Lymphomas, B-Cell - B-Cell Lymphomas

Primary Authors: Miles, Rodney R., MD, PhD. Perkins, Sherrie L., MD, PhD.

  • Key Points
  • Diagnosis
  • Algorithms
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Content

Double- and triple-hit lymphomas

B-cell lymphomas with two recurrent chromosomal breakpoint aberrations are referred to in the WHO classification as “double-hit lymphomas.” These usually involve the MYC oncogene in association with the BCL2 translocation, although other translocation associations with the MYC gene occur (eg, as with the BCL6 gene). If three translocations (eg, involving the MYC, BCL2, and BCL6 genes) are present, these lymphomas are referred to as “triple-hit lymphomas”; these are rare.

Histologically aggressive lymphomas in adults with coexpression of the CD10, bcl6, and bcl2 proteins, with a high Ki67 proliferation index or those that have unusual clinical features (such as peripheral blood involvement), may be worked up to exclude a diagnosis of double- or triple-hit lymphomas. These lymphomas are often placed in the category called “B-cell lymphoma, unclassifiable, with features intermediate between DLBCL (diffuse large B-cell lymphoma) and Burkitt lymphoma” (WHO 2008). It is important to identify these lymphomas as they tend to manifest aggressive behavior and respond poorly to traditional chemotherapy.

Breakpoints Used to Identify Double- or Triple-Hit Lymphomas

Oncogene

Break-apart MYC

BCL2

BCL6

Locus 8q24 18q21 3q27
Biology Accelerator of cell proliferation Apoptosis inhibitor Transcription modifier
Cytogenetics  (translocations) Any MYC translocation BCL2/IGH t(14;18)(q32;21)
  • BCL6 almost always has a non-Ig translocation partner – BCL6 (3q27)
  • Uncommon partner – BCL6/IGH [t(3;14)(q27;q32)]
Specific lymphomas associated with translocation
  • Burkitt lymphoma
  • Diffuse large B-cell lymphoma (DLBCL)
  • Aggressive B-cell lymphoma not otherwise specified (NOS)
  • Follicular lymphoma
  • DLBCL
  • Follicular lymphoma
  • DLBCL
  • High-grade lymphomas (rare)
Other malignancies associated with translocation
  • B-cell acute lymphoblastic lymphoma (ALL) (rare)
  • B-cell ALL (rare)
 

DIAGNOSTIC TESTING

ARUP Tests

  • Individual probes
    • Chromosome FISH, Interphase 2002298 – order probes separately 
  • Panels
    • Aggressive B-Cell Lymphoma FISH Reflex, Tissue 2012710 – if MYC (8q24) gene rearrangement by FISH is positive, then IGH-BCL2 fusion t(14;18) by FISH is added; if IGH-BCL2 fusion, t(14;18) by FISH is negative, then BCL6 (3q27) gene rearrangement by FISH will be added
    • Lymphoma (Aggressive) Panel by FISH 2002650 – probes include IGH/BCL2, BCL6, and MYC
  • For histologically aggressive B-cell lymphomas with either Burkitt-like or diffuse large cell morphologies in adults demonstrating a CD20+, CD10+ phenotype with high proliferative index OR CD20+ neoplasms with morphologic features indeterminate between DLBCL and Burkitt lymphoma, it is reasonable to test for MYC, BCL2, and BCL6 rearrangements using FISH
    • IGH-BCL2 Fusion, t(14;18) by FISH 2001536
    • IGH-MYC t(8;14) by FISH 2001538
    • MYC (8q24) Gene  Rearrangement by FISH 2002345
    • BCL6 (3q27) Gene Rearrangement by FISH 2010107
References:  Aukema SM, 2011; Johnson NA et al, 2009; Salaverria I et al, 2011; Savage et al, 2009; WHO, 2008.

