Laryngeal neurofibroma: case report and review of the literature

Background: Laryngeal neurofibromatosis (LNF) represents an exceedingly rare manifestation of neurofibromatosis type 1 (NF1), a genetic disorder affecting neural tissue development with an incidence of approximately 1:3000 live births. While NF1 typically presents with cutaneous neurofibromas, laryngeal involvement is exceptional.

Methods: A case of LNF associated with NF1 diagnosed at West China Hospital is presented, accompanied by a comprehensive literature review. A 21-year-old female presented with progressive hoarseness over two years. Diagnostic evaluation included physical examination revealing café-au-lait macules and laryngeal submucosal swelling, and computed tomography (CT) identifying a hypodense parapharyngeal space nodule. The patient underwent microlaryngoscopic excision of the mass. Histopathological examination and genetic analysis were performed.

Results: Histopathology confirmed the mass as a neurofibroma. Genetic analysis identified a pathogenic NF1 gene mutation. Microlaryngoscopic excision was successful, achieving complete removal with minimal intraoperative bleeding and no vocal cord damage, resulting in a favorable postoperative outcome.

Conclusions: This case details the successful diagnosis and management of rare laryngeal neurofibromatosis, confirming microlaryngoscopic excision as an effective approach. The integrated literature review synthesizes current understanding of this rare entity.

Introduction

Neurofibromatosis, an array of genetic disorders, consists of two distinct autosomal dominant disorders: neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) (1). It is typified by irregularities in the development of neural tissue, with an approximate incidence of 1 in 3,000 live births (2). The condition most commonly presents as cutaneous and subcutaneous neurofibromas, benign tumors that affect the skin and underlying tissues (3). Yet, in a minority of cases, these growths may proliferate into deeper anatomical regions, such as the larynx, culminating in a form known as laryngeal neurofibromatosis (LNF) (4).

LNF is exceedingly rare, constituting only 0.03 to 0.1 percent of all benign laryngeal tumors (5). The molecular etiology of LNF is associated with mutations in the NF1 gene, which encodes for a protein pivotal in regulating cell growth (6). Disruptions in this regulatory mechanism can lead to the unchecked proliferation of Schwann cells, resulting in tumorigenesis that may significantly encroach upon and exert pressure on essential laryngeal structures (7, 8). LNF grows very slowly and therefore can present later in life with loss or change of voice, dysphagia, dysphonia, and stridor. This study delineates a case of laryngeal neurofibromatosis enrolled in West China hospital and concurrently furnishes a comprehensive literature review, aspiring to enhance the comprehension of this rare yet consequential disorder.

Case report

A 21-year-old female was admitted to our hospital with a 2-year history of progressive hoarseness. It is noteworthy that a definitive diagnosis of neurofibromatosis had not been established prior to this presentation. She did not exhibit symptoms such as choking on liquids, difficulty swallowing, a sensation of a foreign body in the throat, or any respiratory distress, including tightness of breath or chest discomfort.

Upon physical examination, she presented with a deep, hoarse voice and difficulty producing high-pitched sounds. Café-au-lait macules (Figures 1A–E) were observed on the neck, upper arms, abdomen, and back, accompanied by scattered pigmentary deposits (Figures 1F–H) throughout the body. Electronic nasopharyngolaryngoscopy (Figure 1I) revealed the left ventricular band was markedly bulging with a smooth surface, obscuring the laryngeal ventricle and vocal cords, partially blocking the glottis. The right ventricular band and vocal cord appeared structurally normal with normal vocal cord mobility, and the glottal chink is slightly narrower than normal. A neck CT scan (Figure 1J) showed a slightly hypodense nodule in the left paralaryngeal space, measuring approximately 2.8 x 1.8 cm, with clear boundaries and no significant enhancement. The left aryepiglottic fold, laryngopharynx, and surrounding soft tissues were compressed and displaced, leading to stenosis of the laryngopharynx and the left pyriform sinus. Prior to surgery, a preoperative GRBAS score was completed, with the subjective voice assessment rating as G: 3, R: 3, B: 1, A: 1, S: 0, indicating severe hoarseness (Figure 2H red part).

