Cytophagic histiocytic panniculitis leading to a diagnosis of acute myeloid leukemia with monocytic differentiation: A case report and literature review.

Cytophagic histiocytic panniculitis (CHP) is associated with a number of systemic conditions and is characterized by the presence of benign phagocytic histiocytes ("bean bag cells"), including phagocytosed erythrocytes, leukocytes, and platelets. We describe a case of a 72-year-old female who presented with a papular eruption that clinically mimicked pityriasis lichenoides et varioliformis acuta (PLEVA). Given that her skin biopsy had multiple features concerning PLEVA, this diagnosis was classified as a superficial pityriasis lichenoides-like variant of CHP. The histopathologic presence of cytophagic histiocytosis prompted workup for a systemic malignancy, leading to a diagnosis of underlying acute monocytic leukemia of myeloid lineage.

Skinformatics: Navigating the big data landscape of dermatology.

Big data and associated approaches to analyse it are on the rise, especially in healthcare settings. This growth is also seen with unique applications in the field of dermatology. While big data offer a plethora of opportunity for improving our current understanding of disease and ability to deliver care, as with any technology innovation, the potential pitfalls should be addressed. In this piece, we highlight opportunities and challenges associated with big data in dermatology. Opportunities include large and novel data sources that may offer a wealth of information, automated detection, classification and diagnostics and improved public health monitoring. Challenges include data quality, issues of interpretability and disparities within artificial intelligence (AI) training data sets. Clinicians and researchers in the field should be aware of these developments within the field of big data to understand how best it may be used toward improving patient care and health outcomes, particularly in the field of dermatology.

Chronic UV radiation-induced RORγt+ IL-22-producing lymphoid cells are associated with mutant KC clonal expansion.

Chronic ultraviolet (UV) radiation exposure is the greatest risk factor for cutaneous squamous cell carcinoma (cSCC) development, and compromised immunity accelerates this risk. Having previously identified that epidermal Langerhans cells (LC) facilitate the expansion of UV-induced mutant keratinocytes (KC), we sought to more fully elucidate the immune pathways critical to cutaneous carcinogenesis and to identify potential targets of intervention. Herein, we reveal that chronic UV induces and LC enhance a local immune shift toward RORγt+ interleukin (IL)-22/IL-17A-producing cells that occurs in the presence or absence of T cells while identifying a distinct RORγt+ Sca-1+ CD103+ ICOS+ CD2+/- CCR6+ intracellular CD3+ cutaneous innate lymphoid cell type-3 (ILC3) population (uvILC3) that is associated with UV-induced mutant KC growth. We further show that mutant KC clone size is markedly reduced in the absence of RORγt+ lymphocytes or IL-22, both observed in association with expanding KC clones, and find that topical application of a RORγ/γt inhibitor during chronic UV exposure reduces local expression of IL-22 and IL-17A while markedly limiting mutant p53 KC clonal expansion. We implicate upstream Toll-like receptor signaling in driving this immune response to chronic UV exposure, as MyD88/Trif double-deficient mice also show substantially reduced p53 island number and size. These data elucidate key immune components of chronic UV-induced cutaneous carcinogenesis that might represent targets for skin cancer prevention.

Understanding melanoma in situ: Lentigo maligna surgical treatment terminology and guideline adherence, a targeted review.

BACKGROUND: Malignant melanoma in-situ, lentigo maligna (MMIS-LM) can be successfully treated with several different surgical techniques; however, the literature is inconsistent in defining them. OBJECTIVE: To comprehensively define and describe the national guideline recommended surgical techniques used to treat MMIS-LM to help clarify and standardize this terminology to ensure compliance with the guidelines. METHODS: A targeted literature review was performed from 1990 to 2022 focusing on articles that discussed the national guideline recommended surgical techniques of wide local excision, Mohs micrographic surgery (MMS), modified Mohs surgery, and staged excision/Slow-Mohs for MMIS-LM, as well as the related methods of tissue processing. National Comprehensive Cancer Network and American Academy of Dermatology guidelines were reviewed to identify how the techniques need to be employed to be compliant with guideline recommendations. RESULTS: We describe the various surgical and tissue processing techniques and discuss advantages and disadvantages of each. LIMITATIONS: This paper was styled as a narrative review defining and clarifying terminology and technique and does not investigate these topics more broadly. CONCLUSION: Understanding the methodology and terminology for these surgical procedures and tissue processing methods is critical so that both general dermatologists and surgeons can employ these techniques effectively for optimal patient care.

Off-Label Use of Baricitinib in Dermatology.

