Endoscopic submucosal dissection for malignant melanoma and esophageal squamous cell carcinoma: A case report and review of literature

Abstract

BACKGROUND

Primary malignant melanoma of the esophagus (PMME) is a rare and highly aggressive neoplasm, accounting for less than 0.2% of esophageal malignancies. Its synchronous occurrence with esophageal squamous cell carcinoma (SCC) is exceptionally uncommon, with only a few documented cases worldwide. No consensus regarding the optimal management of synchronous PMME and SCC has been established.

CASE SUMMARY

A 60-year-old male underwent gastroscopy as a physical examination, which revealed a superficial elevated lesion 31-36 cm from the incisors. Magnifying endoscopy with narrowband imaging showed type B1 and focal B2 intrapapillary capillary loops (Japan Esophageal Society classification), and iodine staining revealed an iodineunstained area. Contrastenhanced computed tomography showed localized esophageal wall thickening with mild enhancement and several sub-centimeter mediastinal lymph nodes. The patient underwent endoscopic submucosal dissection (ESD). Histopathology combined with immunohistochemistry confirmed synchronous SCC and PMME (HMB-45+, Melan-A+, S-100+). The two tumor components were independent, with a clear interface and no histological intermingling, consistent with a collision tumor. The lesion invaded the muscularis mucosae, and R0 resection was achieved. A selfhelp balloon dilator was used postoperatively. No recurrence was observed at the 19-month follow-up.

CONCLUSION

Synchronous esophageal PMME and SCC is rare, and ESD is a feasible treatment. We achieved R0 resection for our case, with no recurrence within the 19-month follow-up.

Key Words: Primary malignant melanoma of esophagus; Squamous cell carcinoma; Endoscopic submucosal dissection; Immunohistochemistry; Case report

Core Tip: Primary malignant melanoma of the esophagus (PMME) and squamous cell carcinoma (SCC) are rarely synchronous. We report a unique collision tumor comprising PMME with SCC in a 60-year-old male. Endoscopic submucosal dissection (ESD) achieved R0 resection; postoperative stricture was managed with a balloon dilator. No recurrence was observed within the 19-month follow-up. This case suggests that ESD is a feasible treatment modality for incidental microscopic melanoma foci. However, radical surgery remains the standard therapy, and intensive surveillance is mandatory.

INTRODUCTION

Esophageal cancer is the seventh leading cause of cancer-related death globally and the eleventh most prevalent type of cancer, according to the 2022 Global Cancer Observatory (GLOBOCAN) study[1]. Squamous cell carcinoma (SCC) represents approximately 90% of global cases, indicating its high prevalence[2,3]. Melanoma, particularly primary malignant melanoma of the esophagus (PMME), represents a significantly rarer form of malignant tumor[4,5]. The rise in endoscopic examination frequency has correspondingly elevated the incidence of PMME, which accounts for approximately 0.1%-0.2% of malignant esophageal disorders[6-8]. Few cases of PMME occurring simultaneously with SCC have been documented[6,9], and no consensus on the optimal treatment for PMME has been established[10]. We here report a case of PMME concurrent with SCC resected successfully by endoscopic submucosal dissection (ESD).

CASE PRESENTATION

Chief complaints

A 60-year-old male was found to have an esophageal lesion incidentally on routine gastroscopy 1 week before admission.

History of present illness

The patient underwent a routine gastroscopy, which revealed a lesion on the esophageal mucosa. Biopsy revealed high-grade squamous intraepithelial neoplasia.

History of past illness

The patient had no previous medical conditions or history of skin melanoma. There were no signs of melanoma in the eyes, ears, or nasal throat, such as alterations in vision, epistaxis, or dysphonia.

Personal and family history

The patient had no history of smoking or alcohol consumption. No notable personal or family history was reported.

Physical examination

The patient was 1.78 m tall, weighed 90 kg, and had a body mass index of 28.4 kg/m². No pigmented lesions or tumors were observed on the skin or in the oral cavity, nasal cavity, or perianal area. No specific physical indicators were observed during the assessment.

Laboratory examinations

Routine blood tests, liver function tests, renal function tests, and prothrombin tests were within normal limits. Alpha-fetoprotein, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 levels were also within normal limits.

