• BRAF mutation
• Immunotherapy
• Mucosal melanoma
• Targeted therapy
• cKIT mutation

• Humans
• Melanoma/diagnosis
• Melanoma/epidemiology
• Melanoma/genetics
• Skin Neoplasms/therapy
• Prognosis
• Mutation
• Proto-Oncogene Proteins B-raf/genetics

• Università degli Studi di Bari Aldo Moro

• Adjuvant treatment
• Esophageal melanoma
• Nivolumab

• Incidence
• Primary gastrointestinal melanoma
• Prognostic factor
• Survival
• Trend

• Humans
• Aged
• Incidence
• SEER Program
• Gastrointestinal Neoplasms/epidemiology
• Prognosis
• Melanoma/epidemiology

Primary malignant melanoma of the esophagus (PMME) is a rare malignant disease and has not been well characterized in terms of clinicopathology and survival.

To investigate the clinical features and survival factors in Chinese patients with PMME.

The 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.

A 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.

The 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
• Clinicopathological characteristics
• Treatment
• Recurrence
• Survival

According to European consensus-based interdisciplinary guidelines for melanoma, cutaneous melanoma (CM) is the most deadly form of dermatological malignancy, accounting for 90% of the deaths of skin cancer patients. In addition to cutaneous melanoma, mucosal melanoma occurs in four major anatomical sites, including the upper respiratory tract, the conjunctiva, the anorectal region, and the urogenital area. As this cancer type metastasizes, a classification used in the current medical literature is the distinction between secondary lesions and primary malignant melanoma of the abdominal cavity. Given that malignant melanoma is the most common cancer that spreads to the gastrointestinal tract, different imaging modalities compete to diagnose the phenomenon correctly and to measure its extension. Treatment is primarily surgery-based, supported by immunotherapy, and prolongs survival, even when performed at stage IV illness. In the end, special forms of malignant melanoma are discussed, such as melanoma of the genito-urinary tract and amelanotic/achromic melanoma. The importance of this present literature review relies on yielding and grouping consistent and relevant, updated information on the many aspects and challenges that a clinician might encounter during the diagnosis and treatment of a patient with intra-abdominal melanoma.

• esophagus
• genetics
• malignant melanoma
• mucosal melanoma
• neoplasia
• primary
• skin

Primary 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.

A 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.

Immune 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.

• Bladder tumor
• Case report
• Immune checkpoint inhibitor
• Nivolumab
• Primary malignant melanoma of the esophagus

Primary malignant melanoma of the esophagus is a rare and aggressive disease that tends to have a poor response to chemotherapies. Previous studies have indicated that currently available treatment for primary malignant melanoma of the esophagus is insufficient. Here, we describe a case of recurrent primary malignant melanoma of the esophagus successfully treated with the immune checkpoint inhibitor nivolumab.

An 81-year-old Japanese female presented with a 3-month history of dysphagia. She was medicated for hypertension and sarcoidosis. The patient had no past history of cutaneous, ocular, or other-site melanomas. An esophagoscopy identified a 30-mm giant tumor in the lower esophagus, at a site 30 cm from the incisors. Enhanced computed tomography revealed wall thickening measuring 30 mm in size at the middle-third of the intrathoracic esophagus, with no significant lymph node infiltration or distant metastasis. Esophageal biopsy showed proliferation of large round tumor cells and melanophages. On the basis of these findings, the patient was diagnosed with esophageal malignant melanoma and underwent esophagectomy and lymph node dissection with gastric tube reconstruction. Although the pathological diagnosis was primary malignant melanoma of the esophagus, the patient presented with multiple lymph node and bone metastases 4 months after surgery. Subsequently, treatment with nivolumab 240 mg every 2 weeks was administered as the first-line treatment. Diffusion-weighted imaging with background body signal suppression following eight courses of nivolumab revealed that the multiple lymph node and bone metastases were markedly reduced. The patient received 30 courses of nivolumab and has maintained the partial response. No severe adverse events related to the immunotherapy were recorded.

The current study suggests that nivolumab may be a viable option for patients with metastatic primary malignant melanoma of the esophagus. Additional evidence from future clinical trials and research is necessary to fully validate these findings.

