Primary Mucosal Melanoma Research Articles

Mucosal melanoma of the oral cavity

Primary mucosal melanomas of the head and neck region are uncommon but aggressive malignancies. These lesions arise from melanocytes located in mucosal membranes, predominantly in the nasal cavity, paranasal sinuses, and oral cavity. Mucosal melanomas account for less than 4% of all melanoma cases and are often missed, due to their occult initial presentations. This is in contrast to cutaneous melanomas, which constitute approximately 85% of melanoma cases and present on surfaces exposed to ultraviolet (UV) radiation. The mainstay of treatment for mucosal melanoma is surgical resection with adjuvant radiotherapy for patients with high-risk features. Despite advancements in surgical techniques, radiotherapy, and even systemic therapies, patients with mucosal melanoma face unfavourable prognoses (5-year disease-free survival <25%) with high rates of locoregional recurrence and/or distant metastases. The present case addresses a 47 year-old man who presents to Otolaryngology with an apparent mucosal melanoma involving the upper lip. This patient was informed of a pigmented lesion on the mucosal surface of the upper left lip three years prior by his dentist. Although largely asymptomatic, the lesion has increased in size. The patient undergoes surgical resection with clear margins and reconstruction. He continues to follow-up to monitor for disease recurrence, having denied adjuvant radiation. This case illustrates the diagnosis and approach to mucosal melanomas and highlights some of the key distinctions between mucosal and cutaneous melanomas.

Primary Mucosal Malignant Melanoma of the Maxilla: A Case Report and Review of Literature

In this study which was achieved at Izmir Bozyaka Teaching and Research Hospital, identifying the sensitivity and reliability of round window electrocochleographic records on children during cochlear implantation and investigating the applicability of the method on particularly problematic patient groups was aimed

Clinicopathological Characteristics and survival analyses of Primary Mucosal Malignant Melanoma: An Experience from a Cancer of Pakistan

Introduction: Mucosal malignant melanoma (MMM) can arise from the ocular mucosal membranes, and mucosal membranes of respiratory tract, gastrointestinal and genitourinary tract. They are rare and aggressive cancers with poor prognosis. The cornerstone of management is surgical resection along with chemotherapy and radiotherapy. The aim of the study is to analyze the clinicopathological factors and survival analyses of MMM from Pakistan population. Methodology: During 1st January 1995 to 31st December 2018, patients presented with histological diagnosis of Primary MMM at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), Pakistan were selected. It is a retrospective study with convenience sampling. Calculations were performed with Statistical Package for the Social Sciences (SPSS 20) for Windows version 20. Results: During the span of two decades, 269 patients presented with the histological diagnosis of MMM. 163 (60.5%) patients had cutaneous malignant melanoma, 98 (36.4%) patients had MMM, five (1.8%) patients had ocular malignant melanoma and 3 (1.1%) had visceral malignant melanoma. Of all the MMM, anal canal (59.1%) was the most prevalent site, followed by mucosal melanoma of head and neck region (19.4%) and then female genital track (14.1%). One male patient also had malignant melanoma of urethra. Mean age at the diagnosis of mucosal malignant melanoma was 53 years (23-97). Median duration of symptoms was 8 months (3-36). Genital malignant melanoma had the most favorable survival outcomes of 25 months, followed by anorectal MM (22 months). The worst survival outcomes were noticed among patients with melanoma of mucosal origin from head and neck region (10 months). Median overall survival after mucosal malignant melanoma was 19 months (3-97). Conclusion: Our study demonstrates that the overall prognosis of MMM is poor. It varies in patients with different anatomical site. Despite of the adequate treatment, risk of local or distant recurrence is high.

PO-0823: A nomogram to predict locoregional recurrence for primary mucosal melanoma of the head and neck

PO-0823: A nomogram to predict locoregional recurrence for primary mucosal melanoma of the head and neck

Efficacy, Tolerability, and Pharmacokinetics of Combined Targeted MEK and Dual mTORC1/2 Inhibition in a Preclinical Model of Mucosal Melanoma.

