Test Center

My Recent Searches

  • No Recent Search.

My Tests Viewed

  • No Test Viewed.

Lymphoid Neoplasms: Laboratory Support of Diagnosis and Management

Lymphoid Neoplasms: Laboratory Support of Diagnosis and Management

Test Guide

Lymphoid Neoplasms
Laboratory Support of Diagnosis and Management

  

Lymphoid neoplasms are derived from the clonal expansion and proliferation of B- and T-lymphocytes. They encompass a heterogeneous group of lymphomas and leukemias including B-cell, T-cell, and natural killer (NK)-cell disorders.

B-cell neoplasms, which comprise the majority of all lymphoid neoplasms, are a diverse group of tumors that include acute lymphoblastic leukemias/lymphomas and mature B-cell leukemias/lymphomas. To varying degrees, these neoplasms recapitulate normal stages of B-cell differentiation and typically have distinctive immunophenotypes that permit classification according to their postulated cell of origin. In addition, cytogenetic profiles, genotype, and immunophenotype of the malignant cell have had considerable impact on prognostic and therapeutic stratifications of patients with B-cell neoplasms.

T-cell and NK-cell neoplasms also include acute lymphoblastic and mature lymphoid neoplasms. They are relatively uncommon, but many of them are among the most aggressive of all lymphoid neoplasms. Some, however, have a more protracted clinical course. Immunophenotypically, these neoplasms often show aberrant expression or loss of T-cell markers that aid in the differential diagnosis. Additionally, they may be associated with a viral infection. Epstein-Barr virus (EBV) is most often associated with NK-cell leukemias and extranodal NK/T-cell lymphomas. Human T-cell leukemia virus (HTLV-1) is etiologically linked to adult T-cell leukemia/lymphoma. Besides morphologic, immunophenotypic, and genetic characteristics, clinical features play an important part in the definition of these diseases.

Diagnosis and Management of Lymphoid Neoplasms

Suspicion of lymphoid leukemia and lymphoma may arise from clinical symptoms and/or an abnormal
complete blood count (Table 1). Immunophenotyping, morphologic evaluation, cytogenetics, and molecular analysis then form the foundation for the differential diagnosis. Methods used include immunohistochemistry, flow cytometry, chromosome study, fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), and gene sequencing.

Table 1. Clinical and Laboratory Indications of Lymphoid Neoplasms1

Clinical Symptoms and Findings

Peripheral Blood Characteristics (CBC)

  • Fatigue, fever, infection

  • Lymphocytosis ±

  • Bone pain, arthralgia

  • Anemia ±

  • Lymphadenopathy, hepatomegaly, splenomegaly

  • Neutropenia ±

  • Mass in mediastinum, lymph nodes, liver, spleen, Waldeyer’s ring, central nervous system, gonads

  • Thrombocytopenia ±

  • Skin lesions

  • Pleural effusion

CBC, complete blood count.

As outlined in the Figure, immunophenotyping differentiates B- and T-cell neoplasms. B-cell lineage is characterized by the presence of CD19, CD20, CD22, and CD79a as well as the absence of myeloid (eg, MPO) and T-cell (eg, CD3) lineage-specific markers. Likewise, T-cell lineage is characterized by the presence of markers such as CD2, CD3, CD5, and CD7 in the absence of B-cell and myeloid markers. Additional immunophenotypic markers facilitate further classification (Figure).

Figure. Laboratory evaluation of suspected lymphoid neoplasm.

Test codes are included in brackets; figure is based in part on
references 1 and 2.

Case review of immunophenotyping, morphology, molecular and chromosome analysis results usually confirms the diagnosis (Figure, Table 2). Additional tests may be needed in some cases; such tests are listed in Table 3 for B-cell neoplasms and Table 4 for T- and NK-cell neoplasms.

Laboratory test results also help assess prognosis and eligibility for specific therapies and monitor tumor load and therapeutic response. Tests available for these purposes are listed in Tables 3 and 4.

Table 2. Tests Available for Initial Diagnosis and Evaluation of Lymphoid Neoplasms

Test Code Assay Clinical Use

Morphology and Immunophenotyping Tests

35080X

Leukemia/Lymphoma Evaluationa,b

Includes CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11c, CD13, CD19, CD20, CD23, CD33, CD34, CD38, CD45,
CD56, CD64, CD117, HLA-DR, kappa, and lambda, with pathologist interpretation. Additional markers are tested,
at an additional charge, when deemed medically
necessary for the diagnosis.

