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Ongoing controversy exists regarding terminology used to describe atypical melanocytic nevi. Efforts to standardize nomenclature, including the 1992 NIH consensus conference, have been largely unsuccessful. Significant advances have revealed an increasingly detailed genetic picture of melanocytic neoplasms, including strong evidence for the existence of those with "intermediate" behavior.We sent an electronic survey to dermatopathologists (n=846) to assess trends in nomenclature usage and attitudes toward developing new consensus nomenclature for atypical melanocytic nevi.There were 229 complete responses (27.1% response rate). The most used/preferred nomenclature was "dysplastic nevus" (43%/39%, respectively), followed by the NIH-recommended terminology (28%/26%). Three-tier grading systems were most heavily used/preferred (79%/63%). Dermatopathologists based in New England were most likely to use the NIH terminology, whereas "dysplastic nevus" or 'other' were most used elsewhere (p=0.029). Most (76%) expressed at least "moderate" enthusiasm for developing consensus nomenclature, with 47% "very" or "extremely" enthusiastic.Little has changed with the wide variation in terminology for atypical melanocytic nevi. There continues to be no one dominant terminology in use. However, there is enthusiasm for standardization. A new attempt at updated consensus nomenclature may be fruitful.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase–positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase–negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.

Table S3 lists immune-related genes with the most statistically significant differences in induction between clinical responders versus non-responders

Figure S3 shows quantification of new and induced TCR clones in tumor and blood

Purpose:G100 is a toll-like receptor 4 (TLR4) agonist that triggers innate and adaptive antitumor immune responses in preclinical models. This pilot study assessed the safety, efficacy, and immunologic activity of intratumoral (IT) administration of G100 in patients with Merkel cell carcinoma (MCC).Patients and Methods:Patients with locoregional MCC (n = 3; cohort A) received neoadjuvant IT G100 (2 weekly doses at 5 μg/dose) followed by surgery and radiotherapy; patients with metastatic MCC (n = 7; cohort B) received 3 doses in a 6-week cycle and could receive additional cycles with/without radiotherapy.Results:IT G100 was safe and feasible in both neoadjuvant and metastatic settings. Treatment-related adverse events were mostly grade 1 or 2 injection-site reactions. IT G100 led to increased inflammation in the injected tumors with infiltration of CD8+ and CD4+ T cells and activation of immune-related genes. These proinflammatory changes were associated with local tumor regression and appeared to promote systemic immunity. All 3 cohort A patients successfully completed therapy; 2 patients remain recurrence free at 44+ and 41+ months, including 1 with a pathologic complete response after G100 alone. In cohort B, 2 patients achieved sustained partial responses, both lasting 33+ months after 2 cycles of therapy.Conclusions:In this first-in-human study, IT G100 induced antitumor immune responses, demonstrated acceptable safety, and showed encouraging clinical activity.See related commentary by Marquez-Rodas et al., p. 1127

Background Cryoballoon ablation (CBA) is a useful treatment for pulmonary vein isolation (PVI). Some cases, however, are difficult to treat and may require multiple freezing procedures and/or touch-up ablation. Although several predictors of CBA difficulty have been reported, no report has been able to assess the spatial location and morphology of the left atrium (LA) and pulmonary veins (PVs). A polygonal mesh is a collection of vertices, edges, and faces that defines the shape of a polyhedral object, and is able to represent a spatial location with a small amount of information. We hypothesized that a deep learning model that learns mesh representation datasets could more accurately detect the CBA difficulty and that we could establish a novel evaluation method in CBA. Purpose The aim of this study was to create a model to predict CBA difficulty with a 3D deep learning model using polygonal mesh representation. Methods and results All the 140 patients who underwent CBA for drug-resistant atrial fibrillation between January 2015 and January 2022 were included. A 28-mm cryoballoon (Arctic Front Advance, Medtronic) was used in all cases. We defined CBA difficulty as requiring a touch-up ablation procedure to create complete PVI. We converted the volume data in DICOM format of the computed tomography images of PVs and LA to obj file format (shown in Figure 1), which supports the definition of the geometry for object surfaces using polygonal meshes. Next, we developed a deep learning model that could learn polygonal meshes and classify whether the CBA required touch-up ablation or not. Only a training dataset is used to train the deep learning model, and finally, a test dataset is used to evaluate the model metrics. The accuracy, area under the ROC curve, recall, precision, and f1-score of the deep learning model using the test dataset was 86.5%, 87.7%, 66.7%, 75.0%, 70.6%, respectively. Conclusions We developed a 3D deep learning model that can detect a difficulty in CBA using polygonal mesh representation. By predicting difficult cases in advance, we will be able to develop strategies to increase the success rate. Funding Acknowledgement Type of funding sources: None.

