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Rima Chakraborty,1 Carilyn N Wieland,2 Nneka I Comfere2 1University of Missouri-Kansas City Medical School, Kansas City, MO, 2Departments of Dermatology and Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA Abstract: The advent of personalized medicine has ushered in a new era for cancer therapy with a significant impact on the management of advanced melanoma. Molecular targeted therapies have shown promise in the management of various malignancies, including melanoma, with lower toxicity profiles and better overall survival as compared with conventional therapy. The discovery of BRAF mutations in melanoma led to the development of BRAF inhibitors for the treatment of advanced melanoma. However, growing concerns over drug resistance to molecular targeted therapies including BRAF inhibitors, have spurred efforts to elucidate additional molecular targets for the treatment of advanced melanoma. In this review, we discuss the known molecular aberrations in melanoma, current and novel targeted approaches in its treatment, and drug resistance patterns. Keywords: BRAF inhibitors, metastatic melanoma, personalized medicine

Histiocytoid Sweet syndrome (H-SS) is a histopathological variant of Sweet syndrome (SS) defined by cutaneous infiltration of immature myeloid cells morphologically resembling histiocytes. The association of H-SS with underlying malignancy, particularly myelodysplastic syndromes, is well-established. Myelodysplasia cutis (MDS-cutis) has been proposed to describe cases historically diagnosed as H-SS but characterized by shared clonality of the myeloid infiltrate in skin and bone marrow. Therefore, identifying patients who might have MDS-cutis is critical for the management of the associated hematologic malignancy. VEXAS syndrome, an adult-onset autoinflammatory disease, should also be included in the histopathologic differential diagnosis of H-SS, as it shares clinical and pathologic features with MDS-cutis. Through the presentation of two cases, we aim to highlight the defining features and key clinical implications of MDS-cutis and VEXAS syndrome., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Technology has revolutionized not only direct patient care but also diagnostic care processes. This study evaluates the transition from glass-slide microscopy to digital pathology (DP) at a multisite academic institution, using mixed methods to understand user perceptions of digitization and key productivity metrics of practice change., Methods: Participants included dermatopathologists, pathology reporting specialists, and clinicians. Electronic surveys and individual or group interviews included questions related to technology comfort, trust in DP, and rationale for DP adoption. Case volumes and turnaround times were abstracted from the electronic health record from Qtr 4 2020 to Qtr 1 2023 (inclusive). Data were analyzed descriptively, while interviews were analyzed using methods of content analysis., Results: Thirty-four staff completed surveys and 22 participated in an interview. Case volumes and diagnostic turnaround time did not differ across the institution during or after implementation timelines (p = 0.084; p = 0.133, respectively). 82.5% (28/34) of staff agreed that DP improved the sign-out experience, with accessibility, ergonomics, and annotation features described as key factors. Clinicians reported positive perspectives of DP impact on patient safety and interdisciplinary collaboration., Conclusions: Our study demonstrates that DP has a high acceptance rate, does not adversely impact productivity, and may improve patient safety and care collaboration., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

An 11-year-old female was referred from an outside institution after a diagnostic biopsy and subsequent excision of a progressively enlarging reddish-brown nodule demonstrated features concerning for a balloon cell nevus with severe atypia versus a high-grade melanocytoma. Upon review of the initial biopsy specimen and molecular data, we favored the diagnosis to be consistent with a high-grade melanocytoma with balloon cell changes while considering the possibility of balloon cell melanoma due to concerning histopathologic and genetic abnormalities. In this case study, we discuss critical diagnostic considerations in this rare pediatric case and highlight important pathologic and clinical features of melanocytomas and balloon cell melanoma., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Evaluation of basal cell carcinoma (BCC) involves tangential biopsies of a suspicious lesion that is sent for frozen sections and evaluated by a Mohs micrographic surgeon. Advances in artificial intelligence (AI) have made possible the development of sophisticated clinical decision support systems to provide real-time feedback to clinicians that could have a role in optimizing the diagnostic workup of BCC. There were 287 annotated whole-slide images of frozen sections from tangential biopsies, of which 121 contained BCC, that were used to train and test an AI pipeline to recognize BCC. Regions of interest were annotated by a senior dermatology resident, an experienced dermatopathologist and an experienced Mohs surgeon, with concordance of annotations noted on final review. Final performance metrics included a sensitivity and specificity of 0.73 and 0.88, respectively. Our results on a relatively small dataset suggest the feasibility of developing an AI system to aid in the workup and management of BCC., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Patching whole slide images (WSIs) is an important task in computational pathology. While most of them are designed to classify or detect the presence of pathological lesions in a WSI, the confounding role and redundant nature of normal histology are generally overlooked. In this paper, we propose and validate the concept of an "atlas of normal tissue" solely using samples of WSIs obtained from normal biopsies. Such atlases can be employed to eliminate normal fragments of tissue samples and hence increase the representativeness of the remaining patches. We tested our proposed method by establishing a normal atlas using 107 normal skin WSIs and demonstrated how established search engines like Yottixel can be improved. We used 553 WSIs of cutaneous squamous cell carcinoma to demonstrate the advantage. We also validated our method applied to an external dataset of 451 breast WSIs. The number of selected WSI patches was reduced by 30% to 50% after utilizing the proposed normal atlas while maintaining the same indexing and search performance in leave-one-patient-out validation for both datasets. We show that the proposed concept of establishing and using a normal atlas shows promise for unsupervised selection of the most representative patches of the abnormal WSI patches., (© 2024. The Author(s).)

