Multiparametric Monitoring of Disease Progression in Contemporary Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy Initiating Tafamidis Treatment.

BACKGROUND: Recently, a disease modifying therapy has become available for transthyretin amyloid cardiomyopathy (ATTR-CM). A validated monitoring concept of treatment is lacking, but a current expert consensus recommends three clinical domains (clinical, biomarker and ECG/imaging) assessed by several measurable features to define disease progression. METHODS: We retrospectively analyzed data of wild-type ATTR-CM patients initiating tafamidis therapy assessed within our local routine protocol at baseline and 6-months follow-up with respect to the frequency of values beyond the proposed thresholds defining disease progression. Additionally, associations of cardiac magnetic resonance (CMR) tomography with clinical domains were examined within a subgroup. RESULTS: Sixty-two ATTR-CM patients were included (88.7% male, mean age 79 years). In total, 16.1% of patients had progress in the clinical and functional domain, 33.9% in the biomarker domain and 43.5% in the imaging/electrocardiography (ECG) domain, with the latter driven by deterioration of the diastolic dysfunction grade and global longitudinal strain. In total, 35.5% of patients showed progress in none, 35.5% in one, 29.0% in two and no patient in three domains, the latter indicating overall disease progression. A subgroup analysis of twenty-two patients with available baseline and follow-up CMR data revealed an increase in CMR-based extracellular volume by more than 5% in 18.2% of patients, with no significant correlation with progress in one of the clinical domains. CONCLUSIONS: We provide first frequency estimates of the markers of disease progression according to a recent expert consensus statement, which might help refine the multiparametric monitoring concept in patients with ATTR-CM.

Expert Agreement on the Presence and Spatial Localization of Melanocytic Features in Dermoscopy.

Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. In this study, we attempted to evaluate agreement among experts on exemplar images not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least 1 of 31 melanocytic-specific features were submitted by 25 world experts as exemplars. Using a web-based platform that allows for image markup of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with eight achieving excellent agreement (Gwet's AC >0.75) and seven of them being melanoma-specific features. These features were peppering/granularity (0.91), shiny white streaks (0.89), typical pigment network (0.83), blotch irregular (0.82), negative network (0.81), irregular globules (0.78), dotted vessels (0.77), and blue-whitish veil (0.76). By utilizing an exemplar dataset, a good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication, and machine learning experiments.

Dermoscopy of Cutaneous Neoplasms in Skin of Color - A Systematic review by the International Dermoscopy Society "Imaging in Skin of Color" Task Force.

Over the last few decades, dermoscopy has been showed to facilitate the non-invasive diagnosis of both benign and malignant skin tumors, yet literature data mainly comes from studies on light photo-types. However, there is growing evidence that skin neoplasms may benefit from dermoscopic assessment even for skin of color. This systematic literature review evaluated published data in dark-skinned patients (dermoscopic features, used setting, pathological correlation, and level of evidence of studies), also providing a standardized and homogeneous terminology for reported dermoscopic findings. A total of 20 articles describing 46 different tumors (four melanocytic neoplasms, eight keratinocytic tumors, 15 adnexal cutaneous neoplasms, seven vascular tumors, four connective tissue tumors, and eight cystic neoplasms/others) for a total of 1724 instances were included in the analysis. Most of them showed a level of evidence of V (12 single case reports and six case series), with only two studies featuring a level of evidence of IV (case-control analysis). Additionally, this review also underlined that some neoplasms and phototypes are underrepresented in published analyses as they included only small samples and mainly certain tones of "dark skin" spectrum (especially phototype IV). Therefore, further studies considering such limitations are required for a better characterization.

Dermoscopy of Inflammatory Dermatoses (Inflammoscopy) in Skin of Color - A Systematic Review by the International Dermoscopy Society "Imaging in Skin of Color" Task Force.