• Esophagus
• Malignant melanoma
• Nivolumab

• immunotherapy
• molecular pathogenesis
• next-generation sequencing (NGS)
• primary malignant melanoma of the oesophagus (PMME)
• tumour mutation burden (TMB)

• Aged
• Biomarkers, Tumor
• Esophageal Neoplasms/genetics
• Esophageal Neoplasms/pathology
• Esophagus/pathology
• Female
• High-Throughput Nucleotide Sequencing
• Humans
• Immunohistochemistry
• Male
• Melanoma/genetics
• Melanoma/pathology
• Middle Aged
• Mutation
• Neurofibromin 1/genetics
• Oncogenes/genetics
• Prognosis
• Skin Neoplasms/genetics
• Skin Neoplasms/pathology
• Melanoma, Cutaneous Malignant

• #17K08704 General Scientific Research from the Ministry of Education, Science, Sports, and Culture
• #17K08730 General Scientific Research from the Ministry of Education, Science, Sports, and Culture
• JP17am0001009. the Japan Agency for Medical Research and Development
• JP18cm0106502 the Project for Cancer Research And Therapeutic Evolution (P-CREATE)
• JP18kk0205003 the Program for Integrated Database of Clinical and Genomic Information
• JP18ck0106252 the Practical Research for Innovative Cancer Control

• Birmingham approach
• Gastroesophageal junction
• Primary malignant melanoma

• Aged
• Esophageal Neoplasms/pathology
• Esophagus/pathology
• Humans
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Male
• Melanoma/pathology

Primary malignant melanoma of the esophagus accounts for 0.1%-0.2% of all esophageal malignancies, including melanotic and amelanotic melanomas. Primary amelanotic malignant melanoma of the esophagus is extremely rare, and only about 20 cases have been published in the literature to date. Most primary malignant melanomas of the esophagus are diagnosed following development of metastatic lesions and thus have a very poor prognosis. The median survival duration of patients with metastatic melanoma has been reported to be 6.2 mo.

A 49-year-old woman was referred to our hospital with a diagnosis of esophageal cancer. Endoscopy, biopsy, imaging evaluation, and physical examination at our hospital indicated a diagnosis of advanced primary amelanotic malignant melanoma of the esophagus. Immunohistochemical staining confirmed melanoma. Nuclear medicine examination revealed a left iliac bone metastatic lesion. After discharge, the patient self-administered apatinib for 3 mo, followed by oral treatment with Chinese medicines (also self-administered) for 2 mo. No treatments had been taken since then. The patient has survived with no growth out to the most recent follow-up (24 mo post diagnosis), and she always presented with a positive attitude about her condition during this period.

Survival following metastatic melanoma might be related to the pharmaceutical and Chinese medicine treatment and the patient's positive attitude.

• Esophagus
• Amelanotic malignant melanoma
• Immune
• Emotion
• Psychological intervention
• Case report

• Combined modality therapy
• esophageal neoplasms
• esophagectomy
• melanoma
• prognosis
• recurrence

• Adult
• Aged, 80 and over
• Disease Progression
• Esophageal Neoplasms/mortality
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/surgery
• Esophagectomy/adverse effects
• Esophagectomy/mortality
• Female
• Humans
• Lymph Node Excision
• Male
• Melanoma/mortality
• Melanoma/secondary
• Melanoma/surgery
• Middle Aged
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Retreatment
• Retrospective Studies
• Time Factors
• Treatment Outcome

Primary malignant melanoma of the esophagus (PMME) has been reported to be a rare and highly malignant disease, and to date a standard treatment strategy has not been established due to limited evidence. The aim of the present study was to investigate the clinicopathological characteristics of this extremely rare disease. A total of 6 out of 2,093 patients with PMME treated in our institution between 1995 and 2016 were retrospectively analyzed and their clinicopathological parameters including treatment course and long-term survival were investigated. The major clinicopathological characteristics of patients were that they were >70 years of age, male sex, dysphagia at first diagnosis, and macroscopic black protruding tumors located in the lower third of the thoracic esophagus. Four of the five patients receiving pretherapeutic endoscopic biopsy were correctly diagnosed with PMME, and two patients received preoperative treatment with ineffective histopathological responses. There were two unresectable cases, one was treated with an immune-checkpoint inhibitor and the other received palliative care. Three of the four patients receiving curative surgery developed hematogenous recurrence within two years of surgery and only one patient with pT1aN0M0 achieved long-term survival. The median overall survival of all six patients was 19.6 (6.4–40.5) months. Patients with stage I disease exhibited significantly more favorable prognoses than those with stage II–IV (P=0.025) and surgically-treated patients had significantly better prognoses than those who did not receive surgery (P=0.018). In conclusion, PMME was associated with highly malignant features and tended to develop hematogenous metastases even after radical resection. Early diagnosis appears to be important to cure this refractory disease.

• esophageal cancer
• immune-checkpoint inhibitor
• primary malignant melanoma of the esophagus
• prognostic factor

Primary malignant melanoma of the esophagus (PMME) is rare. Patients with advanced melanoma of esophageal origin tend to have lower response rates to traditional therapies than those with other melanomas. We report our experience of 12 patients with PMME administered PD‐1 inhibitors.

