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 matrix. There is evidence that the appearance and growth of neurofibromas may be associated with prior or ongoing mechanical trauma in patients with neurofibromatosis type 1 (NF1). OBJECTIVE To study the histologic characteristics of apparently healthy skin of patients with NF1. DESIGN The histologic features of healthy-looking skin of patients with NF1 were analyzed. SETTING University hospital. PATIENTS Ten patients who fulfilled the criteria for NF1. INTERVENTIONS Punch biopsy specimens of healthy-looking skin of the forearm from 9 volunteer patients and of the upper eyelid during cosmetic operation from 1 volunteer patient were obtained. MAIN OUTCOME MEASURES The main outcomes were not predicted, and the hypothesis was formulated during data collection. RESULTS Apparently unaffected skin of 5 patients with NF1 was studied by routine histologic testing with respect to expression of S100 protein. Unexpectedly, analysis of the samples revealed the presence of a small neurofibroma tumor in one of the samples. The tumor was located in deep dermis around a hair follicle. In addition, neurofibromatous tissue not large enough to be called a tumor was found on the same anatomical location in another patient. In further studies, 10 punch biopsy specimens of apparently healthy skin from patients with NF1 were similarly sectioned and analyzed. No tumors were found in these additional samples. In 4 patients, however, abundant S100 protein-positive cells were located within collagenous extracellular matrix surrounding hair follicles. CONCLUSIONS The skin of patients with NF1 might be more widely affected than previously thought and occult neurofibromas are not rare.