Diagnóstico de fluorescencia e inmunohistoquímico en la enfermedad de Bowen tratada con terapia fotodinámica

Resum

Introduction: Bowen’s disease (BD), also known as in situ squamous cell carcinoma, is a nonmelanoma skin cancer, which may appear on the skin or mucous areas and has the potential of evolve to invasive squamous cell carcinoma. An early diagnosis and treatment may be of great benefit for the patient. Several studies have shown the efficacy and good cosmetic outcome of photodynamic therapy (PDT) for the treatment of BD and has been approved since 2008 as a good option for the treatment of BD.1,2,3 Fluorescence diagnosis (FD) consists on registration of the fluorescence emitted by tissue after application of a photosensitizer, indicating presence of tumoral cells. It has been described as a useful tool for actinic keratosis. Different results have been published about fluorescence diagnosis for basal cell carcinomas. Very few reports about the role of fluorescence diagnosis for BD exist and this is the first one which correlates the fluorescence image after PDT with the histopathological response. There are sparse reports describing immunohistochemical markers of BD, and none of them regard the changes of these markers after PDT. Objective: To assess the efficacy of PDT for BD treatment. To assess the validity of FD comparing it with the gold-standar, which is the histopathological study. A secondary objective was to describe the changes induced by PTD on the expression of immunohistochemical markers such as Ki 67 and p53, as well as determine possible response preditive factors. Patients and methods: We carried out an observational, retrospective and descriptive study. A total of 67 patients with biopsy proven BD lesions were enrolled. All the lesions had been treated with the standard protocol (Topical methylaminolaevulinic acid under occlusion for 3 hours and followed by illumination with red-light (630 nm, 38J/cm2, 7.5 minutes. Two sessions one week appart). Clinical and fluorescence photographs were taken before treatment and one month after the 2nd one with an Olympus Camera® C5060 connected to ultraviolet flashes (ClearStone® VD-DA digital system). Clinical response was classified as partial, complete or no response. Fluorescence response was classified as negative, intermediate or intense. The follow-up period and the adverse events observed including pain were also collected. In 29 BD lesions a post-treatment biopsy was performed one month after the 2nd treatment and compared with the pre-PDT biopsy. In 24 out of those 29 lesions an immunohistochemical study was performed pre-PDT and after-PDT with Ki67 and p53 markers. Intensity of immunohitochemical expression was classified in a qualitative way. A mean follow-up period of 14.28 months and adverse events were registered. Results: A total of 36 men and 32 women with a mean age of 74.58 years received PDT treatment for BD. Lesions were mainly located on the inferior extremities (34.3%). Some kind of response was achieved by 89.6% of the patients, 41.8% of them were complete responses and 47.8% partial responses. Post-PDT all lesions with negative fluorescence had histology without any tumoral rests whereas all lesions with intense fluorescence had tumoral persistence on the histology. Fluorescence trends to decrease o disappear when more clinical response was achieved: partial response was found in most of the lesions with intermediate fluorescence and complete response was found in most of the lesions with negative fluorescence. We found statistical association between fluorescence and the clinical and histopathological evaluations performed after treatment. Fluorescence diagnosis obtained a 100% sensitivity (higher than clinical evaluation alone) and a specificity of 85.7% (CI: 70.8-100). The decrease on the expression of immunohistochemical markers (Ki67 and p53) post-PDT was statistically significant. Discussion: Different therapeutic options exist for BD treatment, most of them with an important cosmetic impact for the patient. PDT has been recently approved for the treatment of BD tumor based on previous studies which suggested the efficacy of this treatment. Our study is the first one performed in our country with a retrospective design and performed during the diary practice. Our results regarding efficacy and security are similar to those previously published in the English literature. The high sensitivity and specificity of FD allow us to classify it as a valid diagnostic tool for BD diagnosis, and it may be useful during the follow-up or this disease. Histological and immunohistochemical modifications induced by PDT suggest that this therapy may have a role in the modulation of the oncogenic molecular mechanisms implied in the BD formation, helping in reverse the carcinogenic process. Conclusion: BD is a frequent entity and it must be differenciated from invasive squamous cell carcinoma. PDT is an effective treatment for BD as it has high rates of response and an excellent cosmetic outcome with good tolerance and minimal adverse events. Fluorescence diagnostic for BD seems a very helpful diagnostic tool during the follow-up of these patients. Modulation of the immunohistochemical markers supports the anticarcinogenic role directly due to PDT. More randomized clinical studies are to be performed comparing PDT with other standar treatments and assessing the efficiency of this treatment as well as larger and prospective studies to asses predictive factors or response.