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. 2025 Jan 20;127:110904. doi: 10.1016/j.ijscr.2025.110904

Ocular invasion in sinonasal malignant melanoma: A case report and review of literature

Bijan Khademi a, Sajjad Soltani a, Alireza Yousefi a, Pouya Heidari a, Zhale Mardani b, Shayan Yousufzai c,⁎
PMCID: PMC11788794  PMID: 39842280

Abstract

Background

Sinonasal mucosal melanoma (SNMM) is a rare and aggressive malignancy associated a poor prognosis, prognosis. It is by delayed presentation and nonspecific symptoms. The incidence of SNMM is low, with and there are challenges in achieving local control and managing distant metastases.

Case Presentation.

We report present case of an 86-year-old female patient with a history of systemic hypertension who presented exhibited symptoms, including blurred vision, rhinorrhea, and facial pain, following initial treatment for SNMM. sinonasal mucosal melanoma (SNMM). studies revealed a heterogeneous lesion in the right nasal cavity and ethmoidal air cells, exhibiting characterized by destruction and invasion into the orbit. The patient underwent functional endoscopic sinus surgery (FESS) for resection, with and analysis confirming confirmed the diagnosis of melanoma.

Discussion

This case underscores the aggressive nature of SNMM and emphasizes importance of early diagnosis and intervention. Despite Although treatment with surgery and radiotherapy leading resulted in resolution for two years, the recurrence of symptoms highlights the challenges in associated with long-term control. The Effective of SNMM requires necessitates multidisciplinary approach, approach that includes resection and the of adjuvant therapies.

Conclusion

SNMM poses presents treatment challenges due to its aggressive behavior nature complex anatomical location. A comprehensive approach involving that includes radiotherapy, and potential systemic therapies is essential for improving enhancing outcomes. Further research is needed necessary explore investigate treatment strategies for this rare malignancy.

Keywords: Sinonasal mucosal melanoma, SNMM, Case report, Functional endoscopic sinus surgery, Prognosis, Adjuvant therapy

Highlights

  • •

    Rarity of Sinonasal Mucosal Melanoma: Sinonasal mucosal melanoma (SNMM) is an exceptionally rare condition, with an estimated annual incidence of only 0.02 to 0.2 cases per 100,000 individuals, representing less than 1 % of all melanoma cases.

  • •

    Diagnostic Imaging: Utilize CT scan and MRI for accurate assessment of SNMM, focusing on tumor size, location, and local invasion characteristics. CT reveals bony erosion, while MRI provides insights into melanin content and hemorrhage presence.

  • •

    Histological Analysis: Confirm diagnosis through immunohistochemistry, highlighting markers such as S100, HMB-45, MELAN-A, and Ki-67. Elevated Ki-67 indicates aggressive tumor behavior, while S100 positivity supports melanocytic origin.

  • •

    Surgical Treatment Options: Prioritize complete surgical resection as the primary treatment modality. Functional endoscopic sinus surgery (FESS) is often preferred for its minimally invasive nature and lower complication rates compared to open surgery.

  • •

    Recurrence Management: Implement a multidisciplinary approach for managing recurrence, combining surgical interventions with adjuvant therapies like radiotherapy to enhance patient outcomes.

  • •

    Prognostic Considerations: Acknowledge the poor prognosis associated with SNMM, with a five-year survival rate around 30 %. Continuous follow-up and early detection are critical for improving survival rates in affected patients.

1. Introduction

Malignant mucosal melanoma (MM) of the nasal cavity and paranasal sinuses is a rare pathological condition, with an estimated annual incidence rate ranging from 0.02 to 0.2 cases per 100,000 individuals [[1], [2], [3], [4], [5], [6]]. In contrast, cutaneous melanoma is a type of neoplasm that arises from melanocytes located in the basal layer of the epidermis. Mucosal melanomas, which occur in the head and neck region, are significantly less prevalent than their cutaneous counterparts, accounting for <1 % of all melanoma cases [18]. The five-year survival rate for patients diagnosed with this condition is approximately 30 % [7,8].

Despite significant advancements in treatment modalities for oncological patients over the past two decades—including improved visualization techniques for endoscopic surgery, three-dimensional radiotherapy, and innovative systemic therapies—achieving local control and effectively managing distant metastases in patients with SNMM remains a considerable challenge, ultimately resulting in a poor prognosis [7,9].

Macroscopically, soft tissue neoplasms of melanocytic origin (SNMM) typically present as polypoid masses that may or may not exhibit pigmentation. These tumors are often ulcerated and can display a variety of nonspecific appearances, including brown, black, red, crimson, gray-white, or even amelanotic characteristics, which can make them resemble other tumor types [[10], [11], [12]].

