A significant diffuse component predicts for inferior survival in grade 3 follicular lymphoma, but cytologic subtypes do not predict survival

Hans, Christine P.; Weisenburger, Dennis D.; Vose, Julie M.; Hock, Lynette M.; Lynch, James C.; Aoun, Patricia; Greiner, Timothy C.; Chan, Wing C.; Bociek, R. Gregory; Bierman, Philip J.; Armitage, Jamés O.

doi:10.1182/blood-2002-07-2298

Cited by 126 publications

(85 citation statements)

References 29 publications

(44 reference statements)

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“…On the other hand, one study suggested that it is not the distinction into FL3A or FL3B that is crucial in assessing prognosis, but the question of whether a diffuse component is present or not. 28 For the time being, it is not clear whether, and if so how, the above findings could be translated into clinical practice. At present, there is certainly no justification for subclassifying FL3 on the basis of immunophenotypic or genetic data, especially because there is still a large overlap in immunophenotypic and genetic features within the cytomorphological groups.…”

Section: Discussionmentioning

confidence: 99%

Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles

Horn¹,

Schmelter²,

Leich³

et al. 2011

Haematologica

143

100

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The online version of this article has a Supplementary Appendix. BackgroundAccording to the current World Health Organization Classification of Lymphoid Tumours, follicular lymphoma is subclassified into three grades according to the number of centroblasts. Follicular lymphoma grade 3 can be further divided into types A and B. Almost all available genetic data on grade 3B follicular lymphomas have been generated from tumors with an additional diffuse large B-cell lymphoma component. The purely follicular type of follicular lymphoma grade 3B is a rare neoplasm. Design and MethodsWe performed a detailed immunohistochemical (CD10, IRF4/MUM1, BCL2, Ig light chains) and genetic (translocations of BCL2, BCL6, MYC, IRF4) characterization of the largest series of purely follicular cases of grade 3B follicular lymphoma available to date, comprising 23 tumor samples. We also included 25 typical grade 1 or 2 follicular lymphomas, 9 follicular lymphomas with large centrocytes and/or high proliferation indices (FL/LCC), 12 cases of follicular lymphoma grade 3A, 16 cases of diffuse large B-cell lymphoma/follicular lymphoma grade 3B and 15 follicular lymphomas in which a straightforward distinction between grades 3A and 3B was not possible. ResultsTranslocations affecting BCL2 and BCL6 genes are rare in grade 3B follicular lymphomas (2/23, 9% and 4/23, 17%) when compared with grade 1 or 2 follicular lymphomas (22/25, 88%, P<0.001 and 0/25, P<0.05), FL/LCC (7/9, 78%, P<0.001 and 2/9, 22%), grade 3A follicular lymphomas (7/12, 58%, P<0.01 and 2/12, 17%), unclassified grade 3 follicular lymphomas (6/15, 40% and 2/15, 13%) and diffuse large B-cell lymphoma/follicular lymphoma grade 3B (2/16, 13% and 8/16, 50%, P<0.05). MYC translocations were detected occasionally in FL/LCC, follicular lymphoma grade 3B, and diffuse large B-cell lymphoma/follicular lymphoma grade 3B (13%-22%), but not in grade 1, 2 or 3A follicular lymphomas (P<0.05 when compared with follicular lymphoma grade 3B). Both follicular lymphoma grade 3B and diffuse large B-cell lymphoma/follicular lymphoma grade 3B were enriched in samples with a CD10 -IRF4/MUM1 + immunophenotype (8/19, 42% and 7/16, 44%), with the vast majority of them lacking BCL2 translocations. In contrast, 42/46 grade 1 or 2 follicular lymphomas, FL/LCC and grade 3A follicular lymphomas were CD10 + (91%) while 0/46 expressed IRF4/MUM1. None of the tumor samples tested with increased IRF4/MUM1-expression harbored a translocation of the IRF4 gene locus. ConclusionsOur results show that grade 3B follicular lymphomas form a distinct category of follicular lymphomas with infrequent BCL2 and BCL6 translocations, while grades 1, 2 and 3A follicular lymphomas and FL/LCC display homogeneous features with frequent BCL2 translocations and a CD10 + IRF4/MUM1 -immunophenotype.

