The rapid increase in telemedicine coupled with recent advances in diagnostic artificial intelligence (AI) create the imperative to consider the opportunities and risks of inserting AI-based support ...into new paradigms of care. Here we build on recent achievements in the accuracy of image-based AI for skin cancer diagnosis to address the effects of varied representations of AI-based support across different levels of clinical expertise and multiple clinical workflows. We find that good quality AI-based support of clinical decision-making improves diagnostic accuracy over that of either AI or physicians alone, and that the least experienced clinicians gain the most from AI-based support. We further find that AI-based multiclass probabilities outperformed content-based image retrieval (CBIR) representations of AI in the mobile technology environment, and AI-based support had utility in simulations of second opinions and of telemedicine triage. In addition to demonstrating the potential benefits associated with good quality AI in the hands of non-expert clinicians, we find that faulty AI can mislead the entire spectrum of clinicians, including experts. Lastly, we show that insights derived from AI class-activation maps can inform improvements in human diagnosis. Together, our approach and findings offer a framework for future studies across the spectrum of image-based diagnostics to improve human-computer collaboration in clinical practice.
The reported prevalence of nevus-associated melanoma varies substantially. We performed a systematic review and meta-analysis to determine the incidence and prevalence of this disease; we also ...performed subanalyses considering age, tumor thickness, and nevus-type classification. In 38 observational cohort and case–control studies, 29.1% of melanomas likely arose from a preexisting nevus and 70.9% de novo. Any given melanoma was 64% less likely to be nevus-associated than de novo (risk ratio 0.36, 95% confidence interval CI 0.29-0.44; P < .001; I2 = 99%); nevus-associated melanomas had a lower mean Breslow thickness than de novo melanomas (mean difference –0.39 mm; 95% CI –0.60 to –0.18; P = .0003; I2 = 66%). No significant differences were noted regarding the association of nevus-associated melanomas with nondysplastic nevi or dysplastic nevi (risk ratio 0.77, 95% CI 0.49-1.20; P = .24; I2 = 98%).
Background Skin aging is thought to be a complex biological process that is traditionally classified as intrinsic and extrinsic aging. Several clinical score and instrumental devices have been ...applied to obtain a precise assessment of skin aging. Among them, confocal microscopy has emerged as a new technique capable of assessing cytoarchitectural changes with a nearly histopathologic resolution. Objective We sought to determine the microscopic skin changes occurring on the face in different age groups by means of confocal microscopy. Methods The skin of the cheek in 63 volunteers belonging to distinct age groups was analyzed by confocal microscopy. In 4 cases, routine histopathology was performed on site-matched surplus areas from routine excisions for obtaining a better comparison with confocal findings. Results Young skin was characterized by regular polygonal keratinocytes and thin reticulated collagen fibers. With aging, more irregularly shaped keratinocytes and areas with unevenly distributed pigmentation and increased compactness of collagen fibers were observed. In the elderly, thinning of the epidermis, marked keratinocyte alterations, and huddles of collagen and curled fibers, corresponding to elastosis, were present. A side-by-side correlation between confocal descriptors and histopathologic aspects has been provided in a few cases. Limitations Reticular dermal changes cannot be assessed because of the limited depth laser penetration. Conclusions Confocal microscopy was successfully applied to identify in vivo skin changes occurring in aged skin at both the epidermal and dermal levels at histopathologic resolution. This offers the possibility to test cosmetic product efficacy and to identify early signs of sun damage.
Immune checkpoint inhibitors are used for treating patients with metastatic melanoma. Since the response to treatment is variable, biomarkers are urgently needed to identify patients who may benefit ...from such therapy. Here, we combine single-cell RNA-sequencing and multiparameter flow cytometry to assess changes in circulating CD8
T cells in 28 patients with metastatic melanoma starting anti-PD-1 therapy, followed for 6 months: 17 responded to therapy, whilst 11 did not. Proportions of activated and proliferating CD8
T cells and of mucosal-associated invariant T (MAIT) cells are significantly higher in responders, prior to and throughout therapy duration. MAIT cells from responders express higher level of CXCR4 and produce more granzyme B. In silico analysis support MAIT presence in the tumor microenvironment. Finally, patients with >1.7% of MAIT among peripheral CD8
population show a better response to treatment. Our results thus suggest that MAIT cells may be considered a biomarker for patients responding to anti-PD-1 therapy.
A recently introduced dermoscopic method for the diagnosis of early lentigo maligna (LM) is based on the absence of prevalent patterns of pigmented actinic keratosis and solar lentigo/flat seborrheic ...keratosis. We term this the inverse approach.
To determine whether training on the inverse approach increases the diagnostic accuracy of readers compared to classic pattern analysis.
We used clinical and dermoscopic images of histopathologically diagnosed LMs, pigmented actinic keratoses, and solar lentigo/flat seborrheic keratoses. Participants in a dermoscopy masterclass classified the lesions at baseline and after training on pattern analysis and the inverse approach. We compared their diagnostic performance among the 3 timepoints and to that of a trained convolutional neural network.
