Genetic mutations in primary and metastatic tumors of a rare mixed neuroendocrine carcinoma and high-grade serous ovarian cancer

Neuroendocrine carcinoma and high-grade serous ovarian cancer (HGSCO) form a rare mixed ovarian tumor. Ovarian cancer is the most lethal gynecological malignancy, with HGSCO being the most common (60–70%) and aggressive subtype, characterized by insidious symptoms and poor prognosis. Neuroendocrine carcinoma (NEC) is a poorly differentiated, high-grade tumor. Their coexistence challenges individualized therapy and confers a poor prognosis. In this case, both components were present in the ovaries, with lung NEC nodules detected 2 years later. Second-generation sequencing revealed shared TP53, PRDM1, and KIT mutations in all three tumors, indicating a common origin from a pluripotent cancer stem cell and suggesting lung NEC metastasized from the ovary. A SPEN mutation was unique to HGSCO, implying a role in HGSCO differentiation, while a PLCG2 mutation occurred only in metastatic lung NEC, indicating a potential key role in lung metastasis.