scholarly journals MYC rearrangements in histologically progressed follicular lymphomas

Blood ◽  
1992 ◽  
Vol 80 (3) ◽  
pp. 758-767 ◽  
Author(s):  
T Yano ◽  
ES Jaffe ◽  
DL Longo ◽  
M Raffeld
Keyword(s):  
Follicular Lymphoma ◽  
Molecular Organization ◽  
Aggressive Lymphoma ◽  
Chain Gene ◽  
Low Grade ◽  
Immunoglobulin Gene ◽  
High Grade ◽  
Light Chain Gene ◽  
Myc Gene ◽  
Follicular Lymphomas

Histologic transformation of low-grade follicular lymphoma to an aggressive-grade lymphoma occurs in 60% to 80% of patients during their clinical course. The events that drive the transformation process are poorly understood. Deregulation of the MYC gene has been implicated in a small number of cases. This observation led us to examine the molecular organization of the MYC oncogene in 38 cases of histologically transformed lymphomas that arose from follicular lymphomas, and in 18 of the initial pretransformation follicular lymphomas. In addition, we examined 58 “control” low-grade follicular lymphomas that had not yet shown evidence of histologic progression. Immunoglobulin heavy chain and light chain gene rearrangements were detected in all biopsies and rearrangements of the BCL-2 locus were seen in 36 of 38 of the transformed lymphomas (consistent with their origin from follicular lymphomas), in 18 of 18 of the pretransformation follicular lymphomas, and in 51 of 58 of the control follicular lymphomas. All 18 pretransformation follicular lymphoma specimens displayed at least one immunoglobulin gene and BCL-2 rearrangement in common with the corresponding histologically progressed lymphoma, indicating a clonal relationship between the original follicular lymphoma and the histologically transformed lymphoma. MYC rearrangements were detected in 3 of 38 (8%) transformed lymphomas and in 1 of 58 (2%) control follicular lymphomas. The latter MYC rearranged follicular lymphoma was clinically aggressive and transformed to a high- grade lymphoma that led to the death of the patient within 20 months. None of the 18 pretransformation follicular lymphomas showed MYC rearrangement, including two from patients who later demonstrated MYC rearrangement in the progressed aggressive lymphoma. PvuII mutational analysis failed to identify additional MYC gene abnormalities in the progressed lymphomas. Because the Epstein-Barr virus (EBV) is associated with a fraction of high-grade lymphomas and is known to upregulate BCL-2, we looked for a potential role for this agent in our progressed lymphomas. We did not detect viral sequences in any case indicating that EBV does not play a major role in progression. The presence of MYC rearrangements in a small fraction of progressed aggressive lymphomas, and not in the corresponding antecedent follicular lymphomas, suggests that acquisition of a MYC rearrangement is in some cases associated with the transformation event.

scholarly journals MYC rearrangements in histologically progressed follicular lymphomas

Blood ◽  
1992 ◽  
Vol 80 (3) ◽  
pp. 758-767 ◽  
Author(s):  
T Yano ◽  
ES Jaffe ◽  
DL Longo ◽  
M Raffeld
Keyword(s):  
Follicular Lymphoma ◽  
Molecular Organization ◽  
Aggressive Lymphoma ◽  
Chain Gene ◽  
Low Grade ◽  
Immunoglobulin Gene ◽  
High Grade ◽  
Light Chain Gene ◽  
Myc Gene ◽  
Follicular Lymphomas

Abstract Histologic transformation of low-grade follicular lymphoma to an aggressive-grade lymphoma occurs in 60% to 80% of patients during their clinical course. The events that drive the transformation process are poorly understood. Deregulation of the MYC gene has been implicated in a small number of cases. This observation led us to examine the molecular organization of the MYC oncogene in 38 cases of histologically transformed lymphomas that arose from follicular lymphomas, and in 18 of the initial pretransformation follicular lymphomas. In addition, we examined 58 “control” low-grade follicular lymphomas that had not yet shown evidence of histologic progression. Immunoglobulin heavy chain and light chain gene rearrangements were detected in all biopsies and rearrangements of the BCL-2 locus were seen in 36 of 38 of the transformed lymphomas (consistent with their origin from follicular lymphomas), in 18 of 18 of the pretransformation follicular lymphomas, and in 51 of 58 of the control follicular lymphomas. All 18 pretransformation follicular lymphoma specimens displayed at least one immunoglobulin gene and BCL-2 rearrangement in common with the corresponding histologically progressed lymphoma, indicating a clonal relationship between the original follicular lymphoma and the histologically transformed lymphoma. MYC rearrangements were detected in 3 of 38 (8%) transformed lymphomas and in 1 of 58 (2%) control follicular lymphomas. The latter MYC rearranged follicular lymphoma was clinically aggressive and transformed to a high- grade lymphoma that led to the death of the patient within 20 months. None of the 18 pretransformation follicular lymphomas showed MYC rearrangement, including two from patients who later demonstrated MYC rearrangement in the progressed aggressive lymphoma. PvuII mutational analysis failed to identify additional MYC gene abnormalities in the progressed lymphomas. Because the Epstein-Barr virus (EBV) is associated with a fraction of high-grade lymphomas and is known to upregulate BCL-2, we looked for a potential role for this agent in our progressed lymphomas. We did not detect viral sequences in any case indicating that EBV does not play a major role in progression. The presence of MYC rearrangements in a small fraction of progressed aggressive lymphomas, and not in the corresponding antecedent follicular lymphomas, suggests that acquisition of a MYC rearrangement is in some cases associated with the transformation event.