Melanomas arising in the mucous membranes are a rare and aggressive subtype. New treatment approaches are needed, yet accumulating sufficient evidence to improve patient outcomes is difficult. Clinical and pathological correlates between human and canine mucosal melanomas are substantial, and the relatively greater incidence of spontaneous naturally occurring mucosal melanoma in dogs represents a promising opportunity for predictive modeling. The genomic landscapes of human and canine mucosal melanoma appear highly diverse and generally lack recurring hotspot mutations associated with cutaneous melanomas. Although much remains to be determined, evidence indicates that Ras/MAPK and/or PI3K/AKT/mTOR signaling pathway activations are common in both species and may represent targets for therapeutic intervention. Sapanisertib, an mTORC1/2 inhibitor, was selected from a PI3K/mTOR inhibitor library to collaborate with MEK inhibition; the latter preclinical efficacy was demonstrated previously for canine mucosal melanoma. Combined inhibition of MEK and mTORC1/2, using trametinib and sapanisertib, produced apoptosis and cell-cycle alteration, synergistically reducing cell survival in canine mucosal melanoma cell lines with varying basal signaling activation levels. Compared with individual inhibitors, a staggered sapanisertib dose, coupled with daily trametinib, was optimal for limiting primary mucosal melanoma xenograft growth in mice, and tumor dissemination in a metastasis model, while minimizing hematologic and renal side effects. Inhibitors downmodulated respective signaling targets and the combination additionally suppressed pathway reciprocal crosstalk. The combination did not significantly change plasma sapanisertib pharmacokinetics; however, trametinib area under the curve was increased in the presence of sapanisertib. Targeting Ras/MAPK and PI3K/AKT/mTOR signal transduction pathways appear rational therapies for canine and human mucosal melanoma.

A Nomogram to Predict Locoregional Recurrence after Surgery and Postoperative Adjuvant Radiation Therapy for Primary Mucosal Melanoma of the Head and Neck

To evaluate postoperative radiotherapy (PORT) on prognosis for patients with mucosal melanoma of the head and neck (MMHN) and create a specific nomogram to predict the probability of locoregional recurrence (LRR) of MMHN after surgery and PORT. We retrospectively reviewed 111 patients with non-metastatic MMHN who underwent definitive surgical treatment with PORT between January 2008 and December 2018. Clinical characteristics and blood test parameters were analyzed for relationships with treatment outcomes, and a nomogram was created to estimate the risk of LRR using R software. The median follow-up was 44.2 months (range, 5.9–111 months), and we identified 17 local recurrence (15.3%), 1 regional lymph node metastasis (0.9%), and 33 distant metastases (29.7%). Relative to later recurrence, early locoregional recurrence (<2 years after surgery and PORT) was associated with poorer overall survival (OS) (P = 0.001). The multivariate analysis revealed that independent risk factors for better locoregional recurrence-free survival (LRRFS) included age > 56 years, bilirubin (BIL) > 8.5 μmol/L, Mg2+ > 0.8 mmol/L, mean corpuscular hemoglobin (MCH) < 32.3 pg and mean platelet volume (MPV) <10.0 fL. These five factors were used for the nomogram which had a C-index of 0.884 for predicting LRR, and internal validation revealed a good discriminative ability. Early locoregional recurrence (<2 years) was associated with poor OS of MMHN after surgery and PORT. Our nomogram may be useful for predicting LRR of MMHN, and internal validation confirmed good discriminative ability.

Immunotherapy in Combination with Surgery and Radiation Improves Local Control for Primary Mucosal Melanomas

Immunotherapy in Combination with Surgery and Radiation Improves Local Control for Primary Mucosal Melanomas

S2223 Dead End in the Small Bowel: Rare Case of Small Bowel Melanoma Presenting as Melena

