Imaging technologies for presurgical margin assessment of basal cell carcinoma.

Basal cell carcinoma is the most common cancer worldwide, necessitating the development of techniques to decrease treatment costs through efficiency and efficacy. Mohs micrographic surgery, a specialized surgical technique involving staged resection of the tumor with complete histologic evaluation of the peripheral margins, is highly utilized. Reducing stages by even 5% to 10% would result in significant improvement in care and economic benefits. Noninvasive imaging could aid in both establishing the diagnosis of suspicious skin lesions and streamlining the surgical management of skin cancers by improving presurgical estimates of tumor sizes. Herein, we review the current state of imaging techniques in dermatology and their applications for diagnosis and tumor margin assessment of basal cell carcinoma prior to Mohs micrographic surgery.

Society of Toxicologic Pathology Nonhuman Primate Special Interest Group: Idiopathic Femoral Head Chondrolysis in Nonclinical Research Macaques.

Idiopathic femoral head chondrolysis is a recognized condition in human adolescents and has previously been reported in two macaques at a biomedical research facility. A cluster of coxofemoral joint abnormalities consistent with this condition affecting seven cynomolgus macaques over a four-month period in 2016 and 2017 was observed at a single, nonclinical contract research facility, prompting enhanced physical examination screening efforts during animal receipt and pre-study evaluation to identify additional affected animals. This article summarizes the results of this investigation from November 2016 to March 2021, yielding 97 total cases for an overall incidence of 0.54% (97/17,898 macaques). Affected animals were presented with one or more of the following unilateral or bilateral findings on physical examination and/or diagnostic imaging: lameness, palpable coxofemoral joint abnormalities, femoral head atrophy with variable loss of articular cartilage and irregularity of the femoral head surface, enlarged joint space with effusion, and increased radiographic density of the femoral head. This condition prevented use of affected animals on study for 54% of the cases (52/97 animals). Recognition of this idiopathic condition is important in drug safety evaluation studies to distinguish it from test article-related effects.

Antecedent immunosuppressive therapy for immune-mediated inflammatory diseases in the setting of a COVID-19 outbreak.

BACKGROUND: Finite clinical data and understanding of COVID-19 immunopathology has led to limited, opinion-based recommendations for the management of patients with immune-mediated inflammatory disease (IMID) receiving immunosuppressive (IS) therapeutics. OBJECTIVE: To determine if IS therapeutic type affects COVID-19 risk among patients with IMID. METHODS: We conducted a retrospective cohort analysis of Henry Ford Health System patients tested for COVID-19 between February 1 and April 18, 2020, treated with IS medication for IMID. Therapeutic class of IS medication, comorbidities, and demographic factors were combined into multivariate models to determine predictors of COVID-19 infection, admission, ventilation, and mortality. RESULTS: Of 213 patients with IMID, 36.2% tested positive for COVID-19, and they had no greater odds of being hospitalized or requiring ventilation relative to the general population. No IS therapeutic worsened the course of disease after multivariate correction, although multidrug regimens and biologics predicted an increased and decreased rate of hospitalization, respectively, with the latter driven by tumor necrosis factor α inhibitors. LIMITATIONS: A single-center study somewhat limits the generalization to community-based settings. Only patients tested for COVID-19 were analyzed. CONCLUSION: IS therapies for IMIDs are not associated with a significantly greater risk of SARS-CoV-2 or severe sequelae when controlling for other factors, and tumor necrosis factor α inhibitors may decrease the odds of severe infection.

Battling Neuropathic Scar Pain With Botulinum Toxin

Botulinum toxin type A (BTA) is a neurotoxic protein that prevents the release of neurotransmitters from presynaptic nerves and has shown promise in treating neuropathic pain. Recently, BTA has been used to treat painful keloids and scars. We present a patient with refractory neuropathic pain in a normotrophic spread-scar treated with the injection of BTA. A 47-year-old Caucasian female with a history of invasive melanoma of the left upper arm presented with pain in her excision scar, which she described as a "pins and needles" sensation alternating with a dull, deep ache. She had previously tried topical lidocaine, topical and intralesional steroids, and oral gabapentin without improvement. We treated the patient with 50 U of onabotulinumtoxinA intradermally at 1-1.5 cm intervals within and immediately around the perimeter of the scar. At 1-week follow-up, she reported a 10% decrease in her pain. Four weeks after the procedure, she reported a 50% decrease in pain with smoothening of the scar surface, which has been durable for over 5 months. Scar pain can significantly impair quality of life and treatment protocols have not been established for normotrophic scars. Many trials have focused on improving appearance and reducing symptoms in hypertrophic and keloid scars, but few have evaluated therapies for normotrophic scars. BTA has been studied as a treatment for painful hypertrophic and keloid scars with promising results. Our patient had a marked reduction in pain and improvement in scar texture at 1-month follow-up, which has been maintained thus far, indicating that intradermal BTA may be a simple and useful tool in treating painful normotrophic scars. J Drugs Dermatol. 2019;18(9):937-938.