Imaging examinations

The chest-enhanced computed tomography (CT) was suspicious for focal mural thickening of the right posterior esophageal wall at the level of the tracheal bifurcation, with a maximum thickness of around 0.9 cm. The lesion exhibited mild progressive enhancement [precontrast, 19 Hounsfield units (HU); arterial phase, 38 HU; and venous phase, 46 HU]. There were also several small mediastinal lymph nodes < 1 cm in diameter across the short axis. The lumen exhibited eccentric constriction at the corresponding level. Chest-enhanced CT also revealed interstitial lung disease. Enhanced abdominal CT showed numerous small liver cysts and bilateral renal cysts. There were no signs of distant metastases or retroperitoneal lymphadenopathy.

The patient underwent a colonoscopy, which revealed multiple polyps in the colon that were subsequently excised. The postoperative pathology results showed that all lesions were tubular adenomas. Colonoscopy revealed no melanotic or nodular lesions suggestive of melanoma metastasis.

Gastroscopy revealed a superficial elevated lesion with a central depression in the esophagus (Paris classification type 0-IIa + IIc), 31-36 cm from the incisors (Figure 1). The surface mucosa appeared uneven and had red patches on it. Narrow-band imaging showed a clear border with a brownish color change. According to the Japan Esophageal Society (JES) classification, magnifying endoscopy with narrow-band imaging (ME-NBI) showed type B1 dilated and twisted intraepithelial papillary capillary loops, with some places showing a B2 vascular pattern[11]. Following iodine staining, a zone devoid of iodine was evident. The postoperative specimen comprised a mucosal tissue fragment measuring approximately 65 mm × 45 mm × 2 mm, with an iodine-unstained region on the mucosal surface measuring approximately 60 mm × 35 mm.

Figure 1 Endoscopic and gross findings of the esophageal lesion. A: Superficial elevated lesion with central depression (Paris type 0-IIa + IIc) located 31-36 cm from the upper incisors; B: Magnifying endoscopy with narrowband imaging showing type B1 and focal B2 intrapapillary capillary loops according to the Japan Esophageal Society classification; C: Iodine staining revealing an iodineunstained area; D: Resected specimen, measuring 65 cm × 4.5 cm × 0.2 cm, with an iodineunstained region of 6.0 cm × 3.5 cm on the mucosal surface.

The cellular morphology aligned with SCC alongside nearby high-grade squamous intraepithelial neoplasia. Two discrete foci of more poorly differentiated cells were identified. The histopathological investigation, incorporating pathology, morphology, and immunophenotypic features, confirmed the diagnosis of malignant melanoma in these clusters. Microscopic evaluation revealed that the largest of these tumors measured approximately 2 mm in diameter. Immunohistochemical staining was positive for HMB-45, S-100 protein, Melan-A, and CD56, and negative for CK5/6, CK7, P63, P40, CgA, and Syn, leading to the diagnosis of melanoma. Upon careful reexamination of the squamous epithelium adjacent to the melanoma component, atypical melanocytes were identified along the basal layer. This finding was consistent with junctional activity and supportive of the primary nature of the esophageal melanoma[12]. Postoperative histopathology and immunohistochemistry confirmed a collision tumor of PMME and SCC (Figure 2), with a clear interface between the two components and no evidence of histological admixture. The lesion invaded the muscularis mucosae (MM), corresponding to pT1a (according to the AJCC, 8^th edition[13]), with negative margins (R0 resection, ly0, v0).

Figure 2 Histological and immunohistochemical findings of the collision tumor. A: Tumor cells are separated from the resection margins by a safety distance of > 1 mm (H&E, × 10); B: Low-power view showing the overall architecture of the collision tumor (H&E, × 40). The dashed line demarcates the boundary between high-grade intraepithelial neoplasia (right) and the primary malignant melanoma of the esophagus (left); C: Higher magnification of the adjacent squamous epithelium revealing melanocytic hyperplasia in the basal layer, consistent with junctional activity (H&E, × 200); D: An adjacent section of the same specimen reveals a distinct focus of invasive squamous cell carcinoma that has broken through the basement membrane, fulfilling the diagnostic criteria for squamous cell carcinoma (H&E, × 200); E: Immunohistochemistry showing diffuse positivity for Melan-A in melanoma cells (× 200); F: Immunohistochemistry showing diffuse positivity for HMB45 in melanoma cells (× 200); G: Immunohistochemistry showing diffuse positivity for S-100 protein in melanoma cells (× 200); H: Reconstructed pathological sample maps showing the spatial distribution of the primary malignant melanoma of the esophagus (yellow line), high-grade intraepithelial neoplasia (blue line), and squamous cell carcinoma (red line).

FINAL DIAGNOSIS

The patient was finally diagnosed with PMME and concurrent SCC (pT1a, N0, M0, stage IA, according to the AJCC 8^th edition[13]).

