Centimetre-scale perovskite solar cells with fill factors of more than 86 per cent.

Owing to rapid development in their efficiency1 and stability2, perovskite solar cells are at the forefront of emerging photovoltaic technologies. State-of-the-art cells exhibit voltage losses3-8 approaching the theoretical minimum and near-unity internal quantum efficiency9-13, but conversion efficiencies are limited by the fill factor (<83%, below the Shockley-Queisser limit of approximately 90%). This limitation results from non-ideal charge transport between the perovskite absorber and the cell's electrodes5,8,13-16. Reducing the electrical series resistance of charge transport layers is therefore crucial for improving efficiency. Here we introduce a reverse-doping process to fabricate nitrogen-doped titanium oxide electron transport layers with outstanding charge transport performance. By incorporating this charge transport material into perovskite solar cells, we demonstrate 1-cm2 cells with fill factors of >86%, and an average fill factor of 85.3%. We also report a certified steady-state efficiency of 22.6% for a 1-cm2 cell (23.33% ± 0.58% from a reverse current-voltage scan).

A cutaneous epithelioid vascular tumor harboring a TPM3::ALK fusion.

Substantial progress has been made in understanding the molecular pathways associated with vascular tumors over the last two decades. In addition to mutations and copy number aberrations, fusions have emerged as significant contributors to the pathogenesis of a notable subset of vascular tumors. In this report, we present a case of an unusual intradermal vascular tumor with epithelioid cytomorphology. Immunohistochemistry revealed diffuse positivity for CD31, ERG and Factor VIII, supporting its endothelial lineage. RNA sequencing (ArcherFusion Plex) revealed the presence of an in-frame fusion between the genes TPM3 Exon 8 and ALK Exon 20. Immunohistochemistry confirmed ALK expression by the endothelial cells. To our knowledge, this is the first documented case of a vascular tumor harboring an ALK fusion. It may fall within the spectrum of epithelioid hemangiomas; nevertheless, we cannot definitively exclude the possibility of it being a distinct and potentially unique benign entity on its own.

Population-based reference values for kidney function and kidney function decline in 25- to 95-year-old Germans without and with diabetes.

Understanding normal aging of kidney function is pivotal to help distinguish individuals at particular risk for chronic kidney disease. Glomerular filtration rate (GFR) is typically estimated via serum creatinine (eGFRcrea) or cystatin C (eGFRcys). Since population-based age-group-specific reference values for eGFR and eGFR-decline are scarce, we aimed to provide such reference values from population-based data of a wide age range. In four German population-based cohorts (KORA-3, KORA-4, AugUR, DIACORE), participants underwent medical exams, interview, and blood draw up to five times within up to 25 years. We analyzed eGFRcrea and eGFRcys cross-sectionally and longitudinally (12,000 individuals, age 25-95 years). Cross-sectionally, we found age-group-specific eGFRcrea to decrease approximately linearly across the full age range, for eGFRcys up to the age of 60 years. Within age-groups, there was little difference by sex or diabetes status. Longitudinally, linear mixed models estimated an annual eGFRcrea decline of -0.80 [95% confidence interval -0.82, -0.77], -0.79 [-0.83, -0.76], and -1.20 mL/min/1.73m2 [-1.33, -1.08] for the general population, "healthy" individuals, or individuals with diabetes, respectively. Reference values for eGFR using cross-sectional data were shown as percentile curves for "healthy" individuals and for individuals with diabetes. Reference values for eGFR-decline using longitudinal data were presented as 95% prediction intervals for "healthy" individuals and for individuals with diabetes, obesity, and/or albuminuria. Thus, our results can help clinicians to judge eGFR values in individuals seen in clinical practice according to their age and to understand the expected range of annual eGFR-decline based on their risk profile.

Mixed histiocytic neoplasms: A multicentre series revealing diverse somatic mutations and responses to targeted therapy.

Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai-Dorfman-Destombes disease (RDD) and Erdheim-Chester disease (ECD), and these have been characterized with respect to clinical phenotypes, driver mutations and treatment paradigms. Less is known about patients with mixed histiocytic neoplasms (MXH), that is two or more coexisting disorders. This international collaboration examined patients with biopsy-proven MXH with respect to component disease subtypes, oncogenic driver mutations and responses to conventional (chemotherapeutic or immunosuppressive) versus targeted (BRAF or MEK inhibitor) therapies. Twenty-seven patients were studied with ECD/LCH (19/27), ECD/RDD (6/27), RDD/LCH (1/27) and ECD/RDD/LCH (1/27). Mutations previously undescribed in MXH were identified, including KRAS, MAP2K2, MAPK3, non-V600-BRAF, RAF1 and a BICD2-BRAF fusion. A repeated-measure generalized estimating equation demonstrated that targeted treatment was statistically significantly (1) more likely to result in a complete response (CR), partial response (PR) or stable disease (SD) (odds ratio [OR]: 17.34, 95% CI: 2.19-137.00, p = 0.007), and (2) less likely to result in progression (OR: 0.08, 95% CI: 0.03-0.23, p < 0.0001). Histiocytic neoplasms represent an entity with underappreciated clinical and molecular diversity, poor responsiveness to conventional therapy and exquisite sensitivity to targeted therapy.

Genome and time-of-day transcriptome of Wolffia australiana link morphological minimization with gene loss and less growth control.

Rootless plants in the genus Wolffia are some of the fastest growing known plants on Earth. Wolffia have a reduced body plan, primarily multiplying through a budding type of asexual reproduction. Here, we generated draft reference genomes for Wolffia australiana (Benth.) Hartog & Plas, which has the smallest genome size in the genus at 357 Mb and has a reduced set of predicted protein-coding genes at about 15,000. Comparison between multiple high-quality draft genome sequences from W. australiana clones confirmed loss of several hundred genes that are highly conserved among flowering plants, including genes involved in root developmental and light signaling pathways. Wolffia has also lost most of the conserved nucleotide-binding leucine-rich repeat (NLR) genes that are known to be involved in innate immunity, as well as those involved in terpene biosynthesis, while having a significant overrepresentation of genes in the sphingolipid pathways that may signify an alternative defense system. Diurnal expression analysis revealed that only 13% of Wolffia genes are expressed in a time-of-day (TOD) fashion, which is less than the typical ∼40% found in several model plants under the same condition. In contrast to the model plants Arabidopsis and rice, many of the pathways associated with multicellular and developmental processes are not under TOD control in W. australiana, where genes that cycle the conditions tested predominantly have carbon processing and chloroplast-related functions. The Wolffia genome and TOD expression data set thus provide insight into the interplay between a streamlined plant body plan and optimized growth.

Phenotypic screening of seed retention and histological analysis of the abscission zone in Festuca pratensis and Lolium perenne.

BACKGROUND: Seed retention is the basic prerequisite for seed harvest. However, only little breeding progress has been achieved for this trait in the major forage grasses. The aim of this study was to evaluate the potential of plant genetic resources of the important fodder grasses Festuca pratensis Huds. and Lolium perenne L. as source for seed retention in the breeding process. Furthermore, the morphology of the abscission zone, where shattering occurs, was studied on the cell tissue level in different developmental stages of contrasting accessions. RESULTS: 150 and 286 accessions of Festuca pratensis and Lolium perenne were screened for seed retention, respectively. Contrasting accessions were selected to be tested in a second year. We found a great variation in seed retention in Festuca pratensis and Lolium perenne, ranging from 13 to 71% (average: 35%) and 12 to 94% (average: 49%), respectively, in the first year. Seed retention was generally lower in the second year. Cultivars were within the accessions with highest seed retention in Festuca pratensis, but had lower seed retention than ecotypes in Lolium perenne. Field-shattered seeds had a lower thousand grain weight than retained seeds. Cell layers of the abscission zone appeared already in early seed stages and were nested within each other in accessions with high seed retention, while there were two to three superimposed layers in accessions with low seed retention. CONCLUSIONS: Plant genetic resources of Lolium perenne might be a valuable source for breeding varieties with high seed retention. However, simultaneous selection for high seed weight is necessary for developing successful commercial cultivars.

Return of the Lemnaceae: duckweed as a model plant system in the genomics and postgenomics era.