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL) and often has an indolent course, particularly for patients presenting with early-stage (patch/plaque) disease. Early-stage MF is primarily managed with skin-directed therapies. Topical mechlorethamine hydrochloride (nitrogen mustard [NM]) gel has increased tolerability compared to prior NM formulations, though contact dermatitis remains a common side effect. The addition of topical steroids can improve tolerability while maintaining the efficacy of NM gel. Real-world experience supports that NM gel also has a role in combination therapy and as adjunctive therapy in advanced-stage disease. Here we review factors that may influence patient selection for use of NM gel, including MF variants, special patient populations, cost effectiveness, and impact on quality of life for patients with MF.

BACKGROUND Early and accurate diagnosis of systemic amyloidosis (SA) is critical for optimal patient outcomes. Biopsy of clinically uninvolved skin and subcutaneous tissue including abdominal skin punch biopsy (ASPB) is often used as a surrogate for affected organ sampling. There is a lack of published data on the sensitivity and specificity of ASPB for diagnosing SA. METHODS Retrospective chart review between 2000 and 2020 of all ASPB was performed to diagnose SA. Amyloid deposition was confirmed by Congo red stain. Study group includes patients with histopathologically and clinically confirmed diagnosis of SA. Control group includes patients without histopathology of amyloid deposition and no clinical SA. RESULTS Forty-one patients meeting inclusion criteria were analyzed; 23 study group and 18 control group patients. The overall diagnostic sensitivity of ASPB was 43% (95% CI 23%-66%) and the specificity 100% (95% CI 81%-100%). The AL amyloidosis diagnostic sensitivity was 64% (95% CI 35%-87%). ASPB >10 mm in depth had 100% (95% CI 54%-100%) sensitivity compared to 24% for depth ≤10 mm (P = .002). CONCLUSIONS ASPB is a minimally invasive and highly specific method of diagnosing SA. It is particularly sensitive for diagnosing AL amyloidosis and the diagnostic sensitivity can be significantly improved with adequate biopsy depth and diameter.

