Lymphomas, B-Cell

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Leukemia and Lymphoma Phenotyping Algorithm

Clinical Background

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

Epidemiology

Incidence -90% of the 755,000 cases of NHL diagnosed yearly
Age - 60s
Sex - slight predominance of males

Classification

Mature B-Cell Neoplasms (WHO classification)
- Diffuse large B-cell lymphoma - 30-40% of NHL
- Follicular lymphoma - 20-25% of NHL
- B-cell chronic lymphocytic leukemia; small lymphocytic lymphoma
- Plasma cell myeloma - plasmacytoma
- Mantle cell lymphoma - 6-8% of NHL
- Splenic marginal zone B-cell lymphoma - rare
- Lymphoplasmacytic lymphoma - rare
- Hairy cell leukemia - rare
- Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type - 8-10% of NHL
- Nodal marginal zone lymphoma (+/- monocytoid B-cells)
- Primary effusion lymphoma - rare
- Burkitt's lymphoma - rare

Risk Factors

Presence of autoimmune diseases or iatrogenic or acquired immune deficiency
- Sjögren syndrome
- Celiac disease
- Rheumatoid arthritis
- Post-transplant immunosuppression
- Immunosuppressive drugs
- HIV infection
Inherited disorders
- Chédiak-Higashi syndrome
- Common variable immune deficiency (CVID)
- Wiskott-Aldrich syndrome
Chronic infection
- Epstein-Barr virus - primary CNS diffuse large B-cell lymphoma
- Helicobacter pylori - gastric mucosa-associated lymphoid tissue (MALT) lymphoma
- Hepatitis C - lymphoplasmacytic lymphoma
- HHV8 - primary effusion lymphomas

Clinical Presentation

Nonspecific fever, fatigue, weight loss
Lymphadenopathy (peripheral)
- Sometimes bulky
Extranodal disease
- Commonly in GI tract and bone marrow

See Also

Epstein-Barr Virus - EBV

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Leukemia and Lymphoma Phenotyping Algorithm

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Leukemia/Lymphoma Phenotyping (Comprehensive-Whole Blood)

ARUP #: 0096299

Methodology: Flow Cytometry

Use:

Identify specific phenotypes associated with B-cell NHL and establish tumor lineage to aid in selection of appropriate therapy, assessment of clinical behavior and prognosis

Available antigens for B-cell: CD10, CD19, CD20, CD22, CD23, CD24, CD79b, CD103, Kappa, Lambda, FMC7, Cytoplasmic Kappa, Cytoplasmic Lambda

Test name: Leukemia/Lymphoma Phenotyping (Comprehensive - Bone Marrow)

ARUP #: 0095244

Methodology: Flow Cytometry

Use:

Identify specific phenotypes associated with B-cell NHL and establish tumor lineage to aid in selection of appropriate therapy, assessment of clinical behavior and prognosis

Available antigens for B-cell: CD10, CD19, CD20, CD22, CD23, CD24, CD79b, CD103, Kappa, Lambda, FMC7, Cytoplasmic Kappa, Cytoplasmic Lambda

Test name: bcl-2/JH, t(14;18) Translocation by PCR, Fluid

ARUP #: 0055616

Methodology: Polymerase Chain Reaction

Use:

Identify the translocation that characterizes most follicular lymphomas and many diffuse large B-cell lymphomas

Detect a majority of bcl/JH gene rearrangements

Limitations:

However, some breakpoints which occur at distant loci will not be identified

Test name: bcl-2/JH, t(14;18) Translocation by PCR, Tissue

ARUP #: 0055619

Methodology: Polymerase Chain Reaction

Use:

Identify the translocation that characterizes most follicular lymphomas and many diffuse large B-cell lymphomas

Detect a majority of bcl-2/JH gene rearrangements

Limitations:

Some breakpoints which occur at distant loci will not be identified

Test name: Chromosome Analysis, FISH-Interphase

ARUP #: 0092615

Methodology: Fluorescence in situ Hybridization

Use:

Detect translocation breakpoints in leukemia (eg, t(9;22) or t(15;17)), and clonal aneuploidy in leukemia

Test name: IgVH Mutation Analysis by Sequencing

ARUP #: 0040227

Methodology: Polymerase Chain Reaction/Sequencing

Use:

Assist in the clinical management of patients with established diagnoses of chronic lymphocytic leukemia. Results of this test should always be correlated with morphologic and clinical information.

