Case report

A 10-year-old patient diagnosed with neurofibromatosis type 1 (NF-1), was admitted to the Department of Otolaryngology due to gradually increasing subjective breathing difficulties without shortness of breath or reductions in oxygen saturation. On paediatric patient examination, numerous café-au-lait spots were visible on the skin, with a cutaneous neurofibroma on the right forearm (Figures 1 A, B). In 2019, the patient was hospitalized for a pathological dislocation of the right hip joint. At that time, an magnetic resonance imaging (MRI) revealed a massive plexiform neurofibroma involving the lumbar and sacral spinal nerves on the right side, the sacral plexus, the sciatic and femoral nerves, and their branches. The compression of the tumour caused dislocation and displacement of the right femoral head beyond the acetabular edge, as well as deformity of the right femoral shaft with a reduction in its AP dimension. An orthosis and orthopaedic insoles assist the patient’s gait due to the shortening of the right lower limb compared to the left.

A non-mobile and painless tumour mass of approximately 8 cm × 5 cm was observed in the left submandibular region of the neck. The skin over the lesion showed no signs of discontinuity, tenderness, or inflammation.

Ophthalmological examination confirmed the presence of Lisch nodules on both irises using a slit lamp. Additionally, the patient has visual impairment, including myopia, astigmatism, and suspected glaucoma in both eyes.

Otolaryngological examination revealed that the tympanic membrane appeared normal on both sides. The nose has no pathological discharge in the nasal passages. Throat: there was no purulent discharge on the tonsils; the left posterior pharyngeal wall protruded at the level of the palatine tonsils, which were enlarged and touched at the midline. The larynx below remained unaltered, and the lower throat narrowed. The glottis was broad, and the vocal folds were smooth and mobile as usual.

During hospitalization, two questions had to be answered: whether the tumour was the cause of dyspnoea, and what was the nature of the tumour? An MRI of the neck was performed, which revealed an extensive, poorly defined hypodense tumour in the paravertebral, cervical, and left parotid spaces, extending from the base of the skull to the level of the thyroid lobes. The described tumour encircled the left carotid vessels: the common carotid artery, external carotid artery, and internal carotid artery – over a long segment. At the level of the hyoid bone, the tumour mass penetrated the laryngeal space toward the piriform recess and infiltrated the left parotid gland. The tumour extended to the level of the thyroid lobes and the base of the skull, penetrating the paravertebral space and causing it to thicken up to 16 mm behind the lymphoid tissue of the nasopharynx (Figures 1 C, D).

The radiological picture, medical history, and family history indicated the diagnosis of NF-1. Due to the child’s increasing dyspnoea, the tumour’s location in the vicinity of large vessels, further possibilities of pharmacological treatment, and the desire to avoid a tracheostomy, a decision was made to perform a tonsillectomy to widen the throat space. The tonsillectomy surgical procedure went without complications.

The patient was discharged home after 4 days of hospitalization. No complications occurred after the surgery.

During a follow-up visit 12 months later, the patient did not report any shortness of breath. A follow-up endoscopic examination and contrast MRI showed a stable tumour without progression compared to the previous year’s examination. The patient remains under the care of otolaryngology, haematology, and orthopaedics departments. She is currently undergoing qualification for further genetic diagnosis before the pharmacological treatment.

Discussion

Neurofibromatosis type 1, commonly known as Recklinghausen’s disease, is a genetic disorder with a frequency of approximately 1 in 3,000 births [1]. It is inherited in an autosomal dominant manner. However, half of NF-1 cases are estimated to be associated with a spontaneous mutation on chromosome 17q11.2, which encodes neurofibromin, a multifunctional regulatory protein. Reduced neurofibromin expression disrupts cell division regulation and cellular transport [2, 3]. As a result, the clinical picture includes the development of tumours, particularly within the nervous system. One such example, and one of the main diagnostic criteria for the disease, is the presence of plexiform neurofibromas (PN). These tumours can appear in any part of the body, and their growth causes the deformation of surrounding tissues and related clinical symptoms. Compared to other locations, plexiform neurofibromas in the head and neck region are common and present a challenge during treatment due to the proximity of critical anatomical structures in this area [4]. This article aims to discuss the problematic therapeutic decisions made in the treatment of a child with NF-1 with lesions located, among other areas, in the neck region. Neurofibromatosis type 1 is a complex disease with symptoms that may include tumours in various body parts, such as the neck and head. Diagnosing and treating these tumours is particularly challenging in children. Half of patients exhibit initial symptoms in early childhood, but the disease typically manifests itself fully at the age of 8 [4]. The need to make treatment decisions arises early in the patient’s life, as the fastest tumour growth is observed primarily during childhood and early adulthood [4].