Dermoscopic patterns of inflammatory dermatoses (inflammoscopy) have been extensively studied in the recent years, though data on patients with darker phototypes (IV-VI) are sparse. The aims of this systematic review were to summarize the current state of knowledge on inflammoscopy applied to skin of color and provide a standardized nomenclature of reported findings. Besides dermoscopic features, type of setting and magnification, number of cases, and histopathological correlation were analyzed. Eighty-five papers addressing 78 different dermatoses (25 papulosquamous dermatoses, 19 hyperpigmented dermatoses, eight hypopigmented dermatoses, four granulomatous dermatoses, two sclerotic dermatoses, five facial inflammatory dermatoses, and 15 miscellaneous conditions) for a total of 2073 instances were retrieved. Only one study showed a level of evidence of III (cross-sectional study), whereas 10 and 74 displayed a level of evidence of IV (case-control studies) and V (case-series and case-reports), respectively. Moreover, our analysis also highlighted that most of papers focalized on a limited number of dermatoses, with several conditions having only single dermoscopic descriptions. Additionally, few studies compared findings among phototypes belonging to the "skin of color" spectrum. Further studies designed according to a systematic approach and considering the above-mentioned issues are therefore needed.

Diagnosis and Management of Acral Pigmented Lesions.

BACKGROUND: Survival outcomes in acral lentiginous melanoma (ALM) are worse than for cutaneous melanoma. Diagnostic delays are believed to contribute to worse outcomes in ALM, including advanced-stage disease at initial presentation. Acral lentiginous melanoma, especially in its early stages, may be difficult to discern from benign pigmented acral lesions. OBJECTIVE: The purpose of this article is to provide a comprehensive review of the diagnosis and management of acral pigmented lesions. MATERIALS AND METHODS: A literature review was performed. The outcomes included were the clinical and dermoscopic features and the management frameworks and considerations for acquired and congenital melanocytic nevi, acral melanosis, nonmelanocytic pigmented lesions, and ALM. RESULTS: Original research studies were primarily included. The use of dermoscopy, such as the 3-step algorithm and blotch (irregular), ridge pattern (parallel), asymmetry of structures, asymmetry of colors, furrow pattern (parallel), fibrillar pattern (BRAAFF) checklist, increases the diagnostic accuracy of acral pigmented lesions with high specificity and sensitivity. Short-term digital dermoscopic surveillance can be used to manage acral lesions, and histopathology should be collected when there is a concern for ALM. CONCLUSION: The use of dermoscopy and an understanding of how to manage acral lesions may limit the number of biopsies performed on the acral skin, decrease the time to diagnosis, and facilitate early detection of ALM.

Thoracic aorta diameters in Marfan patients: Intraindividual comparison of 3D modified relaxation-enhanced angiography without contrast and triggering (REACT) with transthoracic echocardiography.

OBJECTIVE: To compare the measurement of aortic diameters using a novel flow-independent MR-Angiography (3D modified Relaxation-Enhanced Angiography without Contrast and Triggering (modified REACT)) and transthoracic echocardiography (TTE) in Marfan syndrome (MFS) patients. MATERIAL AND METHODS: This retrospective, single-center analysis included 46 examinations of 32 MFS patients (mean age 37.5 ± 11.3 years, 17 women, no prior aortic surgery) who received TTE and 3D modified REACT (ECG- and respiratory-triggering, Compressed SENSE factor 9 for acceleration of image acquisition) of the thoracic aorta. Aortic diameters (sinus of Valsalva (SV), sinotubular junction (STJ), and ascending aorta (AoA)) were independently measured by two cardiologists in TTE (leading-edge) and two radiologists in modified REACT (inner-edge, using multiplanar reconstruction). Intraclass correlation coefficient, Bland-Altman analyses, and Pearson's correlation (r) were used to assess agreement between observers and methods. RESULTS: Interobserver correlation at the SV, STJ, and AoA were excellent for both, TTE (ICC = 0.95-0.98) and modified REACT (ICC = 0.99-1.00). There was no significant difference between TTE and modified REACT for diameters measured at the SV (39.24 ± 3.24 mm vs. 39.63 ± 3.76 mm; p = 0.26; r = 0.78) and the STJ (35.16 ± 4.47 mm vs. 35.37 ± 4.74 mm; p = 0.552; r = 0.87). AoA diameters determined by TTE were larger than in modified REACT (34.29 ± 5.31 mm vs. 30.65 ± 5.64 mm; p < 0.01; r = 0.74). The mean scan time of modified REACT was 05:06 min ± 02:47 min, depending on the patient's breathing frequency and heart rate. CONCLUSIONS: Both TTE and modified REACT showed a strong correlation for all aortic levels; however, at the AoA, diameters were larger using TTE, mostly due to the limited field of view of the latter with measurements being closer to the aortic valve. Given the excellent interobserver correlation and the strong agreement with TTE, modified REACT represents an attractive method to depict the thoracic aorta in MFS patients.

