{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:20:31Z","timestamp":1790252431957,"version":"4.1.0"},"reference-count":119,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Classic Hodgkin lymphoma (CHL) is a well-defined neoplasm characterized by the presence of a minority of pathognomonic Hodgkin and Reed\u2013Sternberg (HRS) cells in a reactive inflammatory background. Although genotypically of B cell origin, HRS cells exhibit a downregulated B cell program and therefore are set apart from other B cell lymphomas in the current WHO classification. However, cases with morphological and phenotypic features overlapping with CHL have been recognized, and the category of B cell lymphoma\u2014unclassifiable\u2014with features intermediate between diffuse large B cell lymphoma (DLBCL) and CHL, also termed grey zone lymphoma, was first introduced into the WHO classification in 2008 as provisional entity. These cases, as well as others raising a differential diagnosis of CHL can present diagnostic problems, as well as therapeutic challenges. Whereas some of these lymphomas only represent biologically unrelated morphological mimics, others, especially mediastinal grey zone lymphoma, exhibit genetic and gene expression profiles which overlap with CHL, indicating a true biological relationship. In this review, we address areas of diagnostic difficulties between CHL and other lymphoma subtypes, discuss the biological basis of true grey zone lymphoma based on recent molecular studies and delineate current concepts for the classification of these rare tumors.<\/jats:p>","DOI":"10.3390\/cancers14030742","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T08:20:29Z","timestamp":1643617229000},"page":"742","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The Grey Zones of Classic Hodgkin Lymphoma"],"prefix":"10.3390","volume":"14","author":[{"given":"Jan","family":"Bosch-Schips","sequence":"first","affiliation":[{"name":"Institute of Pathology and Neuropathology, T\u00fcbingen University Hospital and Comprehensive Cancer Center T\u00fcbingen-Stuttgart, 72076 T\u00fcbingen, Germany"},{"name":"Department of Pathology, Hospital Universitari de Bellvitge\u2014Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8308-0303","authenticated-orcid":false,"given":"Massimo","family":"Granai","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, T\u00fcbingen University Hospital and Comprehensive Cancer Center T\u00fcbingen-Stuttgart, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7156-5365","authenticated-orcid":false,"given":"Leticia","family":"Quintanilla-Martinez","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, T\u00fcbingen University Hospital and Comprehensive Cancer Center T\u00fcbingen-Stuttgart, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5496-293X","authenticated-orcid":false,"given":"Falko","family":"Fend","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, T\u00fcbingen University Hospital and Comprehensive Cancer Center T\u00fcbingen-Stuttgart, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/bjh.15614","article-title":"Diagnosis of Hodgkin lymphoma in the modern era","volume":"184","author":"Wang","year":"2019","journal-title":"Br. 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