Sinonasal mucosal melanoma (SNMM) is clinically characterized by a delayed presentation, often accompanied by nonspecific and potentially misleading symptoms, such as unilateral nasal obstruction and epistaxis. These symptoms may occur either in isolation or in combination [11,13]. Imaging modalities, including computed tomography (CT) and magnetic resonance imaging (MRI), are essential in the diagnosis and assessment of sinonasal mucosal melanoma (SNMM). CT imaging offers critical insights into the size, location, and extent of the tumor, in addition to identifying the presence of cervical lymph node metastasis [14].

The radiographic characteristics of sinonasal mucosal melanomas exhibit considerable variability, particularly on magnetic resonance imaging (MRI), which can be attributed to differing levels of melanin content; approximately one-third of cases are classified as amelanotic. On computed tomography (CT) scans, sinonasal mucosal melanoma is typically identified as a polypoid or mass-like lesion, often associated with bony remodeling or erosion, and demonstrates significant contrast enhancement. Regarding MRI findings, sinonasal mucosal melanoma generally presents a homogeneous T1 signal on T1-weighted images, although an elevated T1 signal may be observed in cases of hemorrhage or melanin presence. Conversely, T2-weighted images typically reveal a low signal for these tumors. Following gadolinium enhancement (T1 C+), either moderate homogeneous or heterogeneous enhancement is noted. Importantly, metastases arising from sinonasal mucosal melanoma exhibit signal characteristics similar to those of the primary lesion, indicating a consistent imaging profile across various stages of the disease [16,17].

Treatment modalities for sinonasal mucosal melanoma (SNMM) include surgical intervention, radiotherapy, chemotherapy, and biological therapy, with surgery being the primary approach. Complete surgical resection is crucial for improving patient prognosis; however, the intricate anatomical structures of the nasal cavity and paranasal sinuses often position tumors near critical areas, such as the base of the skull and the orbit. Consequently, achieving complete surgical resection can be difficult, and in some advanced cases, patients may forfeit the chance for surgical intervention.

In this study, we present a severe case of mucosal malignant melanoma originating from the sinonasal mucosal membrane of the ethmoid sinus, which subsequently invaded the ocular globe.

2. Methods

The current study was written in line with SCARE guideline criteria [15].

2.1. Case presentation

An 86-year-old female patient with a known history of systemic hypertension, managed with Valsartan and Amlodipine, was referred to our ENT clinic. She presented with complaints of blurred vision, excessive tearing, a burning sensation in the affected eye, rhinorrhea, facial pain, and post-nasal discharge (PND) that had persisted for three years prior to her visit.

2.2. Past medical history

Following diagnostic interventions conducted at an alternative facility, which included computed tomography of the paranasal sinuses, the patient underwent right functional endoscopic sinus surgery (FESS) due to the presence of a suspected malignant lesion within the ethmoidal sinus. The immunohistochemistry findings are summarized in Table 1. Additionally, pathological analysis of the biopsy confirmed the diagnosis of malignant melanoma of the paranasal sinus mucosal membrane, and the patient was advised to undergo 30 sessions of radiotherapy. The patient's symptoms have been resolved for the past two years.

Table 1.

Immunohistochemical findings of the patient prior to reoperation in our ward.

Markers Results
S100 Positive
K167 High 20–25 %
CK Negative
HMB45 Positive
MELAN-A Positive
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2.3. Present Illness

Six months prior to her admission, the previously managed signs and symptoms reemerged. A computed tomography (CT) scan of the paranasal sinuses (Fig. 1), along with soft tissue magnetic resonance imaging (MRI) (Fig. 2), was conducted to further evaluate her condition. The MRI revealed a heterogeneous iso‐signal lesion measuring 31 x 27 mm, located in the right nasal cavity and the right ethmoidal air cells. This lesion exhibited bone destruction that extended to the medial aspect of the right orbit and the extraconal space, with an attachment to the extraocular muscle on the right side. Additionally, the immunohistochemical findings from the patient prior to reoperation in our ward indicated that S100 was positive, Ki-67 showed a high expression of 20‐25 %, cytokeratin (CK) was negative, HMB-45 was positive, and MELAN-A was positive. In light of these findings and the patient's prior history of malignancy, the otolaryngology surgeons decided to perform functional endoscopic sinus surgery (FESS) once again (Fig. 3). The histopathological examination performed during the surgical procedure confirmed the diagnosis of malignant melanoma, thereby ruling out the presence of other malignant entities, including squamous cell carcinoma, hemangioma, adenocarcinoma, lymphoma, and nasal polyps. Furthermore, it also excluded the possibility of infectious conditions, such as fungal sinusitis (Fig. 4).

Fig. 1.

