PTEN hamartoma of soft tissue (PHOST) and fibroadipose vascular anomaly (FAVA): a comparative clinicopathologic and molecular analysis.

PTEN hamartoma of soft tissue (PHOST) is a rare entity within the PTEN-related hamartoma tumor syndrome spectrum. It often presents with overlapping clinical features with other vascular anomalies, such as fibroadipose vascular anomaly (FAVA). While both conditions are characterized by intramuscular vascular anomalies, their underlying genetic mutations and histopathological features are distinct. This study aims to elucidate the genetic and clinicopathological characteristics of PHOST, and to compare it with FAVA, highlighting critical diagnostic features. We retrospectively reviewed all cases that underwent surgical treatment in our pathology database from 2021 to 2024 and selected 28 cases with complex vascular malformations, all of which tested negative for PIK3CA mutations by fluorescent quantitative PCR (qPCR). Subsequently, next-generation sequencing (NGS) was performed on these 28 cases to evaluate their mutation profiles. Comprehensive clinicopathological evaluations, including imaging, were conducted. Treatment outcomes and recurrence rates were analyzed during long-term follow-up. The histological and genetic findings were compared between PHOST and FAVA cases. PHOST typically presents with vascular nodules in a fibrous and adipocytic background. It features numerous small vessels resembling arteries and veins, along with indeterminate channels. The presence of larger vessels with arterial-to-venous transitions and thick-walled muscular vessels suggests arteriovenous shunting, a feature absent in FAVA. Unlike PHOST, FAVA cases predominantly harbored PIK3CA mutations and exhibited localized, low-flow vascular anomalies. Detecting PTEN gene mutations in complex vascular malformations is crucial for the accurate diagnosis of PHOST. This study underscores the importance of genetic testing and tailored therapeutic approaches for these rare vascular anomalies.