Pemetrexed-Induced Pseudocellulitis: A Diagnostic Conundrum.

Pemetrexed, an anti-folate, antineoplastic agent, effectively treats various malignancies such as non-small cell lung cancer (NSCLC) and mesothelioma. Here, we report two cases of recurrent pemetrexed-induced lower extremity erythema and edema, one in a 60-year-old male and the other in a 47-year-old male, who were both treated for recurrent cellulitis on multiple occasions before finally being diagnosed with pemetrexed-induced pseudocellulitis (PIP), a rarely reported adverse effect. This is an important diagnostic pitfall for clinicians to be aware of, as early recognition may minimize patient morbidity and prevent unnecessary hospitalization and antibiotic use for presumed cellulitis.

The diagnostic conundrum of acute cutaneous graft-versus-host disease: biomarkers remain elusive.

Hematopoietic stem cell transplantation is increasing in frequency with graft-versus-host disease affecting many recipients. When the skin is involved, biopsy is routinely performed but often does not aid in definitive diagnosis. Here, we examine a cohort of 32 patients for potential biomarkers that can aid in the diagnosis of graft-versus-host disease. Neither blood short tandem repeat testing or neutrophil-lymphocyte ratios were predictive of rash etiology in hematopoietic stem cell transplant patients. However, skin short tandem repeat testing showed promise as a predictor in a small minority of cases in this cohort.

Distinguishing Keratoacanthoma from Well-Differentiated Cutaneous Squamous Cell Carcinoma Using Single-Cell Spatial Pathology.

Keratoacanthoma (KA) is a common keratinocyte neoplasm that is regularly classified as a type of cutaneous squamous cell carcinoma (cSCC) despite demonstrating benign behavior. Differentiating KA from well-differentiated cSCC is difficult in many cases due to the substantial overlap of clinical and histological features. Currently, no reliable discriminating markers have been defined, and consequently, KAs are often treated similarly to cSCC, creating unnecessary surgical morbidity and healthcare costs. In this study, we used RNA sequencing to identify key differences in transcriptomes between KA and cSCC, which suggested divergent keratinocyte populations between each tumor. Imaging mass cytometry was then used to identify single-cell tissue characteristics, including cellular phenotype, frequency, topography, functional status, and interactions between KA and well-differentiated cSCC. We found that cSCC had significantly increased proportions of Ki67+ keratinocytes among tumor keratinocytes, which were dispersed significantly throughout non-basal keratinocyte communities. In cSCC, regulatory T-cells were more prevalent and held greater suppressive capacity. Furthermore, cSCC regulatory T-cells, tumor-associated macrophages, and fibroblasts had significant associations with Ki67+ keratinocytes as opposed to avoidances with KA, indicating a more immunosuppressive environment. Our data suggest that multicellular spatial features can serve as a foundation to enhance the histological discrimination of ambiguous KA and cSCC lesions.

Real world validation of an adjunctive gene expression-profiling assay for melanoma diagnosis and correlation with clinical outcomes at an academic center.

A commercially available diagnostic gene expression profiling (GEP) assay (MyPath™) reportedly has high sensitivity and specificity in distinguishing nevi from melanoma based on manufacturer-conducted studies. However, data regarding the performance of this GEP assay in routine clinical practice are lacking. The purpose of this study was to better assess the real-world performance of GEP in a large academic practice. Retrospective review of GEP scores were compared with final histomorphologic interpretation on a wide spectrum of melanocytic lesions demonstrating some degree of atypia. In a sample of 369 lesions, the sensitivity (76.1%) and specificity (83.9%) of the GEP test as compared with final dermatopathologist-rendered diagnosis in our dataset was appreciably lower than that reported in the prior manufacturer-conducted validation studies. Limitations of this study were that it was a single-center study, its retrospective nature, nonblinded nature of GEP test result, concordance of only two pathologists, and limited follow-up time.The sensitivity and specificity of a commercially available GEP diagnostic assay for melanoma may be lower in routine clinical practice, where melanocytic lesions typically exhibit some degree of histomorphologic atypia. Reported cost effectiveness of GEP testing is questionable if all ambiguous lesions that undergo such testing are re-excised in clinical practice.

