Dermal neurofibromas in von Recklinghausen's disease (vRD) arise after puberty. Subjects with multiple dermal neurofibromas do not frequently present with giant plexiform neurofibromas. Therefore, we hypothesized that a niche may exist that promotes the development of dermal neurofibroma in subjects with vRD and multiple dermal neurofibromas. To test this, we performed immunohistochemistry to examine various proteins expressed in dermal samples. We observed strong staining for polydom in the dermis surrounding dermal neurofibromas. Interestingly, there was a sex difference in the signal intensity of polydom. The expression of integrin α9, a possible candidate receptor for polydom, was similar between samples from vRD with dermal neurofibroma and disease control skin, indicating that another receptor might be involved. To assess the expression level of polydom quantitatively, primary cultured cells were prepared from dermal neurofibroma, and the levels of polydom mRNA were evaluated by quantitative PCR. Polydom mRNA was significantly higher in primary cultured cells derived from neurofibroma compared to normal human dermal fibroblast. These results suggest that the increased expression of polydom in the dermis surrounding neurofibromas may lead to the development of dermal neurofibromas.

Exploring the niche of dermal neurofibroma in von Recklinghausen's disease: evidence for the involvement of polydom