Lichen planus (LP) can affect multiple body sites including skin, mucosae, scalp and nails, causing considerable impact on patients' quality of life. Currently, there are no LP patient-reported outcome measures (PROMs) that address all body sites potentially affected by LP. We developed a LP Quality of Life Questionnaire (LPQoL), informed by an expert consortium and patient survey study, to address this gap. The study was approved by our institution's Institutional Review Board. First, a 22-item LPQoL was designed with input from LP experts at our institution. The tool was then optimized by garnering input from patients recently diagnosed with LP, who were asked to complete the LPQoL, as well as the Dermatology Life Quality Index (DLQI) and a feedback form about the LPQoL. Fifty-eight of 150 patients (39% response rate) returned the questionnaire. Mean DLQI score was 4.9 ± 5.6 SD (range 0-25) and mean LPQoL score was 13.6 ± 10.4 SD (range 0-54). LPQoL score was positively correlated with DLQI score (r = 0.79; p < 0.001). Forty-nine out of 56 (88%) and 6/56 (11%) rated the LPQoL as 'very easy' or 'fairly easy' to complete, respectively. Based on participants' feedback, we increased the recall period from one week to one month and added questions on esophageal involvement. With iterative input from LP experts and patients, we developed a LPQoL to address the gap in a multi-site PROM specific to LP. This is a pilot study and there is ongoing validation studies; therefore, this measure should not be used in clinical practice or research until validated., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Malignant skin tumors in the setting of chronic leg ulcers (CLUs) are often underdiagnosed which may contribute to treatment delay and poor outcomes. The aims of our study were to determine the incidence and clinical characteristics of skin cancers in leg ulcers in the Olmsted County population from 1995 to 2020. We used the Rochester Epidemiology Project (a collaboration between health care providers) infrastructure to describe this epidemiology, allowing "population-based" research. Electronic medical records of adult patients with International Classification of Diseases diagnosis codes for leg ulcers and skin cancers on the legs were queried. Thirty-seven individuals with skin cancers in nonhealing ulcers were identified. The cumulative incidence of skin cancer over the 25-year period was 37:7864 (0.47%). The overall incidence rate was 470 per 100,000 patients. Eleven (29.7%) men and 26 (70.3%) women were identified with mean age of 77 years. History of venous insufficiency was present in 30 (81.1%) patients and diabetes in 13 (35.1%) patients. Clinical characteristics of CLU with skin cancer included abnormal granulation tissue in 36 (94.7%) and irregular borders in 35 (94.6%) cases. Skin cancers among CLUs included 17 (41.5%) basal cell carcinomas, 17 (41.5%) squamous cell carcinomas, 2 (4.9%) melanomas, 2 (4.9%) porocarcinomas, 1 (2.4%) basosquamous cell carcinoma, and 1 (2.4%) eccrine adenocarcinoma. The apparent association between chronic wounds and subsequent biopsy-proven skin cancer of the same site was primarily observed in elderly patients; malignant transformation of wounds favored basal cell carcinoma and squamous cell carcinoma. This retrospective cohort study further characterizes the association between skin cancers and chronic leg wounds., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose: Purpose: Subtotal skin electron beam therapy may be an option for patients with cutaneous lymphoma receiving radiation therapy to treat large areas of their skin but may benefit from sparing specific areas that may have had previous radiation therapy, are of specific cosmetic concern, and/or show no evidence of disease. We report here on the design, implementation, and dosimetric characteristics of a reusable and transparent customizable shield for use with the large fields used to deliver total skin electron beam therapy at extended distance with a conventional linear accelerator., Methods and Materials: A shield was designed and manufactured consisting of acrylic blocks that can be mounted on a steel frame to allow patient-specific shielding. The dosimetry of the device was measured using radiochromic film., Results: The shield is easy to use and well-tolerated for patient treatment, providing minimal electron transmission through the shield with a sharp penumbra at the field edge, with no increase in x-ray dose. We report on the dosimetry of a commercial device that has been used to treat more than 30 patients to date., Conclusions: The customizable shield is well suited to providing patient-specific shielding for subtotal skin electron beam therapy., Competing Interests: William Breen reports being on the scientific advisory board for GE Healthcare, with all payments made to his institution. John Lucido reports receiving an honorarium paid to his institution for work as grant referee for Global Bridges Oncology and consulting fees paid to his institution by Varian Medical Systems. Aaron Mangold reports currently receiving research grants paid to his institution by Regeneron, Corbus, Incyte, Pfizer, Eli Lilly, Argenyx, Palvella, Abbview, Priovant, and Merck and previous research grants in the past 36 months for Kyowa Kirin, Miragen, Sun Pharma, Elorac, Janssen, and Novartis. He also is currently receiving consulting fees paid to him from Janssen and Boehringer Ingelheim and paid to his institution from Argenyx, Incyte, Regeneron, Clarivate, and Pfizer, previously received consulting fees paid to him from Kyowa Kirin, Clarivate, Soligenix, Phlecs, Incyte, Eli Lilly, Momenta, UCB, and Bristol Myers Squibb, and is currently receiving payment for manuscript writing (for a separate manuscript) from Janssen. He holds a patent for “Topical Ruxolitinib for Treating Lichen Planus” (PCT/US2021/053149; 63/086,898) and has filed for a patent for “Methods and Materials for Assessing and Treating Cutaneous Squamous Cell Carcinoma” (63/423,254). Aaron Mangold is also currently on the Advisory Board for Bristol Myers Squibb currently the President of Pacific Dermatology Society, the Chair of the Community Outreach Committee for the American Academy of Dermatology, on the Board of Directors for the US Cutaneous Lymphoma Consortium, was previously the President of the Arizona Dermatology and Dermatological Society and a Board Member for the Arizona Medical Association (all unpaid), has personal stock ownership of Intellia Therapeutics and Editas, and is receiving medical writing support from Pfizer and Janssen. Chris Deufel reports being a board member of the American Brachytherapy Society., (© 2023 The Author(s).)

