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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the present review, the tirbanibulin mechanism of action, based on the relevant literature and the results of several unpublished preclinical studies, is shown.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.

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.

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.

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.