Primary Malignant Melanoma Of The Esophagus Research Articles

Comparative Epigenetic Profiling Reveals Distinct Features of Mucosal Melanomas Associated with Immune Cell Infiltration and Their Clinical Implications.

Mucosal melanoma exhibits limited responsiveness to anti-PD-1 therapy. However, a subgroup of mucosal melanomas, particularly those situated at specific anatomical sites like primary malignant melanoma of the esophagus (PMME), display remarkable sensitivity to anti-PD-1 treatment. The underlying mechanisms driving this superior response and the DNA methylation patterns in mucosal melanoma have not been thoroughly investigated. We collected tumor samples from 50 mucosal melanoma patients, including 31 PMME and 19 non-esophageal mucosal melanoma (NEMM). Targeted bisulfite sequencing was conducted to characterize the DNA methylation landscape of mucosal melanoma and explore the epigenetic profiling differences between PMME and NEMM. Bulk RNA sequencing and multiplex immunofluorescence staining were performed to confirm the impact of methylation on gene expression and immune microenvironment. Our analysis revealed distinct epigenetic signatures that distinguish mucosal melanomas of different origins. Notably, PMME exhibited distinct epigenetic profiling characterized by a global hypermethylation alteration compared to NEMM. The prognostic model based on the methylation scores of a 7-DMR panel could effectively predict the overall survival of PMME patients and potentially serve as a prognostic factor. PMME displayed a substantial enrichment of immune-activating cells in contrast to NEMM. Furthermore, we observed hypermethylation of the TERT promoter in PMME, which correlated with heightened CD8+ T cell infiltration, and patients with hypermethylated TERT were likely to have improved responses to immunotherapy. Our results indicated that PMME shows a distinct methylation landscape compared with NEMM, and the epigenetic status of TERT might be used to estimate prognosis and direct anti-PD-1 treatment for mucosal melanoma.

Endoscopic semiotics and pathological characteristics of primary malignant esophageal melanoma: a case report

Primary malignant melanoma of the esophagus is defined as a tumor, the frequency of which is 0.1-0.2% of all malignant lesions of the esophagus. This type of neoplasia is difficult to diagnose and is characterized by rapid progression, high recurrence rate and metastasis. Despite the diagnostic capabilities of X-ray examination methods, which make it possible to identify a tumor and determine its localization, the correct diagnosis can only be established by endoscopic examination of the upper digestive tract with biopsy and subsequent pathological and immunohistochemical studies. A 78 year-old male patient was admitted to the Herzen Moscow State Medical Institute with suspected esophageal cancer. It is known from the anamnesis, that the patient for 6 months notes a dysphagia, pain in the chest area. Based on the data of our expert endoscopic examination, we suspected primary esophageal melanoma with a mixed growth - exophytic and flat-type. According to the results of pathological examination of the biopsies, pigment epithelial-cell melanoma of the esophagus with high mitotic index (up to 3 mitosis figures per 1 sq.mm) with infiltrative growth type. This clinical case demonstrates the importance of a detailed endoscopic examination and performing a targeted biopsy, followed by expert pathological examination in the differential diagnosis of esophageal diseases characterized by pigmentation of mucosa.

A Case of Superficial Primary Malignant Melanoma of the Esophagus Detected and Treated at Stage 0.

The patient was a 79-year-old male. At three years and eight months after his initial presentation, upper gastrointestinal endoscopy revealed a black-flattened elevated lesion in the middle third of the esophagus, which was diagnosed as malignant melanoma on biopsy. No lymph node or distant metastasis was found. A diagnosis of cT1bN0M0 Stage I was thus made. We performed a robot-assisted, minimally invasive esophagectomy and D2 dissection. The postoperative diagnosis was pT1a (MM), N0, M0, vascular invasion+, stage 0. The patient was recurrence-free for 14 months after surgery. We presume that an aggressive biopsy diagnosis is important for the early detection of malignant melanoma.

Comprehensive molecular findings in primary malignant melanoma of the esophagus: A multicenter study.

