Clinical significance of MYC expression and/or "High-grade" morphology in non-burkitt, diffuse aggressive B-cell lymphomas: A SWOG s9704 correlative study

James R. Cook, Bryan Goldman, Raymond R. Tubbs, Lisa Rimsza, Michael Leblanc, Patrick Stiff, Richard Fisher

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The clinicopathologic findings in Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) may show significant overlap, and MYC abnormalities, found in all BLs, also occur in a subset of DLBCL. The 2008 World Health Organization classification introduced the category of "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL" (BCLU) in recognition of this overlap, but the clinical significance of BCLU (ie, "high-grade") morphology and the relationship between BCLU morphology and MYC abnormalities remains unclear. In this study, we identified 260 cases of non-Burkitt, diffuse aggressive B-cell lymphomas from SWOG S9704, a phase 3 randomized study of standard immunochemotherapy versus autologous stem cell transplantation. Of these, 31 cases (12%) showed BCLU morphology, and 229 (88%) showed typical DLBCL morphology. Of 198, 27 (14%) were positive for MYC by immunohistochemistry. BCLU morphology was associated with an increased incidence of MYC expression but otherwise was not associated with distinct clinicopathologic features or significantly decreased survival. MYC-positive cases were morphologically and phenotypically heterogenous and were associated with poor progression-free and overall survival in multivariate analysis. These findings confirm that BCLU does not represent a distinct clinicopathologic entity and demonstrate that BCLU morphology alone does not significantly impact survival compared with typical DLBCL. In contrast, MYC protein expression is a poor prognostic factor that may be associated with either BCLU or DLBCL morphology, and MYC immunohistochemistry is suggested for routine prognostic evaluation (Clinicaltrials.gov identifier: NCT00004031).

Original languageEnglish (US)
Pages (from-to)494-501
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume38
Issue number4
DOIs
StatePublished - 2014
Externally publishedYes

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Lymphoma, Large B-Cell, Diffuse
B-Cell Lymphoma
Burkitt Lymphoma
Immunohistochemistry
Stem Cell Transplantation
Disease-Free Survival
Multivariate Analysis
Incidence
Proteins

Keywords

  • B-cell lymphoma unclassifiable with features intermediate between DLBCL and BL
  • Diffuse large B-cell lymphoma
  • Immunohistochemistry
  • MYC

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

Clinical significance of MYC expression and/or "High-grade" morphology in non-burkitt, diffuse aggressive B-cell lymphomas : A SWOG s9704 correlative study. / Cook, James R.; Goldman, Bryan; Tubbs, Raymond R.; Rimsza, Lisa; Leblanc, Michael; Stiff, Patrick; Fisher, Richard.

In: American Journal of Surgical Pathology, Vol. 38, No. 4, 2014, p. 494-501.

Research output: Contribution to journalArticle

Cook, James R. ; Goldman, Bryan ; Tubbs, Raymond R. ; Rimsza, Lisa ; Leblanc, Michael ; Stiff, Patrick ; Fisher, Richard. / Clinical significance of MYC expression and/or "High-grade" morphology in non-burkitt, diffuse aggressive B-cell lymphomas : A SWOG s9704 correlative study. In: American Journal of Surgical Pathology. 2014 ; Vol. 38, No. 4. pp. 494-501.
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abstract = "The clinicopathologic findings in Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) may show significant overlap, and MYC abnormalities, found in all BLs, also occur in a subset of DLBCL. The 2008 World Health Organization classification introduced the category of {"}B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL{"} (BCLU) in recognition of this overlap, but the clinical significance of BCLU (ie, {"}high-grade{"}) morphology and the relationship between BCLU morphology and MYC abnormalities remains unclear. In this study, we identified 260 cases of non-Burkitt, diffuse aggressive B-cell lymphomas from SWOG S9704, a phase 3 randomized study of standard immunochemotherapy versus autologous stem cell transplantation. Of these, 31 cases (12{\%}) showed BCLU morphology, and 229 (88{\%}) showed typical DLBCL morphology. Of 198, 27 (14{\%}) were positive for MYC by immunohistochemistry. BCLU morphology was associated with an increased incidence of MYC expression but otherwise was not associated with distinct clinicopathologic features or significantly decreased survival. MYC-positive cases were morphologically and phenotypically heterogenous and were associated with poor progression-free and overall survival in multivariate analysis. These findings confirm that BCLU does not represent a distinct clinicopathologic entity and demonstrate that BCLU morphology alone does not significantly impact survival compared with typical DLBCL. In contrast, MYC protein expression is a poor prognostic factor that may be associated with either BCLU or DLBCL morphology, and MYC immunohistochemistry is suggested for routine prognostic evaluation (Clinicaltrials.gov identifier: NCT00004031).",
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