Indications for Testing

  • Adenopathy
  • Fevers/night sweats
  • Recurrent infections
  • Unexplained lymphocytosis or abnormal manual differential

Laboratory Testing

  • Initial testing involves the following
    • CBC with peripheral smear
    • Liver chemistries
    • Lactate dehydrogenase (LD)
    • Serum uric acid, potassium, calcium, phosphorus
    • HIV for at-risk patients
  • Immunophenotyping to identify the lymphoid proliferation malignancy and to categorize lymphoma type
    • See the Lymphoma Phenotyping algorithm for specific test-ordering recommendations
    • May be performed on peripheral blood, bone marrow

Histology

  • Fine-needle aspiration (FNA) not considered adequate – use incisional biopsy specimen (NCCN, 2015)
  • Follow-up testing with bone marrow biopsy
    • ≥2 cm specimen length
    • Classified as involved or not
  • Immunophenotyping (flow cytometry testing) and immunoperoxidase staining of tissue for specific B-cell antigens or clonality with kappa and lambda light-chain staining
  • Immunohistochemistry – useful in conjunction with phenotyping
    • Most commonly used stains – cyclin D1, Pax-5, Ki-67, MUM1-IRF4, HHV8, EBV, ALK-1, CD3, CD5, CD10 (CALLA), CD19, CD20, CD21 (dendritic cell), CD22, CD23, CD25, CD30 (Ki-1), CD79A, CD138 (Syndecan-1), BCL-2, kappa and lambda light chains, TRAP, and TdT
    • Other available stains – BOB-1, Bax, caspase-3, CD15, CD43, CD45, CD45RA-MT2, CD45RO, CD74, c-Myc, DBA.44, and Oct-2
  • B-cell clonality studies
    • Locate clonal rearrangements of the immunoglobulin gene in B-cell malignancies
    • Provide information regarding prognosis and treatment recommendations
  • T-cell clonality studies

Genetic testing

Disease

Genetics

Comments

B-cell lymphoma, unclassifiable, with features intermediate between DLBCL (diffuse large B-cell lymphoma) and Burkitt lymphoma MYC, BCL2, BCL6 Refer to Key Points
Burkitt lymphoma MYC t(8;14), t(2;8), t(8;22)  
Diffuse large B-cell lymphoma (DLBCL) BCL6, BCL2  
Follicular lymphoma BCL2 t(14;18)(q32;q21) Recommended methodology – FISH or cytogenetics
Hairy cell leukemia BRAF V600E  
Mantle cell lymphoma BCL1(CCND1)  t(11;14)(q13;q32)  
Marginal zone lymphoma (nodal, MALT, splenic) MYD88 Use to differentiate from lymphoplasmacytic lymphoma
Mucosa-associated lymphoid tissue (MALT) (gastric) t(11;14), t(14;18), t(1;14), t(3;14), t(11:18)

FISH or cytogenetics

PCR useful for t(14;18)

Other testing

  • Virus testing
    • EBV – posttransplant lymphomas, endemic nasopharyngeal lymphomas
    • HHV8 – AIDS-related lymphomas
  • Bacteria testing
    • Helicobacter – mucosa-associated lymphoid tissue (MALT) lymphoma
  • Kappa and lambda light-chain clonality in situ hybridization
  • Testing prior to treatment with immunosuppressive therapies
    • HBV – surface antigen and core antibodies for all patients considering rituximab
      • Also include HBV e antigen testing for patients with relevant risk factors
    • HCV – for high-risk patients considering rituximab
    • CMV – PCR quantitative

Prognosis

  • International Prognostic Index scoring system
    • Based on pretreatment clinical factors of age (≤60 years); Ann Arbor tumor stage (I or II); number of extranodal sites (≤1); Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1); and serum LD (≤1 times normal) – all scored as 0
    • Patients placed in four risk groups
    • Limited usefulness in follicular lymphoma, mantle cell lymphoma, NK lymphoma, nasal-type lymphoma, hepatosplenic lymphoma, and enteropathy-type lymphoma
  • Follicular Lymphoma International Prognostic Index scoring system
    • Five risk factors (each scored as one point)
      • Blood hemoglobin <12 g/dL
      • Serum LD >normal
      • Ann Arbor tumor stage (III or IV)
      • >4 nodal sites
      • Age >60 years
    • 0-1 risk factor – low risk (5-year survival 90%)
    • 2 risk factors – intermediate risk (5-year survival 78%)
    • 3 risk factors – high risk (5-year survival 53%)
  • All prognostic indices may change in the future as the IPI and FLIPI indices were developed before immunotherapy
  • Genetic mutations (cytogenetics)
    • Follicular lymphoma
      • Adverse prognosis associated with del 17p, trisomy 12 and abnormalities of 6p
    • Diffuse large B-cell lymphoma (DLBCL)
      • Better prognosis associated with t(14;18)
      • Adverse prognosis with MYC oncogene; BCL2 gene, p53(+)
    • Follicular and DLBCL
      • Dismal outcomes for 8q24/MYC in association with 18q21/BCL2 or 3q27/BCL6
    • Double-hit and triple-hit lymphomas
      • Refer to Key Points for double- and triple-hit lymphomas
    • CLL
      • CD38 and ZAP-70 – mutation status correlates inversely with prognosis