Background Sexual harassment (SH) includes unwelcome sexual advances, requests for sexual favors, and hostile conduct that targets someone based on gender and overlaps with some types of sexual assault (SA). SH/SA in health care can occur between providers or between patient and provider. Most studies of SH in medicine focus on SH perpetrated by one health care provider against another, with very few studies examining SH from patient to provider. Objective This study aimed to describe the prevalence and impact of SH/SA from patient to provider, with a particular focus on SH/SA experienced by dermatologists and trainees. Methods An anonymous electronic survey was sent to professional listservs and an online forum, which included representatives from multiple institutions, practice settings, and medical specialties. Trainees and dermatologists were targeted particularly. Results A total of 330 complete responses were included. In all, 83% of respondents reported experiencing SH from a patient. SH from a patient was more frequently reported by women compared with men (94% vs. 52%; p = .001). Behaviors consistent with SA were experienced by 31% of respondents and were more frequently experienced by women (35% vs. 15%; p = .001). Women were more likely to report that patient-to-provider SH contributed to burnout (33% of women vs. 9% of men; p = .002). Female trainees were significantly more likely to have experienced SH compared with female attendings within the past year (94 of 110 trainees [86%] vs. 83 of 127 attendings [65%]; p = .001). There was no significant difference in the proportion of women reporting ever experiencing SH when comparing dermatology and nondermatology specialties. Limitations The limitations of this study include the relatively small sample size, oversampling of trainees, and a gender-biased sample. Conclusion Patient-to-provider SH/SA is widespread, particularly among women and trainees, and may have a significant impact on burnout.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal neoplasm typically arising on the face of older individuals, most commonly around the eyelids. Histopathologic features include a circumscribed proliferation of low-grade epithelioid cells with areas of cystic and cribriform growth, foci of intracytoplasmic and extracellular mucin, and coexpression of endocrine, neuroendocrine, and cytokeratin markers by immunohistochemistry. Given histopathologic and immunohistochemical similarities, EMPSGC is often likened to solid papillary carcinoma of the breast and endocrine ductal carcinoma in situ, and is thought by many to represent a forme fruste of mucinous carcinoma of the skin. To date, the vast majority of reported cases of EMPSGC have been described as having indolent behavior, with no cases of distant metastasis yet reported. Here we report a unique case of EMPSGC that recurred over several years following standard surgical excision and Mohs micrographic surgery, with subsequent metastasis to the parotid gland and axial skeleton.

Pyoderma gangrenosum (PG) can represent a diagnostic challenge, leading to missed or delayed diagnosis. With prolonged immunosuppressive therapy, the risk of infections is elevated, predisposing patients to receive anti-infective treatments and, in serious cases, amputations. Limb amputations have been reported as complication of PG misdiagnosis but can also occur as a complication of long-standing PG ulcers.We aimed to describe the clinical characteristics of patients with PG leading to limb amputation through a multicenter retrospective case series between 2010 and 2020 including patients with PG who underwent limb amputation. We report a descriptive analysis of these patients' clinical course and outcome.Ten patients with PG who underwent at least one limb amputation were identified. Six were male (60%). Mean age was 65 years. All patients had ulcerative PG on the lower extremities, with a mean PG ulcer duration of 30.6 months. Six patients had PG-related comorbidities such as ulcerative colitis, myelodysplasia, and inflammatory arthritis. Other significant comorbidities included diabetes mellitus (DM) (five patients), coronary artery disease (five patients), and chronic kidney disease (two patients). The majority of patients (8/10) were correctly diagnosed with PG prior to amputation, whereas two patients were misdiagnosed with necrotizing soft tissue infections (NSTIs). All patients received intravenous antibiotics without substantial improvement. Eight patients developed sepsis and shock-like symptoms and the diagnosis of NSTIs was considered. Below-knee amputation was performed in six patients and above-knee amputation in four. Four patients had amputation performed twice because of recurrent NSTIs. Conclusion This multicenter case series sheds light on practice gaps for physician assessing patients with PG, in that limb amputation may result from PG misdiagnosis or complications thereof. Elderly patients (above 65 years) with coexisting lower extremity PG, DM, and/or chronic cardiac or renal disease should be managed with particular care toward preventing infection/NSTIs to prevent further complications such as limb amputations.

Background Merkel cell carcinoma (MCC) is an aggressive, high-grade, cutaneous neuroendocrine tumour (NET). Agents blocking programmed death 1/programmed death ligand 1 have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low- and moderate-grade NETs that express somatostatin receptors (SSTRs). Objectives To assess SSTR expression and the efficacy of SSAs in mMCC, a high-grade NET. Methods In this retrospective study of 40 patients with mMCC,SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; n = 39) and/or immunohistochemically when feasible (n = 9). Nineteen patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control was defined as progression-free survival (PFS) of ≥ 120 days after initiation of SSA. Results Thirty-three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) of SRS uptake. Of 19 patients treated with SSA, seven had a response-evaluable target lesion; three of these seven patients (43%) experienced disease control, with a median PFS of 237 days (range 152-358). Twelve of 19 patients did not have a response-evaluable lesion due to antecedent radiation; five of these 12 (42%) experienced disease control (median PFS of 429 days, range 143-1757). The degree of SSTR expression (determined by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. Conclusions In contrast to other high-grade NETs, mMCC tumours appear frequently to express SSTRs. SSAs can lead to clinically meaningful disease control with minimal side-effects. Targeting of SSTRs using SSA or other novel approaches should be explored further for mMCC.

