I The presence of both metachronous and synchronous tumors creates considerable diagnostic and therapeutic complexity, particularly when one exhibits rare neuroendocrine features. We describe a patient with sarcoidosis who had previously undergone treatment for endometrial and ovarian tumors and later developed recurrent lesions with two different histologies: adenocarcinoma and high-grade neuroendocrine carcinoma, both characterized by microsatellite instability–high (MSI-H) status. Comprehensive targeted next-generation sequencing revealed shared synonymous somatic mutations across all three tumors, indicating a common clonal origin. The patient achieved a favorable response to a customized immunotherapy regimen, with only slight exacerbation of sarcoidosis, allowing uninterrupted treatment. This case emphasizes the value of molecular profiling in selecting optimal therapy for complex synchronous tumors and the necessity of close coordination between surgical and medical oncology teams in managing MSI-H cancers.