Two for One: B-Cell Lymphomas with Features of Marginal and Follicular Lymphomas

2018 ◽  
Vol 139 (2) ◽  
pp. 84-88 ◽  
Author(s):  
Alexey Glazyrin ◽  
Chirag Patel ◽  
Lara Kujtan ◽  
Sheshadri Madhusudhana
Keyword(s):  
Bone Marrow ◽  
Follicular Lymphoma ◽  
Tumor Cells ◽  
Marginal Zone ◽  
Lymph Node Biopsy ◽  
Low Grade ◽  
Circulating Cells ◽  
Diagnosis And Classification ◽  
Follicular Lymphomas ◽  
Normal Architecture

Low-grade follicular lymphomas are genetically characterized by the translocation t(14; 18)(q32;q21) with BCL2 gene rearrangements. Marginal zone lymphomas are often associated with translocations or transcriptional deregulations of the MALT gene. We report 2 cases of lymphomas which harbor both the t(14;18)(q32;q21) translocation and MALT gene upregulation. Patients presented with numerous circulating atypical lymphocytes. Lymph node biopsy in both cases on HE staining demonstrated vague nodularity readily highlighted by CD10, CD23, or BCL6. Staining with CD20 and BCL2 demonstrated monotonous diffuse effacement of normal architecture with tumor cells without obvious follicular structures. Morphologically, tumor cells were consistent with centrocytes. Bone marrow biopsy demonstrated a combined peritrabecular and interstitial distribution of the tumor cells. These cases present substantial difficulties for diagnosis and classification. Clinical and morphological features were mostly consistent with follicular lymphoma, with a few features more often seen in marginal zone lymphomas (leukemic presentation, no CD10 in circulating cells, interstitial location of tumor cells in bone marrow); therefore, these cases were finally classified as follicular lymphoma grade I. Both patients were treated with standard chemotherapy regimens for follicular and nongastric MALT lymphomas with a good response to date.

Duodenal-Type Follicular Lymphoma: A Newly Recognized Entity in the 2016 World Health Organization Classification Update

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S61-S61
Author(s):  
F Rajack ◽  
L Taddasse-Heath ◽  
T J Naab
Keyword(s):  
Small Bowel ◽  
Follicular Lymphoma ◽  
Duodenal Bulb ◽  
World Health ◽  
Deficiency Anemia ◽  
Chain Gene ◽  
Low Grade ◽  
Sessile Polyp ◽  
Term Survival ◽  
Health Organization

Abstract Introduction/Objective Most cases of primary follicular lymphoma (FL) in the gastrointestinal tract occur in the second part of the duodenum, presenting with multiple small polyps. Duodenal type follicular lymphoma (D-FL) is a newly recognized entity in the 2016 WHO classification update. Methods Upper endoscopy in a 72 year old female with iron deficiency anemia revealed a single 8 mm sessile polyp with no bleeding in the duodenal bulb. Histology revealed dense infiltrate of small mature lymphocytes with a nodular growth pattern. Follicles, composed predominantly of centrocytes with scattered centroblasts, diffusely expressed CD20, CD10 and BCL-2. Results This immunoprofile characterizes follicular lymphoma. Real-time polymerase chain restriction assay detected BCL-2 MBR/JH DNA fusion sequence, usually resulting from t(14;18)(q32;q21) translocation and confirming D-FL. D- FL is often asymptomatic, discovered incidentally at endoscopy. It is usually low grade (grade 1–2), presenting at low stage, with immunophenotype and t(14;18)(q32;q21) similar to other FLs. However, in comparison to nodal FL, D-FL has higher selective use of V4 and V5 immunoglobulin heavy chain gene rearrangements, which has been linked to antigen dependent mechanisms in lymphoma development; this feature is shared with Mucosa-Associated Lymphoid Tissue (MALT) lymphoma. Conclusion D-FL often remains localized to the small bowel and has a good outcome even with local small bowel recurrences. It has a long term survival of >12 years. There is a low (<10%) risk of progression to nodal disease and given the indolent clinical course, a watch-and-wait approach is reasonable for most patients.

