Lymphomas, B-Cell - B-Cell Lymphomas
- 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) |
|
| Specific lymphomas associated with translocation |
|
|
|
| Other malignancies associated with translocation |
|
|
|
|
DIAGNOSTIC TESTING ARUP Tests
|
|||
| 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
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%)
- Five risk factors (each scored as one point)
- 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 – mutation status correlates inversely with prognosis
- Follicular lymphoma
Differential Diagnosis
- Infections
- Reactive lymphocytosis
- Malignancy
- Head and neck cancer
- Metastatic cancer
- Other lymphomas – T-cell, Hodgkin
- Sarcoidosis
- 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
Leukemia/Lymphoma Phenotyping by Flow Cytometry 2008003
Method: Flow Cytometry
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
Use to order individual or multiple oncology FISH probes if standard FISH panels are not desired
Fresh tissue sample required
Indicate names of probes needed for testing
B-Cell Clonality Screening (IgH and IgK) by PCR 2006193
Method: Polymerase Chain Reaction/Capillary Electrophoresis
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%
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
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
Diagnose follicular lymphoma in conjunction with clinical, morphologic, and flow cytometric data
Most sensitive method to detect IGH-BCL2 fusion in FFPE tissue specimens
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
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
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
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
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
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
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
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
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
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
Confirm diagnosis of hairy cell leukemia (HCL)
Monitor tumor burden in patients with HCL
Analytic sensitivity – 0.2% mutant allele
Limit of detection – 0.2% mutant allele
IGHV Mutation Analysis by Sequencing 0040227
Method: Polymerase Chain Reaction/Sequencing
Determine risk group in newly diagnosed CLL
Results should always be correlated with morphologic and clinical information
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)
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
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
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)
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
Aid in diagnosis of mantle cell lymphoma (MCL) if cyclin testing is noninformative
FFPE specimen required
Analytic sensitivity – 20%
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
Anaplastic Lymphoma Kinase 1 (ALK-1) by Immunohistochemistry 2003439
Method: Immunohistochemistry
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Use to identify hairy cell leukemia
TdT by Immunohistochemistry 2004142
Method: Immunohistochemistry
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 [Revised Mar 2010; Accessed: Dec 2016]
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 [Revised Oct 2013; Accessed: May 2017]
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
Savage KJ, Johnson NA, Ben-Neriah S, Connors JM, Sehn LH, Farinha P, Horsman DE, Gascoyne RD. 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 BA, 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 Hematopoietic and Lymphoid Tissues, 4th. Lyon, France: IARC Press, 2008.
Wilcox RA. 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 DW, Kim BK, Gao A, Swerdlow SH. 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 DW, Szankasi P, Kulkarni S, Tubbs RR, Cook JR, Swerdlow SH. Use of similar immunoglobulin VH gene segments by MALT lymphomas of the ocular adnexa. Mod Pathol. 2009; 22(6): 833-8. PubMed
Barth MJ, Goldman S, Smith L, Perkins S, Shiramizu B, Gross TG, Harrison L, Sanger W, Geyer MB, Giulino-Roth L, Cairo MS. 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 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
Chen E, Lim MS, Rosic-Kablar S, Liu J, Jolicoeur P, Dubé ID, Hough MR. Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice. Oncogene. 2006; 25(18): 2575-87. PubMed
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