The mean sensitivity for LM without training was 51.5%; after training on pattern analysis, it increased to 56.7%; and after learning the inverse approach, it increased to 83.6%. The mean proportions of correct answers at the 3 timepoints were 62.1%, 65.5, and 78.5%. The percentages of readers outperforming the convolutional neural network were 6.4%, 15.4%, and 53.9%, respectively.
The experimental setting and the inclusion of histopathologically diagnosed lesions only.
The inverse approach, added to the classic pattern analysis, significantly improves the sensitivity of human readers for early LM diagnosis.
PRAME (PReferentially expressed Antigen in MElanoma), a cancer testis antigen expressed in low levels in gonadal, endometrial, and adrenal gland tissues, has been recently considered a valuable tool ...in the differential diagnosis between benign and malignant melanocytic lesions. The aim of the current study is to perform PRAME immunostaining on a large series of benign and malignant acral lesions to evaluate the reproducibility of data reported in the literature and to validate PRAME as an affordable tool in the differential diagnosis between benign and malignant acral melanocytic tumors. Immunohistochemical analysis for PRAME was performed in 127 benign and malignant acral and nail melanocytic lesions. To better correlate PRAME expression with the nature (benign vs. malignant) of the lesions, we categorized PRAME tumor cells percentage positivity and intensity in a cumulative score obtained by adding the quartile of positive tumor cells (0, 1+, 2+, 3+, 4+) to PRAME expression intensity in tumor cells (0, 1+, 2+, 3+). Adopting an arbitrary PRAME expression score of < 5 versus ≥5 resulted in a correct identification of 82.5% of benign and 87.1% of malignant lesions. PRAME immunohistochemistry demonstrated good sensitivity and specificity in the diagnosis of acral melanocytic lesions, however, in line with the previous literature, we identified a subset of challenging cases such as acral Spitz nevi, in situ melanomas, and small, thin, invasive melanomas in which PRAME did not correlate with morphologic features. This suggests that PRAME can be a valid tool to be incorporated in a diagnostic clinicopathologic algorithm, subject to morphologic characteristics.
The strong growth of the aquaculture industry can represent a serious threat to aquatic ecosystems and requires the development of new strategies to control and minimize the impact of such activities ...on the structure and function of biological communities ...
Summary Sentinel lymph node biopsy has been proposed as a diagnostic method for estimation of the malignant potential of atypical Spitz tumours. However, although cell deposits are commonly detected ...in the sentinel lymph nodes of patients with atypical Spitz tumours, their prognosis is substantially better than that of patients with melanoma and positive sentinel lymph node biopsies. We did a systematic review of published reports to assess the role of sentinel lymph node biopsy as a prognostic method in the management of atypical Spitz tumours. The results of our analysis did not show any prognostic benefit of sentinel lymph node biopsy; having a positive sentinel lymph node does not seem to predict a poorer outcome for patients with atypical Spitz tumours. These findings indicate that, especially in the paediatric population, it might be prudent initially to use complete excision with clear margins and careful clinical follow-up in patients with atypical Spitz tumours.
Skin aging is a complex process that causes morphologic variations. Some of these variations havebeen hypothesized to be involved in skin cancer development. This paper reviews current knowledgeof ...the features of aged skin as seen with reflectance confocal microscopy (RCM). Basic principles ofthe technique are described, and the RCM features of healthy skin and skin cancer are briefly discussed.Moreover, the RCM features at different layers of young and elderly skin are described, as arethe variations that occur with passing years and in relation to sun exposure that contribute to photoagingand the development of skin cancer. RCM enables the noninvasive evaluation, at quasi-histologicresolution, of aging-related skin changes, some of which are shared with skin cancer; this ability helpsavoid skin biopsy. Further research is needed to understand the relation between skin aging and skincancer development.
This is the first description of a Mediterranean mesophotic coral reef. The bioconstruction extended for 2.5 km along the Italian Adriatic coast in the bathymetric range -30/-55 m. It appeared as a ...framework of coral blocks mostly built by two scleractinians, Phyllangia americana mouchezii (Lacaze-Duthiers, 1897) and Polycyathus muellerae (Abel, 1959), which were able to edify a secondary substrate with high structural complexity. Scleractinian corallites were cemented by calcified polychaete tubes and organized into an interlocking meshwork that provided the reef stiffness. Aggregates of several individuals of the bivalve Neopycnodonte cochlear (Poli, 1795) contributed to the compactness of the structure. The species composition of the benthic community showed a marked similarity with those described for Mediterranean coralligenous communities and it appeared to be dominated by invertebrates, while calcareous algae, which are usually considered the main coralligenous reef-builders, were poorly represented. Overall, the studied reef can be considered a unique environment, to be included in the wide and diversified category of Mediterranean bioconstructions. The main reef-building scleractinians lacked algal symbionts, suggesting that heterotrophy had a major role in the metabolic processes that supported the production of calcium carbonate. The large amount of available suspended organic matter in the area could be the main nutritional source for these species, as already suggested in the literature referred to Mediterranean cold-water corals.
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