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Section: Discussionmentioning

confidence: 99%

Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles

Horn¹,

Schmelter²,

Leich³

et al. 2011

Haematologica

143

100

View full text Add to dashboard Cite

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“…26 Yet others have observed that the presence of 450% diffuse component portends an inferior outcome after primary therapy for FL grade 3, although such patients were by definition excluded from our analysis. 27 Evaluating the proliferative rate as measured by Ki-67 staining has also been shown to be predictive of more aggressive clinical behavior. 28 One could anticipate that in the future, molecular signatures of individual tumors or the infiltrating immune cells may be the most precise pathologic predictors of outcomes for FL.…”

Section: Discussionmentioning

confidence: 99%

The impact of histologic grade on the outcome of high-dose therapy and autologous stem cell transplantation for follicular lymphoma

Pham

Gooley

Keeney

et al. 2007

Bone Marrow Transplant

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The impact of the follicular lymphoma (FL) histologic grade on outcomes after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) is unknown. We evaluated 219 consecutive patients with grades 1-3 FL who underwent HDT and ASCT at our center. Overall survival (OS), progression-free survival (PFS), relapse and non-relapse mortality (NRM) was estimated for each grade after controlling for other predictive factors. The number of patients with grades 1, 2 and 3 FL was 106 (48%), 75 (34%) and 38 (17%), respectively. Five-year outcome estimates for the entire cohort included 60% OS, 39% PFS and 46% relapse (median follow-up ¼ 7.8 years). PFS and relapse were nearly identical among patients with grade 3 FL versus grades 1-2 FL after adjusting for other contributing factors (hazard ratio (HR) ¼ 0.90, P ¼ 0.68; HR ¼ 1.07, P ¼ 0.80, respectively). The hazard for mortality (HR ¼ 0.70, P ¼ 0.23) and NRM (HR ¼ 0.33, P ¼ 0.07) was non-significantly lower among patients with grade 3 FL compared to patients with grades 1-2 disease. Factors associated with inferior PFS included elevated lactate dehydrogenase (HR ¼ 1.52, P ¼ 0.03), chemoresistance (HR ¼ 1.82, P ¼ 0.02), X2 prior therapies (HR ¼ 1.8, P ¼ 0.03) and prior radiation (HR ¼ 1.99, P ¼ 0.003). These data suggest that the histologic grade of FL does not impact PFS or relapse following HDT and ASCT.

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“…However, this is only true for FL3B with 3q27a abnormalities (BCL6), and FL3B with BCL2 rearrangement is probably similar to FL1-3A. 19 Hans et al 20 reported no difference in survival between patients with grade 3A and 3B FL, whereas those with FL3 and more than 50% diffuse components had inferior survival, similar to those with DLBCL. Because FL3B is rare, most studies base the clinical behavior of FL3 mainly on FL3A cases.…”

Section: Cll/sllmentioning

confidence: 99%

Non-Hodgkin’s Lymphomas

Ad¹,

Js²,

Rh³

et al. 2010

J Natl Compr Canc Netw

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223

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OverviewNon-Hodgkin's lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders originating in B-, T-, or natural killer (NK) lymphocytes. In the United States, B-cell lymphomas represent 80% to 85% of all cases, with 15% to 20% being T-cell lymphomas; NK lymphomas are very rare. In 2009, an estimated 65,980 new cases of NHL will be diagnosed and 19,500 will die of the disease.1 NHL is the sixth leading site of new cancer cases among men and fifth among women, accounting for 4% to 5% of new cancer cases and 3% to 4% of cancer-related deaths. Non-Hodgkin's Lymphomas Clinical Practice Guidelines in OncologyKey Words NCCN Clinical Practice Guidelines, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, cutaneous T-cell lymphoma, mycosis fungoides, Sézary syndrome, marginal zone lymphoma, mucosaassociated lymphoid tissue lymphoma, diagnosis, treatment, hematopathology, immunohistochemistry, treatment guidelines, staging evaluation, lymphoma pathology (JNCCN 2010;8:288-334) NCCN Categories of Evidence and ConsensusCategory 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus. Category 2A: The recommendation is based on lowerlevel evidence and there is uniform NCCN consensus. Category 2B: The recommendation is based on lowerlevel evidence and there is nonuniform NCCN consensus (but no major disagreement). Category 3: The recommendation is based on any level of evidence but reflects major disagreement. Please NoteThese guidelines are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network makes no representation or warranties of any kind regarding their content, use, or application and disclaims any responsibility for their applications or use in any way.These guidelines are copyrighted by the National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not be reproduced in any form without the express written permission of the NCCN © 2010. Disclosures for the NCCN Non-Hodgkin's Lymphomas Guidelines PanelAt the beginning of each NCCN guidelines panel meeting, panel members disclosed any financial support they have received from industry. Through 2008, this information was published in an aggregate statement in JNCCN and online. Furthering NCCN's commitment to public transparency, this disclosure process has now been expanded by listing all potential conflicts of interest respective to each individual expert panel member.Individual disclosures for the NCCN Non-Hodgkin's Lymphomas Guidelines Panel members can be found on page 334. (To view the most recent version of these guideli...

show abstract

A significant diffuse component predicts for inferior survival in grade 3 follicular lymphoma, but cytologic subtypes do not predict survival

Cited by 126 publications

References 29 publications

Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles

Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles

The impact of histologic grade on the outcome of high-dose therapy and autologous stem cell transplantation for follicular lymphoma

Non-Hodgkin’s Lymphomas

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