Single-Fraction Radiation Therapy for Localized Cutaneous T-Cell Lymphoma.

PURPOSE: Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL). Single-fraction radiation therapy has been used as a skin-targeted therapy to treat localized CTCL lesions. The objective of this study was to investigate the treatment outcomes associated with single-fraction radiation therapy for CTCL. METHODS AND MATERIALS: We retrospectively studied the outcomes among patients with CTCL treated with single-fraction radiation therapy at our institution between October 2013 and August 2022. Clinical response (complete response [CR], partial response [PR], or no response [NR]) and retreatment response were evaluated. RESULTS: A total of 242 lesions from 46 patients were analyzed, for an average of 5.3 lesions treated per patient. The majority of lesions presented with a plaque morphology (n = 145, 60.0%). All lesions were treated to a dose of 8 Gy in 1 fraction. Median follow-up was 24.6 months (range, 1-88 months). Of the 242 lesions, 36 (14.8%) had an initial PR or NR; all were retreated with the same regimen to the same site at a median interval of 8 weeks. Eighteen of the retreated lesions (50.0%) went on to have a CR. Thus, the overall CR rate for CTCL lesions was 92.6%. No recurrences were noted in the treated areas after achieving CR. CONCLUSIONS: Single-fraction radiation therapy to a dose of 8 Gy in 1 fraction to localized areas provided a high rate of complete and durable responses in the affected sites.

Dysregulated CD38 expression in blood and skin immune cells of patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a multifactorial, inflammatory skin disease. Increased systemic inflammatory comorbidities and serum cytokines highlight systemic inflammation as a feature of HS. However, the specific immune cell subsets contributing to systemic and cutaneous inflammation have not been resolved. Here, we generated whole-blood immunomes by mass cytometry. We performed a meta-analysis of RNA-seq data, immunohistochemistry, and imaging mass cytometry to characterize the immunological landscape of skin lesions and perilesions from patients with HS. Blood from patients with HS exhibited lower frequencies of natural killer cells, dendritic cells, and classical (CD14+CD16-) and nonclassical (CD14-CD16+) monocytes, as well as higher frequencies of Th17 cells and intermediate (CD14+CD16+) monocytes than blood from healthy controls. Classical and intermediate monocytes from patients with HS had increased expression of skin-homing chemokine receptors. Furthermore, we identified a CD38+ intermediate monocyte subpopulation that was more abundant in the immunome of blood from patients with HS. Meta-analysis of RNA-seq data found higher CD38 expression in lesional HS skin than in perilesional skin, and markers of classical monocyte infiltration. Imaging mass cytometry showed that CD38+ classical monocytes and CD38+ monocyte-derived macrophages were more abundant in lesional HS skin. Overall, we report targeting CD38 may be worth pursuing in clinical trials.

Dysregulated CD38 expression in blood and skin immune cells of patients with hidradenitis suppurativa.

Background: Hidradenitis suppurativa (HS) is a multifactorial, inflammatory skin disease. Increased systemic inflammatory comorbidities and serum cytokines highlight systemic inflammation as a feature of HS. However, the specific immune cell subsets contributing to systemic and cutaneous inflammation have not been resolved. Objective: Identify features of peripheral and cutaneous immune dysregulation. Methods: Here, we generated whole-blood immunomes by mass cytometry. We performed a meta-analysis of RNA-seq data, immunohistochemistry, and imaging mass cytometry to characterize the immunological landscape of skin lesions and perilesions from patients with HS. Results: Blood from patients with HS exhibited lower frequencies of natural killer cells, dendritic cells, and classical (CD14+CD16-) and nonclassical (CD14-CD16+) monocytes, as well as higher frequencies of Th17 cells and intermediate (CD14+CD16+) monocytes than blood from healthy controls. Classical and intermediate monocytes from patients with HS had increased expression of skin-homing chemokine receptors. Furthermore, we identified a CD38+ intermediate monocyte subpopulation that was more abundant in the immunome of blood from patients with HS. Meta-analysis of RNA-seq data found higher CD38 expression in lesional HS skin than in perilesional skin, and markers of classical monocyte infiltration. Imaging mass cytometry showed that CD38+ classical monocytes and CD38+ monocyte-derived macrophages were more abundant in lesional HS skin. Conclusion: Overall, we report targeting CD38 may be worth pursuing in clinical trials. Key Messages: 3.Monocyte subsets express markers of activation in circulation and HS lesionsTargeting CD38 may be a viable strategy for treating systemic and cutaneous inflammation in patients with HS. Capsule Summary: 4.Dysregulated immune cells in patients with HS express CD38 and may be targeting by anti-CD38 immunotherapy.