Differential Diagnosis

Lymphoma Leukemia Phenotyping Testing Algorithm

  • Alemtuzumab (Campath) therapy – risk of CMV reactivation
    • PCR quantitative two to three weeks after start of therapy
  • Rituximab (Rituxan) therapy – high risk of hepatitis reactivation
    • HBV surface antigen and core antibody testing for all patients
      • Add HBV e antigen testing for patients with relevant risk factors
    • HCV testing for at-risk patients

B-cell non-Hodgkin lymphomas (NHL) represent a heterogenous group of malignancies of the lymph system.

Epidemiology

  • Incidence – represents 80-85% of the cases of NHL diagnosed annually
    • >70,000 new cases of NHL (NCCN, 2014)
  • Age – peaks in 60s
  • Sex – M<F (minimal)

WHO Classification of Mature B-Cell Neoplasms (2008)

  • Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
  • B-cell prolymphocytic leukemia
  • Splenic marginal zone lymphoma (MZL)
  • Hairy cell leukemia
  • Splenic lymphoma/leukemia, unclassifiable
  • Lymphoplasmacytic lymphoma
  • Heavy chain diseases
  • Plasma cell neoplasms
  • Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT)
  • Nodal MZL
  • Follicular lymphoma
  • Primary cutaneous follicle center lymphoma
  • Mantle cell lymphoma
  • Diffuse large B-cell lymphoma (DLBCL), NOS (not otherwise specified)
  • T-cell/histiocyte-rich large B-cell lymphoma
  • Primary DLBCL of the central nervous system
  • Primary cutaneous DLBCL, leg type
  • Epstein-Barr virus (EBV)-positive DLBCL of the elderly
  • DLBCL associated with chronic inflammation
  • Lymphomatoid granulomatosis
  • Primary mediastinal (thymic) large B-cell lymphoma
  • Intravascular large B-cell lymphoma
  • ALK-positive large B-cell lymphoma
  • Plasmablastic lymphoma
  • Large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease
  • Primary effusion lymphoma
  • Burkitt lymphoma
  • B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma
  • B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma

Risk Factors

Clinical Presentation of Selected Lymphoma Subtypes (based on WHO classification)

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

Leukemia/Lymphoma Phenotyping by Flow Cytometry 2008003
Method: Flow Cytometry

Chromosome FISH, Interphase 2002298
Method: Fluorescence in situ Hybridization

B-Cell Clonality Screening (IgH and IgK) by PCR 2006193
Method: Polymerase Chain Reaction/Capillary Electrophoresis

Limitations

False-negative results may result from specimen inadequacy and mutations affecting primer sites

Detection of clonally rearranged IgH is seen in a subset of T-cell neoplasms (ie, a positive result in the test should not be used to differentiate between T- and B-cell neoplasms)

Cyclin D1, SP4 by Immunohistochemistry 2003842
Method: Immunohistochemistry

IGH-BCL2 Fusion, t(14;18) by FISH 2001536
Method: Fluorescence in situ Hybridization

Limitations

Not validated for tissue fixed in alcohol-based or non-formalin fixatives

Negative result does not exclude possibility of translocations involving other partners or rule out follicular lymphoma

IGH-MYC Fusion t(8;14) by FISH 2001538
Method: Fluorescence in situ Hybridization

Limitations

Negative result does not rule out BL or B-cell lymphomas with features intermediate between BL and DLBCL involving MYC with other translocation partners, such as t(2;8) or t(8;22)

IGH-MYC t(8;14) by FISH has not been validated for tissue fixed in alcohol-based or non-formalin fixatives

MYC is not specific for BL or B-cell lymphomas with features intermediate between BL and DLBCL

MYC (8q24) Gene Rearrangement by FISH 2002345
Method: Fluorescence in situ Hybridization