Importance: There is a knowledge gap about subcutaneous panniculitis-like T-cell lymphoma (SPTCL) owing to its rarity and diagnostic difficulty, resulting in an absence of well-documented large case series published to date., Objective: To generate consensus knowledge by a joint multi-institutional review of SPTCL and related conditions., Design, Setting, and Participants: This retrospective clinical and pathological review included cases initially diagnosed as SPTCL at 6 large US academic centers. All cases were reviewed by a group of pathologists, dermatologists, and oncologists with expertise in cutaneous lymphomas. Through a process of group consensus applying defined clinical and pathological diagnostic criteria, the cohort was classified as (1) SPTCL or (2) adipotropic lymphoproliferative disorder (ALPD) for similar cases with incomplete histopathological criteria for SPTCL designation., Exposures: Cases of SPTCL diagnosed between 1998 and 2018., Main Outcomes and Measures: The main outcome was disease presentation and evolution, including response to therapy, disease progression, and development of hemophagocytic lymphohistiocytosis., Results: The cohort of 95 patients (median [range] age, 38 [2-81] years; female-to-male ratio, 2.7) included 75 cases of SPTCL and 20 cases of ALPD. The clinical presentation was similar for both groups with multiple (61 of 72 [85%]) or single (11 of 72 [15%]) tender nodules mostly involving extremities, occasionally resulting in lipoatrophy. Hemophagocytic lymphohistiocytosis (HLH) was only observed in SPTCL cases. With a mean follow-up of 56 months, 60 of 90 patients (67%) achieved complete remission with a median (range) of 3 (1-7) cumulative therapies. Relapse was common. None of the patients died of disease progression or HLH. Two patients with ALPD eventually progressed to SPTCL without associated systemic symptoms or HLH., Conclusions and Relevance: In this case series of patients initially diagnosed as having SPTCL, results showed no evidence of systemic tumoral progression beyond the adipose tissue. The SPTCL experience in this study confirmed an indolent course and favorable response to a variety of treatments ranging from immune modulation to chemotherapy followed by hematopoietic stem cell transplantation. Morbidity was primarily associated with HLH.

Autoimmune bullous dermatoses are characterized by the presence of tissue-bound and often circulating pathogenic autoantibodies targeting structural components of the skin and/or mucous membranes. The diagnostic workup for this heterogeneous group of disorders consists of a multi-step process, of which the light microscopic examination is a crucial component. This review is organized following a classification scheme that is based on two main histopathologic features, namely level of intraepithelial split and composition of the inflammatory infiltrate. Overall, we aim to place emphasis on the histopathologic clues that can assist pathologists in differential diagnosis and review the updates in the literature., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Certain autoimmune bullous dermatoses are mediated by autoantibodies of the IgG4 subclass. We determined the diagnostic impact of adding IgG4 to our conventional direct immunofluorescence (DIF) panel., Methods: For all cases submitted to our referral laboratory for DIF over 1 month (n = 630), we performed IgG4 testing and collected consecutive biopsy specimens showing definite or indeterminate linear or cell-surface deposition of IgG, IgG4, and/or C3. On retrospective blinded review, we classified the pattern and whether the findings were definite, indeterminate, or negative. When present, substantial background staining was recorded., Results: Seventy DIF specimens met the inclusion criteria. Of 22 (31.4%) specimens equivocal for linear or cell-surface deposition, 9 (40.9%) had definitive IgG4 findings, either linear (3 of 14 equivocal linear cases; 21.4%) or cell-surface (6 of 8 equivocal cell-surface cases; 75.0%). Background deposition was substantial in 14 cases (20.0%) for IgG but in none for C3 or IgG4., Conclusion: IgG4 allowed the classification of over 40% of DIF cases that were otherwise equivocal by IgG and C3. IgG4 staining showed lower levels of non-specific background staining than IgG or C3. IgG4 appears to contribute most value in cases with cell-surface deposition or with equivocal linear IgG deposition and negative C3 results., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests., Methods: RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2., Results: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain.", Limitations: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded., Conclusions: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite being frequently overlooked during the examination of histopathological sections, eccrine sweat glands can offer clues for diagnosing various skin conditions. They provide important functions and can lead to several diseases when inflamed or injured. This review article provides information regarding eccrine physiology as well as well-established and novel entities that occur in association with eccrine gland pathology., (Copyright © 2021. Published by Elsevier Inc.)

