Tumor risk in patients with DSD
Jacqueline Morin, MD, Frances Fei, MD, Justin Indyk, MD, PhD, Venkata R. Jayanthi, MD.
Nationwide Children's Hospital, Columbus, OH, USA.
BACKGROUND: Differences of sex development (DSD) is an umbrella term that describes a wide range of clinical presentations and diagnoses. Some patients are at elevated risk of germ cell tumors (GCT), usually due to the presence of dysgenetic gonads or intra-abdominal testes. However, even within these conditions, the risk for each specific diagnosis is unknown and likely lower than previously thought.
Methods: This is a retrospective cohort study of patients presenting for care from 2007-2021 with a diagnosis of complete androgen insensitivity syndrome (CAIS), 45X/46XY or 46XX/46XY mixed gonadal dysgenesis (MGD), 46XY complete gonadal dysgenesis (CGD), ovotesticular DSD, and 46XY partial gonadal dysgenesis (PGD), identified by ICD-9 and ICD-10 codes. These are the most common DSD conditions with intra-abdominal testicular tissue or dysgenetic gonads. Data were collected on demographics, imaging studies, diagnosis, pathology reports, and clinical presentation. Descriptive statistics and linear correlation analysis were used to summarize the data. This study was IRB approved.
Results: 70 patients met inclusion criteria and were included in the study, including 42 patients with MGD, 20 CGD, 4 PGD, and 4 ovotesticular DSD. Of the patients with MGD, 16 underwent bilateral gonadectomy and 9 unilateral gonadectomy. Bilateral gonadectomy occurred at average age 4.8 years (range 0-17 years). Average age at gonadectomy did not change over the course of the study. 12.5% of patients were found to have gonadoblastoma or dysgerminoma at the time of surgery. The patient with dysgerminoma had solid and cystic regions on pelvic ultrasound (PUS); the patient with gonadoblastoma had no concerning findings on PUS. These patients were diagnosed at ages 16 and 12 years, respectively. Of patients with CGD, all patients who underwent gonadectomy had bilateral resection (n=14). Surgery occurred at average age 8.6 years (range 0-18 years). Almost half (43%) of patients were diagnosed with gonadoblastoma and/or dysgerminoma at the time of surgery. Patients with gonadoblastoma were diagnosed at ages 14-15 years and dysgerminoma at ages 10-18 years. One patient with bilateral gonadoblastoma and unilateral dysgerminoma had bilateral echogenic foci in the gonads on PUS and no abnormal findings on magnetic resonance imaging (MRI). All other cases had no abnormalities on PUS or MRI. One patient with ovotesticular DSD and one with PGD each underwent bilateral gonadectomy. Two other patients in each group underwent unilateral gonadectomy. No cases of GCT were identified. CONCLUSIONS:
The risk of GCT varies widely based on the DSD diagnosis. Patients with CGD are at very high risk of developing neoplasms and should undergo prophylactic gonadectomy, either at time of diagnosis or in early childhood. Patients with MGD are also at an increased risk, but likely much lower than those with CGD.
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