Limitations

Negative result does not rule out BL or B-cell lymphomas with features intermediate between BL and DLBCL

MYC (8q24) gene rearrangement by FISH has not been validated for tissue fixed in alcohol-based or non-formalin fixatives

MYC is not specific for BL or B-cell lymphomas with features intermediate between BL and DLBCL

BCL6 (3q27) Gene Rearrangement by FISH 2010107
Method: Fluorescence in situ Hybridization

Aggressive B-Cell Lymphoma FISH Reflex, Tissue 2012710
Method: Fluorescence in situ Hybridization

Limitations

Interpretation of results requires correlation with morphology and immunophenotype

MYC and/or BCL2 overexpression can be due to other mechanisms not detected by this test

Chromosome alterations outside probe region are not detected

Lymphoma (Aggressive) Panel by FISH 2002650
Method: Fluorescence in situ Hybridization

Limitations

Interpretation of results requires correlation with morphology and immunophenotype

MYC and/or BCL2 overexpression can be due to other mechanisms not detected by this test

Chromosome alterations outside probe region are not detected

FFPE and frozen specimens unacceptable

BRAF V600E Mutation Detection in Hairy Cell Leukemia by Real-Time PCR, Quantitative 2007132
Method: Polymerase Chain Reaction

Limitations

Limit of detection – 0.2% mutant allele

ZAP-70 Analysis by Flow Cytometry 0092392
Method: Flow Cytometry

Limitations

Cell viability must be >98%

IGHV Mutation Analysis by Sequencing 0040227
Method: Polymerase Chain Reaction/Sequencing

Limitations

Samples that do not yield amplification product may contain too few CLL cells (<50% B cells) or express VH genes with high numbers of mutations that may compromise clonal B-cell amplification

Not intended to detect minimal residual disease

Cytogenomic SNP Microarray - Oncology 2006325
Method: Genomic Microarray (Oligo-SNP Array)

Limitations

Panel only detects prognostically important imbalances (gain or loss of DNA) in the chromosomes of interest

Chromosome alterations outside the regions complementary to these FISH probes will not be detected

Ideal testing is when significant disease is present

Chromosome FISH, CLL Panel 2002295
Method: Fluorescence in situ Hybridization

Limitations

Panel only detects prognostically important imbalances (gain or loss of DNA) in the chromosomes of interest

Chromosome alterations outside the regions complementary to these FISH probes will not be detected

Ideal testing is when significant disease is present

IGH-CCND1 Fusion, t(11;14) by FISH 2007226
Method: Fluorescence in situ Hybridization

Limitations

Not validated for tissue fixed in alcohol-based or nonformalin fixatives or decalcified tissue

Negative result does not exclude the possibility of translocations involving other partners

This mutation is not specific for MCL; results should be analyzed in conjunction with morphology, immunohistochemistry, and immunophenotyping results

IGH-CCND1 (BCL-1/JH) Translocation, t(11;14) by PCR 0055557
Method: Polymerase Chain Reaction

Limitations

Not validated for tissue fixed in alcohol-based or nonformalin fixatives or decalcified tissue

Negative result does not exclude the possibility of translocations involving other partners

This mutation is not specific for MCL; results need to be analyzed in conjunction with morphology, immunohistochemistry, and immunophenotyping results

Anaplastic Lymphoma Kinase 1 (ALK-1) by Immunohistochemistry 2003439
Method: Immunohistochemistry

BCL-2 by Immunohistochemistry 2004513
Method: Immunohistochemistry

BCL-6 by Immunohistochemistry 2003457
Method: Immunohistochemistry

CD3 by Immunohistochemistry 2003508
Method: Immunohistochemistry

CD5 by Immunohistochemistry 2003514
Method: Immunohistochemistry

CD10 (CALLA) by Immunohistochemistry 2003523
Method: Immunohistochemistry

CD19 by Immunohistochemistry 2005114
Method: Immunohistochemistry

CD20, L26 by Immunohistochemistry 2003532
Method: Immunohistochemistry

CD21 (Dendritic Cell) by Immunohistochemistry 2003535
Method: Immunohistochemistry

