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AimTo retrospectively evaluate the characteristic clinicopathological spectrum in patients with suspicion of IgG4-related disease (IgG4RD).MethodsWinpath histology database from January 2011 to April 2018 identified all suspected IgG4RD cases wherein IgG4 immunohistochemistry was performed. The histology slides were reviewed to categorise cases into Boston criteria groups—highly suggestive of IgG4RD, probable IgG4RD and insufficient evidence. Information regarding clinical data, treatment received, follow-up and serum IgG4 levels was obtained from medical records and AllScripts Patient Administration System (APAS) clinical database.ResultsThe study included 204 patients and the most common sites of biopsy/resection were pancreas and duodenum. The most common clinical presentation was fibroinflammatory lesion or mass/lump. On histology, 54/204 (26.47%) cases showed typical storiform fibrosis, 65/204 (32.64%) had >10 IgG4+ plasma cells per high power field and only one case showed thrombophlebitis (0.49%). There were 14/204 (6.78%) cases categorised as highly suggestive of IgG4RD; 8 of these showed high serum IgG4 levels and were managed clinically as true IgG4RD.ConclusionHistological diagnosis of IgG4RD remains challenging, as not all characteristic features are always present especially in small biopsies. Due to the novelty of its experience, fear of over diagnosis in the context of malignancy and features overlapping with diseases of similar clinical scenario, diagnosis of IgG4RD has become more puzzling. Further multicentre clinical trials/studies are advisable.

Eosinophilic Oesophagitis (EO) is characterised by large numbers of eosinophils in oesophageal mucosa in response to food or inhaled antigens. Treatment with elimination diet or corticosteroids lead to improvement in some children, but their efficacy is not optimal.Aimof this study is to identify clinical, endoscopic and/or histological features associated with response to treatment with swallowed fluticasone propionate.Patients and methodsIn the last 12 years 34 children (M/F 25/9) with EO were treated with fluticasone propionate spray 250 μg/puff by inhaler without spacer, three puffs three times a day for 6 weeks, and returned for a follow-up endoscopy. At histology 25 of them were found to be responders to therapy (73.5%) and 9 were non-responders. Anthropometric characteristics, symptoms at presentation, endoscopic and histological data at baseline between responders and non-responders were compared.ResultsAge, sex, height, duration and type of main symptom at presentation, type of allergy and number of allergens, peripheral eosinophil counts an serum IgE were similar in responders and non-responders. At baseline histology findings responders had a more severe inflammation: median peak eosinophils/high power field was higher (76 vs 44 in non responders p=0.04), eosinophilic microabscesses were present in a significantly higher number of responders (p=0.04) and peak mast cells/ high power field was significantly higher (p=0.001).ConclusionsClinical characteristics of children with EO at baseline were similar in responders and non-responders, but a more severe inflammation in oesophageal mucosa was associated with a higher response rate to fluticasone treatment.

AimsUrethral caruncle is a benign, polypoid urethral mass that occurs almost exclusively in postmenopausal women. Despite that these lesions are routinely managed with topical medications or excision, their pathogenesis is not well understood. We investigated the possibilities of autoimmune, viral and inflammatory myofibroblastic proliferations as possible aetiologies.MethodsIn 38 patients with urethral caruncle, we utilised immunohistochemistry for immunoglobulin G (IgG) and IgG4 to assess for a potential autoimmune aetiology. Immunohistochemistry was performed in nine patients for Epstein–Barr virus, BK virus, human herpesvirus 8, human papillomavirus, adenovirus and anaplastic lymphoma kinase.ResultsFour patients (11%) showed infiltrates of ≥50 IgG4-positive plasma cells per high power field, of which all showed an IgG4 to IgG ratio greater than 40%. A statistically significant difference (pConclusionsUrethral caruncle is a benign inflammatory and fibrous polypoid urethral mass of unclear aetiology. It appears unrelated to viral infection and lacks the abnormal expression of anaplastic lymphoma kinase protein, as seen in inflammatory myofibroblastic tumours. Increased numbers of IgG4-positive plasma cells in a subset of lesions raise the possibility that some cases may be related to the autoimmune phenomena of IgG4-associated disease.