Fig. 1

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The coronal view of the PNS CT showing the lesion extending from ethmoidal sinus to the ipsilateral orbit.

Fig. 2.

Fig. 2

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The coronal view of the PNS MRI confirming the lesion extending from ethmoidal sinus to the ipsilateral orbit.

Fig. 3.

Fig. 3

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Endoscopic view of the lesion within nasal cavity.

Fig. 4.

Fig. 4

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Histopathological examination demonstrated polygonal, hyperpigmented nuclei, and spindle cells indicative of malignant melanoma.

2.4. Patient follow-up

The patient was scheduled for an appointment with an oncologist to further evaluate the recurrence of the condition and to discuss potential adjuvant therapies.

3. Discussion

Mucosal melanoma is a rare form of malignant melanoma, representing only 1.3 % of all cases, with 55 % of these tumors located in the head and neck region. The incidence of mucosal melanoma remains stable, in contrast to the rising prevalence of cutaneous melanoma. The average age at diagnosis for patients with this condition is 64 years. While exposure to ultraviolet radiation is recognized as the primary factor contributing to tumor development, lesions in the paranasal sinuses are more significantly influenced by chemical agents found in cigarette smoke and formaldehyde vapors. The most common sites for mucosal melanoma are the nasal cavity and paranasal sinuses, which account for 50 % of cases, closely followed by the oral cavity at 45 % [[18], [19], [20], [21], [22]].

The initial clinical presentation of the patient—characterized by blurred vision, excessive tearing, rhinorrhea, and facial pain—aligns with the typical manifestations of sinonasal mucosal melanoma (SNMM). This condition often presents with nonspecific symptoms that can hinder timely diagnosis. Existing literature indicates that such symptoms may be erroneously attributed to more common conditions, resulting in prolonged diagnostic delays. In this case, the patient's symptoms persisted for three years before a diagnosis was established, highlighting the necessity for increased awareness among healthcare providers regarding the potential for SNMM in patients exhibiting these symptoms, particularly within the elderly population [11,13].

Imaging modalities, particularly computed tomography (CT) and magnetic resonance imaging (MRI), play a crucial role in assessing sinonasal mucosal melanoma (SNMM) by providing essential information regarding tumor size, localization, and the extent of local invasion. In the present case, imaging studies revealed significant osseous destruction and orbital invasion, which are consistent with the aggressive nature of SNMM and are supported by prior research. This is particularly relevant given that complete surgical excision is often complicated by the tumors' proximity to vital anatomical structures, such as the skull base and orbit, as demonstrated in this case [7,9].

In the evaluation of surgical techniques for sinonasal mucosal melanoma (SNMM), particularly within the ethmoid sinus, both functional endoscopic sinus surgery (FESS) and open surgery (OS) offer distinct advantages and disadvantages. The selection of a surgical approach can significantly impact patient outcomes, including survival rates, the incidence of postoperative complications, and overall quality of life. Research suggests that endoscopic resection (ER) may provide overall survival rates that are either comparable to or potentially superior to those achieved through open resection (OR). A meta-analysis indicated that the overall survival rate was higher in the ER cohort, with a hazard ratio (HR) of 0.68 when compared to the OR cohort. However, the rates of disease-free survival did not show significant differences between the two surgical techniques [23].

Both surgical methodologies have demonstrated comparable rates of local recurrence. In one study, the local failure rates were reported as 23 % for open resection (OR) and 8 % for endoscopic resection (ER); however, these differences did not reach statistical significance. Additionally, another investigation found no significant differences in disease-free survival between the two cohorts [24,25].

Endoscopic approaches (ER) are generally associated with lower complication rates. For instance, cerebrospinal fluid leaks occurred in 15 % of patients who underwent open resection (OR), compared to 8 % in the ER cohort; however, this difference did not reach statistical significance. Furthermore, ER is associated with reduced facial scarring and a more rapid recovery period, which can be attributed to its minimally invasive nature.

In terms of cosmetic outcomes, patients who undergo endoscopic rhinoplasty (ER) frequently report improved aesthetic results due to the minimally invasive techniques employed. This aspect is particularly significant for individuals who prioritize their facial appearance after surgical procedures [24,25].

The accessibility of tumors significantly influences the choice of surgical approach, which is determined by both the anatomical location and the extent of the tumor. Endoscopic resection (ER) is generally effective for smaller tumors and those located in areas of the nasal cavity that are easily accessible. In contrast, larger or more advanced tumors may necessitate an open surgical (OS) approach to achieve clear margins [26]. Considering the patient's history of recurrence, advanced age, and tumor size measuring 31 × 27 mm, our surgical team has determined that Functional Endoscopic Sinus Surgery (FESS) is the most appropriate intervention to minimize potential complications for the patient.