Figure 1

Figure 1. Preoperative physical and specialist examination findings. (A–E) Café-au-lait macules were observed on the neck, upper arms, abdomen, back and inguinal region. (F–H) Generalized scattered pigmentary macules throughout the body. (I). Laryngoscopy showed a submucosal swelling on the left ventricular band with a smooth surface, obstructing the view of the left vocal cord. (J) Computed tomography (CT) scan of the neck showed a slightly hypodense nodule in the left parapharyngeal space, measuring approximately 2.8 x 1.8 cm, with clear boundaries and no significant enhancement.

Figure 2

Figure 2. Intraoperative surgery overview, postoperative pathology, and follow-up outcomes. (A) Submucosal tumor with clear boundaries and no significant adhesion was separated along the tumor margin. (B) Intraoperative findings included a bulging left ventricular band, smooth mucosa of the laryngeal ventricle, and a submucosal yellowish, firm mass measuring approximately 1 cm x 2 cm x 5 cm, encapsulated. (C) After complete tumor resection, hemostasis was secured and the wound was cleaned without damaging the vocal cords. (D) The majority of the tumor consisted spindle cell proliferation and myxoid degeneration of the stromacytoplasm (HE staining, 20×). (E) Immunohistochemistry was positive for S100 (20×). (F) Immunohistochemistry was positive for SOX-10 (20×). (G) Immunohistochemistry was positive for CD34 (20×). (H) Preoperative vs Postoperative GRBAS Scores Comparison. (I) No tumor recurrence was found in follow-up laryngoscopy, with both vocal cords having smooth surfaces and normal mobility.

Given that the CT findings indicated a localized tumor with benign characteristics and the comprehensive physical examination suggested a high likelihood of a neurogenic tumor, we opted for transoral endoscopic surgery while also preparing for the possibility of open surgical intervention. Under general anesthesia, a laryngoscope was inserted to fully expose the left ventricular band. Intraoperatively, the left ventricular band was observed to bulge inward, compressing and obscuring the laryngeal ventricle and vocal cords, with a smooth mucosal surface. A plasma incision was made on the mucosal surface, revealing a smooth submucosal tumor that was soft in consistency, well-demarcated from the surrounding tissue, and without significant adhesion (Figure 2A). Dissection was carried out along the tumor’s boundary, with extensions of the incision made as necessary, until the medial, lateral, and anterior aspects were completely freed from the surrounding tissue. After the tumor was completely excised, hemostasis was thoroughly achieved and the wound was cleaned, with care taken not to damage the vocal cords or other normal tissues (Figure 2B). The surgery lasted 30 minutes, with minimal bleeding of less than 2 ml. The patient recovered well after surgery, with the voice returning to normal on the second day postoperatively, and normal breathing and swallowing functions. There were no significant discomforts such as fever, sore throat, or hemoptysis, and the patient was discharged smoothly on the third day postoperatively.

The tumor measuring approximately 1 cm x 2 cm x 5 cm was completely excised (Figure 2C). Postoperative pathological results (Figures 2D–G) demonstrated S100 (+), SOX10 (+), H3K27me3 (not lost), CD34 (+), D2-40 (-), p53 (+), p16 (+), SMA(-), Desmin (−), with a Ki67 positive rate of approximately 2%.

One month postoperatively, the patient underwent GRBAS score again, with a subjective voice assessment rating of G: 0, R: 0, B: 0, A: 0, S: 0 (Figure 2H blue part), representing a normal voice, marking a significant change from the preoperative condition. At the eight-month follow-up laryngoscopy postoperatively, the laryngeal cavity appeared smooth, with no evidence of recurrence (Figure 2I). The patient’s vocal quality was assessed as normal, with no clinically significant dysphonia observed.

To elucidate the diagnosis, genetic analysis was conducted on the patient. The findings disclosed a heterozygous mutation within the NFI locus: a nucleotide transition from adenine to guanine at position 1466 (c.1466A>G), culminating in an amino acid substitution at codon 489, where tyrosine is replaced by cysteine (p.Tyr489Cys). The chronological sequence of key events from initial presentation through surgery and follow-up is summarized in Figure 3.

Figure 3

Figure 3. Timeline of diagnosis, treatment, and follow-up for the patient with laryngeal neurofibroma. Key events from symptom onset through postoperative follow-up are chronologically displayed.

Through a comprehensive assessment of histological diagnosis and genetic testing, the patient was ultimately diagnosed with laryngeal neurofibromatosis.

