Tumor risk in patients with differences in sex development (DSD) statements and recommendations from the first update of the German guideline for DSD.

INTRODUCTION: Management of gonadal tumor risk in individuals with differences of sex development (DSD) has changed considerably over recent decades. Historically, prophylactic gonadectomy was frequently performed because of concerns regarding malignant germ cell tumors (GCT). Current evidence suggests that tumor risk varies substantially between different DSD conditions and is often lower than previously assumed. OBJECTIVE: To summarize current evidence regarding gonadal tumor risk in DSD and present the updated recommendations of the revised German national DSD guideline. STUDY DESIGN: A comprehensive literature review on gonadal tumors in DSD was performed during revision of the German national guideline. Evidence regarding epidemiology, histopathology, surveillance, biopsy strategies, fertility preservation, and gonadectomy was evaluated. Consensus recommendations were developed jointly by clinicians and patient representatives according to the available evidence. RESULTS: Tumor risk differs considerably among DSD entities and is influenced by factors including Y chromosomal material, gonadal location, degree of gonadal dysgenesis, age, and specific genetic alterations such as TSPY or WT1 mutations. High-risk groups include complete and partial gonadal dysgenesis, particularly in the presence of Y chromosomal material. In contrast, tumor risk appears substantially lower in conditions such as androgen insensitivity syndrome, ovotesticular DSD, and congenital adrenal hyperplasia. Current management increasingly favors individualized risk assessment, surveillance, delayed gonadectomy whenever medically acceptable, and shared decision-making. CONCLUSION: The revised German guideline supports a more conservative and individualized approach to gonadal management in DSD. Decisions regarding surveillance and gonadectomy should balance tumor risk with endocrine function, fertility potential, psychosocial aspects, and patient autonomy. Long-term multidisciplinary follow-up in specialized DSD centers remains essential.