Use of Next-Generation Sequencing Techniques in the Accurate Diagnosis of Neural Crest Cell-Derived Tumors

The increasing adoption of next-generation sequencing (NGS) techniques in daily practice has led to the incorporation of molecular information in the diagnosis and management of cancer patients. Taking advantage of these new tools could clearly impact the outcome of cases we present the case of a 39-year-old woman who attended the emergency department for fever and dysphagia. Computed axial tomography revealed a solid lesion in the subcarinal region. Histologically, the mass showed a tumor with proliferation of spindle cells containing elongated, hyperchromatic nuclei and brownish pigment in the cytoplasm. On immunohistochemical staining, the cells were positive for S-100, SOX10, P16 and HMB 45 and negative for CKAE1/AE3 and actin. Consequently, given the location and clinical findings, the mass was tentatively diagnosed as locally advanced esophageal mucosal melanoma. Further genetic testing with an NGS panel identified EWSR1-ATF1 fusion, resulting from translocation t(12;22)(q13-14;Q12). These new data were combined with all the available information, and the patient was diagnosed with clear cell sarcoma, which was treated with radical-intent radiotherapy. The use of NGS platforms to determine the genetic profile of the tumor facilitated the correct diagnosis of this rare neoplasm with melanocytic differentiation, an entity that presents a broad differential diagnosis with other neural crest cell-derived tumors. As a result, the patient received proper treatment based in precision medicine in line with the new molecular findings described.