Case Report: Long-term disease control with immunotherapy in primary mandibular adenoid cystic carcinoma presenting with pulmonary metastasis.

Primary intraosseous adenoid cystic carcinoma (PIACC) of the mandible is an exceptionally rare malignancy. While radical surgery and radiotherapy provide locoregional control, managing distant metastases remains challenging due to the lack of standard systemic therapies and the characteristically "cold" immune microenvironment of adenoid cystic carcinoma (ACC). We report the case of a 62-year-old male diagnosed with PIACC of the mandible presenting with synchronous bilateral pulmonary metastases (Stage IVC). Following radical resection and adjuvant radiotherapy, the patient received first-line maintenance with oral S-1, achieving stable disease for 36 months. Upon pulmonary progression, after a brief and poorly tolerated trial of sintilimab plus S-1 and subsequent docetaxel, therapy was optimized to a metronomic combination of the PD-1 inhibitor sintilimab and oral capecitabine. This immuno-metronomic regimen achieved durable disease stabilization exceeding 47 months with minimal toxicity. Upon discontinuing immunotherapy due to financial constraints, rapid disease progression ensued, underscoring the critical role of the combination. The patient subsequently received salvage anlotinib, achieving brief stabilization, but passed away from severe pneumonia, yielding a total overall survival of 101 months (~8.4 years). This case challenges the paradigm that ACC is intrinsically refractory to immunotherapy. We hypothesize that systemic interventions, potentially including immunogenic cell death induced by intervening chemotherapy and microenvironment remodeling by fluoropyrimidines, may sensitize ACC to PD-1 blockade. While limited by the lack of archival tissue for translational validation, this hypothesis-generating case warrants further investigation into combination immunotherapy strategies for metastatic ACC.