Primary Sinonasal Mucosal Melanoma Research Articles

Morphological and Immunohistochemical Aspects with Prognostic Implications and Therapeutic Targets of Primary Sinonasal Mucosal Melanoma: A Retrospective Study.

Sinonasal mucosal melanoma originates from melanocytes and it is a rare malignancy in the sinonasal tract. It is an aggressive melanocytic neoplasm with a very poor prognosis. The symptoms are nonspecific and the diagnosis is delayed, usually until the advanced stages of the disease. The current study performs a correlation between the histopathological aspects of sinonasal mucosal melanoma and different types of immune cells present in the microenvironment, with prognostic and therapeutic implications. The endpoint is to quantify the cellular immune microenvironment and correlate it with patient survival. This study presents nine cases of primary sinonasal mucosal melanomas diagnosed at the Emergency City Hospital Timisoara, Romania during a period of 15 years. The histopathological examination was performed in the Department of Pathology of the same hospital, using morphological hematoxylin-eosin staining. Additional immunohistochemical reactions were performed to confirm the diagnosis and evaluate the components of the tumor immune microenvironment. This study identifies eosinophils, macrophages, natural killer cells and plasma cells as favorable prognostic factors. Therefore, a CD8:CD4 ratio of more than 3 is correlated with a good response to PD-1 inhibitor therapy.

Endoscopic resection of primary sinonasal mucosal melanoma with orbital invasion: How I do it

Primary sinonasal mucosal melanoma is a rare aggressive malignancy. In this video, a case of a 68-year-old female who presented with diplopia for 2 weeks is described. The present video reports the endoscopic endonasal surgical excision of a primary sinonasal mucosal melanoma. The video contains patient's medical history, preoperative radiological evaluations and step-by-step description of surgical steps of the procedure with the utilization of computer-assisted navigation system.

Endoscopic surgery combined chemoradiotherapy and PD-1 blockade in patients with sinonasal mucosal melanoma.

e21552 Background: Primary sinonasal mucosal melanoma (SNMM) is a rare and aggressive disease different from cutaneous melanoma. The best treatment modality including the role of immune checkpoint blockade in SNMM has not been defined. Methods: Between 2021 and 2023, patients with previously untreated sinonasal melanoma were enrolled by three single-center investigator-initiated phase II clinical trials (ChiCTR2100046498 / ChiCTR2100045797/ ChiCTR2100049031). Eligible patients in ChiCTR2100045797 trial received postoperative radical chemoradiotherapy combined with toripalimab (a PD-1 inhibitor) for a year or until the disease progressed. Eligible participants in ChiCTR2100046498 study received surgery combined with radiation without immunotherapy. And for patients in ChiCTR2100049031 study, preoperative radiation was carried out firstly. The locoregional control, distant metastasis-free survival (DMFS), and overall survival (OS) were the main efficacy goals. Results: Fifty-four patients were enrolled (mean age 62 years, 33 males [61.1%] and 21 women [38.9%]) with 2y-OS rate 62.3±7.9%, 2y-RFS rate 67.1±8.2%, and 2y-DMFS rate 63.9±8.1%. Patients with T3 (n = 23), T4a (n = 14), and T4b (n = 17) stages, including12 patients with node-positive disease, were included at baseline. During a median follow-up of 11 months, 19 patients ultimately died, 10 experienced relapses, and 17 developed metastases. Tumor T staging was demonstrated to be an independent prognostic predictor according to the Cox univariate analysis. The primary factor contributing to a poor prognosis and the primary cause of death for 73.7% of patients was distant metastases. Preoperative radiation had an improved long-term survival with 2y-OS rate of 85.7±13.2%, and it can considerably lower the risk of distant metastases (p≤0.05). The overall survival rate for patients receiving postoperative chemoradiotherapy combined with immunotherapy was higher than that for patients not receiving immunotherapy (2y-OS rate 74.1±11.4% vs. 39.3±15.8%), although the difference was not statistically significant due to a small number of patients (p = 0.16). No immune-related adverse effects grade≥3 was recorded. Conclusions: The primary cause of the poor prognostic performance of SNMM is distant metastasis. The risk of distant metastases might be considerably decreased by preoperative radiation treatment. Surgery combined with radiation and immunotherapy could bring promising survival benefit. The way forward may involve investigating the combination of immunotherapy and preoperative radiotherapy. Clinical trial information: NCT04879654 ; NCT05009446 .