Test name: ZAP-70 Analysis by Flow Cytometry

ARUP #: 0092392

Methodology: Flow Cytometry

Use:

Assist in the clinical management of patients with established diagnoses of chronic lymphocytic leukemia. Results of this test should always be correlated with morphologic and clinical information.

Test name: Chromosome Analysis, Chronic Lymphocytic Leukemia (CLL) Panel by FISH

ARUP #: 0092616

Methodology: Fluorescence in situ Hybridization

Use:

Use for CLL prognosis; specific genomic abnormalities tested include ATM, D13S25, Trisomy 12, p53

Test name: t(11;14) IgH-CCND1 Translocation by FISH

ARUP #: 0049381

Methodology: Fluorescence in situ Hybridization

Use:

Identification of the translocation that characterizes mantle cell lymphomas - t(11;14) IgH-CCND1

Fixed tissue sample required

Test name: bcl-1/JH, t(11;14) Translocation by PCR, Fluid

ARUP #: 0055557

Methodology: Polymerase Chain Reaction

Use:

Identification of the translocation that characterizes mantle cell lymphomas - t(11;14) IgH-CCND1

Test name: bcl-2/JH, t(14;18) Translocation by PCR, Paraffin

ARUP #: 0055625

Methodology: Polymerase Chain Reaction

Use:

Identification of the translocation that characterizes most follicular lymphomas and many diffuse large B-cell lymphomas - bcl/JH, t(14;18)

Fixed tissue sample required

Test name: Epstein-Barr Virus (EBV) Probe, Paraffin

ARUP #: 8030630

Methodology: In situ Hybridization

Use:

Immunosuppression related NHL

Requires paraffin-embedded tissue sample

Test name: Kappa Light Chain Immunoglobulin mRNA by in situ Hybridization

ARUP #: 8033750

Methodology: in situ Hybridization

Use:

Identify increasing concentrations of monoclonal free kappa or free lambda light chains in the serum of patients with evolving or relapsing myelomas

Additional Tests Available

Test name: B-Cell CD20 Expression

ARUP #: 0092099

Methodology: Flow Cytometry

Comments:

Test name: B-Cell Clonality Screening Assay by PCR, Fluid

ARUP #: 0055552

Methodology: Polymerase Chain Reaction

Comments:

Test name: B-Cell Clonality Screening Assay by PCR, Paraffin

ARUP #: 0055626

Methodology: Polymerase Chain Reaction

Comments:

Test name: B-Cell Clonality Screening Assay by PCR, Tissue

ARUP #: 0055556

Methodology: Polymerase Chain Reaction

Comments:

Test name: Leukemia/Lymphoma Phenotyping (Comprehensive - Miscellaneous)

ARUP #: 0095243

Methodology: Flow Cytometry

Comments:

Test name: B-Cell Clonality Assessment by Restriction Fragment Southern Blot Hybridization, Fluid

ARUP #: 0055592

Methodology: Restriction Fragment Southern Blot Hybridization

Comments:

Test name: B-Cell Clonality Assessment by Restriction Fragment-Southern Blot Hybridization, Tissue

ARUP #: 0055590

Methodology: Restriction Fragment Southern Blot Hybridization

Comments:

Test name: Chromosome Analysis, Bone Marrow

ARUP #: 0097605

Methodology: Giemsa-Band Analysis

Comments: To identify neoplastic populations in marrow

Test name: B-Cell & T-Cell Clonality Assessment by PCR, Fluid

ARUP #: 0055610

Methodology: Polymerase Chain Reaction

Comments:

