Development of a second primary tumor during maintenance immunotherapy in metastatic gingival squamous cell carcinoma: a case report

Multiple primary tumors are defined as two or more distinct malignancies occurring simultaneously or metachronously in the same patient. This report describes a patient with extensively metastatic gingival squamous cell carcinoma who achieved radiologic complete remission (CR) through combined immunotherapy, chemotherapy, and local radiotherapy. The patient continued immunotherapy maintenance for 38 months. Two years after CR, a second primary tumor emerged. The second tumor was surgically resected, followed by postoperative maintenance therapy with oral Tegafur-Gimeracil-Oteracil (S-1) capsules. As of the last follow-up on January 14, 2025, nearly two years after the second surgery, the patient showed no local recurrence or distant metastasis. This case suggests that while immunotherapy provided excellent overall tumor control, it failed to prevent the occurrence of the second primary tumor. Whether prolonged immunotherapy (38 months vs. the standard 24 months) positively impacts patient prognosis requires further exploration. This case highlights that even after achieving CR with immunotherapy, vigilance for the development of second primary tumors during maintenance therapy is crucial.