The current US Food and Drug Administration (FDA) indications for baricitinib include alopecia areata, rheumatoid arthritis, and COVID-19. However, increasing evidence indicates that baricitinib is effective in treating a variety of dermatological conditions. This review article comprehensively presents the available literature on this topic and will be of interest to practitioners in the field. These disorders may be broadly classified as connective tissue diseases, eczematous dermatoses, alopecias, vascular disorders, granulomatous diseases, neutrophilic dermatoses, vitiligo, psoriasis, lichenoid disorders, and other miscellaneous disorders. Shah A, Yumeen S, Qureshi A, et al. Off-label use of baricitinib in dermatology. J Drugs Dermatol. 2023;22(8):795-801. doi:10.36849/JDD.7360.

Coffee, Citrus, and Alcohol: A Review of What We Drink and How it May Affect our Risk for Skin Cancer.

Climate change and environmental health are closely linked with agriculture and food supply. The environment influences accessibility, quality, and variety of foods and drinks that are available for consumption, which in turn influences population health. A growing area of research is the role of dietary intake of nutrients and how they may influence risk for skin cancer. In recent years, our group has studied dietary nutrients, particularly those found in commonly consumed beverages, such as those containing caffeine, citrus products, and alcohol, in large prospective cohorts to evaluate how their intake may influence risk for skin cancer. Our data suggest that intake of citrus juices, when consumed around once per day or more, or around 5 to 6 times per week, may be associated with increased risk for both keratinocyte carcinomas (KC) and malignant melanoma (MM). With regards to alcohol consumption, we have found that intake of white wine may be associated with increased risk for both KC and MM, while beer and red wine have not shown such associations. Lastly, our work suggests caffeinated beverages, including coffee, tea, and cola, may be associated with decreased risk for basal cell carcinoma (BCC) and MM. While the associations between food intake and skin cancer development are complex, and remain to be further analyzed in future studies, we hope that our summary may help guide individuals to small changes they may make towards potentially reducing their risk for certain skin cancers.

Considering Sun Safety Policies in the United States.

As they are collectively the most common malignancies, the personal and systemic burden of skin cancers represent a significant public health concern in the United States. Ultraviolet radiation from the sun as well as from artificial sources such as tanning beds is a carcinogen well-known to increase the risk of developing skin cancer in individuals. Public health policies can help mitigate these risks. In this perspectives article, we review sunscreen and sunglasses standards, tanning bed utilization, and workplace sun protection guidelines in the US and provide focused examples for improvement from Australia and the United Kingdom where skin cancer is a well-documented public health concern. These comparative examples can inform interventions in the US that have the potential to modify exposure to risk factors associated with skin cancer.

Insights Into the Molecular and Cellular Underpinnings of Cutaneous T Cell Lymphoma.

Cutaneous T cell lymphoma (CTCL) is a rare malignancy of skin-homing T lymphocytes. Advances in whole exome sequencing have identified a vast number of both single nucleotide variants (SNVs) and genomic copy number alterations (GCNAs) as driver mutations present in CTCL cells. These alterations cluster within several key pathways - T cell/NF-κB/JAK-STAT activation, cell cycle dysregulation/apoptosis, and DNA structural dysregulation affecting gene expression - allowing the maintenance of a population of proliferating, activated malignant T lymphocytes. While much of the clinical spectrum, genetic alterations, and oncogenic behavior of CTCL have been elucidated, little is known about the etiology that underlies CTCL malignant transformation and progression. Herein, we review the epidemiology, clinical presentation, and pathophysiology of CTCL to provide a perspective on CTCL pathogenesis. We outline a series of alterations by which mature, activated T lymphocytes are endowed with apoptosis resistance and cutaneous persistence. Subsequent genomic alterations including the loss of chromosomal structural controls further promote proliferation and constitutive T cell activation. CTCL cells are both malignant cells and highly functional T cells that can have major cutaneous and immunologic effects on the patient, including the suppression of cell-mediated immunity that facilitates malignant cell expansion. A deeper understanding of the molecular and cellular underpinnings of CTCL can help guide clinical management as well as inform prognosis and therapeutic discovery.

Carcinoembryonic Antigen Cell Adhesion Molecule 1 long isoform modulates malignancy of poorly differentiated colon cancer cells.

