Bowen disease on the foot associated with HPV

A 94 years old Japanese female was presented to our hospital with a skin lesion on her left foot. A physical examination found a markedly hyperkeratotic reddish-brown plaque, measuring 3 cm in diameter. A biopsy specimen showed prominent papillomatosis, hyperkeratosis, and atypical keratinocytes throughout the epidermis. Individual cell keratinization, multinucleated keratinocytes, and many keratinocytes with clear cytoplasm were seen. We excised the lesion, and the skin grafting was used for covering the skin defect. We investigated whether human papillomavirus (HPV) was present in the lesion, and HPV 16 DNA was detected using the polymerase chain reaction. Immunohistochemical analysis showed several HPV-positive cells in the upper epidermis. In addition, the tumor cells showed strong and diffuse expression of p16INK4a. Bowen disease (BD) is an intraepidermal squamous cell carcinoma. The precise pathogenesis of BD is unclear, but it involves various factors. HPV infection is one of these factors and is a well-known cause of BD of the genitalia and fingers. It has been shown that some BD lesions occurring at other locations are also associated with HPV. Dysregulation of the Rb / p16INK4a pathway is considered to play an important role in HPV-induced BD, but the precise mechanism remains to be elucidated

Molecular carcinogenesis of squamous cell carcinomas of the skin

Squamous cell carcinomas (SCCs) of the skin were suggested to develop through a multistep process that involves activation of proto-oncogenes and/or inactivation of tumor suppressor genes in the human skin keratinocytes. Exposure to ultra-violet (UV), especially UV-B, radiation is the most common cause for these genetic abnormalities in cells. We review causation of SCCs and genetic abnormalities in human SCCs with the current work. To elucidate the multistep process, we developed a method for examining the combinatorial function in vivo of plural genes in human keratinocytes. Using high efficiency retroviral transductions, we could express plural genes serially in normal human primary keratinocytes and use these cells to regenerate human skin on SCID mice. A combinatorial transduction of H-RasV12 and cyclin dependent kinase 4 (CDK4) produced human epidermal neoplasia resembling SCC. These findings were consistent with our previous results of mutation analysis in SCCs, one of which had both mutations of H-Ras gene and the INK4a locus. Therefore, it is suggested that a combination of these genetic abnormalities might be crucial to the carcinogenesis at least in a subset of SCCs

The involvement of fibroblast growth factor receptor signaling pathways in dermatofibroma and dermatofibrosarcoma protuberans

Fibroblast growth factors (FGFs) and their receptors (FGFRs) control a wide range of biological functions ; however, their involvement in the pathogenesis of dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) is currently unknown. In this study, we first confirmed the histological diagnosis by detecting fusion COL1A1-PDGFB transcripts in DFSP, and examined the expression of all FGFRs (FGFR1-4), some of their ligands (FGF1, 2, 9), and forkhead box N1 (FOXN1) as a downstream target of FGFR3 in DF and DFSP by immunohistochemical analysis. Although we failed to detect the expression of FGF1 and FGF9 as specific ligands for FGFR3 in DF, overexpression of FGFR3 and FOXN1 was observed in the epidermal regions of DF, suggesting that the epidermal regions of DF were similar to seborrhoeic keratosis both in terms of histological features and the activation of FGFR3/FOXN1. In addition, strong expression of FGF2 and FGFR4 was observed in the tumor lesions of DF. Expression patterns of FGFR3/FOXN1 and FGF2/FGFR4 in DF were in contrast with those of DFSP. The activation of FGFR signaling pathways may be not only relevant to the pathogenesis of DF, but also very useful in the differential diagnosis of DF and DFSP

Effect of biopsy on survival of melanoma patients

Background Cutaneous malignant melanoma has a poor prognosis. The detrimental effect of incisional biopsies on the outcome of malignant melanoma has been debated. The aim of this study was to determine the effect of the presence and type of biopsy on the prognosis of malignant melanoma. Methods The medical records of 109 malignant melanoma patients treated at Tokushima University Hospital from 1983 to 2007 were reviewed. After excluding 28 cases with stage 0 disease or incomplete data, 81 cases were analyzed in detail with respect to patient sex, age, tumor site, clinical stage at diagnosis, presence of ulceration or lymph node metastasis, and prognosis. The five-year survival and five-year disease-free survival rates of patients who underwent incisional or excisional biopsies were compared with those who did not undergo a biopsy. Results The male-to-female ratio was 1:1.19. The mean age was 61.3 years (range, 19–93 years). The most common site was a lower extremity, and the most common clinical stage was stage II. No significant differences in clinicopathological features, five-year survival rates, and five-year disease-free survival rates were observed among the three groups. Conclusions The presence and type of biopsy neither affected the metastatic rate nor the prognosis of malignant melanoma. The use of incisional biopsies is not encouraged because tumor thickness cannot be measured accurately. However, they may be helpful for confirming the diagnosis if an excisional biopsy cannot be performed

Resin splint as a new conservative treatment for ingrown toenails

Several conservative as well as surgical methods are used for the treatment of ingrown toenails until date. The conservative methods are either based on nail splinting or on orthonyxia, but no methods employing both principles have been reported thus far. Moreover, surgical methods usually involve postoperative pain, prolonged wound healing and restricted activities of daily living. Therefore, considering the need of a simplified, non-invasive method, in this study, we applied a novel splint to treat patients with ingrown toenails and estimated the clinical efficacy as well as rate of recurrence following treatment. The splint is a plate made of resin that is attached to the lateral edge of the nail using a bandage. We studied 61 patients (19 men and 42 women ;mean age 36 years), with an average application duration of 9.3 months and an average follow-up period of 10 months in all patients. All patients experienced pain relief within a week of splint application and a decrease in the degree of nail deformity. Moreover, follow-up revealed a recurrence rate of 8.2%. Therefore, we believe that this new device is an excellent conservative treatment method for patients with ingrown toenails

トコズレ ノ ザイタク ケア

A large proportion of home care patients are at risk of pressure ulcer. The occurrence rate of pressure ulcer is higher in home care patients than that in the patients of hospitals and welfare facilities. The home care patients need long-term conservative treatment because of the depth of the pressure ulcers.Treatment of the pressure ulcers at home results in increase of caregivers burden. Therefore,prevention and early detection of pressure ulcers are important in home nursing. In early stage of pressure ulcers，“deep tissue injury”should be taken into consideration because of its progressive nature. It is a new concept which presents deep tissue damage remaining superficial skin intact.One of clinical features in this condition is induration in a deep layer.The past decade has seen a huge growth in the application of pressure relieving mattresses,absorbent products for urinary and faecal incontinence, and skin barrier products to prevention of the pressure ulcers. Economical, physical, and psychological burden of nursing at home should be decreased with an accumulation of these information and utilization of the products. Therefore, it is important for caregivers to consult with their care managers and acquire new knowledge and information

Molecular tumorigenesis of the skin

Skin tumors are supposed to develop through accumulations of genetic and/or epigenetic events in normal cells of the skin. Among them, we focus on common skin tumors, including benign, seborrheic keratosis, and malignant, squamous cell carcinoma and melanoma. Many important molecules have been detected on the molecular tumorigenesis of each of them to date, and some drugs targeted for their molecules have been already developed. We review updates on the molecular tumorigenesis of these tumors with our current works