Introduction
Intranasal melanoma (IM) is a rare, aggressive malignancy occurring within the nasal cavity or paranasal sinuses. IM comprises 3–6 per cent of all sinonasal malignancies.Reference Holdcraft and Gallagher1 Prognosis is poor, with five-year survival rates reported between 20 and 30 per cent.Reference Gal, Silver and Huang2, Reference Moreno, Roberts, Kupferman, DeMonte, El‐Naggar and Williams3 Presenting symptoms, such as mild epistaxis and nasal obstruction, can be subtle and overlap with benign disease, potentially leading to delayed diagnosis.Reference Cheng, Lai, Ho, Shu and Lin4 Amelanotic cases are described, complicating diagnosis further.Reference Apoorva, Bhatia, Shenoy, Hegde, Gowthuvalli and Aggarwal5 Little progress has been made in the management of sinonasal malignancies. A case series published in 1997 showed that survival of such patients had not improved, with a longer survival time in those cases treated before 1980 (60–80 months).Reference Brandwein, Rothstein, Lawson, Bodian and Urken6 The relative rarity of IM means that large-scale studies are challenging, with the majority of work existing in the form of case series or reports.
Treatment strategies include surgical resection and systemic therapies. Incomplete local surgical control has been demonstrated to be a predictor of low survival in IM, although the impact of surgery may be perceived to be limited due to the presence of microscopic occult disease.Reference Lee, Shimizu, Tran, Juillard and Calcaterra7 Despite this, current consensus recommends surgical excision with intention to cure by means of a wide local excision.Reference Lund, Stammberger, Nicolai, Castelnuovo, Beal and Beham8, Reference Owens, Roberts and Myers9 Evidence for post-operative radiotherapy is conflicting. Several studies found that radiotherapy conferred benefit in preventing or delaying local recurrence, but no long-term survival improvement was observed.Reference Owens, Roberts and Myers9, Reference Wada, Nemoto, Ogawa, Hareyama, Yoshida and Takamura10 However, one study of 250 patients found radiotherapy had no impact on local control.Reference Nandapalan, Roland, Helliwell, Williams, Hamilton and Jones11 Despite these bleak data, there is evidence to suggest that IM confined to the nasal septum is associated with an improved prognosis compared to other sinonasal subsites.Reference Dauer, Lewis, Rohlinger, Weaver and Olsen12
Following surgery, early and aggressive recurrence is common. Mean time to local recurrence has been reported as five months, with regional recurrence occurring at a mean time of 7.5 months.Reference Huang, Liao, Kan and Chen13 When wide local excision of the nasal septum (septectomy) is performed for malignant lesions such as melanoma, all layers of the nasal septum including the mucosa should be taken to ensure negative resection margins.Reference Sireci, Dispenza, Lorusso, Immordino, Immordino and Gallina14
This retrospective study explores IM management in a high-volume cancer centre in both localised and advanced disease. Results are contextualised by a concurrent literature review. We report non-inferior survival with an aggressive strategy of wide local excision to achieve negative surgical margins in cases limited to the nasal septum, avoiding the morbidity associated with more invasive approaches. We hypothesise that, in select patients, endoscopic septectomy may achieve negative margins, suggesting a curative role for minimally invasive surgery where it is often written off.
Materials and methods
Cohort study
Medical informatics was utilised to identify patients with International Classification of Diseases – Revision 10 (ICD-10) diagnostic code C300, with cases individually reviewed to identify those patients with IM. Patient records were retrospectively analysed. Data were collected pre-, intra- and post-operatively, including age at diagnosis, imaging, surgical findings and survival time. Achievement of negative resection margins was also recorded where appropriate, as were the treatment modalities undertaken. Kaplan–Meier survival analysis was performed using GraphPad Prism 10.6.1 (GraphPad Software, Boston, Massachussetts USA).
All patients were examined with rigid or flexible nasendoscopic examination and cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging [MRI]). A supplementary positron emission tomography (PET) -CT was performed in some cases. Tumours were staged according to the 8th edition of the American Joint Committee on Cancer manual. All patients underwent tissue biopsy confirming intranasal melanoma. Patients were offered surgical management following multi-disciplinary team discussion. The surgical approach employed can be defined as either (a) transfacial or open resection, (b) endoscopic septectomy for localised disease and (c) endoscopic debulking. The debulking approach aims to symptomatically improve a patient’s airway by clearing any obstructing tumour.