INTRODUCTION: Malignant melanoma accounts for only 1% of all malignant tumors of the small bowel. The majority are usually metastatic from the skin eye or anorectum. Less than 50 cases of truly primary small bowel melanomas have been described in literature with overt bleeding as a presenting complaint even rarer. We present such a case of an elderly man with middle gastrointestinal bleeding who was found to have unresectable small bowel melanoma on device assisted enteroscopy. CASE DESCRIPTION/METHODS: An 80-year-old man with stage IV Chronic kidney disease presented to the hospital with a few months of dark tarry stools and symptomatic iron deficiency anemia refractory to iron supplementation needing up to 7 transfusions. He did not endorse Non-steroidal anti-inflammatory drug use. An esophagoduodenoscopy and colonoscopy at an outside facility was unremarkable. Video capsule endoscopy showed hematin in the the proximal jejunum with a possible ulcer more distally. A single balloon enteroscopy revealed a 10 mm cratered jejunal ulcer with slight pigmentation in the base (Figure 1). This was biopsied. Pathology revealed malignant melanoma with BRAF V600E mutation. Subsequent positron emission tomography (PET) showed a 6 cm small bowel mass compatible with primary site and metastatic lesions in the mesentery, perihepatic and subdiaphragmatic region (Figure 2). Following tumor board discussion, he was referred for palliative radiotherapy. DISCUSSION: Primary mucosal melanoma most commonly arises from the anal canal (31.4%), rectum (22.2%) and oropharynx (33%). Only 2.3% of cases have been reported from the small bowel. Presence of melanocytes has not yet been demonstrated in the small intestine, and the origin of primary melanoma of the small intestine remains unknown. Blecker et al. suggested a strict criteria for the diagnosis of primary intestinal melanoma: no evidence of concurrent cutaneous lesions, absence of extraintestinal metastatic spread of melanoma, and presence of intramucosal lesions in the overlying intestinal epithelium. This form of melanoma is more aggressive and associated with worse prognosis. Other factors of poor prognosis include lymph node involvement, advanced age and failure to undertake surgical resection (which remains the primary treatment option). Our case highlights the importance of keeping a broad differential in patients presenting with middle GI bleeding and aggressively pursuing tissue diagnosis in such cases.Figure 1.: Proximal Jejunum ulcer.Figure 2.: PET scan image with metastatic melanoma.

S2770 When Two Rarities Occur, the Bowel Cringes

INTRODUCTION: Intussusception is a rare cause of mechanical intestinal obstruction in adults and is more frequently observed in pediatric patients. It tends to occur in association with a pathologic lead point, in most cases, a malignancy. Malignancies that commonly cause intussusception include lymphoma, colonic adenocarcinoma, and metastatic melanoma. Primary intestinal melanoma, however, is extremely rare and here we describe a case that presented as intussusception. CASE DESCRIPTION/METHODS: A 64-year-old female with asthma, COPD, OSA, HTN, HLD, GERD presented with a one week history of abdominal pain and nausea that progressed to coffee-ground emesis and melena a few days prior to admission. She endorsed a 22 pound unintentional weight loss and initial exam showed a soft but diffusely tender abdomen with labs only significant for a normocytic anemia that was near baseline. Computed tomography (CT) of the abdomen revealed intussusception and wall thickening involving the proximal small bowel (Figure 1). A small bowel enteroscopy demonstrated a 3-4 cm ulcerated, non-circumferential, non-obstructing mass in the proximal jejunum (Figure 2). A few non-bleeding superficial jejunal ulcers in the surrounding area which were presumed ischemic from the intussusception were also noted. Biopsies were sent for pathology and revealed sheets of infiltrating malignant cells with moderate amphiphilic cytoplasm and enlarged nuclei, some with pseudo inclusions. Immunohistochemical staining was done and the tumor cells stained positive for S100 and MelanA/MART1 and negative for CK7, CK20, CDX12, and CD45 which was concerning for metastatic melanoma (Figure 3). Patient underwent exploratory laparotomy with excision of the jejunal mass with surgical pathology confirming a malignant melanoma. Extensive imaging and examination of all cutaneous surfaces did not reveal a primary source. The patient was deemed to have a primary small bowel melanoma. DISCUSSION: Primary small bowel melanoma is extremely rare and should always be on the differential for neoplasms that can cause intussusception. Most intestinal melanomas represent metastatic disease and definite diagnosis can only be made after thoroughly excluding a primary lesion. It is important to recognize primary mucosal melanomas, as they are more aggressive and carry a worse prognosis, partly due to late diagnosis. Early recognition and diagnosis may allow for curative resection of the tumor, which remains the treatment of choice.Figure 1.: Proximal jejunal intussusception.Figure 2.: Push enteroscopy showing proximal jejunal mass.Figure 3.: Top left, immunohistochemical stain positive for s100. Top right, immunohistochemical stain positive for MelanA. Bottom left, H&E stain showing malignant cells with lymphovascular invasion. Bottom right, H&E stain, high power showing amphophilic cytoplasm, pleomorphic nuclei, and numerous mitotic figures.

