scholarly journals “Double hit” follicular lymphoma with low proliferation index: A unique case and literature review

2017 ◽  
Vol 3 (2) ◽  
Author(s):  
Pardis Vafaii ◽  
Haipeng Shao
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Clinical Course ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Proliferation Index ◽  
Low Grade ◽  
Gene Rearrangements ◽  
Double Hit ◽  
Indolent Disease

<p>“Double hit” lymphomas (DHLs) are aggressive B-cell lymphomas with concurrent <em>c-MYC</em> and <em>BCL2</em> and/or <em>BCL6</em> gene rearrangements. DHLs are usually classified morphologically as B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, and less commonly as DLBCL. Follicular lymphoma (FL) is characterized genetically by the presence of <em>IGH-BCL2</em> rearrangement. A subset of DHLs arises from FL by the acquisition of <em>c-MYC</em> gene rearrangement during disease progression, but FL with concurrent <em>IGH-BCL2</em> and <em>c-MYC</em> gene initial rearrangements is rarely reported. The few reported cases had different clinical courses, including some with indolent disease. We report a case of “double hit” low grade FL with both <em>c-MYC</em> and <em>BCL2</em> gene rearrangements but at low proliferation rate. Unlike the usual DHLs with aggressive clinical course, our patient showed at least partial response to intense chemotherapy. Review of the literature shows a few similar cases with variable clinical course, including a few indolent cases. These patients appear to respond better with more intense chemotherapy for DHL.</p>

scholarly journals Transformation of Follicular Lymphoma to Double Hit B-Cell Lymphoma Causing Hypercalcemia in a 69-Year-Old Female: A Case Report and Review of the Literature

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Sakshi Kapur ◽  
Miles B. Levin
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Care Center ◽  
Tertiary Care ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Severe Hypercalcemia ◽  
Double Hit

Double hit B-cell lymphomas are rare tumors that are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint, mainly a t(14;18)(q32;q21) involving BCL2. These tumors mostly occur in adults and carry a very poor prognosis. Double hit lymphomas can occur de novo, or arise from transformation of follicular lymphoma. We report a case of a 69-year-old female with abdominal distention and progressively worsening weakness over six months. Patient presented with severe hypercalcemia and multiple intra-abdominal/pelvic masses. Histopathology results of the abdominal mass were compatible with a double hit B-cell lymphoma. However, bone marrow biopsy results showed a low grade follicular lymphoma, thus suggesting peripheral transformation of follicular lymphoma to double hit B-cell lymphoma. Patient was transferred to a tertiary care center and was started on combination chemotherapy (EPOCH: doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone). Our paper highlights not only transformation of follicular lymphoma to double hit B-cell lymphoma and the challenges encountered in diagnosing and treating these aggressive tumors, but also the association of new onset/worsening hypercalcemia in such patients.

MYC/BCL2/BCL6 triple hit lymphoma: A study of 33 patients who had an aggressive clinical course similar to patients with double hit lymphomas.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7559-7559
Author(s):  
Shaoying Li ◽  
Wenting Huang ◽  
Yasuhiro Oki ◽  
L Jeffrey Medeiros
Keyword(s):  
B Cell ◽  
De Novo ◽  
Clinical Course ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Significant Difference ◽  
History Of ◽  
Double Hit ◽  
Aggressive Clinical Course

