RF14 | PMON320 Ovarian Malignancy, Familial Multinodular Goiter Associated with DICER1 Mutation

Abstract

Abstract Background DICER1 syndrome, a rare autosomal dominant disorder, places affected individuals at risk for benign and malignant tumors of multiple organs, including thyroid, ovaries, lungs, kidneys, CNS. These tumors occur in childhood and usually before 40 years of age. Clinical Case A 15-year old female presented with worsening abdominal pain and vomiting. She noted a "hard spot" on her abdomen and reported secondary amenorrhea with worsening acne and development of hirsutism over the previous 12 months. Imaging evaluation showed a 9 cm×19 cm×13 cm right ovarian mass with no enlarged lymph nodes. Initially, tumor markers and hormone levels were elevated: Alpha Fetoprotein 424 ng/mL [0-7], Testosterone 208 ng/dL [12-60], Free Testosterone 6.03 ng/dL [0.04-1.09], Inhibin A 129 pg/mL [97.5], Inhibin B 817 pg/mL [< 136], LDH 742 unit/L [370-645]. Patient underwent right salpingo-oophorectomy, lymph node and omentum biopsy; pathologic exam showed Stage 1C Sertoli-Leydig tumor of the right ovary (intermediate to poorly differentiated). She received chemotherapy with Cisplatin, Etoposide, Bleomycin. Genetic analysis revealed that she is heterozygous for a likely pathogenic variant, c.343del (p.Thr115Leufs*13) in DICER1, consistent with a diagnosis of autosomal dominant DICER1-associated disease. After therapy ended, her tumor markers and hormone levels normalized. Patient was found to have a multinodular goiter with benign pathology; her thyroid function remained normal. A 2 mm right middle lobe pulmonary nodule, stable, has been present on chest CT. Family history is significant for an euthyroid multinodular goiter with benign nodules in her 2-year older brother who has the same DICER1 pathogenic variant. Their mother and maternal grandmother also had total thyroidectomy for multinodular goiter. Conclusion A cluster of certain tumors in family members involving successive generations, should prompt evaluation for a genetic cause, as early diagnosis, management and appropriate surveillance improve patients’ quality of life. Presentation: Sunday, June 12, 2022 12:54 p.m. - 12:59 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.