Differential diagnosis of leukemia and lymphoma

16002X

Leukemia/Lymphoma Evaluation, Histogram
Only (No Interpretation)a,b

Includes CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11c, CD13, CD19, CD20, CD23, CD33, CD34, CD38, CD45,
CD56, CD64, CD117, HLA-DR, kappa, and lambda.

Differential diagnosis of leukemia and lymphoma

40031X

Lymphoma Panel, IHCa

Includes BCL-1, BCL-2, BCL-6, CD1a, CD3, CD4, CD5,
CD8, CD10, CD20, CD23, CD30, CD43, CD56, CD79a,
kappa (ISH), Ki67, lambda (ISH), Pax-5, TdT, and interpretation.

Differential diagnosis of leukemia and lymphoma

17734X

Comprehensive Hematopathology Report

Includes hematopathologist interpretation of morphologic and ancillary studies. Additional tests are performed, at
an additional charge, when deemed medically necessary
for the diagnosis. Such tests may include IHC and flow
cytometric markers as well as chromosomal, FISH, or
PCR genetic studies.

Diagnose hematologic disorders

3541X

Diagnostic Consultation, Paraffin Block or
Referred Slidesa

Includes hematopathologist interpretation of morphologic and IHC studies. Additional IHC tests are performed, at
an additional charge, when deemed medically necessary for the diagnosis.

Diagnose hematologic disorders

19771X

Hematopathology Morphologic Evaluation

Includes hematopathologist interpretation of bone
marrow and/or peripheral blood smear morphology.

Diagnose hematologic disorders

Molecular and Chromosome Tests

14868X

B-Cell Gene Rearrangement, Qualitative PCR,
Cell-basedc

Determine clonality

16119X

B-Cell Gene Rearrangement, Qualitative PCR,
Plasma-based, Leumeta®c

Determine clonality

14600X

Chromosome Analysis, Hematologic Malignancy

Differential diagnosis and classification of hematologic disorders

14601

Chromosome Analysis, CLL/LPD

Differential diagnosis and classification of lymphoid disorders

14602X

Chromosome Analysis, Lymph Node

Differential diagnosis and classification of lymphoid disorders

15930X

T-Cell Receptor (TCR) Gene Rearrangement,
Qualitative PCR, Cell-basedc

Determine clonality

17862X

T-Cell Receptor (TCR) Gene Rearrangement,
Qualitative PCR, Leumetac

Determine clonality

IHC, immunohistochemistry; FISH, fluorescence in situ hybridization; PCR, polymerase chain reaction; ISH, in situ hybridization; LPD, lymphoproliferative disease.
a This test was developed and its performance characteristics have been determined by Quest Diagnostics Nichols Institute. It has not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. Performance characteristics refer to the analytical performance of the test.
b Testing performed by flow cytometry.
c This test was developed and its performance characteristics have been determined by Quest Diagnostics Nichols Institute. Performance characteristics refer to the analytical performance of the test.

Table 3. Additional Tests Available for Diagnosis and Evaluation of B-Cell Neoplasms
Test Code Assay Clinical Use

B-Cell Acute Lymphoblastic Leukemia (B-ALL)

16029X

ABL Kinase Domain Mutation in CML,
Cell-baseda

Predict imatinib drug-resistance in patients with Ph-positive ALL; identify patients who may benefit from alternative therapy

16031X

ABL Kinase Domain Mutation in CML,
Plasma-based, Leumetaa

Predict imatinib drug-resistance in patients with Ph-positive ALL; identify patients who may benefit from alternative therapy

19783X

ABL T315I Mutation in CML, Cell-baseda

Predict a high degree of resistance to imatinib and related drugs in patients with Ph-positive ALL; identify individuals who may benefit from alternative therapy

19782X

ABL T315I Mutation in CML, Plasma-based, Leumetaa

Predict a high degree of resistance to imatinib and related drugs in patients with Ph-positive ALL; identify individuals who may benefit from alternative therapy

17821X

Acute Leukemia Follow-up Panelb

Includes CD3, CD7, CD13, CD19, CD20, CD33, CD34, CD45, CD64, and interpretation. Additional markers are tested, at an additional charge, when deemed medically necessary for the diagnosis.