The patient is a 73-year-old woman who was diagnosed with nodular melanoma of the calf almost 2 years prior to presentation. The melanoma was treated with wide-margin surgical resection (pT4b, 21 mitoses/high power field, 8 mm depth), followed by sentinel lymph node biopsy, which was negative. However, surveillance CT scan done less than a year after the original excision showed metastases to the liver, bone, lungs and adrenal glands. After oncological assessment, the patient had decided not to proceed with chemotherapy. The gastroenterology service was consulted when the patient presented with melena and significant anaemia (haemoglobin 54 g/L, haematocrit 0.17 L/L). Her haemoglobin level was normal 1 year prior (128 g/L). She also had mild renal impairment (creatinine 135 μmol/L, urea 11.4 mmol/L, glomerular filtration rate 32 mL/min/1.73 m2). She was resuscitated, including blood transfusions, and underwent urgent gastroscopy. …

A subset of patients with irritable bowel syndrome (IBS) have an increased number of mast cells (MCs) in the colonic mucosa. Psychological factors are believed to contribute to the course of IBS.To examine associations between fatigue, depression and MCs of the colonic mucosa in IBS.Colonic biopsies were taken from 50 Rome II IBS patients, 21 healthy controls and 11 depressed/fatigued patients without IBS. The cellularity of the lamina propria was determined as the number of inflammatory cells per high power field (hpf) through a 400x microscope. The Fatigue Impact Scale (FIS) and the short form Beck Depression Inventory (BDI) evaluated the severity of fatigue and depression.IBS patients had a significant increase in the cellularity of the lamina propria compared with controls or with depressed patients (mean (SD) 94.5 (48-110) vs 68 (58-82) and 78 (87-90) cells per hpf, p = 0.005 and p = 0.05, respectively), in particular of MCs (9.3 (5.6-11.7) vs 4.0 (2.7-6.8) and 4.3 (2.8-7.8) cells per hpf, p = 0.001 and p = 0.005, respectively). Both the FIS and BDI scores were significantly higher in IBS or in depressed patients than in controls (p0.001). In IBS, the FIS score correlated significantly with the cellularity of the lamina propria (r = 0.51, p0.0001) and MCs (r = 0.64, p0.0001). In IBS, the BDI score correlated significantly with MCs (r = 0.29, p = 0.03).Elevated MCs counts are a key feature of the low-grade inflammatory infiltrate in the caecal mucosa of IBS. Fatigue and depression are associated with mucosal cell counts, in particular MCs, suggesting that psychological factors are associated with the low-grade inflammatory infiltrate in IBS.

Background—Apoptosis, or programmed cell death, can be induced by radiotherapy. The extent of apoptosis in a tumour before treatment may have important implications for response to radiotherapy and long term survival. Aim—To examine the extent of apoptosis in tumour tissue from patients with squamous carcinoma of the cervix before radiotherapy, and to correlate this with response to treatment and prognosis. Methods—The percentage of apoptotic cells was assessed in 146 carcinomas of the cervix from patients scheduled to receive radiotherapy. The CAS 200 static image analysis system was used to count the number of tumour nuclei per high power field, while the numbers of apoptotic cells in the same field were visualised simultaneously on the image analyser and recorded manually. Results—The median apoptotic level was 0.73%. Patients were divided into two groups around the median. There was no statistically significant difference in outcome between the two groups as determined by long term survival following radiotherapy. Conclusions—The CAS 200 static image analyser system can be used to assist in the rapid semiautomated assessment of apoptosis in conventionally prepared tissue. The results suggest that the apoptotic state of a tumour before treatment is of no value in predicting response to radiotherapy and subsequent prognosis. Tumour stage, size, and BrdU labelling index, as a measure of proliferation rate, remain the most important prognostic factors in terms of predicting local tumour control. Key Words: apoptosis • uterine cervix • squamous cell carcinoma

Introduction Eosinophilic oesophagitis (EoE) is a chronic condition of the oesophagus characterised by a dense eosinophilic infiltrate defined as >15 eosinophils/high power field (eos/hpf). The aim of this study was to capture the prevalence of EoE in a tertiary referral centre in London, to identify factors associated with a positive diagnosis and interrogate optimal response to therapy. Methods From February 2013 to November 2015, all patients presenting with solid food dysphagia to University College Hospital had a high resolution white light endoscopy. Those with cancer, achalasia, postoperative stricture or endotherapy for Barrett’s were excluded. Endoscopy, histology and clinical data were collected. >15 oes/hpf were defined as positive for EoE. A separate histopathology search identified patients with >15 eos/hpf and no dysphagia. A prospective follow-up was conducted in focusing on therapy and response in those with >15 eos/hpf. Results Out of the 1566 patients with dysphagia, 524 were excluded for reasons stated. 736/1042 (71%) had oesophageal biopsies. Of those, 67 (9.1%) had more than 15 eos/hpf. Another 14 patients with >15 eos/hpf with symptoms other than dysphagia were identified from histology records, making the total number with eosiniphilia 81. The mean number of biopsies taken in those with >15 eos/hpf (6.3) was greater than those with Conclusion A higher number of biopsies taken raises the diagnostic yield; however still up to 1/3 patients in a modern referral centre have no biopsies taken. EoE should be excluded in those with no dysphagia and refractory reflux symptoms. Although PPIs are provided as first-line therapy, a positive response to steroids is more likely in those with higher numbers eos/hpf, while those with fewer numbers and no endoscopic features could be considered for PPI therapy first. Such findings might be a useful tool to help tailor therapy. Disclosure of Interest None Declared

