Primary Sinonasal Melanoma Research Articles

Primary sinonasal malignant melanoma with systemic metastasis in a non-gray horse

A 27-y-old Anglo-Arabian gelding with bay coat color was presented with a swelling of the left maxillary region. Fenestration on the left maxilla revealed that the left maxillary sinus was filled with black-red tissue. A portion of the tissue was excised and diagnosed histologically as malignant melanoma. Genotyping of the STX17 gene for gray coat color revealed that the horse did not have the "gray" factor. The horse was euthanized ~3 mo after first presentation. During autopsy, a black-to-gray mass extended from the left nasal cavity to the surrounding paranasal sinus and invaded the hard palate, cribriform plate, and the cranial portion of the left olfactory bulb. Moreover, identical black nodules were present in lymph nodes from the mandible to the larynx, and in the spleen, liver, kidney, and adrenal glands. However, masses were not found in the skin, perineal region, or pelvic cavity. All of the black-to-gray nodules were malignant melanomas that were histologically identical to the initial biopsy; tumor emboli were also found in the kidney. Sinonasal mucosal melanoma is a rare disease in horses.

Morpho-Molecular Assessment Indicates New Prognostic Aspects and Personalized Therapeutic Options in Sinonasal Melanoma.

Sinonasal melanoma is a rare subtype of melanoma and little is known about its molecular fingerprint. Systemic treatment options are limited, as targetable BRAF mutations are rare compared to cutaneous melanoma. Currently, metastatic sinonasal melanoma is being treated according to the guidelines of cutaneous melanoma. In this study, we investigated the molecular profile of 19 primary sinonasal melanomas, using a novel customized melanoma-specific next generation sequencing (NGS) panel (MelArray) of 190 genes. Results were correlated to histological and clinical features to further characterize this rare, aggressive type of melanoma and screen for prognostic markers and possible treatment options. Molecular profiles encompassed predominantly mutations in NRAS (25%), whereas KIT or BRAF p.V600 mutations were not detected. Tumor mutational burden was overall low. High level of copy number variations (CNVs) were associated with alterations in DNA-repair genes and shorter distant metastasis-free survival (p = 0.005). Monomorphic (vs. pleomorphic) morphology was found to be significantly associated with worse disease-specific survival (p < 0.001), however no correlation between morphology and molecular aberrations was found. A variety of alterations in different pathways were detected, justifying molecular testing and opening potential personalized treatment options in current study or compassionate use settings.

Sinonasal malignant melanoma: a case report

&lt;p class="abstract"&gt;Primary sinonasal malignant melanoma (SNMM) is a rare aggressive neoplasm of mucosal melanoma. It is more commonly affect adult with late presentation. Here, we report a case of SNMM in a 56-year-old lady who presented with worsening left sided nasal blockage in 1-month duration associated with black pigmented mass in nasal cavity, epistaxis and diplopia. Computerized tomographic scan showed sinonasal mass with orbital involvement and tissue biopsy confirmed the diagnosis. Surgery was performed to remove the tumour and patient had recovered well with no sign of recurrence.&lt;/p&gt;&lt;p class="abstract"&gt; &lt;/p&gt;

TERT promoter mutations in sinonasal malignant melanoma: a study of 49 cases.

Sinonasal malignant melanoma (SNMM) comprises less than 1% of all melanomas and is located in the nasal cavity and the paranasal sinuses. The majority of SNMMs have unknown underlying oncogenic driver mutations. The recent identification of a high frequency of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene in cutaneous melanoma led us to investigate whether these mutations also occur in SNMM. Our aim was to determine the TERT promoter mutation frequencies in primary SNMMs. Laser capture microdissection and manual dissection were used to isolate tumour cells from 49 formalin-fixed paraffin-embedded tissues. The tumours were screened for TERT promoter mutations by direct Sanger sequencing. Information on NRAS, BRAF and KIT mutation was available from an earlier study. Overall, 8% (4/49) of SNMMs harboured TERT promoter mutations. One of these mutated tumours had a coexistent NRAS mutation and one had a BRAF mutation. Our findings show that TERT promoter mutations are present in a moderate proportion of SNMM. No conclusion can be drawn on their potential influence on the clinical outcome or tumour progression.