Monitor therapy and/or MRD; detect relapse

15052X

bcr/abl Gene Rearrangement, Quantitative PCR, Cell-baseda

Diagnose Ph-positive ALL; assess prognosis, monitor therapy and MRD; detect relapse in patients with Ph-positive ALL

17853X

bcr/abl Gene Rearrangement, Quantitative PCR, Plasma-based, Leumetab,c

Diagnose Ph-positive ALL; assess prognosis, monitor therapy and MRD; detect relapse in patients with Ph-positive ALL

15101X

bcr/abl Gene Rearrangement, Quantitative PCR with Reflex to Subtypea,c

Distinguish ALL (subtype e1a2) from CML (subtypes b2a2/b3a2); diagnose Ph-positive ALL

14601X

Chromosome Analysis, CLL/LPD

Assess prognosis

19856X

FISH, ALL, +4, +10, +17b

Diagnose ALL; assess prognosis

40050X

FISH, ALL, Extended Panelb

Includes 4, 10, 17, 8q (MYC), 9p (CDKN2A), 11q (MLL),
14q (IGH), 19p (E2A), t(9;22) BCR/ABL1, and t(12;21)
 TEL/AML1

Diagnose ALL; assess prognosis

40052X

FISH, ALL, Pre-B Panelb

Includes 4, 10, 17, 11q (MLL), t(9;22) BCR/ABL1, and
t(12;21) TEL/AML1

Diagnose ALL; assess prognosis

14706X

FISH, ALL/NHL, MYC-BA, 8q24 Rearrangementb

Diagnose ALL, Burkitt lymphoma, and other NHL associated with break-apart MYC (MYC-BA)

14618X

FISH, ALL, TEL/AML1 Translocation 12;21b

Diagnose ALL; assess prognosis and detect MRD and relapse

17352X

FISH, Burkitt’s/NHL/ALL, IGH/MYC, t(8;14)b

Diagnose B-ALL (Burkitt lymphoma)

12070X

FISH, CML/ALL, bcr/abl Translocation 9;22b

Diagnose Ph-positive ALL; assess prognosis in patients with Ph-positive ALL; monitor therapy

10248X

 

Intracellular Markers by Flow Cytometryb

Specify 1 or more of the following markers: CD3,
CD22, IgM, MPO, TdT.

Differential diagnosis of leukemia and lymphoma; detect relapse

Chronic Lymphocytic Leukemia (CLL)

852

Beta-2-Microglobulin, Serum

Assess prognosis

10980X

Campath-1H Sensitivity (CD52)b

Determine eligibility for alemtuzumab therapy

37074X

CD25, IHC with Interpretationb

Determine eligibility for denileukin diftitox therapy

14601X

Chromosome Analysis, CLL/LPD

Assess prognosis

17817X

Chronic Lymphocytic Leukemia (CLL)/Lymphoma Diagnostic Panelb

Includes CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, CD56, CD64, FMC7, kappa, lambda, and interpretation. Additional markers are tested, at an additional charge, when deemed medically necessary for the diagnosis.

Differential diagnose of leukemia and lymphoma; monitor therapy; detect relapse

17818X

Chronic Lymphocytic Leukemia (CLL)/Lymphoma Follow-up Panelb

Includes CD3, CD4, CD5, CD7, CD8, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, HLA-DR, kappa, lambda, and interpretation. Additional markers are tested, at an additional charge, when deemed medically necessary
for the diagnosis.

Monitor therapy and MRD; detect relapse

15480X

Chronic Lymphocytic Leukemia, IgVH Mutation Status, Cell-baseda

Assess prognosis

17702X

Chronic Lymphocytic Leukemia, IgVH Mutation Status, Leumetaa,c

Assess prognosis

17239

CLL Prognostic Panel, Comprehensiveb

Includes IgVH Mutation; ZAP-70; CD38/CD19; FISH,
B-CLL Panel; Beta-2-Microglobulin; and Chromosome Analysis, CLL/LPD

Assess prognosis

17312

CLL Prognostic Panel, Comprehensive without Karyotypeb

Includes IgVH Mutation; ZAP-70; CD38/CD19; FISH,
B-CLL Panel; and Beta-2-Microglobulin

