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 Topics
  • Videos

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

  • 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)

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

Recommended Use 

Aid in evaluation of hematopoietic neoplasms (ie, leukemia, lymphoma)

Specimens include peripheral blood, bone marrow or tissue

Monitor therapy in patients with established diagnosis of hematopoietic neoplasms

Markers selected based on provided clinical history and/or previous test results

Antigens included

T cell: CD1, CD2, CD3, CD4, CD5, CD7, CD8, TCR α-β, TCR γ-δ,, cytoplasmic CD3

B cell: CD10, CD19, CD20, CD22, CD23, CD103, kappa, lambda, FMC7, cytoplasmic kappa, cytoplasmic lambda

Myelo/Mono: CD11b, CD13, CD14 (Mo2), CD14 (MY4), CD15, CD33, CD64, CD117, myeloperoxidase

Misc: CD11c, CD16, CD25, CD30, CD34, CD38, CD41, CD42b, CD45, CD56, CD57, CD61, HLA-DR, glycophorin, TdT, bcl-2, ALK-1, CD123, CD138, CD200, CD26, CD45

Clinical sensitivity – limit of detection 0.01-1.0% depending on phenotype and disease

Chromosome FISH, Interphase 2002298
Method: Fluorescence in situ Hybridization

Recommended Use 

Use for ordering individual or multiple oncology FISH probes if standard FISH panels are not desired

Fresh tissue sample required

Indicate names of probes needed for testing

ARUP Oncology FISH Probes menu

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

Recommended Use 

Aid in the diagnosis of lymphoproliferative disorders

Aid in differentiating malignant from reactive lymphoid proliferations

Equally sensitive for both kappa and lambda restricted populations

Clinical sensitivity - >95% for mature B-cell non-Hodgkin lymphomas

Analytical sensitivity - clone must represent at least 1-5% of population examined\

Analytic specificity - >98%

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

Recommended Use 

Diagnose mantle cell lymphoma in conjunction with morphology and immunohistochemical studies

Formalin-fixed, paraffin-embedded (FFPE) tissue specimens only

Stained and returned to client pathologist for interpretation; consultation available if needed

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

Recommended Use 

Diagnose follicular lymphoma in conjunction with clinical, morphologic, and flow cytometric data

Most sensitive method to detect IGH-BCL2 fusion in FFPE tissue specimens

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

Recommended Use 

Diagnose Burkitt lymphoma (BL) or diffuse large B-cell lymphoma (DLBCL) with features intermediate between BL and DLBCL in conjunction with clinical, morphologic, and flow cytometric data

Requires FFPE tissue

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

Recommended Use 

Diagnose BL or DLBCL with features intermediate between BL and DLBCL in conjunction with clinical, morphologic, and flow cytometric data

Detects all MYC rearrangements including t(8;14), t(2;8), and t(8;22) rearrangements; does not identify translocation partner

Requires FFPE tissue

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

Recommended Use 

Diagnose BL or DLBCL with features intermediate between BL and DLBCL in conjunction with clinical, morphologic, and flow cytometric data

Sensitive method to detect MYC rearrangement in FFPE

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

Recommended Use 

Aid in diagnosis of aggressive large B-cell lymphoma with intermediate features between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL) and confirmation of suspected double hit lymphoma

Reflex pattern – if MYC (8q24) gene rearrangements 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

Specimens – formalin-fixed, paraffin-embedded (FFPE) tissue specimens

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

Recommended Use 

Aid in diagnosis of aggressive large B-cell lymphoma with intermediate features between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL) and confirmation of suspected double hit lymphoma

For reflex test, refer to Aggressive B-Cell Lymphoma FISH Reflex, Tissue

Specimens – bone marrow or whole blood specimens; other specimens may be acceptable

Probes in this panel include MYC, BCL2, IGH, BCL6

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

Recommended Use 

Confirm diagnosis of hairy cell leukemia (HCL)

Monitor tumor burden in patients with HCL

Analytic sensitivity – 0.2% mutant allele

Limitations 

Limit of detection – 0.2% mutant allele

ZAP-70 Analysis by Flow Cytometry (Temporary Referral as of 08/05/16) 0092392
Method: Flow Cytometry

Recommended Use 

Determine risk group in newly diagnosed CLL

Results should always be correlated with morphologic and clinical information

Limitations 

Cell viability must be >98%

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

Recommended Use 

Determine risk group in newly diagnosed CLL

Results should always be correlated with morphologic and clinical information

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)

Recommended Use 

Preferred test at time of diagnosis for detecting prognostically important genomic abnormalities in leukemias/lymphomas and solid tumors involving loss/gain of DNA; loss of heterozygosity