Primary malignant melanoma of the esophagus (PMME) is an extremely rare but highly aggressive malignancy with a poor prognosis. Due to the scarcity of driver gene alterations, there is a need for more clinical data to comprehensively depict its molecular alterations. This study reviewed 26 PMME cases from three medical centers. Hybrid capture-based targeted sequencing of 295 and 1021 genes was performed in 14 and 12 cases, respectively. We found that PMME patients had a relatively low tumor mutation burden (median, 2.88 mutations per Mb) and were simultaneously accompanied by mutations in genes such as KIT (6/26, 23%), TP53 (6/26, 23%), SF3B1 (4/26, 15%), and NRAS (3/26, 12%). KIT, NRAS, and BRAF were mutually exclusive, and SF3B1 co-occurred with KIT mutation and amplification. The most common pathways affected were the mitogen-activated protein kinases and DNA damage response (DDR) pathways. Stage IV was a risk factor for both progression-free survival (hazard ratio [HR] = 5.14, 95% confidence interval [CI] = 1.32-19.91) and overall survival (OS), HR = 4.33, 95% CI = 1.22-15.30). Treatment with immune-checkpoint inhibitors (ICIs) was an independent factor for favorable OS (HR = 0.10, 95% CI = 0.01-0.91). Overall, PMME is a complex malignancy with diverse gene alterations, especially with harboring DDR alterations for potentially response from ICIs.

Molecular underpinnings of exceptional response in primary malignant melanoma of the esophagus to anti-PD-1 monotherapy

BackgroundAccumulating data suggest that mucosal melanoma, well known for its poor response to immune checkpoint blockade (ICB) and abysmal prognosis, is a heterogeneous subtype of melanoma with distinct genomic and...

A CT-Based Radiomics Nomogram Model for Differentiating Primary Malignant Melanoma of the Esophagus from Esophageal Squamous Cell Carcinoma.

The diagnosis of primary malignant melanoma of the esophagus (PMME) before treatment is essential for clinical decision-making. However, PMME may be misdiagnosed as esophageal squamous cell carcinoma (ESCC) sometimes. This research is aimed at devising a radiomics nomogram model of CT for distinguishing PMME from ESCC. In this retrospective analysis, 122 individuals with proven pathologically PMME (n = 28) and ESCC (n = 94) were registered from our hospital. PyRadiomics was applied to derive radiomics features from plain and enhanced CT images after resampling image into an isotropic resolution of 0.625 × 0.625 × 0.625 mm3. The diagnostic efficiency of the model was evaluated by an independent validation group. For the purpose of differentiation between PMME and ESCC, a radiomics model was constructed using 5 radiomics features obtained from nonenhanced CT and 4 radiomics features derived from enhanced CT. A radiomics model including multiple radiomics features showed excellent discrimination efficiency with AUCs of 0.975 and 0.906 in the primary and validation cohorts, respectively. Then, a radiomics nomogram model was developed. The decision curve analysis has shown remarkable performance of this nomogram model for distinguishing PMME from ESCC. The proposed radiomics nomogram model based on CT could be used for distinguishing PMME from ESCC. Moreover, this model also contributed to helping clinicians determine an appropriate treatment strategy for esophageal neoplasms.

A case of long-term survival treated with three metastasectomies and two subsequent adjuvant nivolumab therapies for recurrent malignant melanoma of the esophagus