Correlation of MET and PD-L1 Expression in Malignant Melanoma.

The proto-oncogene MET, the hepatocyte growth factor (HGF) receptor, is a transmembrane receptor tyrosine kinase (RTK) with a prominent role in tumor metastasis and resistance to anti-cancer therapies. Melanoma demonstrates relatively frequent MET aberrations, including MET gene amplification. Concurrently, programmed death-ligand 1 (PD-L1), with its ability to evade anti-tumor immune responses, has emerged as a prominent therapeutic target in melanoma and other malignancies and its expression is used as a predictive biomarker of response to immunotherapy. We performed immunohistochemistry analysis of MET and PD-L1 in 18 human melanoma cell lines derived from both primary and metastatic lesions, and in a human melanoma tissue microarray containing one hundreds melanocytic lesions, including primary cutaneous melanomas, primary mucosal melanomas, metastatic melanomas and benign melanocytic nevi as controls. After color deconvolution, each core was segmented to isolate staining and calculate the percentage of positive cells. Overall, MET expression was higher in tumors with increased PD-L1 expression. Moreover, a robust correlation between MET and PD-L1 expression was found in samples from metastatic melanoma and not in primary cutaneous or mucosal melanoma. These data suggest that relative expression levels of these proteins in combination is a marker of advanced disease and testing for expression of these markers should be considered in patients with melanoma.

Primary mucosal malignant melanoma of the nasal cavity

&lt;p&gt;Primary mucosal melanoma of the nasal cavity and paranasal sinuses is a very aggressive and rare disease with only about 0.5 % of malignant melanoma arising from the nasal cavity. There are only few reports from India. We report a rare case of sino-nasal mucosal malignant melanoma in a 58 years old female who presented with blackish coloured sino-nasal mass involving right nasal cavity, spontaneous and recurrent epistaxis and obliteration of the right naso-labial fold with occasional pain in the past 10 months. Contrast enhanced computed tomography scan showed a heterogenous mass involving right nasal cavity, right maxillary antrum and right ethmoidal area. A positron emission tomography computed tomography was also done which showed increased uptake in the region mentioned above. Initial biopsy, the mass was diagnosed as malignant melanoma. Total maxillectomy was performed with plan of post-operative radiotherapy.&lt;/p&gt;

Immune-related adverse events correlate with improved survival in patients with advanced mucosal melanoma treated with nivolumab: A single-center retrospective study in Japan.

Immune-related adverse events (irAE) were reported to be associated with better outcomes in various cancers treated with the immune checkpoint inhibitor nivolumab. Considering that their development depends on host immune activation, irAE may reflect antitumor response in mucosal melanoma (MM). This single-center retrospective study including patients with advanced MM receiving nivolumab monotherapy between August 2014 and September 2018 investigated whether the development of irAE was associated with clinical efficacy. The study patients were divided into those with and without irAE, and treatment efficacy and safety were evaluated. The study cohort of 27 patients included 20 (74%), six (22%) and one (4%) patient with primary MM in the head and neck, genitourinary and anorectal regions, respectively. The irAE onset was not significantly associated with the objective response rate in patients while it was significantly associated with the disease control rate. The median progression-free survival in patients with and without irAE was 301 and 63days, respectively. The median overall survival (OS) in patients with and without irAE was 723 and 199days, respectively. According to the timing of irAE onset, the OS was better in seven patients who developed irAE after 180days than in nine patients who developed irAE within 180days. Although 16 patients (59%) experienced any grade irAE, including three (11%) with grade 3 or more irAE, there were no treatment-related deaths. These results indicated that the development of irAE may correlate with improved survival in patients with MM treated with nivolumab monotherapy. Further studies are necessary to confirm these findings.

