The rope sign, a typical and yet infrequent clue.

Cutaneous granulomatous reactions are diverse, both from the clinical and the pathological perspective. Most underlying pathophysiological aspects remain elusive. Interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis have been claimed to be reactions to systemic disorders, such as infectious, inflammatory, or neoplastic conditions. Recently, the overarching term "reactive granulomatous dermatitis" has been coined to unify both entities. We herein report two cases of reactive granulomatous dermatitis presenting with the widely known, albeit infrequent "rope sign" and provide clinicopathological correlation. The two patients included a 53-year-old woman with enlarging erythematous plaques and underlying palpable cords on both sides of trunk near axillae (rope sign), and a 51-year-old woman with personal history of rheumatoid arthritis and a palpable cord on the left aspect of the trunk. Pathological findings were compatible with reactive granulomatous dermatitis in both cases. In conclusion, the rope sign represents a strikingly infrequent but decisive diagnostic clue of reactive granulomatous dermatitis.

Tirbanibulin: review of its novel mechanism of action and how it fits into the treatment of actinic keratosis. / Tirbanibulina: revisión de su mecanismo de acción novedoso y de cómo encaja en el tratamiento de la queratosis actínica.

Actinic keratosis (AK) is a skin condition characterized by the proliferation of mutated keratinocytes that can develop into squamous cell carcinoma. Available therapies, although effective, are associated with a high frequency of severe local skin reactions. Tirbanibulin, one of the treatments for AK currently in development, is a new synthetic chemical entity with anti-proliferative and anti-tumor effects, both in vitro and in vivo, with proved efficacy in the treatment of AK, which has been recently demonstrated in two phase III clinical trials. In the present review, the tirbanibulin mechanism of action, based on the relevant literature and the results of several unpublished preclinical studies, is shown. In addition, the current scenario regarding the available treatments and how the novel tirbanibulin mechanism of action fits into the treatment of AK is raised.

MicroRNA31 and MMP-1 contribute to the differentiated pathway of invasion -with enhanced epithelial-to-mesenchymal transition- in squamous cell carcinoma of the skin.

Epithelial to mesenchymal transition (EMT) is an important mechanism of invasion in cutaneous squamous cell carcinomas (cSCCs) and has been found to be enhanced in tumors originated from actinic keratosis with transformation limited to the basal epithelial layer -differentiated pathway-, compared to cases with invasion subsequent to complete epidermal transformation -classical pathway-. Several microRNAs and proteins can contribute to EMT modulation in cSCCs. MicroRNA21 and microRNA31 are involved in posttranscriptional regulation of protein expression and could play a relevant role in EMT and cSCC progression. Throughout the EMT process upregulation of matrix metalloproteinases (MMPs) enhances invasiveness and MMP-1 and MMP-3 contribute to local invasion, angiogenesis and metastasis in cSCCs. Additionally, cSCC development is associated with PTEN loss and NF-κB, NOTCH-1 and p63 activation. The aim of this work is to identify differences in the expression of those molecules between both pathways of cSCCs development. Eight tissue microarrays from 80 consecutive cSCCs were analyzed using LNA-based miRNA in situ hybridization for miRNA21 and miRNA31 evaluation, and immunohistochemistry for MMP-1, MMP-3, PTEN, NOTCH-1, NF-κB, p63 and CD31. Significantly higher expression of miRNA31 (p < 0.0001) and MMP-1 (p = 0.0072) and angiogenesis (p = 0.0199) were found in the differentiated pathway, whereas PTEN loss (p = 0.0430) was more marked in the classical pathway. No significant differences were found for the other markers. Our findings support a contribution of miRNA31 and MMP-1 in the differentiated pathway, associated to EMT and increased microvascularization. The greater PTEN loss in the classical pathway indicate that its relevance in cSCC is not EMT-related.

Position paper on a simplified histopathological classification of basal cell carcinoma: results of the European Consensus Project.

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.

Protocol for the Histologic Diagnosis of Cutaneous Melanoma: Consensus Statement of the Spanish Society of Pathology and the Spanish Academy of Dermatology and Venereology (AEDV) for the National Cutaneous Melanoma Registry. / Protocolo de diagnóstico histológico para muestras de pacientes con melanoma cutáneo. Documento de consenso de la SEAP y la AEDV para el Registro Nacional de Melanoma.

This article describes a proposed protocol for the histologic diagnosis of cutaneous melanoma developed for the National Cutaneous Melanoma Registry managed by the Spanish Academy of Dermatology and Venereology (AEDV). Following a review of the literature, 36 variables relating to primary tumors, sentinel lymph nodes, and lymph node dissection were evaluated using the modified Delphi method by a panel of 8 specialists (including 7 pathologists). Consensus was reached on the 30 variables that should be included in all pathology reports for cutaneous melanoma and submitted to the Melanoma Registry. This list can also serve as a model to guide routine reporting in pathology departments.

Diagnosis and Treatment of Merkel Cell Carcinoma in Specialized Dermatology Units: A Clinical Practice Guideline of the Spanish Academy of Dermatology and Venereology. / Carcinoma de células de Merkel: diagnóstico y tratamiento en atención especializada dermatológica. Guía de práctica clínica de la Academia Española de Dermatología y Venerología.

BACKGROUND AND OBJECTIVE: Merkel cell carcinoma is a rare, aggressive skin cancer that is managed in a great variety of ways. However, international clinical practice guidelines give only partial coverage to issues considered major problems.The recommendations presented here aim to provide Spanish dermatologists with a guide to improving disputed aspects of diagnosis, staging, and treatment of localized Merkel cell carcinomas. MATERIAL AND METHODS: The ADAPTE process was used. Members of the Spanish Group of Oncologic Dermatology and Surgery (GEDOC) with experience in treating Merkel cell carcinoma and interest in drafting these guidelines were selected. The group described the care process and listed the most important clinical questions. They then searched for guidelines and assessed them with the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. After consulting the guidelines for answers to their clinical questions, the group drafted the present statementand sent it for external review. RESULTS: The guidelines that scored highest in the AGREE II assessment step were the consensus-based interdisciplinary guideline of the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer, and those of the Comprehensive Cancer Network, the Alberta Health Services in Canada, the American Cancer Society, and the Cutaneous Oncology Group of the French Society of Dermatology. A total of 9 clinical questions were answered based on these guidelines. CONCLUSIONS: The guidelines presented here answer clinical questions that arise in routine practice. They can provide dermatologists with a starting point for decision-making, although available resources and patient preferences must always be borne in mind.

Derm Dotting: A New Technique That Improves Diagnostic Precision in the Evaluation of Skin Lesions. / Derm dotting: una técnica novedosa para mejorar la precisión diagnóstica de lesiones cutáneas.

Dermoscopy has improved diagnostic precision in the clinical evaluation of complex skin lesions by helping to pinpoint small clinically suspicious areas that are not visible to the naked eye but require histopathologic examination. Derm dotting is a new technique for selectively marking areas of interest to ensure they are examined under a microscope. Left unmarked, suspicious areas might not appear in routinely prepared cross sections or might be difficult to correlate with dermoscopic images. In vivo or ex vivo derm dotting involves the application of nail polish, which, unlike stains, leaves tissues unaltered. Dots can be placed by the dermatologist or laboratory staff during macroscopic preparation of the sample. Derm dotting is a simple, inexpensive technique that any dermatopathology laboratory can quickly adopt to improve diagnostic precision through better dermoscopic-histologic correlation.