Discussion

As previously mentioned, LNF is an exceedingly rare laryngeal tumor that are mainly located in the supraglottic, and awareness of it remains limited. As of July 2024, even though there have been approximately 134 well-documented cases of LNF reported in the literature, timely and effective diagnosis and treatment remain limited. In order to provide a comprehensive elucidation of the most recent epidemiological trends, as well as current diagnostic and therapeutic prospects for LNF, we have delved into the characteristics of laryngeal neurofibromatosis as gleaned from our case series (Table 1), highlighting the clinical manifestations, systemic associations, and treatment modalities that define this complex condition (Table 2).

Table 1

Table 1. Cases of laryngeal neurofibroma in recent 30 years.

Table 2

Table 2. Patient characteristics of laryngeal neurofibroma in recent 30 years.

The epidemiological characteristics of LNF, as derived from our extensive analysis of 134 cases, reveal a disease with a wide age distribution, affecting both pediatric (9) to geriatric (10) populations. This extensive age range is further detailed in the provided table, which indicates that the majority of the cases fall within the 0–78 year-old age bracket, highlighting the disease’s potential to impact individuals across the lifespan. The gender distribution among the cases is fairly balanced, with 70 males (52.24%) and 64 females (47.76%) identified in the study. This balance suggests that LNF does not exhibit a significant gender predilection, which is consistent with the broader understanding of neurofibromatosis type 1 (NF1), a condition that is known to affect both sexes equally (11).

The local manifestations of LNF are diverse and can include respiratory symptoms (12), voice changes (10, 13), pharyngeal discomfort (14, 15), and sleep disorders (16, 17). Firstly, the primary complaints in our series of 134 cases of LNF are predominantly characterized by respiratory symptoms (18–21). These symptoms, which may include shortness of breath, coughing, and chest tightness, underscore the significant impact that LNF can have on an individual’s respiratory function. Secondly, voice changes represent another common presentation (21–23). These changes can range from mild huskiness to complete voice loss and are indicative of the tumors’ potential to affect the function of the vocal cords. The vocal cords are delicate structures responsible for voice production, and any mass effect from a neurofibroma can disrupt their normal movement and coordination. In the specific case mentioned, the patient was admitted to the hospital with hoarseness as the main complaint, which is a direct consequence of the tumor’s impact on vocal cord function. Thirdly, while less frequently reported than respiratory symptoms or voice changes, pharyngeal discomfort and sleep disorders are also part of the clinical picture of LNF (14–17). Pharyngeal discomfort can result from the physical presence of the tumor in the throat, causing a sensation of irritation or a lump. Sleep disorders, such as sleep apnea or insomnia, can arise due to the respiratory disturbances caused by the neurofibroma. Patients with LNF can experience a combination of respiratory symptoms, voice changes, pharyngeal discomfort, and sleep disorders (21–23). The co-occurrence of these symptoms can complicate the clinical presentation and may require a multidisciplinary approach to management.

LNF primarily affects the supraglottic region (16, 24, 25), with a particular predilection for the arytenoepiglottic and/or arytenoid folds due to its rich lymphatic tissue and extensive network of nerves and blood vessels. Under laryngoscopy, LNF typically present as round or oval-shaped tumors with a smooth surface and a solid capsule (4, 21, 26). These tumors are often well-circumscribed and may appear as soft tissue masses within the larynx. Correspondingly, LNF on CT imaging are also characterized by their appearance as well-circumscribed, round, or oval-shaped tumors with a smooth surface and solid capsule (27). They often present as soft tissue masses within the larynx and are typically hypoattenuating and may show minimal enhancement after contrast administration (7). This suggests a composition rich in nerve sheath cells and fibrous tissue (28).

LNF are a distinct manifestation of NF that specifically affect the laryngeal region. Given this, a meticulous and comprehensive physical examination is of significant importance for the diagnosis of LNF. Patients with LNF often exhibit systemic café-au-lait macules, which are among the most characteristic cutaneous features of the condition (15, 27, 29, 30). These macules, along with other clinical features such as neurofibromas, axillary or inguinal freckling, optic pathway gliomas (OPG), more than two Lisch nodules, sphenoid dysplasia, or long bone abnormalities, are part of the diagnostic criteria (31). A thorough evaluation can reveal these features, aiding in the identification of LNF. In particular, the presence of café-au-lait macules and extensive freckling, as seen in the presented case, are key indicators.