Monitor disease progression and response to therapy

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

Recommended Use 

Alternate test to detect prognostically important genomic abnormalities in CLL

Probes include ATM (11q22.3), chromosome 12 centromere (trisomy 12), D13S319 (13q14.3), and p53 (17p13.1)

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

Recommended Use 

Aids in diagnosis of mantle cell lymphoma (MCL) if cyclin testing is noninformative

FFPE specimen required

Analytic sensitivity – 20%

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

Recommended Use 

Aids in diagnosis of MCL if cyclin testing is noninformative

Blood, bone marrow, fresh frozen tissue, and FFPE tissue specimens are acceptable

Analytical sensitivity – 1 in 105

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

Recommended Use 

Aid histologic diagnosis of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

BCL-2 by Immunohistochemistry 2004513
Method: Immunohistochemistry

Recommended Use 

Aids in identifying colorectal adenomas, carcinomas; distinguishes follicular lymphoma from reactive follicles

Stained and returned to client pathologist for interpretation; consultation available if needed

BCL-6 by Immunohistochemistry 2003457
Method: Immunohistochemistry

Recommended Use 

Aid in identifying large cell lymphomas, BL, and Hodgkin lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

CD3 by Immunohistochemistry 2003508
Method: Immunohistochemistry

Recommended Use 

Aid histologic diagnosis of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

CD5 by Immunohistochemistry 2003514
Method: Immunohistochemistry

Recommended Use 

Aid histologic diagnosis of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

CD10 (CALLA) by Immunohistochemistry 2003523
Method: Immunohistochemistry

Recommended Use 

Aid histologic diagnosis of lymphoblastic lymphoma, BL, follicular lymphoma, and CML

Aid differential diagnosis of small B-cell lymphomas and subtyping of lymphoblastic leukemias

Stained and returned to client pathologist for interpretation; consultation available if needed

CD19 by Immunohistochemistry 2005114
Method: Immunohistochemistry

Recommended Use 

Aid histologic diagnosis of B-cell leukemia/lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

CD20, L26 by Immunohistochemistry 2003532
Method: Immunohistochemistry

Recommended Use 

Aid in identifying common acute lymphoblastic leukemia, pre-B ALL, CLL, prolymphocytic leukemia, hairy cell leukemia, lymphoma cell leukemia, B-cell lymphomas, including BL, Waldenstrom, macroglobulinemia, and immunoblastic B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

CD21 (Dendritic Cell) by Immunohistochemistry 2003535
Method: Immunohistochemistry

Recommended Use 

Aid in identifying B-cell CLL, follicular lymphoma, low-grade MALT-type B-cell lymphoma, primary salivary gland and gastric lymphoma, T-cell and histiocyte-rich B-cell lymphoma, angioimmunoblastic T-cell lymphoma, nodular lymphocyte-predominant Hodgkin lymphoma, follicular dendritic sarcoma and some Reed-Sternberg cells not expressing other B- or T-cell-associated markers

Stained and returned to client pathologist for interpretation; consultation available if needed

CD23 by Immunohistochemistry 2003541
Method: Immunohistochemistry

Recommended Use 

Aid in differentiating small lymphocytic lymphoma (+) and mantle cell lymphoma (-)

Stained and returned to client pathologist for interpretation; consultation available if needed

CD25 by Immunohistochemistry 2003544
Method: Immunohistochemistry

Recommended Use 

Aid histologic diagnosis of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

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

Recommended Use 

Aid histologic diagnosis of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

CD79A by Immunohistochemistry 2003800
Method: Immunohistochemistry

Recommended Use 

Aid in identifying acute leukemia of precursor B-cell type, B-cell lymphomas and some myelomas

Stained and returned to client pathologist for interpretation; consultation available if needed

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

Recommended Use 

Aid histologic diagnosis of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

CD200 by Immunohistochemistry 2012844
Method: Immunohistochemistry

Recommended Use 

Primarily aids the distinction between CLL/SLL and mantle cell lymphoma where CD200 is usually positive in CLL/SLL and negative in mantle cell lymphoma; CD200 is also positive in other B-cell lymphoproliferative disorders

Stained and returned to client pathologist for interpretation; consultation available if needed

Herpes Virus 8 by Immunohistochemistry 2003932
Method: Immunohistochemistry

Recommended Use 

Aid histologic diagnosis of multicentric Castleman disease, angioimmunoblastic lymphadenopathies, and Kaposi sarcoma

Stained and returned to client pathologist for interpretation; consultation available if needed