BackgroundThe treatment strategy for metastatic lesions of primary malignant melanoma of the esophagus (PMME) is currently determined on a case-by-case basis, based on the National Comprehensive Cancer Network (NCCN) guidelines for cutaneous melanoma. The NCCN guidelines state that resection should be considered in patients with resectable metastatic recurrence. Herein, we report a case of long-term survival treated with three metastasectomies and two subsequent adjuvant nivolumab therapies for the metastatic recurrence of PMME.Case presentationA 65-year-old female patient with PMME underwent thoracoscopic subtotal esophagectomy, gastric tube reconstruction via the posterior mediastinal route, and cervical esophagogastric anastomosis. Histopathological examination of the resected specimen revealed that the tumor was PMME with tumor invasion into the muscularis propria and no lymph node metastasis. At the age of 68 years, she developed intestinal invagination due to jejunal metastasis of malignant melanoma and underwent resection of the jejunum. Histopathological examination of the resected specimen revealed two metastases of malignant melanoma in the jejunum and one metastasis to the mesenteric lymph node. At the age of 75 years, a recurrence of malignant melanoma was found in the cervical esophagus. She underwent thoracoscopic mobilization of the gastric tube and esophagus followed by cervical esophagectomy and reconstruction with a free jejunum flap. She received 24 courses of nivolumab therapy for 1 year as a postoperative adjuvant therapy. Subsequently, at the age of 78 years, an enlarged left cervical lymph node and a mass in the right lower lobe of the lung were found. She underwent left cervical lymph node dissection and thoracoscopic wedge resection of the right lung. Histopathological examination of the resected specimens revealed that both tumors were metastases of malignant melanoma. At age 79 years, she received eight courses of nivolumab therapy as a second postoperative adjuvant therapy, with no sign of recurrence in a 9-month follow-up period after the third metastasectomy.ConclusionIn cases of metastatic recurrence of PMME, aggressive resection of oligometastasis with postoperative adjuvant nivolumab therapy may result in long-term survival.

Comprehensive genomic analysis of primary malignant melanoma of the esophagus reveals similar genetic patterns compared with epithelium-associated melanomas

AbstractPrimary malignant melanoma of the esophagus (PMME) is an exceedingly rare disease with a poor prognosis. The etiology of PMME remains largely unknown and genetic characteristics are yet to be clarified, essential for identifying potential therapeutic targets and defining treatment guidelines. Here, we performed whole-exome sequencing on 47 formalin-fixed paraffin-embedded specimens from 18 patients with PMME, including 23 tumor samples, 6 metastatic lymph nodes, and 18 tumor-adjacent normal tissues. The genomic features of PMME were comprehensively characterized, and comparative genomic analysis was further performed between these specimens and 398 skin cutaneous melanomas (SKCM), 67 non-esophagus mucosal melanomas (NEMM), and 79 uveal melanomas (UVM). In the PMME cohort, recurrently mutated driver genes, such as MUC16, RANBP2, NRAS, TP53, PTPRT, NF1, MUC4, KMT2C, and BRAF, were identified. All RANBP2 mutations were putatively deleterious, and most affected samples had multipoint mutations. Furthermore, RANBP2 showed parallel evolution by multiregional analysis. Whole-genome doubling was an early truncal event that occurred before most driver mutations, except for in TP53. An ultraviolet radiation-related mutational signature, SBS38, was identified as specific to epithelial melanomas and could predict inferior survival outcomes in both PMME and SKCM patients. Comparing the mutational and copy number landscapes between PMME and other subtypes of melanoma revealed that PMME has a similar genomic pattern and biological characteristics to SKCM. In summary, we comprehensively defined the key genomic aberrations and mutational processes driving PMME and suggested for the first time that PMME may share similar genomic patterns with SKCM; therefore, patients with rare melanomas, such as PMME, may benefit from the current treatment used for common cutaneous melanoma.

Clinicopathological characterization of ten patients with primary malignant melanoma of the esophagus and literature review.