The pathological hallmarks of LNF are attributable to its cellular constituent (11). The pathological hallmarks of laryngeal neurofibromas (LNF) are defined by their cellular composition. On hematoxylin and eosin (HE) staining, neurofibromas are characterized by spindle-shaped Schwann cells and fibroblasts interwoven within a collagenous and myxoid stroma, forming a loosely textured neurofibrous matrix. These tumors typically exhibit a low mitotic index, with fewer than 2 mitoses per 10 high-power fields (HPF), and minimal cellular atypia. Immunohistochemically, LNF demonstrate diffuse positivity for S-100 protein, a marker predominantly expressed by Schwann cells in the nervous system. This immunohistochemical feature is indicative of the neural crest origin of the tumor cells (32). Additionally, SOX10, a transcription factor, is also positive in neurofibromas, further supporting their neural crest derivation (11). The identification of a positive fibroblastic network through CD34 immunostaining is characteristic of neurofibromas, highlighting the presence of fibroblasts within the tumor matrix. The tumor does not express cytokeratins, smooth muscle actin (SMA), or desmin (33). Furthermore, neurofibromas typically display a low Ki-67 proliferation index, below 2-5%, which is reflective of their benign nature and suggests a low rate of cellular proliferation (34). The postoperative immunohistochemical profile of this case was highly consistent with the characteristics of LNF.

Family history data reveal a strong positive association in the majority of cases(67.26%), reinforcing the genetic basis of neurofibromatosis and emphasizing the importance of genetic counseling and family screening (20, 25, 35, 36). Genetic counseling is also an important aspect of care for individuals with NF1, as it can help manage the condition and understand the potential for disease progression or complications. In this case, the patient does not have a family history of NF, but genetic testing has identified a mutation in the NF1 gene (26).

Genetic testing plays a pivotal role in the classification of neurofibromatosis. Neurofibromatosis encompasses two distinct types: NF1 and NF2, which share some clinical similarities but have entirely different genetic bases and causative genes (32). NF1 is caused by mutations in the NF1 gene, located on chromosome 17q11.2 (14). This gene encodes neurofibromin, a protein that negatively regulates cell growth and differentiation. Mutations in NF1 lead to uncontrolled cell proliferation, resulting in cutaneous and neurofibromatous lesions. NF2, on the other hand, is caused by mutations in the NF2 gene on chromosome 22q12. The protein encoded by NF2 (37), merlin, plays a crucial role in cell adhesion and growth control. Mutations in NF2 typically lead to bilateral vestibular schwannomas (acoustic neuromas). Genetic testing can precisely identify the mutation types of NF1 and NF2, enabling molecular-level diagnosis and preventing misdiagnoses or missed diagnoses that may occur based solely on clinical presentations.

Treatment modalities are heavily skewed toward endoscopic surgeries (9, 30, 38, 39), reflecting a preference for minimally invasive approaches that may offer reduced morbidity and faster recovery times. Open and excision surgeries remain a viable option for more complex or extensive tumors. 30.5% were resected endoscopically (40), including in this case with the procedure taking only 30 minutes and blood loss being less than 2 ml. The key points of the surgical procedure involve adequate exposure of the tumor, complete resection along its borders, and preservation of healthy tissue. As a novelty in the treatment of this pathology, in 2018, Arnold et al (24) published the first case of LNF treated with robotic surgery transoral in a pediatric patient, with excellent results functional and without recurrence at 5 months of tracking. Because there are few studies carried out and all based on case reports and reviews retrospective, there is no absolute evidence about of the diagnostic algorithm or the treatment gold standard. Prospective studies are limited due to the rarity of the LNF. Complications may occur bleeding, airway obstruction. In some cases it is necessary to perform a tracheostomy, which requires about 40% of patients (19).

A critical consideration in the management of laryngeal neurofibromas is the recognition of histological subtypes, particularly the distinction of the plexiform variant. Unlike their solitary or localized counterparts, plexiform neurofibromas exhibit a diffuse, multi-fascicular growth pattern that infiltrates along the course of nerve branches (32). This subtype is highly characteristic of, and often pathognomonic for, NF1. Of paramount clinical importance is the well-established association between plexiform neurofibromas and a significantly elevated risk of malignant transformation into Malignant Peripheral Nerve Sheath Tumors (MPNST) (32). For individuals with NF1, the lifetime risk of this transformation is estimated to be between 5% and 15% (33). Therefore, identifying a plexiform pattern is not merely an academic exercise but carries direct and serious implications for prognostic stratification, patient counseling, and mandating vigilant, long-term clinical and radiographic surveillance.

