Occult neurofibroma and increased S100 protein in the skin of patients with neurofibromatosis type 1 - New insight to the etiopathomechanism of neurofibromas

Background: Neurofibromas represent proliferation of the connective tissue cells of peripheral nerves and deposition of collagenous extracellular matr ix. There is evidence that the appearance and growth of neurofibromas may h e associated with prior or ongoing mechanical trauma in patients with neuro fibromatosis type 1 (NF1). Objective: To study the histologic characteristics of apparently healthy sk in of patients with NF1. Design: The histologic features of healthy-looking skin of patients with NF 1 were analyzed. Setting: University hospital. Patients: Ten patients who fulfilled the criteria for NF1. Interventions: Punch biopsy specimens of healthy-looking skin of the forear m from 9 volunteer patients and of the upper eyelid during cosmetic operati on from 1 volunteer patient were obtained. Main Outcome Measures: The main outcomes were not predicted, and the hypoth esis was formulated during data collection. Results: Apparently unaffected skin of 5 patients with NF1 was studied by r outine histologic testing with respect to expression of S100 protein. Unexp ectedly, analysis of the samples revealed the presence of a small neurofibr oma tumor in one of the samples. The tumor was located in deep dermis aroun d a hair follicle. In addition, neurofibromatous tissue not large enough to be called a tumor was found on the same anatomical location in another pat ient. In further studies, 10 punch biopsy specimens of apparently healthy s kin from patients with NF1 were similarly sectioned and analyzed. No tumors were found in these additional samples. In 4 patients, however, abundant S 100 protein-positive cells were located within collagenous extracellular ma trix surrounding hair follicles. Conclusions: The skin of patients with NF1 might be more widely affected th an previously thought and occult neurofibromas are not rare.