{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T13:06:47Z","timestamp":1785589607751,"version":"3.56.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,2,29]],"date-time":"2020-02-29T00:00:00Z","timestamp":1582934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To better characterize the clinicopathologic presentation and outcomes of follicular lymphoma with MYC and BCL2 and\/or BCL6 rearrangements (double-hit and triple-hit follicular lymphoma), we present three cases from our institution and perform a literature review of 37 published cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cases were identified using institutional SoftPath software and the MEDLINE database via the PubMed search engine. Clinical and pathologic data were collected with subsequent stratification by histologic grade and treatment for comparison.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Similar to classic follicular lymphoma, patients presented most often with low-grade (1-2) but high-stage (III-IV) disease with absence of B symptoms; however, overall survival was worse than that of traditional follicular lymphoma. In a small sample size, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) achieved better outcomes than a regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Specific pathologic features that might prompt testing for MYC rearrangement include elevated proliferation index out of proportion to cytology and aggressive features such as angioinvasion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Double-hit and triple-hit follicular lymphoma may be better classified as a distinct entity from classical follicular lymphoma with a worse prognosis. Aggressive therapy with a treatment regimen used for high-grade B-cell lymphoma with MYC and BCL2 and\/or BCL6 rearrangements might be beneficial, but more evidence is needed to justify aggressive treatment as standard of care.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ajcp\/aqz208","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T20:14:29Z","timestamp":1582834469000},"page":"672-685","source":"Crossref","is-referenced-by-count":17,"title":["Double-Hit and Triple-Hit Follicular Lymphoma"],"prefix":"10.1093","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5982-7411","authenticated-orcid":false,"given":"Jessica B","family":"Ziemba","sequence":"first","affiliation":[{"name":"Department of Pathology, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zena","family":"Wolf","sequence":"first","affiliation":[{"name":"Department of Pathology, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Weinstock","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Beth Israel Deaconess Medical Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saja","family":"Asakrah","sequence":"first","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, Emory University Hospital, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,29]]},"reference":[{"key":"2020041521554373700_CIT0001","author":"National Institutes of Health (NIH) National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results Program (SEER)"},{"key":"2020041521554373700_CIT0002","author":"US Census Bureau"},{"key":"2020041521554373700_CIT0003","first-page":"266","article-title":"Follicular lymphoma.","volume-title":"World Health Organization\u2019s Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Jaffe","year":"2017","edition":"4th ed"},{"key":"2020041521554373700_CIT0004","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1097\/MOH.0000000000000159","article-title":"Premalignant cell dynamics in indolent B-cell malignancies","volume":"22","author":"Milpied","year":"2015","journal-title":"Curr Opin Hematol."},{"key":"2020041521554373700_CIT0005","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.celrep.2013.12.027","article-title":"Genetics of follicular lymphoma transformation","volume":"6","author":"Pasqualucci","year":"2014","journal-title":"Cell Rep."},{"key":"2020041521554373700_CIT0006","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.3324\/haematol.2011.042531","article-title":"Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles","volume":"96","author":"Horn","year":"2011","journal-title":"Haematologica."},{"key":"2020041521554373700_CIT0007","first-page":"335","article-title":"High-grade B-cell lymphoma.","volume-title":"World Health Organization\u2019s Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Kluin","year":"2017","edition":"4th ed"},{"key":"2020041521554373700_CIT0008","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1080\/10428194.2017.1357172","article-title":"Does double-hit follicular lymphoma with translocations of MYC and BCL2 change the definition of transformation?","volume":"59","author":"Katsushima","year":"2018","journal-title":"Leuk Lymphoma."},{"key":"2020041521554373700_CIT0009","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/modpathol.2017.134","article-title":"Clinicopathological and genomic analysis of double-hit follicular lymphoma: comparison with high-grade B-cell lymphoma with MYC and BCL2 and\/or BCL6 rearrangements","volume":"31","author":"Miyaoka","year":"2018","journal-title":"Mod Pathol."},{"key":"2020041521554373700_CIT0010","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.humpath.2016.07.025","article-title":"Double-hit follicular lymphoma with MYC and BCL2 translocations: a study of 7 cases with a review of literature","volume":"58","author":"Miao","year":"2016","journal-title":"Hum Pathol."