The vast majority of patients with LNF experience a favorable prognosis after surgical resection (4, 28, 37, 41). Postoperative follow-up indicates an improvement in clinical symptoms, with no recurrence of the tumor observed (42–45). However, these findings must be interpreted with caution, as they likely reflect limited long-term follow-up data and publication bias rather than an absence of risk. Given the well-documented infiltrative growth pattern of neurofibromas—particularly the plexiform subtype—and the possibility of multifocal disease in NF1, a lifelong potential for local recurrence or new lesion development persists. Symptoms such as hoarseness and dyspnea are significantly ameliorated (40, 46). Long-term follow-up is of utmost importance because of the risk of malignancy (2% to 5%) (47). There is no consensus on frequency, but it should be performed by direct laryngoscopy to warn of recurrences.

Conclusion

This case is an unusual presentation of NF-1 with laryngeal lesions, and our case series underscored the multifaceted nature of LNF, with a focus on respiratory and vocal manifestations. The predominance of dermatological findings and the supraglottic region involvement reinforces the link to NF1, mandating a multidisciplinary approach to patient care. The preference for endoscopic treatment reflects a trend toward minimally invasive techniques, with the need for continued evaluation of long-term outcomes. The genetic predisposition highlighted by family history data underscores the importance of genetic assessment and counseling in disease management. Future research should aim to provide more detailed phenotypic characterization and long-term outcome data to further refine treatment strategies and prognostic estimations.

Data availability statement

Requests to access the datasets should be directed to YG, Z2FveWF5YV94anR1QDE2My5jb20=.

Ethics statement

The studies involving humans were approved by Ethics Committee of West China Hospital, Sichuan University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Author contributions

YG: Writing – original draft, Writing – review & editing. WM: Visualization, Writing – review & editing. HZ: Data curation, Writing – review & editing. YZ: Investigation, Writing – review & editing. HY: Resources, Supervision, Writing – review & editing.

Funding

The author(s) declared that financial support was received for this work and/or its publication. The authors acknowledge financial support from the “Sichuan University-Zigong Municipal Government Science and Technology Cooperation Special Fund” (Grant No. 2023CDZG-18).

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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References

1. Lucas CG, Gross AM, Romo CG, Dehner CA, Lazar AJ, Miettinen M, et al. Consensus recommendations for an integrated diagnostic approach to peripheral nerve sheath tumors arising in the setting of Neurofibromatosis type 1 (NF1). Neuro Oncol. (2024) 27(3):616–24. doi: 10.1093/neuonc/noae235

PubMed Abstract | Crossref Full Text | Google Scholar

2. Walker L, Thompson D, Easton D, Ponder B, Ponder M, Frayling I, et al. A prospective study of neurofibromatosis type 1 cancer incidence in the UK. Br J Cancer. (2006) 95:233–8. doi: 10.1038/sj.bjc.6603227

PubMed Abstract | Crossref Full Text | Google Scholar

3. Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson SM, et al. Birth incidence and prevalence of tumor-prone syndromes: Estimates from a UK family genetic register service. Am J Med Genet A. (2010) 152A:327–32. doi: 10.1002/ajmg.a.33139

PubMed Abstract | Crossref Full Text | Google Scholar

4. Naunheim MR, Plotkin SR, Franco RA, and Song PC. Laryngeal manifestations of neurofibromatosis. Otolaryngol Head Neck Surg. (2016) 154:494–7. doi: 10.1177/0194599815626133

PubMed Abstract | Crossref Full Text | Google Scholar

5. Jones SR, Myers EN, and Barnes L. Benign neoplasms of the larynx. Otolaryngol Clin North Am. (1984) 17:151–78. doi: 10.1016/S0030-6665(20)32005-3

Crossref Full Text | Google Scholar

6. Hirsch NP, Murphy A, and Radcliffe JJ. Neurofibromatosis: Clinical presentations and anaesthetic implications. Br J Anaesth. (2001) 86:555–64. doi: 10.1093/bja/86.4.555

