Search

Actinic keratosis (AK), a skin condition characterized by the proliferation of atypical keratinocytes, can progress to squamous cell carcinoma. Existing treatments are effective but cause high rates of local skin reactions. Tirbanibulin, one of the treatments under development for AK, is a novel synthetic drug with powerful in vitro and in vivo antiproliferative and antitumor effects. Its efficacy in this setting was recently demonstrated in 2 phase 3 clinical trials. We review tirbanibulin’s mechanism of action based on the current literature and several unpublished preclinical studies. We also review treatments available for AK and discuss how tirbanibulin, with its novel mechanism of action, fits into the therapeutic landscape. Resumen: La queratosis actínica (QA) es una afección cutánea caracterizada por la proliferación de queratinocitos mutados que pueden convertirse en carcinoma escamoso cutáneo. Las terapias disponibles, aunque efectivas, están asociadas con una alta frecuencia de reacciones cutáneas locales graves. Tirbanibulina, uno de los tratamientos para la QA actualmente en desarrollo, es un nuevo fármaco sintético de origen químico con potentes efectos antiproliferativos y antitumorales in vitro e in vivo con eficacia probada en el tratamiento de la QA, demostrada recientemente en dos ensayos clínicos de fase III. En la presente revisión, se muestra el mecanismo de acción de tirbanibulina en base a la literatura relevante y los resultados de varios estudios preclínicos no publicados. Además, se plantea el escenario actual en cuanto a los tratamientos disponibles y cómo el mecanismo de acción novedoso de tirbanibulina encaja en el tratamiento de la QA.

Part 2 of this series on granulomatous diseases focuses on skin biopsy findings. Whereas the first part treated noninfectious conditions (metabolic disorders and tumors, among other conditions), this part mainly deals with various types of infectious disease along with other conditions seen fairly often by clinical dermatologists.

This series of 2 articles on dermatopathologic diagnoses reviews conditions in which granulomas form. Part 1 clarifies concepts, discusses the presentation of different types of granulomas and giant cells, and considers a large variety of noninfectious diseases. Some granulomatous diseases have a metabolic origin, as in necrobiosis lipoidica. Others, such as granulomatous mycosis fungoides, are related to lymphomas. Still others, such as rosacea, are so common that dermatologists see them nearly daily in clinical practice.

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.

Resumen Antecedentes y objetivo El carcinoma de celulas de Merkel es un tipo de cancer de piel infrecuente y agresivo. Hay una gran variacion en su manejo y las diferentes guias extranjeras que existen cubren parcialmente los problemas identificados como principales. El objetivo de la presente guia es servir de referencia a los dermatologos espanoles para mejorar aspectos controvertidos del diagnostico, estadificacion y tratamiento del carcinoma de celulas de Merkel. Materiales y metodos Se empleo el metodo ADAPTE: se escogio a miembros del Grupo Espanol de Dermato-Oncologia y Cirugia (GEDOC) con experiencia en el tratamiento de estos tumores y con interes en participar en la elaboracion de la guia. Tras resumir el proceso de atencion y elaborar las preguntas clinicas relevantes, se hizo una busqueda de guias, que se seleccionaron segun su puntuacion mediante el instrumento Appraisal of Guidelines for Research and Evaluation (AGREE II). Tras la busqueda de las respuestas en dichas guias, se elaboraron posteriormente las recomendaciones. Por ultimo, se sometio la guia a revision externa. Resultados Las guias con mejor puntuacion fueron las de National Comprehensive Cancer Network, la European consensus-based interdisciplinary guideline, Alberta Healthservices Clinical practice guideline, American Cancer Society y Cutaneous Oncology Group of the French Society of Dermatology. Se obtuvieron en total 9 preguntas clinicas, contestadas a partir de estas guias. Conclusiones Esta guia responde a preguntas habituales en la practica clinica diaria y sirve a los dermatologos como referencia en la toma de decisiones, siempre teniendo presentes los recursos y preferencias del paciente.

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 statement and 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.