METABOLIC-RELATED AND STEM CELL MARKERS IN A SERIES OF PRIMARY ORAL MUCOSAL MELANOMAS AND ORAL NEVI

Primary oral mucosal melanomas (POMM) are rare and aggressive neoplasms arising in the melanocytes from the epithelial lining of the oral cavity, and currently few prognostic markers are described. Objective: In this study, we investigated the expression of glucose transporter 1 (GLUT1), antimitochondrial antibody (AMT), and stem cell markers (CD44) in a series of 3 POMM and 3 oral nevi. Methods: Immunostainings of GLUT1, CD44, and AMT were quantitatively assessed by digital analyses. Results: POMM showed a proliferation of epithelioid or fusiform variable-pigmented melanocytes. GLUT1, CD44, and AMT were negative in all nevi and strongly expressed in the melanomas. Conclusion: Our results suggest that overexpression of mitochondrial and stem cells markers can help confirm the diagnosis of melanomas and they can be associated with the aggressive behavior of these rare tumors.

Conjunctival melanoma is a molecular distinct mucosal melanoma with high expression of PD‐L1

AbstractPurposeConjunctival melanoma is a unique mucosal melanoma due to its location in the sunexposed conjunctiva. The purpose of this study was to contextualize conjunctival melanoma as a mucosal melanoma based on molecular profiling. This is the first study of its kind.Material and Methods12 primary conjunctival melanomas and 28 primary mucosal melanomas from non‐sunexposed sites (nasal cavity, vagina, and rectum) were subjected to molecular profiling using targeted next‐generation sequencing (Oncomine Comprehensive Cancer Panel) and NanoString gene expression profiling (PanCancer Pathways Panel, 770 cancer genes). Normal conjunctiva and mucosa were used as internal controls.ResultsGenetically, conjunctival melanomas harboured BRAF‐V600E mutations and NF1 mutations, whereas other mucosal melanomas harboured more unspecific mutations, such as atypical BRAF mutations and mutations in KIT. Non‐sunexposed mucosal melanomas frequently presented amplification of MYC. When comparing the gene expression profile of conjunctival melanoma and non‐sunexposed mucosal melanoma, 41 genes were found to be significantly deregulated. 24 genes were upregulated, whereas 17 were downregulated in conjunctival melanoma. Many of the deregulated genes were involved in immunological pathways when performing an in silico pathway analysis. Most intriguingly, programmed death‐ligand 1 (PD‐L1) presented a significant 6‐fold upregulation in conjunctival melanoma. This finding could be validated with immunohistochemistry (p = 0.041, Fisher’s exact test). A network analysis revealed that PD‐L1 was co‐expressed with 8 other genes.ConclusionsComprehensive molecular profiling on the DNA and mRNA level revealed that conjunctival melanoma is a distinct molecular mucosal melanoma characterized by a higher frequency of BRAF‐V600E mutations, low expression of MYC and a high expression of PD‐L1 and other genes involved in immune response. This finding is important, as this suggests a higher response to checkpoint inhibition in conjunctival melanoma metastases when compared to other mucosal melanomas.

Advances in the management of genitourinary melanomas

Primary mucosal melanomas of the genitourinary (GU) tract are rare but aggressive tumors that can affect mucosal surfaces of the GU tract and urinary tract. They exhibit distinct biological differences compared to cutaneous melanomas and other mucosal melanomas. There is also significant variation among genitourinary melanoma subtypes. Little is known about the etiology of this disease or the natural history and there is currently no established staging system. Treatment is challenging as diagnosis is typically made at a later stage of disease and response to immunotherapy is not robust. Targetable activating mutations are infrequent, the most common being in c-KIT , expressed in one-third or less of patients. Surgical resection remains the standard of care, and emphasis on less invasive resection is recommended whenever possible. Initial adjuvant treatment typically consisted of dacarbazine-based chemotherapy, though recent advances in effective systemic immunotherapies have shown promising results. Existing data are insufficient to make evidence-based recommendations regarding the best course of treatment and much remains unknown regarding the best management of this disease. Given the rarity of GU melanomas, specific clinical trials are difficult to design. Ongoing trials of mucosal melanomas are underway which may identify new effect treatment modalities.