PubMed Abstract | Crossref Full Text | Google Scholar

7. Zhang L, Jiang J, Hu C, Yang H, Deng P, and Li Y. Diagnosis and management of solitary laryngeal neurofibromas. Am J Med Sci. (2018) 356:79–83. doi: 10.1016/j.amjms.2017.12.005

PubMed Abstract | Crossref Full Text | Google Scholar

8. Chang-Lo M. Laryngeal involvement in Von Recklinghausen’s disease: A case report and review of the literature. Laryngoscope. (1977) 87:435–42. doi: 10.1288/00005537-197703000-00017

PubMed Abstract | Crossref Full Text | Google Scholar

9. Wang Z, Zhang Y, Cui H, and Yao W. Endoscopic low-temperature plasma radiofrequency ablation for laryngeal plexiform neurobromatosis-1 in an infant: Case report and review of the literature. Technol Health Care. (2016) 24:775–80. doi: 10.3233/THC-161218

PubMed Abstract | Crossref Full Text | Google Scholar

10. Liu J, Wong CF, Lim F, and Kanagalingam J. Glottic neurofibroma in an elderly patient: A case report. J Voice. (2013) 27:644–6. doi: 10.1016/j.jvoice.2013.02.002

PubMed Abstract | Crossref Full Text | Google Scholar

11. Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, and Johnson KJ. Neurofibromatosis type 1. Nat Rev Dis Primers. (2017) 3:17004. doi: 10.1038/nrdp.2017.4

PubMed Abstract | Crossref Full Text | Google Scholar

12. Goonewardene TW. An unusual case of respiratory obstruction following anaesthesia. Case report. Br J Anaesth. (1967) 39(12):983–5. doi: 10.1093/bja/39.12.983

PubMed Abstract | Crossref Full Text | Google Scholar

13. Cosyns M, Mortier G, Corthals P, Janssens S, and van Borsel J. Voice characteristics in adults with neurofibromatosis type 1. J Voice. (2011) 25:759–64. doi: 10.1016/j.jvoice.2010.07.007

PubMed Abstract | Crossref Full Text | Google Scholar

14. Dave SP, Farooq U, and Civantos FJ. Management of advanced laryngeal and hypopharyngeal plexiform neurofibroma in adults. Am J Otolaryngol. (2008) 29:279–83. doi: 10.1016/j.amjoto.2006.06.021

PubMed Abstract | Crossref Full Text | Google Scholar

15. Sarkar S, Seth C, Dutta M, and Bandyopadhyay SN. Solitary isolated oropharyngeal neurofibroma presenting with dysphagia in the setting of von recklinghausen’s disease. Ear Nose Throat J. (2024) 2024:1455613241249022. doi: 10.1177/01455613241249022

PubMed Abstract | Crossref Full Text | Google Scholar

16. Hutnik R, Chen PG, and Mortensen MM. A solitary supraglottic neurofibroma presenting with obstructive sleep apnea in an adolescent. J Clin Sleep Med. (2020) 16:635–8. doi: 10.5664/jcsm.8290

PubMed Abstract | Crossref Full Text | Google Scholar

17. Setabutr D, Perez MR, Truong MT, Senders CW, and Rubinstein BK. Neurofibromatosis of the larynx causing stridor and sleep apnea. Am J Otolaryngol. (2014) 35:631–5. doi: 10.1016/j.amjoto.2014.04.009

PubMed Abstract | Crossref Full Text | Google Scholar

18. Schuster-Bruce J, Kelly M, Bernic A, Brar S, Barber J, and Modayil P. Coblation debulking of a paediatric laryngeal plexiform neurofibroma: A pragmatic response to a rare tumour. J Surg Case Rep. (2022) 2022:rjab646. doi: 10.1093/jscr/rjab646

PubMed Abstract | Crossref Full Text | Google Scholar

19. Kasapoglu F, Ozdemircan T, and Erisen L. Laryngeal plexiform neurofibroma in a child. Ear Nose Throat J. (2013) 92:E31. doi: 10.1177/014556131309200619

PubMed Abstract | Crossref Full Text | Google Scholar

20. Gstöttner M, Galvan O, Gschwendtner A, and Neher A. Solitary subglottic neurofibroma: A report of an unusual manifestation. Eur Arch Otorhinolaryngol. (2005) 262:705–7. doi: 10.1007/s00405-004-0886-x