OBJECTIVE: To ascertain whether the presence of genital infection adversely affects smear quality. METHOD: A prospective study of all patients having cytology performed. The presence of genital infection was recorded and compared with the smear result. RESULTS: The presence of genital infection was not associated with inadequate cytology. Inflammatory changes were found in association with symptomatic candidiasis, trichomoniasis, Chlamydia trachomatis infection, primary herpes simplex, and the finding of 21-30 polymorphs per high power field (averaged over 10 fields) on cervical samples. Inadequate cytology was significantly associated with the smear taker. CONCLUSION: The presence of genital infection at the time of cytology does not increase the rates of inadequacy, and opportunistic cytology should not be deferred as the patient may default from further appointments.

IgG4-related disease is a fibroinflammatory disorder of unknown etiology that can affect any organs. It is characterized by diffuse or localized infiltration of the involved tissue by IgG4- positive plasma cells associated with lymphoplasmacellular inflammation, storiform fibrosis and obliterative phlebitis. Elevated serum concentrations of IgG4 are present in many patients. Here we report the case of a patient with multi organ involvement due to IgG4-related disease. A 71-year-old Caucasian man presented with sialadenitis of the left submandibulary gland. Biopsy of the gland revealed distinct chronic sclerosis as well as lymphoplasmacytic infiltration with more than 100 IgG4-positive plasma cells per high power field. The patient developed progressive dyspnea and a chest CT scan showed thickening of the interlobular septum and alveolar walls as well as bilateral infiltrates and ground glass opacities. Serum concentration of IgG4 was 1050mg/dl (reference value 5 - 125mg/dl). The patient was initially treated with steroids with substantial clinical improvement and decrease of IgG4 serum levels. As the steroids were tapered, the patient developed cholangitis and pancreatitis. Another course of glucocorticoid therapy and adjunctive Rituximab therapy resulted in full clinical remission. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.6187

Background The cut-off of ≥5 polymorphs/high power field (p/hpf) in a Gram stained male urethral smear (GSUS) for diagnosing non-gonococcal urethritis derives from evaluations using Chlamydia trachomatis (CT) culture as gold standard. There is also significant observer variation in performing microscopy. Objective To compare automated flow cytometry of first void urine white cell count (FVU-UWC) to GSUS for prediction of CT infection in men. Methods First void urines from 227 symptomatic male patients, all undergoing GSUS, were collected and patients stratified into: those treated for urethritis, diagnosed by GSUS result, history and examination (n=114) and; those not thought to have urethritis (n=113). First void urines were analysed by automated flow cytometry using the bench-top Sysmex UF-100 Analyser. Results CT was found in 11.6% and 6.2% urethritis and non-urethritis patients respectively and gonorrhoea (GC) in 3.6% and 1.1% respectively. There was no difference in UWC between urethritis and non-urethritis (p=0.690) nor association between GSUS grade and UWC (p=0.933). Median GSUS was higher for CT positive compared to negative patients (≥5/hpf vs 0). UWC were higher in CT (p=0.001) and GC (p≤0.001) positives. ROC area under the curve (AUC) for predicting CT was 0.844 (p≤0.001) with an optimal cut-off of >29 UWC/μl giving sensitivity of 90% and specificity of 76%. For predicting CT in urethritis and non-urethritis: the positive predictive values using the >29 UWC/μl cut-off were 20% (95%CI 9.1% to 37.5%) and 34.4% (19.2% to 53.2%) and the negative predictive values NPVs 100% (94.2% to 100%) and 97.5% (90.4% to 99.6%) respectively; for GSUS, using ≥5/hpf, positive predictive values were 10.5% (5.4% to 18.9%) and 0% (0% to 60.4%) and negative predictive values were 82.4% (55.8% to 95.3%) and 93.6% (86.8% to 97.2%) respectively. Conclusion UWC is (1) higher in CT and GC infection; (2) is a better predictor of urethral CT than GSUS and; (3) possibly more useful for determining non-gonococcal urethritis. Automated rapid flow cytometry may offer significantly improved utility over microscopy in the clinic.