A Rare Case of Primary Gastric Melanoma

Primary melanomas in the gastrointestinal tract are extremely rare, with an estimated prevalence of 0.5 to 1 case per million. Primary mucosal melanomas of gastric origin account for approximately 1–3% of all primary melanomas in the gastrointestinal tract. We present the case of a patient who underwent surgery due to primary gastric melanoma.

Atypical BRAF and NRAS Mutations in Mucosal Melanoma

Primary mucosal melanomas represent a minority of melanomas, but have a significantly worse prognosis than cutaneous melanomas. A better characterization of the molecular pathogenesis of this melanoma subtype could help us understand the risk factors associated with the development of mucosal melanomas and highlight therapeutic targets. Because the Mitogen-Activated Protein Kinase (MAPK) pathway plays such a significant role in melanoma development, we explore v-raf murine sarcoma viral oncogene homolog B (BRAF) and neuroblastoma RAS viral oncogene homolog (NRAS) mutations in mucosal melanoma and compare them to the mutation profiles in cutaneous melanoma and other tumors with BRAF and NRAS mutations. We show that in addition to being less frequent, BRAF and NRAS mutations are different in mucosal melanoma compared to cutaneous melanomas. Strikingly, the BRAF and NRAS mutation profiles in mucosal melanoma are closer to those found in cancers such as lung cancer, suggesting that mutations in mucosal melanoma could be linked to some genotoxic agents that remain to be identified. We also show that the atypical BRAF and NRAS mutations found in mucosal melanomas have particular effects on protein activities, which could be essential for the transformation of mucosal melanocytes.

Mucosal melanoma of the female genital tract: Operation modalities.

e21060 Background: Primary melanomas originating from the female genital tract are rare and aggressive. There are still no established guidelines for its primary surgery , so we analyzed the effect of the surgical approach on its relapse free survival (RFS) and overall survival (OS ) based on a phase 3 randomized trial (NCT03435302). Methods: Mucosal melanoma patients with female genital tract primary which were stageⅠ-Ⅲ and completely resected were enrolled as part of the multicenter, randomized, controlled, phase 3 trial for the comparison of adjuvant chemotherapy (TMZ plus DDP 6 cycles) vs. High-dose interferon group (HDI, 1 year).The RFS and OS was compared between local and extensive excision group. Results: Seventy eight female genital tract primary melanoma patients were enrolled from Feb 2014 to Jun 2016, Surgical approach was chosen by the surgeon, 39.2% (29/74) took local excision and 60.8% (45/74) extensive excision. The average age was 52.3 years. Of all these patients 46.2% were vulvar primary, 53.8% vaginal, and 85.3%stage I/II, 14.7% stage III. Primary ulceration was found in 68.1% lesions, 7 cases harbored with BRAF mutation. 57.7% patients randomized to adjuvant chemotherapy and 42.3% in HDI group. All these factors showed no difference in local excision and extensive excision group. At a median follow-up of 31.2 months (range: 5.3-60.0m), 64.4% got metastases and 23.1% showed local recurrence. RFS (8.0m vs. 11.4m, p = 0.523) and local recurrence rate (13.8% vs.31.1%, p = 0.105 ) did not show significant difference between local excision group and extensive excision group. OS in whole cohort was 28.9 months, it also did not show significant difference between two groups(local 25.5m vs. extensive 40.1m, p = 0.653). In univariate analysis there was also no relation between surgical approach and OS in this cohort. Conclusions: Based on this trial, for resectable female genital tract primary mucosal melanoma, there was no difference of local control rate, RFS and OS between local excision and extensive excision group. Local excision might be adequate for the primary leision. Still more prospective data are needed for this subtype of melanoma. Clinical trial information: NCT03435302.