Deffenbacher KE, Iqbal J, Sanger W, Shen Y, Lachel C, Liu Z, Liu Y, Lim MS, Perkins SL, Fu K, Smith L, Lynch J, Staudt LM, Rimsza LM, Jaffe E, Rosenwald A, Ott GK, Delabie J, Campo E, Gascoyne RD, Cairo MS, Weisenburger DD, Greiner TC, Gross TG, Chan WC. Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic profiling. Blood. 2012; 119(16): 3757-66. PubMed
Dunphy CH, Perkins SL. Large cell variants of CD5+, CD23- B-cell lymphoma/leukemia. Arch Pathol Lab Med. 2001; 125(4): 513-8. PubMed
Everton KL, Abbott DR, Crockett DK, Elenitoba-Johnson KS, Lim MS. 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 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
Gerrard M, Cairo MS, Weston C, Auperin A, Pinkerton R, Lambilliote A, Sposto R, McCarthy K, Lacombe MT, Perkins SL, 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 IM, Sposto R, Auperin A, Perkins SL, Goldman S, Harrison L, Pinkerton R, McCarthy K, Raphael M, Patte C, Cairo MS, 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
Gomez-Gelvez JC, Salama ME, Perkins SL, Leavitt M, Inamdar KV. Prognostic Impact of Tumor Microenvironment in Diffuse Large B-Cell Lymphoma Uniformly Treated With R-CHOP Chemotherapy. Am J Clin Pathol. 2016; 145(4): 514-23. PubMed
Kiel MJ, Velusamy T, Betz BL, Zhao L, Weigelin HG, Chiang MY, Huebner-Chan DR, Bailey NG, Yang DT, Bhagat G, Miranda RN, Bahler DW, Medeiros J, Lim MS, Elenitoba-Johnson KS. Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma. J Exp Med. 2012; 209(9): 1553-65. PubMed
Klinger M, Zheng J, Elenitoba-Johnson KS, Perkins SL, Faham M, Bahler DW. Next-generation IgVH sequencing CLL-like monoclonal B-cell lymphocytosis reveals frequent oligoclonality and ongoing hypermutation. Leukemia. 2016; 30(5): 1055-61. PubMed
Leventaki V, Rodic V, Tripp SR, Bayerl MG, Perkins SL, Barnette P, Schiffman JD, Miles RR. 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
Liew M, Rowe L, Clement PW, Miles RR, Salama ME. Validation of break-apart and fusion MYC probes using a digital fluorescence in situ hybridization capture and imaging system. J Pathol Inform. 2016; 7: 20. PubMed
Meda BA, Frost M, Newell J, Bohling SD, Huebner-Chan DR, Perkins SL, Lim MS, Medeiros J, Elenitoba-Johnson KS. 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
Meyer JA, Zhou D, Mason CC, Downie JM, Rodic V, Abromowitch M, Wistinghausen B, Termuhlen AM, Angiolillo AL, Perkins SL, Lones MA, Barnette P, Schiffman JD, Miles RR. Genomic characterization of pediatric B-lymphoblastic lymphoma and B-lymphoblastic leukemia using formalin-fixed tissues. Pediatr Blood Cancer. 2016; PubMed
Meznarich J, Miles R, Paxton CN, Afify Z. Pediatric B-Cell Lymphoma With Lymphoblastic Morphology, TdT Expression, MYC Rearrangement, and Features Overlapping With Burkitt Lymphoma. Pediatr Blood Cancer. 2016; 63(5): 938-40. PubMed
Miles RR, Raphael M, McCarthy K, Wotherspoon A, Lones MA, Terrier-Lacombe MJ, Patte C, Gerrard M, Auperin A, Sposto R, Davenport V, Cairo MS, Perkins SL, 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
Miles RR, Shah RK, Frazer K. Molecular genetics of childhood, adolescent and young adult non-Hodgkin lymphoma. Br J Haematol. 2016; 173(4): 582-96. PubMed
Mosse CA, Stumph JR, Best H, Vnencak-Jones CL. 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 SL, McCarthy K, Cairo MS, 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 HA, Cairo MS, Heerema NA, Swansbury J, Aupérin A, Launay E, Sanger WG, Talley P, Perkins SL, 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 LR, Willmore-Payne C, Tripp SR, Perkins SL, Bentz JS. 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 ME, Lossos IS, Warnke RA, 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 JT, 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 CP, Prchal JT, Bahler DW, Kelley TW. 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 CP, Crockett DK, Lim MS, Elenitoba-Johnson KS. 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 CP, Crockett DK, Lin Z, Lim MS, Elenitoba-Johnson KS. Identification of proteins released by follicular lymphoma-derived cells using a mass spectrometry-based approach. Proteomics. 2006; 6(10): 3223-30. PubMed
Wallentine JC, Perkins SL, Tripp SR, Bruggman RD, Bayerl MG. 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
Zhou D, Paxton CN, Kelley TW, Afify Z, South ST, Miles RR. Two Unrelated Burkitt Lymphomas Seven Years Apart in a Patient With X-Linked Lymphoproliferative Disease Type 1 (XLP1). Am J Clin Pathol. 2016; 146(2): 248-53. PubMed
Medical Reviewers
- Human Immunodeficiency Virus in Adults Testing Algorithm
- Human Immunodeficiency Virus in Infants Testing Algorithm
- Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
- Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm
Last Update: July 2017