This is a retrospective analysis of the clinical data of 76 patients with PMME who attended Peking University Cancer Hospital between January 2008 and September 2017. Objective response rates (ORRs) and progression‐free survival (PFS) were assessed.

The 76 PMMEs were classified as unresectable or metastatic. The patients were allocated to three cohorts according to their treatment: chemotherapy (C: 46 patients), targeted therapy (T: 2 patients), and PD‐1 inhibitors (IT: 12 patients). The PFS in the C cohort was three months with a limited ORR of 10.9%. In the IT cohort, seven patients (75.0%) achieved a partial response and three had stable disease for 4+ months. The median PFS in the IT cohort was not reached and the mean was 15.6 months, which was much longer than in cohort C (P < 0.001).

Although this cohort of patients was small, it is the largest series investigated thus far. To the best of our knowledge, this is the first report of the outcomes of advanced PMMEs treated with PD‐1 inhibitors. Dramatic responses can occur in patients with advanced PMMEs.

• Adjuvant therapy
• immunotherapy
• melanoma of esophagus

• gastric mucinous adenocarcinoma
• multiple primary malignant neoplasms
• primary malignant melanoma of the esophagus

• Adenocarcinoma, Mucinous/diagnosis
• Adenocarcinoma, Mucinous/pathology
• Adenocarcinoma, Mucinous/surgery
• Diagnosis, Differential
• Esophageal Neoplasms/diagnosis
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/surgery
• Fatal Outcome
• Humans
• Male
• Melanoma/diagnosis
• Melanoma/pathology
• Melanoma/surgery
• Middle Aged
• Neoplasms, Multiple Primary/diagnosis
• Neoplasms, Multiple Primary/pathology
• Neoplasms, Multiple Primary/surgery
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery

Primary amelanotic malignant melanoma of esophagus, which is a subtype of primary malignant melanoma of the esophagus (PMME), is a very rare disease with a poor prognosis. We herein report a case of the amelanotic type of PMME.

An 86-year-old woman was admitted to our hospital with symptoms of dysphagia. An endoscopic examination and constructed radiography revealed an elevated and semipedunculated lesion with an ulcer in the lower thoracic esophagus accompanied by another submucosal lesion of the esophagus. She was diagnosed with esophageal squamous cell carcinoma by a preoperative endoscopic biopsy. We performed thoracoscopy- and laparoscopy-assisted subtotal esophagectomy with lymphadenectomy. Based on the surgical specimens, although there were no melanocytes, we made a diagnosis of a malignant melanoma immunohistochemically; the tumor cells were positive for S-100 protein and HMB45 focally and partially for Melan-A.

We experienced a case of primary amelanotic malignant melanoma, and the patient has remained disease-free for 1 year since the surgery. Since the diagnosis of amelanotic type of PMME is difficult, it should be made by the combination of a morphological examination, pathological examination, and immunohistochemistry.

• Amelanotic melanoma
• Diagnosis
• Esophagus
• Pathology
• Prognosis

• classification
• esophagus
• melanoma
• surgery
• survival analysis

• PMME
• malignant melanoma
• primary malignant melanoma of the esophagus

• Aged
• Biopsy/methods
• Early Detection of Cancer/methods
• Endoscopy/methods
• Esophageal Neoplasms/diagnosis
• Esophageal Neoplasms/diagnostic imaging
• Esophageal Neoplasms/pathology
• Humans
• Male
• Melanoma/diagnosis
• Melanoma/pathology
• Melanosis/diagnosis
• Melanosis/pathology
• Retrospective Studies
• Skin Neoplasms/diagnosis
• Skin Neoplasms/pathology
• Melanoma, Cutaneous Malignant

• CT
• MRI
• PET
• melanoma

• PMME
• esophageal cancer
• esophagectomy
• primary malignant melanoma of the esophagus
• prognosis

Primary malignant melanoma of the esophagus (PMME) is an extremely rare disease with poor prognosis. We summarized and analyzed the characteristics of 17 PMME patients (with average age of 57.5 ± 10.3 years) who had received surgical resection in our center. The majority (13/17, 76.5%) of the patients were male. The percentage of patients with smoking and alcohol consumption was 41.2% and 23.5%, respectively. The preoperative diagnosis rate was 35.3%. Lymph node metastasis mainly involved the mid-lower mediastinal and upper abdominal area. Primary tumors that invaded beyond the submucosa layer (T2–T4) had much higher tendency of lymph node metastasis than those restricted to the submucosa layer (T1) (6/8, 75.0% vs. 3/9, 33.3%, p = 0.086). The 1-year and 5-year survival rate of the patients was 51% and 10%, respectively, with median survival time being 18.1 months. Survival analysis showed that TNM stage was a predictor for PMME prognosis (median survival time of 47.3 months vs. 8.0 months for stage I/II vs. stage III, respectively, p = 0.018), and multivariable Cox regression analysis revealed the independence of its prognostic value [HR (95% CI): 5.678 (1.125–28.658), p = 0.035].