CD23 by Immunohistochemistry 2003541
Method: Immunohistochemistry

CD25 by Immunohistochemistry 2003544
Method: Immunohistochemistry

CD30 (Ki-1) by Immunohistochemistry 2003547
Method: Immunohistochemistry

CD79A by Immunohistochemistry 2003800
Method: Immunohistochemistry

CD138 (Syndecan-1) by Immunohistochemistry 2003812
Method: Immunohistochemistry

CD200 by Immunohistochemistry 2012844
Method: Immunohistochemistry

Herpes Virus 8 by Immunohistochemistry 2003932
Method: Immunohistochemistry

Kappa Light Chains by Immunohistochemistry 2003981
Method: Immunohistochemistry

Ki-67 with Interpretation by Immunohistochemistry 2007182
Method: Immunohistochemistry

Lambda Light Chains by Immunohistochemistry 2003984
Method: Immunohistochemistry

MUM1/IRF4 by Immunohistochemistry 2003975
Method: Immunohistochemistry

Pax-5 by Immunohistochemistry 2004082
Method: Immunohistochemistry

SOX11 by Immunohistochemistry 2012561
Method: Immunohistochemistry

Tartrate-Resistant Acid Phosphatase (TRAP) by Immunohistochemistry 2004160
Method: Immunohistochemistry

TdT by Immunohistochemistry 2004142
Method: Immunohistochemistry

Additional Tests Available

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Comments

Initial test to evaluate lymphoma

May provide prognostic information

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Comments

Initial test to evaluate lymphoma

May provide prognostic information

Lactate Dehydrogenase, Serum or Plasma 0020006
Method: Quantitative Enzymatic

Comments

Initial test to evaluate lymphoma

May provide prognostic information

Uric Acid, Serum or Plasma 0020026
Method: Quantitative Spectrophotometry

Comments

Initial test to evaluate lymphoma

May provide prognostic information

Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite) but only when concentrations are at or above those expected during acetaminophen overdose

B-Cell CD20 Expression 0092099
Method: Flow Cytometry

Comments

Order for rituximab monitoring

Chromosome Analysis, Bone Marrow 2002292
Method: Giemsa Band

Comments

Identify neoplastic populations in marrow

B Cell Specific Octamer Binding Protein-1 (BOB-1) by Immunohistochemistry 2003442
Method: Immunohistochemistry

Caspase-3 by Immunohistochemistry 2003496
Method: Immunohistochemistry

CD15, Leu M1 by Immunohistochemistry 2003529
Method: Immunohistochemistry

CD43, L60 (Leu 22) by Immunohistochemistry 2003568
Method: Immunohistochemistry

CD45 by Immunohistochemistry 2003574
Method: Immunohistochemistry

Hairy Cell Leukemia, DBA.44 by Immunohistochemistry 2003860
Method: Immunohistochemistry

Hepatitis B Virus Core Antibodies (Total) 0020091
Method: Qualitative Chemiluminescent Immunoassay

Comments

Identify HBV status if considering rituximab therapy

Octamer Transcription Factor-2 (Oct 2) by Immunohistochemistry 2004061
Method: Immunohistochemistry

Hepatitis B Virus Surface Antigen, Confirmation 0020128
Method: Chemiluminescent Immunoassay

Comments

Identify HBV status if considering rituximab therapy

Hepatitis C Virus Antibody by CIA 2002483
Method: Qualitative Chemiluminescent Immunoassay

Comments

Screen for hepatitis C virus (HCV) infection in at-risk individuals

Screen for IgG antibodies to HCV

Cytomegalovirus by Quantitative PCR 0051813
Method: Quantitative Polymerase Chain Reaction

Comments

Preferred test for posttransplant surveillance

Quantify CMV viral load in plasma

Human Immunodeficiency Virus Types 1 and 2 (HIV-1, HIV-2) Antibodies by CIA with Reflex to HIV-1 Antibody Confirmation by Western Blot 2005377
Method: Qualitative Chemiluminescent Immunoassay/Qualitative Western Blot

Comments

Use for at-risk patients

Guidelines

NCCN Clinical Practice Guidelines in Oncology, Non-Hodgkin's Lymphomas. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Jun 2015]

Protocol for the Examination of Specimens from Patients with Hematopoietic Neoplasms of the Ocular Adnexa. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: March 2010. College of American Pathologists (CAP). Northfield, IL [Accessed: May 2015]

Protocol for the Examination of Specimens From Patients With Non-Hodgkin Lymphoma/Lymphoid Neoplasms. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: June 2010. College of American Pathologists (CAP). Northfield, IL [Accessed: Jun 2015]