Simultaneous Phenotypically Distinct but Clonally Identical Mucosa-Associated Lymphoid Tissue and Follicular Lymphoma in a Patient With Sjögren’s Syndrome

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2247-2251 ◽  
Author(s):  
Antonella Aiello ◽  
Ming-Qing Du ◽  
Tim C. Diss ◽  
Huai-Zheng Peng ◽  
Francesco Pezzella ◽  
...  
Keyword(s):  
Lymph Node ◽  
Parotid Gland ◽  
Follicular Lymphoma ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Molecular Genetic ◽  
Pcr Amplification ◽  
Pcr Analysis ◽  
Chain Gene ◽  
Low Grade

A 44-year-old woman with a 12-year history of Sjögren’s syndrome (SS) developed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the parotid gland. Two years later, she presented with generalized lymphadenopathy and hepatosplenomegaly and a follicular lymphoma was diagnosed. To investigate the relationship of the two histologically distinct lymphomas, we re-examined their histology and immunophenotype and studied the lymphomatous tissue from the parotid, cervical lymph node, and spleen using molecular genetic methods. Histologic and immunophenotypic studies confirmed the previous diagnoses and also identified a previously unnoticed focus of follicular lymphoma in the second parotid gland biopsy. Polymerase chain reaction (PCR) amplification of the rearranged Ig heavy-chain gene showed the same sized dominant product in the MALT lymphoma and the follicular lymphoma. Similarly, PCR analysis of the t(14:18) translocation yielded an identical sized band from both MALT and follicular lymphoma. Cloning and sequencing of the Ig PCR products showed an identical CDR3 sequence from each lesion, indicating a common clonal lineage. The follicular lymphoma of the parotid gland lymph node and the follicular lymphoma of the spleen showed an identical mutation signature to that of the salivary gland MALT lymphoma. We propose that follicular lymphoma in the parotid gland lymph node may have resulted from colonization of lymphoid follicles by MALT lymphoma cells, following which the tumor cells were induced to express a follicular lymphoma phenotype, due to Bcl-2 overexpression caused by t(14;18), leading to a change in clinical behavior resulting in rapid widespread dissemination of disease. These observations suggest that the distinct phenotypes of low-grade B-cell lymphomas may be the consequence of interplay between genetic and local microenvironmental factors.

scholarly journals p53 mutation is associated with progression in follicular lymphomas

Blood ◽  
1993 ◽  
Vol 82 (7) ◽  
pp. 1994-2004 ◽  
Author(s):  
CA Sander ◽  
T Yano ◽  
HM Clark ◽  
C Harris ◽  
DL Longo ◽  
...  
Keyword(s):  
Complete Remission ◽  
Follicular Lymphoma ◽  
Molecular Mechanisms ◽  
Single Strand Conformation Polymorphism ◽  
Suppressor Gene ◽  
Neoplastic Cell ◽  
P53 Mutation ◽  
Polymorphism Analysis ◽  
Low Grade ◽  
Follicular Lymphomas

