Whole-exome sequencing in a patient with a history of esophageal squamous cell carcinoma to discriminate recurrent disease from a second primary tumor.

A 52-year-old man who previously underwent McKeown esophagectomy to treat lower thoracic esophageal squamous cell carcinoma (ESCC) and subsequently received radical radiotherapy to treat cervical lymph node malignancy (squamous cell carcinoma on pathology; presumed to be metastasis of the primary tumor) presented with recurrent cervical lymphadenopathy during periodic reexamination. On admission, gastroscopy revealed a 0.5 × 0.5-cm lesion on the cervical remnant esophagus, and biopsies of both the lesion and cervical lymph nodes confirmed SCC. Whole-exome sequencing revealed that there were no comutations between the tumor samples from the primary ESCC from 2017 and the other malignancies (tumor samples from the remaining ESCC in 2022 and cervical lymph node malignancies on two occasions). Interestingly, the first and second cervical lymph node malignancies and the tumor in the cervical remnant esophagus shared many comutations, suggesting that the tumor in the cervical remnant esophagus is a second primary tumor with cervical lymph node metastasis and is not amenable to radical radiotherapy. Significant regression of lymphadenopathy was achieved after 2 cycles of immunochemotherapy; however, the patient declined further surgical intervention. Six months later, positron emission tomography-computed tomography (PET-CT) revealed tumor progression with multiple metastases. Herein, we show the importance of regular examination of the remnant esophagus and the significance of whole-exome sequencing for distinguishing the source of malignancy, which could aid in the formulation of appropriate treatment plans.