Cerebral revascularization surgery reduces cerebrovascular events in children with sickle cell disease and moyamoya syndrome: Results of the stroke in sickle cell revascularization surgery retrospective study.

BACKGROUND: Recent studies suggest that cerebral revascularization surgery may be a safe and effective therapy to reduce stroke risk in patients with sickle cell disease and moyamoya syndrome (SCD-MMS). METHODS: We performed a multicenter, retrospective study of children with SCD-MMS treated with conservative management alone (conservative group)-chronic blood transfusion and/or hydroxyurea-versus conservative management plus surgical revascularization (surgery group). We monitored cerebrovascular event (CVE) rates-a composite of strokes and transient ischemic attacks. Multivariable logistic regression was used to compare CVE occurrence and multivariable Poisson regression was used to compare incidence rates between groups. Covariates in multivariable models included age at treatment start, age at moyamoya diagnosis, antiplatelet use, CVE history, and the risk period length. RESULTS: We identified 141 patients with SCD-MMS, 78 (55.3%) in the surgery group and 63 (44.7%) in the conservative group. Compared with the conservative group, preoperatively the surgery group had a younger age at moyamoya diagnosis, worse baseline modified Rankin scale scores, and increased prevalence of CVEs. Despite more severe pretreatment disease, the surgery group had reduced odds of new CVEs after surgery (odds ratio = 0.27, 95% confidence interval [CI] = 0.08-0.94, p = .040). Furthermore, comparing surgery group patients during presurgical versus postsurgical periods, CVEs odds were significantly reduced after surgery (odds ratio = 0.22, 95% CI = 0.08-0.58, p = .002). CONCLUSIONS: When added to conservative management, cerebral revascularization surgery appears to reduce the risk of CVEs in patients with SCD-MMS. A prospective study will be needed to validate these findings.

International Dermoscopy Society (IDS) Criteria for Skin Tumors: Validation for Skin of Color Through a Delphi Expert Consensus by the "Imaging in Skin of Color" IDS Task Force.

INTRODUCTION: A structured set of eight basic dermoscopic parameters (lines, clods, dots, circles, pseudopods, structureless, else, and vessels) including a total of 77 variables with corresponding descriptive and metaphoric vocabulary has been released for evaluation of skin tumors by the International Dermoscopy Society (IDS). OBJECTIVES: To validate the aforementioned criteria for the use in darker phototypes (phototypes IV-VI) via an expert consensus. METHODS: The two-round "Delphi method" was adopted, with an iterative process including two rounds of email questionnaires. Potential panelists were asked to take part in the procedure via email on the basis of their expertise in the dermoscopy of skin tumors in dark phototypes. RESULTS: A total of 17 participants were involved. All the original variables of the eight basic parameters reached agreement during the first round, except for "pink small clods" ("milky red globules") and "structureless pink zone" ("milky red areas"). Moreover, during the first round, panelists proposed a change of three existing items and the introduction of four new items, i.e., "black, small clods" ("black globules"), "follicular plugs", "erosions/ulcerations", and "white color around vessels" ("perivascular white halo"). All such proposals achieved agreement, thus being included in the final list, for a total of 79 items. There was consistency between the descriptive and metaphoric approaches in terms of scoring. CONCLUSIONS: Albeit most of the original items were considered applicable even for skin of color, there are some points of differences that physicians need to know. No significant preference was found between descriptive and metaphoric terminology among panelists.

