A Rare Presentation of Multiple Primary Cancers with Extensive Abdominopelvic Cross-Metastasis and Tumor-to-Tumor Metastasis: High-Grade Serous Carcinoma of the Ovary and Well-Differentiated Mucinous Adenocarcinoma of the Appendix

This study reports an exceptionally rare clinical encounter of synchronous multiple primary cancers involving high-grade serous ovarian carcinoma (HGSOC) and well-differentiated appendiceal mucinous adenocarcinoma in a 73-year-old woman. Presenting with abdominal distension and complex abdominopelvic masses, the patient's ascitic fluid revealed 2 morphologically distinct malignant cell populations. Following cytoreductive surgery, histopathological and immunohistochemical (IHC) analyses confirmed a dual-origin malignancy: ovarian lesions exhibited PAX8, WT1, and mutant-pattern TP53 expression, while the appendiceal lesion demonstrated strong keratin 20 positivity. Crucially, targeted gene sequencing validated these findings by identifying mutually exclusive mutational profiles—the HGSOC harbored a TP53 c.549del mutation, whereas the well-differentiated appendiceal mucinous adenocarcinoma carried KRAS p.G12D, GNAS p.R201C, and ATR p.R1951* mutations. Beyond simple coexistence, this patient had extensive cross-metastasis and tumor-to-tumor metastasis within both primary sites and metastatic deposits, likely facilitated by mucinous ascitic dissemination and lymphovascular invasion. Such diagnostic complexity necessitates a multidimensional approach integrating histomorphology, IHC, and molecular profiling to prevent misdiagnosis. Our findings emphasize that when imaging or cytology suggests multiorigin components, clinicians should pursue thorough intraoperative exploration, multisite biopsies, and prophylactic appendectomy. Ultimately, the management of such patients requires highly individualized surgical and chemotherapeutic strategies that account for the divergent biological behaviors and therapeutic sensitivities of both HGSOC and well-differentiated appendiceal mucinous adenocarcinoma to optimize oncological outcomes.