Paraganglioma and other tumour detection rates in individuals with SDHx pathogenic variants by age of diagnosis and after the age of 50

Objective: Patients with SDHx germline mutations (SDHA, AF2, B, C, D) are at risk for paragangliomas (PGLs), renal cell carcinoma and gastrointestinal stromal tumours. The aim of this study was to evaluate the age of SDHx tumour diagnosis in those with pathogenic variants (PVs), notably tumour detection after the age of 50 years.

Study design: Longitudinal retrospective observational analysis.

Patients: Individuals with SDHx PVs.

Measurements: Demographic, clinical, genetic, screening and tumour detection and treatment data were abstracted from the electronic medical record. Descriptive analysis was utilised.

Results: A total of 165 patients with SDHx PVs from 34 families were evaluated. Sixty-eight patients (41.2%) had at least one known SDHx-related tumour in their history, identified through symptoms, screening or incidentally. The average age of SDHx-related tumour diagnosis was 32.0 years. Age of diagnosis varied by the gene. Nine patients (n = 50; 18.0%) were identified with a tumour after the age of 50, identified via baseline screening after PV identification, or due to symptoms before molecular SDHx diagnosis.

Conclusions: Though tumours were identified in individuals above the age of 50; they were all identified on baseline screening or due to symptoms, confirming that baseline screening is essential. Given the slow-growing nature of PGLs, these tumours might have been discovered before age 50 if molecular diagnosis and baseline screening had occurred earlier. Considering discontinuing screening after age 50 may be warranted if baseline screen imaging is negative and the individual does not have a prior tumour history.