PIK3CA Mutation in FAVA of Adults With Unusual Anatomical Localization

To the Editor: Fibroadipose vascular anomaly (FAVA) is a vascular anomaly categorized under “unclassified vascular anomalies” in the 2018 classification by the International Society for the Study of Vascular Anomalies. This anomaly consists of dysmorphic blood vessels (primarily venous, occasionally lymphatic) embedded within fibroadipose tissue that often extends intramuscularly, dissecting and separating bundles of striated muscle, frequently occupying almost the entire muscle. Although traditionally described in childhood and often localized to the muscles of the lower extremities, it is highly likely that FAVA has been overlooked in adults for a long time and has been mistakenly diagnosed as lipomas, angiolipomas, or hemangiomas. Recognizing this entity will undoubtedly lead to a more accurate understanding of FAVA's epidemiology and anatomical distribution in adults. In this context, we recently reported 2 cases of FAVA in adults in this same journal, presenting in atypical anatomical locations (for what is typically described in children): the temporal and pectoral muscles.1 However, at the time of publication, we were unable to investigate the presence of PIK3CA gene mutations in either case. Although PIK3CA mutations are not a requisite for FAVA diagnosis (the mutation is demonstrable in only approximately 70% of pediatric cases),2 its presence supports the diagnosis. Recently, we acquired the technical capability to investigate PIK3CA and AKT1 mutations in these 2 cases. The PIK3CA gene is implicated in several overgrowth syndromes, known collectively as PIK3CA-related overgrowth spectrum. AKT1 is another gene implicated in some overgrowth syndromes, such as Proteus syndrome.3 The molecular study was performed using the Idylla PIK3CA-AKT1 Mutation Assay. In the case of the FAVA located in the temporal muscle, a mutation in the PIK3CA gene was detected with a nucleotide change c.1258T>C (Cq C420R 31.9; ΔCq C420R 4.2), which led to a protein change p.Cys420Arg. No mutations were observed in AKT1. In the case of the FAVA in the pectoral muscle, despite repeating the mutational analysis twice, the result was invalid on both occasions. A possible explanation is that the material came from a paraffin block dated 2016, a time when formalin fixation in the department had not yet been standardized. These findings reinforce the notion that FAVA is also an adult pathology and that its locations are not necessarily similar to those described in children. Likely, the misdiagnosis of these lesions in adults has obscured the clinical and anatomical understanding of FAVA until now.