Multiple segmental neurofibromatosis

Dear Editor, Neurofibromatosis (NF) is a genetically-inherited disorder in which nerve tissue gives rise to tumors. Riccardi classified NF into eight subtypes, based upon clinical manifestations, genetic transmission and prognosis. Segmental NF (neurofibromatosis type V) is a rare variant of NF in which café-au-lait macules and ⁄ or neurofibromas are confined to a circumscribed body segment. The affected area, however, can vary in size from a narrow strip to an area encompassing half of the body. Lesions are usually unilateral, although there are reports of bilateral segmental NF. We describe a patient who showed multiple segmental expressions of the disease. To our knowledge, this is the first case of multiple segmental NF. A 52-year-old woman presented with a 5-year history of asymptomatic skin lesions on the trunk and extremities. She had no medical illness and no family history of genetic skin tumors such as NF. Examination of the skin showed multiple, soft, dome-shaped, fleshcolored papules and nodules over circumscribed areas showing a multisegmental arrangement on the left back, and bilateral distribution on the abdomen, chest and extremities (Fig. 1). Café-au-lait macules, axillary freckling, Lisch nodules on the iris, spine scoliosis or muscular abnormalities were not observed. A detailed neurological examination revealed normal findings. A biopsy specimen from two nodules on the right arm showed typical features of neurofibroma with positive staining for S-100 protein (Fig. 2). A diagnosis of segmental NF was made based on the presence of neurofibromas in circumscribed body areas, lack of systemic involvement and negative family history. To date, more than 100 cases of segmental NF have been reported, and approximately 6% were bilateral. The age of onset of segmental NF shows a bimodal distribution, with peaks at 10–30 and 50–70 years. Females are affected twice as often as males, and the right side of the body is more commonly affected than the left (4:3). Areas that are predisposed to segmental NF are the thorax, abdomen, arms, lower limbs and face. Segmental NF lesions may be misdiagnosed as birth marks by physicians or ignored by patients because of their unusual and asymptomatic features. Segmental NF should be differentiated from certain similar-appearing lesions, such as soft fibroma, epidermal nevus and nevus lipomatosus cutaneous superficialis. In contrast to NF type I, systemic involvement and malignant transformation in segmental NF are uncommon. However, segmental NF was recently reported to be a paraneoplastic manifestation. Such malignancies include malignant peripheral nerve sheath tumor, malignant melanoma, breast cancer, colon cancer, gastric cancer and lung cancer. Segmental NF results from a post-zygotic mutation in the NF1 gene leading to somatic mosaicism. This concept of mosaicism explains the variety of clinical presentations of segmental NF, which may be predicted by the timing of the NF1 mutation, the particular lineage and the viability of the cells bearing the mutation. Our case is unique because the patient showed multiple segmental NF affecting multiple bilateral segments of the body. Therefore, we propose the name ‘‘multiple segmental NF’’ to describe this extremely rare variant of segmental NF.