RESUMEN
Cutaneous lichen planus (CLP) and psoriasis (PSO) are both common chronic inflammatory skin diseases for which development of new treatments requires the identification of key targets. While PSO is a typical Th17/IL-17-disorder, there is some evidence that Th1/IFN-É£ dominate the inflammatory process in CLP. Nonetheless, the immunopathogenesis of CLP is not fully explained and key immunological factors still have to be recognized. In this study, we compared the immune signature of CLP lesions with the well-characterized inflammation present in PSO skin. First, we analysed the histological and immunohistological characteristics of CLP and PSO. Second, we assessed the cytokine expression (IL1A, IL1B, IL4, IL6, IL8, IL10, IL17A, IL19, IL21, IL22, IL23A, IL13, IFNG, TNF, IL12A, IL12B and IL36G) of lesional skin of CLP with PSO by qPCR. Histology revealed a similar epidermal thickness in CLP and PSO. Immunohistochemically, both diseases presented with an inflammatory infiltrate mainly composed by CD3+ CD4+ T cells rather than CD3+ CD8+ . Importantly, mRNA analysis showed a distinct cytokine signature: while levels of IL12B, IL1A, IL6 and IL23 were similar between the two groups, the characteristic PSO-associated cytokines IL8, IL17A, IL22, IL19 and IL36G were expressed at very low levels in CLP. In contrast, CLP lesional skin was dominated by the expression of IFNG, IL21, IL4, IL12A and TNF. Immunohistochemistry confirmed the dominance of IL-21, IFN-É£ and also pSTAT1 in the dermal infiltrate of CLP, while IL-17A was more present in PSO. Collectively, this study improves our understanding of the immunological factors dominating CLP. The dominating cytokines and signalling proteins identified suggest that anti-cytokine therapeutics like JAK inhibitors may be beneficial in CLP.
Asunto(s)
Citocinas/genética , Liquen Plano/genética , Liquen Plano/inmunología , Psoriasis/genética , Psoriasis/inmunología , Adolescente , Adulto , Anciano , Linfocitos T CD4-Positivos/patología , Niño , Citocinas/metabolismo , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Interferón gamma/genética , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Interleucina-8/genética , Interleucinas/genética , Interleucinas/metabolismo , Janus Quinasa 1/antagonistas & inhibidores , Liquen Plano/tratamiento farmacológico , Liquen Plano/patología , Masculino , Persona de Mediana Edad , Psoriasis/patología , ARN Mensajero/metabolismo , Factor de Transcripción STAT1/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Due to rising skin cancer incidence rates there is an urgent need for a quick, reliable and cost-effective therapy. Previous studies showed that fresh tumor tissue and margins could be directly examined microscopically with high sensitivity and specificity. OBJECTIVE: Comparing the accuracy of rapid lump examination (RLE) for the detection of basal cell carcinoma (BCC) during micrographic surgery with formalin-fixed paraffin-embedded hematoxylin and eosin (HE)-stained sections. METHODS AND MATERIALS: 382 specimens of 118 excised samples with suspected BCC were examined with RLE and compared with formalin-fixed paraffin-embedded HE-stained sections. For RLE, following a standardized 60 sec staining protocol, the fresh tissue samples were observed directly with a stereomicroscope. RESULTS: For BCC, RLE had a high but insufficient diagnostic accuracy compared to the gold standard of formalin-fixed paraffin-embedded HE-stained sections. The sensitivity was 76 % (95 % CI = [66.18 %; 84.5 %]) and specificity was 91 % (95 % CI = [86.73 %; 93.75 %]). CONCLUSIONS: RLE is a fast and simple technique for microscopically controlled surgery (MCS) of basal cell carcinomas that requires training. The experience of the examiner has a major influence on the results. RLE has great potential to speed up the workflow in Mohs surgery but should be improved in the future.