Showing papers by "Adrian C Bateman published in 2015"

Branched chain in situ hybridization for albumin as a marker of hepatocellular differentiation: evaluation of manual and automated in situ hybridization platforms.

Abstract: Albumin, widely recognized as a highly sensitive and specific marker of hepatocellular carcinoma (HCC), is currently unavailable in the diagnostic laboratory because of the lack of a robust platform. In a prior study we detected albumin mRNA in the majority of intrahepatic cholangiocarcinomas using a novel branched chain RNA in situ hybridization (ISH) platform. We now explore the utility of albumin ISH as a marker of hepatocellular differentiation in HCCs, and compare its sensitivity with Hep Par 1 and Arginase-1. We evaluated 93 HCCs and its mimics including neuroendocrine tumors of the gastrointestinal tract (n=31), neuroendocrine tumors of the pancreas (n=163), melanoma (n=15), and gallbladder carcinoma (n=34). We performed ISH for albumin and immunohistochemistry for Hep Par 1 and Arginase-1. Five previously uncharacterized hepatic neoplasms from our files were also evaluated. Immunohistochemistry for Arginase-1 was performed on 59 intrahepatic cholangiocarcinomas. In addition, 43 HCCs evaluated on the manual platform were also examined on the automated instrument. Fifty-five percent of HCCs were moderately differentiated and 39% poorly differentiated. The sensitivity of ISH for albumin was 99%, with 92 of 93 HCCs staining positive for albumin. In contrast to ISH, the sensitivity of immunohistochemistry for Hep Par 1 and Arginase-1 was 84% and 83%, respectively. The sensitivity of albumin for poorly differentiated HCCs was 99%, whereas that for Arginase-1 and Hep Par 1 was 71% and 64%, respectively. Ninety-seven percent of the HCCs showed albumin positivity in >50% of tumor cells using the ISH platform, as compared with 76% and 70% for Hep Par 1 and Arginase-1 immunohistochemistry, respectively. Three of the 5 previously uncharacterized neoplasms were positive for albumin ISH. Automated albumin ISH platform performed equivalently to the manual format, with albumin reactivity in >50% of tumor cells in all 43 cases that were tested on both platforms. All non-HCCs were negative for albumin. All 59 intrahepatic cholangiocarcinomas were negative for Arginase-1. In conclusion, branched chain ISH performed on manual and automated mode is a robust assay for detecting albumin with sensitivity for poorly differentiated HCCs superior to Arginase-1 and Hep Par 1. When interpreted in conjunction with Arginase-1, albumin ISH offers a high level of sensitivity and specificity.

Are plasma cell-rich inflammatory conditions of the oral mucosa manifestations of IgG4-related disease?

Abstract: Aim The aim of this study was to characterise plasma cell infiltrates, in terms of IgG4 positivity, in specific and non-specific plasma cell-rich chronic inflammatory conditions of the oral mucosa. Exploring the possibility that specific plasma cell-rich oral inflammatory conditions have association with or represent an oral manifestation of immunoglobulin G4-related disease (IgG4-RD). Methods Ten patients with plasma cell-rich chronic inflammatory conditions of the oral mucosa were identified (seven—plasma cell mucositis and three—non-specific diffuse oral mucosal inflammation with ulceration). For each patient, the clinical record and H&E-stained sections were reviewed. Immunohistochemistry for IgG and IgG4 antibodies was performed on sections from the corresponding paraffin block, permitting calculation of the mean number of IgG4+ plasma cells per high-power field (HPF) and the IgG4+/IgG+ plasma cell ratio. Results In all the cases, only one histological hallmark of IgG4-RD—a dense lymphoplasmacytic infiltrate—was seen. Review of the medical histories did not reveal any features representing other manifestations of IgG4-RD. The number of IgG4+ plasma cells exceeded 100 per HPF in half of the cases. Only two cases had an IgG4+/IgG+ plasma cell ratio of >40%; both of which were in the non-specific oral inflammatory group. Conclusions Our study suggests that plasma cell mucositis does not meet microscopic criteria for IgG4-RD. It importantly reinforces the opinion that IgG4+ plasma cells are major components of chronic inflammation in the oral cavity and the pertinence of correct contextual interpretation of histopathological features with clinical findings.

