Actinic keratoses show variable histological basal growth patterns - a proposed classification adjustment

Background: Common histological classification schemes of actinic keratoses (AK) do not evaluate growth patterns at basal epidermal aspects of AK. Until now, the importance of basal epidermal growth patterns of AK has not been studied. Objective: To investigate the extent of atypical keratinocytes throughout the epidermis and variation in basal growth patterns of AK. Methods: AK lesions occurring on the head/face from patients seen in routine practice were assessed histologically. We determined histological grade (AK I-III), basal growth patterns of atypical keratinocytes (crowding, budding, papillary sprouting) and accompanying parameters. Results: Of the 246 lesions included, 28.0% were histologically classified as AK I, 46.7% as AK II, and 25.2% as AK III. 26.4% of the basal growth patterns were classified as crowding (pro I), 49.6% as budding (pro II), 17.9% as papillary sprouting (pro III) and 6.1% without basal directed growth. No significant correlation of the histological AK I-III grading and underlying growth patterns was observed (P= 0.4666). However, adnexal structure involvement (OR= 2.37; 95%CI 1.21-4.65), infiltration (OR= 2.53; 95%CI 1.31-4.90) and increased number of vessels (OR= 2.56; 95%CI 1.42-4.65) were independent positive predictive markers for pro II and pro III basal growth patterns. Conclusions: Basal growth patterns (pro I-III) in AK do not correlate with the established AK I-III histological grading system. Besides the degree of upward extension, varying degrees of downward extension exist. Histological classification should consider both, upwards and downward growth patterns when assessing AK

Primary merkel cell carcinoma clinically presenting as deep oedematous mass of the groin

Merkel cell carcinoma (MCC) is a relatively rare, polyomavirus associated, primary neuroendocrine carcinoma of the skin which is usually arising from dermal skin layers. However, the origin of MCC in the subcutaneous tissue is debatable. We report a 58-yearold female patient with an oedematous mass on her left groin that was firm in consistency and had no discoloration or other visible abnormality of the overlying skin. On histology and immunohistology the tumour was consistent with the diagnosis of MCC showing a predominant subcutanous growth pattern. Pelvic magnetic resonance tomography revealed a tumour conglomerate reaching from the subcutis of the left groin to the left paraaortal and parailiacal region indicating widespread lymphogenic metastisation. Despite complete medical work-up no other MCC primary could be detected. In conclusion, predominant subcutaneous growth pattern as well as tumour localization in the groin are uncommon features of MCC. MCC showing the aforementioned features may be associated with significant delay of diagnosis and therefore represents an unfavourable prognostic factor

Actinic keratosis area and severity index (AKASI) is associated with the incidence of squamous cell carcinoma

Background: Actinic keratoses (AKs) are commonly diagnosed clinically. Actinic keratosis area and severity index (AKASI) is a new easy-to-use tool to assess the severity of AK on the head. Objective: To determine the association between chronically UV-induced tumours such as basal cell carcinomas (BCC) or squamous cell carcinomas (SCC) and AKASI. Methods: We performed a retrospective analysis of patients who had undergone oncological surgery due to UV-induced tumours and who were assessed for AKASI and Physician's Global Assessment (PGA) prior to surgery. Statistical analysis was performed to evaluate correlation between AKASI, PGA and invasive carcinomas. Results: Of the 210 patients included, 26 patients had histologically diagnosed SCCs and presented with a median (range) AKASI of 6.9 (0 – 13.0) and PGA of 2 (0 - 4). In contrast, the 82 patients with BCCs showed a median (range) AKASI of 3.3 (0 -15.2) and PGA of 1 (0 - 4). The Mann-Whitney U test showed significant differences (p= 0.0018) between AKASI of patients with SCC and BCC. In addition, we found a significantly higher AKASI in patients with SCC compared to patients with non-invasive lesions like AK and Bowen disease (BD) (p= 0.0275). Spearman's coefficient of rank correlation between AKASI and PGA indicates that these measures of AK severity were strongly correlated (p< 0.0001; r = 0.90; 95%CI 0,865 to 0,920). Conclusions: Patients with SCC show significantly higher AKASI than patients with BCC or patients without invasive tumours. Hence, AKASI may be used to stratify risk for developing invasive SCC

Ultraviolet A1 Phototherapy for Fibrosing Conditions

In this article we describe efficacy and safety aspects of ultraviolet A1 (UV-A1) phototherapy in fibrosing conditions. UV-A1 is a specific phototherapeutic modality that is defined by a selective spectral range (340–400 nm). UV-A1 includes distinct modes of action qualifying this method for therapy of a variety of conditions, in particular fibrosing skin diseases. Concerning efficacy of UV-A1 phototherapy in fibrosing conditions, the best evidence obtained from randomized controlled trials exists for localized scleroderma. Moreover, fibrosing disorders such as lichen sclerosus and graft-vs.-host disease can be treated successfully by means of UV- A1. Regarding the optimal dosage regimen medium-dose UV-A1 seems to be linked to the best benefit/risk ratio. Possible acute adverse events of UV-A1 phototherapy include erythema and provocation of photodermatoses. Skin ageing and skin cancer formation belong to the chronic adverse events that may occur after long-term UV-A1 phototherapy

Modulation of cathepsin G expression in severe atopic dermatitis following medium-dose UVA1 phototherapy