7559 Background: Large B cell lymphomas with MYC, BCL2, and BCL6 rearrangements, designated as triple hit lymphoma (THL), are uncommon. Large series studies of THL are scant and studies comparing THL to different types of double hit lymphoma (DHL) are lacking. Methods: We studied the clinicopathologic features and prognosis of 33 patients with THL and compared them to 83 patients with MYC/BCL2 DHL and 13 patients with MYC/BCL6DHL. Results: There were 21 men and 12 women, with a median age of 63 years (range, 34-85). Six patients had a history of low-grade B cell lymphoma and 27 had de novo lymphoma. These tumors were classified histologically as: 21 DLBCL, 10 high grade B-cell lymphoma, one concurrent DLBCL and follicular lymphoma (FL), and one concurrent DLBCL and mantle cell lymphoma. Immunohistochemical analysis showed that these tumors were positive for CD10 (94%), BCL6 (80%), BCL2 (93%), and MYC (69%, 40% as cutoff). 62% of tumors (8/13) with available data showed coexpression of MYC and BCL2. Using the Hans algorithm, 30 of 33 (91%) tumors had a germinal center B cell like (GCB) immunophenotype. All 7 cases tested by conventional cytogenetics showed a complex karyotype. Although BCL2 was always translocated with IGH, BCL6 translocated to MYC in 2of 7 cases of THL. Twenty-nine patients had treatment information available and all received immune-chemotherapy induction, including 11 with R-CHOP, 14 with R-EPOCH, 3 with R-HyperCVAD, and one with RICE (patient had a history of FL). The clinicopathological features of THL including induction chemotherapy were very similar to both the MYC/BCL2 DHL and MYC/BCL6 DHL (all P>0.05). There was no significant difference in median overall survival (OS) between patients with de novo lymphoma and those with a history of low-grade lymphoma (P=0.99). The OS in THL patients was 17.9 months, similar to the OS (17.2 months) of patients with MYC/BCL6 DHL and those with MYC/BCL2DHL (19.9 months) (P=0.60). Conclusions: MYC/BCL2/BCL6 THL is an aggressive B cell lymphoma and >90% of cases have a GCB immunophenotype. THL patients usually have an aggressive clinical course and a poor prognosis, similar to patients with double hit lymphomas.

scholarly journals High-grade B-cell Lymphoma with MYC and BCL2 Rearrangement Arising from Follicular Lymphoma: Presentation as a Large Peripancreatic Mass

Diagnostics ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 157
Author(s):  
Anna Shestakova ◽  
Sherif Rezk ◽  
Dara Ghasemizadeh ◽  
Ali Nael ◽  
Xiaohui Zhao
Keyword(s):  
Lymph Node ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
Inguinal Lymph Node ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
High Grade ◽  
Double Hit Lymphoma ◽  
Double Hit

Follicular lymphoma, the second most common non-Hodgkin lymphoma (NHL), primarily affects adults and shows an indolent clinical course. Rare cases of follicular lymphoma transform to a high-grade B-cell lymphoma with MYC and BCL2 rearrangements or “double-hit lymphoma”. Transformation to a “double-hit lymphoma” portends a worse prognosis and requires aggressive treatment. We report a comprehensive clinical, pathologic and radiographic review of a patient with previously undiagnosed low-grade follicular lymphoma that transformed into a “double-hit lymphoma”. The patient presented with a large heterogeneous mass 16 x 19 cm involving pancreatic head and neck and a mildly enlarged inguinal lymph node. Positron emission tomography (PET) study demonstrated Fluorodeoxyglucose (18F) (FDG)-avid peripancreatic mass. Tissue biopsy demonstrated a high-grade B-cell lymphoma with rearrangements t(14;18) and MYC, leading to the diagnosis of high-grade B-cell lymphoma with MYC and BCL2 rearrangements. Excisional biopsy of an inguinal lymph node demonstrated low-grade follicular lymphoma. Clonality studies demonstrated the same immunoglobulin clone V7-4 in inguinal lymph node and peripancreatic mass. Therefore, diagnosis of a high-grade B-cell lymphoma with MYC and BCL2 rearrangements that transformed from a low-grade follicular lymphoma was rendered. It is ultimately important to establish a tissue-based diagnosis at the different sites that are involved with lymphoma. Patient proceeded with the aggressive treatment with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R) treatment.

Survival outcomes of diffuse large B-cell lymphoma by association with concurrent or antecedent follicular lymphoma and double hit status

2019 ◽  
Vol 60 (13) ◽  
pp. 3266-3271
Author(s):  
Amir Behdad ◽  
Craig S. Boddy ◽  
Angela J. Fought ◽  
Timothy Taxter ◽  
Marissa K. Falkiewicz ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Survival Outcomes ◽  
Large B Cell Lymphoma ◽  
Double Hit ◽  
Large B Cell