Sinonasal mucosal melanoma: 20‐year experience at a tertiary referral center

Sinonasal melanoma (SNM) is a rare cancer with extremely poor prognosis. Detecting melanoma on frozen section has historically been considered to be unreliable. A review of cases of sinonasal melanoma treated at a tertiary referral center was conducted to analyze treatment outcomes and identify prognostic factors for survival. In addition, an investigation was performed correlating sinonasal melanoma on frozen section and permanent analysis. An institutional review board-approved search of the pathology database for cases of primary sinonasal melanoma treated between 1991 and 2011 was performed. Fourteen cases were identified and the medical charts were reviewed. Eleven patients had tumors arising from the nasal cavity, 2 arose from the maxillary sinus, and 1 from the ethmoid sinuses. Mean duration of follow-up was 20.7 (range, 1.4 to 84.5) months. Overall, 5-year recurrence-free survival and overall survival was 23% and 35%, respectively. All patients had surgical resection with intent for cure and all but 1 patient had adjuvant therapy. Survival analysis showed that positive margin status (log rank p = 0.031) and the presence of perineural/lymphovascular invasion (log rank p = 0.021) negatively affected recurrence-free survival and overall survival, respectively. Nine cases had evaluation of intraoperative frozen sections with 32 total sections submitted for analysis. When compared with final pathology, there was a 0% false negative rate. Based on this series, positive margins and the presence of perineural/lymphovascular invasion are negative predictors of survival. In addition, intraoperative frozen section analysis of sinonasal mucosal melanoma correlates well with final pathology.

Primary sinonasal malignant melanoma: a nationwide study of the Swedish population, 1960-2000

To establish population-based trends for sinonasal mucosal melanoma (SNMM) in Sweden. We identified 186 patients from the Swedish National Cancer Registry diagnosed with primary melanomas arising from the nasal cavity, paranasal sinuses, or both, during the period 1960 through 2000. Incidence, gender and age, primary anatomical sites, geographic distribution, treatment and survival were investigated. The age-standardized incidence of SNMM increased significantly during the 41-year-period, with a higher overall incidence for females than males, but with a more rapid increase for males than for females. The incidence increased with age, peaking after the eightieth year in both genders. About 70 % of the cases were clinically amelanotic. The most common primary treatment was surgery. Five-year, disease-specific survival rates were poor for all these patients, but women had a significantly better survival time than men. For both genders the survival rate lengthened during the study period, irrespective of therapeutic strategy. SNMM is a rare disease, but the incidence in Sweden has increased significantly from 1960 through 2000, although not at the same pace as that of cutaneous malignant melanoma. Both the incidence and the survival were significantly higher in females than in males, but the reason for these gender differences is unknown.

Primary sinonasal malignant melanoma: a nationwide study of the Swedish population, 1960–2000

Primary sinonasal malignant melanoma: a nationwide study of the Swedish population, 1960–2000

Malignant melanoma of nasal cavity and paranasal sinuses: report of 24 patients and literature review

To report our experience of the management of patients with primary sinonasal malignant melanoma, and to review the relevant medical literature. Retrospective review examining treatment and outcomes. Twenty-four patients were treated between 1982 and 2007. The mean age at presentation was 67.5 years. The overall five-year survival was 30 per cent; mean survival was three years and eight months. Sinonasal malignant melanoma is associated with a poor outcome, and survival statistics have not improved over the last 40 years. Treatment should include radical surgery wherever possible. Local recurrence is common; radiotherapy may help control this but does not appear to affect overall survival. The limited evidence available suggests that endoscopic removal of sinonasal malignant melanoma is as effective as other local surgical means, but that craniofacial resection remains the 'gold standard' for tumours that contact or traverse the skull base. Novel biological treatments are emerging and hold promise for the future.

Immunophenotypic Heterogeneity of Primary Sinonasal Melanoma With Aberrant Expression of Neuroendocrine Markers and Calponin

Primary sinonasal melanoma is an aggressive tumor that often presents a diagnostic challenge owing to its rarity and variable morphology. Unusual immunophenotypic expression of sinonasal melanoma compounds the problem particularly in a limited tissue sample. We studied immunohistochemical patterns of 5 primary sinonasal melanoma using antibodies against pan-cytokeratin, S-100, HMB-45, Melan-A, chromogranin, synaptophysin, neurofilament protein, and calponin and correlated these patterns with histologic appearance. Sinus/nasal mucosa from non-neoplastic cases were stained for Melan-A to evaluate prevalence of melanocytes in the benign mucosa in comparison to the staining pattern of the mucosa adjacent to the tumor. Similar to previous report, small cell pattern appeared to be over represented in the sinonasal melanoma. Small cell population in 4 cases was almost devoid of pigment, and also was either completely negative or only focally positive for S-100. Three cases stained positive for neuroendocrine markers and neurofilament protein bringing olfactory neuroblastoma and small cell neuroendocrine carcinoma in as differential diagnosis. Three cases were focally positive for calponin without spindle cell morphology or desmoplastic reaction. Immunophenotypic heterogeneity along with the unconventional histomorphology of sinonasal melanoma compounds diagnostic problem and warrants a precautionary approach to avoid misinterpretation. It is necessary to apply a broad panel of immunohistochemistry for the purpose of screening when sinonasal melanoma is considered as a differential diagnosis.

