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Tissue analysis of lymphoproliferative disease in the clinical or research settings demands multiple immunohistochemistry with the assessment of co-localisation of expression of markers. Multiplex immunohistochemistry (MIHC) is ideally suited to this task, enabling simultaneous assessment of a number of markers on a single section, thus reducing interpretive errors and preserving tissue for further analyses. The range of current and emerging MIHC platforms offer an opportunity to gain unprecedented insight into the cellular and immunological milieu of lymphoproliferative disease and have been applied in research. These include techniques which use more traditional chromogenic and fluorescent detection systems. They have been refined in the recent years with improved chemistries, iterative rounds of staining and advanced imaging techniques such as multispectral analysis. The newer generation of MIHC have overcome the limitations of the traditional techniques by utilizing novel detection systems such as imaging mass cytometry and molecular barcoding. In addition, by combining the identification of morphological features, large panels of proteins and mRNA transcripts into "digital spatial profiling", MIHC techniques are contributing to the in-situ 'multi-omic' approach to pathology. MIHC has improved our understanding in several areas of lymphoma pathology, in particular, the role of the immune microenvironment in pathogenesis, prognosis and treatment stratification. Despite the exciting opportunities offered by MIHC platforms, few are used in routine diagnostics, reflecting the need for validation studies in the clinical settings. This paper provides an overview of MIHC, with notable examples of application in the research of lymphoproliferative processes and some relating to potential use in routine diagnosis. [ABSTRACT FROM AUTHOR]

Plasmablastic lymphoma (PBL) is a clinicopathological entity with a spectrum of epidemiological, clinical, morphological, phenotypic and genetic features. However, plasmablastic features (PB/F) also define other B-cell neoplasms including ALK positive large B-cell lymphoma, primary effusion lymphoma, HHV8 positive diffuse large B-cell lymphoma and plasmablastic myeloma, which, respectively, also have other characteristic clinical, and pathological determinants. In addition, late post follicular B-cell differentiation with partial plasma cell phenotypes can be variably encountered in EBV associated B-cell lymphomas and diffuse large B-cell lymphoma NOS, bringing them within differential diagnosis with the entities characterized by PB/F. While in many instances characteristics other than PB/F are crucial and result in specific diagnosis, there are considerable overlaps rendering on occasion distinction problematic, with significant management implications. Diagnostic difficulties may also emanate from conceptual issues and variable understanding as to what is a plasmablast. In this review we discuss the conceptual and definition aspects and the commonly encountered differential diagnoses surrounding entities with PB/F, providing recommendations for routine practice. [ABSTRACT FROM AUTHOR]

The 2016 World Health Organization classification of lymphoid malignancies has further improved basis for pathological diagnosis and better characterization of lymphoproliferative conditions. It includes a range of new entities and expanded requirements for molecular analysis, but reliance on close integration of the clinical, pathological and molecular features still remains the cornerstone for diagnosis. Despite the advances in knowledge and refined diagnostic criteria, certain areas of lymphoma pathology remain difficult and contentious. We provide a review of some entities which continue to represent diagnostic "grey zones", with potentially overlapping pathological, molecular or clinical features, but in most instances require specific treatments to achieve best clinical outcomes. We focus on: clarifying diagnostic ambiguity between nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte rich B-cell lymphoma, including the relevant differential diagnoses; key features and differential diagnosis of mediastinal grey zone lymphoma; characteristics of high grade B-cell lymphomas, with particular reference to their genetic features as defining diagnostic parameters; pathological overlaps of EBV-positive lymphoproliferations and their differential diagnosis with EBV-positive classic Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

The efficacy of Cognitive Behavioral Therapy–based Guided Self-Help for mild to moderate bulimia and binge eating disorders has been well supported. However, limited research has explored in-depth individual experiences of this treatment approach. In-depth semi-structured interviews were conducted with 4 individuals who had completed Cognitive Behavioral Therapy–based Guided Self-Help (CBT-GSH) for bulimic or binge eating disorders. The interviews were transcribed verbatim and subsequently analyzed using Interpretative Phenomenological Analysis (IPA). Three superordinate themes emerged: Autonomy and volition ; A dynamic relationship: the guided and the guide; and The unwanted friend . The reciprocal nature of the guide/guided relationship was identified as integral to the success of the therapeutic approach. However, participants expressed initial uncertainty towards the therapeutic process, and experienced an uncomfortable dissonance between a lack of volition in therapy seeking and the need to continually self-prescribe CBT-GSH. The findings affirm the central role of the guide in promoting motivation to engage with therapy and highlight the potential benefits of in-session weighing. However, it may be necessary to provide additional support on commencing CBT-GSH to address concerns about the therapeutic approach in this group. [ABSTRACT FROM AUTHOR]

Cancer therapy with immune checkpoint inhibitors can cause colitis and colon perforation. We investigated whether infection with Epstein Barr virus (EBV) associates with development and severity of colitis in patients receiving immune checkpoint inhibitor therapies. We performed a retrospective analysis of fixed colon tissues from 16 patients (12 men, 4 women, median age, 69.5 y) with colitis after immune checkpoint inhibitor therapy (9 patients treated with anti-CTLA4, 3 patients treated with anti-PD1, and 4 patients received a combination). Ten tissue samples were biopsies and 6 were collected during resection (4 surgeries for colon perforation). Patients were treated between 2010 and 2018 in the United Kingdom. The tissues were analyzed by pathology, in situ hybridization (to detect EBV-encoded small RNAs [EBERs]), and immunohistochemistry. Clinical data were also collected. Colon tissues from 4 of the 13 patients who received anti-CTLA4 (alone or in combination, 4 with colon perforation) had EBV-positive lymphoproliferations that manifested as florid ulcers associated with polymorphous infiltrates containing EBV-positive blasts (CD30+ or CD30-negative, CD20+, CD3-negative, and EBER+), plasma cells (CD138+, CD20-negative, and EBER+ or EBER-negative), and small B cells (CD20+, CD3-negative, and EBER+ or EBER-negative), consistent with EBV-positive mucocutaneous ulcers (EBVMCUs). In analyses of biopsies collected from 2 patients with EBVMCUs over multiple time points, we found that earlier biopsies had no or only a few EBV-positive cells, whereas 1 later biopsy had EBVMCU and co-infection with cytomegalovirus. EBVMCUs were associated with steroid-refractory colitis (100% of EBV-positive patients vs 12.5% of EBV-negative patients; P =.008) and colon perforation (100% of EBV-positive patients vs no EBV-negative patients; P =.001). We found that colon tissues from 4/13 patients with colitis after anti-CTLA4 therapy (4/6 patients who underwent resection and 4/4 patients with colon perforation) contained EBVMCUs. EBVMCUs seem to arise secondarily in areas of inflamed colon due to immunosuppressive treatment for colitis. EBVMCUs are associated with steroid-refractory colitis and colon perforation. [ABSTRACT FROM AUTHOR]