Histopathological features of Proteus syndrome.

ABSTRACT

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. 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 regard to descriptive features of the underlying tissue abnormality. RESULTS: There were 18 surgical specimens from nine patients, median age 4 years (range 1-9), classified into four main categories soft-tissue swellings (lipomatous lesions), vascular anomalies (vascular malformation and haemangioma), macrodactyly (hamartomatous overgrowth) and others (sebaceous naevus and nonspecific features). In all cases, the clinical features of overgrowth were due to increased amounts of disorganized 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.