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

Horn, Heike; Schmelter, Christopher; Leich, Ellen; Salaverría, Itziar; Katzenberger, Tiemo; Ott, M. Michaela; Kalla, Jörg; Romero, Mónica Duarte; Siebert, Reiner; Rosenwald, Andreas; Ott, German

doi:10.3324/haematol.2011.042531

Cited by 143 publications

(125 citation statements)

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“…Others have confirmed similar findings. 27 Jaglowski et al, 10 in a SEER review of follicular lymphoma in adolescents and young adults, cite that the relative frequency of low-grade follicular lymphoma increases with age due to the general trend of more aggressive lymphomas in the young population. In patients aged 15-24 years, grades 1 through 3 occur with approximately equal frequencies, whereas in the 35-39 age group, grade 1 represents B55% of diagnoses, followed by grade 2 at 30% and grade 3 at 18%.…”

Section: Discussionmentioning

confidence: 99%

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

et al. 2013

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Follicular lymphoma is clinically heterogenous, and therefore necessitates the identification of prognostic markers to stratify risk groups and optimize clinical management. It is relatively rare in patients younger than 40 years, and the clinicopathologic characteristics and biological behavior in this age group are poorly understood. In the current study, samples from a cohort of 200 patients between 19 and 40 years were evaluated retrospectively with respect to clinical, histologic, and genetic features. These were then correlated with clinical outcome. The median age at presentation was 35 years with a slight female prepoderance (56%). Most of the cases are presented with nodal disease (90%). Concomitant follicular lymphoma and diffuse large B-cell lymphoma were observed in 7 (4%) patients. Immunohistologic studies showed the expression of CD10 (91%), BCL6 (97%), BCL2 (95%), MUM1/IRF4 (12%), MDM2 (17%), and CD23 (25%). BCL2 rearrangement was present in 74%, and BCL6 in 20%. The estimated overall survival of patients was 13 years (mean). The presence of anemia, elevated lactose dehydrogenase, bone marrow involvement, and high-risk follicular lymphoma international prognostic index correlated with adverse overall survival. Our findings revealed that follicular lymphoma in young adults demonstrate similarities with that of older adults, including the frequency of presentation at various anatomic sites, grade, and adverse prognostic factors.

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Section: Discussionmentioning

confidence: 99%

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

et al. 2013

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“…[12][13][14][15][16] According 17,18 representing on average a DHL in 50-60%. 14,[16][17][18][19][20] This also implies that the remaining 40-50% of MYC + lymphomas are "single-hit" and that their importance, despite this high percentage, might have been underappreciated. These lymphomas with MYC translocations, including DHL, have received increased attention because several studies showed them to run an aggressive clinical course.…”

Section: Introductionmentioning

confidence: 99%

“…4 All other lymphomas with a MYC breakpoint, irrespective of the presence of other aberrations, are called "single-hit" lymphomas (SHL). MYC breaks are seen in approximately 10% (3-17%) of all DLBCL and 15-20% of FL grade 3B, 17,18 representing on average a DHL in 50-60%. 14,[16][17][18][19][20] This also implies that the remaining 40-50% of MYC + lymphomas are "single-hit" and that their importance, despite this high percentage, might have been underappreciated.…”