Clinically, two types of neurofibromas are distinguished: cutaneous and plexiform. The former are usually numerous, up to a few centimetres in size, and do not penetrate more deeply than the subcutaneous tissue. On the other hand, PN are invasive, can reach significant sizes, and can disrupt aesthetics and the function of the affected organ or region. More importantly, they are classified as benign lesions with a risk of malignancy. Approximately 5–10% of PNs transform into malignant peripheral nerve sheath tumours [5–7]. The most common problems faced by patients with neurofibromas in the head and neck region include facial deformity, pain, dysphagia, and dyspnoea [6, 8]. Regardless of the lesion type, treating patients with head and neck tumours should be based on a multidisciplinary approach. One of the therapeutic options is surgical treatment; however, achieving complete resection while preserving healthy tissues is challenging in the case of extensive lesions.

For this reason, most procedures are limited to partial excision of the lesion, which exposes the patient to the risk of recurrence. The risk of recurrence depends on the size of the initial tumour and the patient’s age – about 50% show progression within a 10-year observation period, and this risk increases when the lesions are located in the head and neck region, mainly when surgery is performed in patients under the age of ten [6]. Patients with NF often undergo multiple surgeries, frequently in the same area. Long postoperative recovery, aesthetic and functional impairments, and the aforementioned high risk of recurrence suggest that, in the case of children, a watchful waiting approach and conservative treatment should be considered. Conservative treatment of PN in NF-1 focuses on patient observation, assessing tumour size, and emphasizing reducing symptoms related to tumour growth and delaying the need for surgical intervention. Imaging studies such as computed tomography (CT) and MRI play a key role in identifying the tumour’s location, size, and characteristics. Due to the enhanced imaging of neurofibromas in the presence of gadolinium, contrast-enhanced imaging is recommended [6].

Plexiform neurofibromas do not respond to radiation therapy. Conventional chemotherapy offers limited benefits and does not inhibit tumour growth effectively [6]. The formation and growth of tumours in neurofibromatosis result from excessive activation of the RAS protein due to the malfunctioning of neurofibromin, which leads, among other things, to the stimulation of the Ras/MAPK signalling pathway [1]. Newly developed drugs from the MEK inhibitor group work by inhibiting the protein kinase MEK, which can affect the Ras/MAPK pathway and is often overactive in specific proliferative processes. They are used in the treatment of certain cancers, such as melanoma and colon cancer [9]. In 2020, the US FDA approved selumetinib (named Koselugo), a MEK1/2 inhibitor. The drug has been approved for use in the European Union since 2021. Selumetinib reduces the size of plexiform neurofibromas and alleviates symptoms in children [10, 11], and is currently recommended for use from the age of 2 in patients with plexiform neurofibromas that are not eligible for surgical treatment. Like any drug, selumetinib can cause side effects. The most common include dry skin, rash, itching, nausea, vomiting, diarrhoea, abdominal pain, musculoskeletal pain, headaches, and fatigue. If side effects become severe, a dose reduction or even discontinuation of therapy is recommended [10]. It is always important to remember pain management, as the growth of a lesion in NF can cause severe pain in patients. Chronic administration of analgesics is associated with side effects, but reducing the tumour itself, whether through surgical removal or, for example, treatment with selumetinib, also results in a reduction of pain symptoms. Regular neurological, audiological, and ophthalmological check-ups are recommended to assess peripheral nerve function. In our case, aiming to improve the patient’s condition, we chose a partially watchful waiting approach combined with surgical treatment. The tonsillectomy procedure allowed for the expansion of the lower pharyngeal space without the risk of damaging major cervical vessels. The qualification for pharmacological therapy allows the patient to stop the growth progression of the tumours growth or even reduce its size without surgical intervention.

Due to the patient’s family history, Recklinghausen’s disease (also present in the patient’s father and brother) was diagnosed. According to Legius et al. (Table 1), the patient meets 6 out of 7 diagnostic criteria for NF-1 [12].

Conclusions

The treatment of patients with head and neck tumours, especially in children, is a complex process requiring interdisciplinary collaboration among various specialists, such as otolaryngologists, oncologists, paediatricians, neurosurgeons, radiologists, haematologists, and ophthalmologists. Each patient with a neck tumour should be treated individually. The symptoms presented will depend on the extent and location of the tumour. For some patients, a watchful waiting approach and, for example, pharmacological treatment will be sufficient, while in other cases, procedures such as partial or complete tumour removal will be necessary. Diagnosis of a tumour in the neck and head area, particularly when associated with gradually increasing breathing difficulties, may require unconventional therapeutic decisions. Accurate diagnostic evaluation and treatment method selection is crucial to minimize the risk of complications and improve the patient’s quality of life.

Funding

No external funding.

Ethical approval

Not applicable.

Conflict of interest

The authors declare no conflict of interest.

References