pinecone/core-2020-05-10-deduplication huggingface dataset:
Incidence and Survival for Merkel Cell Carcinoma in Queensland, Australia, 1993-2010

Importance:  Merkel cell carcinoma (MCC) is an uncommon but highly invasive form of skin cancer.  The mechanisms that cause MCC are yet to be fully determined.   Objective:  To examine the incidence and survival of MCC within a population known to be at high risk of other skin cancers.  Design:  Retrospective cohort study. Setting:  Population-based administrative data for MCC collected by the Queensland Cancer Registry, supplemented with detailed histopathological data.   Participants:  De-identified records were obtained of all Queensland residents diagnosed with MCC during the period from 1993 to 2010.  A sub-sample of histopathology records were reviewed by a senior dermatopathologist to determine the potential for misclassification.  A total of 879 eligible cases of MCC were included in the study.      Main Outcomes and Measures:  Incidence rates were directly age-standardised to the 2000 United States Standard Population.  Trends were examined using JoinPoint software with results expressed in terms of the annual percentage change.  The period method was used to calculate five-year relative survival and adjusted hazard ratios were obtained from multivariate Poisson models. Results:  There were 340 cases of MCC diagnosed in Queensland between 2006 and 2010, corresponding to an incidence rate of 1.6/100,000 population. Males (2.5/100,000) had higher incidence than females (0.9/100,000) and rates peaked at 20.7/100,000 for persons aged 80 years and over. The overall incidence of MCC increased by an average of 2.6% per year from 1993 onwards. Relative survival was 41% after 5 years, with significantly better survival found for those aged under 70 years old at diagnosis (between 56-60%), tumours on the face/ears (51%) and stage I lesions (49%).       Conclusions and Relevance:  Incidence rates for MCC in Queensland are at least double any that have been previously published elsewhere in the world.  It is likely that Queensland's combination of exposure to sunlight, predominantly Caucasian population and outdoor lifestyle has played a role in this unwanted result.  Interventions are required to increase awareness of MCC among clinicians and the public.Full Tex
The phenotypic and genotypic spectra of ichthyosis with confetti plus novel genetic variation in the 3' end of KRT10: from disease to a syndrome

Ichthyosis with confetti (IWC) is a genodermatosis caused by dominant negative mutations in the gene encoding keratin 10 (KRT10). We investigated clinical and genetic details of a substantial number of patients with IWC in order to define major and minor criteria for diagnosis of this rare disorder.; Parallel clinical investigation of 6 patients with IWC revealed a novel spectrum of phenotypes. We found several features that qualify as major criteria for diagnosis, which are clearly and consistently associated with the condition. These included malformation of ears, hypoplasia of mammillae, and dorsal acral hypertrichosis. Genetic analysis of patients revealed several different frameshift mutations in intron 6 or exon 7 of KRT10. Analysis of this locus in 17 unrelated control individuals revealed 2 novel polymorphisms of KRT10.; We present for the first time to our knowledge the spectrum of clinical variability of IWC in 6 patients with confirmed mutations in KRT10. From this, we have extracted major and minor criteria to aid early and correct clinical diagnosis. Ectodermal malformations, present in all patients, suggest a novel classification of IWC as a syndrome. There is remarkable genetic variation at the IWC disease locus within control individuals from the general population
Redefining dermatologists’ role in skin cancer early detection and follow-up care

