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Heterogeneity in the clinical course of MCL\u2014indolent vs aggressive\u2014is further delineated by a correlation with the mutational status of the variable region of immunoglobulin heavy chain, methylation status, and SOX\u201011 expression. Cyclin\u2010D1 negative MCL, in situ MCL neoplasia, and impact of the karyotype on prognosis are distinguished. Apart from Ki\u201067% and morphology pattern (classic vs blastoid\/pleomorphic), the proliferation gene signature has helped to further refine prognostication. Studies focusing on mutational dynamics and clonal evolution on Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and\/or Bcl2 antagonists (venetoclax) have further clarified the prognostic impact of somatic mutations in <jats:italic>TP53<\/jats:italic>, <jats:italic>BIRC3<\/jats:italic>, <jats:italic>CDKN2A<\/jats:italic>, <jats:italic>MAP3K14<\/jats:italic>, <jats:italic>NOTCH2<\/jats:italic>, <jats:italic>NSD2<\/jats:italic>, and <jats:italic>SMARCA4<\/jats:italic> genes. In therapy, long\u2010term follow\u2010up on chemo\u2010immunotherapy studies has demonstrated durable remissions in some patients; however, long\u2010term toxicities, especially from second cancers, are a serious concern with chemotherapy. The therapeutic options in MCL are constantly evolving, with dramatic responses from nonchemotherapeutic agents (ibrutinib, acalabrutinib, and venetoclax). Chimeric antigen receptor therapy and combinations of nonchemotherapeutic agents are actively being studied and our focus is shifting toward making the treatment of MCL chemotherapy\u2010free. Still, MCL remains incurable. The following aspects of MCL continue to pose a challenge: disease transformation, role of the cytokine\u2010microenvironmental milieu, incorporation of positron emission tomography\u2010computerized tomography imaging, minimal residual disease in the prognosis, circulating tumor DNA testing for clonal evolution, predicting resistance to BTK inhibitors, and optimal management of patients who progress on BTK\/Bcl2 inhibitors. Next\u2010generation clinical trials should incorporate nonchemotherapeutic agents and personalize the treatment based upon the genomic profile of individual patient. Recent advances in the field of MCL are reviewed.<\/jats:p>","DOI":"10.1002\/ajh.25487","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T04:46:02Z","timestamp":1554785162000},"page":"710-725","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":210,"title":["Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2735-168X","authenticated-orcid":false,"given":"Preetesh","family":"Jain","sequence":"first","affiliation":[{"name":"Division of Cancer Medicine, Department of Lymphoma\/Myeloma The University of Texas MD Anderson Cancer Center  Houston 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