Kappa Light Chains by Immunohistochemistry 2003981
Method: Immunohistochemistry

Recommended Use 

Aid histologic diagnosis of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

Ki-67 with Interpretation by Immunohistochemistry 2007182
Method: Immunohistochemistry

Recommended Use 

Aids in the prognostic determination of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

Lambda Light Chains by Immunohistochemistry 2003984
Method: Immunohistochemistry

Recommended Use 

Aid histologic diagnosis of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

MUM1/IRF4 by Immunohistochemistry 2003975
Method: Immunohistochemistry

Recommended Use 

Aid histologic diagnosis of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

Pax-5 by Immunohistochemistry 2004082
Method: Immunohistochemistry

Recommended Use 

Aid histologic diagnosis of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

SOX11 by Immunohistochemistry 2012561
Method: Immunohistochemistry

Recommended Use 

Useful for cyclin D1-negative MCL that is difficult to distinguish from other small B-cell lymphomas

Highly specific marker for both cyclin D1-positive and negative MCL

Stained and returned to client pathologist for interpretation; consultation available if needed

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

Recommended Use 

Aid histologic diagnosis of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

Tartrate-Resistant Acid Phosphatase, Cytochemical Stain Only 2013275
Method: Cytochemical Stain

Recommended Use 

Use to identify hairy cell leukemia

TdT by Immunohistochemistry 2004142
Method: Immunohistochemistry

Recommended Use 

Aid histologic diagnosis of B-cell lymphoma

Stained and returned to client pathologist for interpretation; consultation available if needed

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: Mar 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: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Accessed: Jun 2015]

General References

Aukema SM, Siebert R, Schuuring E, van Imhoff GW, Kluin-Nelemans HC, Boerma E, Kluin PM. Double-hit B-cell lymphomas. Blood. 2011; 117(8): 2319-31. PubMed

Behdad A, Bailey NG. 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 RM. 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 RD, Rosenwald A, Poppema S, Lenz G. Prognostic biomarkers in malignant lymphomas. Leuk Lymphoma. 2010; 51 Suppl 1: 11-9. PubMed

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

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

Ondrejka SL, Hsi ED. 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 SA, Sabattini E, Pileri SA. 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

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References from the ARUP Institute for Clinical and Experimental Pathology®

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Cairo MS, Gerrard M, Sposto R, Auperin A, Pinkerton R, Michon J, Weston C, Perkins SL, 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 AP, Perkins SL. 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 RP, Trzpuc T, Vesole DH, Logan B, Kajdacsy-Balla A, Perkins SL. 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

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Curry CV, Ewton AA, Olsen RJ, Logan BR, Preti HA, Liu Y, Perkins SL, Chang C. Prognostic impact of C-REL expression in diffuse large B-cell lymphoma. J Hematop. 2009; 2(1): 20-6. PubMed

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

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

Galardy PJ, Hochberg J, Perkins SL, Harrison L, Goldman S, Cairo MS. 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

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Medical Reviewers

Hussong, Jerry W., MD, DDS, MS, Vice President, Chief Medical Officer and Director of Laboratories, and Medical Director, Hematologic Flow Cytometry at ARUP Laboratories ; Associate Professor of Clinical Pathology, University of Utah

Kelley, Todd, MD, MS, Medical Director, Molecular Hematopathology and Hematopathology at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Lamb, Allen N., PhD, FACMG, Medical Director, Cytogenetics and Genomic Microarray, ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Miles, Rodney R., MD, PhD, Staff Hematopathologist at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Perkins, Sherrie L., MD, PhD, Senior Vice President, Research and Development; Executive Director, ARUP Institute for Clinical and Experimental Pathology; Chief, Clinical Pathology Division; Section Chief, Hematopathology at ARUP Laboratories ; Vice Chair of Pathology and Professor of Clinical Pathology, University of Utah

Salama, Mohamed E., MD, Medical Director, Hematopathology and Immunohistochemistry Staining at ARUP Laboratories; Associate Professor of Clinical Pathology, Director of Hematopathology Fellowship Program, University of Utah

Acute Lymphoblastic Leukemia - ALL
Chronic Lymphocytic Leukemia - CLL
Cold Agglutinin Disease
Epstein-Barr Virus - EBV
Helicobacter pylori
Hemolytic Anemias
Human Immunodeficiency Virus - HIV
Lymphoma Phenotyping
Lymphomas, T-Cell/NK-Cell - T-Cell/NK-Cell Lymphomas
Paraneoplastic Neurological Syndromes and Associated Disorders - PNS
Tumor Markers
Miles
Perkins

Last Update: September 2016

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