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We investigated a PTLD cohort (<jats:italic>n<\/jats:italic>\u2009=\u200950) consisting of \u2018early lesions\u2019 (infectious mononucleosis\u2010like PTLD, plasmacytic and follicular hyperplasias), polymorphic PTLD and post\u2010transplant diffuse large B\u2010cell lymphomas (PT\u2010DLBCL). The study also included 15 DLBCL with autoimmune\/immunocompromised backgrounds (IS\u2010DLBCL) and 14 DLBCL, not otherwise specified (DLBCL, NOS), as control. To investigate microarchitectural and genetic changes, immunohistochemistry, multiplex immunofluorescence (mIF), fluorescence <jats:italic>in\u00a0situ<\/jats:italic> hybridisation and high\u2010throughput sequencing were performed. Scarcity of viral infections other than Epstein\u2013Barr virus (EBV) was observed. mIF revealed lower Treg infiltration in PT\u2010DLBCL and high CD8<jats:sup>+<\/jats:sup>\/PD1<jats:sup>+<\/jats:sup> T cells in IS\u2010DLBCL. <jats:italic>MYC<\/jats:italic> rearrangements were most common in PT\u2010DLBCL, followed by IS\u2010DLBCL and DLBCL, NOS, all EBV\u2010negative. <jats:italic>TP53<\/jats:italic> mutations were frequent in EBV\u2010negative PT\u2010DLBCL and DLBCL, NOS but absent in \u2018early lesions\u2019. <jats:italic>NOTCH1<\/jats:italic> mutations were predominant in PT\u2010DLBCL (N1 DLBCL\u2010subgroup). Gene expression profiling showed a significant overlap between \u2018early lesions\u2019 and polymorphic PTLD. The presence of clonal haematopoiesis of indeterminate potential (CHIP)\u2010like mutations and the absence of immune\u2010escape gene mutations in \u2018early lesions\u2019 suggest these disorders may represent clonal expansions driven by exogenic immunosuppression and\/or EBV infection \u2018substituting\u2019 for mutations of the latter group of genes.<\/jats:p>","DOI":"10.1111\/bjh.19952","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T07:34:52Z","timestamp":1736321692000},"page":"484-504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Distinct subtypes of post\u2010transplant lymphoproliferative disorders: <scp>CHIP<\/scp>\u2010like mutations in early lesions and substantial mutational differences between <scp>EBV<\/scp>\u2010positive and <scp>EBV<\/scp>\u2010negative diffuse large B\u2010cell lymphomas"],"prefix":"10.1111","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5271-537X","authenticated-orcid":false,"given":"Vanesa\u2010Sindi","family":"Ivanova","sequence":"first","affiliation":[{"name":"Pathology, Institute of Medical Genetics and Pathology University Hospital Basel, University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0847-6156","authenticated-orcid":false,"given":"Thomas","family":"Menter","sequence":"additional","affiliation":[{"name":"Pathology, Institute of Medical Genetics and Pathology University Hospital Basel, University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningxuan","family":"Cui","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cancer Research University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Leary","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cancer Research University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl","family":"Zinner","sequence":"additional","affiliation":[{"name":"Pathology, Institute of Medical Genetics and Pathology University Hospital Basel, University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg P.","family":"Halter","sequence":"additional","affiliation":[{"name":"Haematology University Hospital Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Stenner","sequence":"additional","affiliation":[{"name":"Oncology University Hospital Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Dirnhofer","sequence":"additional","affiliation":[{"name":"Pathology, Institute of Medical Genetics and Pathology University Hospital Basel, University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cancer Research University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1100-3819","authenticated-orcid":false,"given":"Alexandar","family":"Tzankov","sequence":"additional","affiliation":[{"name":"Pathology, Institute of Medical Genetics and Pathology University Hospital Basel, University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"e_1_2_13_2_1","volume-title":"Haematopoietic and lymphoid tissues","author":"World Health Organization","year":"2016"},{"key":"e_1_2_13_3_1","unstructured":"Leukemia & Lymphoma Society.Post\u2010transplant lymphoproliferative disorders (fact sheet). 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