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Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o nphomas. In BL the MYC translocation always involves one of the immunoglobulin loci (most commonly IGH, alternatively IGL or IGK) and is considered a disease-initiating event which occurs in the context of a rather simple karyotype. Indeed, the genomic complexity in BL is, overall, low. [6][7][8] In contrast, MYC translocations in other mature Bcell lymphomas frequently involve non-IG partners and are mostly found in complex karyotypes, often in addition to well-known primary aberrations including the IGH-BCL2 translocation.6,9-11 Consequently, they likely occur during disease progression rather than disease initiation. Indeed, in 20-80% of cases of DLBCL and BCLU with a MYC breakpoint, there is an accompanying BCL2 and/or BCL6 breakpoint. [12][13][14][15][16] According to the World Health Organization (WHO) classification, lymphomas in which such a combination of a MYC break with a BCL2 break and/or a BCL6 break (fur- (DHL). 4 All other lymphomas with a MYC breakpoint, irrespective of the presence of other aberrations, are called "single-hit" lymphomas (SHL). MYC breaks are seen in approximately 10% (3-17%) of all DLBCL and 15-20% of FL grade 3B, 17,18 representing on average a DHL in 50-60%. 14,[16][17][18][19][20] This also implies that the remaining 40-50% of MYC + lymphomas are "single-hit" and that their importance, despite this high percentage, might have been underappreciated. These lymphomas with MYC translocations, including DHL, have received increased attention because several studies showed them to run an aggressive clinical course. 9,11,21 However, gene expression and other molecular genetic data are scarce 3,22 and, consequently, the molecular make up of DHL and SHL other than BL remains largely unknown. Moreover, it is unclear in which pathological and molecular aspects DHL differs from SHL other than molecular Burkitt lymphoma (mBL).therIn that respect it should be noted that, in the presence or absence of a MYC break, oncogenes other than BCL2 and BCL6, including BCL3, chromosomal locus 9p13 (potentially affecting PAX5), CCNE1, as well as unknown partners involved in IGH breaks, can be deregulated through juxtaposition to one of the IG-loci. 16,[23][24][25][26] Breakpoints affecting both MYC and these genes might, therefore, also point to a DHL, although according to the WHO classification they are defined as SHL. 4 To investigate differences and similarities between SHL and DHL as well as between BCL2 + /MYC + and BCL6+ /MYC + DHL we explored the morphological, immunohistochemical, genetic and gene expression features of 80 adult MYC + mature aggressive B-cell lymphomas other than mBL. Methods Sample selection and pathology reviewAll lymphomas were investigated as part of the Molecular Mechanisms in Malignant Lymphomas (MMML) network project. The MMML protocols have been approved centrally by the institutional review board of the coordination center in Göttingen, Germany. All cases with an mBL gene expression signature (see Bioinformatica...

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“…4 BCL6 rearrangement has also been detected in a subset of follicular lymphomas, especially some cases of grade 3 follicular lymphoma and those lacking BCL2 rearrangement. 3,[5][6][7][8][9] Furthermore, BCL6 mutations occur in diffuse large B-cell lymphomas and other types of germinal center or postgerminal center-derived lymphomas; this has been suggested as a mechanism for aberrant BCL6 expression, although the presence of similar changes following somatic hypermutation in benign B cells complicates the interpretation of this finding. 1,[10][11][12][13][14] Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is another B-cell lymphoma of germinal center stage differentiation in which BCL6 translocations have been identified.…”

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confidence: 67%

Fluorescence Immunophenotyping and Interphase Cytogenetics (FICTION) Detects BCL6 Abnormalities, Including Gene Amplification, in Most Cases of Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Bakhirev

Vasef

Zhang

et al. 2014

Archives of Pathology &Amp; Laboratory Medicine

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Context.— BCL6 translocations are a frequent finding in B-cell lymphomas of diverse subtypes, including some cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). However, reliable analysis of BCL6 rearrangements using fluorescence in situ hybridization is difficult in NLPHL because of the relative paucity of neoplastic cells. Combined immunofluorescence microscopy and fluorescence in situ hybridization, or fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION), permits targeted analysis of neoplastic cells. Objective.—To better define the spectrum of BCL6 abnormalities in NLPHL using FICTION analysis. Design.—We performed an optimized FICTION analysis of 24 lymph nodes, including 11 NLPHL, 5 follicular hyperplasia with prominent progressive transformation of germinal centers, and 8 follicular hyperplasia without progressive transformation of germinal centers. Results.— BCL6 rearrangement was identified in 5 of 11 cases of NLPHL (46%). In addition, BCL6 gene amplification, with large clusters of BCL6 signals in the absence of chromosome 3 aneuploidy, was detected in 3 of 11 cases of NLPHL (27%). One NLPHL showed extra copies of BCL6 present in conjunction with multiple copies of chromosome 3. Altogether, we detected BCL6 abnormalities in 9 of 11 cases of NLPHL (82%). None of the progressive transformation of germinal centers or follicular hyperplasia cases showed BCL6 abnormalities by FICTION. Conclusions.—To our knowledge, this is the first report of BCL6 gene amplification in NLPHL. Our optimized protocol for FICTION permits detection of cytogenetic abnormalities in most NLPHL cases and may represent a useful ancillary diagnostic technique.

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

Cited by 143 publications

References 29 publications

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma

Fluorescence Immunophenotyping and Interphase Cytogenetics (FICTION) Detects BCL6 Abnormalities, Including Gene Amplification, in Most Cases of Nodular Lymphocyte-Predominant Hodgkin Lymphoma

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