Peripheral blood involvement by cutaneous T-cell lymphoma is typically assessed by flow cytometry and plays a critical role in diagnosis, classification, and prognosis. Simplified strategies to detect tumor cells (Sezary cells) fail to exclude reactive subsets, whereas tumor-specific abnormalities are subtle and inconsistently present. We implemented a flow cytometric strategy to detect clonal Sezary cells based on the monotypic expression of one of two mutually exclusive TCR constant β chains, TRBC1 and TRBC2. Analysis of CD4 + T-cell subsets and TCR variable β classes from healthy donors showed polytypic TRBC1 staining. Clonal Sezary cells were identified by TRBC1 staining in 56 of 111 (50%) samples from patients with cutaneous T-cell lymphoma, accounting for 7-18,155 cells/μl and including 13 cases (23%) lacking tumor-specific immunophenotypic abnormalities. CD4 + T-cell subsets from 86 patients without T-cell lymphoma showed polytypic TRBC1 staining, except for five patients (6%) with minute T-cell clones of uncertain significance accounting for 53-136 cells/μl. Assessment of TRBC1 expression within a comprehensive single-tube flow cytometry assay effectively overcomes interpretative uncertainties in the identification of Sezary cells without the need for a separate T-cell clonality assay., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Context.—: Autopsy rates have decreased dramatically despite providing important clinical information to medical practices and social benefits to decedents' families., Objective.—: To assess the impact of an institutional Office of Decedent Affairs (ODA), a direct communication link between pathology and decedents' families, on hospital autopsy consent rates, autopsy-related communication, practitioner views, and next-of-kin experiences., Design.—: A before and after study involving all hospital decedents whose deaths did not fall within the jurisdiction of the medical examiner's office from 2013 to 2018. A pathology-run ODA launched in May 2016 to guide next-of-kin through the hospital death process (including autopsy-related decisions) and serve as the next-of-kin's contact for any subsequent autopsy-related communication. Critical care and hematology/oncology practitioners were assessed for their autopsy-related views and decedents' next-of-kin were assessed for their autopsy-related experiences. Autopsy consent rates for non-medical examiner hospital deaths, autopsy-related communication rates, practitioner views on the role and value of autopsy, and next-of-kin autopsy experiences and decisions factors were compared prior to and after ODA launch., Results.—: Autopsy consent rates significantly increased from 13.2% to 17.3% (480 of 3647 deaths versus 544 of 3148 deaths; P < .001). There were significant increases in the rate of autopsy-related discussions and bereavement counseling provided to decedents' families. Practitioner views on the positive role of autopsy for any hospital death and those with advanced stage cancer also significantly increased. Next-of-kin indicated more consistent autopsy-related discussions with the potential benefits of autopsy discussed becoming key decision factors., Conclusions.—: An ODA improves hospital autopsy consent rates, autopsy-related communication, providers' autopsy-related views, and next-of-kins autopsy experiences., (© 2021 College of American Pathologists.)

Background: Atypical cutaneous lymphoid infiltrates are challenging lesions in dermatopathology. We present a summary of the literature regarding kappa and lambda immunohistochemistry (IHC) and in situ hybridization (ISH) in the evaluation of atypical cutaneous or mucosal lymphoid infiltrates., Methods: Relevant articles from 1967 to 2018 in the English language were identified and summarized. In the absence of larger studies, case series of n ≥ 3 were included., Results: Sixty-three articles assessing kappa and lambda IHC and/or ISH were identified. Most focused on marginal zone lymphomas. Other lymphomas included follicle center lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma, plasmablastic lymphoma, multiple myeloma, monoclonal gammopathy of undetermined significance, and polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS). Non-neoplastic lesions included reactive lymphoid hyperplasia, cutaneous plasmacytosis, connective tissue disease, IgG4-related disease, acrodermatitis chronic atrophicans, Zoon balanitis, dermatitides, and infiltrates around epithelial dysplasias/neoplasias., Conclusion: Kappa and lambda IHC and ISH are useful tools in the evaluation of cutaneous B-cell lymphomas and plasma cell neoplasms. The literature supports that the detection of light-chain restriction by IHC and ISH is one of the most useful findings in the differential diagnosis of reactive lymphoid hyperplasia vs B-cell lymphoma with plasmacytic differentiation., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Granulomatous dermatoses may represent primary skin inflammation or can serve as the harbinger of a multitude of underlying systemic disorders or drug reactions. Taken together with clinical findings, the microscopic features from skin biopsy can allow recognition of various patterns and facilitate a precise diagnosis. Accurate classification of entities in this category of inflammatory dermatoses may prompt clinicians to investigate for underlying systemic problems, thereby allowing the pathologist to add considerable value in the care of affected patients. This review article categorizes clinical and microscopic features of common and uncommon causes of noninfectious dermal and subcutaneous granulomatous inflammation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The relationship between age-related macular degeneration (AMD) and malignancy, especially cutaneous malignancies, is not well studied. We investigated a possible association between AMD and cutaneous malignancies., Methods: A retrospective, consecutive review of all patients who had received at least 1 intravitreal injection for wet AMD between January 1, 2004, and December 31, 2013, was conducted using the Rochester Epidemiology Project in Olmsted County, Minnesota. Age- and sex-matched control groups included 473 pre-anti-vascular endothelial growth factor era wet AMD patients, 504 concurrent time dry AMD patients, and 504 patients with no AMD. The rates of AMD and overall malignancy, cutaneous malignancies, and specific types of cutaneous malignancies were compared between groups of patients., Results: Patients with wet AMD incurred an increased rate of overall malignancies compared to patients with dry AMD {52.8% wet AMD (confidence interval [CI]: 48.3-57.2) vs. 43.7% dry AMD (CI: 39.3-48.1); P= 0.003} or those without AMD (52.8% wet AMD [CI: 48.3-57.2] vs. 35.3% no AMD [CI: 31.1-39.7]; P = <0.001). Patients with dry AMD also had higher rates of malignancy than those without AMD (43.7% dry AMD [CI: 39.3-48.1] vs. 35.3% no AMD [CI: 31.1-39.7]; P = 0.007). Rate of cutaneous malignancies was increased in patients with wet AMD compared to patients with dry AMD (24.4% wet AMD [CI: 20.7-28.4] vs. 14.6% dry AMD [CI: 11.5-17.9]; P = <0.001) and those with no AMD (24.4% wet AMD [CI: 20.7-28.4] vs. 9.7% no AMD [CI: 7.3-12.7]; P = <0.001)., Conclusion and Relevance: To the best of our knowledge, this is the first report to establish an association between AMD and cutaneous malignancies, supporting a possible discussion of the association when a patient presents with one of the two conditions.