The majority of low-grade follicular lymphomas will eventually transform to an aggressive intermediate, or high-grade lymphoma. The molecular mechanisms responsible for this transformation have not been determined. We studied serial biopsies from 34 patients with follicular lymphomas that underwent histologic transformation, for abnormalities of the p53 tumor suppressor gene by a combination of immunohistochemistry, single strand conformation polymorphism analysis (SSCP), and sequencing. We found overexpression of p53 in 10 of the 34 transformed aggressive lymphomas, 9 of which contained mutations identified by SSCP analysis and subsequent sequencing. Matched pretransformation low-grade follicular lymphoma biopsies were available for 7 of the 10 cases. None of six studied by immunohistochemistry showed overexpression of p53 and only 1 of 4 studied by SSCP/sequencing showed the presence of mutation in the pretransformation biopsy. Interestingly, an eighth p53 positive transformed lymphoma recurred with a clonally related, p53 negative low-grade lymphoma 5 years after the patient had achieved a complete remission. Immunohistochemistry also showed that several pretransformation biopsies from p53 positive transformed cases showed rare p53 positive cells and in one case we could document an increase in their number over time. Twenty-five additional low-grade follicular lymphoma biopsies were also examined. Three patients had lymphomas positive for p53 mutation. One of the three subsequently transformed within a year of the biopsy studied; the second patient had an earlier (unavailable) biopsy at a different site that showed transformed histology. The third patient was treated with ProMACE-MOPP combination chemotherapy and attained a complete remission. We conclude that (1) mutations of p53 are associated with histologic transformation in approximately 25% to 30% of follicular lymphomas and (2) p53 positive cells can be detected before histologic transformation, but do not comprise a significant percentage of the neoplastic cell population (identifiable by SSCP) until late in the disease, just before or after histologic progression. Finally, the data also suggest that p53 positive low-grade lymphomas are at risk for progression and that in this subset, aggressive therapy may be warranted.

scholarly journals Immunoglobulin gene rearrangements and expression in diffuse histiocytic lymphomas reveal cellular lineage, molecular defects, and sites of chromosomal translocation

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 391-397 ◽  
Author(s):  
KA Siminovitch ◽  
JP Jensen ◽  
AL Epstein ◽  
SJ Korsmeyer
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Heavy Chain ◽  
Light Chain ◽  
Cell Lineage ◽  
Chromosomal Translocation ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
Immunoglobulin Gene ◽  
Light Chain Gene

Abstract We have examined the immunoglobulin gene configurations in cell lines from eight patients with diffuse histiocytic lymphoma in order to establish the cellular lineage and stage of differentiation of these lymphomas. The presence of heavy and light chain gene rearrangements as well as heavy chain class switching in seven cells placed these tumors within the B cell lineage. In contrast, one cell (SU-DHL-1), which lacks B cell-restricted surface antigens, retained germline heavy and light chain loci, indicating that it may represent a true histiocyte or uncommitted cell. Truncated RNAs for both the heavy and light chain immunoglobulins were responsible for the lack of surface immunoglobulin in the SU-DHL-2 cell line. Another cell line (SU-DHL-6), which possesses a t(14;18)(q32;q21) translocation, demonstrated an unexpected recombination within its heavy chain gene locus that may be the interchromosomal breakpoint.

scholarly journals Lack of Bcl-2 expression in feline follicular lymphomas

2019 ◽  
Vol 31 (6) ◽  
pp. 809-817
Author(s):  
Manfred Henrich ◽  
Anna Bauknecht ◽  
Werner Hecht ◽  
Manfred Reinacher
Keyword(s):  
Follicular Lymphoma ◽  
Single Cells ◽  
Leukemia Virus ◽  
Receptor Gene ◽  
Chromosomal Translocation ◽  
Feline Leukemia Virus ◽  
Immunoglobulin Gene ◽  
Follicular Hyperplasia ◽  
Significant Difference ◽  
Follicular Lymphomas

Bcl-2, an anti-apoptotic protein, is commonly overexpressed in follicular lymphomas in humans. This is usually the result of a chromosomal translocation that transposes the Bcl-2 gene into the immunoglobulin gene locus. The immunohistochemical assessment of this overexpression can be used as a tool for the differentiation of follicular lymphoma and follicular hyperplasia. In cats, little information about the expression of Bcl-2 in follicular lymphoma exists. We investigated 18 follicular lymphomas histologically and immunohistochemically for the expression of Bcl-2, CD3, CD45R, and feline leukemia virus. Clonality was assessed by PCR for antigen receptor gene rearrangements. Although the histology resembled that of their human counterparts, diffuse expression of Bcl-2 within the follicles of the feline lymphomas, as seen in human cases, was not present. Only single cells within the follicles, comparable to the reactive controls, were positive for Bcl-2 expression. The mean survival time of 4.6 y confirmed the indolent character of the tumor. None of the clinical parameters assessed were statistically significant predictors of survival. Furthermore, a statistically significant difference in survival of animals with or without anti-neoplastic therapy was also not demonstrable.