Literature review
To contextualise our regional experience, a literature review was performed using the MEDLINE database. Boolean operators were used to create a search strategy comprising of ([“intranasal melanoma” OR “nasal mucosal melanoma” OR “sinonasal melanoma” OR “sinonasal mucosal melanoma”] AND [“surgical technique” OR “septectomy” OR “wide local excision” OR “resection”]).
Inclusion criteria were studies comparing survival in IM across different surgical treatment modalities. Studies not measuring differences in survival outcomes between surgical approach were excluded, as were studies that compared outcomes between systemic therapy and surgery. Studies were reviewed by two independent reviewers.
Results and analysis
Cohort study
This case series identified 11 patients treated surgically for intranasal melanoma over a 14-year period from January 2010 to December 2024. Patient ages at diagnosis ranged from 43 to 92 years (median 75.7). All patients had biopsy-proven intranasal melanoma, and eight of these patients underwent surgery with or without systemic therapy (either chemotherapy, radiotherapy or immunotherapy). Three patients did not undergo surgery as they were deemed too unfit (n = 2) or refused surgery (n = 1). The breakdown of frequency of surgical approach is displayed in Table 1, with the most common procedure being endoscopic debulking (n = 5). A summary of patient characteristics is listed in Table 2.
Breakdown of primary surgical approach
Table 1 Long description
Percentages of patients are listed by primary surgical approach. Endoscopic debulking is the most common approach at 36.4%. No operation accounts for 27.2% of patients. Septectomy and open or transfacial approach are tied, each used in 18.2% of patients. Overall, operative approaches collectively exceed nonoperative management, with endoscopic debulking leading by a clear margin over the other surgical options. Percentages may not reflect patient counts or rounding details beyond what is shown.
Summary of patient characteristics involved in this study
Table 2 Long description
Patient-level data for 11 cases summarize age at diagnosis, TNM stage, surgical approach, presence of distant metastasis, systemic therapy, overall survival in weeks, and recurrence status. Ages range from 43 to 89, with most tumors staged T3 or T4 and nodal involvement present in several patients. Distant metastasis is recorded in four patients, including two with M1 at diagnosis and two marked as having distant metastasis despite M0 staging. Surgical management varies from no resection or biopsy only to endoscopic debulking and more extensive open procedures; three patients were not resected and therefore list recurrence as not applicable. Systemic therapy ranges from none to adjuvant or palliative radiotherapy and immunotherapy, with several patients receiving combined immunotherapy and radiotherapy. Overall survival spans from 20 weeks to 344 weeks, with one patient reported alive at 209 weeks at publication. Recurrence is frequent among resected patients and is most often local, with one locoregional neck recurrence and one distant recurrence. Interpretation should be cautious because outcomes reflect individual cases with differing treatments, resection status, and follow-up timing, including one survival value censored as alive at publication.
Overall survival time ranged from 20 to 344 weeks following initial diagnosis (median = 75.7 weeks). Regarding the two patients who underwent septectomy, one survived for 76 weeks, the other was discharged from follow-up with no signs of recurrence at 344 weeks. Kaplan–Meier survival analysis is depicted in Figure 1. The log-rank test was performed to compare survival curves between each of the four groups. No statistically significant difference in survival was observed between either surgical group (p = 0.101). Recurrence was observed in seven (87.5 per cent) of the eight patients who underwent surgical management. One patient underwent a partial septectomy for disease recurrence after having undergone initial open inferior turbinectomy.
Kaplan-Meier survival analysis as a function of surgical approach (time in weeks).
Literature review
Our literature review identified 11 original articles comparing outcomes between surgical modality in IM. Surgical approaches for managing IM can be broadly categorised into open (transfacial) and endoscopic. There are a number of existing studies comparing survival between patients undergoing either of these two surgical techniques. However, there is a lack of research specifically looking at targeted septectomy for localised IM.