Characterization of the tumor-infiltrating lymphocyte landscape in sinonasal mucosal melanoma

Tumor-infiltrating lymphocytes (TILs) are important prognostic biomarkers in several types of cancers. The interplay between TIL subgroups and immune checkpoint molecules like programmed cell death ligand 1 (PD-L1) is a promising target for immunotherapy. However, the TIL landscape in sinonasal mucosal melanoma (SNMM) has not been sufficiently characterized yet and the prognostic value of TIL subgroups and PD-L1 expression remains uncertain. Here, we investigated subsets of TILs (CD3+, CD4+, CD8+, CD20+) and PD-L1 expression patterns in SNMM and assessed their prognostic value for recurrence-free and overall survival. Immunohistochemical staining for CD3, CD4, CD8, CD20 and PD-L1 was performed on tumor tissue from 27 patients with primary SNMM. Patient history was obtained and associations between TIL subgroups or PD-L1 expression and AJCC tumor stage, overall survival, and recurrence-free survival were retrospectively analyzed. Patients with high CD3+ and CD8+ TILs in the primary tumor survived significantly longer than patients with SNMMs with a low number of CD3+ and CD8+ TILs. High CD3+ and high CD8+ TILs were associated with the lower T3 stage and increased 5-year survival. PD-L1 positivity in tumor cells was associated with advanced tumor stage. Our results indicate that high densities of CD3+ and CD8+ TILs are strong positive prognostic biomarkers for survival in SNMM. Prospective studies with larger case numbers are warranted to confirm our findings.

Sinonasal Mucosal Melanoma: An Update and Review of the Literature.

Primary sinonasal mucosal melanoma (SNMM) is an aggressive tumor with high metastatic potential and poor outcomes. Presenting symptoms are nonspecific, and the nasal cavity is the most common site of origin followed by the maxillary and ethmoid sinuses. Histopathologically, SNMMs are pleomorphic and predominantly composed of epithelioid cell type. Identifying these tumors requires a high index of suspicion for melanoma and the use of a panel of immunohistochemical markers when typical histopathological features are missing. Not infrequently, these tumors are undifferentiated and/or amelanotic. Currently, SNMM falls into 2 different staging systems proposed by the American Joint Committee on Cancer, one for carcinoma of the nasal cavity and sinuses and the other for head and neck melanoma. Although therapeutic standards do not exist, surgical resection with adjuvant radiotherapy and/or systemic therapy may offer the best outcome. Lymphadenectomy including possible parotidectomy and neck dissection should be considered in patients with regional lymph node metastasis. However, the role of elective lymph node dissection is controversial. Genetic profiling has identified a number of recurrent gene mutations that may prove useful in providing targets for novel, emerging biological treatments. In this article, we provide an update on clinicopathological features, staging, molecular discoveries, and treatment options for SNMM.

Prognostic Value of Tumor-Infiltrating Lymphocytes in Sinonasal Mucosal Melanoma.

Tumor-infiltrating lymphocytes (TILs) predict better outcome in several types of cancers. However, the prognostic value of TILs in sinonasal mucosal melanoma (SNMM) is uncertain. Here, we investigated whether TILs can be used as a prognostic indicator for survival in SNMM. Retrospective cohort study. Patient history and histologic specimens from 27 patients with primary SNMM were retrospectively analyzed. TIL grade was determined and associations between TILs and AJCC tumor stage, overall survival, and recurrence-free survival were analyzed. Patients with TILs in the primary tumor classified as brisk or non-brisk survived significantly longer than patients with SNMMs lacking lymphocyte infiltrates. Brisk TILs were associated with the lower T3 stage and increased recurrence-free and 5-year survival. Our results indicate that TIL density is a strong prognostic factor for better survival in SNMM. Prospective studies with larger case numbers are warranted to determine whether TILs should be included in future AJCC staging guidelines. 3 Laryngoscope, 132:1334-1339, 2022.

Surgical Treatment of Sinonasal Mucosal Melanoma in Patients Treated with Systemic Immunotherapy.

Objective Surgical resection is widely accepted as a critical component for definitive treatment of sinonasal mucosal melanoma. Systemic immunotherapy, including multiple newer agents, has been used to treat metastatic or unresectable disease. In this study, we examine its efficacy in locoregional control when used in conjunction with surgical resection for primary mucosal lesions. Design Present study is a retrospective review of all patients at a tertiary academic medical center with primary sinonasal mucosal melanoma and distant metastatic disease. Results A total of four patients were identified. In all cases, patients were treated with a combination of surgical resection of the primary tumor and systemic immunotherapy. Three patients were initially treated with surgery at the primary site followed by immunotherapy for distant metastases. Response to immunotherapy at the sites of primary and metastatic disease was seen in two patients. All four patients developed progression or recurrence at the primary site following initiation of immunotherapy for which they underwent surgical resection. One patient remains in follow-up without evidence of disease 20 months after initial treatment; three succumbed to the disease at 135, 37, and 16 months after initial treatment. Conclusion Surgical resection for local control plays a critically important role in the treatment of sinonasal mucosal melanoma regardless of the presence of metastases and whether immunotherapy will be given. This case series suggests that, though immunotherapy may demonstrate efficacy in managing distant disease, surgery should remain the first-line treatment for the primary site.

