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The classification of primary cutaneous lymphomas and lymphoproliferative disorders (LPD) is continuously evolving by integrating novel clinical, pathological and molecular data. Recently two new classifications for haematological malignancies including entities of cutaneous lymphomas were proposed: the 5th edition of the WHO classification of haematolymphoid tumours and the International Consensus Classification (ICC) of mature lymphoid neoplasms. This article provides an overview of the changes introduced in these two classifications compared to the previous WHO classification. The main changes shared by both classifications include the downgrading of CD8+ acral T‐cell lymphoma to CD8+ acral T‐cell LPD, and the recognition of entities that were previously categorized as provisional and have now been designated as definite types including primary cutaneous small or medium CD4+ T‐cell LPD, primary cutaneous gamma/delta T‐cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T‐cell lymphoma, Epstein–Barr virus‐positive mucocutaneous ulcer. Both classifications consider primary cutaneous marginal zone B‐cell clonal neoplasm as an indolent disease but use a different terminology: primary cutaneous marginal zone lymphoma (WHO) and primary cutaneous marginal zone LPD (ICC). The 5th WHO classification further introduces and provides essential and desirable diagnostic criteria for each disease type and includes chapters on reactive B‐ or T‐cell rich lymphoid proliferations formerly referred as cutaneous pseudolymphomas, as well as histiocyte and CD8 T‐cell rich LPD in patients with inborn error of immunity. As already emphasized in previous lymphoma classifications, the importance of integrating clinical, histological, phenotypic and molecular features remains the crucial conceptual base for defining cutaneous (and extracutaneous) lymphomas. [ABSTRACT FROM AUTHOR]

Background: Histopathological classification of basal cell carcinoma (BCC) has important prognostic and therapeutic implications, but reproducibility of BCC subtyping among dermatopathologists is poor. Objectives: To obtain a consensus paper on BCC classification and subtype definitions. Methods: A panel of 12 recognized dermatopathologists (G12) from nine European countries used a modified Delphi method and evaluated 100 BCC cases uploaded to a website. The strategy involved five steps: (I) agreement on definitions for WHO 2018 BCC subtypes; (II) classification of 100 BCCs using the agreed definitions; (III) discussion on the weak points of the WHO classification and proposal of a new classification with clinical insights; (IV) re‐evaluation of the 100 BCCs using the new classification; and (V) external independent evaluation by 10 experienced dermatopathologists (G10). Results: A simplified classification unifying infiltrating, sclerosing, and micronodular BCCs into a single "infiltrative BCC" subtype improved reproducibility and was practical from a clinical standpoint. Fleiss' κ values increased for all subtypes, and the level of agreement improved from fair to moderate for the nodular and the unified infiltrative BCC groups, respectively. The agreement for basosquamous cell carcinoma remained fair, but κ values increased from 0.276 to 0.342. The results were similar for the G10 group. Delphi consensus was not achieved for the concept of trichoblastic carcinoma. In histopathological reports of BCC displaying multiple subtypes, only the most aggressive subtype should be mentioned, except superficial BCC involving margins. Conclusions: The three BCC subtypes with infiltrative growth pattern, characteristically associated with higher risk of deep involvement (infiltrating, sclerosing, and micronodular), should be unified in a single group. The concise and encompassing term "infiltrative BCCs" can be used for these tumors. A binary classification of BCC into low‐risk and high‐risk subtypes on histopathological grounds alone is questionable; correlation with clinical factors is necessary to determine BCC risk and therapeutic approach. [ABSTRACT FROM AUTHOR]

Hair restoration surgery is considered for the treatment of alopecia when pharmacological therapy is insufficient for a satisfactory result and synthetic hair fibres in patients without adequate donor hair for autologous transplantation. This case observation demonstrates yet another long-term complication of synthetic hair implants and illuminates a therapeutic option for topical treatment of scalp calcinosis. Biofibre ® artificial hair implant: Retrospective study on 1,518 patients with alopecia and present role in hair surgery. [Extracted from the article]

Background: Cutaneous peripheral T‐cell lymphoma, not otherwise specified (PTL NOS) is an aggressive, but poorly characterized neoplasm. Objectives: The European Organization for Research and Treatment of Cancer cutaneous lymphoma taskforce (EORTC CLTF) investigated 33 biopsies of 30 patients with primary cutaneous PTL NOS to analyse their clinical, histological, immunophenotypic features and outcome. Methods: Retrospective analysis of clinical data and histopathological features by an expert panel. Results: Cutaneous PTL NOS manifested clinically either with solitary or disseminated rapidly grown ulcerated tumours or disseminated papulo‐nodular lesions. Histologically, a mostly diffuse or nodular infiltrate in the dermis and often extending into the subcutis was found. Epidermotropism was rarely present and only mild and focal. Unusual phenotypes were frequent, e.g. CD3+/CD4−/CD8− and CD3+/CD4+/CD8+. Moreover, 18% of the cases exhibited an aberrant expression of the B‐cell marker CD20 by the tumour cells. All solitary tumours were located on the limbs and presented a high expression of GATA‐3 but this did not correlate with outcome and therefore could not serve as a prognostic factor. The prognosis was shown to be generally poor with 10 of 30 patients (33%) dying of lymphoma within the follow‐up of 36 months (mean value; range 3–144). The survival rates were 61% after 3 years (CI, 43–85%) and 54% after 5 years (CI, 36–81%). Small to medium‐sized morphology of tumour cells was associated with a better outcome than medium to large or large tumour cells. Age, gender, clinical stage, CD4/CD8 phenotype and GATA‐3 expression were not associated with prognosis. Chemotherapy was the most common treatment modality, but surgical excision and/or radiotherapy may represent an appropriate first‐line treatment for solitary lesions. Conclusions: Cutaneous PTL NOS shows an aggressive course in most patients independent of initial presentation, age and phenotype. Cytomorphology was identified as a prognostic factor. The data indicate a need for more effective treatment modalities in PTL NOS. [ABSTRACT FROM AUTHOR]

COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. It is still unclear which component of the Moderna vaccine is responsible for the induction of post-vaccine EAC. Post-vaccine EAC represents the histomorphological correlate for a localized DTHR known as COVID arm due mRNA vaccines. [Extracted from the article]

Background: Key pathogenic events of psoriasis and atopic eczema (AE) are misguided immune reactions of the skin. IL‐17C is an epithelial‐derived cytokine, whose impact on skin inflammation is unclear. Objective: We sought to characterize the role of IL‐17C in human ISD. Methods: IL‐17C gene and protein expression was assessed by immunohistochemistry and transcriptome analysis. Primary human keratinocytes were stimulated and expression of cytokines chemokines was determined by qRT‐PCR and luminex assay. Neutrophil migration towards supernatant of stimulated keratinocytes was assessed. IL‐17C was depleted using a new IL‐17C‐specific antibody (MOR106) in murine models of psoriasis (IL‐23 injection model) and AE (MC903 model) as well as in human skin biopsies of psoriasis and AE. Effects on cell influx (mouse models) and gene expression (human explant cultures) were determined. Results: Expression of IL‐17C mRNA and protein was elevated in various ISD. We demonstrate that IL‐17C potentiates the expression of innate cytokines, antimicrobial peptides (IL‐36G, S100A7 and HBD2) and chemokines (CXCL8, CXCL10, CCL5 and VEGF) and the autocrine induction of IL‐17C in keratinocytes. Cell‐free supernatant of keratinocytes stimulated with IL‐17C was strongly chemotactic for neutrophils, thus demonstrating a critical role for IL‐17C in immune cell recruitment. IL‐17C depletion significantly reduced cell numbers of T cells, neutrophils and eosinophils in murine models of psoriasis and AE and led to a significant downregulation of inflammatory mediators in human skin biopsies of psoriasis and AE ex vivo. Conclusion: IL‐17C amplifies epithelial inflammation in Th2 and Th17 dominated skin inflammation and represents a promising target for the treatment of ISD. [ABSTRACT FROM AUTHOR]

6 Parodi A, Micalizzi C, Rebora A. Intralesional natural interferon alpha in thetreatment of Crosti's lymphoma (primary cutaneous B follicular centre-cell lymphoma): report of four cases. Primary cutaneous follicle centre lymphoma, spindle cell type, presenting with multicentre figurated erythema and complete remission after intralesional injections of ultra-low-dose Interferon alpha-2a Spindle-cell cariants of primary cutaneous follicle center B-cell lymphomas are germinal center B-cell lymphomas by gene expression profiling using a formalin-fixed paraffin-embedded specimen. [Extracted from the article]

Background The stromal vascular fraction ( SVF) of adipose tissue consists of cellular subpopulations with distinct regenerative potential. Objective To investigate the regenerative capacities of autologous SVF cells in the treatment of chronic leg ulcers of venous ( VLU) and arterial-venous ( AVLU) origin. Methods Multimorbid ulcer patients received a singular topical treatment with 9-15 × 106 SVF cells, separated from abdominal lipoaspirates by digestion with collagenase and neutral protease and applied immediately after isolation. The primary endpoints were the change in wound size 12 weeks after treatment and evaluation of adverse events. Secondary endpoints included the time to complete wound epithelialization and change in pain levels. Postoperative wound treatment modalities and treatment of comorbidities were not intensified compared with pre-operative management. Follow-up period was at least 6 months. Results Sixteen elderly ulcer patients (seven with VLU, nine with AVLU) were treated as described. All VLU patients (median ulcer size: 48.25 cm2) and four of nine AVLU patients showed complete epithelialization of the ulcers within 71-174 days. In three patients with large ulcerations on both legs, ulcerations on the non-treated, contralateral leg also epithelialized. Patients reported a considerable rapid decrease in pain intensity by 2.5 points on average on a visual scale from 1 to 5 within the first 2 weeks after treatment. The patients were followed up for 9-44 months (median: 30 months). No severe side-effects were observed. Conclusions The use of SVF cells presents an effective, minimally invasive option for the treatment of VLU and AVLU even in multimorbid patients. In patients with larger predominantly ischaemic AVLU and comorbidities, one-time application of the used amounts of SVF cells was not sufficient in the majority of cases. [ABSTRACT FROM AUTHOR]