“Double-Hit” Cytogenetic Status Is Not Predicted By Baseline Clinicopathologic Characteristics and Is Highly Associated With Overall Survival In B Cell Lymphoma Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4338-4338
Author(s):  
Daniel J. Landsburg ◽  
Sunita Dwivedy Nasta ◽  
Jakub Svoboda ◽  
Jennifer JD Morrissette ◽  
Stephen J. Schuster
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Gene Rearrangement ◽  
Median Overall Survival ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Gene Rearrangements ◽  
Myc Gene ◽  
Double Hit ◽  
The Impact

Abstract Background “Double-Hit” (DH) lymphomas are most commonly defined as B cell lymphomas demonstrating a MYC gene rearrangement and additional rearrangement(s) involving BCL2 and/or BCL6. DH lymphomas respond poorly to standard immunochemotherapy regimens, often prompting the use of more intensive treatments. DH gene rearrangements can be identified through metaphase cytogenetic testing or more sensitive fluorescence in situ hybridization (FISH) on diagnostic tissue specimens, although these studies are not routinely performed. Here, we analyze a cohort of B cell lymphoma patients to determine whether DH status can be predicted by clinicopathologic features as well as the impact of DH status on survival. Methods Fifty-three patients diagnosed with B cell lymphoma treated at the University of Pennsylvania from 2006-2013 who underwent diagnostic FISH for MYC gene rearrangements using probes to detect either an 8q24 split or t(8;14) were included in this analysis. FISH was performed at request of the interpreting pathologist or treating clinician. Patients with classic Burkitt lymphoma were excluded. Cases of DH lymphoma (DH+) were defined as demonstrating at least one of either 8q24 split, t(8;14), t(2;8) or t(8;22) as well as a BCL2, BCL6 and/or BCL1 rearrangement. Therapy was given at the discretion of the treating clinician. Response was defined using the Revised Response Criteria for Malignant Lymphoma (J Clin Oncol. 2007 Feb 10;25(5):579-86.). Results DH+ was detected in 17 patients (32%) and a sole MYC gene rearrangement was detected in an additional 9 patients (17%). MYC gene rearrangements were detected by metaphase cytogenetics in 4 (15%) and by FISH in 22 (85%) of these patients. No factor, including age, LDH, stage, International Prognostic Index (IPI) or histology was predictive of DH status (Table I). DH+ patients were treated with R-hyperCVAD (41%), R-CHOP (41%) and other regimens (18%). Complete response was less frequent in DH+ compared to non-DH patients (41% vs. 81%, p=0.002). With a median follow-up of 10.4 months (range 1.2-72.4), the median overall survival was significantly shorter for DH+ compared to non-DH patients (8.2 vs. 56.8 months, p<0.001). Median overall survival was not significantly different for non-DH patients with and without a sole MYC gene rearrangement (50.8 months vs. not yet reached, p=0.33). Univariate Cox regression analysis showed that the presence of a MYC gene rearrangement (MYC+) and DH+ had statistically significant associations with overall survival; however, only DH+ retained statistical significance on multivariate analysis (Table II). Conclusions DH status cannot be inferred by baseline disease- or patient-related characteristics and is most predictive of overall survival in this cohort of B cell lymphoma patients. These findings support the practice of routine FISH for DH gene rearrangements in order to better identify DH+ patients who may benefit from risk-adapted and/or targeted therapies. We plan to validate our findings in a larger unselected cohort of diffuse large B cell lymphoma patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Clinico-Genotypic Prognostic Index for De Novo Composite Diffuse Large B-Cell Lymphoma Arising from Follicular Lymphoma in the Rituximab Era

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5396-5396
Author(s):  
Ryan Mao Heng Lim ◽  
Natalie Pei Xin Chan ◽  
Lay Poh Khoo ◽  
Chee Leong Cheng ◽  
Leonard Tan ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Multivariate Model ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Double Hit ◽  
Large B Cell

