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

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

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

Kaposi sarcoma in a HIV uninfected man who has sex with men

Kaposi's sarcoma (KS) is a rare angioproliferative tumor associated with human herpesvirus 8 (HHV-8) infection. Four clinical variants of KS have been described: classic, endemic, iatrogenic and HIV-associated. We describe a 53-year-old men who had sex with men with a rapidly growing nodule on his left foot. Histologically KS was confirmed. Our patient did not match the clinical subgroups as HIV infection or other immune disorders could be ruled out. KS in HIV-negative MSM has only been reported sporadically. It was shown that KS in these patients clinically resembles classic KS but occurs at a younger age, is limited to the skin, and is associated with a good prognosis

The effect of stellar encounters on the dark matter annihilation signal from prompt cusps

Prompt cusps are the densest quasi-equilibrium dark matter objects; one forms at the instant of collapse within every isolated peak of the initial cosmological density field. They have power-law density profiles, $\rho \propto r^{-1.5}$ with central phase-space density set by the primordial velocity dispersion of the dark matter. At late times they account for $\sim 1\%$ of the dark matter mass but for $>90\%$ of its annihilation luminosity in all but the densest regions, where they are tidally disrupted. Here we demonstrate that individual stellar encounters, rather than the mean galactic tide, are the dominant disruptors of prompt cusps within galaxies. Their cumulative effect is fully (though stochastically) characterised by an impulsive shock strength $B_* = 2\pi G\int\rho_*({\bf x}(t))\, \mathrm{d}t$ where $\rho_*$, the total mass density in stars, is integrated over a cusp's entire post-formation trajectory. Stellar encounters and mean tides have only a small effect on the halo annihilation luminosity seen by distant observers, but this is not true for the Galactic halo because of the Sun's position. For a 100 GeV WIMP, Earth-mass prompt cusps are predicted, and stellar encounters suppress their mean annihilation luminosity by a factor of two already at 20 kpc, so that their annihilation emission is predicted to appear almost uniform over the sky. The Galactic Center $\gamma$-ray Excess is thus unaffected by cusps. If it is indeed dark matter annihilation radiation, then prompt cusps in the outer Galactic halo and beyond must account for 20-80% of the observed isotropic $\gamma$-ray background in the 1 to 10 GeV range.Comment: 22 pages, 23 figures, for a video and code see https://github.com/jstuecker/cusp-encounter

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

A semi-parametric approach to estimate risk functions associated with multi-dimensional exposure profiles: application to smoking and lung cancer

A common characteristic of environmental epidemiology is the multi-dimensional aspect of exposure patterns, frequently reduced to a cumulative exposure for simplicity of analysis. By adopting a flexible Bayesian clustering approach, we explore the risk function linking exposure history to disease. This approach is applied here to study the relationship between different smoking characteristics and lung cancer in the framework of a population based case control study

Water displacement leg volumetry in clinical studies - A discussion of error sources

<p>Abstract</p> <p>Background</p> <p>Water displacement leg volumetry is a highly reproducible method, allowing the confirmation of efficacy of vasoactive substances. Nevertheless errors of its execution and the selection of unsuitable patients are likely to negatively affect the outcome of clinical studies in chronic venous insufficiency (CVI).</p> <p>Discussion</p> <p>Placebo controlled double-blind drug studies in CVI were searched (Cochrane Review 2005, MedLine Search until December 2007) and assessed with regard to efficacy (volume reduction of the leg), patient characteristics, and potential methodological error sources. Almost every second study reported only small drug effects (≤ 30 mL volume reduction). As the most relevant error source the conduct of volumetry was identified. Because the practical use of available equipment varies, volume differences of more than 300 mL - which is a multifold of a potential treatment effect - have been reported between consecutive measurements. Other potential error sources were insufficient patient guidance or difficulties with the transition from the Widmer CVI classification to the CEAP (Clinical Etiological Anatomical Pathophysiological) grading.</p> <p>Summary</p> <p>Patients should be properly diagnosed with CVI and selected for stable oedema and further clinical symptoms relevant for the specific study. Centres require a thorough training on the use of the volumeter and on patient guidance. Volumetry should be performed under constant conditions. The reproducibility of short term repeat measurements has to be ensured.</p

UDP-glucuronosyltransferase UGT1A7 genetic polymorphisms in hepatocellular carcinoma: a differential impact according to seropositivity of HBV or HCV markers?

<p>Abstract</p> <p>Background:</p> <p>We conducted a case-control study to evaluate the role of UDP-glucuronosyltransferase 1A7 (UGT1A7) polymorphisms in the onset of hepatocellular carcinoma (HCC).</p> <p>Methods:</p> <p>The study included 165 patients with HCC, 134 with cirrhosis and 142 controls without liver disease, matched for age and hospital. All were men younger than 75 years. HCC and cirrhosis patients were stratified according to time since cirrhosis diagnosis.</p> <p>Results:</p> <p>We found a positive association between the UGT1A7*3/*3 genotype and HCC when the comparison was restricted to patients whose disease was of viral origin [OR = 3.4 (0.3–45)] but a negative association when it included only alcoholic patients [OR = 0.1 (0.02–0.6), p = 0.01].</p> <p>Conclusion:</p> <p>Our study shows that UGT1A7 may play a role in hepatocellular carcinogenesis and that this role may differ according to the primary cause of the cirrhosis.</p