BACKGROUNDPrimary malignant melanoma of the esophagus (PMME) is a rare malignant disease and has not been well characterized in terms of clinicopathology and survival.AIMTo investigate the clinical features and survival factors in Chinese patients with PMME.METHODSThe clinicopathological findings of ten cases with PMME treated at Henan Provincial People’s Hospital were summarized. Moreover, the English- and Chinese-language literature that focused on Chinese patients with PMME from 1980 to September 2021 was reviewed and analyzed. Univariate and multivariate analyses were employed to investigate the clinicopathologic factors that might be associated with survival.RESULTSA total of 290 Chinese patients with PMME, including ten from our hospital and 280 from the literature were enrolled in the present study. Only about half of the patients (55.8%) were accurately diagnosed before surgery. Additionally, 91.1% of the patients received esophagectomy, and 88 patients (36.5%) received adjuvant therapy after surgery. The frequency of lymph node metastasis (LNM) was 51.2% (107/209), and LNM had a positive rate of 45.3% even when the tumor was confined to the submucosal layer. The risk of LNM increased significantly with the pT stage [P < 0.001, odds ratio (OR): 2.47, 95% confidence interval (CI): 1.72-3.56] and larger tumor size (P = 0.006, OR: 1.21, 95%CI: 1.05-1.38). The median overall survival (OS) was 11.0 mo (range: 1-204 mo). The multivariate Cox analysis showed both the pT stage [P = 0.005, hazard ratio (HR): 1.70, 95%CI: 1.17-2.47] and LNM (P = 0.009, HR: 1.78, 95%CI: 1.15-2.74) were independent prognostic factors for OS. The median disease-free survival (DFS) was 5.3 mo (range: 0.8-114.1 mo). The multivariate analysis indicated that only the advanced pT stage (P = 0.02, HR: 1.93, 95%CI: 1.09-3.42) was a significant independent indicator of poor RFS in patients with PMME.CONCLUSIONThe correct diagnosis of PMME before surgery is low, and physicians should pay more attention to avoid a misdiagnosis or missed diagnosis. Extended lymph node dissection should be emphasized in surgery for PMME even though the tumor is confined to the submucosal layer. Both the LNM and pT stage are independent prognosis factors for OS, and the pT stage is the prognosis factor for DFS in patients with PMME.

Primary malignant melanoma of the esophagus successfully treated with camrelizumab: A case report and literature review*

Abstract An 83-year-old Chinese woman presented with a 3-month history of dysphagia. She also had a history of hypertension, type 2 diabetes, fundus hemorrhage, and cataract but no history of cutaneous, ocular, or other-site melanomas. Upper gastrointestinal tract angiography revealed gastritis and duodenal diverticulum; thus, an endoscopic review was recommended. Enhanced computed tomography of the chest and upper abdomen revealed the following: (1) Esophageal space-occupying lesions and mediastinal lymph node enlargement (considering the high possibility of esophageal cancer, further endoscopy was recommended) and (2) A small amount of right pleural effusion, with no significant lymph node infiltration or distant metastasis. Esophagoscopy identified a bulge mass blocking the esophagus from 23 to 30 cm from the incisors. The upper mass had a spherical clustering, while the lower mass significantly festered. Pathological biopsy samples were obtained from the esophagus 23 and 28 cm from the incisors. Tissue biopsy showed proliferation of large round tumor cells and melanocytes. Immunohistochemistry showed positive findings for HMB45 and MelanA; partially positive findings for S100, CK7, CK5/6, CAM5.2, LCA, P63, and TTF-1; and negative findings for Syn. The Ki-67 positivity index was approximately 60%. Based on these findings, the patient was diagnosed with malignant esophageal melanoma with enlarged mediastinal lymph nodes. She was then treated with five cycles of camrelizumab therapy combined with chemotherapy from October 18, 2019, to May 5, 2020. Gastroscopy review following two courses of combination therapy revealed that the esophagus was 23-25 cm away from the incisors, and there were two continuous uplifted and beaded masses that had a smooth and black surface, with each of them having a length and diameter of approximately 1 cm. Melanosis of the mucosa around the lumen was observed at 40 cm from the incisors to the cardia; the dentate margin was clear; and the cardia had no stenosis. The patient then received five courses of combination therapy and became consistently stable after partial remission. No severe adverse events related to the immunotherapy were recorded. Camrelizumab may be a viable treatment option for patients with PMME. Additional evidence from future clinical trials and research is necessary to fully validate our findings.

The Thousand Faces of Malignant Melanoma: A Systematic Review of the Primary Malignant Melanoma of the Esophagus.

