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BackgroundDeep penetrating nevus (DPN) is not a widely recognised lesion on the conjunctiva and only a few cases consistent with combined DPN have been reported.MethodsA review of all excised and histopathologically diagnosed conjunctival melanocytic lesions between 2003 and 2018 was performed in order to identify melanocytic nevi morphologically consistent with DPN.ResultsThirty-four DPN were identified among 361 histopathologically examined conjunctival nevi (9.4%), including 33 (97%) combined with a common nevus and 1 (3%) pure DPN. The patients’ age ranged from 7 to 51 years (median, 22 years). Clinically, 21 of 29 (72%) lesions with available data were darkly pigmented, and an increase in size and/or pigmentation was noted in 13 of 18 (72%) lesions with known history. All 24 lesions in which an immunohistochemical analysis was possible were diffusely positive for BRAFV600E (in DPN and common nevus components) and showed a diffuse nuclear positivity for beta catenin and cyclin D1 in the DPN component. None of the 21 lesions with available follow-up data recurred during a follow-up period from 0.3 to 16.3 years (median, 7.5 years).ConclusionsDPN of the conjunctiva is a relatively common lesion and usually presents as a combined nevus. Genetically, DPN of the conjunctiva are characterised by a combination of BRAFV600E mutation and activation of the beta catenin pathway. Recognition of DPN of the conjunctiva is important in order not to overdiagnose it as a melanoma, and to explain its potential atypical clinical features. DPN of the conjunctiva seems to be a benign lesion.

Background:Immunopathology of giant cell arteritis (GCA) results from dysregulated interactions between arterial wall-resident non-immune cells, e.g. vascular smooth muscle cells (VSMCs), and components of the immune system [1]. In spite of several efforts at identifying microRNAs (miRNAs) implicated in the pathogenesis of GCA, the overall information on miRNA involvement in GCA and its related arterial fibro-sclerotic alterations remains scarce.Objectives:To analyze miRNA expression and identify target genes of dysregulated miRNAs in temporal arteries from GCA patients, and to determine their association with GCA-associated arterial wall remodeling.Methods:The study included formalin-fixed, paraffin-embedded temporal artery biopsies (TABs) from 71 clinically diagnosed treatment-naïve patients fulfilling the ACR 1990 classification criteria, and 22 non-GCA subjects (control group). Of GCA patients, 54 histologically positive and 17 histologically negative TABs were included. miRNA expression profiling was performed with quantitative real-time PCR (qPCR)-based miRNA PCR panels and qPCR. The miRDB database and STRING protein-protein network analysis were used for identification of miRNA gene targets and their pathway enrichment analysis, respectively.Results:Of 356 detected miRNAs, we determined significant under-expression of 78 and significant over-expression of 22 miRNAs (≥ 2-fold; p < 0.05) in TAB-positive GCA arteries compared to non-GCA controls, pointing to a strong dysregulation of miRNA expression in inflamed GCA arteries. Several dysregulated miRNAs targeted genes involved in the ubiquitin-proteasome system and the RNA silencing complex, suggesting a novel role of these pathways in GCA. qPCR validation confirmed a 1.9–14.2-fold (p < 0.001) over-expression of “pro-synthetic” (miR-21-3p/-21-5p/-146a-5p/-146b-5p/-424-5p) and 3.4–9.4-fold (p < 0.001) under-expression of “pro-contractile” (miR-23b-3p/-125a-5p/-143-3p/-143-5p/-145-3p/-145-5p/-195-5p/-365a-3p) VSMC phenotype-associated regulatory miRNAs in TAB-positive GCA arteries. These miRNAs targeted gene pathways involved in the arterial remodeling and regulation of the immune system, and their expression significantly correlated with the extent of intimal hyperplasia in TABs from GCA patients (p ≤ 0.015). Additionally, the expression of miR-21-3p/-21-5p/-146a-5p/-146b-5p/-365a-3p differentiated TAB-negative GCA arteries from non-GCA temporal arteries, making these miRNAs potential biomarkers of GCA.Conclusion:Our study demonstrated an extensive dysregulation of arterial miRNA networks in GCA, favoring the pathogenic switch in the VSMC phenotype and associated intimal hyperplasia. We identified several miRNAs, which could represent potential novel GCA biomarkers. Furthermore, our results imply that the ubiquitin-proteasome system and the RNA silencing complex are targets of dysregulated arterial miRNA networks in GCA lesions, providing new insight into the complexity of GCA pathogenesis.References:[1]Weyand CM, Goronzy JJ. Immune mechanisms in medium and large-vessel vasculitis. Nat Rev Rheumatol 2013;9:731–40.Acknowledgments:This work was supported by the Slovenian Research Agency [research core funding No. P3-0054].Disclosure of Interests:None declared

Background Giant cell arteritis (GCA) is the most common systemic vasculitis in adults aged 50 years or above. Annual incidence rates vary widely from 6.9–76.6 per 10 5 of adults in this age group, depending on the region. 1 Objectives To determine the incidence rate of GCA in our population. Methods We prospectively collected incident cases of GCA from January 1st 2011 to December 31st 2012 at our department of rheumatology which is a part of an integrated secondary/tertiary university teaching hospital that is the only referral center serving a region representing approximately a quarter of the national adult population. Additionally, newly diagnosed cases of GCA between January 1st 2009 and December 31st 2010 were retrospectively identified by searching the electronic patient records for ICD-10 codes M31.5 and M31.6 at our department. The retrospective approach and search strategy was also applied on electronic medical records at the departments of infectious diseases and ophthalmology between January 1st 2009 and December 31st 2012. To further reduce possibility of underreporting, the attached medical faculty9s Institute of Pathology provided a list of all temporal artery biopsies examined during the observation period which were then cross-referenced with the hospital9s electronic medical records. Annual incidence rate for GCA was then calculated. Results During the four year observation period we identified 97 new cases of GCA (68% female; mean (SD) age 75.6 (8.1) years) from a well-defined adult white Caucasian population of 232,041 inhabitants aged 50 or above. The temporal artery biopsy was consistent with GCA, negative or not performed in 75.3%, 18.6, and 6.2% of cases, respectively. Thus, the annual incidence of GCA in our population is 10.5 (95% CI 8.5–12.7), and 4.7 (95% CI 3.8–5.7) per 10 5 adults aged 50, and 20 years or above, respectively. Conclusions The annual incidence rate of 10.5 per 10 5 adults aged 50 or above makes GCA the most common systemic vasculitis in this age group of our population. Although the GCA almost exclusively affects adults over 50 years of age, the incidence rate of 4.7 per 10 5 adults aged 20 and above, also makes it the most common systemic vasculitis in the adult population overall, with IgA vasculitis coming a close second with 3.7 per 10 5 adults aged 20 years or above. References Gonzalez-Gay MA, Vazquez-Rodriguez TR, Lopez-Diaz MJ et al. Epidemiology of Giant Cell Arteritis and Polymyalgia Rheumatica. Arthritis Rheum 2009;61:1454-61. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1968