Resumen La dermatoscopia ha aumentado la precision en el diagnostico clinico de lesiones cutaneas complejas. Es una herramienta que permite identificar pequenas areas de sospecha, no apreciables a simple vista y que requieren examen histopatologico especifico. El derm dotting es un metodo de marcaje selectivo de zonas de interes para asegurar que estos focos son estudiados microscopicamente, puesto que por su pequeno tamano podrian no aparecer en las secciones de rutina o ser dificiles de correlacionar con la imagen dermatoscopica. Combina la dermatoscopia in vivo o ex vivo con la aplicacion de esmalte ungueal. A diferencia de los colorantes usuales, el uso de esmalte ungueal no altera la histologia. Puede ser aplicado por parte del dermatologo o durante el procesamiento macroscopico en el laboratorio. El derm dotting es una tecnica novedosa, sencilla y economica, que puede implementarse rapidamente en cualquier Laboratorio de Dermatopatologia. Mejora la precision diagnostica ya que traslada los hallazgos dermatoscopicos al estudio histologico.

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.

Resumen Este ultimo ano ha sido rico en novedades dermatopatologicas que se vislumbran como el inicio de una nueva era. Los avances en las tecnicas de biologia molecular y su simplificacion, que las hace asequibles al uso rutinario, han supuesto un cambio radical en el concepto de lesiones como el melanoma, cuya caracterizacion genetica sera en el futuro un requisito indispensable para establecer el diagnostico, el pronostico y la terapeutica. Las innovaciones tecnologicas tambien han llegado a los servicios de Dermatologia; la introduccion de ecografos ha propiciado el uso de tecnicas de citologia por puncion-aspiracion que pueden ser tenidas y estudiadas de manera inmediata, facilitando el diagnostico de lesiones superficiales y ganglionares, y permitiendo la estadificacion de neoplasias como el melanoma. La aparicion de tratamientos oncologicos dirigidos contra «dianas terapeuticas» ha conllevado la introduccion de sistemas mas sensibles y especificos para su idetificacion, ha reactivado el interes por patologias olvidadas como el carcinoma basocelular agresivo y ha comportado la aparicion de reacciones dermatologicas que, junto con las secundarias a farmacos biologicos, empezamos a reconocer. Tecnicas consolidadas como la inmunohistoquimica continuan progresando con la incorporacion de nuevos anticuerpos que contribuyen de manera notable al diagnostico. Este ano, ademas, se han descrito o caracterizado nuevas entidades clinicopatologicas, y entre ellas 2 nuevos tipos de melanoma. Tambien se ha avanzado en el conocimiento de otras, como el linfoma T pleomorfico CD4+ de celulas pequenas/medianas. Estos temas, junto con novedades en tumores anexiales, alopecias y otras lesiones, seran comentados en esta revision.

Background: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias. Objective: To examine whether EV is associated with cutaneous MCPyV infection. Methods: We used MCPyV-specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient with acquired EV. Results: In all congenital EV patients, MCPyV DNA was found in carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In 4 of these patients, the MCPyV-positive skin lesions were from different anatomic locations. In addition, 1 immunosuppressed patient suffering from acquired EV harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of 30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV DNA. Conclusions: The strong association of EV-associated skin neoplasms with MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV. Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the development of EV-associated skin neoplasms.

Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology. The presence of mycobacterial nucleic acid components in patients with sarcoidosis has been demonstrated with varying degrees of success. Objectives: The aim of this study was to estimate the presence of Mycobacterium tuberculosis DNA in tissues from sarcoidosis patients, in Catalonia, Spain, as well as to assess the long-term clinical course in these patients. Methods: Fifty-eight paraffin-embedded tissue biopsies corresponding to cases of sarcoidosis (n = 23), lung neoplasm (n = 23), and lung tuberculosis (n = 12) available in 1996 were analyzed in a retrospective study by means of a nested polymerase chain reaction using primers corresponding to the insertion element IS6110 of M. tuberculosis complex. For greater sensitivity, Southern blot hybridization was performed. Clinical data were recorded prior to and after PCR analysis (follow-up reported until 2002). Results:M. tuberculosis DNA was present in 9 out of 23 sarcoidosis biopsies (39%), in 1 out of 23 control patients (4%) (p < 0.01), and in all tissue samples from the 12 control patients with tuberculosis. To date, none of these sarcoidosis patients has developed tuberculosis over a mean (±SD) follow-up period of 11 (±3.4) years. Conclusion: In our setting, M. tuberculosis DNA is present in tissue biopsies of significantly more sarcoidosis patients than controls. However, these results do not demonstrate causality, although they may suggest a link between M. tuberculosis infection and sarcoidosis in some cases. Follow-up of these patients suggests that M. tuberculosis-DNA-positive sarcoidosis patients are not at greater risk of developing tuberculosis than M. tuberculosis-DNA-negative patients.