Outcome of sinonasal melanoma: Clinical experience and review of the literature

Primary sinonasal malignant melanoma (SNMM) is a rare clinical entity. There is neither a classification nor a staging system nor an evidence-based treatment concept established. Our objective was to find potential risk factors predicting the outcome. Twenty-five patients with histologically confirmed SNMM were consecutively included and retrospectively analyzed. Staging methods were nasal endoscopy, CT, MRI, and positron emission tomography (PET) scan. Patients were selected for a curative or palliative concept. All patients had postoperative follow-up with control-MRI at 3 and 6 months. Restaging was performed when local recurrence occurred. Nineteen patients underwent primary surgery with curative intention; in 16 cases with tumor free margins. Thirteen patients (68%) had transnasal endoscopic surgery, 4 lateral rhinotomy, and 2 transfacial approach with orbital exenteration. Six patients (32%) had palliative therapy and 7 patients (37%) had adjuvant radiotherapy. Despite radical operations, 6 patients (37%) showed local recurrence and 8 patients (50%) developed distant metastasis. In 2 patients with incomplete surgery, regional metastasis was noted. The median disease-free interval was 18 months, and the median overall survival rate was 23 months. SNMMs of the ethmoid and maxillary sinuses have a worse prognosis than other localizations in the nasal cavity; infiltration into the skull base, orbit, or facial soft tissue correlates with a very poor outcome corresponding to the palliative situations. Furthermore, local recurrence insinuates aggressive disease with short survival rate. A main difference from its cutaneous counterpart seems to be a primary tendency to hematogenic spread. Further research is needed to confirm these findings.

Primary Sinonasal Malignant Melanoma: A Clinicopathologic and Prognostic Study

We conducted a retrospective study to evaluate the clinicopathologic features and prognostic factors associated with primary sinonasal malignant melanoma. We reviewed the records of 10 patients-7 men and 3 women, aged 35 to 70 years (mean: 51.4)-who had been treated at our referral center over a 9-year period. The tumors were located in the nasal cavity in 7 patients and in a paranasal sinus in the other 3. Medial maxillectomy was performed in 4 patients, wide local excision in 3, and endoscopic excision in 2; the remaining patient, who had presented with a liver metastasis, received chemotherapy and palliative local radiotherapy. Two patients who presented with a neck node metastasis also underwent concurrent radical neck dissection. Follow-up ranged from 8 to 70 months (median: 25). Only 4 patients remained alive through the duration of follow-up. The 2- and 5-year survival rates were 60 and 40%, respectively. Based on the findings of our small study, we conclude that primary sinonasal malignant melanoma carries a generally poor prognosis despite aggressive treatment. The primary cause of death in our series was a distant metastasis (n = 5) despite adequate locoregional control in most cases. This finding confirms the aggressive nature of this disease. Other factors that appeared to be associated with a poor prognosis were (1) older age, (2) a primary tumor location in a paranasal sinus, (3) an advanced tumor stage, (4) an external approach to surgery, and (5) the absence of adjuvant radiotherapy.

Primary Melanoma of the Sphenoid Sinus

Background and Aim: Malignant melanoma is a very rare disorder in the paranasal sinuses. It accounts for less than 1% of all malignant melanomas and less than 3% of paranasal malignancies. It is also rare for a melanoma to metastasize to this region. However, a thorough investigation is always needed to rule out a metastasis as opposed to a primary sinonasal melanoma. Malignant melanomas arising from the sphenoid sinus with unilateral invasion of the skull base are also extremely rare. Whether the sella turcica or sphenoid sinus is the site of origin is difficult to determine based on neuroradiological findings. These tumors have poor prognosis owing to higher rates of locoregional recurrence and distant metastasis.

Melan‐A as a useful diagnostic immunohistochemical stain for the diagnosis of primary sinonasal melanomas

Sinonasal melanomas are rare neoplasms whose diagnosis may require confirmatory immunohistochemical stains. S-100 protein and HMB-45, the stains most commonly used, have varying sensitivities and specificities. Melan-A, a more recent melanoma-specific marker, may prove helpful when S-100 protein and HMB-45 stains are negative or equivocal. Seven cases of sinonasal melanoma were assessed for reactivity with Melan-A, S-100 protein and HMB-45. The study group consisted of two women and five men ages 40 to 83. Six of the neoplasms were strongly positive for S-100 protein. One case was negative for S-100 protein and HMB-45 but positive for Melan-A. HMB-45 staining varied between diffusely positive (three cases), focally positive (two cases), and negative (two cases). All cases were positive for Melan-A either diffusely (four cases) or focally (three cases). Because Melan-A can be positive in cases that are S-100 protein or HMB-45 negative, it is a useful component in the immunohistochemical panel for the diagnosis of sinonasal melanomas.

