Neurofibromatose Type 1 - Een Diepgaande Verkenning van Huidziekten

INTRODUCTION

Neurofibroma is a benign neural tumor which derives from the peripheral nerve sheath, and it consists of the variable mixture of Schwann cells, perineurial-like cells and fibroblasts.[1] Although it is the most common skin lesion, neurofibromas present within the oral cavity are not uncommon.[2] Neurofibromatosis (NF) often involves 5 th cranial nerve and upper cervical nerves, with common sites being tongue, gingiva, major salivary glands and jaw bones.[3] It has also been noticed on lips and mucosa.[4]

Neurofibromas are classified into two types: neurofibromatosis type 1 or von Recklinghausen disease and neurofibromatosis type 2.

Neurofibromatosis type 1 was first described by Frederich von Recklinghausen in 1882.[6] Neurofibromatosis type 1 (NF-1) or von Recklinghausen disease is an autosomal dominant disorder with a basic defect in the embryonic neural crest cells which give rise to ectodermal and mesodermal derivatives that affect one in 3000 live births.[2] Oral manifestations of NF have been reported in only 4%–7% of the affected persons.[7] Palatal swellings may occur from a variety of etiological factors and can originate from the structures within the palate or beyond it. They may be painful when secondarily infected. The mean age of occurrence is 27.5 years with a slight predilection toward females.[8] Treatment for both NF-1 and NF-2 is directed toward controlling symptoms and managing the complications. In dental literature to date, there is one case report of neurofibroma in the palate diagnosed at the age of 18 years with a chief complaint of the lump in the maxillary right palate, and 4–5 café au lait macules were seen in his thoracic region.[9]

We report an unusual case of a palatal neurofibroma with well-demarcated radiolucency diagnosed using cone-beam computed tomography (CBCT) and other findings like several café au lait macules on extremities.

Neurofibromatosis Complications

Possible NF1 complications include:

• Neurological problems like trouble learning or thinking
• Anxiety or distress with changes to your appearance, like large numbers of cafe au lait spots
• Skeletal problems, like bowing of the legs, scoliosis, fractures that don’t heal, or low bone density that increases your risk of osteoporosis
• Vision problems due to a tumor pressing against the optic nerve
• Problems during times of hormonal changes, such as puberty or pregnancy
• Cardiovascular problems like high blood pressure
• Breathing problems
• Higher risk of some cancers, such as breast cancer, leukemia, colorectal cancer, brain tumors, and some soft tissue cancers
• Benign adrenal gland tumor that could cause high blood pressure

Possible NF2 complications include:

• Partial hearing loss or deafness
• Nerve damage in the face
• Benign skin tumors or schwannomas
• Vision problems
• Weakness or numbness in your extremities
• Benign brain or spine tumors that need to be removed with surgery

One possible schwannomatosis complication is severe pain that requires specialist medical treatment or even surgery.

CASE REPORT

A 12-year-old female child reported to the Department of Pedodontics and Preventive Dentistry, with a painless swelling on the right side of the hard palate and displaced tooth on the same side. It had become noticeable for the past 6 years which gradually increased over a period of time. There was a positive family history and no relevant medical history. On physical examination, several café au lait macules and freckling spots on the patient's legs and palms were evident [Figure ​ [Figure1b 1b and ​ andc]. c ]. The patient was referred to dermatologic evaluation.

(a) Intraoral view showing the swelling involving the right side of the hard palate and extending to mid palate. (b and c) Several café au lait macules and freckling spots on the patient's neck and palms. (d) Cone-beam computed tomography showing the signs of intrabony defects

Radiographic investigations such as CBCT scan (HDX WILL, On demand 3D, North Korea), axial and coronal sections, which showed a solitary, intraosseous, well-defined, homogenous isodense to hypodense mass arising from within the right maxilla [ Figure 1d ].

Fine-needle aspiration cytology of the lesion was carried out, which was nondiagnostic [ Figure 2a ], considering the patient's age and site of the swelling, the differential diagnosis of pleomorphic adenoma, mucoepidermoid carcinoma, polymorphous low-grade adenocarcinoma, Non-Hodgkin lymphoma and neurofibroma was given. A decision was taken to carry out an incisional biopsy under general anesthesia followed by the primary closure [ Figure 2b ].

Hintergründe zur Studie

Methoden:

Es erfolgte ein mehrschrittiger Prozess, der mit der Delphi Methode (ein systematisches, mehrstufiges Befragungsverfahren unter Experten) startete und damit weltweit NF-Experten zur Abstimmung und Meinungsbildung zusammenführte. Im Anschluss wurden Experten einbezogen, die nicht spezifisch auf dem Gebiet der NF ausgewiesen sind, sowie Patienten, Selbsthilfe- und Patientenvertretergruppen, um die so formulierten Kriterien auch durch diese Gruppen zu überprüfen.

Ergebnisse:

(1) die diagnostische Wertigkeit der geänderten Kriterien weiter zu überprüfen ist,

(2) bislang nicht einbezogenen Kriterien zu berücksichtigen sind und/oder

(3) neue klinische oder andere Merkmale dieser Erkrankungen definiert werden.

Aus diesen Gründen wurde vorgeschlagen, die diagnostischen Kriterien für NF1 und Legius Syndrom regelmäßig zu überprüfen und auf den neuesten Stand zu bringen.

Begriffe und Geschichte:

Neurofibromatose Typ 1 (NF1, OMIM 613113) wird autosomal-dominant vererbt und ist charakterisiert durch multiple Café-au-lait Flecken (CAL), Sommersprossen der Hautfalten (Freckling oder genauer definiert als lentigenöse Maculae, weil nur in Bereichen auftretend, die nicht der Sonne ausgesetzt sind), Lischknötchen, Tumore des Nervensystems und andere Merkmale. Die Krankheitsmerkmale können in jedem Körperabschnitt bzw. Körpersystem auftreten (1, 2). Es besteht ein signifikant erhöhtes Risiko für das Auftreten bestimmter Tumoren einschließlich Brustkrebs bei Frauen < 50 Jahre, für maligne periphere Nervenscheidentumoren (MPNST) und Gehirntumoren (3).

Das NF1-Gen wurde im Jahr 1990 genetisch identifiziert (9, 10). Nachfolgende zellbiologische Studien zeigen, dass das Protein des NF1-Gens, das sogenannte Neurofibromin weitgehend als GTPase aktivierendes Protein (GAP) funktioniert und ein negativer Regulator des RAS/MAPKinase Pathways ist (11). Fortschritte in der Zellbiologie und Tiermodellstudien führten zur Identifikation der MEK-Inhibitoren, die das Wachstum der plexiformen Neurofibrome (PNF) reduzieren und zur Regression bringen können. Im April 2020 wurde das Medikament Selumetinib von der amerikanischen Behörde FDA (Food and Drug Administration) zugelassen, das zur Behandlung von Kindern und Jugendlichen mit NF1-assoziierten symptomatischen PNF eingesetzt wird (11).

CONCLUSION

NF is a multisystem disorder requiring management by multiple disciplines, often coordinated through a primary care physician, dentist and a dermatologist. Considering other advanced investigations such as CBCT, immunohistochemical (S-100 protein test) is often beneficial for an accurate diagnosis. Hence, early detection with advanced techniques and investigations with complete resection minimizes the reoccurrence of such tumors.

Pediatric dentists should be aware of the characteristics of the disease in children, in particular about the malocclusions caused, because the lesion and the radiological findings to prevent further complications and to manage the therapies in a more systematic way. Moreover, they should monitor the patients with a long-term follow-up to screen the possible development of other lesions in the hard and soft tissue.

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.