Background Unilesional mycosis fungoides (UMF) and pagetoid reticulosis (PR) are variants of mycosis fungoides. Conventional therapy comprises surgical excision or radiotherapy, which may be associated with long-term side effects, especially when the lesion is located at a special site like the palms and soles. Therefore, alternative treatment options are needed to treat solitary lesions in the case of UMF or PR. Recently, topical photodynamic therapy (PDT) has been described to be an efficient and non-invasive therapeutical option with excellent clinical outcome. Objective The objective of this study was to report a 43-year-old woman with plantar UMF treated successfully with PDT, and to compare our findings with the data on PDT in UMF and PR reported in the literature. Methods The literature was analysed for articles on UMF and PR, respectively, treated with topical PDT. Various parameters including form of PDT and response to treatment were analysed and compared with our case. Results A total of 24 patients were documented with 24 lesions treated with PDT, either using aminolevulinic acid (ALA) or methylaminolevulinate (MAL). In average, a single lesion was treated 4 times with PDT. In 21 cases (88%), complete response could be achieved, whereas three cases (13%) showed partial remission. None of the cases showed stable or progressive disease. Conclusions PDT is a safe, efficient and non-invasive therapeutical approach for the treatment of UMF and PR. It has no long-standing adverse events and therefore is of high therapeutic value especially in cases of UMF and PR located at special sites like the palms and soles. We propose to include topical PDT as therapeutic option for the treatment of UMF and PR in future guidelines on the management MF. [ABSTRACT FROM AUTHOR]

Background Epidermodysplasia verruciformis ( EV) is a genodermatosis leading to infections with cutaneous HPV, persistent plane warts and a high rate of non-melanoma skin cancer ( NMSC). Biallelic loss-of-function mutations in TMC6 and TMC8 are known to be causative. Objective The aim of this study was to report EV-causing mutations in four patients with EV and to give an overview of all described patients with EV. Patients and methods We investigated four patients with classical features of EV from two families. All patients were affected by plane warts with typical EV histology since early childhood, and β- HPVs were detected on their skin. One patient had recurring cutaneous squamous cell carcinomas ( cSCC) and carcinomas in situ (Bowen type). We sequenced both TMC6/8 for disease-causing mutations and quantified levels of gene expression. We also performed a systematic literature review to discuss these patients in the context of previously reported cases, mutations already identified, as well as HPV types. Results Three patients of one family carried a homozygous splice site mutation in TMC8 resulting in aberrantly spliced transcripts that were not degraded. By contrast, no TMC6/8 mutation was detected in the patient from the other family. A systematic literature review revealed 501 described patients with EV. Around 40% of patients with EV analysed for genetic alterations carried no mutation in TMC6/8. While β- HPVs were identified in the majority of cases, α- HPVs were detected in several individuals. Conclusion The relatively high proportion of EV patients without mutation in TMC6/8 indicates the existence of EV-causing mutations in additional, presently unknown gene(s). However, a homozygous TMC8 splice site mutation in our patients resulted in aberrant transcripts which cannot retain the healthy phenotype. The literature review revealed that HPV-5 is the most commonly identified HPV in patients with EV, but HPV-3, HPV-14 and HPV-20 were unexpectedly identified more frequently than HPV-8. [ABSTRACT FROM AUTHOR]

Many clinical trials have been conducted on the treatment of pityriasis rosea ( PR). Our aim was to establish a position statement for the management of adults with PR based on the best available evidence. We searched PubMed for all reports on randomized controlled trials for the treatment of PR published in the past 30 years. We retrieved 14 articles reporting randomized controlled trials, and found five which met our quality requirements for in-depth analyses. Erythromycin was found in a well-conducted triple-blind study to cast significant impacts on clinical outcomes. However, adverse gastrointestinal effects were fairly common. Another well-conducted study on azithromycin reported no significant benefit. It was reported in three well-conducted studies on oral acyclovir in low dose (400 mg three times daily for 7 days or 400 mg five times daily for 7 days) and high dose (800 mg five times daily for 7 days), that acyclovir is effective in attaining rash regression and lessening the pruritus. When compared against each other, the high-dose regimen demonstrated no benefit over the low-dose regimens. Our statement comprises the follows: (i) The diagnosis of PR should be ascertained; (ii) The patients should be assessed for rash severity and impacts on quality of life; (iii) PR is a self-limiting disease, and most patients do not necessitate any treatment; (iv) For patients necessitating active treatment, oral acyclovir as 400 mg three times daily for 7 days can be considered; (v) Attention should be given to adverse effects and contraindications of acyclovir; (vi) When PR occurs in early pregnancy, oral antiviral therapy could be considered after consulting experienced clinicians; (vii) Inadequate information exists in the use of acyclovir to treatment PR in children and breastfeeding women; and (viii) Treating PR is an off-label use of acyclovir, and this has to be discussed with experienced colleagues and the patients. [ABSTRACT FROM AUTHOR]

Identifies the diagnostic signs of cutaneous lymphomas. Clinical manifestations; Histomorphology; Phenotyping and genotyping.