Early diagnosis of melanoma leads to the best prognosis for patients and may be more likely achieved when those who are at high risk for melanoma undergo regular and systematic monitoring. However, many people rarely or never see a dermatologist. Risk prediction models (recently reviewed by Usher-Smith et al ) could assist to triage people into preventive care appropriate for their risk profile. Most risk prediction models contain measures of phenotype including skin, eye and hair colour as well as genetic mutations. Almost all also contain the number and size of naevi, as well as the presence of naevi with atypical features which are independently associated with melanoma risk. In the absence of formal population-based screening programs for melanoma in most countries worldwide, people with  high risk phenotypes may need to consider regular monitoring or self-monitoring of their naevi , especially since the vast majority of melanomas are found by people themselves or their friend and relatives. Another group of patients that will require regular monitoring are patients who have been successfully treated for their first melanoma, whose risk to develop a second melanoma is greatly increased . In a US study of 89,515 melanoma survivors those with a previous diagnosis of melanoma had a 9-fold increased risk of developing subsequent melanoma compared with the general population, equating to a rate of 3.76 per 1000 person-years, while in an Australian study, risk of subsequent melanoma was 6 per 1000 person-years. Regular follow-up is therefore essential for melanoma survivors, especially during the first few years after initial melanoma diagnosis
Multiple BRAF Wild-Type Melanomas During Dabrafenib Treatment for Metastatic BRAF-Mutant Melanoma.

IMPORTANCE: BRAF inhibitors have become the standard of care in metastatic BRAF-mutant melanomas. Compared with chemotherapies, BRAF inhibitors improve overall and disease-free survival and speed the recovery of symptomatic patients with metastatic disease. The most worrisome finding is the possible development of resistance to new malignant tumors. OBSERVATIONS: A patient in her 30s developed massive BRAFV600E melanoma metastasis during her 30th week of pregnancy. After emergency cesarean delivery, oral dabrafenib treatment was initiated, and a partial radiologic response was confirmed within 1 month. At dermatologic digital follow-up aided by confocal microscopy 8 weeks after initiation of dabrafenib treatment, 4 melanomas were detected. Unfortunately, within the next month, the melanoma rapidly progressed. The 4 new melanomas were wild-type BRAFmelanomas, whereas the new metastasis carried a different BRAF mutation (S467L). CONCLUSIONS AND RELEVANCE: Cutaneous malignant tumors are the most frequent adverse events of BRAF inhibitors; therefore, strict dermatologic surveillance in a referral center aided by digital follow-up is mandatory, especially when multiple nevi are present and these drugs are used in an adjuvant setting. In view of our findings, the pathogenesis of the development of new melanomas seems to be different from therapy resistance. Whether paradoxical RAF activation could explain these BRAF wild-type secondary malignant tumors is still unknown
Fitzpatrick skin type, individual typology angle, and melanin index in an African population : steps toward universally applicable skin photosensitivity assessments

Calculation of the individual typology angle (ITA) based on spectrophotometric measurements has been used to classify skin types into 6 physiologically relevant groups: very light, light, intermediate, tan, brown, and dark. This study directly compares ITA values with the melanin index (MI), which is frequently used in assigning Fitzpatrick skin type (FST), to improve understanding of how these measurements correlate when used in a study that primarily includes participants with FSTs V and VI.National Science Foundation Graduate Research Fellowship Program under Grant No. (grant number NSF DGE-1144153) and an international travel allowance co-funded through the Graduate
Research Opportunities Worldwide (GROW) and United States Agency for International Development agencies. CSIR Parliamentary Grant
funding, Cancer Association of South Africa ad-hoc grant. Cancer Society of New Zealand Inc. and the University of Otago.http://archderm.jamanetwork.com/journal.aspxhb2016Geography, Geoinformatics and Meteorolog
Skin Cancer Diagnosis With Reflectance Confocal Microscopy: Reproducibility of Feature Recognition and Accuracy of Diagnosis