The patient underwent two functional endoscopic sinus surgeries (FESS) as part of her treatment regimen. Histopathological examination following the surgeries confirmed the presence of malignant melanoma. Immunohistochemical analysis revealed positive markers for S100, HMB-45, and MELAN-A, which are indicative of melanocytic differentiation. Additionally, a high proliferation index was observed, as evidenced by Ki-67 positivity [14]. These findings are consistent with the existing literature, which suggests that a combination of immunohistochemical markers is essential for the definitive diagnosis of mucosal melanoma [10,12].

The detection of the S100 protein is commonly associated with melanocytic tumors, thereby reinforcing a diagnosis of melanoma. While the presence of S100 is beneficial for diagnostic purposes, its prognostic implications are somewhat limited. Research suggests that, although S100 expression is prevalent in melanoma, its correlation with survival outcomes may vary depending on the specific tumor type and stage [29].

Ki-67 is a well-established biomarker that indicates cellular proliferation. An elevated Ki-67 index signifies an increased rate of tumor cell proliferation, which has been correlated with a poorer prognosis in patients with melanoma. Specifically, higher levels of Ki-67 are associated with an increased likelihood of metastasis and a decrease in overall survival rates [30].

Consequently, the expression level of 20‐25 % in this patient indicates a potentially more aggressive tumor phenotype. The absence of cytokeratin (CK) expression is particularly significant, as CK positivity is often associated with epithelial differentiation or more aggressive variants of melanoma. In contrast, negative CK expression is generally linked to a more conventional melanoma phenotype, which may carry distinct prognostic implications when compared to CK-positive tumors [31].

HMB45 serves as a specific marker for melanocytes and is particularly important in the diagnosis of amelanotic melanoma. Although the presence of HMB45 indicates a melanocytic origin for the tumor, its prognostic implications remain a subject of debate. Some studies suggest that HMB45 may not exhibit a strong correlation with survival outcomes; nevertheless, it remains a crucial component of the diagnostic process [32].

MELAN-A, akin to HMB45, serves as an additional marker indicative of melanocytic differentiation and is frequently utilized alongside other markers for diagnostic purposes. The detection of MELAN-A generally reinforces a diagnosis of melanoma; however, it does not yield definitive prognostic information when assessed in isolation [33].

Following the initial treatment, the patient's symptoms subsided for a period of two years, consistent with the typical pattern observed in sinonasal mucosal melanoma (SNMM), where patients may experience intervals of remission followed by recurrence. Unfortunately, as noted in this patient, recurrence is a common phenomenon in mucosal melanoma, which has a documented five-year survival rate of approximately 30 % [8]. The recurrence necessitated further imaging studies, which revealed significant disease progression, thereby requiring additional surgical intervention.

In the context of treatment, a multidisciplinary approach that encompasses surgical management, radiotherapy, and potential systemic therapies is essential. Although surgery is regarded as the cornerstone of treatment, the complex nature of SNMM often hinders complete resection, necessitating the use of adjunctive therapies such as radiotherapy, which the patient received for her initial tumor [7,9]. The management of recurrences typically involves a combination of further surgical interventions and adjuvant therapies, underscoring the importance of ongoing follow-up with oncology specialists, as recommended to the patient following reoperation [[26], [27], [28]].

4. Conclusion

This case underscores the paramount importance of early detection and proactive management of sinonasal mucosal melanoma, particularly in elderly patients. Further research is essential to explore innovative treatment strategies and enhance prognostic outcomes for this complex malignancy. The case highlights the necessity of a collaborative care model that integrates surgical, radiological, and oncological expertise to optimize patient management in instances of sinonasal mucosal melanoma.

Author contribution

Bijan Khademi established the conceptual framework for the research, whereas Sajjad Soltani, Alireza Yousefi, and Pouya Heidari executed the surgical interventions. Shayan Yousufzai oversaw the project, composed the initial draft, cured the data, and conducted a review of the relevant literature. Zhale Mardani was involved in data visualization, verification of the diagnosis, and analysis of histopathological examinations.

Informed consent

Written informed consent was obtained from the patient for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

This research was deemed exempt from ethical approval in accordance with the regulations set forth by Shiraz Medical School Ethical Committee.

Guarantor

Shayan Yousufzai and Alireza Yousefi.

Research registration number

Non applicable.

Consent for publication

Written informed consent was obtained from the patient's parents/ legal guardian for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work the author used Wordvice.AI/ Paraphrasing and proofreading tool in order to avoid either plagiarism or grammar errors. After using this tool/service, the author reviewed and edited the content as needed and takes full responsibility for the content of the publication.

Funding

This study was not funded.

Approval of the research protocol by an institutional reviewer board

Non applicable.

Declaration of competing interest

The authors declare no competing interests.

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