Spitz melanocytic tumours – a review

Spitz tumours comprise a spectrum of melanocytic proliferations that share a set of distinct cytological features and molecular pathways. They include benign naevi, intermediate or indeterminate tumours and rare melanomas. Spitz tumours are notorious for the difficulty of distinguishing benign neoplasms with atypical features from melanomas and the related diagnostic uncertainty. Advances in the knowledge of the molecular pathways and genomic aberrations associated with these neoplasms have permitted opportunities for a reduction in the number of uncertain diagnoses and a more objective distinction between Spitz tumours from Spitz-like neoplasms. The presence of a Spitz molecular pathway, such as Harvey rat sarcoma viral oncogene homologue (HRAS) aberrations or kinase fusions, distinguishes a bona fide Spitz neoplasm from Spitz-like naevi or melanomas with conventional driver mutations. Spitz neoplasms with benign histopathological features and, if such testing is performed, benign cytogenetic and molecular findings, are termed Spitz naevi. Spitz neoplasms with frankly malignant histopathological findings or ambiguous microscopic findings associated with genetic or genomic aberrations most in keeping with melanoma are designated as Spitz melanoma. Tumours with microscopic features and genetic/genomic aberrations in between naevi and melanomas are classified as Spitz melanocytoma.     

Cross‐sectional and longitudinal association of sports participation,media consumption and motor competence in youth

The beneficial associations of physical activity (PA) and sports with motor competence have been well documented. Similarly, high media time has been associated with poor motor competence. Limited information, however, is available on the combined effects of sport participation and media consumption on motor competence. The present study followed 213 Austrian middle‐school students (57% male; age at baseline: 10.4 ± 0.6 years) over a 4‐year period. Annual assessments included the German Motor Test 6‐18, along with self‐reported participation in club sports, time spent watching TV and using the computer. There were no interaction effects between sports participation and media time on motor competence. Club sports participation, however, was associated with higher motor competence, while there was an inverse association between media time and motor competence. Further, motor competence affected future participation in club sports while club sports had limited effects on subsequent motor development. High media time, on the other hand, impaired subsequent motor development, while effects of motor competence on media time were limited. Taken together, these results emphasize the importance of motor competence in the facilitation of sports participation during adolescence. Accordingly, a wide variety of movement experiences should be provided at young ages to promote motor development. In addition, the detrimental effects of media time on motor competence warrant that sedentary behaviors are targeted separately, particularly in youth not participating in sports.     

Ursachenzusammenhang zwischen langjähriger Querschnittlähmung und malignen Harnblasentumoren

Trauma und Berufskrankheit - Zur Zusammenhangsbeurteilung traumatisch bedingter Querschnittlähmungen und Jahre später auftretender Harnblasenkarzinome gibt es keine aussagefähige...     

Active Surveillance Versus Radical Prostatectomy in Favorable-risk Localized Prostate Cancer

BackgroundActive surveillance (AS) and radical prostatectomy (RP) are both accepted treatments for men with favorable-risk localized prostate cancer (PCa) (ie, clinical tumor category 1-2b, Gleason Grade Group 1-2, and prostate-specific antigen < 20 ng/mL). However, head-to-head studies comparing oncologic outcomes and survival between these 2 treatment strategies are warranted. The objective of this study was to compare the use of prostate cancer treatments and PCa death in men managed on AS and men who underwent immediate RP.Patients and MethodsThis was an observational study including 647 men on AS and 647 men treated with RP propensity score matched. We examined the 10-year cumulative incidence of salvage radiotherapy, hormonal therapy, castration-resistant PCa, and PCa death.ResultsThe 10-year curative treatment-free survival for men on AS was 61% (95% confidence interval [CI], 57%-65%). No differences in use of salvage radiotherapy (AS, 2.7%; 95% CI, 1.4%-4.1% vs. RP 5.4%; 95% CI, 3.4%-7.3%), hormonal therapy (AS, 6.9%; 95% CI, 4.4%-9.4% vs. RP, 4.1%; 95% CI, 2.5%-5.6%), developing castration-resistant PCa (AS, 1.7%; 95% CI, 0.5%-2.9% vs. RP, 2.0%; 95% CI, 0.7%-3.4%), or cumulative PCa mortality (AS, 0.4%; 95% CI, 0%-1.0% vs. RP, 0.5%; 95% CI, 0%-1.5%) were observed between the treatment strategies. The main limitation was the non-random allocation to treatment strategy.ConclusionIn this observational study on men with favorable-risk localized PCa, we found similar PCa mortality at 10 years between men on AS and men who underwent immediate RP. Moreover, there were no differences in the use of PCa therapies between the groups. Our study supports active surveillance as a treatment strategy for men with favorable-risk localized PCa.     

Detection of recombinant and endogenous mouse melatonin receptors by monoclonal antibodies targeting the C‐terminal domain

Melatonin receptors play important roles in the regulation of circadian and seasonal rhythms, sleep, retinal functions, the immune system, depression, and type 2 diabetes development. Melatonin receptors are approved drug targets for insomnia, non‐24‐hour sleep‐wake disorders, and major depressive disorders. In mammals, two melatonin receptors (MTRs) exist, MT₁ and MT₂, belonging to the G protein‐coupled receptor (GPCR) superfamily. Similar to most other GPCRs, reliable antibodies recognizing melatonin receptors proved to be difficult to obtain. Here, we describe the development of the first monoclonal antibodies (mABs) for mouse MT₁ and MT₂. Purified antibodies were extensively characterized for specific reactivity with mouse, rat, and human MT₁ and MT₂ by Western blot, immunoprecipitation, immunofluorescence, and proximity ligation assay. Several mABs were specific for either mouse MT₁ or MT₂. None of the mABs cross‐reacted with rat MTRs, and some were able to react with human MTRs. The specificity of the selected mABs was validated by immunofluorescence microscopy in three established locations (retina, suprachiasmatic nuclei, pituitary gland) for MTR expression in mice using MTR‐KO mice as control. MT₂ expression was not detected in mouse insulinoma MIN6 cells or pancreatic beta‐cells. Collectively, we report the first monoclonal antibodies recognizing recombinant and native mouse melatonin receptors that will be valuable tools for future studies.     

Occurrence of newly discovered human polyomaviruses in skin of liver transplant recipients and their relation with squamous cell carcinoma in situ and actinic keratosis – a single‐center cohort study

To date 14 human polyomaviruses (HPyVs) have been identified. The newly found HPyVs have not been examined with regard to post‐transplant skin carcinogenesis. To determine the occurrences in skin and possible pathological associations of the HPyVs, we studied their genoprevalences in squamous cell carcinoma (SCC) in situ or actinic keratosis and benign skin in liver transplant recipients (LiTRs); and of healthy skin in immunocompetent adults. We used highly sensitive and specific HPyV PCRs of two types. Overall, Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), human polyomavirus 7 (HPyV7), trichodysplasia spinulosa polyomavirus (TSPyV), and Lyon IARC polyomavirus (LIPyV) were found in 58/221 (26.2%) skin biopsies. MCPyV DNA was detected in 5/14 (35.7%) premalignant vs. 32/127 (25.2%) benign skin of LiTRs, and in 12/80 (15%) healthy skin of immunocompetent adults, with no statistically significant difference in viral DNA prevalence or load. TSPyV DNA was found in a single skin lesion. LIPyV, HPyV6 and HPyV7 DNAs occurred exclusively in benign skin. Overall, the viral findings in premalignant versus benign skin were alike. The occurrences of HPyVs in skin of LiTRs and immunocompetent individuals speak against a role for any of the 14 HPyVs in SCC development.