UK guidance for the pathological reporting of serrated lesions of the colorectum

Abstract: Bowel cancer screening programmes have highlighted to endoscopists and clinicians the spectrum of serrated colorectal lesions. One of the most significant developments has been the recognition that sessile serrated lesions (SSLs), while bearing histological resemblance to hyperplastic polyps (HPs), may be associated with the enhanced development of epithelial dysplasia and colorectal adenocarcinoma. Different minimum criteria exist for the diagnosis of SSLs and their differentiation from HPs. Furthermore, the spectrum of terminology used to describe the entire range of serrated lesions is wide. This variability has impaired interobserver agreement during their histopathological assessment. Here, we provide guidance for the histopathological reporting of serrated lesions, including a simplified nomenclature system. Essentially, we recommend use of the following terms: HP, SSL, SSL with dysplasia, traditional serrated adenoma (TSA) and mixed polyp. It is hoped that this standardisation of nomenclature will facilitate studies of the biological significance of serrated lesions in terms of the relative risk of disease progression.

A 63-year-old man with a recurrent right-sided pleural effusion

Abstract: JPC : A 63-year-old Caucasian man was seen in clinic having been referred by his general practitioner with a 10 -week history of progressive exertional dyspnoea, associated with dry cough and retrosternal discomfort over the preceding fortnight. There was no history of fever, weight loss, anorexia, haemoptysis, dysphagia or other localising systemic symptoms. His past medical history included psoriatic arthropathy, atrial fibrillation, hypertension and gastro-oesophageal reflux; of note, there was no recent history of palpitations or worsening peripheral oedema, while his joint disease remained quiescent. Current medications (all long-standing) included methotrexate, omeprazole, bisoprolol, aspirin, ramipril and simvastatin. He was a lifelong non-smoker and retired solicitor with no occupational risk factors for lung disease. On examination he was afebrile with no palpable lymphadenopathy or clubbing. Cardiovascular examination demonstrated rate-controlled atrial fibrillation only; abdominal examination was normal. Respiratory examination revealed dull percussion note and reduced breath sounds at the right lung base, with normal resting oxygen saturations. Chest radiograph and thoracic ultrasound confirmed the presence of a large right-sided pleural effusion. Routine bloods including full blood count, clotting studies, renal function, liver function and serum calcium were unremarkable. I performed a diagnostic and therapeutic pleural aspiration, draining 1500 mL of straw-coloured fluid with no complications. Laboratory analysis showed the effusion to be an exudate (protein 46 g/L, lactate dehydrogenase (LDH) 961 IU/L, glucose 0.4 mmol/L); pleural fluid culture and cytology (including flow cytometry) were negative. NMR : The presence of a cytology-negative exudative pleural effusion of unknown aetiology in a previously well individual requires urgent further investigation. The low pleural fluid glucose and high LDH may imply infection, although these findings are non-specific and can also be seen in the context of chronic inflammation or malignancy; furthermore, the clinical history and negative culture go against an infective cause. The presence of an inflammatory arthropathy may prompt consideration …

Lymph node granulomas in immunoglobulin G4-related disease.

Abstract: Aims Immunoglobulin (Ig)G4-related disease (IgG4-RD) is an increasingly recognized fibroinflammatory condition that commonly exhibits multisystem involvement, with localized (e.g. inflammatory pseudotumours that can mimic malignancy) or diffuse (leading to organ dysfunction) patterns of tissue involvement. The 2012 Boston criteria have standardized the histopathological approach to the diagnosis of IgG4-RD and require one or more of the cardinal morphological features with prominence of IgG4+ plasma cells and an IgG4+/IgG+ plasma cell ratio of at least 40%. The relative prevalence of the morphological criteria varies between anatomical sites, but granulomas are rarely found and, indeed, their presence would usually deter a pathologist from making this diagnosis. The aim was to characterize two cases of IgG4-RD in which granulomas were present and to highlight this as an unusual feature of the condition. Methods and results We describe two cases in which the features of IgG4-RD were present within lymph nodes, together with granulomas. This is a recognized but rare morphological pattern of IgG4-RD. Conclusions While an unusual finding, the presence of granulomas should not preclude a diagnosis of IgG4-RD in the appropriate clinicopathological context.