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Competing Interests: Conflicts of interest None disclosed.

Psoriasis is an inflammatory skin disorder that is characterized by keratinocyte hyperproliferation in response to immune cell infiltration and cytokine secretion in the dermis. γδ T cells expressing the Vγ4 TCR chain are among the highest contributors of IL-17A, which is a major cytokine that drives a psoriasis flare, making Vγ4 + γδ T cells a suitable target to restrict psoriasis progression. In this study, we demonstrate that mitochondrial translation inhibition within Vγ4 + γδ T cells effectively reduced erythema, scaling, and skin thickening in a murine model of psoriatic disease. The antibiotic linezolid, which blocks mitochondrial translation, inhibited the production of mitochondrial-encoded protein cytochrome c oxidase in Vγ4 + γδ T cells and systemically reduced the frequencies of IL-17A + Vγ4 + γδ T cells, effectively resolving IL-17A-dependent inflammation. Inhibiting mitochondrial translation could be a novel metabolic approach to interrupt IL-17A signaling in Vγ4 + T cells and reduce psoriasis-like skin pathophysiology., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Selected patients with early-stage melanoma have a "hidden high risk" of poor oncologic outcomes. They might benefit from clinical trials, and ultimately, if warranted by trial results, judicious everyday use of adjuvant therapy. A promising tool to identify these individuals is the immunoprint ® assay. This immunohistochemical 7-biomarker prognostic test was clinically validated in three independent cohorts (N = 762) to classify early-stage patients as high-risk or low-risk regarding melanoma recurrence and mortality. Using College of American Pathologists (CAP) recommendations, we analytically validated this assay in primary melanoma specimens (N = 20 patients). We assessed assay precision by determining consistency of risk classification under repeated identical conditions (repeatability) or across varying conditions (reproducibility), involving separate assay runs, operators (laboratory scientists), and/or observers (e.g., dermatopathologists). Reference classification was followed by five analytical validation phases: intra-run/intra-operator, intra-observer, inter-run, inter-operator, and inter-observer. Concordance of classifications in each phase was assessed via Fleiss' kappa (primary endpoint) and percent agreement (secondary endpoint). Seven-marker signature classification demonstrated high consistency across validation categories (Fleiss' kappa 0.864-1.000; overall percent agreement 95-100%), in 9/10 cases, exceeding, and in 1/10 cases, closely approaching, CAP's recommended 0.9 level. The 7-marker assay has now been verified to provide excellent repeatability, reproducibility, and precision, besides having been clinically validated.

Psoriasis is a chronic inflammatory skin disease driven by the IL-23/IL-17 axis. It results from excessive activation of effector T cells, including T helper (Th) and cytotoxic T (Tc) cells, and is associated with dysfunctional regulatory T cells (Tregs). Acetyl-CoA carboxylase 1 (ACC1), a rate-limiting enzyme of fatty acid synthesis (FAS), directs cell fate decisions between Th17 and Tregs and thus could be a promising therapeutic target for psoriasis treatment. Here, we demonstrate that targeting ACC1 in T cells by genetic ablation ameliorates skin inflammation in an experimental model of psoriasis by limiting Th17, Tc17, Th1, and Tc1 cells in skin lesions and increasing the frequency of effector Tregs in skin-draining lymph nodes (LNs). KEY MESSAGES : ACC1 deficiency in T cells ameliorates psoriatic skin inflammation in mice. ACC1 deficiency in T cells reduces IL-17A-producing Th17/Tc17/dysfunctional Treg populations in psoriatic lesions. ACC1 deficiency in T cells restrains IFN-γ-producing Th1/Tc1 populations in psoriatic skin lesions and skin-draining LNs. ACC1 deficiency promotes activated CD44 + CD25 + Tregs and effector CD62L - CD44 + Tregs under homeostasis and psoriatic conditions., (© 2023. The Author(s).)

Introduction: Ever evolving research in medical field has reached an exciting stage with advent of newer technologies. With the introduction of digital microscopy, pathology has transitioned to become more digitally oriented speciality. The potential of artificial intelligence (AI) in dermatopathology is to aid the diagnosis, and it requires dermatopathologists' guidance for efficient functioning of artificial intelligence., Method: Comprehensive literature search was performed using electronic online databases "PubMed" and "Google Scholar." Articles published in English language were considered for the review., Results: Convolutional neural network, a type of deep neural network, is considered as an ideal tool in image recognition, processing, classification, and segmentation. Implementation of AI in tumor pathology is involved in the diagnosis, grading, staging, and prognostic prediction as well as in identification of genetic or pathological features. In this review, we attempt to discuss the use of AI in dermatopathology, the attitude of patients and clinicians, its challenges, limitation, and potential opportunities in future implementation., (© 2022 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background and Objectives: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphomas, characterized by mature, skin-tropic CD4+ T-helper cells. In order to study the immune tumor microenvironment in MF patients, we performed immunohistochemical stains on MF biopsies, digitized whole-slide tissue sections, and performed quantitative analysis of the different immune cell subsets to correlate tissue parameters with the clinical data of patients, such as progression-free survival or overall survival., Patients and Methods: Overall, 35 patients who were treated between 2009 and 2019 and for whom one or more paraffin tissue blocks were available have been included in the present study (58 tissue specimens in total). Conventional immunohistochemistry stains for CD3, CD4, CD8, CD20 and CD30 were used for the analysis of the immune phenotype, and quantitative analysis was performed using QuPath as a quantitative digital pathology tool for bioimage analysis of whole slides., Results: Analysis of tissue parameters for prognostic significance revealed that patients with a stronger infiltration by CD8+ lymphocytes within the tumor cell compartment had a higher risk of disease progression ( p = 0.031) and showed a shorter progress-free survival ( p = 0.038). Furthermore, a significant association of the percentage of CD30+ cells (median: 7.8%) with the risk of disease progression ( p = 0.023) and progression-free survival ( p = 0.023) was found. In relation to the clinical features of our patient cohort, a higher risk of disease progression ( p = 0.015) and a shorter progression-free survival ( p = 0.032) for older patients (>61 years) were observed., Conclusions: Our results demonstrated the prognostic relevance of large-cell transformation in mycosis fungoides and its strong association with the presence of CD30+ lymphocytes. Unlike previous reports, our study suggests an adverse prognostic role for CD8+ T cells in patients with mycosis fungoides. Moreover, our data indicate that the immune phenotype within the tumor microenvironment shows strong temporal heterogeneity and is altered in the course of tumor progression.