The aquatic Lemnaceae family, commonly called duckweed, comprises some of the smallest and fastest growing angiosperms known on Earth. Their tiny size, rapid growth by clonal propagation, and facile uptake of labeled compounds from the media were attractive features that made them a well-known model for plant biology from 1950 to 1990. Interest in duckweed has steadily regained momentum over the past decade, driven in part by the growing need to identify alternative plants from traditional agricultural crops that can help tackle urgent societal challenges, such as climate change and rapid population expansion. Propelled by rapid advances in genomic technologies, recent studies with duckweed again highlight the potential of these small plants to enable discoveries in diverse fields from ecology to chronobiology. Building on established community resources, duckweed is reemerging as a platform to study plant processes at the systems level and to translate knowledge gained for field deployment to address some of society's pressing needs. This review details the anatomy, development, physiology, and molecular characteristics of the Lemnaceae to introduce them to the broader plant research community. We highlight recent research enabled by Lemnaceae to demonstrate how these plants can be used for quantitative studies of complex processes and for revealing potentially novel strategies in plant defense and genome maintenance.

Perifollicular linear projections: A dermatoscopic criterion for the diagnosis of lentigo maligna on the face.

BACKGROUND: Lentigo maligna (LM) can mimic benign, flat, pigmented lesions and can be challenging to diagnose. OBJECTIVE: To describe a new dermatoscopic feature termed "perifollicular linear projections (PLP)" as a diagnostic criterion for LM on the face. METHODS: Retrospective study on reflectance confocal microscopy and dermatoscopy images of flat facial pigmented lesions originating from 2 databases. PLP were defined as short, linear, pigmented projections emanating from hair follicles. Dermatoscopy readers were blinded to the final histopathologic diagnosis. RESULTS: From 83 consecutive LMs, 21/83 (25.3%) displayed "bulging of hair follicles" on reflectance confocal microscopy and 18 of these 21 (85.7%), displayed PLP on dermatoscopy. From a database of 2873 consecutively imaged and biopsied lesions, 252 flat-pigmented facial lesions were included. PLP was seen in 47/76 melanomas (61.8%), compared with 7/176 lesions (3.9%) with other diagnosis (P < .001). The sensitivity was 61.8% (95% CI, 49.9%-72.7%), specificity 96.0% (95% CI, 92.9%-98.4%). PLP was independently associated with LM diagnosis on multivariate analysis (OR 26.1 [95% CI, 9.6%-71.0]). LIMITATIONS: Retrospective study. CONCLUSION: PLP is a newly described dermatoscopic criterion that may add specificity and sensitivity to the early diagnosis of LM located on the face. We postulate that PLP constitutes an intermediary step in the LM progression model.

Extramammary Paget disease. Part I. epidemiology, pathogenesis, clinical features, and diagnosis.

Extramammary Paget disease (EMPD) is a rare skin cancer of apocrine-rich skin that mimics common inflammatory and infectious dermatoses, leading to delays in diagnosis and increased patient morbidity. Better clinical recognition of this entity, multidisciplinary patient assessment, and deeper understanding of the underlying pathophysiology are essential to improve patient care and disease outcomes. It is important to distinguish primary intraepithelial/micro-invasive EMPD from invasive EMPD or cases with adenocarcinoma arising within EMPD. This 2-part continuing medical education series provides a complete picture of EMPD. Part 1 of this continuing medical education series reviews the epidemiology, oncogenesis, clinical and histopathologic presentation, workup, and prognosis of this rare cancer.

Spindle cell porocarcinoma with a novel YAP1::MAML3 fusion.

Porocarcinomas are rare sweat gland cancers representing the malignant counterpart to benign poromas. Their diagnosis can be challenging, especially in the absence of an associated poroma or when the tumor is poorly differentiated. Since recurrent YAP1::MAML2 and YAP1::NUTM1 fusions have been identified in poroid tumors, molecular studies provide an opportunity to support the diagnosis in challenging cases. We describe a case of a female patient in her early 90s, with a polypoid mass of the hip. Histopathologically, there was a poorly differentiated malignant spindle cell tumor adjacent to a poroma. Because of the close association with a poroma and immunoreactivity for p40, a diagnosis of spindle cell porocarcinoma was rendered, which was further supported by YAP1 immunohistochemical studies. Antibodies targeting both the N-terminus and C-terminus confirmed YAP1 rearrangement in both the poroma and the spindle cell neoplasm. Subsequent targeted RNA sequencing revealed a YAP1::MAML3 gene fusion. MAML3 has previously not yet been reported as a YAP1 fusion partner in porocarcinoma. With the illustration of a rare spindle cell variant of porocarcinoma and the identification of a novel gene fusion, this case report expands the spectrum of morphologic and genomic aberrations associated with porocarcinoma.