PubMed Abstract | Crossref Full Text | Google Scholar

21. Kang H, Kim JP, Kwon OJ, and Woo SH. A case of neurofibroma arising from the aryepiglottic fold of type I neurofibromatosis. Korean J Otorhinolaryngol-Head Neck Surg. (2015) 58:351. doi: 10.3342/kjorl-hns.2015.58.5.351

Crossref Full Text | Google Scholar

22. Chhablani N, Verma H, Bhatnagar S, Shukla S, and Acharya S. Schwannoma of the larynxA rare case report. JCDR. (2019). doi: 10.7860/JCDR/2019/39585.12661

Crossref Full Text | Google Scholar

23. Chen YC, Lee KS, Yang CC, and Chang KC. Laryngeal neurofibroma: case report of a child. Int J Pediatr Otorhinolaryngol. (2002) 65(2):167–70. doi: 10.1016/S0165-5876(02)00151-9

PubMed Abstract | Crossref Full Text | Google Scholar

24. Arnold MA, Mortelliti AJ, and Marzouk MF. Transoral resection of extensive pediatric supraglottic neurofibroma. Laryngoscope. (2018) 128:2525–8. doi: 10.1002/lary.27186

PubMed Abstract | Crossref Full Text | Google Scholar

25. Czinger J and Fekete-Szabó G. Neurofibroma of the supraglottic larynx in childhood. J Laryngol Otol. (1994) 108:156–8. doi: 10.1017/s0022215100126155

PubMed Abstract | Crossref Full Text | Google Scholar

26. Cunha B, Pacheco R, Fonseca I, and Borges A. Solitary neurofibroma of the larynx: A diagnostic challenge. BMJ Case Rep. (2021) 14(1):e236682. doi: 10.1136/bcr-2020-236682

PubMed Abstract | Crossref Full Text | Google Scholar

27. Seth C, Dutta M, and Kadambott S. Solitary laryngeal neurofibroma in an elderly patient with von recklinghausen’s disease. Ear Nose Throat J. (2025) 104(2):81–4. doi: 10.1177/01455613221098275

PubMed Abstract | Crossref Full Text | Google Scholar

28. Sunny F, Jishana J, Naik P, and Kurien M. Shredded carrots in the larynx: A rare case of neurofibroma of vocal cord. J Curr Res Sci Med. (2019) 5:65. doi: 10.4103/jcrsm.jcrsm_37_18

Crossref Full Text | Google Scholar

29. Ghosh A, Kundu P, Dhar S, and Bhattacharya A. A child with multiple café au lait macules: Rare presentation of plexiform neurofibromatosis with facial dysmorphism, alopecia, proptosis, stridor, and limb length discrepancy. Indian J Paediatr Dermatol. (2018) 19:263. doi: 10.4103/ijpd.IJPD_12_17

Crossref Full Text | Google Scholar

30. Zou Q, Yao H, Yang Y, and Tang X. Application of peroral endoscopic-assisted laryngeal microsurgery in children with laryngeal neurofibromas. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. (2023) 37:960–3. doi: 10.13201/j.issn.2096-7993.2023.12.006

PubMed Abstract | Crossref Full Text | Google Scholar

31. Legius E, Messiaen L, Wolkenstein P, Pancza P, Avery RA, Berman Y, et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: An international consensus recommendation. Genet Med. (2021) 23:1506–13. doi: 10.1093/hmg/9.20.3055

PubMed Abstract | Crossref Full Text | Google Scholar

32. Belakhoua SM and Rodriguez FJ. Diagnostic pathology of tumors of peripheral nerve. Neurosurgery. (2021) 88:443–56. doi: 10.1093/neuros/nyab021

Crossref Full Text | Google Scholar

33. Miettinen MM, Antonescu CR, Fletcher CDM, Kim A, Lazar AJ, Quezado MM, et al. Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into Malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1-a consensus overview. Hum Pathol. (2017) 67:1–10. doi: 10.1016/j.humpath.2017.05.010

PubMed Abstract | Crossref Full Text | Google Scholar

34. Chinn SB, Collar RM, McHugh JB, Hogikyan ND, and Thorne MC. Pediatric laryngeal neurofibroma: Case report and review of the literature. Int J Pediatr Otorhinolaryngol. (2014) 78:142–7. doi: 10.1016/j.ijporl.2013.10.047