Simple SummaryPrimary malignant melanoma of the esophagus (PMME) represents a fairly described and represented entity in the literature, although only in the middle of the last century was it recognized as actually existing. In this systematic review we address the history of PMME starting from 1906, the year in which Bauer made the first description of this entity, passing through his first demonstration on an autopsy series by De Pava et al. and we come to the most recent notions of molecular biology and immunotherapy.Primary Malignant Melanoma of the Esophagus (PMME) is an extremely rare cancer of the esophagus, accounting for 0.1–0.8% of all oro-esophageal cancers and <0.05% of all melanoma subtypes, with an estimated incidence of 0.0036 cases per million/year. We conduct a careful analysis of the literature starting from 1906 to the beginning of 2022, searching the PubMed, Science.gov, Scopus and Web of Science (WoS) databases. A total of 457 records were initially identified in the literature search, of which 17 were duplicates. After screening for eligibility and inclusion criteria, 303 publications were ultimately included, related to 347 patients with PMME. PMME represents a very rare entity whose very existence has been the subject of debate for a long time. Over time, an increasing number of cases have been reported in the literature, leading to an increase in knowledge and laying the foundations for a discussion on the treatment of this pathology, which still remains largely represented by surgery. In recent times, the possibility of discovering greater mutations in gene hotspots has made it possible to develop new therapeutic strategies of which nivolumab is an example. Future studies with large case series, with clinicopathological and molecular data, will be necessary to improve the outcome of patients with PMME.

Clinicopathological Features, Staging Classification, and Clinical Outcomes of Esophageal Melanoma: Evaluation of a Pooled Case Series.

Studies that have attempted to validate the staging systems and the predictors of survival for patients with primary malignant melanoma of the esophagus (PMME) have been underpowered given their scarcity and small scale. We aimed to review a large number of PMME cases to know more about its clinicopathological features, TNM staging systems, and survival predictors of PMME. Case reports on PMME were extracted from PubMed/Medline through bibliography search and our center. A total of 287 PMME cases were identified. The majority of the patient population was male (72.08%). The most common location of PMME was the lower esophagus (50.62%) and middle esophagus (35.39%). Among the patients, 82.28% received surgical intervention. The median overall survival (OS) duration was 15 months (0.5–244). The American Joint Commission on Cancer staging classification (AJCC) for the mucosal melanoma of the upper aerodigestive tract with stage IVB and IVC integrated in stage IVA showed better distribution of OS than that for esophageal carcinoma. T stage, N stage, and surgery had significant impacts on OS duration in univariate analysis. However, only T stage and N stage were identified as independent factors for OS duration in the multivariate Cox models. PMME is an aggressive tumor with poor prognosis. The AJCC staging system for mucosal melanoma with stage IVB and IVC integrated in stage IVA may be a better option for staging PMME patients. T stage and N stage are independent factors for OS.

Primary malignant melanoma of the esophagus: differentiation from esophageal squamous cell carcinoma and leiomyoma using dynamic contrast-enhanced CT findings

PurposeThis study aimed to summarize the computed tomography (CT) findings of PMME and differentiate it from esophageal SCC and leiomyoma using CT analysis.MethodsThis was a retrospective study including 23 patients with PMME, 69 patients with SCC, and 21 patients with leiomyoma in our hospital. Qualitative CT morphological characteristics of each lesion included the location, tumor range, ulcer, enhanced pattern, and so on. For quantitative CT analysis, thickness, length and area of tumor, size of largest lymph node, number of metastatic lymph node, and CT value of tumor in plain, arterial, and delayed phases were measured. The associated factors for differentiating PMME from SCC and leiomyoma were examined with univariate and multivariate analysis. Receive operating characteristic curve (ROC) was used to determine the performance of CT models in discriminating PMME from SCC and leiomyoma.ResultsThe thickness, mean CT value in arterial phase, and range of tumor were the independent factors for diagnosing PMME from SCC. These parameters were used to establish a diagnostic CT model with area under the ROC (AUC) of 0.969, and accuracy of 90.2%. In pathology, interstitial vessels in PMME were more abundant than that of SCC, and the stromal fibrosis was more obvious in SCC. PMME commonly exhibited intraluminal expansively growth pattern and SCC often showed infiltrative pattern. The postcontrast attenuation difference in maximum CT attenuation value between plain and arterial phases was the independent factor for diagnosing PMME from leiomyoma. This parameter was applied to differentiate PMME from leiomyoma with AUC of 0.929 and accuracy of 86.4%.ConclusionThe qualitative and quantitative CT analysis had excellent performance for differentiating PMME from SCC and esophageal leiomyoma.Graphical abstract

