Nestin, a marker of neural stem cells, is expressed in hair follicle stem cells. The nestin-expressing hair follicle stem cells in mice and humans that are negative for the keratinocyte marker keratin 15 (K15) can differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes. Recent studies suggest that epithelial stem cells are important in tumorigenesis. Previous reports have also suggested that nestin-expressing hair follicle stem cells are undifferentiated and pluripotent and that nestin expression in some tumors indicates poor differentiation and a high grade of malignancy. We immunohistochemically examined the expression of three hair follicle stem cell and progenitor cell markers, nestin, K15, and CD34, in epidermal and follicular tumors, trichilemmoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). In these tumor tissues, nestin immunoreactivity was observed in trichilemmoma but not in BCC or SCC. Furthermore, K15 immunoreactivity was strong in BCC, weak in trichilemmoma, and only partially positive in SCC tissues. No CD34 immunoreactivity was observed in any of the tissues. These results suggest that trichilemmoma originates in the nestin-positive/K15-positive/CD34-negative outer-root sheath cells below the sebaceous glands, and that BCC tumor cells originate in the more mature nestin-negative/K15-positive/CD34-negative outer-root sheath cells. The keratinocyte growth and differentiation switch, which is tightly regulated by several mechanisms, is generally associated with decreased proliferation, cell cycle arrest in the G0/G1 phase, and expression of epidermal differentiation markers such as involucrin. We studied keratinocyte switching from a proliferating to a differentiated state by assaying nestin expression in a normal human keratinocyte and a trichilemmoma cell line. Because culture conditions can play a role in changes in cellular responses, the cells were cultured in a medium specific for keratinocyte growth. For Ca2+ induction, keratinocytes were treated with media containing Ca2+ at either a concentration of 2.8 or 0.03 mM. At low Ca2+ concentration, FACS and RT-PCR analysis revealed an increase in the expression of the stem cell marker nestin and a decrease in the differentiation marker involucrin. These results suggest that nestin-expression in skin tumor cells is an important marker of the undifferentiated state. We have shown that nestin is a marker of HMB-45-negative melanoma cells in dermal invasive lesions of nodular malignant melanoma. We examined nestin expression in malignant melanoma and investigated the relationship between nestin expression and prognosis in patients. The 5-year survival rate of stage I and II nestin-positive cases was significantly decreased compared to the nestin-negative cases. These results suggest that nestin expression is a predictor of poor prognosis in patients with malignant melanoma. In addition, we identified HPV-DNA in Bowen’s disease (BD) and Bowen’s carcinoma (BC) by in situ hybridization analysis and determined nestin expression by immunohistochemical staining. We detected HPV-DNA in 68% of BD and in 87% of BC. Nestin expression was statistically higher in the BC group than in the BD group. These results suggest that HPV-DNA was integrated into the genome of tumor cells from patients with these diseases and contributed to malignant alternation.
We assessed the clinical features of 66 patients with pustulosis palmaris et plantaris who visited our hospital from January through May of 2010. Twenty-one patients were men and 45 were women. For the evaluation of tonsillectomy, improvement of skin lesions was classified into 4 grades; remarkably improved, improved, slightly improved and unchanged. The rate of improvement (remarkably improved and improved) by standard treatments other than tonsillectomy were 41.2% (21/51). The rate of improvement after tonsillectomy was 53.3% (8/15), but the rate of improvement of arthropathy was 16.7% (1/6). Tonsillectomy is considered as a helpful treatment for moderate to severe cases with pustulosis palmaris et plantaris.
We measured 3-month outcomes of surgical therapy for varicose veins in 38 legs between October 2008 and September 2009. We used the venous clinical severity score (VCSS), the visual analog scale (VAS), and duplex ultrasound (DU) scanning to evaluate outcomes. For flow reversal via the sapheno-femoral junction, partial stripping or high ligation was performed. For the flow reversal via the sapheno-popliteal junction, high ligation was performed. Insufficient perforating veins were interrupted under direct or endoscopic visualization. Saphenous varicose veins in all legs were treated with foam sclerotherapy. Thirty-two legs (84%) showed satisfactory progress, but 6 did not (16%). Their VCSS and VAS after surgery did not improve, and DU scanning revealed that reverse flow remained from the deep vein to the saphenous varicose vein via insufficient perforating veins. All cases were classified as C4 in the CEAP classification and had severe stasis dermatitis. The cause of failure was determined to be incomplete treatment of reverse flows via insufficient perforating veins. Insufficient perforating veins and deactivation of the sclerosing agent caused by reverse flow led to the survival of varicose veins. In cases with severe stasis dermatitis, complete treatment of reverse flows in combination with form sclerotherapy is important.
Recently, epidermal growth factor receptor (EGFR) inhibitors have been approved for treating non-small cell lung cancer and metastatic colon cancer. These targeted therapies are less harmful to normal cells, but dermatological toxicities, including paronychia, occur in very high incidence. We utilized a simple bandage type device in four cases with paronychia during anti-EGFR therapy and succeeded in resolving their symptoms.