Graft-versus-host disease (GvHD) is a major complication following stem-cell or solid-organ transplantation. Accurate diagnosis of cutaneous GvHD is challenging, given that drug eruptions and viral rashes may present with similar clinical/histological manifestations. Specific markers are not available. We performed the histological examination of biopsy samples from acute GvHD (aGvHD; n = 54), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN; n = 27), maculopapular drug eruption (MDE; n = 26) and healthy controls (n = 26). Samples of aGvHD showed a decrease in Langerhans cells (LC, p = 0.0001) and an increase in macrophages (MΦ, p = 0.0001) compared to healthy skin. Compared to SJS/TEN, MDE and healthy skin, aGvHD biopsies contained greater numbers of CD4 + and CD8 + T cells. The majority of CD4 + T-helper cells were localized in the upper dermis, whereas cytotoxic CD8 + T cells were found in the epidermis. Increased numbers of CD56 + natural killer (NK) cells in the upper dermis of aGvHD skin (p = 0.007) were not observed in controls or SJS/TEN and MDE. There were no differences in elafin staining between aGvHD and the latter two conditions. Acute GvHD appears to have a distinct inflammatory cell profile (T cells/NK cells) that may aid establishing in a more accurate diagnosis, especially when used to rule out differential diagnoses such as SJS/TEN or MDE., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Angiosarcomas (ASs) are aggressive tumors of vascular endothelial origin, occurring sporadically or in association with prior radiotherapy or chronic lymphedema. With only 1-5% of all sarcomas, the incidence seems low, but for the affected patient due to the extremely poor prognosis and the limited treatment options, the fate is often inevitable. Radiotherapy, chemotherapy, or "target therapy" have been used in the management of AS, but represent individual case decisions without lasting evidence. Over the past few years, breast-conserving surgery followed by radiation therapy, known as breast-conserving therapy (BCT), is being employed as a standard treatment for early-stage breast cancer, but there has been an increase in reports of AS following BCT. We report two cases of AS following BCT and one case of primary AS involving the lower limb., (© 2020 Wiley Periodicals, Inc.)

The palisading granulomatous dermatitides comprise a group of different skin diseases with similar histomorphologic forms of granuloma in the skin. Histopathologically characteristic are areas in the reticular dermis and subcutaneous fat with degenerated bundles of collagen surrounded by histiocytes and multinucleate giant cells aligned in a palisade (necrobiotic granuloma). Within the center of palisaded granulomas, mucin or fibrin can be found. The skin diseases presenting histologically with palisading granuloma are granuloma annulare and necrobiosis lipoidica. Palisading granuloma may also be an expression of systemic disease in rheumatoid nodules and necrobiotic xanthogranuloma. Little is known about the pathogenesis. The clinical presentation of the diseases is variable. Therapy is challenging and may not be satisfying.

Ductal carcinoma in situ (DCIS) in the mammary glands consists of a proliferation of ductal luminal cells with preserved polarity but lacking the marked intercellular cohesion of hyperplastic cells. We report two cases of DCIS arising in the apocrine glandular structures of a nevus sebaceus (NS). The first patient was a 44-year-old woman with a ductal neoplasm composed of multilayered ductal elements with a monomorphous cellularity and a polar orientation of nuclei. The neoplastic cells were positive for Cm5.2 and CK7. The second patient was a 67-year-old woman with phacomatosis pigmentokeratotica. A skin biopsy of an erythematous plaque within her NS showed an epithelioid monomorphous tumor with eosinophilic and slightly granular cytoplasm. Slight nuclear pleomorphism with some hyperchromatic nuclei was seen. The tumor cells were positive for CK7 and gross cystic disease fluid protein-15. Actin showed a preserved layer of myoepithelial cells in both cases. Our cases are noteworthy, as secondary malignancies or multiple tumors arising in NS are rare, and the presence of multiple neoplasms in phacomatosis pigmentokeratotica is even rarer. Moreover, these tumors expand the spectrum of secondary malignant neoplasms arising in NS, as they closely resemble mammary DCIS., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)