BACKGROUND: During the last decade, medium-dose UVA1 phototherapy (50 J/cm(2)) has achieved great value within the treatment of severe atopic dermatitis (AD). The purpose of our study was to investigate to what extent UVA1 irradiation is able to modulate the status of protease activity by the use of a monoclonal antibody labeling cathepsin G. METHODS: In order to further elucidate the mechanisms by which medium-dose UVA1 irradiation leads to an improvement of skin status in patients with AD, biopsy specimens from 15 patients before and after treatment were analyzed immunohistochemically for proteolytic activation. RESULTS: Compared to lesional skin of patients with AD before UVA1 irradiation, the number of cells positive for cathepsin G within the dermal infiltrate decreased significantly after treatment. The decrease of cathepsin G(+) cells was closely linked to a substantial clinical improvement in skin condition. CONCLUSIONS: In summary, our findings demonstrated that medium-dose UVA1 irradiation leads to a modulation of the expression of cathepsin G in the dermal inflammatory infiltrate in patients with severe AD. Cathepsin G may attack laminin, proteoglycans, collagen I and insoluble fibronectin, to provoke proinflammatory events, to degrade the basement membrane, to destroy the tissue inhibitor of metalloproteinases and to increase the endothelial permeability. Therefore, its down-regulation by UVA1 phototherapy may induce the reduction of skin inflammation as well as improvement of the skin condition

Cutaneous squamous cell carcinomas are associated with basal proliferating actinic keratoses

Background: In addition to the extent of atypical keratinocytes throughout the epidermis, actinic keratoses (AKs) are histologically characterized by downward directed basal layer expansion. It is not known if this growth pattern correlates with the risk of developing invasive squamous cell carcinoma (iSCC). Objective: To characterize the prevalence of downward directed basal layer expansion of AKs adjacent to iSCC. Methods: The epidermis overlying and adjacent to iSCCs was assessed histologically. We determined the histological grade (AKI‐III), basal growth pattern (PROI‐III) and accompanying parameters such as adnexal involvement. Results: Of 307 lesions, 52.4% of AKs were histologically classified as AKI, 38.1% as AKII, and 6.8% as AKIII (chi‐squared; P<0.0001). 2.6% of adjacent epidermis did not show any atypical keratinocytes. The epidermis adjacent to iSCCs was classified as having a PROI basal growth pattern in 25.7%, PROII in 31.9%, and PROIII in 39.4% cases. 2.9% of AKs showed no basal growth (chi‐squared; P<0.0001).118 (48.8%) AKs showed extension into adnexal structures. These AKs were graded as PROI in 18.6%, PROII in 30.5%, and PROIII in 50.8%. The epidermis above iSCCs could only be assessed for upwards directed growth and showed no significant differences in the three AK grades (P=0.4211). Conclusions: Basal proliferative AKs as well as atypical keratinocytes restricted to the lower third of the epidermis are most commonly seen adjacent to iSCC with less evidence for full thickness epidermal dysplasia. Our study supports the important role of dysplastic keratinocytes in the epidermal basal layer and their potential association with iSCC

Protection against ultraviolet radiation by commercial summer clothing: need for standardised testing and labelling

BACKGROUND: The use of clothing as a means of sun protection has been recommended in recent education campaigns. Contrary to popular opinion, however, some fabrics provide insufficient ultraviolet (UV) protection. MATERIAL AND METHODS: We investigated 236 apparel textiles of the spring/summer collections 2000 and 2001. In accordance with the forthcoming European standard the UV protection factor (UPF) of the fabrics was determined spectrophotometrically. RESULTS: Seventy-eight (33%) fabrics had UPF < 15, 45 (19%) had UPF = or > 15 and < 30, and 113 (48%) had UPF = or > 30 (30+). More than 70% of the wool, polyester, and fabric blends, and only less than 30% of the cotton, linen, and viscose fabrics had UPF values of 30+. Fabrics with black, navy-blue, white, green, or beige colours provided most frequently UPF values of 30+. CONCLUSIONS: It is difficult for the sun-aware consumer to choose the 'right' garment, with a third of summer clothing providing insufficient UV protection and only half of the fabrics having UPF 30+, the UPF recommended by the European standard. Therefore, apparel summer fabrics should be measured and labelled in accordance with a standard document

Impact of UVA exposure on psychological parameters and circulating serotonin and melatonin

BACKGROUND: People tend to feel better after exposure to ultraviolet (UV) radiation. This study was performed to investigate the impact of UVA exposure on psychological and neuroendocrine parameters. METHODS: Fifty-three volunteers were separated into 42 individuals who had UVA exposure and 11 individuals who had no UVA exposure. The UVA-exposed volunteers had irradiation sessions six times in a three-week period. All volunteers completed two questionnaires at baseline (T1) and at the end of the study (T3). For the determination of serotonin and melatonin serum levels of all volunteers blood samples were collected at baseline (T1), after the first UVA exposure (T2), and at the end of the study after the sixth exposure (T3). RESULTS: UVA-exposed volunteers felt significantly more balanced, less nervous, more strengthened, and more satisfied with their appearance at T3. By contrast, the controls did not show significant changes of psychological parameters. In comparison to T1 and T3, serum serotonin was significantly higher and the serum melatonin was significantly lower for the volunteers exposed to UVA at T2. Both, for exposed and non-exposed volunteers serotonin and melatonin levels did not significantly differ at T1 and T3. CONCLUSIONS: It remains obscure, whether the exposure to UVA or other components of the treatment were responsible for the psychological benefits observed. The changes of circulating neuroendocrine mediators found after UVA exposure at T2 may be due to an UVA-induced effect via a cutaneous pathway. Nevertheless, the positive psychological effects observed in our study cannot be attributed to circulating serotonin or melatonin