General References

Aukema S, Siebert R, Schuuring E, van Imhoff G, Kluin-Nelemans H, Boerma E, Kluin P. Double-hit B-cell lymphomas. Blood. 2011; 117(8): 2319-31. PubMed

Behdad A, Bailey N. Diagnosis of splenic B-cell lymphomas in the bone marrow: a review of histopathologic, immunophenotypic, and genetic findings. Arch Pathol Lab Med. 2014; 138(10): 1295-301. PubMed

Carbone A, Gloghini A, Aiello A, Testi A, Cabras A. B-cell lymphomas with features intermediate between distinct pathologic entities. From pathogenesis to pathology. Hum Pathol. 2010; 41(5): 621-31. PubMed

de Tute R. Flow cytometry and its use in the diagnosis and management of mature lymphoid malignancies. Histopathology. 2011; 58(1): 90-105. PubMed

Elenitoba-Johnson K, Lim M, Kjeldsberg C. Mature B-cell Neoplasms with Primary Tissue Manifestations. In Kjeldsberg C and Perkins SL. Practical Diagnosis of Hematologic Disorders, 5th ed. Chicago: ASCP Press, 2010.

Gascoyne R, Rosenwald A, Poppema S, Lenz G. Prognostic biomarkers in malignant lymphomas. Leuk Lymphoma. 2010; 51 Suppl 1: 11-9. PubMed

Good D, Gascoyne R. Classification of non-Hodgkin's lymphoma. Hematol Oncol Clin North Am. 2008; 22(5): 781-805, vii. PubMed

Johnson N, Savage K, Ludkovski O, Ben-Neriah S, Woods R, Steidl C, Dyer M, Siebert R, Kuruvilla J, Klasa R, Connors J, Gascoyne R, Horsman D. Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival. Blood. 2009; 114(11): 2273-9. PubMed

Ondrejka S, Hsi E. Pathology of B-cell lymphomas: diagnosis and biomarker discovery. Cancer Treat Res. 2015; 165: 27-50. PubMed

Peterson L. Mature B-cell Neoplasms with Leukemic Manifestations. In Kjeldsberg C and Perkins SL. Practical Diagnosis of Hematologic Disorders, 5th ed. Chicago: ASCP Press, 2010.

Peterson L. Mature B-cell Neoplasms with Plasma Cell or Plasmacytoid Differentiation. In Kjeldsberg C and Perkins SL. Practical Diagnosis of Hematologic Disorders, 5th ed. Chicago: ASCP Press, 2010.

Pizzi M, Gazzola A, Mannu C, Pileri S, Sabattini E, Pileri S. The role of molecular biology in the diagnosis of lymphoid neoplasms. Front Biosci (Landmark Ed). 2014; 19: 1088-104. PubMed

Salaverria I, Siebert R. The gray zone between Burkitt's lymphoma and diffuse large B-cell lymphoma from a genetics perspective. J Clin Oncol. 2011; 29(14): 1835-43. PubMed

Savage K, Johnson N, Ben-Neriah S, Connors J, Sehn L, Farinha P, Horsman D, Gascoyne R. MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy. Blood. 2009; 114(17): 3533-7. PubMed

Shi M, Xiao R, Woda B, Yu H. Five important advances in hematopathology. Arch Pathol Lab Med. 2014; 138(3): 410-9. PubMed

Vardiman J, et al. Myeloproliferative Neoplasms. In Swerdlow SH, et al. WHO Classification of Tumours of Haematoietic and Lymphoid Tissues, Lyon, France: IARC Press, 2008.

Wilcox R. Cutaneous B-cell lymphomas: 2015 update on diagnosis, risk-stratification, and management. Am J Hematol. 2015; 90(1): 73-6. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Bahler D, Kim B, Gao A, Swerdlow S. Analysis of immunoglobulin V genes suggests cutaneous marginal zone B-cell lymphomas recognise similar antigens. Br J Haematol. 2006; 132(5): 571-5. PubMed

Bahler D, Szankasi P, Kulkarni S, Tubbs R, Cook J, Swerdlow S. Use of similar immunoglobulin VH gene segments by MALT lymphomas of the ocular adnexa. Mod Pathol. 2009; 22(6): 833-8. PubMed