Assess prognosis

17240

CLL Prognostic Panel, Limitedb

Includes IgVH Mutation; ZAP-70; and FISH, B-CLL Panel

Assess prognosis

17290

CLL Prognostic Panel, Monitoringb

Includes ZAP-70; CD38/CD19; FISH, B-CLL Panel; and Beta-2-Microglobulin

Assess prognosis; monitor therapy and MRD

16171X

Fibroblast Growth Factor (FGF2)d

Assess prognosis

16864

FISH, B-Cell Chronic Lymphocytic Leukemia
Panelb

Includes 6q23 (MYB), 11q22.3 (ATM), cen 12, 13q14.3, 13q34, 17p13 (TP53)

Assess prognosis and monitor therapy

17348X

FISH, B-Cell Malignancy, IGH, 14q32 Rearrangementb

Diagnose and monitor B-cell neoplasm

16515X

p53 Mutation Analysis, Plasma-based,
Leumetaa

Assess prognosis in patients with CLL

10981X

Rituxan® Sensitivity (CD20)b

Determine eligibility for rituximab therapy

16000

ZAP-70b

Assess prognosis

Non-CLL Mature B-Cell Neoplasms

852

Beta-2-Microglobulin, Serum

Assess prognosis

10980X

Campath-1H Sensitivity (CD52)b

Determine eligibility for alemtuzumab therapy

37074X

CD25, IHC with Interpretationb

Determine eligibility for denileukin diftitox therapy

14601

Chromosome Analysis, CLL/LPD

Assess prognosis

14706X

FISH, ALL/NHL, MYC-BA, 8q24 Rearrangementb

Diagnose ALL, Burkitt lymphoma, and other NHL associated with break-apart MYC (MYC-BA)

17348X

FISH, B-Cell Malignancy, IGH, 14q32 Rearrangementb

Diagnose and monitor B-cell neoplasm

17352X

FISH, Burkitt’s/NHL/ALL, IGH/MYC, t(8;14)b

Diagnose B-ALL (Burkitt lymphoma)

17347X

FISH, Follicular Lymphoma, IGH/BCL2, t(14;18)b

Diagnose follicular lymphoma and some large cell lymphomas

40056X

FISH, MALT Lymphoma, AP12/MALT1, t(11;18)b

Subclassify MALT lymphoma; assess prognosis

40053X

FISH, MALT Lymphoma, MALT1, 18q21 Rearrangementb

Subclassify MALT lymphoma; assess prognosis

40057X

FISH, MALT Lymphoma, MALT1, rea18q21 with Reflex to AP12/MALT1, t(11;18)b,c

Subclassify MALT lymphoma; assess prognosis

17346X

FISH, Mantle Cell Lymphoma, IGH/CCND1,
t(11;14)b

Diagnose mantle cell lymphoma

15007

Follicular Lymphoma, bcl-2/JH, t(14;18),
Real-time PCR, Cell-baseda

Diagnose follicular lymphoma and other B-cell lymphomas; assess prognosis in patients with diffuse large B-cell lymphoma; monitor therapy and MRD; detect relapse

17690X

Follicular Lymphoma, bcl-2/JH, t(14;18),
Real-time PCR, Leumetaa

Diagnose follicular lymphoma and other B-cell lymphomas; assess prognosis in patients with diffuse large B-cell lymphoma; monitor therapy and MRD; detect relapse

17819X

Hairy Cell Leukemia (HCL)/Lymphoma
Follow-up Panelb

Includes CD11c, CD19, CD20, CD22, CD25, CD45,
CD103, kappa, lambda, and interpretation. Additional
markers are tested, at an additional charge, when
deemed medically necessary for the diagnosis.

Monitor therapy and MRD; detect relapse

40028X

Hairy Cell Leukemia Panel, IHCb

Includes CD3, CD20, CD25, CD79a, DBA.44, TRAP,
and interpretation.

Diagnose hairy cell leukemia

19936X

Hodgkin’s Lymphoma Panel, IHCb

Includes Bob1, CD3, CD15, CD20, CD30, CD45RB
(LCA), CD79a, EBV, Oct-2, and interpretation.

Diagnose Hodgkin lymphoma

10248X

Intracellular Markers by Flow Cytometryb

Specify 1 or more of the following markers: CD3,
CD22, IgM, MPO, TdT.