TREATMENT

One month post-ESD, surveillance endoscopy revealed a well-formed scar at 31 cm but a benign stricture at 34 cm, precluding ultrathin endoscope passage. A self-help esophageal balloon dilator was placed endoscopically, distal to the stricture. The patient was educated on a home dilation protocol commencing on postoperative day 4: Five daily sessions (15-20 minutes each) with 30-35 mL air insufflation, performed approximately 1 hour before meals. Adjunctive therapy included esomeprazole 20 mg twice daily and L-glutamine granules. A liquid or semi-liquid diet was followed during the dilatation period, with a strict liquid diet for 1-2 days before each biweekly surveillance endoscopy.

OUTCOME AND FOLLOW-UP

Post-ESD surveillance was conducted according to the following schedule: Endoscopy at months 1, 3, 6, 12, and 19; contrast-enhanced CT of the chest and abdomen at months 6 and 18; and serum tumor markers (CEA, CA19-9) at each visit. Positron emission tomography-CT (PET-CT) was not performed during follow-up due to patient preference and economic constraints. The self-help balloon dilator was removed at month 5 post-ESD (Figure 3). At the 19-month follow-up, the patient remained asymptomatic, and endoscopic examination revealed no evidence of local recurrence.

Figure 3 Endoscopic findings during followup after endoscopic submucosal dissection. A: Narrow-band imaging view of the post-endoscopic submucosal dissection (ESD) scar at 5 months, after removal of the selfexpanding balloon dilator; B: Scar at the original lesion site at 19 months post-ESD (white light), showing satisfactory healing with no signs of recurrence; C: Scar at the original lesion site at 19 months post-ESD (narrow-band imaging), showing satisfactory healing with no signs of recurrence.

DISCUSSION

According to the 2022 GLOBOCAN study, esophageal cancer is the seventh leading cause of cancer-related mortality and the eleventh most common malignancy globally, imposing a substantial healthcare burden[1]. Esophageal cancer has a variety of forms. SCC is the most prevalent, accounting for approximately 90% of cases globally[2,3], whereas PMME is a rare condition accounting for < 1% of all esophageal tumors[6-8,14]. In 1906, Baur[15] documented the first case of esophageal malignant melanoma. Although the histogenesis of PMME remains a subject of debate, the presence of melanocytes in the basal layer of the esophageal mucosa, confirmed by De La Pava et al[16] and Oshiro et al[17], provides a pathological basis for its diagnosis as a primary disorder.

There are limited documented instances of PMME occurring concurrently with SCC[9,18,19]. This case exhibits a unique collision tumor pattern, in contrast to earlier recorded occurrences where malignancies were spatially discrete. Our patient was effectively treated with ESD, resulting in R0 resection and organ preservation, in contrast to traditional radical esophagectomy. A self-expanding balloon dilator effectively treated post-procedural stricture, offering a cost-effective substitute for repeated inpatient dilatation.

PMME is a highly aggressive neoplasm with a propensity for early hematogenous and lymphatic metastasis to the liver, lungs, and brain[20-22]. The pathogenesis of PMME is still unclear. It usually occurs in the middle and lower esophagus[22-24]. Some scholars suggest that increasing numbers of melanocytes in cases of esophagitis and hyperplastic esophagus may serve as precursor lesions for PMME. Multiple reports illustrate the progression of esophageal melanomas to malignant melanomas[6,17,25,26]. There are no obvious symptoms in the early tumor stages. As disease progresses, symptoms gradually appear. Dysphagia and epigastric pain are the most common symptoms[4,22]. Clinical symptoms lack specificity so are readily overlooked, thereby delaying diagnosis.

The male-to-female ratio and age of onset for PMME vary significantly by region (China: 2.2:1 ratio, mean of 58.5 ± 9.7 years, respectively; Japan: 3.5:1, median of 64.5 years; Western populations: 1:3.1, mean of 71.8 ± 13.6 years)[7,27,28]. The main endoscopic signs of PMME are large basal polypoid or myxoid lesions that bleed easily, have different colors (from white to black)[22,27,29,30], and sometimes form ulcers (about 25% of the time)[14]. Conclusive diagnosis of PMME relies on immunohistochemical staining, with positive S-100 protein, Melan A and HMB-45, and negative cytokeratin, CEA, p-53, estrogen receptor, and progesterone receptor. Among these, HMB-45, Melan A and S-100 have superior specificity[31]. Sex, lymph node metastases, the extent of lymph node dissection, and postoperative therapy are independent prognostic factors[10]. A reduced T-stage and the absence of lymph node metastases signify a more favorable prognosis[32,33].