Barth M, Goldman S, Smith L, Perkins S, Shiramizu B, Gross T, Harrison L, Sanger W, Geyer M, Giulino-Roth L, Cairo M. Rituximab pharmacokinetics in children and adolescents with de novo intermediate and advanced mature B-cell lymphoma/leukaemia: a Children's Oncology Group report. Br J Haematol. 2013; 162(5): 678-83. PubMed

Cairo M, Gerrard M, Sposto R, Auperin A, Pinkerton R, Michon J, Weston C, Perkins S, Raphael M, McCarthy K, Patte C, FAB LMB96 International Study Committee. Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents. Blood. 2007; 109(7): 2736-43. PubMed

Chang C, Kampalath B, Schultz C, Bunyi-Teopengco E, Logan B, Eshoa C, Dincer A, Perkins S. Expression of p53, c-Myc, or Bcl-6 suggests a poor prognosis in primary central nervous system diffuse large B-cell lymphoma among immunocompetent individuals. Arch Pathol Lab Med. 2003; 127(2): 208-12. PubMed

Chang C, McClintock S, Cleveland R, Trzpuc T, Vesole D, Logan B, Kajdacsy-Balla A, Perkins S. Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma. Am J Surg Pathol. 2004; 28(4): 464-70. PubMed

Chen E, Lim M, Rosic-Kablar S, Liu J, Jolicoeur P, Dubé I, Hough M. Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice. Oncogene. 2006; 25(18): 2575-87. PubMed

Curry C, Ewton A, Olsen R, Logan B, Preti H, Liu Y, Perkins S, Chang C. Prognostic impact of C-REL expression in diffuse large B-cell lymphoma. J Hematop. 2009; 2(1): 20-6. PubMed

Deffenbacher K, Iqbal J, Sanger W, Shen Y, Lachel C, Liu Z, Liu Y, Lim M, Perkins S, Fu K, Smith L, Lynch J, Staudt L, Rimsza L, Jaffe E, Rosenwald A, Ott G, Delabie J, Campo E, Gascoyne R, Cairo M, Weisenburger D, Greiner T, Gross T, Chan W. Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic profiling. Blood. 2012; 119(16): 3757-66. PubMed

Dunphy C, Perkins S. Large cell variants of CD5+, CD23- B-cell lymphoma/leukemia. Arch Pathol Lab Med. 2001; 125(4): 513-8. PubMed

Everton K, Abbott D, Crockett D, Elenitoba-Johnson K, Lim M. Quantitative proteomic analysis of follicular lymphoma cells in response to rituximab. J Chromatogr B Analyt Technol Biomed Life Sci. 2009; 877(13): 1335-43. PubMed

Frost M, Newell J, Lones M, Tripp S, Cairo M, Perkins S. Comparative immunohistochemical analysis of pediatric Burkitt lymphoma and diffuse large B-cell lymphoma. Am J Clin Pathol. 2004; 121(3): 384-92. PubMed

Galardy P, Hochberg J, Perkins S, Harrison L, Goldman S, Cairo M. Rasburicase in the prevention of laboratory/clinical tumour lysis syndrome in children with advanced mature B-NHL: a Children's Oncology Group Report. Br J Haematol. 2013; 163(3): 365-72. PubMed

Gerrard M, Cairo M, Weston C, Auperin A, Pinkerton R, Lambilliote A, Sposto R, McCarthy K, Lacombe M, Perkins S, Patte C, FAB LMB96 International Study Committee. Excellent survival following two courses of COPAD chemotherapy in children and adolescents with resected localized B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study. Br J Haematol. 2008; 141(6): 840-7. PubMed

Gerrard M, Waxman I, Sposto R, Auperin A, Perkins S, Goldman S, Harrison L, Pinkerton R, McCarthy K, Raphael M, Patte C, Cairo M, French-American-British/Lymphome Malins de Burkitt 96 (FAB/LMB 96) International Study Committee. Outcome and pathologic classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy. Blood. 2013; 121(2): 278-85. PubMed

Kiel M, Velusamy T, Betz B, Zhao L, Weigelin H, Chiang M, Huebner-Chan D, Bailey N, Yang D, Bhagat G, Miranda R, Bahler D, Medeiros J, Lim M, Elenitoba-Johnson K. Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma. J Exp Med. 2012; 209(9): 1553-65. PubMed