Significant communication occurs between pathologists and clinicians through the dermatopathology report. Our objective was to describe clinician preference about reporting of the margin status of skin biopsies of nonmelanoma skin cancers. An anonymous survey was sent to 243 medical providers who submitted specimens to a single institution university medical center; 50 complete responses from attending-level providers and advance practice providers were received. The majority (96%) of those surveyed indicated margins should be reported on skin biopsies of neoplasms, particularly nonmelanoma skin cancers (basal cell carcinoma 96% and squamous cell carcinoma 92%) and atypical nevi (96%). When asked about particular language used to describe the margin status, some phrasing led to more variance in respondents' clinical management decisions, with 96%-98% of respondents making the same decision when presented with "unambiguous" terms and 58%-84% of respondents making the same decision when presented with "ambiguous" language (P < 0.001). Respondents generally preferred "unambiguous" margin descriptions when shown an involved margin (70% vs. 30%, P < 0.001) but accepted "ambiguous" language when the margin was clearly uninvolved (68% vs. 32%, P = 0.015). Most respondents (88%) desire inclusion of treatment recommendations in dermatopathology reports. Microscopic descriptions were highly utilized, particularly by nondermatology trained clinicians (97% vs. 80%, P = 0.09). Clinicians desire inclusion of margins for skin biopsies in dermatopathology reports, at least in some circumstances. The choice of language used to describe the margin status in dermatopathology reports has important implications for patient care. Margin descriptors that are unclear or ambiguous may lead to more variance in clinical management.

We report a case of an unusual and aggressive gamma delta T-cell lymphoproliferative disorder/lymphoma presenting in the skin that lacked the expected cytotoxic markers and had increased expression of CD5, CD20, CD79a, CD30, and PD-1 without CD56. Monoclonal TCR-γ gene rearrangement was identified. A computed tomography scan of the chest, abdomen, and pelvis revealed a 7.7-cm soft-tissue inguinal mass and prominent retroperitoneal and pelvic lymphadenopathy, without hepatosplenomegaly. Flow cytometry finding on peripheral blood was normal. The clinical, morphologic, and immunophenotypic features of this case defy the current World Health Organization and European Organization for Research and Treatment of Cancer classifications, and a similar case has not been reported previously.

ImportanceCutaneous T-cell lymphoma (CTCL) is a group of rare, complex cutaneous malignant neoplasms associated with significant disease burden on patients and the health care system. Currently, the population of patients with CTCL admitted to the hospital remains largely uncharacterized and poorly understood.ObjectiveTo characterize the clinical characteristics, course of hospitalization, and mortality outcomes of an inpatient CTCL cohort.Design, Setting, and ParticipantsThis multicenter retrospective cohort study reviewed medical records for adult patients (age ≥18 years) with a CTCL diagnosis per National Comprehensive Cancer Network guidelines admitted for inpatient hospitalization at 5 US academic medical centers with inpatient dermatology consult services and CTCL clinics between August 2016 and August 2020.Main Outcomes and MeasuresPatient demographics, clinical history and findings, hospitalization courses, and mortality outcomes.ResultsA total of 79 hospitalized patients with CTCL were identified, including 52 (70.3%) men and 22 (29.7%) women, with a median (IQR) age at hospitalization of 62.9 (27-92) years. The majority of admitted patients with CTCL were White (65 patients [82.3%]), had disease classified as mycosis fungoides (48 patients [61.5%]), and had advanced-stage disease (≥IIB, 70 patients [89.7%]). Most hospitalizations were complicated by infection (45 patients [57.0%]) and required intravenous antibiotic therapy (45 patients [57.0%]). In-hospital mortality occurred in 6 patients (7.6%) and was associated with higher body mass index (36.5 vs 25.3), history of thromboembolic disease (50.0% vs 12.3%), and diagnosis of sepsis on admission (66.7% vs 20.5%). At 1-year postdischarge, 36 patients (49.3%) patients had died, and mortality was associated with history of solid organ cancers (27.8% vs 10.8%), wound care as the reason for dermatology consultation (58.3% vs 24.3%), and presence of large cell transformation (58.3% vs 22.9%).Conclusions and RelevanceThe findings of this cohort study improve the understanding of hospitalized patients with CTCL and lend valuable insight into identifying factors associated with both in-hospital and long-term mortality outcomes. This refined understanding of the inpatient CTCL population provides a foundation for larger, more robust studies to identify causal risk factors associated with mortality, development of prognostic scoring systems to estimate the probability of hospital mortality. Overall, the findings may prompt physicians caring for patients with CTCL to implement preventive strategies to diminish hospitalization and improve clinical management across this unique disease spectrum.

