PIK3CA Mutational Analysis in Patients With Macrodactyly

• Published in: Pediatric and developmental pathology 2022-11, Vol.25 (6), p.624-634
• Main Authors: Becker, Jakob, Gross, Ulrike Camenisch, Weber, Daniel M, Weibel, Lisa, Theiler, Martin, Brandt, Simone, Bode, Peter K
• Format: Article
• Language: English
• Subjects: Class I Phosphatidylinositol 3-Kinases - genetics; Humans; Infant; Musculoskeletal Abnormalities - genetics; Mutation; Phosphatidylinositol 3-Kinases - genetics; Retrospective Studies
• ISSN: 1093-5266; 1615-5742
• DOI: 10.1177/10935266221080155

Background Somatic mosaicism for PIK3CA mutations causes various types of growth disorders, which have been summarized under the term PROS (PIK3CA related overgrowth spectrum). Targeted therapy with PI3K inhibitors seems to be a promising alternative for severe PROS cases. Therefore, PIK3CA testing may become more relevant in the future. Methods We report on 14 PROS patients, who had surgery for macrodactyly in the majority of cases. Clinical data were retrieved from the patient’s records. Macroscopic and microscopic findings were retrospectively reviewed. Mutational analysis was performed on formalin-fixed paraffin-embedded (FFPE) material. Results Patient age ranged from 7 months to 35 years. Five patients showed additional anomalies. One patient had CLOVES syndrome. The majority of the specimens were ray resections characterized by hypertrophic fat tissue. Overall, microscopy was subtle. The abnormal adipose tissue showed lobules exhibiting at least focally fibrous septa. In each case, we could detect a PIK3CA mutation. Conclusion Histology of affected fat tissue in PROS patients is overall nonspecific. Therefore, mutational analysis represents the key to the diagnosis, especially in unclear clinical cases. We demonstrated that FFPE material is suitable for PIK3CA testing, which can be considered as basis for targeted therapy with PI3K inhibitors.