A multivariate analysis of 72 patients found no significant difference in both local recurrence-free and overall survival between patients undergoing endoscopic or traditional open or craniofacial resection.Reference Sayed, Migliacci, Cracchiolo, Barker, Lee and McBride15 These findings are echoed by a further three cohort studies comparing surgical approach, all of which found no significant difference in overall survival between both surgical approaches.Reference Swegal, Koyfman, Scharpf, Sindwani, Greskovich and Borden16–Reference Vandenhende, Leroy, Chevalier and Mortuaire18 These studies did not report on the use of adjuvant radiotherapy, which may have affected survival rates in these select studies. Furthermore, a large, national-scale survival analysis found no significant difference in either overall survival or use of adjuvant therapy when comparing open and endoscopically managed patients with IM.Reference Farber, Bavier, Crippen, Vatsa, Hsueh and Eloy19 A further three cohort studies did not demonstrate a survival advantage when comparing surgical approach.Reference Lund, Howard, Harding and Wei20–Reference Ledderose and Leunig22
However, one 20-patient case series reported favourable survival when endoscopic surgical resection is utilised compared with open approaches. This study found a statistically significant improvement in overall survival with endoscopic resection compared to open approaches.Reference Almutuawa, Strohl, Gruss, van Zante, Yom and McDermott23 Another study spanning a period of 15 years found that negative resection margins were achieved more frequently in patients treated with endoscopic surgery versus open surgery, although overall survival time was not significantly improved in these patients.Reference Miglani, Patel, Kosiorek, Hinni, Hayden and Lal24
Resection margin status is a relevant clinical factor that is also likely to influence rates of local control. Traditionally, open approaches have been thought to afford improved ability to achieve negative surgical margins. Our literature review found only one study which found that negative resection margins were achieved more frequently with endoscopic resection.Reference Miglani, Patel, Kosiorek, Hinni, Hayden and Lal24 Finally, a 12-year study of 58 patients with IM found a significant improvement in overall survival when endoscopic approaches were employed, although no difference in event-free survival was demonstrable.Reference Lombardi, Bottazzoli, Turri–Zanoni, Raffetti, Villaret and Morassi25
Overall, the literature does not appear to consistently demonstrate a significant difference in survival in IM when comparing open and endoscopic approaches. It is important to note that consensus guidelines currently recommend both endoscopic treatment (where possible) and achieving negative margins.Reference Homer, Winter, Abbey, Aga, Agrawal and Ap Dafydd26 Achieving negative margins of 5 mm within the anatomical constraints of the nasal cavity is difficult and, therefore, may only be achievable endoscopically for small lesions. It is important to note this as this may be a source of selection bias in the studies reporting negative resection margins or survival in the endoscopic cohorts.
Discussion
IM provides challenges to clinicians, with recurrence common and a five-year survival poor.Reference Todorovic, Djurkovic, Krstic, Tomanovic, Milanovic and Kablar27, Reference Pandrangi, Mace, Abiri, Adappa, Beswick and Chang28 Surgical management has been shown to afford improved survival when combined with singular chemotherapy or radiotherapy,Reference Abt, Miller, Mokhtari, Lin, Richmon and Deschler29, Reference Gaze, Kerr and Smyth30 but disease burden at presentation is often widespread. In our case series, we observed disproportionately long survival in patients undergoing either open resection or targeted septectomy. Septectomy may represent a chance at early cure for patients with IM limited to the nasal septum compared with extra-septal disease and, therefore, may represent a specific treatment strategy in this subset of patients.
Our case series highlights the challenges encountered in managing IM and underline its poor prognosis but poses an interesting question regarding the utility of endoscopic septectomy. Two patients in our cohort survived disproportionately long (survival of greater than six years), which may be at least partially explained by early radical surgical management. One of these patients underwent total rhinectomy whilst the other was managed with endoscopic subtotal septectomy. Whilst our findings do not reach statistical significance, this may provide a platform from which larger studies may be performed. Specifically, there is a paucity of data on survival in patients undergoing septectomy in septal-limited IM. Our findings provide the basis for the hypothesis that early septectomy improves survival in a subset of IM patients, potentially altering these patients’ treatment paradigm.
At the same time, this study highlights the challenges in diagnosis and rapid treatment initiation in such a rare and aggressive sinonasal neoplasm; cases often display insidious symptom onset and, therefore, are too extensive at presentation for septectomy to be a viable curative treatment option. As well as this, identification of sinonasal melanoma has been shown to be challenging, comprising one of the rarest head and neck malignancies.Reference Filippini, Carosi, Querzoli, Sabbioni, Fermi and Chiari31 Diagnosis is challenging not only due to insidious onset but also attributing common symptoms such as epistaxis to alternative diagnoses. Amelanotic cases can also occur, further confusing the diagnostic process. All of these factors contribute to diagnostic delay in an already rare disease entity and, therefore, it is common for disease to present extensively at the time of initial review. Identifying cases early enough to “catch” those with septal-limited disease, therefore, is extremely challenging, but the potential benefits of endoscopic septectomy in these patients may be significant. Our findings raise this as a possibility.