• Aged
• Biopsy
• Esophageal Neoplasms/diagnosis
• Esophageal Neoplasms/pathology
• Esophagoscopy
• Esophagus/pathology
• Fatal Outcome
• Humans
• Male
• Melanoma/diagnostic imaging
• Melanoma/pathology
• Necrosis
• Tomography, X-Ray Computed

• Endoscopy, Digestive System
• Esophageal Neoplasms/diagnosis
• Esophageal Neoplasms/pathology
• Female
• Histocytochemistry
• Humans
• Immunohistochemistry
• Melanoma/diagnosis
• Melanoma/pathology
• Melanoma-Specific Antigens/analysis
• Microscopy
• Middle Aged
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/pathology
• gp100 Melanoma Antigen

• esophagus
• malignant melanoma
• primary malignant melanoma of the esophagus

Primary upper gastrointestinal tract melanoma is a rare but well recognised entity, with a poor prognosis because of delay in diagnosis. Furthermore, it may be difficult to determine whether a gastrointestinal melanoma represents a metastasis or a primary tumour. We report a 67-year-old man with a primary oesophageal melanoma, treated with surgical resection, who remains disease-free two years post resection.

Primary malignant melanoma of the oesophagus is a rare and aggressive malignancy. This tumour entity accounts for 0.1–0.2% of all oesophageal malignancies and risk factors are yet to be established, although melanosis of the oesophagus may reflect its precursor form. Dysphagia is the commonest symptom. On gastroscopy, it appears as an elevated pigmented mass with satellite lesions in some cases. Unfortunately, most patients present late with metastatic disease. The prognosis is poor with a mean survival time post-operatively of 10–14 months and a 5-year survival rate of 4.5%. Although adjuvant therapy offers some loco-regional control, complete surgical resection offers the best hope for survival.

Metastatic melanoma involving the esophagus is rare; the occurrence of metastatic melanoma in a background of Barrett esophagus is rarer still. We report a case of an 80 year-old male who presented to our institution for workup of Barrett esophagus with high-grade dysplasia and who proved to have metastatic melanoma occurring in the background of Barrett esophagus, the first report of this kind, to our knowledge, in the English literature.

An 80 year-old Caucasian male was diagnosed at an outside institution with Barrett’s esophagus with high grade dysplasia and presented to our institution for therapy. The patient underwent endoscopic mucosal resection using a band ligation technique of an area of nodularity within the Barrett esophagus. Microscopic examination demonstrated extensive Barrett esophagus with high-grade dysplasia as well as a second tumor which was morphologically different from the surrounding high-grade dysplasia and which was positive for S-100, HMB 45 and Melan-A on immunohistochemistry, consistent with melanoma. Further workup of the patient demonstrated multiple radiologic lesions consistent with metastases. Molecular studies demonstrated that the melanoma was positive for the 1799T>A (V600E) mutation in the BRAF gene. The overall features of the tumor were most consistent with metastatic melanoma occurring in a background of Barrett esophagus with high-grade dysplasia.

This case demonstrates a unique intersection between a premalignant condition (Barrett esophagus with high grade dysplasia) and a separate malignancy (melanoma). This report also shows the utility of molecular testing to support the hypothesis of primary versus metastatic disease in melanoma.

Primary malignant melanoma of the esophagus is an uncommon tumor, with approximately 300 cases having been reported thus far. The purpose of this study was to describe a case of a 60 year-old man with a 10 month history of progressive dysphagia and thoracic pain, the investigations of which led to a diagnosis of primary malignant melanoma of the esophagus. The patient underwent a transhiatal esophagectomy with subcarinal lymphadenectomy, and isoperistaltic gastric tube replacement of the esophagus. Nine months after surgery, he developed ischemic colitis, and metastasis in the mesentery was diagnosed. His disease progressed and he died one year after the esophagectomy. A review of the literature was performed.

Primary malignant melanoma of the esophagus (PMME) comprises only 0.1–0.2% of all malignant esophageal tumors. PMME tumors are highly aggressive and metastasize early via hematogenic and lymphatic pathways. Treatment outcome is poor because the cancer has often advanced at the time of diagnosis. Inoperability, unsuccessful treatment with radiotherapy and chemotherapy in advanced tumors and metastases have contributed to its poor prognosis. Here, we present the endoscopic features, endoscopic ultrasonography findings and management of a PMME case.

• Endoscopic features
• Endoscopic ultrasonography
• Esophagus
• Malignant melanoma
• Treatment

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