IMPORTANCE: Reflectance confocal microscopy (RCM) studies have been performed to identify criteria for diagnosis of skin neoplasms. However, RCM-based diagnosis is operator dependent. Hence, reproducibility of RCM criteria needs to be tested. OBJECTIVE: To test interobserver reproducibility of recognition of previously published RCM descriptors and accuracy of RCM-based skin cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Observational retrospective web-based study of a set of RCM images collected at a tertiary academic medical center. Nine dermatologists (6 of whom had ≥3 years of RCM experience) from 6 countries evaluated an RCM study set from 100 biopsy-proven lesions, including 55 melanocytic nevi, 20 melanomas, 15 basal cell carcinomas, 7 solar lentigines or seborrheic keratoses, and 3 actinic keratoses. Between June 15, 2010, and October 21, 2010, participanting dermatologists, blinded to histopathological diagnosis, evaluated 3 RCM mosaic images per lesion for the presence of predefined RCM descriptors. MAIN OUTCOMES AND MEASURES: The main outcome was identification of RCM descriptors with fair to good interrater agreement (κ statistic, ≥0.3) and independent correlation with malignant vs benign diagnosis on discriminant analysis. Additional measures included sensitivity and specificity for diagnosis of malignant vs benign for each evaluator, for majority diagnosis (rendered by ≥5 of 9 evaluators), and for experienced vs recent RCM users. RESULTS: Eight RCM descriptors showed fair to good reproducibility and were independently associated with a specific diagnosis. Of these, the presence of pagetoid cells, atypical cells at the dermal-epidermal junction, and irregular epidermal architecture were associated with melanoma. Aspecific junctional pattern, basaloid cords, and ulceration were associated with basal cell carcinomas. Ringed junctional pattern and dermal nests were associated with nevi. The mean sensitivity for the group of evaluators was 88.9% (range, 82.9%-100%), and the mean specificity was 79.3% (range, 69.2%-90.8%). Majority diagnosis showed sensitivity of 100% and specificity of 80.0%. Sensitivity was higher for experienced vs recent RCM users (91.0% vs. 84.8%), but specificity was similar (80.0% vs. 77.9%). CONCLUSIONS AND RELEVANCE: The study highlights key RCM diagnostic criteria for melanoma and basal cell carcinoma that are reproducibly recognized among RCM users. Diagnostic accuracy increases with experience. The higher accuracy of majority diagnosis suggests that there is intrinsically more diagnostic information in RCM images than is currently used by individual evaluators
A Digital Dermoscopy Follow-up Illustration and a Histopathologic Correlation for Angulated Lines in Extrafacial Lentigo Maligna.

IMPORTANCE: The diagnosis of extrafacial lentigo maligna can be a challenge because the dermoscopic features are not well described. These features can share some of the criteria of superficial spreading melanoma and some of facial lentigo maligna; however, these features are often absent. A new dermoscopic pattern has recently been described as forming angulated lines. OBSERVATIONS: We report 4 cases of extrafacial lentiginous lesions in 3 patients in whom straight angulated lines have been observed as the only key for diagnosis. This is the first time, to our knowledge, that these lines were seen in the follow-up by digital dermoscopy during a lapse time of a few months. This morphologic change led to the excision of the lesion. The pathologic diagnosis of lentigo maligna was established in each case. Moreover, a histologic correlation of these straight angulated lines is documented. CONCLUSIONS AND RELEVANCE: Angulated lines could be considered as a new warning sign during the follow-up of extrafacial lentigo. More studies are required to establish the sensitivity and specificity of this newly described dermoscopic feature
Prevalence of MITF p.E318K in patients with melanoma independent of the presence of CDKN2A causative mutations