Perceptual and adaptive learning modules (PALM's) provide a large number of visual examples for evaluation and accommodate to learner performance by actively adjusting the module parameters.We developed a module for discriminating 5 inflammatory reaction patterns using the Novel Diagnostic Educational Resource (NDER) platform. The module included a 20 question pre-test, a 200 question training section, and a 20 question post-test. During the pre-test and post-test, images were displayed for an indefinite period of time with no feedback given. In the training section, images were displayed for a duration inverse to learner performance, and after submitting their response learners were immediately shown the correct answer. The performance of module participants was compared to a control group who completed pre-test and post-test only.26 pathology and dermatology residents completed the module and were included in analysis. Pre-test and post-test scores showed an average increase of 17.1 percentage points (95% CI 13.0 to 21.2,Our findings validate the use of NDER for teaching inflammatory reaction patterns. Participants generally had favorable feedback regarding the interface and teaching potential of the module. Including a late re-test as part of the module would be beneficial in further validating future iterations. Next steps include optimizing module performance and developing module content for more advanced learners.

Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin cancer, has a high rate (20%) of distant metastasis. Within a prospective registry of 582 patients with metastatic MCC (mMCC) diagnosed between 2003–2021, we identified 9 (1.5%) patients who developed cardiac metastatic MCC (mMCC). We compared overall survival (OS) between patients with cardiac and non-cardiac metastases in a matched case–control study. Cardiac metastasis was a late event (median 925 days from initial MCC diagnosis). The right heart was predominantly involved (8 of 9; 89%). Among 7 patients treated with immunotherapy, 6 achieved a complete or partial response of the cardiac lesion. Among these 6 responders, 5 received concurrent cardiac radiotherapy (median 20 Gray) with immunotherapy; 4 of 5 did not have local disease progression or recurrence in the treated cardiac lesion. One-year OS was 44%, which was not significantly different from non-cardiac mMCC patients (45%, p = 0.96). Though it occurs relatively late in the disease course, cardiac mMCC responded to immunotherapy and/or radiotherapy and was not associated with worse prognosis compared to mMCC at other anatomic sites. These results are timely as cardiac mMCC may be increasingly encountered in the era of immunotherapy as patients with metastatic MCC live longer.

Calciphylaxis is an uncommon but devastating disorder characterized by vascular calcification and subsequent cutaneous tissue necrosis. This results in exquisitely painful and slow healing wounds that portend exceptionally high morbidity and mortality. The diagnosis of this condition can be complicated because there are no conclusive serologic, radiographic or visual signs that this disease is manifesting. The differential of tissue necrosis is broad, and identifying calciphylaxis requires an adroit understanding of the risk factors and physical signs that should raise suspicion of this condition. Reviews on this subject are uncommon and lack directed commentary from disease experts on the best diagnostic approach for patients suffering from this disease. The goal of this article is to update practicing dermatologists on the current standard of care for calciphylaxis.