Lymphomas with pseudo–double-hit BCL6-MYC translocations due to t(3;8)(q27;q24) are associated with a germinal center immunophenotype, extranodal involvement, and frequent BCL2 translocations

Steven M. Johnson, Jayadev Manikkam Umakanthan, Ji Yuan, Yuri Fedoriw, Robert G Bociek, Kathleen Kaiser-Rogers, Jennifer N Sanmann, Nathan D. Montgomery

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

High-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements, “double-hit” or “triple-hit” lymphomas (DTHL), are aggressive neoplasms associated with a poor prognosis. A t(3;8)(q27;q24) rarely occurs in B-cell lymphomas that results in a unique “pseudo–double-hit” BCL6-MYC fusion, indistinguishable by interphase fluorescence in situ hybridization (FISH) from more conventional DTHL with independent MYC and BCL6 translocations. Reports of t(3;8)(q27;q24) lymphomas are sparse, and to better characterize their pathologic, cytogenetic, and clinical features, 6 new cases from 2 institutions and 19 previously published cases were reviewed. All new cases displayed aggressive morphologic features, and most previously published cases were classified as aggressive lymphomas. Collectively, all t(3;8)(q27;q24) cases had a germinal center (GC) phenotype, and most had complex karyotypes (22/24, 92%), including frequent concomitant BCL2 rearrangements (17/24, 71%). When compared to two large published DTHL cohorts, t(3;8)(q27;q24) lymphomas less often expressed BCL2 (P <.01), had a greater likelihood of extranodal involvement (P <.01), and more frequently appeared triple-hit by FISH analysis (P <.01). Despite presenting with aggressive clinicopathologic features, 100% (6/6) of t(3;8;)(q27;q24) patients achieved complete remission after intensive induction regimens, and 2- and 3-year overall survival rates were 63% (10/16) and 57% (8/14), respectively. These findings suggest that lymphomas with t(3;8)(q27;q24) may represent a subset of GC B-cell lymphomas distinct from conventional DTHL. Our results further highlight the value of routine karyotype assessment in aggressive B-cell lymphomas, and the importance of recognizing the t(3;8)(q27;q24) so that its clinical significance can be more fully explored.

Original languageEnglish (US)
Pages (from-to)192-200
Number of pages9
JournalHuman Pathology
Volume80
DOIs
StatePublished - Oct 2018

Fingerprint

Germinal Center
Lymphoma
B-Cell Lymphoma
Fluorescence In Situ Hybridization
Karyotype
Interphase
Cytogenetics
Non-Hodgkin's Lymphoma
Survival Rate
Phenotype

Keywords

  • Double-hit lymphoma
  • High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
  • Lymphoma cytogenetics
  • Triple-hit lymphoma
  • t(3;8)(q27;q24)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Lymphomas with pseudo–double-hit BCL6-MYC translocations due to t(3;8)(q27;q24) are associated with a germinal center immunophenotype, extranodal involvement, and frequent BCL2 translocations. / Johnson, Steven M.; Umakanthan, Jayadev Manikkam; Yuan, Ji; Fedoriw, Yuri; Bociek, Robert G; Kaiser-Rogers, Kathleen; Sanmann, Jennifer N; Montgomery, Nathan D.

In: Human Pathology, Vol. 80, 10.2018, p. 192-200.

Research output: Contribution to journalArticle

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title = "Lymphomas with pseudo–double-hit BCL6-MYC translocations due to t(3;8)(q27;q24) are associated with a germinal center immunophenotype, extranodal involvement, and frequent BCL2 translocations",
abstract = "High-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements, “double-hit” or “triple-hit” lymphomas (DTHL), are aggressive neoplasms associated with a poor prognosis. A t(3;8)(q27;q24) rarely occurs in B-cell lymphomas that results in a unique “pseudo–double-hit” BCL6-MYC fusion, indistinguishable by interphase fluorescence in situ hybridization (FISH) from more conventional DTHL with independent MYC and BCL6 translocations. Reports of t(3;8)(q27;q24) lymphomas are sparse, and to better characterize their pathologic, cytogenetic, and clinical features, 6 new cases from 2 institutions and 19 previously published cases were reviewed. All new cases displayed aggressive morphologic features, and most previously published cases were classified as aggressive lymphomas. Collectively, all t(3;8)(q27;q24) cases had a germinal center (GC) phenotype, and most had complex karyotypes (22/24, 92{\%}), including frequent concomitant BCL2 rearrangements (17/24, 71{\%}). When compared to two large published DTHL cohorts, t(3;8)(q27;q24) lymphomas less often expressed BCL2 (P <.01), had a greater likelihood of extranodal involvement (P <.01), and more frequently appeared triple-hit by FISH analysis (P <.01). Despite presenting with aggressive clinicopathologic features, 100{\%} (6/6) of t(3;8;)(q27;q24) patients achieved complete remission after intensive induction regimens, and 2- and 3-year overall survival rates were 63{\%} (10/16) and 57{\%} (8/14), respectively. These findings suggest that lymphomas with t(3;8)(q27;q24) may represent a subset of GC B-cell lymphomas distinct from conventional DTHL. Our results further highlight the value of routine karyotype assessment in aggressive B-cell lymphomas, and the importance of recognizing the t(3;8)(q27;q24) so that its clinical significance can be more fully explored.",
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AU - Johnson, Steven M.