Frequency of atopic dermatitis and psoriasis in the elderly - Cross-sectional findings from the German AugUR study.

Introduction Atopic Dermatitis (AD) and psoriasis appear to affect 2-3% (lifetime prevalence) people worldwide. However, there is little epidemiological data on the prevalence of those two chronic inflammatory skin diseases in the elderly. The aim of this study was to provide frequency estimates of AD and psoriasis obtained from an elderly population in Germany. Methods We examined baseline data from the AugUR study, a cohort study focusing on an aging population within the vicinity of Regensburg, Germany (comprising 1,133 participants with a median age of 76.7 years, 45% being female). We estimated raw frequencies of physician-diagnosed AD and psoriasis from participants' self-reports in personal interviews. These frequencies were adjusted to reflect the demographic distribution of the Bavarian population, considering both gender and age groupings spanning five or ten years. Results Data from 1,133 participants aged 70-95 (45.1% women) were available for analysis. Physician-diagnosed AD was reported by 3.3 % of participants (2.4% from men, 4.3% from women) and 5.6% (95%-CI: 4.3-7.1%) reported physician-diagnosed psoriasis (6.6% in men, 4.3% in women). Age- and gender-standardized frequency estimates for AD were 3.4% (95%-CI: 2.4-4.6, 2.6% in men, 4.3% in women) and 5.3% for psoriasis (95%-CI: 4.1-6.8, 6.3% in men and 4.1% in women). Conclusion This study indicates a lower than previously reported lifetime-prevalence of AD (3.4% vs. 8-10%) and a higher one regarding psoriasis (5.3% vs. 2-4%) in highly aged individuals. More epidemiological research in elderly populations using validated physician diagnoses are desirable.

In Situ Protein Expression Analysis of Melanocyte Differentiation Antigen TRP1 (Tyrosinase-Related Protein-1).

ABSTRACT: Melanocyte differentiation antigens refer to molecules expressed in cells of melanocytic lineage such as gp100/PMEL, tyrosinase, and Melan-A. Corresponding antibodies such as HMB45, T311, and A103 have become key immunohistochemical tools in surgical pathology for the diagnosis of pigmented and related lesions. Little is known about tyrosinase-related protein 1 (TRP1), another melanocyte differentiation antigen, which is an enzymatic component of melanogenesis and known as the brown locus in mice. In this study, we tested several commercial reagents to TRP1 and identified one clone, EPR13063, which we further characterized by testing its specificity and usefulness for surgical pathology. Subsequently, we analyzed the expression of TRP1 in panels of normal tissues and tumors. TRP1 is regularly expressed in normal skin and in cutaneous nevi predominantly present in junctional and to a lesser extent in dermal nevocytes. In melanoma, TRP1 is present in 100% and 44% of primary and metastatic melanomas, respectively. TRP1 was absent in 5 desmoplastic melanomas but heterogeneously present in 9 of 11 PEComas/angiomyolipomas. No TRP1 was found in neoplasms of nonmelanocytic lineage. We demonstrate that EPR13063 is a valuable reagent for the analysis of TRP1 expression in archival surgical pathology material. The TRP1 expression pattern in melanocytic and related lesions appears to parallel other melanocyte differentiation antigens with a higher incidence in primary and a lower incidence in metastatic melanomas.

Superficial Wnt-Activated Melanocytic Nevi/Melanocytomas With a Junctional Component: A Case Series.

