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      Reactive Eosinophil Proliferations in Tissue and the Lymphocytic Variant of Hypereosinophilic Syndrome

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          Abstract

          Objectives

          The 2019 Society for Hematopathology and European Association for Haematopathology Workshop reviewed the spectrum of neoplastic, nonneoplastic, and borderline entities associated with reactive eosinophilia in tissue.

          Methods

          The workshop panel reviewed 46 cases covered in 2 workshop sessions.

          Results

          The 46 cases were presented with their consensus diagnoses during the workshop. Reactive eosinophilia in lymph nodes and other tissues may be accompanied by or be distinct from peripheral blood eosinophilia. Reactive etiologies included inflammatory disorders such as Kimura disease and IgG4-related disease, which may show overlapping pathologic features and reactions to infectious agents and hypersensitivity (covered in a separate review). Hodgkin, T-cell, and B-cell lymphomas and histiocytic neoplasms can result in reactive eosinophilia. The spectrum of these diseases is discussed and illustrated through representative cases.

          Conclusions

          Reactive eosinophilia in lymph nodes and tissues may be related to both nonneoplastic and neoplastic lymphoid proliferations and histiocytic and nonhematolymphoid processes. Understanding the differential diagnosis of reactive eosinophilia and the potential for overlapping clinical and pathologic findings is critical in reaching the correct diagnosis so that patients can be treated appropriately.

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          Most cited references85

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          The 2016 revision of the World Health Organization classification of lymphoid neoplasms.

          A revision of the nearly 8-year-old World Health Organization classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists, and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities. The revision clarifies the diagnosis and management of lesions at the very early stages of lymphomagenesis, refines the diagnostic criteria for some entities, details the expanding genetic/molecular landscape of numerous lymphoid neoplasms and their clinical correlates, and refers to investigations leading to more targeted therapeutic strategies. The major changes are reviewed with an emphasis on the most important advances in our understanding that impact our diagnostic approach, clinical expectations, and therapeutic strategies for the lymphoid neoplasms.
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            Type 2 innate lymphoid cells control eosinophil homeostasis

            Eosinophils are specialized myeloid cells associated with allergy and helminth infections. Blood eosinophils demonstrate circadian cycling, as described over 80 years ago, 1 and are abundant in the healthy gastrointestinal tract. Although a cytokine, interleukin (IL)-5, and chemokines such as eotaxins, mediate eosinophil development and survival, 2 and tissue recruitment, 3 respectively, the processes underlying the basal regulation of these signals remain unknown. Here, we show that serum IL-5 is maintained by long-lived type 2 innate lymphoid cells (ILC2) resident in peripheral tissues. ILC2 secrete IL-5 constitutively and are induced to co-express IL-13 during type 2 inflammation, resulting in localized eotaxin production and eosinophil accumulation. In the small intestine where eosinophils and eotaxin are constitutive, 4 ILC2 co-express IL-5 and IL-13, which is enhanced after caloric intake. The circadian synchronizer vasoactive intestinal peptide (VIP) also stimulates ILC2 through the VPAC2 receptor to release IL-5, linking eosinophil levels with metabolic cycling. Tissue ILC2 regulate basal eosinophilopoiesis and tissue eosinophil accumulation through constitutive and stimulated cytokine expression, and this dissociated regulation can be tuned by nutrient intake and central circadian rhythms.
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              Consensus statement on the pathology of IgG4-related disease.

              IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and-often but not always-elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4-7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4⁺ plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum.
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                Author and article information

                Journal
                American Journal of Clinical Pathology
                Oxford University Press (OUP)
                0002-9173
                1943-7722
                February 01 2021
                February 04 2021
                December 25 2020
                February 01 2021
                February 04 2021
                December 25 2020
                : 155
                : 2
                : 211-238
                Affiliations
                [1 ]Division of Hematopathology, Mayo Clinic, Rochester, MN
                [2 ]Division of Hematopathology, Stanford University, Stanford, CA
                [3 ]Division of Hematopathology, Mayo Clinic, Phoenix, AZ
                [4 ]Department of Pathology, University of Utah School of Medicine, Salt Lake City
                [5 ]Institute of Pathology, University of Munich (LMU), Munich, Germany
                [6 ]Department of Pathology, TexasTech University Health Sciences Center, P.L. Foster School of Medicine, El Paso
                [7 ]Department of Hematopathology, MD Anderson Cancer Center, Houston, TX
                [8 ]Institute of Pathology, University of Würzburg, Würzburg, Germany
                [9 ]Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, Tübingen University Hospital, Tübingen, Germany
                Article
                10.1093/ajcp/aqaa227
                6c38c6c9-0624-4104-97e8-aed5e2715e58
                © 2020

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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