Outcomes in ovarian Sertoli-Leydig cell tumor: A report from the International Pleuropulmonary Blastoma/DICER1 and Ovarian and Testicular Stromal Tumor Registries

Alexander T Nelson; Anne K Harris; Dave Watson; Junne Kamihara; Kenneth S Chen; Jennifer N Stall; Kyle M Devins; Robert H Young; Damon R Olson; Paige H R Mallinger; Sarah G Mitchell; Lindsey M Hoffman; Gail Halliday; Amina M Suleymanova; Julia L Glade Bender; Yoav H Messinger; Cynthia E Herzog; Amanda L Field; A Lindsay Frazier; Douglas R Stewart; Louis P Dehner; D Ashley Hill; Deborah F Billmire; Dominik T Schneider; Kris Ann P Schultz

doi:10.1016/j.ygyno.2024.04.005

Outcomes in ovarian Sertoli-Leydig cell tumor: A report from the International Pleuropulmonary Blastoma/DICER1 and Ovarian and Testicular Stromal Tumor Registries

Gynecol Oncol. 2024 Apr 22:186:117-125. doi: 10.1016/j.ygyno.2024.04.005. Online ahead of print.

Authors

Alexander T Nelson¹, Anne K Harris², Dave Watson³, Junne Kamihara⁴, Kenneth S Chen⁵, Jennifer N Stall⁶, Kyle M Devins⁷, Robert H Young⁷, Damon R Olson⁸, Paige H R Mallinger², Sarah G Mitchell⁹, Lindsey M Hoffman¹⁰, Gail Halliday¹¹, Amina M Suleymanova¹², Julia L Glade Bender¹³, Yoav H Messinger², Cynthia E Herzog¹⁴, Amanda L Field¹⁵, A Lindsay Frazier⁴, Douglas R Stewart¹⁶, Louis P Dehner¹⁷, D Ashley Hill¹⁸, Deborah F Billmire¹⁹, Dominik T Schneider²⁰, Kris Ann P Schultz²¹

Affiliations

¹ International Pleuropulmonary Blastoma/DICER1 Registry, Children's Minnesota, Minneapolis, MN, USA; International Ovarian and Testicular Stromal Tumor Registry, Children's Minnesota, Minneapolis, MN, USA; Cancer and Blood Disorders, Children's Minnesota, Minneapolis, MN, USA; University of Minnesota Medical School, Minneapolis, MN, USA.
² International Pleuropulmonary Blastoma/DICER1 Registry, Children's Minnesota, Minneapolis, MN, USA; International Ovarian and Testicular Stromal Tumor Registry, Children's Minnesota, Minneapolis, MN, USA; Cancer and Blood Disorders, Children's Minnesota, Minneapolis, MN, USA.
³ Research Institute, Children's Minnesota, Minneapolis, MN, USA.
⁴ Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA.
⁵ Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA; Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX, USA.
⁶ Hospital Pathology Associates, Minneapolis, MN, USA.
⁷ James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Department of Pathology and Laboratory Medicine, Children's Minnesota, Minneapolis, MN, USA.
⁹ Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
¹⁰ Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, USA.
¹¹ Department of Paediatric Oncology, Great North Children's Hospital, Newcastle-upon-Tyne, UK.
¹² Institute of Pediatric Oncology, Federal State Budgetary Institution N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, Moscow, Russia.
¹³ Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁴ Division of Pediatrics, Department of Pediatric Patient Care, The University of Texas MD Anderson Cancer Care Center, Houston, TX, USA.
¹⁵ ResourcePath LLC, Sterling, VA, USA.
¹⁶ Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
¹⁷ Lauren V. Ackerman Laboratory of Surgical Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
¹⁸ ResourcePath LLC, Sterling, VA, USA; Lauren V. Ackerman Laboratory of Surgical Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
¹⁹ Division of Pediatric Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
²⁰ Clinic of Pediatrics, Municipal Hospital Dortmund, University Witten/Herdecke, Germany.
²¹ International Pleuropulmonary Blastoma/DICER1 Registry, Children's Minnesota, Minneapolis, MN, USA; International Ovarian and Testicular Stromal Tumor Registry, Children's Minnesota, Minneapolis, MN, USA; Cancer and Blood Disorders, Children's Minnesota, Minneapolis, MN, USA. Electronic address: KrisAnn.Schultz@childrensmn.org.

PMID: 38657450
DOI: 10.1016/j.ygyno.2024.04.005

Abstract

Objective: Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ovarian SLCT.

Methods: Individuals with SLCT were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and pathology was centrally reviewed when available.

Results: In total, 191 participants with ovarian SLCT enrolled, with most (92%, 175/191) presenting with FIGO stage I disease. Germline DICER1 results were available for 156 patients; of these 58% had a pathogenic or likely pathogenic germline variant. Somatic (tumor) DICER1 testing showed RNase IIIb hotspot variants in 97% (88/91) of intermediately and poorly differentiated tumors. Adjuvant chemotherapy was administered in 40% (77/191) of cases, and among these, nearly all patients received platinum-based regimens (95%, 73/77), and 30% (23/77) received regimens that included an alkylating agent. Three-year recurrence-free survival for patients with stage IA tumors was 93.6% (95% CI: 88.2-99.3%) compared to 67.1% (95% CI: 55.2-81.6%) for all stage IC and 60.6% (95% CI: 40.3-91.0%) for stage II-IV (p < .001) tumors. Among patients with FIGO stage I tumors, those with mesenchymal heterologous elements treated with surgery alone were at higher risk for recurrence (HR: 74.18, 95% CI: 17.99-305.85).

Conclusion: Most individuals with SLCT fare well, though specific risk factors such as mesenchymal heterologous elements are associated with poor prognosis. We also highlight the role of DICER1 surveillance in early detection of SLCT, facilitating stage IA resection.

Keywords: DICER1; DICER1-related tumor predisposition; Gynandroblastoma; Sertoli-Leydig cell tumor; Sex cord-stromal tumor.