ABSTRACT: The conventional morphological characteristics of Wnt-activated deep penetrating/plexiform melanocytomas/nevi (DPN) are those of large spindled or epithelioid melanocytes with distinctive voluminous amphophilic cytoplasm, fine pigmented granules, and surrounding melanophages. The central molecular hallmark is the activation of the Wnt-pathway predominantly driven by mutations in the beta-catenin ( CTNNB1 ) gene. Although typically lacking a junctional component, a lesser-known superficial variant with a junctional component has been identified, which could potentially lead to diagnostic challenges. This study presents a cohort of 11 such cases displaying a junctional component of DPN from 10 patients (5 women and 5 men; age range: 27-78 years; median age: 51 years). The nevi were distributed as follows: 1 conjunctival, 1 scalp, 2 lower limb, and 6 truncal lesions. Eight cases were combined with a conventional nevus, 2 cases displayed pure DPN cytology exhibiting only a junctional element, and 9 cases exhibited some degree of lentiginous architecture. All cases demonstrated a low mitotic index (<1 mitosis/mm 2 ). Immunohistochemistry revealed positive BRAF V600E staining in 8 cases (8/11), whereas all cases tested (11/11) were PRAME negative. Nuclear beta-catenin and LEF1 staining was consistently strong and diffuse with DPN cytology (11/11), along with robust cyclin D1 staining in all cases tested (11/11). By contrast, all 9 conventional nevi showed an absence of nuclear beta-catenin staining (0/9) and weaker, mosaic-type LEF1 and cyclin D1 staining was observed. This study emphasizes the diagnostic challenge these nevi can pose in the absence of a conventional, deeper DPN component, which can potentially be misdiagnosed as melanoma.

Validation of the AO Spine CROST (Clinician Reported Outcome Spine Trauma) in the clinical setting.

PURPOSE: To evaluate feasibility, internal consistency, inter-rater reliability, and prospective validity of AO Spine CROST (Clinician Reported Outcome Spine Trauma) in the clinical setting. METHODS: Patients were included from four trauma centers. Two surgeons with substantial amount of experience in spine trauma care were included from each center. Two separate questionnaires were administered at baseline, 6-months and 1-year: one to surgeons (mainly CROST) and another to patients (AO Spine PROST-Patient Reported Outcome Spine Trauma). Descriptive statistics were used to analyze patient characteristics and feasibility, Cronbach's α for internal consistency. Inter-rater reliability through exact agreement, Kappa statistics and Intraclass Correlation Coefficient (ICC). Prospective analysis, and relationships between CROST and PROST were explored through descriptive statistics and Spearman correlations. RESULTS: In total, 92 patients were included. CROST showed excellent feasibility results. Internal consistency (α = 0.58-0.70) and reliability (ICC = 0.52 and 0.55) were moderate. Mean total scores between surgeons only differed 0.2-0.9 with exact agreement 48.9-57.6%. Exact agreement per CROST item showed good results (73.9-98.9%). Kappa statistics revealed moderate agreement for most CROST items. In the prospective analysis a trend was only seen when no concerns at all were expressed by the surgeon (CROST = 0), and moderate to strong positive Spearman correlations were found between CROST at baseline and the scores at follow-up (rs = 0.41-0.64). Comparing the CROST with PROST showed no specific association, nor any Spearman correlations (rs = -0.33-0.07). CONCLUSIONS: The AO Spine CROST showed moderate validity in a true clinical setting including patients from the daily clinical practice.

KidneyGPS: a user-friendly web application to help prioritize kidney function genes and variants based on evidence from genome-wide association studies.

