Background: Proteus Syndrome is a rare, sporadic overgrowth disorder for which the underlying genetic defect remains unknown. Although the clinical course is well-described, there is no systematic histopathological description of the lesional pathology.

Objective: To describe the histopathological features encountered in a series of patients with Proteus syndrome from a single centre.

Patients/Methods: Patients with Proteus syndrome who had undergone therapeutic surgical resection or biopsy were identified from a database and the histopathological findings were reviewed, with particular reference to descriptive features of the underlying tissue abnormality.

Results: There were 18 surgical specimens from nine patients, median age 4 (range 1–9) years, including four main categories; soft tissue swellings (lipomatous lesions), vascular anomalies (vascular malformation and haeman-gioma), macrodactyly (hamartomatous overgrowth) and others (sebaceous naevus and non-specific features). In all cases the clinical features of overgrowth were due to increased amounts of disorganised tissue, indicating a hamartomatous-type defect in which normal tissue constituents were present but with an abnormal distribution and architecture. Vascular malformations represented a prominent category of lesions, accounting for 50% of the specimens, predominantly comprising lymphatic and lymphovascular malformations. No malignancy or cytological atypia was identified in any case.

Conclusions: The histopathological features of lesions resected from children with Proteus syndrome predominantly include hamartomatous mixed connective tissue lesions, benign neoplasms such as lipomata and lymphatic-rich vascular malformations.