Importance The main high-penetrance melanoma susceptibility gene is CDKN2A, encoding p16INK4A and p14ARF. The gene MITF variant p.E318K also predisposes to melanoma and renal cell carcinoma. To date, the prevalence of MITF p.E318K and its clinical and phenotypical implications has not been previously assessed in a single cohort of Spanish patients with melanoma or in p16INK4A mutation carriers.Objectives To evaluate the prevalence of MITF p.E318K in Spanish patients with melanoma and assess the association with clinical and phenotypic features.Design, Setting, and Participants A hospital-based, case-control study was conducted at the Melanoma Unit of Hospital Clinic of Barcelona, with MITF p.E318K genotyped in all patients using TaqMan probes. We included 531 patients: 271 patients with multiple primary melanoma (MPM) without mutations affecting p16INK4A (wild-type p16INK4A); 191 probands from melanoma-prone families with a single melanoma diagnosis and without mutations affecting p16INK4A, and 69 probands from different families carrying CDKN2A mutations affecting p16INK4A. A population-based series of 499 age- and sex-matched cancer-free individuals from the Spanish National Bank of DNA were included as controls. Patients were recruited between January 1, 1992, and June 30, 2014; data analysis was conducted from September 1 to November 30, 2014.Main Outcomes and Measures The genetic results of the MITF p.E318K variant were correlated with clinical and phenotypic features.Results Among the 531 patients, the prevalence of the MITF p.E318K variant was calculated among the different subsets of patients included and was 1.9% (9 of 462) in all melanoma patients with wild-type p16INK4A, 2.6% (7 of 271) in those with MPM, and 2.9% (2 of 69) in the probands of families with p16INK4A mutations. With results reported as odds ratio (95% CI), the MITF p.E318K was associated with an increased melanoma risk (3.3 [1.43-7.43]; P < .01), especially in MPM (4.5 [1.83-11.01]; P < .01) and high nevi count (>200 nevi) (8.4 [2.14-33.19]; P < .01). Two fast-growing melanomas were detected among 2 MITF p.E318K carriers during dermatologic digital follow-up.Conclusions and Relevance In addition to melanoma risk, MITF p.E318K is associated with a high nevi count and could play a role in fast-growing melanomas. Testing for MITF p.E318K should not exclude patients with known mutations in p16INK4A. Strict dermatologic surveillance, periodic self-examination, and renal cell carcinoma surveillance should be encouraged in this context
Comparison of ex vivo and in vivo dermoscopy in dermatopathologic evaluation of skin tumors

IMPORTANCE: Ex vivo dermoscopy (EVD) can be a valuable tool in routine diagnostic dermatopathologic evaluation. 
OBJECTIVES: To compare in vivo dermoscopy (IVD) and EVD and to provide guidance for routine dermatopathologic evaluations. 
DESIGN, SETTING, AND PARTICIPANTS: This observational study collected 101 consecutive IVD and EVD images of skin tumors from a private dermatology practice from March 1 to September 30, 2013. Four observers (3 dermatologists and 1 dermatopathologist) blinded to the histopathologic diagnoses independently scored and compared the colors, structures, and vessels of EVD images with those of the corresponding IVD images. Data were analyzed from January 1 to March 31, 2014. 
MAIN OUTCOMES AND MEASURES: Concordance between the EVD and IVD images and gain or loss of colors, structures, and vessels on EVD relative to IVD images. 
RESULTS: The final analysis included 404 observations of 101 images. The EVD image was generally similar to the corresponding IVD image but clearly darker, with new areas of blue in 130 of 404 observations (32.2%) and white in 100 of 404 observations (24.8%) and loss of red in 283 of 404 observations (70.0%). Most structures were well preserved. New structureless areas were found in 78 of 404 observations of EVD images (19.3%), and new crystalline structures were detected in 68 of 404 observations of EVD images (16.8%). On EVD images, squames and crusts were lost in 56 of 404 observations (13.9%) and 43 of 404 observations (10.6%), respectively. Blood vessels were lost in 142 of 404 observations of EVD images (35.1%). 
CONCLUSIONS AND RELEVANCE: The EVD image is an important new tool in dermatopathology and may give direction to targeted tissue processing and examination of skin tumors
Association between confocal morphologic classification and clinical phenotypes of multiple primary and familial melanomas