Due to its rarity, no consensus on the optimal treatment for PMME has been established. Radical surgical excision with lymphadenectomy is the primary treatment for patients with early operable PMME[8,22,33,34], yet 5-year survival correlates strongly with TNM stage (62.9% for stages 0-I vs 8.9% for stages IVa-IVb)[8], and postoperative recurrence risk is high (median time to recurrence: 6 months)[35]. Esophagectomy imposes substantial morbidity and quality-of-life burdens. In recent years, ESD has been the benchmark for managing early gastrointestinal malignancies, offering organ preservation and favorable en bloc resection rates[36-38]. However, PMME is an aggressive mucosal melanoma with a high propensity for distant metastasis even after R0 resection; the 5-year survival for mucosal melanoma is approximately 14%[35]. The role of ESD has remained uncertain. In the present case, ESD enabled accurate pathological staging (pT1a) and complete local resection (R0, ly0, v0) in a setting where the melanoma component was an incidental 2-mm microscopic focus, a presentation that diverges from typical bulky PMME.

Preoperative ME-NBI revealed type B1 and focal B2 vessels according to the JES classification. In typical esophageal SCC, type B2 vessels suggest invasion into the MM or superficial submucosa. The final pathology in this case confirmed pT1a (invasion limited to the MM), consistent with the JES criteria for B2 vessels. This clinicopathological correlation suggests that, while the vascular morphology itself was not substantially altered by the admixed melanoma component, the presence of such a composite lesion should alert endoscopists to the possibility that type B2 vessels, though reliable in this case, may occasionally lead to overestimation of invasion depth. This observation, while derived from a single case, adds to the limited data on ME-NBI findings in rare esophageal combined tumors.

This case holds educational value for three reasons. First, it documents an extraordinarily rare histological phenomenon of melanoma concurrent with SCC, enriching the spectrum of esophageal collision tumors. Second, it provides a precise clinicopathological correlation showing that JES type B2 vessels may overestimate invasion depth in such composite lesions. Third, it serves as a cautionary reminder that even minute incidental melanoma foci carry a substantive risk of systemic spread, necessitating vigilant long-term surveillance despite successful local resection.

Several limitations and unresolved clinical concerns should be acknowledged. First and foremost, although ESD achieved local control, it cannot eliminate the risk of systemic recurrence[39], a major concern in mucosal melanoma. The role of adjuvant immunotherapy remains ill-defined; response rates in mucosal melanoma are inferior to those in cutaneous disease, and its efficacy for PMME awaits validation in large-scale prospective trials[35,40]. Second, PET-CT was not performed due to economic constraints and patient preference, so we cannot definitively exclude occult distant metastases given the aggressive nature of the melanoma component. Nevertheless, contrast-enhanced CT revealed no evidence of distant metastasis, and the patient has remained disease-free for 19 months after ESD alone, which indirectly supports the absence of systemic spread at presentation. Third, formal ophthalmological and otorhinolaryngological examinations were not conducted. However, thorough physical inspection of the skin and accessible mucosal surfaces revealed no pigmented lesions. Fourth, the findings are not generalizable as they pertain to a singular case study. Fifth, while current adjuvant immunotherapies have shown limited efficacy in mucosal melanoma, the absence of molecular profiling in this case (e.g., BRAF and KIT mutations) represents a missed opportunity for genotype-directed targeted therapy, which is a potential future direction for personalized treatment in such patients. An increased sample size and prolonged follow-up are essential to validate the long-term efficacy of ESD for PMME combined with SCC.

CONCLUSION

Synchronous PMME and SCC represents an exceptionally rare and clinically challenging entity. In the present case, the melanoma component was an incidental microscopic focus measuring only 2 mm, confined to the MM (pT1a). This presentation diverges markedly from the typical PMME, which usually presents as a large polypoid lesion with substantial risk of submucosal invasion and early metastasis. Under these highly atypical and strictly selected circumstances, ESD achieved complete local resection and allowed organ preservation. However, given the aggressive nature and high metastatic potential of PMME, this single-case experience cannot be generalized. Radical surgical resection with lymphadenectomy remains the standard of care for the vast majority of PMME patients. In the rare scenario of an incidental minute melanoma component detected in a superficial lesion, ESD may serve as a diagnostic and staging tool, but stringent postoperative surveillance (every 3-6 months) is mandatory, and the role of adjuvant therapy should be evaluated on a case-by-case basis.