OBJECTIVE: Nearly 20%-29% of patients with colorectal cancer (CRC) succumb to liver or lung metastasis and there is a dire need for novel targets to improve the survival of patients with metastasis. The long isoform of the Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1-L or CC1-L) is a key regulator of immune surveillance in primary CRC, but its role in metastasis remains largely unexplored. We have examined how CC1-L expression impacts on colon cancer liver metastasis. DESIGN: Murine MC38 transfected with CC1-L were evaluated in vitro for proliferation, migration and invasion, and for in vivo experimental liver metastasis. Using shRNA silencing or pharmacological inhibition, we delineated the role in liver metastasis of Chemokine (C-C motif) Ligand 2 (CCL2) and Signal Transducer and Activator of Transcription 3 (STAT3) downstream of CC1-L. We further assessed the clinical relevance of these findings in a cohort of patients with CRC. RESULTS: MC38-CC1-L-expressing cells exhibited significantly reduced in vivo liver metastasis and displayed decreased CCL2 chemokine secretion and reduced STAT3 activity. Down-modulation of CCL2 expression and pharmacological inhibition of STAT3 activity in MC38 cells led to reduced cell invasion capacity and decreased liver metastasis. The clinical relevance of our findings is illustrated by the fact that high CC1 expression in patients with CRC combined with some inflammation-regulated and STAT3-regulated genes correlate with improved 10-year survival. CONCLUSIONS: CC1-L regulates inflammation and STAT3 signalling and contributes to the maintenance of a less-invasive CRC metastatic phenotype of poorly differentiated carcinomas.

The use of biologics and JAK inhibitors in the management of moderate to severe Hidradenitis Suppurativa treatment: a scoping review.

This scoping review aims to characterize the use of biologics and Janus Kinase inhibitors (JAKi) in the treatment of Hidradenitis Suppurativa (HS), which is a chronic inflammatory condition. A comprehensive literature search was conducted in PubMed/NCBI, Embase, Web of Science databases, and the Clinicaltrials.gov register. The search included interventional trials assessing the use of biologics or JAKi in HS, with no geographic or time restrictions. Secukinumab and adalimumab were identified as the only two drugs approved by the FDA for treating moderate to severe HS in adults. Several other drug classes showed promising results based on clinical studies reviewed. IL-12/23 inhibitor ustekinumab demonstrated improvements in disease severity scores and HiSCR rates in small trials. IL-17 inhibitors such as brodalumab, bimekizumab, and CJM112 showed preliminary positive responses in early-phase clinical studies and case reports. While evidence was mixed, some TNF-α inhibitors such as infliximab provided benefits according to a randomized controlled trial, though etanercept trials yielded non-significant or inconsistent findings. Larger, well-designed studies are required to further establish their efficacy and safety, but biologics and JAKis show potential as alternative treatment options for moderate to severe HS. The findings of this review contribute to the growing interest among patients and to enhancing the understanding of physician's regarding potential alternative therapeutic options for HS and provide a basis for further research in this field.

Two Features of Annular Lichenoid Dermatitis of Youth (ALDY).

A healthy 14-year-old boy presented with a 2-month history of two slowly expanding asymptomatic lesions on his right trunk. No etymology of any new medications, recent travel, or tick bites was reported. Physical examination demonstrated two 4.5×2.5- cm and 3.5×2-cm annular hyperpigmented plaques with slightly elicited red borders on the right lower abdomen and right inferior flank. No evidence of atrophy or sclerosis was noted (Figure 1A). A 4-mm punch biopsy revealed irregular epidermal hyperplasia with alteration of thinned and quadrangular rete ridges, a dense band-like lichenoid infiltrate in the papillary dermis admixed with numerous melanophages and occasional necrotic keratinocytes. No evidence of epidermotropism was observed (Figure 1B). The dermal infiltrate was predominantly composed of CD3+ T-lymphocytes admixed with rare CD20+ B-lymphocytes and increased CD8-CD4 ratio. The patient showed significant improvement following the application of a potent steroid ointment for several weeks.

Applications and Best Practices for Geospatial Analysis Research in Dermatology.

Dermatologic diseases often exhibit distinct geographic patterns, underscoring the significant role of regional environmental, genetic, and sociocultural factors in driving their prevalence and manifestations. Geographic information and geospatial analysis enable researchers to investigate the spatial distribution of adverse health outcomes and their relationship with socioeconomic and environmental risk factors that are inherently geographic. Health geographers and spatial epidemiologists have developed numerous geospatial analytical tools to collect, process, visualize, and analyze geographic data. These tools help provide vital spatial context to the comprehension of the underlying dynamics behind health outcomes. By identifying areas with high rates of dermatologic disease and areas with barriers to access to quality dermatologic care, findings from studies utilizing geospatial analysis can inform the design and targeting of policy and intervention to help improve dermatologic healthcare outcomes and promote health equity. This article emphasizes the significance of geospatial data and analysis in dermatology research. We explore the common processes in data acquisition, harmonization, and geospatial analytics while conducting spatially and dermatologically relevant research. The article also highlights the practical application of geospatial analysis through instances drawn from the dermatology literature.