Importance: The improved knowledge of clinical, morphologic, and epidemiologic heterogeneity of melanoma in the context of multiple primary and familial melanomas may improve prevention, diagnosis, and prognosis of melanoma. Objective: To characterize reflectance confocal microscopy (RCM) morphologic patterns of melanomas in multiple primary and familial melanomas. Design, Setting, and Participants: In this cross-sectional, retrospective study, patients in a hospital-based referral center were recruited from March 1, 2010, through August 31, 2013; data analysis was conducted from September 1, 2013, through May 31, 2014. Consecutive primary melanomas, documented by dermoscopic and confocal examination, from multiple primary and familial melanomas with known CDKN2A mutational status were studied. Main Outcomes and Measures: Epidemiologic, genetic, dermoscopic, and histologic data were evaluated according to an RCM morphologic classification: dendritic cell, round cell, dermal nest, combined, and nonclassifiable types. Results: Fifty-seven melanomas from 50 patients (28 women [56%] and 49 white patients [98%]) were included: 23 dendritic cell (40%), 21 round cell (37%), 2 dermal nests (4%), 2 combined (4%), and 9 nonclassifiable (16%). The median (SD) age of the participants was 53.0 (16.9) years (interquartile range, 41.8-71.2 years), and the median (SD) age at the first melanoma was 46.0 (17.1) years (interquartile range, 35.8-61.5 years). Dendritic cell melanoma was characterized by older age at diagnosis, phototypes 2 and 3, more intense solar exposure, and moderate to severe solar lentigines; it was the most prevalent confocal type in facial lesions and was associated with the lentigo maligna histologic subtype. Round cell melanomas were identified more often in the familial context and in individuals with phototype 1 skin types; RCM features, such as junctional thickening, dense dermal nests, and nucleated cells within papillary dermis, were more frequently found in this subtype. Dermal nest and combined melanoma were associated with the absence of pigmented network on dermoscopy and thicker tumors on histologic analysis. Nonclassifiable type was associated, by RCM, with the absence of pagetoid cells on confocal examination and lower frequency of marked atypia on melanocytes in the basal cell layer; it presented with lower ABCD Total Dermoscopy Scores and RCM scores compared with the other types. CDKN2A mutation carriers may develop any RCM type of melanoma. Conclusions and Relevance: Different routes to develop melanoma can be identified according to RCM morphologic classification, with dendritic cell melanomas being associated with chronic sun damage and round cell melanoma with early age at onset and phototype 1 in the context of multiple primary and familial melanomas. The morphologic expression of melanomas via dermoscopy and confocal examination varies according to differences in tumor stage and biological behavior
Pathologic evaluation of skin tumors with ex vivo dermoscopy with derm dotting

IMPORTANCE : Ex vivo dermoscopy (EVD) with derm dotting (DD) improves clinicopathologic correlation and the quality of diagnosis in skin tumors. 
OBJECTIVE : To compare the diagnostic performance of the standard method of skin biopsy processing with the practice of EVD with DD. 
DESIGN, SETTING, AND PARTICIPANTS : This retrospective study compares the diagnostic performance in 6526 skin biopsy specimens examined from 2008 to 2010 with a standard method of processing with 8584 biopsy specimens examined in 2015 with EVD and DD. Data were analyzed from January 1 to March 31, 2016. A total of 15 110 skin biopsy specimens were included. The biopsy specimens from 2008 to 2010 were processed in a hospital-based general pathology laboratory; the biopsy specimens from 2015 were processed in a private dermatopathology laboratory. Biopsy specimens from both periods were diagnosed by the same dermatopathologist. 
MAIN OUTCOMES AND MEASURES : The primary outcome measures were clinicopathological characteristics, usefulness of EVD with DD, and turnaround times (TATs). 
RESULTS : Use of EVD with DD increased the detection of positive section margins in nonmelanoma skin cancer from 8.4% to 12.8%. The most significant increase was seen in Bowen disease, invasive squamous cell carcinoma, and a superficial type of basal cell carcinoma (BCC). With EVD and DD, a specific clinicopathologic diagnosis was made in 27.7% of nevi compared with only 10.3% using the standard method. The incidence of moderately and severely dysplastic nevi increased from 1.0% to 7.2% and from 0.6% to 1.4%, respectively. The detection of ulceration in melanomas with thicker than 1 mm increased from 24.0% to 31.3%. The number of nevi-associated melanomas increased from 15.5% to 33.3%. The number of collision lesions from 0.07% to 1.07%. The TAT for nevi decreased from 2 days to 1 day, for melanomas from 5 days to 2 days, and for BCC from 2 days to 1 day. 
CONCLUSIONS AND RELEVANCE : Ex vivo dermoscopy and DD with adapted sectioning in a dermatopathology setting allows a more accurate and less time consuming histopathologic diagnosis of skin tumors. These findings suggest that pathologists involved in skin tumor evaluation should be encouraged to learn dermoscopy and replace random transverse cutting with lesion-specific and DD-guided cutting