Early Detection and Prognostic Assessment of Cutaneous Melanoma: Consensus on Optimal Practice and the Role of Gene Expression Profile Testing.

Importance: Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined. Objective: To provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM. Evidence Review: Case scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45). Findings: The panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status. Conclusions and Relevance: For this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.

Expert Consensus Statement on Proficiency Standards for Dermoscopy Education in Primary Care.

BACKGROUND: Primary care providers (PCPs) frequently address dermatologic concerns and perform skin examinations during clinical encounters. For PCPs who evaluate concerning skin lesions, dermoscopy (a noninvasive skin visualization technique) has been shown to increase the sensitivity for skin cancer diagnosis compared with unassisted clinical examinations. Because no formal consensus existed on the fundamental knowledge and skills that PCPs should have with respect to dermoscopy for skin cancer detection, the objective of this study was to develop an expert consensus statement on proficiency standards for PCPs learning or using dermoscopy. METHODS: A 2-phase modified Delphi method was used to develop 2 proficiency standards. In the study's first phase, a focus group of PCPs and dermatologists generated a list of dermoscopic diagnoses and associated features. In the second phase, a larger panel evaluated the proposed list and determined whether each diagnosis was reflective of a foundational or intermediate proficiency or neither. RESULTS: Of the 35 initial panelists, 5 PCPs were lost to follow-up or withdrew; 30 completed the fifth and last round. The final consensus-based list contained 39 dermoscopic diagnoses and associated features. CONCLUSIONS: This consensus statement will inform the development of PCP-targeted dermoscopy training initiatives designed to support early cancer detection.

Dermoscopy of acquired pigmentary disorders: a comprehensive review.

Dermoscopy has traditionally been used for the diagnosis of neoplasms and more recently in the evaluation of inflammatory conditions. Recent observational studies have suggested a role for dermoscopy in identifying and differentiating acquired pigmentary disorders. This comprehensive review will summarize the growing literature on the use of dermoscopy for pigmentary disorders. A literature review was performed on PubMed dating from inception to October 2020. The following pigmentary disorders were included in this study: melasma, solar lentigines, poikiloderma of Civatte, exogenous ochronosis, lichen planus pigmentosus, erythromelanosis follicularis faciei et colli, pigmented contact dermatitis, Riehl's melanosis, postinflammatory hyperpigmentation, erythema dyschromicum perstans, ashy dermatosis, confluent and reticulated papillomatosis, acanthosis nigricans, pityriasis versicolor, tinea versicolor, idiopathic guttate hypomelanosis, and vitiligo. Search terms used included each pigmentary disorder along with the terms "dermoscopy" or "dermatoscopy." Relevant case reports and case series were included. Many pigmentary disorders have unique and distinguishable features on dermoscopy. Given that these disorders can be clinically challenging for clinicians and emotionally distressing for patients, dermoscopy provides an additional, useful tool in the evaluation and assessment process.

Acral Lentiginous Melanoma: A United States Multi-Center Substage Survival Analysis.