BACKGROUND: Genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with kidney function. By combining these findings with post-GWAS information (e.g., statistical fine-mapping to identify independent association signals and to narrow down signals to causal variants; or different sources of annotation data), new hypotheses regarding physiology and disease aetiology can be obtained. These hypotheses need to be tested in laboratory experiments, for example, to identify new therapeutic targets. For this purpose, the evidence obtained from GWAS and post-GWAS analyses must be processed and presented in a way that they are easily accessible to kidney researchers without specific GWAS expertise. MAIN: Here we present KidneyGPS, a user-friendly web-application that combines genetic variant association for estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics consortium with annotation of (i) genetic variants with functional or regulatory effects ("SNP-to-gene" mapping), (ii) genes with kidney phenotypes in mice or human ("gene-to-phenotype"), and (iii) drugability of genes (to support re-purposing). KidneyGPS adopts a comprehensive approach summarizing evidence for all 5906 genes in the 424 GWAS loci for eGFR identified previously and the 35,885 variants in the 99% credible sets of 594 independent signals. KidneyGPS enables user-friendly access to the abundance of information by search functions for genes, variants, and regions. KidneyGPS also provides a function ("GPS tab") to generate lists of genes with specific characteristics thus enabling customizable Gene Prioritisation (GPS). These specific characteristics can be as broad as any gene in the 424 loci with a known kidney phenotype in mice or human; or they can be highly focussed on genes mapping to genetic variants or signals with particularly with high statistical support. KidneyGPS is implemented with RShiny in a modularized fashion to facilitate update of input data ( https://kidneygps.ur.de/gps/ ). CONCLUSION: With the focus on kidney function related evidence, KidneyGPS fills a gap between large general platforms for accessing GWAS and post-GWAS results and the specific needs of the kidney research community. This makes KidneyGPS an important platform for kidney researchers to help translate in silico research results into in vitro or in vivo research.

Phenotypic variation of root-system architecture under high P and low P conditions in potato (Solanum tuberosum L.).

BACKGROUND: Phosphorus (P) is an essential macronutrient required for plant metabolism and growth. Its acquisition by plants depends on the availability of dissolved P in the rhizosphere and on the characteristics of P uptake mechanisms such as root-system architecture (RSA). Compared to other crops, potato (Solanum tuberosum L.) has a relatively poor P acquisition efficiency. This is mainly due to its shallow and sparsely branched root system, resulting in a rather limited exploitable soil volume. Information about potato genotypes with RSA traits suitable to improve adaptation to nutrient scarcity is quite rare. Aim of this study is to assess phenotypic variation of RSA in a potato diversity set and its reactions to P deficiency. RESULTS: Only one out of 22 RSA-traits showed a significant increase under low-P conditions. This indicates an overall negative effect of P scarcity on potato root growth. Differences among genotypes, however, were statistically significant for 21 traits, revealing a high variability in potato RSA. Using a principal component analysis (PCA), we were able to classify genotypes into three groups with regard to their root-system size. Genotypes with both small and large root systems reacted to low-P conditions by in- or decreasing their relative root-system size to medium, whereas genotypes with an intermediate root system size showed little to no changes. CONCLUSIONS: We observed a huge variation in both the potato root system itself and its adaptation to P deficiency. This may enable the selection of potato genotypes with an improved root-zone exploitation. Eventually, these could be utilized to develop new cultivars adapted to low-P environments with better resource-use efficiencies.

Undifferentiated and Dedifferentiated Metastatic Melanomas Masquerading as Soft Tissue Sarcomas: Mutational Signature Analysis and Immunotherapy Response.

The distinction between undifferentiated melanoma (UM) or dedifferentiated melanoma (DM) from undifferentiated or unclassifiable sarcoma can be difficult and requires the careful correlation of clinical, pathologic, and genomic findings. In this study, we examined the utility of mutational signatures to identify patients with UM/DM with particular attention as to whether this distinction matters for treatment because the survival of patients with metastatic melanoma has dramatically improved with immunologic therapy, whereas durable responses are less frequent in sarcomas. We identified 19 cases of UM/DM that were initially reported as unclassified or undifferentiated malignant neoplasm or sarcoma and submitted for targeted next-generation sequencing analysis. These cases were confirmed as UM/DM by harboring melanoma driver mutations, UV signature, and high tumor mutation burden. One case of DM showed melanoma in situ. Meanwhile, 18 cases represented metastatic UM/DM. Eleven patients had a prior history of melanoma. Thirteen of 19 (68%) of the tumors were immunohistochemically completely negative for 4 melanocytic markers (S100, SOX10, HMB45, and MELAN-A). All cases harbored a dominant UV signature. Frequent driver mutations involved BRAF (26%), NRAS (32%), and NF1 (42%). In contrast, the control cohort of undifferentiated pleomorphic sarcomas (UPS) of deep soft tissue exhibited a dominant aging signature in 46.6% (7/15) without evidence of UV signature. The median tumor mutation burden for DM/UM vs UPS was 31.5 vs 7.0 mutations/Mb (P < .001). A favorable response to immune checkpoint inhibitor therapy was observed in 66.6% (12/18) of patients with UM/DM. Eight patients exhibited a complete response and were alive with no evidence of disease at the last follow-up (median 45.5 months). Our findings support the usefulness of the UV signature in discriminating DM/UM vs UPS. Furthermore, we present evidence suggesting that patients with DM/UM and UV signatures can benefit from immune checkpoint inhibitor therapy.