Leventaki V, Rodic V, Tripp S, Bayerl M, Perkins S, Barnette P, Schiffman J, Miles R. TP53 pathway analysis in paediatric Burkitt lymphoma reveals increased MDM4 expression as the only TP53 pathway abnormality detected in a subset of cases. Br J Haematol. 2012; 158(6): 763-71. PubMed

Meda B, Frost M, Newell J, Bohling S, Huebner-Chan D, Perkins S, Lim M, Medeiros J, Elenitoba-Johnson K. BCL-2 is consistently expressed in hyperplastic marginal zones of the spleen, abdominal lymph nodes, and ileal lymphoid tissue. Am J Surg Pathol. 2003; 27(7): 888-94. PubMed

Miles R, Raphael M, McCarthy K, Wotherspoon A, Lones M, Terrier-Lacombe M, Patte C, Gerrard M, Auperin A, Sposto R, Davenport V, Cairo M, Perkins S, SFOP/LMB96/CCG5961/UKCCSG/NHL 9600 Study Group. Pediatric diffuse large B-cell lymphoma demonstrates a high proliferation index, frequent c-Myc protein expression, and a high incidence of germinal center subtype: Report of the French-American-British (FAB) international study group. Pediatr Blood Cancer. 2008; 51(3): 369-74. PubMed

Mosse C, Stumph J, Best H, Vnencak-Jones C. A B-cell lymphoma diagnosed in "floater" tissue: implications of the diagnosis and resolution of a laboratory error. Am J Med Sci. 2009; 338(3): 248-51. PubMed

Patte C, Auperin A, Gerrard M, Michon J, Pinkerton R, Sposto R, Weston C, Raphael M, Perkins S, McCarthy K, Cairo M, FAB/LMB96 International Study Committee. Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood. 2007; 109(7): 2773-80. PubMed

Poirel H, Cairo M, Heerema N, Swansbury J, Aupérin A, Launay E, Sanger W, Talley P, Perkins S, Raphaël M, McCarthy K, Sposto R, Gerrard M, Bernheim A, Patte C, FAB/LMB 96 International Study Committee. Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study. Leukemia. 2009; 23(2): 323-31. PubMed

Rowe L, Willmore-Payne C, Tripp S, Perkins S, Bentz J. Tumor cell nuclei extraction from paraffin-embedded lymphoid tissue for fluorescence in situ hybridization. Appl Immunohistochem Mol Morphol. 2006; 14(2): 220-4. PubMed

Salama M, Lossos I, Warnke R, Natkunam Y. Immunoarchitectural patterns in nodal marginal zone B-cell lymphoma: a study of 51 cases. Am J Clin Pathol. 2009; 132(1): 39-49. PubMed

Swierczek S, Nausova J, Jelinek J, Liu E, Roda P, Kucerova J, Jarosova M, Urbankova H, Indrak K, Prchal J, Divoky V. Concomitant JAK2 V617F-positive polycythemia vera and B-cell chronic lymphocytic leukemia in three patients originating from two separate hematopoietic stem cells. Am J Hematol. 2013; 88(2): 157-8. PubMed

Szankasi P, Reading S, Vaughn C, Prchal J, Bahler D, Kelley T. A quantitative allele-specific PCR test for the BRAF V600E mutation using a single heterozygous control plasmid for quantitation: a model for qPCR testing without standard curves. J Mol Diagn. 2013; 15(2): 248-54. PubMed

Vaughn C, Crockett D, Lim M, Elenitoba-Johnson K. Analytical characteristics of cleavable isotope-coded affinity tag-LC-tandem mass spectrometry for quantitative proteomic studies. J Mol Diagn. 2006; 8(4): 513-20. PubMed

Vaughn C, Crockett D, Lin Z, Lim M, Elenitoba-Johnson K. Identification of proteins released by follicular lymphoma-derived cells using a mass spectrometry-based approach. Proteomics. 2006; 6(10): 3223-30. PubMed

Wallentine J, Perkins S, Tripp S, Bruggman R, Bayerl M. Diffuse large B-cell lymphoma with coexpression of CD3 in a pediatric patient: a case report, review of the literature, and tissue microarray study. J Pediatr Hematol Oncol. 2009; 31(2): 124-7. PubMed

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Last Update: January 2016