Working Formulation (WF) and Revised European-American classification of Lymphoma (REAL): Inter-observer agreement in conflicting lymphoma cases

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17567-17567
Author(s):  
S. Latifzadeh ◽  
T. Riahi ◽  
V. Entezari
Keyword(s):  
Kappa Statistic ◽  
Clinical Findings ◽  
Observer Agreement ◽  
Aggressive Lymphoma ◽  
Low Grade ◽  
High Grade ◽  
Diagnosis And Classification ◽  
Clinical Risks ◽  
High Level

17567 Background: Immunophenotypic and genetic studies play an increasingly important role in diagnosis and classification of lymphoid neoplasm. This study tried to re-evaluate a number of conflicting lymphoma cases which were reported by WF previously, with REAL classification and to measure the agreement between these two methods of classification. Methods: In a three year period, a panel of expert pathologists evaluated referral cases by WF. Those cases (n = 60, Mean age = 40.9 ± 16.4) whose evaluations did not reached to a definitive pathologic diagnosis or there was a discrepancy between their pathologic and clinical findings were reviewed in Keil institute of hematopathology in Germany based on REAL classification. The primary and secondary diagnoses each were classified in five subgroups with equivalent clinical risks (see Table ). Results: Disagreement was detected in 23 cases (38%), while exact kappa statistic was 0.50. Sixteen cases (70%) of difference belonged to group of low grade lymphoma (kappa = 0.35) in which 11 cases (69%) changed to aggressive lymphoma and one case changed to highly aggressive subgroups. Four cases (25%) of difference occurred in the group of low probability lymphoma in which neoplasia was documented. High grade and Hodgkin lymphoma subgroups showed a high level of agreement (kappa = 0.84 and 0.74 respectively). Conclusions: Based on this study’s results, it can be concluded that there is a moderate agreement between WF and REAL classifications in conflicting lymphoma cases. WF underestimates clinical risk of low grade lymphoma in a considerable amount of patients but in high grade lymphoma the disagreement is not so high. [Table: see text] No significant financial relationships to disclose.

Molecular analysis of the BCL-3 locus at chromosome 17q22 in B-cell neoplasms

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1813-1819
Author(s):  
T Yano ◽  
CA Sander ◽  
RE Andrade ◽  
CE Gauwerky ◽  
CM Croce ◽  
...  
Keyword(s):  
B Cell ◽  
Large Cell ◽  
Follicular Phase ◽  
Small Subset ◽  
Low Grade ◽  
Biologically Relevant ◽  
Myc Gene ◽  
Hodgkin's Lymphomas ◽  
Follicular Lymphomas ◽  
Center Cell

To better understand the role of the BCL-3 locus at chromosome 17q22 in the pathogenesis and progression of leukemias and lymphomas, we examined its genomic configuration in 264 B-cell malignancies and its expression in a smaller subset. Cases studied included 39 chronic lymphocytic leukemias, 58 low-grade follicular lymphomas, 20 mantle cell lymphomas, 30 small noncleaved cell lymphomas, 25 acute lymphoblastic leukemias, 10 acquired immunodeficiency syndrome--related non-Hodgkin's lymphomas, and 44 diffuse mixed- or diffuse large-cell lymphomas. In addition, 38 aggressive lymphomas (transformed follicular lymphomas) derived from previously indolent follicular lymphomas were examined. Southern blot analysis showed BCL-3 locus rearrangement in 4 cases (1.5%), ie, in 3 transformed follicular lymphomas and in 1 indolent follicular lymphoma. All 4 also had BCL-2 rearrangements consistent with their follicular center cell origin. None of the BCL-3 rearranged cases showed MYC gene rearrangement, as reported for the original leukemia that led to the discovery of BCL-3. Pretransformation specimens of all three transformed follicular lymphomas showed the presence of the BCL-3 alteration before histologic progression. In 1 case, serial pretransformation biopsies showed that the BCL-3 rearrangement was acquired during the indolent follicular phase of the patient's disease. Thirty lymphomas, including 2 of the 4 with BCL-3 rearrangement, were also examined for BCL-3 message. All 30, including the 2 with BCL-3 rearrangements, expressed the normal 1.7-kb BCL-3 transcript, at approximately equivalent levels. The data indicate that, although BCL-3 locus alterations are found in only a small fraction of B-cell lymphoid malignancies, they occur primarily in a subset of follicular center cell lymphomas. Interestingly, these alterations appear to be acquired during the indolent (follicular) phase of the disease and they are maintained when histologic transformation takes place. The data also suggest that BCL-3 locus alterations do not result in gross changes of BCL-3 gene expression and do not necessarily involve the MYC gene. Although the preferential involvement of BCL-3 alterations in a small subset of follicular lymphomas that transform suggests a possible link between these abnormalities and progression, further studies are needed to ensure that these alterations are biologically relevant and not simply a manifestation of genomic instability.

Sign in / Sign up

Export Citation Format

Share Document