異型静脈奇形 - 他の良性軟部腫瘍を模倣する皮下型：小児症例シリーズ

Verrucous venous malformation (VVM) is a rare, congenital, slow-flow vascular anomaly typically involving the dermis and epidermis, with progressive verrucous changes. A recently recognized subcutaneous variant (VVM-SC), which lacks cutaneous involvement, challenges current nomenclature and presents diagnostic difficulties in pediatric patients.

To describe the clinical, imaging, histopathological, and molecular features of VVM-SC and highlight diagnostic pitfalls and implications for classification.

This case series includes three paediatric patients (ages 8-16 years) evaluated between 2021 and 2025 at a tertiary referral center. All presented with well-demarcated, painless subcutaneous nodules without overlying skin changes. Clinical and imaging assessments favored benign soft tissue tumors, including lipomas and infantile haemangiomas. One patient received pharmacologic treatment based on a presumptive diagnosis of haemangioma. All lesions were surgically excised and evaluated using histopathology, immunohistochemistry, and targeted next-generation sequencing.

All lesions were solitary, skin-coloured or bluish subcutaneous nodules, lacking epidermal alteration. Imaging findings were non-specific and misleading. Histopathology revealed lobular proliferations of dilated, congested venous channels within fibrous stroma, sparing the dermis and epidermis. One case exhibited focal perieccrine and subepidermal vascular congestion without epidermal hyperplasia. Immunohistochemical analysis showed diffuse CD31 and CD34 positivity, focal GLUT-1 expression, and negativity for D2-40, consistent with a venous phenotype. All cases harbored the recurrent somatic MAP3K3 c.1323C>G (p.Ile441Met) mutation, confirming the diagnosis of VVM-SC. Surgical excision was curative in all patients, with no recurrence observed during follow-up.

Subcutaneous VVM lacks the hallmark superficial features of classical VVM and may mimic other paediatric soft tissue tumors, such as lipomas or haemangiomas, leading to diagnostic error and unnecessary treatment. Despite sharing the same MAP3K3 mutation, these lesions differ in depth, clinical presentation, and behavior. We propose reconsidering the terminology, suggesting "cutaneous MAP3K3-related slow-flow vascular malformation" to encompass both superficial and subcutaneous variants. Recognition of this phenotype and its defining features, including focal GLUT-1 expression and MAP3K3 mutation, can support accurate diagnosis and reduce the risk of overtreatment. Further studies are needed to determine whether subcutaneous variants differ in recurrence risk, natural history, or systemic associations.