid area, right arytenoid, and pyriform sinus. She was transferred to Texas Children's Hospital where CT scanning demonstrated a mass in the anterior superior mediastinum that surrounded the trachea and extended into the lower neck. Neck exploration revealed a poorly defined mass adjacent to the trachea; biopsies were consistent with plexiform neurofibromatosis. Upon extubation she had marked stridor and an elective tracheostomy was performed. Because of the extent of the tumor, conservative management was planned. For many years she was able to phonate around her tracheostomy tube and had normal language development. However, her physical growth and development fell below the fifth percentile for height and weight. This became an increasing concern for the patient and her family. By age 12 she was experiencing progressive dysphagia and intermittent aphonia. Imaging studies revealed an extensive soft tissue mass that surrounded the larynx and extended into the superior mediastinum. Because of the progressive nature of her symptoms, it was elected to proceed with surgical resection at that time. She underwent a total laryngopharyngectomy and was reconstructed with a jejunal free graft. Subsequent tracheo-esophageal puncture was performed.