Differential diagnosis of leukemia and lymphoma; detect relapse

14991

Mantle Cell Lymphoma, bcl-1/JH, t(11;14),
Real-time PCR, Cell-baseda

Diagnose mantle cell lymphoma, monitor therapy and MRD; detect relapse

17679X

Mantle Cell Lymphoma, bcl-1/JH, t(11;14),
Real-time PCR, Leumetaa

Diagnose mantle cell lymphoma, monitor therapy and MRD; detect relapse

40033X

Mantle Cell Lymphoma (Small Lymphocytic)
Panel, IHCb

Includes BCL-1, BCL-2, BCL-6, CD3, CD5, CD10, CD20, CD23, CD79a, kappa (ISH), lambda (ISH), and interpretation.

Differential diagnosis of non-large cell B-cell lymphoma

11237X

Ontak® Sensitivity (CD25)b

Determine eligibility for denileukin diftitox therapy

16515X

p53 Gene Mutation Analysis, Plasma-based, Leumetaa

Assess prognosis in some types of leukemia and lymphoma

10981X

Rituxan®  Sensitivity (CD20)b

Determine eligibility for rituximab therapy

CML, chronic myelogenous leukemia; Ph, Philadelphia chromosome; MRD, minimal residual disease; PCR, polymerase chain reaction; FISH, fluorescence in situ hybridization; NHL, non-Hodgkin lymphoma; IHC, immunohistochemistry; ISH, in situ hybridization.
a This test was developed and its performance characteristics have been determined by Quest Diagnostics Nichols Institute. Performance characteristics refer to the analytical performance of the test.
b This test was developed and its performance characteristics have been determined by Quest Diagnostics Nichols Institute. It has not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. Performance characteristics refer to the analytical performance of the test.
c Reflex tests are performed at an additional charge and are associated with an additional CPT code(s).
d This test was performed using a kit that has not been cleared or approved by the FDA. The analytical performance characteristics of this test have been determined by Quest Diagnostics Nichols Institute. This test should not be used for diagnosis without confirmation by other medically established means.

Table 4. Additional Tests Available for Diagnosis and Evaluation of T-Cell and NK-Cell Neoplasms
Test Code Assay Clinical Use

T-Cell Acute Lymphoblastic Leukemia (T-ALL)

17821X

Acute Leukemia Follow-up Panela

Includes CD3, CD7, CD13, CD19, CD20, CD33, CD34,
CD45, CD64, and interpretation. Additional markers are tested, at an additional charge, when deemed medically
necessary for the diagnosis.

Monitor therapy and/or MRD; detect relapse

Mature T-Cell and NK-Cell Neoplasms

10980X

Campath-1H Sensitivity (CD52)a

Determine eligibility for alemtuzumab therapy

37074X

CD25, IHC with Interpretationa

Determine eligibility for denileukin diftitox therapy

16114X

FISH, ALCL, ALK, 2p23 Rearrangementsa

Diagnose ALCL and assess prognosis

36175

HTLV-I/II Antibody, EIA with Reflex to Confirmation Assayb

Differential diagnosis of adult T-cell leukemia/lymphoma

11237X

Ontak® Sensitivity (CD25)a

Determine eligibility for denileukin diftitox therapy

40029X

T-Cell, Natural Killer Cell, and Anaplastic Large
Cell Lymphoma Panel, IHCa

Includes ALK-1, CD1a, CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD20, CD21, CD30, CD35, CD56, EBV, EMA, TdT, and interpretation

Differential diagnosis of T-cell and NK-cell neoplasms, and ALCL

MRD, minimal residual disease; PCR, polymerase chain reaction; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization; ALCL, anaplastic large cell lymphoma; EIA, enzyme immunoassay.
a This test was developed and its performance characteristics have been determined by Quest Diagnostics Nichols Institute. It has not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. Performance characteristics refer to the analytical performance of the test.
b Reflex tests are performed at an additional charge and are associated with an additional CPT code.

References

  1. Jaffe ES, Harris NL, Stein H, et al. eds. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Hematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001.

  2. NCCN Clinical Practice Guidelines in Oncology. Guidelines for Treatment of Cancer by Site. Non-Hodgkin�s Lymphomas. V3.2008. http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf. Accessed May 5, 2008.
     

Polymerase chain reaction (PCR) is performed pursuant to a license with Roche Molecular Systems, Inc.

Content reviewed 12/2011
top of page

* The tests listed by specialist are a select group of tests offered. For a complete list of Quest Diagnostics tests, please refer to our Directory of Services.