Case Report: S-100 negative primary esophageal malignant melanoma: surgical challenges and phenotypic evolution

Primary malignant melanoma of the esophagus (PMME) is a rare malignancy associated with a dismal prognosis. Diagnosis typically relies on immunohistochemical markers such as HMB-45 and S-100. However, unlike its cutaneous counterpart, mucosal melanoma can present with an S-100 negative phenotype in a notable subset of cases, posing a significant diagnostic challenge. Furthermore, the optimal extent of lymphadenectomy (2-field vs. 3-field) remains controversial, particularly for elderly patients with limited physiological reserve.

We report the case of a 64-year-old male presenting with progressive dysphagia. Endoscopy revealed a pigmented, polypoid mass in the middle esophagus. Due to severe abdominal adhesions from prior surgeries and the patient's advanced age, the surgical team adopted a "safety-first" strategy, performing an Ivor-Lewis esophagectomy with 2-field lymphadenectomy. Postoperative pathology confirmed PMME (pT1bN0M0). Immunohistochemistry revealed a rare phenotype: HMB-45 positive (+) but S-100 negative (-). Despite adjuvant maintenance therapy with Toripalimab (a PD-1 inhibitor), the patient developed a rapid cervical lymph node recurrence four months postoperatively. Notably, the recurrent tumor cells exhibited partial S-100 positivity, indicating phenotypic heterogeneity and antigenic drift.

This case highlights the potential diagnostic pitfall of S-100 negativity in PMME and the phenomenon of phenotypic switching during metastasis. For elderly patients where 3-field lymphadenectomy is deemed too risky, the high potential for cervical skip metastasis necessitates rigorous postoperative surveillance. The rapid disease progression despite immunotherapy underscores the urgent need to explore more effective multimodal treatment strategies.