Surgery for Treatment of Primary Sinonasal Mucosal Melanoma in Patients Treated with Systemic Immunotherapy for Distant Disease

Surgery for Treatment of Primary Sinonasal Mucosal Melanoma in Patients Treated with Systemic Immunotherapy for Distant Disease

Adjuvant radiotherapy in sinonasal mucosal melanoma: A retrospective analysis.

Evaluation of outcome after curative treatment for sinonasal mucosal melanoma focused on the effect of adjuvant radiotherapy on recurrence and survival. Retrospective chart analysis. Tertiary referral hospital. Fifty-one patients with primary sinonasal mucosal melanoma who underwent surgical resection with curative intention between 1980 and 2016 at Erasmus Medical Center, Rotterdam. Patients were categorised into 2 groups: surgery alone and surgery with adjuvant radiotherapy. Log-rank test was used to compare rates of recurrence and survival between treatment groups. Predictors for treatment modality, recurrence and survival were assessed with multivariate statistical analysis. Of all patients, 23.5% developed local recurrence and 47.1% developed distant metastasis. Estimated 5-year disease-free survival was 25.2%, and 5-year overall survival (OS) was 38.1%. Forty-three patients (84.3%) were treated with post-operative radiotherapy. Patients who underwent surgery with adjuvant radiotherapy presented more often with high tumour stage, tumour involving multiple sites and positive margins. Post-operative radiotherapy seemed to be associated with better local control (P=.549). No effect was found on occurrence of distant metastasis and OS. Positive margin status was an independent negative predictor for distant metastasis-free survival and overall survival. Our treatment outcomes are consistent with literature. Post-operative radiotherapy seems to be associated with improved local control despite advanced disease and positive margin status in this treatment group.

Primary sinonasal mucosal melanoma – Case report and literature review

Abstract BACKGROUND. Primary sinonasal mucosal melanoma is a rare tumor with a poor survival rate. There is an inherent difficulty in diagnosing these lesions, especially because their complex anatomic locations and symptoms can be frequently confused with other benign or malignant processes. The purpose of our study was to report a difficult case and review the literature and recent research on therapeutic modalities. MATERIAL AND METHODS. We herein report a 61-year-old female patient, with a history of right eye enucleation and prosthesis, who presented with obstruction of the left nostril, anterior and posterior mucopurulent rhinorrhea, anosmia, left facial numbness, left exophthalmia accompanied by ipsilateral epiphora and decreased visual acuity. RESULTS. Clinical and imagistic testing revealed a large, grayish, fleshy tumor localized in the left maxillary sinus, with extension to the left orbit (producing osteolysis of the inferior and medial orbital walls), nasopharynx, ethmoidal cells and left frontal sinus. Pathological and immunohistochemical examination confirmed the diagnosis of mucosal melanoma. Other primary sites were excluded. The patient succumbed shortly after, following only palliative treatment. CONCLUSION. Early diagnosis of primary sinonasal mucosal melanoma is essential but very difficult to detect. Any symptoms such as unilateral epistaxis or nasal obstruction in a patient over the age of 60 should be rendered suspicious. Pathological and immunohistochemical examination for diagnosis and prognostic factors are important. Although surgery is the first option for treatment, one must consider, according to tumor staging, radiotherapy and chemotherapy with immunotherapy as a viable course of treatment for advanced cases.

Prognosis analysis of multidisciplinary treatment on nasal mucosa malignant melanoma

Objective:The aim of this study is to investigate the facters affecting prognosis of primary sinonasal mucosal malignant melanoma and analyze the optimal therapeutic strategies.Method:Among the 33 patients with sinonasal mucosal malignant melanoma,twenty-six patients received surgical treatment,nineteen patients accepted radiotherapy,and twenty-one patients had the biotherapy.The Kaplan-Meier and log-rank methods was used to assess the prognosis of different treatment.Result:the patient's 3-year-survival rate was 48.3% and 5-year-survival rate was 30.3%.Surgical treatment is the important factor for the 5-year-survival rate(P <0.05),while the chemotherapy and biotherapy had no effect on overall survival rate(P>0.05).Conclusion:The surgical treatment is the preferred method of treatment,and endoscopic surgery has the satisfactory effect.Adjuvant radiotherapy can improve local tumor control rates.Immunotherapy is the development direction of treatment for nasal mucosal malignant melanoma.