PubMed Abstract | Crossref Full Text | Google Scholar

35. Nishino H, Ishikawa K, Ishida T, and Kitamura K. A case of laryngeal neurinoma with neurofibromatosis. Auris Nasus Larynx. (1998) 21(1):95–9. doi: 10.1016/s0385-8146(98)00052-2

PubMed Abstract | Crossref Full Text | Google Scholar

36. Chen Y-C, Lee K-S, Yang C-C, and Chang K-C. Laryngeal neurofibroma: Case report of a child. Int J Pediatr Otorhinolaryngol. (2002) 65:167–70. doi: 10.1016/s0165-5876(02)00151-9

PubMed Abstract | Crossref Full Text | Google Scholar

37. Garabédian EN, Ducroz V, Ayache D, and Triglia JM. Results of partial laryngectomy for benign neural tumors of the larynx in children. Ann Otol Rhinol Laryngol. (1999) 108:666–71. doi: 10.1177/000348949910800709

PubMed Abstract | Crossref Full Text | Google Scholar

38. Seyedian M, Supance JS, Quenelle DJ, and Crissman J. Endolaryngeal neurofibromas. Otolaryngol Head Neck Surg. (1979) 88(1):74–8. doi: 10.1177/019459988008800118

PubMed Abstract | Crossref Full Text | Google Scholar

39. Hisa Y, Tatemoto K, DeJima K, Nishiyama Y, and Masuda Y. Laser vestibulectomy for endolaryngeal neurofibroma. Otolaryngol Head Neck Surg. (1995) 113:459–61. doi: 10.1016/S0194-59989570085-4

PubMed Abstract | Crossref Full Text | Google Scholar

40. Varela-Goodall N, Acosta MB, Scatolini ML, and Cocciaglia A. Pediatric neurofibromatosis of the larynx: Report ofatypical location. Arch Argent Pediatr. (2023) 121:e202202782. doi: 10.5546/aap.2022-02782.eng

PubMed Abstract | Crossref Full Text | Google Scholar

41. Mobashir MK, Mohamed AES, El-Anwar MW, El Sayed AE, and Fouad MA. Massive plexiform neurofibroma of the neck and larynx. Int Arch Otorhinolaryngol. (2015) 19:349–53. doi: 10.1055/s-0034-1396793

PubMed Abstract | Crossref Full Text | Google Scholar

42. Weber R and Kronsbein H. Der seltene Fall–Neurilemmom der Stimmlippe. Laryngorhinootologie. (1992) 71:426–8. doi: 10.1055/s-2007-997328

PubMed Abstract | Crossref Full Text | Google Scholar

43. Ejnell H, Järund M, Bailey M, and Lindeman P. Airway obstruction in children due to plexiform neurofibroma of the larynx. J Laryngol Otol. (1996) 110:1065–8. doi: 10.1017/s0022215100135765

PubMed Abstract | Crossref Full Text | Google Scholar

44. Nishino H, Ishikawa K, Ishida T, and Kitamura K. A case of laryngeal neurinoma with neurofibromatosis 2. Auris Nasus Larynx. (1999) 26:95–9. doi: 10.1016/s0385-8146(98)00052-2

PubMed Abstract | Crossref Full Text | Google Scholar

45. Ishii T, Nitta M, Masaki T, and Nakayama T. A case of multiple neurofibroma of the larynx and cervical esophagus. Acta Otolaryngol Suppl. (2002) 547):54–6. doi: 10.1080/000164802760057581

PubMed Abstract | Crossref Full Text | Google Scholar

46. Kang GG, Kang MK, Park HS, and Hong JC. A case of solitary neurofibroma arising from the arytenoid treated by transoral laser surgery. Korean J Otorhinolaryngol-Head Neck Surg. (2013) 56:163. doi: 10.3342/kjorl-hns.2013.56.3.163

Crossref Full Text | Google Scholar

47. Greinwald J, Derkay CS, and Schechter GL. Management of massive head and neck neurofibromas in children. Am J Otolaryngol. (1996) 17:136–42. doi: 10.1016/s0196-0709(96)90011-3

PubMed Abstract | Crossref Full Text | Google Scholar