Radiological evaluation of the natural history of PIK3CA-related overgrowth spectrum (PROS)

PIK3CA-related overgrowth spectrum (PROS) comprises a heterogeneous group of disorders caused by postzygotic activating variants in PIK3CA, leading to mosaic activation of the PI3K pathway. The natural history of PROS is highly variable and depends on the timing and distribution of the somatic mutation. To better characterize its radiological progression, we analyzed a cohort of patients with PROS.

This multicenter study was conducted at Hôpital Femme Mère Enfant (Lyon) and Hôpital Necker-Enfants Malades (Paris). Pediatric and adult patients with a confirmed PIK3CA variant and at least two MRI examinations performed ≥ 2 months apart were included. Patients who underwent interventional surgical or radiological procedures, or who received targeted therapies, were excluded. Target lesions were identified on baseline MRI and evaluated on follow-up scans according to RECIST criteria.

Among 67 PROS patients screened between 2008 and 2021, 30 met the inclusion criteria, including 43.3 % children (13/30) and 43.3 % females (13/30). The median age at first MRI was 19 years (interquartile range 5-34). Lesions involved the head and neck region (10/30), trunk and upper limbs (10/30), and lower limbs (10/30), with some patients presenting multisite involvement. Over a median follow-up of 75.7 months (range 2.1-160.3), 83.3 % (n = 25) of patients had progressive disease, with a median increase of 36.6 % in lesion size (range 2.6-230.7 %) and a median annualized growth rate of 7.2 %/year (range 0.6-40.1 %).

This study provides the first radiological description of PROS natural history, showing that tissue malformations generally enlarge over time and often continue progressing into adulthood.