Two cases of eruptive vellus hair cysts associated with chronic renal failure are reported. Histologically the lesions of both cases showed cystic structures in the dermis lined by squamous epithelium which contained varying amounts of vellus hair shafts. Immunohistochemical studies using monoclonal anti-AGE (advanced glycation end product) antibody demonstrated that keratinous materials within the cystic structures were immunoreactive to the antibody, whereas those of cystic lesions (epidermal cyst, eruptive vellus hair cyst, steatocystoma multiplex, trichofolliculoma and trichilemmal cyst) seen in otherwise healthy individuals were negative. Because it has been reported that plasma and skin levels of AGE are elevated in renal failure patients, AGE-modified keratinous materials may be associated with the formation of cystic structures by stimulating the occlusion of the epithelium.
Pilomatricoma consists of the cells differentiating towards hair matrix cells. Immunohistochemical study revealed the deposition of type II collagen in the overlying dermo-epidermal junction (DEJ) of this benign tumor. Proalpha(1)(II) mRNA was detected by RT-PCR in the overlying epidermal layer but not in the dermal layer prepared from the lesional skin of pilomatricoma. The neutral salt-soluble proteins extracted from the tumor of pilomatricoma induced proalpha(1)(II) mRNA in the cultured human keratinocytes but not in the cultured dermal fibroblasts. Bone morphogenetic protein 2 or 4 (BMP2 or 4) was immunohistochemically detected in some shadow cells of pilomatricoma. Recombinant BMP2 and BMP4 were found to induce proalpha(1)(II) mRNA concentration dependently in the cultured human keratinocytes but not in the cultured fibroblasts. Proalpha(1)(II) mRNA induced by BMP2 and in cultured keratinocytes contained exon 2, indicating that the mRNA species is non-chondrogenic type IIA form. The results strongly suggest that BMP2 or 4 expressed in pilomatricoma is responsible for the induction of proalpha(1)(II) collagen mRNA in the overlying epidermal cells resulting in the deposition of type II collagen in the DEJ. When human keratinocytes were cultured on type II collagen substratum in vitro, the cell proliferation was accelerated at the early period of culture but was inhibited at the late period of culture, whereas the cell proliferation was persistently accelerated by type I or IV collagen substratum. Type II collagen deposition in the DEJ may potentially exert profound effects on keratinocyte proliferation and differentiation.
The expression of type II collagen in pilomatricoma is dependent upon the chronological stage of pilomatricoma. Type II collagen expression in the overlying DEJ and chondroid matrix in CMT may be induced by BMP via the same mechanism as in pilomatricoma.
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