Longitudinal genomic alternations and clonal dynamics analysis of primary malignant melanoma of the esophagus

Primary malignant melanoma of the esophagus (PMME) is a rare gastrointestinal melanoma with a high rate of recurrence and metastasis. The standard of care for PMME has not been established yet due to a lack of understanding of its clinical and molecular pathogenesis. Thus, we performed genomic profiling on a recurrent PMME case to seek novel opportunities for the management of this rare disease. Between 2013 and 2016, 6 tissue samples including 3 from the primary tumors, 2 from the relapsed tumors, and 1 from a normal control were collected from a patient diagnosed with PMME and were subjected to whole-exome sequencing to track the dynamic genetic changes. Additionally, we also analyzed a cohort of 398 samples obtained from the TCGA skin cutanesous melanoma (TCGA-SKCM) dataset to assess the frequency and determine the clinical implications of genomic events found in the presented study. ARHGAP35 (p.L1022M) was the only mutation shared across temporal PMME lesions. The PMME samples showed higher levels of genetic instability and intra-tumor heterogeneity. They also shared several concordant copy number variations (CNV). All lesions were concordant with the evolution trajectory, and shrinkage of the founding clone caused the subclonal population to become dominant in PT1c, which was likely the reason behind metastatic seeding. ARHGAP35 mutations were found in 6% of the TCGA-SKCM cohort samples. The presence of the mutations was associated with poor progression-free survival (PFS) by both univariate and multivariate Cox regression analyses. Our study showed that the primary tumor clone disseminates earlier in PMME. This highlights the need to understand the mechanism involved in the early PMME recurrence to optimize treatment.

Primary Malignant Melanoma of the Esophagus: A Case Report

Primary Malignant Melanoma of the Esophagus (PMME) is an aggressive tumor with a median survival of about 13 months. Surgical extirpation is the only treatment for PMME. The most common clinical presentation is the onset of progressive dysphagia. Endoscopy presents a polypoid lesion occasionally in the middle and lower third of the esophagus. Definitive diagnoses are based on pathology and immunohistochemical examination with positive results for S-100, Human Melanoma Black (HMB)-45, and Melanoma-specific Antigen (Melan-A) proteins. We presented a 46-year-old man complaining of dysphagia and melena from the past two months. Gasteroesophagoscopy demonstrated a large polypoid in the lower third of the esophagus extending to the cardia. Histopathology of the biopsy specimen from the esophagus revealed positive staining for S-100, Human Melanoma Black (HMB)-45, and Melanoma-specific Antigen (Melan A) proteins that were all compatible with malignant melanoma of the esophagus. The patient underwent surgery followed by radiotherapy and Immunotherapy. The postoperative period was uneventful. No metastasis and recurrence was observed after more than 6 months of initial treatment. PMME is a rare but highly aggressive tumor. The diagnosis of PMME should be made by clinical symptoms, auxiliary examination, pathological examination, and immunohistochemistry markers. The problem of exact diagnosis at the early stages of the disease and effective treatment is still a challenge.