Test name: B-Cell & T-Cell Clonality Assessment by PCR, Tissue

ARUP #: 0055611

Methodology: Polymerase Chain Reaction

Comments: For known B-cell disease, use B-cell tests listed above

Test name: B-Cell & T-Cell Clonality Assessment by PCR, Paraffin

ARUP #: 0055627

Methodology: Polymerase Chain Reaction

Comments: For known B-cell disease, use B-cell tests listed above

Test name: B-Cell & T-Cell Comprehensive Clonality Assessment, Fluid

ARUP #: 0055612

Methodology: Polymerase Chain Reaction/Restriction Fragment Southern Blot Hybridization

Comments: For known B-cell disease, use B-cell tests listed abovePanel includes B-cell and T-cell screening assays and clonality assessment by restriction fragment southern blot hybridization testing

Test name: B-Cell & T-Cell Comprehensive Clonality Assessment, Tissue

ARUP #: 0055613

Methodology: Polymerase Chain Reaction/Restriction Fragment Southern Blot Hybridization

References

General References

Abbott BL. Diagnosis and management of lymphoma. Clin Lymphoma Myeloma. 2006;7(1):30-32.

Ansell SM, Armitage J. Non-Hodgkin lymphoma: diagnosis and treatment. Mayo Clin Proc. 2005;80(8):1087-1097.

Copson E. Non-Hodgkin's lymphoma (diffuse large B cell lymphoma). Clin Evid. 2006;(15):30-44.

De Paepe P, De Wolf-Peeters C. Diffuse large B-cell lymphoma: a heterogeneous group of non-Hodgkin lymphomas comprising several distinct clinicopathological entities. Leukemia. 2007;21(1):37-43.

Henrickson SE, Hartmann EM, Ott G, Rosenwald A. Gene expression profiling in malignant lymphomas. Adv Exp Med Biol. 2007;593:134-146.

Inokuchi T, Shincho M, Moriwaki Y, Ka T, Takahashi S, Tsutsumi Z, Lin Y, Hirota S, Yamamoto T. Coexistent B-cell lymphoma and cutaneous T-cell lymphoma. Intern Med. 2006;45(9):641-647.

Lossos IS, Morgensztern D. Prognostic biomarkers in diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(6):995-1007.

Sharpe RW, Bethel KJ. Hairy cell leukemia: diagnostic pathology. Hematol Oncol Clin North Am. 2006;20(5):1023-1049.

Vose JM, Neumann M, Harris ME. Update on lymphoma management: diffuse large B-cell NHL. Hematology. 2005;10 Suppl 1:10-14.

Wundisch T, Stolte M. Current status of gastric MALT lymphoma. Curr Gastroenterol Rep. 2006;8(5):343-346.

Yang W, Listinsky CM. Aggressive B-cell lymphomas. Adv Exp Med Biol. 2005;563:125-134.

References from the ARUP Institute for Clinical and Experimental Pathology Research®

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):571-575.

Chang CC, 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):208-212.

Chang CC, 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):464-470.

Chen E, Lim MS, Rosic-Kablar S, Liu J, Jolicoeur P, Dube ID, Hough MR. Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice. Oncogene. 2006;25(18):2575-2587.

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):384-392.

Meda BA, Frost M, Newell J, Bohling SD, Huebner-Chan DR, Perkins SL, Lim MS, Medeiros LJ, 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):888-894.

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):220-224.

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):513-520.

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):3223-3230.

Medical Reviewers

Bahler, David W., M.D., Ph.D. Medical Director, Hematologic Flow Cytometry, and Acting Medical Director, Molecular Hematopathology at ARUP Laboratories; Associate Professor, Pathology, University of Utah

Perkins, Sherrie L. , M.D., Ph.D. Medical Director, Hematopathology at ARUP Laboratories; Professor, Anatomic Pathology, University of Utah

Comprehensive Review: September 2008
Last Update: September 2008