Context.—: Preanalytic errors, including specimen labeling errors and specimen loss, occur frequently during specimen collection, transit, and accessioning. Radio-frequency identification tags can decrease specimen identification and tracking errors through continuous and automated tracking of specimens., Objective.—: To implement a specimen tracking infrastructure to reduce preanalytic errors (specimen mislabeling or loss) between specimen collection and laboratory accessioning. Specific goals were to decrease preanalytic errors by at least 70% and to simultaneously decrease employee effort dedicated to resolving preanalytic errors or investigating lost specimens., Design.—: A radio-frequency identification specimen-tracking system was developed. Major features included integral radio-frequency identification labels (radio-frequency identification tags and traditional bar codes in a single printed label) printed by point-of-care printers in collection suites; dispersed radio-frequency identification readers at major transit points; and systems integration of the electronic health record, laboratory information system, and radio-frequency identification tracking system to allow for computerized physician order entry driven label generation, specimen transit time tracking, interval-based alarms, and automated accessioning., Results.—: In the 6-month postimplementation period, 6 mislabeling events occurred in collection areas using the radio-frequency identification system, compared with 24 events in the 6-month preimplementation period (75% decrease; P = .001). In addition, the system led to the timely recovery of 3 lost specimens. Labeling expenses were decreased substantially in the transition from high-frequency to ultrahigh frequency radio-frequency identification tags., Conclusions.—: Radio-frequency identification specimen tracking prevented several potential specimen-loss events, decreased specimen recovery time, and decreased specimen labeling errors. Increases in labeling/tracking expenses for the system were more than offset by time savings and loss avoidance through error mitigation.

Background: Little research has been done in teledermatology to examine the effects of standardized templates and subject-specific learning modules., Methods: We performed a prospective study examining the effects of standardized templates and standardized cutaneous oncology learning modules on teledermatology referrals at Mayo Clinic. This data was then compared to previous teledermatology referrals before standardized templates were adopted., Results: A total of 42 teledermatology consultations were performed during the 4-month study period. The use of standardized templates resulted in an absolute reduction in face-to-face referrals. Teledermatology consultation increased the absolute diagnostic and management concordance by 26.2% (P = 0.02) and 33.3% (P < 0.01), respectively, and decreased the absolute diagnostic and management discordance by 19.1% (P = 0.03) and 31.0% (P < 0.01), respectively. The largest knowledge gaps were identified in cutaneous oncology. Educational intervention improved theoretical referral rates and confidence in diagnosis and management overall., Conclusion: The implementation of standardized intake templates reduces the rate of face-to-face referrals. Teledermatology improves primary care-based dermatological care and reduces theoretical referral rates., (© 2019 The International Society of Dermatology.)

The recently published 2016 revision of the WHO classification of lymphoid neoplasms includes primary cutaneous acral CD8-positive T-cell lymphoma (PCATCL) as a provisional entity. This is a rare indolent lymphoma characterized by papules or nodules on the ear and a dermal infiltrate of CD8-positive T-lymphocytes with cytotoxic marker expression. A retrospective review of a single institutional experience with PCATCL identified 3 patients (mean age 54; range 49-62) with papules or nodules on the ear. Lesional biopsies demonstrated a dense diffuse dermal infiltrate of atypical lymphocytes with a Grenz zone in 2 cases and focal epidermotropism in 1 case. The atypical lymphocytes were predominantly CD3 and CD8 positive with expression of cytotoxic marker TIA1. Staging evaluation failed to reveal systemic disease. Two patients underwent local excision, and the third received local radiation therapy all with complete response and no disease recurrence at last follow-up 3 months (range 2-5 months). Our cases add to the existing limited literature on the clinical and histopathological features of PCATCL. We also performed an updated systematic literature view of the entity.

A common challenge faced by researchers associated with healthcare institutions is that data of interest are often contained in electronic medical informatics systems that are centered on optimizing clinician/clinician and patient/clinician communication. While this focus naturally enhances the primary goal of care delivery, it is often suboptimal for secondary research purposes. For example at our institution while it is easy for a clinician to view images associated with a specific patient visit, it remains a challenge for an investigator to assemble a cohort of specific images in order to further research objectives. In order to address this important optimization gap we have developed a system for automated image categorization based on a deep neural network. This image classifier organizes the contents of an electronic health record system in a manner which is more amenable to further research by specifically dividing all available images into a lexicon of subclasses. While the current study is focused on dermatology-related images collected by a combined primary and tertiary care center, we expect similar approaches to aid a variety of institutions and clinical specialties.