A Case of Primary Malignant Melanoma of the Esophagus with Essential Thrombocythemia

症例は74歳の男性で，食事のつかえ感と体重減少を主訴に近医を受診．上部消化管内視鏡にて食道胸部中部から胸部下部の腫瘤を指摘，精査加療目的で当院へ紹介．術前の画像では，不整潰瘍を有する9cmの腫瘍性病変の診断であったが，生検では悪性所見は認めなかった．また，以前より血小板増多を指摘されており，当院初診時の血小板が高値であった．骨髄生検の所見，血液遺伝子検査の結果，骨髄増殖性腫瘍の一病型である本態性血小板血症の診断となった．食道の腫瘍性病変の術前診断でcytoreductive therapyを開始し，血小板数をコントロールの上，安全に胸腔鏡下食道亜全摘術が可能であった．血栓症や出血などの合併症なく，経過は順調で退院となった．

A Case of Postoperative Recurrence of Primary Malignant Melanoma of the Esophagus in the Liver with Complete Response with Nivolumab Therapy

A Case of Postoperative Recurrence of Primary Malignant Melanoma of the Esophagus in the Liver with Complete Response with Nivolumab Therapy

Complete remission in metastatic primary malignant melanoma of the esophagus with nivolumab: a case report

BackgroundPrimary malignant melanoma of the esophagus is a rare form of mucosal melanoma with a poor prognosis. While immune checkpoint inhibitors have recently extended overall survival in metastatic melanoma, data on their effects on primary malignant melanoma of the esophagus are limited because of its rarity. Here, we report the first case of long-term complete remission of metastatic primary malignant melanoma of the esophagus after nivolumab monotherapy.Case presentationA 79-year-old Asian man with a history of prostate cancer, gallbladder cancer, deep vein thrombosis, hypertension, and diabetes mellitus presented with gross hematuria. Cystoscopy revealed a solitary tumor on the right posterior wall of the bladder, and transurethral resection of bladder tumor was performed. Pathology was consistent with metastatic melanoma. A pigmented submucosal tumor-like growth in the esophagus was discovered on esophagogastroduodenoscopy. Computed tomography showed widespread metastases. The patient was diagnosed as having primary malignant melanoma of the esophagus with metastases to the stomach, subcutaneous tissue, lung, bladder, pleura, and peritoneum. Complete remission was achieved after seven cycles of triweekly nivolumab monotherapy. While nivolumab was discontinued because of kidney injury, the patient has remained tumor-free for over 4 years without further treatment.ConclusionImmune checkpoint inhibitors may have astonishing curative effects in selected populations. More research is warranted to identify factors that increase the likelihood of achieving complete remission in primary malignant melanoma of the esophagus as well as in other melanomas.

Bone Lysis Revealing Primary Malignant Melanoma of the Esophagus: Case Report and Review of the Literature

Primary malignant melanoma of the esophagus is a rare, very aggressive entity with a bad prognosis. It is metastatic in 40 to 80% of cases at diagnosis. The symptoms are non-specific and the diagnosis is confirmed by histology. The treatment of choice is surgery in the early forms. We report the case of a metastatic primary melanoma of the esophagus discovered by retro sternal pain.

Primary Malignant Melanoma of the Esophagus: Prognosis and Therapeutic Challenges

Primary malignant melanoma of the esophagus (PMME) is a very rare and highly aggressive tumor, representing <1% of esophageal malignancies. We are reporting a case of PMME in a 54-year-old White, Non-Hispanic male, who presented to the hospital with dysphagia and weight loss. Computed tomography (CT) of the chest revealed a large mid-to-distal esophageal mass with mass effect on adjacent structures, with no evidence of invasion. The patient subsequently underwent esophagogastroduodenoscopy (EGD) with guided biopsy of the esophageal mass. Histopathology and immunohistochemistry of the biopsied specimen were performed and consistent with malignant melanoma. Tumor staging by positron emission tomography and computed tomography (PET/CT) scans revealed extensive, locally advanced disease with lymph node involvement. Subsequently, esophageal ultrasound (EUS) with biopsy of the involved lymph node was performed and was positive for malignant melanoma. The mass was deemed unresectable due to the extensive degree of locally advanced disease. To assist in our therapeutic decision making, the patient was screened for the presence of a BRAF V600 mutation. He was then started on a combination of the BRAF inhibitor (dabrafenib) in combination with the mitogen-activated extracellular kinase (MEK) Inhibitor (trametinib) given the presence of a BRAF V600 mutation.