Purpose To investigate the changes of EPCs proliferation and related factors in peripheral blood after the CSWT treatment. Methods A total of 26 CAD patients undergoing extracorporeal cardiac shock wave therapy were selected. Mononuclear cells obtained from peripheral blood were cultured in EGM-2-MV medium. Cell morphology and the number of colonies formed were observed and analysed. After 7 days of culture, adherent cells were analysed and counted. Whether EPCs differentiated or not was identified by laser confocal microscopy; the number of circulating EPCs were studied by flow cytometry; the plasma level of VEGF, IL-8, SDF-1 and MMP-9 was determined by enzyme linked immunosorbent assay. Results The cultured EPCs and EPC-CFU number in vitro were significantly increase after therapy (EPCs (18.85±4.30) cell/high power field vs (30.12±6.77) cell/high power field (5.08±1.79) cell/high power field vs (12.27±2.75) cell/high power field, all p 0.05), compared with the group before treatment. Conclusions The CSWT appears to promote the expression of VEGF and IL-8 proteins, also stimulates the EPCs proliferation, significantly increases the EPCs and improves its function in peripheral blood, whereas the CSWT likes not influence so obviously on the expression of SDF-1, MMP-9.

It was generally admitted that there was no specific rheumatoid lesion in the kidney and that most renal disease in patients with rheumatoid arthritis (RA) was usually linked to amyloid or secondary effects of drugs. Nevertheless, the necropsy study of Boers et al had shown that 19.7% of RA patients had a glomerulonephritis (GN) at death.1 Recent review of renal biopsy findings in RA patients showed that the most common histopathological finding was mesangial GN followed by amyloidosis and membranous GN.2 3 To evaluate the renal involvement in Chinese patients with RA, a short retrospective clinical study was performed from data of 1468 inpatients of a rheumatology section from 1984 to 1996. Patients having transient mild proteinuria, haematuria or both were not included in the current analysis. Only RA patients with persistent abnormality of haematuria (at least 4 RBC/high power field in two consecutive urine samples), increased …

Aim—To compare the performance of leucocyte esterase and nitrite dipstick tests with microscopic examination and culture offirst morning urines (n = 420) of hospital inpatients. Results—The sensitivity, specificity, and negative predictive value of the leucocyte esterase test for the cutoV of > 10 WBC/µl were 57%, 94%, and 68%, respectively. For > 5 WBC per high powerfield (HPF) these variables were 84%, 90%, and 93%. For >1 0 5 colony counts/ml, the sensitivity of the nitrite test was 27%, specificity 94%, and negative predictive value 87%. When either leucocyte esterase or nitrite positivity was accepted as a marker of urinary tract infection, the sensitivity was 78%, specificity 75%, and negative predictive value 94%, and there were 22% false negative results. Semiquantitative microscopic estimation of bacteria per HPF yielded 40% false positives. Conclusions—Leucocyte esterase and nitrite dipstick tests are not suitable for screening for urinary tract infections. (J Clin Pathol 1998;51:471‐472)

One hundred consecutively submitted corneas removed by penetrating keratoplasty were studied histologically to determine the frequency in which eosinophils are found. In 20 corneas eosinophils occurred in densities ranging from 0.2 to more than 50 per high power field (HPF), and accounted for 1.5% to 100% of the total leucocytes counted. More than half of the corneal specimens containing eosinophils, including six of seven corneas having the highest eosinophil concentrations, were failed grafts. Because the concentration of eosinophils was in many cases beyond that attributable to non-specific vascular permeability, the existence of eosinophil chemotaxic substances in the cornea is postulated.

The two standard tests for the initial diagnosis of non-gonococcal urethritis (NGU), microscopic examination of gram stained urethral smears and the two glass urine test, have the disadvantage of being insensitive and subjective. The leucocyte esterase test detects enzymes specific to polymorphonuclear leucocytes and can therefore be used as a sensitive indicator of pyuria. This study sought to evaluate its use as a rapid, sensitive, and non-subjective method of screening for NGU. Of the 81 men with urethral symptoms in the study group, 26 had more than 5 polymorphonuclear leucocytes per high power field (x 1000) and all 26 were leucocyte esterase test positive; whereas 55 had fewer than 5 polymorphonuclear leucocytes per high power field, but 29 (53%) of them had a positive leucocyte esterase test result. In addition, 25 patients in the study group yielded Chlamydia trachomatis on culture. Of these 25, 24 (96%) were leucocyte esterase test positive, whereas only 11 (44%) were Gram stain positive. All 40 patients in the control group (without urethral symptoms or signs) were leucocyte esterase test negative. The leucocyte esterase test is thus a rapid, sensitive, and non-subjective screening aid in the diagnosis of NGU.