Predominance of triple wild-type and IGF2R mutations in mucosal melanomas

BackgroundPrimary mucosal melanoma (MM) is a rare subtype of melanoma that arises from melanocytes in the mucosa. MM has not been well profiled for mutations and its etiology is not well understood, rendering current treatment strategies unsuccessful. Hence, we investigated mutational landscape for MM to understand its etiology and to clarify mutations that are potentially relevant for MM treatment.MethodsForty one MM and 48 cutaneous melanoma (CM) tissues were profiled for mutations using targeted deep next-generation sequencing (NGS) for 89 cancer-related genes. A total of 997 mutations within exons were analyzed for their mutational spectrum and prevalence of mutation, and 685 non-synonymous variants were investigated to identify mutations in individual genes and pathways. PD-L1 expression from 21 MM and 18 CM were assessed by immunohistochemistry.ResultsMutational spectrum analysis revealed a lower frequency of UV-induced DNA damage in MM than in CM (p = 0.001), while tobacco exposure was indicated as a potential etiologic factor for MM. In accordance with low UV damage signatures, MM demonstrated an overall lower number of mutations compared to CM (6.5 mutations/Mb vs 14.8 mutations/Mb, p = 0.001), and less PD-L1 expression (p = 0.003). Compared to CM, which showed frequent mutations in known driver genes (BRAF 50.0%, NRAS 29.2%), MM displayed lower mutation frequencies (BRAF; 12.2%, p < 0.001, NRAS; 17.1%), and was significantly more enriched for triple wild-type (no mutations in BRAF, RAS, or NF1, 70.7% vs 25.0%, p < 0.001), IGF2R mutation (31.7% vs 6.3%, p = 0.002), and KIT mutation (9.8% vs 0%, p = 0.042). Of clinical relevance, presence of DCC mutations was significantly associated with poorer overall survival in MM (log-rank test, p = 0.02). Furthermore, mutational spectrum analysis distinguished primary anorectal MM from CM metastasized to the bowel (spectrum analysis p < 0.001, number of mutations p = 0.002).ConclusionsThese findings demonstrated a potential etiologic factor and driver mutation for MM and strongly suggested that MM initiation or progression involves distinct molecular-mechanisms from CM. This study also identified mutational signatures that are clinically relevant for MM treatment.

Clinical characteristic and prognostic analyses of 117 cases of head and neck mucosal melanoma

Objective: To study the clinical characteristics of mucosal melanoma in the head and neck, including the risk factors affecting distant metastasis, recurrence and survival rate, and to provide the basis for the individualized treatment of mucosal melanoma in the head and neck. Methods: The clinical data of 117 cases of mucosal melanoma in the head and neck treated from January 2004 to June 2016 in Beijing Tongren Hospital were analyzed retrospectively, and the risk factors affecting the prognosis, distant metastasis and local recurrence were analyzed.Kaplan-Meier analysis was used for survival analysis, and Log-Rank test was used for comparison between groups. Results: The follow-up time was 5-139 months, with a median of 32 months, and the median survival time was 34 months.The 3 and 5 year cumulative survival rates were 47.0% and 25.0%, respectively.Local recurrence occurred in 27 patients (23.1%), and distant metastasis in 37 cases (31.6%). After the operation, 50 patients received radiotherapy.Multiple factor Cox regression analysis showed that distant metastasis, AJCC staging, and two operations were risk factors affecting survival (P<0.05), and immunologic/targeted therapy was a protective factor affecting survival prognosis(P=0.008). Postoperative radiotherapy and distant metastasis were important factors affecting recurrence (P<0.05). AJCC staging, pigmentation, and postoperative recurrence were risk factors for distant metastasis (P<0.05). Conclusion: The 3 and 5 year survival rates of primary mucosal melanoma in head and neck are low, and the incidence of local recurrence and distant metastasis are high. Surgery is the first choice and the integrity of the initial operation has an important impact on the prognosis of the patients. Postoperative adjuvant radiotherapy is recommended to improve the local control rate, and immunotherapy and targeted therapy should be applied in time to improve survival.