AU - Umakanthan, Jayadev Manikkam

AU - Yuan, Ji

AU - Fedoriw, Yuri

AU - Bociek, Robert G

AU - Kaiser-Rogers, Kathleen

AU - Sanmann, Jennifer N

AU - Montgomery, Nathan D.

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N2 - High-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements, “double-hit” or “triple-hit” lymphomas (DTHL), are aggressive neoplasms associated with a poor prognosis. A t(3;8)(q27;q24) rarely occurs in B-cell lymphomas that results in a unique “pseudo–double-hit” BCL6-MYC fusion, indistinguishable by interphase fluorescence in situ hybridization (FISH) from more conventional DTHL with independent MYC and BCL6 translocations. Reports of t(3;8)(q27;q24) lymphomas are sparse, and to better characterize their pathologic, cytogenetic, and clinical features, 6 new cases from 2 institutions and 19 previously published cases were reviewed. All new cases displayed aggressive morphologic features, and most previously published cases were classified as aggressive lymphomas. Collectively, all t(3;8)(q27;q24) cases had a germinal center (GC) phenotype, and most had complex karyotypes (22/24, 92%), including frequent concomitant BCL2 rearrangements (17/24, 71%). When compared to two large published DTHL cohorts, t(3;8)(q27;q24) lymphomas less often expressed BCL2 (P <.01), had a greater likelihood of extranodal involvement (P <.01), and more frequently appeared triple-hit by FISH analysis (P <.01). Despite presenting with aggressive clinicopathologic features, 100% (6/6) of t(3;8;)(q27;q24) patients achieved complete remission after intensive induction regimens, and 2- and 3-year overall survival rates were 63% (10/16) and 57% (8/14), respectively. These findings suggest that lymphomas with t(3;8)(q27;q24) may represent a subset of GC B-cell lymphomas distinct from conventional DTHL. Our results further highlight the value of routine karyotype assessment in aggressive B-cell lymphomas, and the importance of recognizing the t(3;8)(q27;q24) so that its clinical significance can be more fully explored.

AB - High-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements, “double-hit” or “triple-hit” lymphomas (DTHL), are aggressive neoplasms associated with a poor prognosis. A t(3;8)(q27;q24) rarely occurs in B-cell lymphomas that results in a unique “pseudo–double-hit” BCL6-MYC fusion, indistinguishable by interphase fluorescence in situ hybridization (FISH) from more conventional DTHL with independent MYC and BCL6 translocations. Reports of t(3;8)(q27;q24) lymphomas are sparse, and to better characterize their pathologic, cytogenetic, and clinical features, 6 new cases from 2 institutions and 19 previously published cases were reviewed. All new cases displayed aggressive morphologic features, and most previously published cases were classified as aggressive lymphomas. Collectively, all t(3;8)(q27;q24) cases had a germinal center (GC) phenotype, and most had complex karyotypes (22/24, 92%), including frequent concomitant BCL2 rearrangements (17/24, 71%). When compared to two large published DTHL cohorts, t(3;8)(q27;q24) lymphomas less often expressed BCL2 (P <.01), had a greater likelihood of extranodal involvement (P <.01), and more frequently appeared triple-hit by FISH analysis (P <.01). Despite presenting with aggressive clinicopathologic features, 100% (6/6) of t(3;8;)(q27;q24) patients achieved complete remission after intensive induction regimens, and 2- and 3-year overall survival rates were 63% (10/16) and 57% (8/14), respectively. These findings suggest that lymphomas with t(3;8)(q27;q24) may represent a subset of GC B-cell lymphomas distinct from conventional DTHL. Our results further highlight the value of routine karyotype assessment in aggressive B-cell lymphomas, and the importance of recognizing the t(3;8)(q27;q24) so that its clinical significance can be more fully explored.

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