Primary Malignant Melanoma of the Esophagus Treated with Surgical Resection at an Early Stage

Abstract

Introduction

Primary malignant melanoma of the esophagus is a very rare disease with a poor prognosis. We herein report a patient with primary malignant melanoma of the esophagus who underwent surgical resection.

Case Presentation

A 73-year-old female underwent an upper gastrointestinal endoscopy during follow-up for colonic diverticulitis. An endoscopic examination and constructed radiography revealed a slightly elevated black pigmented lesion in the upper esophagus and a black pigmented area in the esophagogastric junction. Through a preoperative endoscopic biopsy, she was diagnosed with malignant melanoma of the esophagus. We performed thoracoscopy-assisted and laparoscopy-assisted subtotal esophagectomy with lymphadenectomy. The surgical specimens were subjected to immunohistochemical analysis, resulting in a diagnosis of malignant melanoma. The tumor cells were positive for Melan-A and HMB-45 diffusely, supporting that diagnosis. We performed surgical resection in a case of primary malignant melanoma of the esophagus, and the patient has remained disease free for 2 years since the surgery.

Conclusion

Early diagnosis and radical resection may be essential for long-term survival in patients with malignant melanoma of the esophagus.

Introduction

Primary malignant melanoma of the esophagus is an extremely rare disease, accounting for only 0.1–0.2% of all primary esophageal malignancies [1]. Primary malignant melanoma of the esophagus is more common in the elderly and is usually diagnosed in the advanced stages of the disease; it has a worse prognosis than cutaneous melanoma [2]. The clinicopathological characteristics of malignant melanoma of the esophagus have rarely been reported, and no comprehensive treatment strategy has been established because of the lack of accumulated cases. This paper reports a 73-year-old woman with malignant melanoma of the esophagus who underwent surgical resection and had a favorable prognosis.

Case Presentation

During follow-up for colonic diverticulitis, a 73-year-old female underwent an upper intestinal endoscopy, which revealed an esophageal tumor. Her family history was unremarkable. Physical examination revealed no significant pigmented skin lesion or lymph node swelling. No abnormalities in vital signs were noted. Routine blood and urine profiles were also unremarkable. Tumor markers, such as carcinoembryonic antigen (CEA) and squamous cell carcinoma-associated antigen (SCC), were not elevated. Upper gastrointestinal endoscopy showed a slightly elevated black pigmented lesion in the upper esophagus, 24 cm from an incisor tooth (Fig. 1a). There was also a black pigmented area in the esophagogastric junction (Fig. 1b). This lesion was considered intramural metastasis. Constructed radiography showed the slightly elevated lesion in the upper esophagus. Immunohistochemistry was performed on a biopsy specimen, which was positive for human melanoma black (HMB)-45 and Melan-A. The main lesion had good extension on its basal part, indicating that the invasion had reached the submucosal level. On contrast-enhanced computed tomography (CT), the esophageal tumor lesions were difficult to detect and neither lymph node nor distant metastasis was detected (Fig. 2a). Positron emission tomography-CT revealed no fluorodeoxyglucose (FDG) uptake in esophageal lesions and no findings of lymph node or distant metastasis (Fig. 2b). Based on these preoperative analyses, the patient was diagnosed with cT1bN0M0, indicating cStageI malignant melanoma of the esophagus. There were not lifestyle habits or risk factors for the disease in this patient. During thoracoscopy and laparoscopy, we conducted a subtotal esophagectomy and lymphadenectomy and utilized the retrosternal route for reconstruction. The total operation time was 430 min, and intraoperative blood loss was 30 mL. An oral diet was initiated 6 days after the operation, and the patient was transferred to another hospital for rehabilitation on day 15 in a good general condition.

Fig. 1.

a Upper gastrointestinal endoscopy showed a slightly elevated black pigmented lesion in the upper esophagus. b Upper gastrointestinal endoscopy showed a black pigmented area in the esophagogastric junction. c Constructed radiography showed the slightly elevated lesion in the upper esophagus (arrow).

Fig. 2.

a On contrast-enhanced computed tomography (CT), the esophageal tumor lesions were difficult to detect and neither lymph node nor distant metastasis was detected. b Positron emission tomography-CT (PET-CT) revealed no fluorodeoxyglucose (FDG) uptake in esophageal lesions and no findings of lymph node or distant metastasis.

A pathological examination showed that the tumors were located at the mucosa and submucosa of the esophageal wall (Fig. 3a). Immunohistochemically, atypical melanocytes were positive diffusely for Melan-A and HMB-45 (Fig. 3b, c). There was no lymph node metastasis. The pathological diagnosis was pT1bN0M0 indicating pStageI. The postoperative adjuvant therapy was not performed. A CT scan performed 2 years after surgery showed no evidence of recurrence. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000538161).

Fig. 3.

a Hematoxylin-eosin staining of tumor cells. Spindle-shaped atypical cells contained melanin pigmentation and irregularly demarcated nucleoli. The atypical melanocytes were round and displayed a focal pattern of proliferation that extended from the mucosal layer and slightly infiltrated the submucosa, surpassing the muscularis mucosa (original magnification, ×40). b Melan-A immunostaining. Tumor cells were diffusely positive (original magnification, ×100). c HMB-45 immunostaining. Tumor cells were diffusely positive (original magnification, ×100).