Single-center retrospective series of fourteen patients with mucosal melanoma of the nasal cavity and paranasal sinuses

ObjectivesMucosal melanoma of the nasal cavity and paranasal sinuses is a rare and highly aggressive tumor. We report our experience over 20 years in management of this tumor. Patients and methodsA retrospective study included 14 patients with primary sinonasal mucosal melanoma. ResultsThe series comprised 8 male and 6 female patients, with a median age at diagnosis of 67 years. Staging on the American Joint Committee on Cancer classification of sinus cancer was 14% T2, 22% T3, 75% T4a and 7% T4b. All patients underwent primary surgical treatment; 71% received adjuvant external radiotherapy. Median recurrence-free interval was 28.7 months. Two- and 5-year overall survival was 43% and 32%, respectively. Median follow-up was 43 months. ConclusionsMucosal melanomas of the nasal cavity and paranasal sinuses are very specific entities. Limited pathophysiological knowledge still precludes effective medium- and long-term management. Future treatment will probably be based on global adjuvant or neoadjuvant-targeted chemotherapy.

Mucosal Malignant Melanoma of Inferior Concha and Nasal Septum: A Case Report with Mutation Analysis

Mucosal Malignant Melanoma of Inferior Concha and Nasal Septum: A Case Report with Mutation Analysis Nasal and paranasal Mucosal Malign Melanoma’s occurs 0.5% of all Malign Melanomas. Sinonasal Mucosal Malign Melanoma often arises from lateral nasal wall and septum. We present molecular features (BRAF, NRAS, c-KIT and PDGFRA mutations) of a sixty-three-year-old male patient with primary sinonasal mucosal malignant melanoma with rarely localized synchronously in inferior concha and nasal septum. The patient underwent melanoma resection via endoscopic approach with negative surgical margins, right functional neck dissection and 6000 Gy radiotherapy after surgery. There was no tumor recurrence and metastasis at the ten month follow-up of the patient. Pathological studies revealed no mutations in the KIT gene (exons 9, 11, 13, 17 and 18), NRAS gene (exons 2 and 3), BRAF gene (exon 15) and the PDGFRA gene (exons 12 and 18) in this tumor. Our case is also unique with its concurrent localization in the nasal septum and inferior turbinate and with no mutations in BRAF, NRAS, c-KIT and PDGFRA genes. Primary sinonasal mucosal malignant melanomas are biologically different from cutaneous malignant melanomas and molecular features of these tumors need more investigation.

Primary sinonasal mucosal melanoma: a report on five cases

Introduction Les melanomes primitifs des muqueuses nasosinusiennes sont rares, mais tres agressives, ils representent seulement 0,5 a 2 % des melanomes et se manifestent souvent par un syndrome tumoral obstructif unilateral, volontiers hemorragique. Le diagnostic histologique de certitude est aise depuis l’apport de l’immunohistochimie. Leur pronostic reste cependant defavorable. L’objectif de notre travail est de discuter les donnees epidemiologiques et anatomocliniques des melanomes primitifs des muqueuses nasosinusiennes et de degager leurs potentiels evolutifs et les elements pronostiques.

Toward a Better Understanding of Sinonasal Mucosal Melanoma: Clinical Review of 23 Cases

Primary sinonasal mucosal melanoma is a rare disease, occurring far less often than cutaneous lesions. The objective of this study was to review the records of patients diagnosed with primary sinonasal mucosal melanoma. We performed a retrospective review of the medical records of 23 patients with sinonasal mucosal melanoma who were treated at Taipei Veterans General Hospital between 1982 and 2002. Sixteen of the 23 patients were male and 7 were female; their mean age was 68.2 years (range, 39-87 years). At diagnosis, the melanoma was limited to lesions located in the sinonasal area in 20 patients, and had spread in 3 patients. Local recurrence developed in 9 patients, neck metastasis in 5, and distant metastasis in 19. The 5-year disease-specific survival and local control rates were 22.26% and 52.30%, respectively. In our experience, primary sinonasal mucosa melanoma is prone to spread from the site of origin. The major obstacle in improving overall survival is achieving systemic control.