Background: Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy, and physician decision-making., Objectives: The American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology., Methods: The RAND/UCLA appropriateness methodology, which combines evidence-based medicine, clinical experience, and expert judgment, was used to develop AUC in dermatopathology., Results: With the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate" and 52 (25%) "rarely appropriate" and 43 (20%) having "uncertain appropriateness.", Limitations: The methodology requires a focus on appropriateness without comparison between tests and irrespective of cost., Conclusions: The ultimate decision to order specific tests rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness-the AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed "uncertain appropriateness" and where consensus was not reached may benefit from further research., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy and physician decision-making., Objectives: The American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology., Methods: The RAND/UCLA appropriateness methodology, which combines evidence-based medicine, clinical experience and expert judgment, was used to develop AUC in dermatopathology., Results: With the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate," 52 (25%) "rarely appropriate" and 43 (20%) "uncertain appropriateness.", Limitations: The methodology requires a focus on appropriateness without comparison between tests and irrespective of cost., Conclusions: The ultimate decision of when to order specific test rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness-AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed "uncertain appropriateness" and where consensus was not reached may benefit from further research., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: PhotoExam is a mobile app that incorporates digital photographs into the electronic health record (EHR) using iPhone operating system (iOS, Apple Inc)-based mobile devices., Objective: The aim of this study was to describe usage patterns of PhotoExam in primary care and to assess clinician-level factors that influence the use of the PhotoExam app for teledermatology (TD) purposes., Methods: Retrospective record review of primary care patients who had one or more photos taken with the PhotoExam app between February 16, 2015 to February 29, 2016 were reviewed for 30-day outcomes for rates of dermatology consult request, mode of dermatology consultation (curbside phone consult, eConsult, and in-person consult), specialty and training level of clinician using the app, performance of skin biopsy, and final pathological diagnosis (benign vs malignant)., Results: During the study period, there were 1139 photo sessions on 1059 unique patients. Of the 1139 sessions, 395 (34.68%) sessions documented dermatologist input in the EHR via dermatology curbside consultation, eConsult, and in-person dermatology consult. Clinicians utilized curbside phone consults preferentially over eConsults for TD. By clinician type, nurse practitioners (NPs) and physician assistants (PAs) were more likely to utilize the PhotoExam for TD as compared with physicians. By specialty type, pediatric clinicians were more likely to utilize the PhotoExam for TD as compared with family medicine and internal medicine clinicians. A total of 108 (9.5%) photo sessions had a biopsy performed of the photographed site. Of these, 46 biopsies (42.6%) were performed by a primary care clinician, and 27 (25.0%) biopsies were interpreted as a malignancy. Of the 27 biopsies that revealed malignant findings, 6 (22%) had a TD consultation before biopsy, and 10 (37%) of these biopsies were obtained by primary care clinicians., Conclusions: Clinicians primarily used the PhotoExam for non-TD purposes. Nurse practitioners and PAs utilized the app for TD purposes more than physicians. Primary care clinicians requested curbside dermatology consults more frequently than dermatology eConsults., (©Jennifer L Pecina, Kirk D Wyatt, Nneka I Comfere, Matthew E Bernard, Frederick North. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 08.11.2017.)

Background: Untreated calciphylaxis is a fatal disease of intra- and extravascular calcification, most commonly presenting in end-stage renal disease (ESRD) patients. While early identification is critical for timely treatment, early-stage clinical and histopathological descriptions have not, to our knowledge, been elucidated. As early clinical recognition is essential to prompt definitive histopathological diagnosis, this study describes a range of clinical and histopathological manifestations of early-stage calciphylaxis., Methods: Five patients with clinical photographs of lesions of early-phase calciphylaxis were chosen from a recent database of 101 patients. Their clinical histories were reviewed and correlated with their respective clinical and histopathological images of early-stage disease and progression of the disease., Results: Two of the five patients were identified early to have calciphylaxis and were promptly initiated on aggressive, multimodal therapy, resulting in complete resolution and remission of calciphylaxis. The other three patients were also recognized in early stages, one without renal disease, although the disease had progressed to more advanced stages associated with greater morbidity and mortality., Conclusions: These cases demonstrate that calciphylaxis may be clinically misdiagnosed due to ill-defined presentations, particularly in the early stages without the characteristic features of livedo racemosa and ulceration. However, recognition in the early stages is critical to implement timely treatment. As such, definitively diagnostic skin biopsy should be considered early in suspected cases to confirm the diagnosis of calciphylaxis and ensure prompt management of this lethal disease., (© 2017 The International Society of Dermatology.)

