Familial germ cell tumors: A case of ovarian yolk sac tumor in a patient with lynch syndrome and two brothers diagnosed with testicular seminomas

Background Malignant ovarian germ cell tumors (OGCTs) account for only 2–5% of ovarian cancers, and familial clustering of germ cell tumors in the ovaries and testes is rare. Lynch syndrome confers elevated colorectal, endometrial, and ovarian cancer risk, but germ cell histologies are not well recognized within its tumor spectrum. Case A 41-year-old woman presented with abdominal pain. Imaging demonstrated an 11.4 × 6.4 × 10.4 cm mass involving both adnexa with small-volume ascites and elevated tumor markers, including CEA, CA-125, AFP, and LDH. She underwent robotic-assisted hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, partial omentectomy, and staging biopsies. Pathology showed FIGO stage IA yolk sac tumor with intestinal/glandular differentiation. Immunohistochemistry demonstrated diffuse SALL4, patchy glypican-3, focal AFP, mutant-pattern p53, and loss of MSH6 expression with retained internal controls. Germline testing identified a pathogenic MSH6 variant. Both of her brothers had been diagnosed with testicular seminoma, and her paternal grandmother had colon cancer. She completed four cycles of bleomycin, etoposide, and cisplatin and remains without evidence of disease. Conclusion We report an ovarian yolk sac tumor arising in a woman with germline MSH6-associated Lynch syndrome and two brothers with testicular seminoma. The concordance between her germline variant and MSH6 loss within the tumor suggests the variant could affect tumorigenesis and raises the question whether germ cell tumors are an under-recognized component of the Lynch spectrum. A separate familial germ cell tumor susceptibility allele cannot be excluded. Cascade testing is strongly indicated but remains incomplete in this family, underscoring a persistent gap between identifying a hereditary cancer syndrome and delivering genetic services to relatives.