},{"key":"2020041521554373700_CIT0011","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/pin.12335","article-title":"Clinicopathological features of double-hit B-cell lymphomas with MYC and BCL2, BCL6 or CCND1 rearrangements","volume":"65","author":"Yoshida","year":"2015","journal-title":"Pathol Int."},{"key":"2020041521554373700_CIT0012","doi-asserted-by":"crossref","first-page":"935","DOI":"10.3324\/haematol.2008.005355","article-title":"Clinicopathological features of lymphoma\/leukemia patients carrying both BCL2 and MYC translocations","volume":"94","author":"Tomita","year":"2009","journal-title":"Haematologica."},{"key":"2020041521554373700_CIT0013","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1080\/10428190701836845","article-title":"C-MYC translocation in t(14;18) positive follicular lymphoma at presentation: an adverse prognostic indicator?","volume":"49","author":"Christie","year":"2008","journal-title":"Leuk Lymphoma."},{"key":"2020041521554373700_CIT0014","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/modpathol.3800500","article-title":"Lymphoid neoplasms associated with concurrent t(14;18) and 8q24\/c-MYC translocation generally have a poor prognosis","volume":"19","author":"Kanungo","year":"2006","journal-title":"Mod Pathol."},{"key":"2020041521554373700_CIT0015","doi-asserted-by":"crossref","first-page":"210","DOI":"10.5858\/2004-128-210-FLWABT","article-title":"Follicular lymphoma with a Burkitt translocation\u2014predictor of an aggressive clinical course: a case report and review of the literature","volume":"128","author":"Voorhees","year":"2004","journal-title":"Arch Pathol Lab Med."},{"key":"2020041521554373700_CIT0016","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1080\/10428190310001625674","article-title":"Molecular-cytogenetic characterization of non-Hodgkin\u2019s lymphoma with double and cryptic translocations of the immunoglobulin heavy chain gene","volume":"45","author":"Kanda-Akano","year":"2004","journal-title":"Leuk Lymphoma."},{"key":"2020041521554373700_CIT0017","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1080\/10428190310001593120","article-title":"The spectrum of lymphoma with 8q24 aberrations: a clinical, pathological and cytogenetic study of 87 consecutive cases","volume":"45","author":"Au","year":"2004","journal-title":"Leuk Lymphoma."},{"key":"2020041521554373700_CIT0018","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1182\/blood.V80.3.758.758","article-title":"MYC rearrangements in histologically progressed follicular lymphomas","volume":"80","author":"Yano","year":"1992","journal-title":"Blood."},{"key":"2020041521554373700_CIT0019","volume-title":"An International System for Human Cytogenomic Nomenclature","author":"McGowan-Jordan","year":"2016"},{"key":"2020041521554373700_CIT0020","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1182\/asheducation-2013.1.575","article-title":"Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification","volume":"1","author":"Ott","year":"2013","journal-title":"Hematology."},{"key":"2020041521554373700_CIT0021","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s11864-015-0374-0","article-title":"Aggressive B-cell lymphoma: optimal therapy for MYC-positive, double-hit, and triple-hit DLBCL","volume":"16","author":"Dunleavy","year":"2015","journal-title":"Curr Treat Options Oncol."},{"key":"2020041521554373700_CIT0022","first-page":"9602","article-title":"The t(14;18)(q32;q21) with extra MYC signal\u2014is it a gray zone lymphoma?","volume":"8","author":"Chang","year":"2015","journal-title":"Int J Clin Exp Pathol."},{"key":"2020041521554373700_CIT0023","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1111\/his.13316","article-title":"MYC expression and translocation analyses in low-grade and transformed follicular lymphoma","volume":"71","author":"Aukema","year":"2017","journal-title":"Histopathology."},{"key":"2020041521554373700_CIT0024","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1084\/jem.169.3.613","article-title":"Translocation t(14;18) in B cell lymphomas as a cause for defective immunoglobulin production","volume":"169","author":"de Jong","year":"1989","journal-title":"J Exp Med."},{"key":"2020041521554373700_CIT0025","volume-title":"SEER Cancer Statistics Review, 1975-2016","author":"Howlader"}],"container-title":["American Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ajcp\/article-pdf\/153\/5\/672\/33049444\/aqz208.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ajcp\/article-pdf\/153\/5\/672\/33049444\/aqz208.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T06:20:28Z","timestamp":1614579628000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajcp\/article\/153\/5\/672\/5770930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,29]]},"references-count":25,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,2,29]]},"published-print":{"date-parts":[[2020,4,15]]}},"URL":"https:\/\/doi.org\/10.1093\/ajcp\/aqz208","relation":{},"ISSN":["0002-9173","1943-7722"],"issn-type":[{"value":"0002-9173","type":"print"},{"value":"1943-7722","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,5]]},"published":{"date-parts":[[2020,2,29]]}}}