Objective: To identify patients evaluated in an outpatient setting at our institution with a presentation of recurrent orofacial swelling and to review the spectrum of causes to outline a diagnostic approach., Patients and Methods: A retrospective study of 104 patients with more than 1 episode of orofacial swelling lasting for more than 5 days identified through a keyword search of the electronic health record from January 2, 2000, through July 5, 2011., Results: Patients were categorized according to final cause of orofacial swelling: idiopathic orofacial granulomatosis, solid facial edema due to rosacea and acne vulgaris, Crohn disease, contact dermatitis, sarcoidosis, exfoliative cheilitis, lichen planus, actinic cheilitis, cheilitis glandularis, lymphedema, miscellaneous, and multifactorial. Granulomatous inflammation was noted on biopsy in 40 of 85 patients (47%). Oral involvement was associated with Crohn disease (P<.001), and facial and periorbital swelling was associated with solid facial edema in the setting of rosacea and acne vulgaris (P<.001)., Conclusion: The broad range of diagnoses responsible for recurrent orofacial swelling underscores the diagnostic challenge and importance of a thorough multidisciplinary evaluation to identify underlying causes., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Timely pathologic diagnosis relies on the communication of specific clinical information in the requisition form (RF). Clinical information may use nonspecific terms such as "rule out", the use of which may result in diagnostic delays and the unnecessary application of pathology stains and sections., Objective: This study was designed to evaluate the relationship between use of the term "rule out" and time to diagnosis, and the use of additional pathology stains and sections in integrated and non-integrated dermatopathology practices., Methods: A retrospective double-cohort study of 475 RFs from the integrated practice (of which 182 used the term "rule out" [RO] and 293 did not [NRO]) and 412 RFs from the non-integrated practice (RO, n = 126; NRO, n = 286) was performed., Results: No significant differences emerged between groups of patients with, respectively, RO and NRO RFs in the integrated practice with respect to time to diagnosis, and numbers of additional tissue sections or stains applied. By contrast, the use of RFs containing the term "rule out" was associated with significantly longer times to diagnosis and higher rates of use of pathology stains and sections in comparison with NRO RFs in the non-integrated practice. However, the study is limited by its status as a retrospective review of data sourced from a single institution., Conclusions: Use of the term "rule out" in RFs may not significantly impact key care delivery outcomes in an integrated practice. However, it may cause diagnostic delays and the use of unnecessary pathology services in a non-integrated practice., (© 2016 The International Society of Dermatology.)

Objectives: To define indices of completeness and accuracy of clinical information in the skin biopsy requisition form (RF) and correlate them with health care delivery outcomes and pathology service utilization., Methods: RFs in our pathology information system were reviewed and assessed for the presence of 10 clinical elements considered critical for dermatopathologic diagnosis. Accuracy was determined by reviewing corresponding clinical notes., Results: In total, 249 RFs were reviewed. In inflammatory dermatoses, provision of a clinical impression, provision of more than two elements, and achieving more than 75% accuracy were associated with improved outcomes and decreased utilization. For all nonlymphoproliferative cases, higher quality clinical information was associated with decreased turnaround time (P < .001). More clinical information was associated with increased utilization and turnaround time (P = .0235) for lymphoproliferative cases and higher resampling rates for melanocytic lesions (P = .0066)., Conclusions: In inflammatory dermatoses, providing high-quality clinical information on the RF promotes optimal histopathologic diagnostic performance and appropriate pathology service utilization., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Teledermatopathology has evolved from static images to whole slide imaging (WSI), which allows for remote viewing and manipulation of tissue sections. Previous studies of WSI in teledermatopathology predated College of American Pathologists (CAP) telepathology validation guidelines., Objective: We conducted a comprehensive retrospective WSI validation study of routine dermatopathology cases, adhering to CAP guidelines., Method: In all, 181 consecutive cases arranged into 3 categories (inflammatory, melanocytic, nonmelanocytic proliferations) were reviewed by 3 board-certified dermatopathologists via traditional microscopy (TM) and WSI. Intraobserver (TM vs WSI), TM intraobserver and interobserver (TM vs TM), and WSI interobserver (WSI vs WSI) concordance was interpreted using a 3-tier system., Results: TM versus WSI intraobserver concordance (86.9%; 95% confidence interval [CI] 83.7-89.6) did not differ from TM versus TM intraobserver concordance (90.3%; 95% CI 86.7-93.1) or interobserver concordance (WSI: 89.9%; 95% CI 87.0-92.2, and TM: 89.5%; 95% CI 86.5-91.9). Melanocytic proliferations had the lowest TM versus WSI intraobserver concordance (75.6%; 95% CI 68.5-81.5), whereas inflammatory lesions had the highest TM versus WSI intraobserver concordance (96.1%; 95% CI 91.8-98.3). Nonmelanocytic proliferations had an intraobserver concordance of 89.1% (95% CI 83.4-93.0)., Limitations: Efficiency and other logistical WSI parameters were not evaluated., Conclusion: Intraobserver and interobserver diagnostic concordance between WSI and TM was equivalent. Therefore, WSI appears to be a reliable diagnostic modality for dermatopathology., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a rare and aggressive disease either originating in or secondarily involving the skin., Objective: We sought to assess clinical, histopathologic, and prognostic features of patients with cutaneous PTCL-NOS., Methods: This was a retrospective chart review of patients with cutaneous PTCL-NOS between 1993 and 2013., Results: Thirty patients with PTCL-NOS were included. Fourteen had skin-only disease and 15 had concurrent skin and systemic disease at presentation. In primary cutaneous PTCL-NOS, the overall survival rate at 5 years was 61% (95% confidence interval, 37-100%; number still at risk, 2). The median overall survival was 5.6 years. Patients were diagnosed a median of 2.4 months from symptom onset. Patients with concurrent disease died a median of 2.1 years after diagnosis. The estimated overall survival rate at 5 years after diagnosis was 29% (95% confidence interval, 13-67%; number at risk, 3). The median overall survival was 3.9 years. Patients were diagnosed a median of 6 months from symptom onset, with a 53% increased risk of death for each year from symptom onset to diagnosis., Limitations: This was a retrospective study with a limited number of cases., Conclusions: Age at diagnosis and B-symptoms predict poor survival in patients with cutaneous PTCL-NOS. In addition, poorer survival is observed in patients with multifocal lesions and concomitant skin and systemic PTCL-NOS., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The skin biopsy requisition form (RF) serves as a key communication tool for transfer of relevant information related to skin biopsy between clinicians and pathologists. Clinical information in the skin biopsy RF is frequently missing or incomplete., Objective: To determine the rates of provision of critical clinical information necessary for histopathologic interpretation in the skin biopsy RF and encounter visit note (EVN)., Methods: A retrospective review of 300 RFs and corresponding EVNs from May 1 to 7, 2012, in a tertiary care dermatology practice., Results: Age (100%), lesion location (100%), and clinical impression (93%) were the most commonly supplied elements in the RF and EVN. Clinical elements that were commonly not provided in the RF but present in the EVN included sampling method - partial versus complete (46%), duration of lesion (54%), morphology of lesion (97%), clinical symptoms (63%), clinical photos (63%), previous clinical (97%), and dermatopathologic diagnoses (82%)., Limitations: Retrospective study design., Conclusions: These data suggest that while missing critical clinical information in the RF is often present in the EVN, some information is still not present in either source.