Discussion

It is believed that primary malignant melanoma of the esophagus shares similarities with those occurring in the skin as the melanocytes found in the esophageal epithelium are thought to originate from neural crest tissue and migrate during embryogenesis [3]. It is a rare disease, with an estimated frequency of 0.1–0.2% of all malignancies in the esophagus [1, 4]. Malignant melanoma of the esophagus occurs more commonly in men, with a male to-female ratio of 2.17:1. The majority of patients with malignant melanoma of the esophagus are symptomatic on diagnosis; dysphagia is the most common major symptom [5]. The prognosis is exceedingly grim, often resulting from late-stage diagnosis, with concurrent metastases observed in 30–40% of cases. The most commonly involved sites are the paraesophageal lymph nodes (10.8%), supraclavicular lymph nodes (7%), liver (7%), lungs (6%), celiac lymph nodes (4%), and bones (2.9%) [6]. The roles of FDG PET/CT are established in both the staging and follow-up of malignant melanoma. Due to its exceptional sensitivity in detecting malignant lesions and the ability to comprehensively scan the entire body in a single examination, FDG PET/CT can serve as a valuable adjunct to other staging tools. Because of the high tumor-to-background ratio, FDG/PET can highlight metastases at unusual sites that conventional imaging modalities miss [7]. Gao reported that the median survival time of patients with malignant melanoma of the esophagus is 18.1 months, and the 1- and 5-year survival rates are 51% and 10%, respectively [8]. According to the literature, malignant melanomas of the esophagus are located in the middle and lower thirds of the thoracic esophagus in approximately 90% of cases, probably because of the greater concentration of melanocytes in these regions [4]. Macroscopically, tumors usually show a focally ulcerated polypoid mass that is mostly covered by intact squamous mucosa. In endoscopic biopsy, these findings sometimes lead to a misdiagnosis of poorly differentiated squamous cell carcinoma [9]. A previous study reported that biopsies were conducted in approximately 70% of patients, with a diagnostic accuracy of approximately 80%, while 20–50% of patients are reported to be misdiagnosed with poorly differentiated carcinoma due to the absence of melanin granules [6]. The diagnostic criteria for determining that a melanoma originates in the esophagus include the presence of melanin granules in the tumor cells, melanocytes in the overlying epithelial layer, and a junction between squamous epithelium and adjacent epithelium. A more accurate diagnosis is confirmed by immunohistochemical studies: primary malignant melanoma of the esophagus is generally found to have a positive antibody-specific cytoplasmic reaction to HMB-45 and S-100 proteins as well as a negative reaction to cytokeratin or carcinoembryonic antigen [2]. If endoscopy reveals unusual findings in esophageal tumors, especially tumors of unusual color, it is important to perform a comprehensive examination with malignant melanoma of the esophagus in mind. Surgical resection is the preferred treatment for this type of cancer. Because the tumor spreads longitudinally, a total or near-total esophagectomy is required. Thus far, radiation therapy, chemotherapy, and immunotherapy have not proved effective. However, these alternative treatments play palliative roles when surgery is not possible [4]. Some authors have reported the efficacy of neoadjuvant and adjuvant chemotherapy [10]. Chemotherapy was also reported to be beneficial for recurrent cases [11]. Other authors have noted that immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1 antibodies, benefit patients with advanced malignant melanoma of the esophagus [11, 12]. Suzuki et al. [13] reported that patients with malignant melanoma of the esophagus who received neoadjuvant chemotherapy, adjuvant chemotherapy, and immunotherapy after surgery showed better long-term survival than those who had received none of these. Adjuvant chemotherapy and immunotherapy may be of benefit to patients with malignant melanoma of the esophagus; however, further studies will be needed to prove their effectiveness. In conclusion, we treated a patient with early-stage malignant melanoma of the esophagus, and the patient remains alive and without relapse 2 year after surgery. Malignant melanoma of the esophagus appears to be a highly malignant tumor with high metastatic potential and a dismal prognosis. Diagnosis during the early stage and radical resection may be essential for long-term survival in patients with malignant melanoma of the esophagus.

Statement of Ethics

This case study was approved by the Biomedical Ethics Committee. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. This study was approved by the Ethics Committee of National Hospital Organization Nagasaki Medical Center (Approval Reference No. 2023027).

Conflict of Interest Statement

The authors have no conflict of interest to declare.

Funding Sources

No financial support was received for this study.

Author Contributions

Akira Yoneda, Ryousuke Ogata, Shintaro Ryu, Kyohei Yoshino, Saeko Fukui,Takahiro Ikeda, Amane Kitasato, Nozomu Sugiyama, Hiroaki Takeshita, Shigeki Minami, Masahiro Ito, and Tamotsu Kuroki: manuscript writing and literature review. All authors have read and approved the final manuscript.

Funding Statement

No financial support was received for this study.

Data Availability Statement

All data collected during this study are available from the corresponding author. Further inquiries can be directed to the corresponding author.