Advocates of endoscopic resection for IM point to studies demonstrating improved overall survival or improved local disease control when an endoscopic approach is employed.Reference Farber, Bavier, Crippen, Vatsa, Hsueh and Eloy19, Reference Almutuawa, Strohl, Gruss, van Zante, Yom and McDermott23 Higher rates of negative resection margins may be explained by greater visualisation of tumour margin with an endoscope, although no study was able to demonstrate a significant relationship between endoscopic surgery and negative resection margin. Further benefits of endoscopic surgery are quicker recovery time, shorter total surgical time and a lack of an external facial scar when comparing with an open, transfacial approach. Achieving negative resection margins in septal-only IM may be afforded by improved tumour visualisation with an endoscopic approach and facilitate complete excision of IM localised to the nasal septum.
Current UK consensus guidelines recommend that surgical resection to achieve negative margins gives the best chance of cure,Reference Homer, Winter, Abbey, Aga, Agrawal and Ap Dafydd26 and resection is either endoscopic or open. When disease is extensive, endoscopic debulking is less likely to achieve negative margins, and open approaches are often deemed too co-morbid to embark upon. Despite this, in our centre, endoscopic debulking plays an important role in alleviating symptoms by clearing the nasal airway. Our approach is that the improvement in quality of life achieved by clearing the airway and reducing symptoms due to local mass effect should not be ignored, and endoscopic debulking should still be considered even in those patients in whom cure may not be possible.
The utility of endoscopic approaches in clearing disease is likely affected by selection bias in those patients where disease is small and limited enough to be amenable to an endoscopic approach. Our approach mirrors this, and our experience is that early septectomy in patients with disease limited to the septum affords the best chance of cure. In our practice, we follow up patients for at least five years post-surgery.
Finally, the use of adjuvant therapies also has a role to play. Whilst there is no evidence to support the use of radiotherapy with respect to overall survival,Reference Homer, Winter, Abbey, Aga, Agrawal and Ap Dafydd26 it is often offered on an individual basis post-operatively by multi-disciplinary team (MDT) opinion, potentially improving regional control. This is the approach taken at our centre where radiotherapy is offered on a select patient basis. Immunotherapy is also utilised for those with metastatic sinonasal melanoma, as is standard of care in the UK.Reference Griffin, Scotto, Josephs, Mele, Crescioli and Bax32
Our study is not without limitations, primarily the small cohort size, although this is a limitation inherent to sinonasal melanoma given its rarity. Our findings raise an interesting question regarding the utility of targeted septectomy but have limited inferential significance given the low sample size of such a rare patient cohort. Indeed, we are exploring the utility of septectomy in a subset of an already rare subset of patients, and this limits the conclusions regarding survival benefit that can be made. Our cohort is heterogeneous, with some patients managed purely surgically whilst others received adjuvant therapy. Finally, an end date of December 2024 may be too recent to assess long-term survival in this patient; however, our cohort only comprising eleven patients during a 14-year period underlines the rarity of IM and the subsequent challenges in performing robust survival analyses. However, we hope to provide a foundation from which further, larger scale studies can be performed. The survival of the two patients undergoing septectomy raises an interesting question regarding its use. In IM, where surgical debridement is often viewed as futile, septectomy represents a potential caveat in the treatment strategy for these patients. Selection bias is also a clear problem in the management of IM patients in general, not only in our study. Patients presenting late due to the natural history of the disease will not be amenable to septectomy, and this clearly influences survival and treatment strategy adopted. Our study also underlines the importance of early and rapid diagnosis of IM patients given the challenges in its diagnosis, and the need for continuing education in this disease subset. Lastly, the surgical approach chosen is influenced by operator experience, preference and local expertise and, thus, is subject to the same selection bias.
• Intranasal melanoma has poor cure rates despite surgical debulking and adjuvant therapy
• Patients with disease limited to the nasal septum may achieve cure with early targeted septectomy to ensure negative resection margins
• Surgical treatment strategies should be targeted to disease distribution, with endoscopic debulking preferred for symptomatic relief in advanced disease
Conclusions
IM is a rare disease entity, commonly extensive at diagnosis and associated with a high mortality and recurrence rate despite treatment. Identification of the limited subset of patients with localised disease is critical. Such patients may achieve long-term remission, such as in the case of targeted endoscopic septectomy. Targeted septectomy may also confer similar survival benefits whilst avoiding significant morbidity, and further studies are required to elucidate its benefit in a selected subset of IM patients.
Compliance with ethical standards
The authors declare no conflicts of interest and received no funding for this study. This study was a retrospective review of anonymised case notes and, therefore, did not require ethical approval, in line with guidance set out in the Declaration of Helsinki.
Competing interests
The authors declare no competing interests.