Purpose: To summarize characteristics and validity evidence of tools that assess teamwork in undergraduate medical education (UME), and provide recommendations for addressing the interprofessional collaboration competencies of the Association of American Medical Colleges (AAMC)., Method: The authors conducted a systematic review, searching MEDLINE, MEDLINE In-process, CINAHL, and PsycINFO from January 1, 1979, through April 1, 2014; they searched reference lists and national meeting abstracts. They included original research reports that described a quantitative tool used to assess teamwork in UME. They abstracted characteristics and validity evidence for the tools, plus study quality, according to established frameworks. Two authors independently abstracted 25% of articles and calculated agreement. Authors then applied predefined criteria to identify tools best suited to address the AAMC's teamwork competencies., Results: Of 13,549 citations, 70 articles describing 64 teamwork assessment tools were included. Of these 64 tools, 27 (42%) assessed teamwork in classroom, 31 (48%) in simulation, and only 7 (11%) in actual clinical settings. The majority (47; 73%) of tools assessed medical students' teamwork in interprofessional teams. On the basis of content concordance, strength of validity evidence, generalizability of scores, and level of outcomes, four published tools were recommended to assess the AAMC's teamwork competencies: the Collaborative Healthcare Interdisciplinary Relationship Planning Scale, Readiness for Interprofessional Learning Scale, Communication and Teamwork Skills assessment, and Teamwork Mini-Clinical Evaluation Exercise., Conclusions: Substantial validity evidence supports the use of several UME teamwork assessments. Four tools have been appropriately designed and sufficiently studied to constitute appropriate assessments of the AAMC's teamwork competencies.

Patient-centered emergency diagnostic imaging relies on efficient communication and multispecialty care coordination to ensure optimal imaging utilization. The construct of the emergency diagnostic imaging care coordination cycle with three main phases (pretest, test, and posttest) provides a useful framework to evaluate care coordination in patient-centered emergency diagnostic imaging. This article summarizes findings reached during the patient-centered outcomes session of the 2015 Academic Emergency Medicine consensus conference "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization." The primary objective was to develop a research agenda focused on 1) defining component parts of the emergency diagnostic imaging care coordination process, 2) identifying gaps in communication that affect emergency diagnostic imaging, and 3) defining optimal methods of communication and multidisciplinary care coordination that ensure patient-centered emergency diagnostic imaging. Prioritized research questions provided the framework to define a research agenda for multidisciplinary care coordination in emergency diagnostic imaging., (© 2015 by the Society for Academic Emergency Medicine.)

Background: Milestone-based assessments of resident physicians inform critical decisions regarding resident competence and advancement. Thus, it is essential that milestone evaluations are based upon strong validity evidence and that consistent evaluation criteria are used across residency programs. A common approach to assessment of interprofessional collaboration milestones is particularly important since standardized measures of individual resident competence in interprofessional collaboration have not been established., Discussion: We propose that assessments of interprofessional collaboration in graduate medical education meet common criteria, namely, these assessments should: 1) measure competency of an individual resident, 2) occur in the context of an interprofessional team, 3) be ascertained via direct observation of the resident, 4) be performed in a real-world clinical practice setting (such as a hospital ward, outpatient clinic, or operating room). We present the evidence-based rationale for these criteria and cite examples of published assessment instruments that fulfill one or more of the criteria, however further research is needed to ensure fidelity of assessments. The proposed criteria may assist residency educators as they endeavor to provide robust and consistent assessments of interprofessional collaboration milestones.

Frozen section pathology is routinely used for margin assessment of non-melanoma skin cancer (NMSC). Frozen section can also be used for the primary diagnosis of several skin lesions. Limited data exist on the accuracy of frozen section in the diagnosis of NMSC. We performed a retrospective chart review of 300 cases in which frozen section diagnoses were compared with permanent section diagnoses of NMSC. Frozen section and permanent section pathology were concordant 83.3% of the time, with the highest concordance rates noted for basal cell carcinoma (145/153, 95%). Our results show a high level of concordance between frozen section and corresponding permanent section pathology diagnosis for NMSC. The rapidity of frozen section tissue processing and pathology reporting makes this technique useful in dermatologic practice for immediate diagnosis and management of NMSC. Further studies should explore strategies to decrease or eliminate discrepancies between frozen and permanent section diagnosis., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)