• diagnosis
• differential diagnosis
• digestive tract
• malignant melanoma
• pathology

• Case report
• Immune checkpoint inhibitors
• Pathologic complete response
• Primary malignant melanoma of the esophagus
• Surgical resection

• Humans
• Ipilimumab/administration & dosage
• Ipilimumab/therapeutic use
• Male
• Nivolumab/therapeutic use
• Nivolumab/administration & dosage
• Melanoma/drug therapy
• Melanoma/pathology
• Melanoma/surgery
• Melanoma/secondary
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/drug therapy
• Esophageal Neoplasms/surgery
• Aged
• Esophagectomy
• Lymphatic Metastasis
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Neoadjuvant Therapy
• Lymph Node Excision
• Pathologic Complete Response

• CT
• Diagnosis and treatment
• Primary malignant melanoma of the esophagus

• Clinical significance
• Genetic alterations
• Mucosal melanoma
• Primary site
• Prognosis

• 2020A1515010313 Natural Science Foundation of Guangdong Province

Primary malignant melanoma of the esophagus (PMME) is a rare malignant disease whose clinical and molecular pathological features, origin and pathogenesis, diagnosis and treatment have not been elucidated.

In this paper, we report a case of a 73-year-old male with PMME. The patient complained of progressive dysphagia accompanied by substantial weight loss. Gastroscopy revealed a purple black bulging-type mass in the lower esophagus with easy bleeding on contact and scattered satellite lesions in the stomach. Histopathological biopsy revealed melanocytes in the esophageal mucosa. Physical examination and multidisciplinary consultation led to diagnostic exclusion of melanoma originating in other organs, such as the skin. Through this case report and literature review, we aimed to describe the clinical and molecular pathological features of PMME and summarize possible pathways of pathogenesis as well as cutting-edge therapeutic advances.

PMME is a rare malignancy of the esophagus with a poor prognosis. Clinicians should raise their awareness and be able to identify early lesions.

• Primary malignant melanoma of the esophagus
• Clinicopathological features
• Diagnosis and treatment
• Pathogenesis
• Prognosis
• Case report

• cancer
• esophagectomy
• esophagus
• malignancy
• melanoma

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

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

•

Primary malignant melanoma of the esophagus (PMME) is a rare disease with a poor prognosis.

Primary malignant melanoma of the esophagus (PMME) is a rare disease with a poor prognosis. Here, we report a case of retroperitoneal recurrence of PMME successfully treated with the anti-programmed cell death 1 antibody, nivolumab.

A 70-year-old male with dysphagia was referred to our hospital. Esophagogastroscopy showed an elevated tumor in the lower thoracic esophagus. A histopathological examination of the biopsy revealed poorly differentiated squamous cell carcinoma. The patient was diagnosed with clinical T3N1M0 stage III esophageal squamous cell carcinoma and was treated with neoadjuvant chemotherapy followed by radical esophagectomy. A postoperative histopathological examination revealed that atypical cells with a brown pigment were scattered in the tumor. Immunohistochemical staining demonstrated positive expression of human melanoma black 45, melan A, and S100. A pathological diagnosis of PMME was confirmed. Sixteen months after surgery, abdominal computed tomography revealed solitary retroperitoneal recurrence in the lateral portion of the ascending colon. Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) showed hypermetabolic accumulation with a maximum standardized uptake value of 5.8. The patient was treated with nivolumab (240 mg) every two weeks. After eight courses of nivolumab, abnormal accumulation of the retroperitoneal mass disappeared on PET, and this therapeutic effect continued for 20 months.

Nivolumab was effective for recurrence of PMME in our case. There are few reports of treatment with nivolumab for PMME. Further studies are necessary to establish the usefulness of nivolumab for PMME in the future.

• Anti-PD-1 antibody
• Esophagus
• Malignant melanoma
• Nivolumab
• Retroperitoneal recurrence

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

• 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