Commentary: Pigmented spot during esophagoscopy—a mole or melanoma?

Abstract

Central MessageSurgical resection accompanied by systematic lymphadenectomy and adjuvant therapy may improve survival for primary malignant melanoma of the esophagus, which remains a diagnostic dilemma.See Article page 294. Surgical resection accompanied by systematic lymphadenectomy and adjuvant therapy may improve survival for primary malignant melanoma of the esophagus, which remains a diagnostic dilemma. See Article page 294. Primary malignant melanoma of the esophagus (PMME) is a very rare noncutaneous tumor first described in 1906 but not histopathologically proven until 1952.1Garfinkle J.M. Cahan W.G. Primary melanocarcinoma of the esophagus; first histologically proved case.Cancer. 1952; 5: 921-926Crossref PubMed Scopus (45) Google Scholar It is thought to arise in this organ from the anomalous migration of neural crest cells during development. The world literature contains fewer than 350 cases of reported PMME.2Lasota J. Kowalik A. Felisiak-Golabek A. Zięba S. Waloszczyk P. Masiuk M. et al.Primary malignant melanoma of esophagus: clinicopathologic characterization of 20 cases including molecular genetic profiling of 15 tumors.Mod Pathol. 2019; 32: 957-966Crossref PubMed Scopus (13) Google Scholar Consequently, a standard-of-care treatment approach for this disease remains largely undefined, although surgical intervention is a mainstay for this serious cancer, with poor overall survival rates. Dai and colleagues, in this issue of the Journal, assess outcomes of 70 patients from 10 hospitals accrued over a 20-year period with locally advanced PMME.3Dai L. Wanga Z.-M. Xue Z.-Q. He M. Yuan Y. Shang X.-Q. et al.Results of surgical treatment for primary malignant melanoma of the esophagus: a multicenter retrospective study (2019 International Thoracic Oncology Summit #P5).J Thorac Cardiovasc Surg. 2021; 161: 294-302Abstract Full Text Full Text PDF Scopus (5) Google Scholar This report represents the largest case series of surgically treated PMME to date. As the authors highlight, there is a significant diagnostic challenge posed by PMME. Pathologic workup correctly identified less than half of patients preoperatively. Compounding this dilemma, a handful of patients in their series presented with no pigment at all (amelanotic melanoma). The authors' experience reminds clinicians to have a high index of suspicion for PMME when the expected histologies common to esophageal cancer are not encountered during routine workup, prompting more extensive tests such as melanoma-specific staining to obtain a correct diagnosis. A major observation from this study is that more than 50% of patients presented with lymph node metastasis regardless of stage differences, although, consistently, the greater the number of surgically dissected lymph nodes (≥12), the more favorable was prognosis. Finally, the use of adjuvant therapy in these surgical patients correlated with improved survival, although due to limited subgroup numbers and diverse therapeutic modalities, the authors could not extensively explore this aspect of care. Most intriguingly, in the context of systemic therapies for melanoma, the modern success of small molecule targeted therapy (ie, BRAF plus MEK inhibitors4Robert C. Grob J.J. Stroyakovskiy D. Karaszewska B. Hauschild A. Levchenko E. et al.Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma.N Engl J Med. 2019; 381: 626-636Crossref PubMed Scopus (512) Google Scholar) and immune checkpoint inhibition (ie, anti-PD-1 alone or in combination with anti-CTLA-4 immunotherapy5Larkin J. Chiarion-Sileni V. Gonzalez R. Grob J.J. Rutkowski P. Lao C.D. et al.Five-year survival with combined nivolumab and ipilimumab in advanced melanoma.N Engl J Med. 2019; 381: 1535-1546Crossref PubMed Scopus (1335) Google Scholar) lend optimism to how multimodality care could potentially be improved for this rare tumor. Integrating these agents as adjuvants to surgical treatment or perhaps exploring their role in a neoadjuvant setting are logical next steps to consider. The paucity of PMME, reliably and consistently diagnosed, will practically deny any future attempts at prospective, much less large-scale, evaluations of multimodality therapeutic interventions. For now, we look to this reference data set presented by Dai and colleagues for clinical guidance. They have emphasized the importance of curative intent resection combined with some kind of adjuvant therapy toward being able to achieve better survival for patients with this aggressive disease. Results of surgical treatment for primary malignant melanoma of the esophagus: A multicenter retrospective studyThe Journal of Thoracic and Cardiovascular SurgeryVol. 161Issue 1PreviewFew large-sample research data sets exist on long-term survival and prognostic factors among patients with primary malignant melanoma of the esophagus (PMME), a rare malignancy associated with poor outcomes. We sought to investigate postoperative survival and prognostic factors in patients with PMME. Full-Text PDF