Abstract Aim Composite follicular lymphoma with diffuse large B-cell lymphoma (FL/DLBCL) is an uncommon hematological neoplasm. The aim of this study was to examine clinico-pathological features of patients with FL/DLBCL and investigate relevant predictors of survival outcome. Methodology Patients with histologically-proven FL/DLBCL at diagnosis (n=106) and who were subsequently treated with Rituximab-based chemotherapy from 2002-2017 at the National Cancer Centre Singapore were retrospectively analyzed. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. Results The cohort consisted of 72 men and 34 women with a median age of 59 years (range, 24-82). The cell of origin by Han's algorithm was GCB in 37.7%, ABC in 58.5% and unknown in 3.8%. Eight patients (7.5%) were double-hit for c-MYC, BCL2 and/or BCL6 rearrangements. In a multivariate model inclusive of known clinico-pathological parameters at diagnosis, presence of B symptoms (p = 0.0122), stage 3 or 4 lymphoma (p = 0.0166) and double-hit genotype (p = 0.0045) were independently prognostic for worse overall survival (OS). These factors, excluding B symptoms, were similarly prognostic for progression-free survival (PFS). Including first-line treatment data in the multivariate model, lack of complete response (p < 0.0001) and use of chemotherapy regimens other than R-CHOP (p = 0.0360) alongside presence of B symptoms (p = 0.0022), were the only remaining independent prognostic variables for worse OS. Classification by cell of origin was not prognostic. A Clinico-Genotypic Index derived from point-wise addition of all five adverse parameters (score of 0, 1, 2, 3-4) revealed four prognostic risk groups accounting for 25%, 30%, 25% and 20% of the cohort, with a predicted 5-year OS of 100%, 95%, 57% and 19% respectively (p < 0.0001). Conclusion A Clinico-Genotypic Index derived from clinical and molecular factors can classify patients with composite FL/DLBCL into distinct prognostic groups. Han's algorithm has no prognostic value in this disease entity. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Differential Outcomes of Synchronous and Metachronous Diffuse Large B-Cell Lymphoma Transformed from Follicular Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5409-5409
Author(s):  
Natalie Pei Xin Chan ◽  
Ryan Mao Heng Lim ◽  
Lay Poh Khoo ◽  
Chee Leong Cheng ◽  
Leonard Kwan Cheong Tan ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Pathological Characteristics ◽  
Large B Cell Lymphoma ◽  
Response To Chemotherapy ◽  
Double Hit ◽  
Large B Cell

Abstract Aim: Composite histologies of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) may be present synchronously at diagnosis or metachronously at the time of transformation of a formerly diagnosed FL. The aim of this study was to examine their clinico-pathological characteristics and treatment outcomes. Method: Patients who were consecutively diagnosed with composite FL/DLBCL (n=120) and FL (n=346) from 2001-2017 at the National Cancer Centre Singapore were retrospectively analyzed. Chi-squared tests and multivariate logistic regression were performed to evaluate clinico-pathological associations between the two cohorts. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. Results: Amongst the FL cases, 21 patients (6.1%) with metachronous transformed FL/DLBCL were identified. The median lag time from diagnosis of FL to DLBCL transformation was 47 months (range, 7.8-168). Clinico-pathological features in synchronous and metachronous FL/DLBCL were similar, with both entities demonstrating a male preponderance (67% male and 33% female). Median age at diagnosis was 67 years (range, 41-81) and 60 years (range, 24-90) for metachronous and synchronous FL/DLBCL, respectively. The cell-of-origin by Han's criteria was similar (metachronous: GCB 52%, ABC 43%, unknown 5%; synchronous: GCB 38%, ABC 57%, unknown 5%; p = 0.21), as were the occurrence of C-MYC/BCL2/BCL6 double-hit rearrangements. However, survival from the time of DLBCL development was significantly worse (median, 3 vs 12 years) for metachronous compared to synchronous FL/DLBCL (HR 2.20, 95%CI 0.88-5.49, p = 0.022). Double-hit, advanced stage, and use of non-RCHOP regimens (OR 7.54, 95%CI 2.84-20.1, p = 0.0001) were associated with lack of complete response to chemotherapy. In metachronous FL/DLBCL, the R-CHOP regimen was less commonly used (77% vs 56%, p = 0.049). Correspondingly, complete response to chemotherapy was less likely in metachronous cases (38% vs 63%, p = 0.037). Conclusion: Metachronous and synchronous FL/DLBCL share similar clinico-pathological characteristics. A preceding diagnosis of FL however, predicts for significantly worse survival outcomes and suboptimal responses to chemotherapy. Disclosures No relevant conflicts of interest to declare.

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