Low risk of embryonic and other cancers in <i>PIK3CA</i><scp>‐related</scp> overgrowth spectrum: Impact on screening recommendations
Laurence Faivre, J Crépin, Manon Réda, Sophie Nambot, Virginie Carmignac, Caroline Abadie, Tristan Mirault, Cécile Faure‐Conter, J. Mazereeuw‐Hautier, Aude Maza, E. Puzenat, Marie‐Agnès Collonge‐Rame, A.‐C. Bursztejn, Christophe Philippe, Christel Thauvin‐Robinet, Martin Chevarin, C. Abasq‐Thomas, Jeanne Amiel, Stéphanie Arpin, S. Barbarot, Geneviève Baujat, D. Bessis, E. Bourrat, Odile Boute, Nicolas Chassaing, Christine Coubes, Bénédicte Demeer, Patrick Edery, Salima El Chehadeh, Alice Goldenberg, S. Hadj‐Rabia, Damien Haye, Bertrand Isidor, Marie‐Line Jacquemont, Philippe Khau Van Kien, Didier Lacombe, Daphné Lehalle, Laëtitia Lambert, Ludovic Martin, A. Maruani, Fanny Morice‐Picard, Florence Petit, Alice Phan, Lucile Pinson, Massimiliano Rossi, Renaud Touraine, Clémence Vanlerberghe, Marie Vincent, Catherine Vincent‐Delorme, Sandra Whalen, Marjolaine Willems, Nathalie Marle, Virginie Verkarre, Christine Devalland, Mojgan Devouassoux‐Shisheboran, Marine Abad, Nathalie Rioux‐Leclercq, B. Bonniaud, Yannis Duffourd, Jéhanne Martel, Christine Binquet, Paul Kuentz, P. Vabres
Abstract
The PIK3CA-related overgrowth spectrum (PROS) encompasses various conditions caused by mosaic activating PIK3CA variants. PIK3CA somatic variants are also involved in various cancer types. Some generalized overgrowth syndromes are associated with an increased risk of Wilms tumor (WT). In PROS, abdominal ultrasound surveillance has been advocated to detect WT. We aimed to determine the risk of embryonic and other types of tumors in patients with PROS in order to evaluate surveillance relevance. We searched the clinical charts from 267 PROS patients for the diagnosis of cancer, and reviewed the medical literature for the risk of cancer. In our cohort, six patients developed a cancer (2.2%), and Kaplan Meier analyses estimated cumulative probabilities of cancer occurrence at 45 years of age was 5.6% (95% CI = 1.35%-21.8%). The presence of the PIK3CA variant was only confirmed in two out of four tumor samples. In the literature and our cohort, six cases of Wilms tumor/nephrogenic rests (0.12%) and four cases of other cancers have been reported out of 483 proven PIK3CA patients, in particular the p.(His1047Leu/Arg) variant. The risk of WT in PROS being lower than 5%, this is insufficient evidence to recommend routine abdominal imaging. Long-term follow-up studies are needed to evaluate the risk of other cancer types, as well as the relationship with the extent of tissue mosaicism and the presence or not of the variant in the tumor samples.