CD44 expression in sinonasal melanomas: is loss of isoform expression associated with advanced tumour stage?

The expression of the adhesion molecule CD44 was examined in 14 primary sinonasal melanomas (SMs), aggressive neoplasms with short survival times, as CD44 overexpression has been linked to poor survival in human cancers. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections with CD44 isoform-specific monoclonal antibodies to the CD44 standard (s) and variant isoforms (v) v5 and v6. CD44s, v5, and v6 were strongly expressed in a membranous pattern in SM in situ, early invasive SM, and in uninvolved respiratory/squamous epithelium. In invasive SM, membranous CD44s expression was identified in a large proportion of melanoma cells. Membranous staining of CD44v5 and v6 was lost in invasive SM, independently of the histological subtype. Diffuse cytoplasmic staining was observed focally in invasive SM and loss of cytoplasmic expression of CD44v6 and v5 was associated with advanced tumour stage in the linear-by-linear association test (p = 0·042 and 0·066, respectively). CD44s may not be important for malignant transformation, as it is expressed in both benign and malignant melanocytes. Loss of membranous CD44 isoform expression in widely invasive SM suggests that loss of cellular adhesion facilitates matrix and vascular infiltration and dissemination of sinonasal melanoma cells. Copyright © 1999 John Wiley & Sons, Ltd.

CD44 expression in sinonasal melanomas: is loss of isoform expression associated with advanced tumour stage?

The expression of the adhesion molecule CD44 was examined in 14 primary sinonasal melanomas (SMs), aggressive neoplasms with short survival times, as CD44 overexpression has been linked to poor survival in human cancers. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections with CD44 isoform-specific monoclonal antibodies to the CD44 standard (s) and variant isoforms (v) v5 and v6. CD44s, v5, and v6 were strongly expressed in a membranous pattern in SM in situ, early invasive SM, and in uninvolved respiratory/squamous epithelium. In invasive SM, membranous CD44s expression was identified in a large proportion of melanoma cells. Membranous staining of CD44v5 and v6 was lost in invasive SM, independently of the histological subtype. Diffuse cytoplasmic staining was observed focally in invasive SM and loss of cytoplasmic expression of CD44v6 and v5 was associated with advanced tumour stage in the linear-by-linear association test (p = 0.042 and 0.066, respectively). CD44s may not be important for malignant transformation, as it is expressed in both benign and malignant melanocytes. Loss of membranous CD44 isoform expression in widely invasive SM suggests that loss of cellular adhesion facilitates matrix and vascular infiltration and dissemination of sinonasal melanoma cells.

Primary mucosal melanomas of the nasal cavity and paranasal sinuses. A clinicopathological analysis of 14 cases.

We present 14 patients with primary sinonasal melanomas (SM) identified from 1984-1997 in our archives (11/14 lateral nose, 1/14 nasal septum, 2/14 paranasal sinuses; 8M/6F, mean age 67.7 years, range 39-88 years). Survival was poor (median 9 months) with death related to extensive local disease and/or widespread hematogenous metastases. The following histological subtypes were identified in descending order: amelanotic small blue cell, pleomorphic, epithelioid, spindle cell and myxoid. High mitotic rate and vascular invasion, absence of tumor-infiltrating lymphocytes and regression were features shared by all SM. Negative staining of B- and T-cell markers, LCA, neuroendocrine markers such as NSE, chromogranin and synaptophysin, and CK-negativity excluded olfactory neuroblastoma, small cell undifferentiated carcinoma, and lymphoma. S-100 protein was expressed in all SM, but demonstrated variable staining intensity with areas of complete negativity. HMB45 was strongly and uniformly (>80%) expressed in all undifferentiated small blue cell SM. The pigmented SM were predominantly HMB45-negative. The strong HMB45 staining in amelanotic small blue cell SM is explained by the reaction of HMB45 antibody with an oncofetal antigen found in immature melanosomes. In these poorly differentiated amelanotic malignant melanomas, antibody to HMB45 proved to be a superb diagnostic marker. We therefore strongly advocate the inclusion of HMB45 antibody in the panel of antibodies for initial work-up of undifferentiated mucosal neoplasms, since a negative S-100 stain in small biopsy material may result in incorrect classification of these neoplasms.

Melanoma botryoides: a distinctive myxoid pattern of sino-nasal malignant melanoma.

Two primary sino-nasal melanomas are presented which were characterized by their botryoid growth pattern and myxoid stroma. These polypoid tumours contained small amounts of melanin and only focal areas of epithelioid cells. An in situ component was present in both of the tumours. Malignant melanoma should be considered when confronted by a myxoid tumour (with or without melanin) in the sino-nasal region. These tumours are widely infiltrative, and there is no evidence to suggest that they will behave any differently from conventional, non-botryoid, non-myxoid sino-nasal melanomas.