Lentigo maligna melanoma mapping using reflectance confocal microscopy correlates with staged excision: A prospective study.

BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) can present with subclinical extension that may be difficult to define preoperatively and lead to incomplete excision and potential recurrence. Preliminarily studies have used reflectance confocal microscopy (RCM) to assess LM/LMM margins. OBJECTIVE: To evaluate the correlation of LM/LMM subclinical extension defined by RCM compared with the gold standard histopathology. METHODS: Prospective study of LM/LMM patients referred for dermatologic surgery. RCM was performed at the clinically defined initial surgical margin followed by margin-controlled staged excision with paraffin-embedded tissue, and histopathology was correlated with RCM results. RESULTS: Seventy-two patients were included. Mean age was 66.8 years (standard deviation, 11.1; range, 38-89); 69.4% were men. Seventy of 72 lesions (97.2%) were located on the head and neck with mean largest clinical diameter of 1.3 cm (range, 0.3-5). Diagnostic accuracy for detection of residual melanoma in the tumor debulk (after biopsy) had a sensitivity of 96.7% and a specificity of 66.7% when compared with histopathology. RCM margin assessment revealed an overall agreement with final histopathology of 85.9% (κ = 0.71; P < .001). LIMITATIONS: No RCM imaging beyond initial planned margins was performed. CONCLUSION: RCM showed moderate to excellent overall agreement between RCM imaging of LM/LMM and histopathology of staged excision margins.

Staging System Performance and Clinical Outcomes for Cutaneous Squamous Cell Carcinoma of the Ear: A Single-Center Retrospective Study.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) of the ear is associated with poor outcomes. No studies have evaluated current staging system performance in this specific location. OBJECTIVE: Describe clinicopathologic characteristics and outcomes of ear cSCC and evaluate the performance of current staging systems. METHODS: Retrospective study including cases diagnosed and treated at a cancer center from January 2000 to December 2014. Demographic, clinical, and pathologic data were collected from clinical records. Biopsy slides were rereviewed and patients were staged according to the American Joint Committee on Cancer (AJCC) seventh, eighth, and Brigham Women's Hospital (BWH) staging. RESULTS: Of 125 patients, the mean age at diagnosis was 71.9 years (SD 12.5), with most men (89.6%, n = 112). Median follow-up was 22.3 months. Local recurrence and survival risk factors were similar to cSCC outside the ear. The Akaike's Information Criterion (AIC) estimates showed that the BWH system better predicted outcomes than the AJCC seventh, and the AJCC eighth, with AIC values of 189.9, 270.5, and 274.1, respectively. Limitations of the study include retrospective design, single center study, and no control group. CONCLUSION: Current staging systems perform well at stratifying risk in ear cSCC.

Immunohistochemistry for PRAME in Dermatopathology.

ABSTRACT: Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen first identified in a melanoma patient and found to be expressed in most melanomas as well as in variable levels in other malignant neoplasms of epithelial, mesenchymal, or hematolymphoid lineage. Detection of PRAME expression in formalin-fixed paraffin-embedded tissue is possible by immunohistochemistry (IHC) with commercially available monoclonal antibodies. In situ and invasive melanoma frequently show a diffuse pattern of nuclear PRAME immunoreactivity which contrasts with the infrequent and typically nondiffuse staining seen in nevi. In many challenging melanocytic tumors, results of PRAME IHC and other ancillary tests correlate well, but not always: The tests are not interchangeable. Most metastatic melanomas are positive for PRAME, whereas nodal nevi are not. Numerous studies on PRAME IHC have become available in the past few years with results supporting the value of PRAME IHC as an ancillary tool in the evaluation of melanocytic lesions and providing insights into limitations in sensitivity and specificity as well as possible pitfalls that need to be kept in mind by practicing pathologists.