Description: Boger P C, Shutt J D, Neale J R, Wilson S J, Bateman A C, Holloway J W, Patel P & Sampson A P (2012) Histopathology Increased expression of the 5-lipoxygenase pathway and its cellular localization in Barrett’s adenocarcinoma Aims:  Up-regulation of the 5-lipoxygenase (5-LOX) leukotriene pathway is evident in numerous tumour types, and has been linked to the promotion of cancer cell growth. The aim of this study was to evaluate the immunohistochemical expression of 5-LOX pathway proteins in oesophageal adenocarcinoma and its premalignant lesion, Barrett’s metaplasia. Methods and results:  Tissue samples were collected at endoscopy from 16 patients with Barrett’s metaplasia and from seven with oesophageal adenocarcinoma; five proximal squamous oesophagus samples were used as controls. Immunohistochemical analyses were performed on stromal and epithelial areas with optimized concentrations of primary antibodies for 5-LOX, 5-LOX-activating protein (FLAP), and the distal enzymes leukotriene (LT) A 4 hydrolase (LTA 4 H) and LTC 4 synthase (LTC 4 S). the diagnosis was histologically confirmed from adjacent sections by a gastrointestinal pathologist. Striking increases in the stromal immunoexpression of 5-LOX ( P  = 0.041), FLAP ( P  = 0.038), LTA 4 H ( P  = 0.0008) and LTC 4 S ( P  = 0.036) were seen in adenocarcinoma tissue. Stromal FLAP and LTA 4 H immunostaining correlated with elevated neutrophil counts ( P  〈 0.001). LTC 4 S was also notably overexpressed within epithelial cells in both Barrett’s metaplasia ( P  〈 0.001) and adenocarcinoma ( P  〈 0.01) tissue. Conclusions:  Key biosynthetic enzymes of the LTB 4 and LTC 4 biosynthetic pathways are incrementally expressed across the spectrum of squamous, Barrett’s metaplasia and oesophageal adenocarcinoma tissues, suggesting, for the first time, a role for both LT subfamilies in disease progression.

Description: Aims To describe the features of 100 consecutive cases referred to a single UK institution, in which a diagnosis of IgG4-related disease (IgG4-RD) was under consideration. Methods and results The histological features were reviewed by a single histopathologist and cases categorised using the 2012 Boston criteria: Category 1 – histologically highly suggestive of IgG4-RD; 2 – probable histopathological features of IgG4-RD; 3 – insufficient histopathological features of IgG4-RD. A ‘global assessment’ was performed using the available clinical information: Assessment group 1 – ‘definite/very likely IgG4-RD’; group 2 – ‘possible IgG4-RD’; group 3 – ‘not IgG4-RD’; group 4 – insufficient information. The mean IgG4+ plasma cell count and IgG4+/IgG+ ratio were highest in Category 1 (134/HPF; 57%) and Assessment group 1 (113/HPF; 52%); and lowest in Category 3 (11/HPF; 18%) and Assessment group 3 (43/HPF and 31%) (Category comparison IgG4+ count and ratio, both p〈0.001; Assessment group comparison IgG4+ count p〈0.0002 and ratio p=0.04). A non-IgG4-RD diagnosis was rare in Category 1 (7%) but common in 2 (60%) and 3 (47%). Stromal reactions to neoplasia and chronic oral ulceration were simulants of IgG4-RD. Conclusions The Boston criteria are linked to the likelihood of IgG4-RD. Other conditions may show some histological features of IgG4-RD. The likelihood of IgG4-RD is much greater where the histological features reach the threshold for Category 1 , than for Categories 2 and 3 . Despite the utility of the Boston criteria, this study highlights the crucial importance of careful clinicopathological correlation when a diagnosis of IgG4-RD is under consideration. This article is protected by copyright. All rights reserved.

Description: Aims IgG4-related disease (IgG4-RD) is an increasingly recognised fibroinflammatory condition that commonly exhibits multisystem involvement, with localised (e.g. inflammatory pseudotumours that can mimic malignancy) or diffuse (leading to organ dysfunction) patterns of tissue involvement. The 2012 Boston criteria have standardised 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 characterise 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 recognised 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. This article is protected by copyright. All rights reserved.