BACKGROUND: Acral lentiginous melanoma is associated with worse survival than other subtypes of melanoma. Understanding prognostic factors for survival and recurrence can help better inform follow-up care. OBJECTIVES: To analyze the clinicopathologic features, melanoma-specific survival, and recurrence-free survival by substage in a large, multi-institutional cohort of primary acral lentiginous melanoma patients. METHODS: Retrospective review of the United States Melanoma Consortium database, a multi-center prospectively collected database of acral lentiginous melanoma patients treated between January 2000 and December 2017. RESULTS: Of the 433 primary acral lentiginous melanoma patients identified (median [range] age: 66 [8-97] years; 53% female, 83% white), 66% presented with stage 0-2 disease and the median time of follow-up for the 392 patients included in the survival analysis was 32.5 months (range: 0-259). The 5-year melanoma-specific survivals by stage were 0 = 100%, I = 93.8%, II = 76.2%, III = 63.4%, IIIA = 80.8%, and IV = 0%. Thicker Breslow depth ((HR) = 1.13; 95% CI = 1.05-1.21; P < .001)) and positive nodal status ((HR) = 1.79; 95% CI = 1.00-3.22; P = .050)) were independent prognostic factors for melanoma-specific survival. Breslow depth ((HR = 1.13; 95% CI = 1.07-1.20; P < .001), and positive nodal status (HR = 2.12; 95% CI = 1.38-3.80; P = .001) were also prognostic factors for recurrence-free survival. CONCLUSION: In this cohort of patients, acral lentiginous melanoma was associated with poor outcomes even in early stage disease, consistent with prior reports. Stage IIB and IIC disease were associated with particularly low melanoma-specific and recurrence-free survival. This suggests that studies investigating adjuvant therapies in stage II patients may be especially valuable in acral lentiginous melanoma patients.

Revisiting Solitary Pedunculated Lipofibromas.

OBJECTIVES: Pedunculated lipofibromas are soft, compressible, skin-colored nodules that typically present as an acquired solitary lesion, predominantly located on the buttocks and thighs. We aimed to differentiate between pedunculated lipofibromas and nevus lipomatosus superficialis. Although benign, this may be important as treatment options vary. METHODS: We describe 3 cases of solitary pedunculated lipofibromas occurring in older, obese adults that required clinicopathologic correlation for the correct diagnosis. RESULTS: The histopathologic features of pedunculated lipofibromas include a broad-based lesion with aggregates of mature adipocytes extending upwards into the dermis without an associated inflammatory infiltrate. The primary histopathologic differential diagnoses include fibroepithelial polyps with adipocytes and nevus lipomatosus superficialis, which is more frequently found in children or young adults and is typically characterized clinically by multiple lesions with a cerebriform to verrucoid surface. CONCLUSIONS: While the precise relationship between pedunculated lipofibromas and nevus lipomatosus is still unknown, we propose using pedunculated lipofibroma as a more specific clinical term to refer to solitary pedunculated or broad-based fatty lesions with a smooth surface that occur in older patients and in a wide anatomic distribution.

Dermoscopic features of neoplasms in skin of color: A review.

BACKGROUND: Dermoscopy is undoubtedly a useful tool to improve diagnostic accuracy and minimize the number of unnecessary biopsies. However, much of the literature on dermoscopy focuses on findings in lighter-skin phototypes, leaving potential gaps of knowledge regarding its use in skin of color (SoC). As the clinical applications of dermoscopy continue to increase, understanding dermoscopic patterns in SoC is imperative. OBJECTIVE: This review discusses the literature on dermoscopic findings of neoplasms in SoC, highlighting unique and characteristic dermoscopic features. METHODS: A literature review was performed using the PubMed database. Case reports, case series, case-control studies, and systematic reviews were included. RESULTS: A total of 8326 studies were identified based on the selected search terms, and 41 were included in this review based on relevance. CONCLUSION: There are specific dermoscopic characteristics in SoC for benign nevi, acral lentiginous melanoma, ethnic melanonychia, and dermatofibroma; however, there is a lack of published data about specific features of cutaneous melanoma, subungual melanoma, pigmented basal cell carcinoma, and pigmented squamous cell carcinoma in SoC. Because pigmented basal cell carcinoma, pigmented squamous cell carcinoma, ethnic melanonychia, and acral lentiginous melanoma are diagnosed at later stages in this population, it is important to understand their dermoscopic features. Further descriptive studies are needed to better characterize unique dermoscopic features in neoplasms in SoC.