A Case of Multifocal Venous Malformation With Two Somatic Pathogenic Variants in the TEK Gene

Multifocal venous malformation (VM) is a rare vascular disorder characterized by multiple cutaneous and visceral venous malformations caused by somatic variants in the TEK gene, which encodes the TIE2 receptor. We report a 30-year-old man presenting with multiple subcutaneous nodules and oral lesions. MRI revealed multiple masses around the left scapula. A biopsy from a lumbar lesion showed dilated venous channels, and immunohistochemistry was positive for CD31. There was no evidence of anemia. Genetic analysis using next-generation sequencing of both skin and blood identified two somatic TEK variants, p.(Tyr897Cys) and p.(Arg918His), restricted to the lesion tissue. Bulk phasing analysis revealed that Y897C and R918H existed both as single variants and as double variants in cis. The absence of these variants in blood confirmed their somatic origin. Based on clinical and pathological findings, the patient was diagnosed with multifocal VM. Clinically, this case resembled multifocal sporadic VM; however, the genetic profile was consistent with blue rubber bleb nevus syndrome, suggesting this case may represent an intermediate phenotype between the two entities. The involvement of the PI3K/AKT/mTOR signaling pathway implies potential therapeutic benefit from mTOR inhibitors, such as sirolimus. Close follow-up is ongoing due to progressive oral involvement.