Tests
1st tests to order
CBC with differential
Test
May show anemia, thrombocytopenia, leukopenia, or pancytopenia due to bone marrow involvement.
May show thrombocytopenia from liver involvement.
Lymphocytosis may be present in some subtypes of NHL (e.g., adult T-cell leukemia/lymphoma [ATLL], T-cell prolymphocytic leukemia [T-PLL]).
Result
anemia, thrombocytopenia, leukopenia, pancytopenia, lymphocytosis
peripheral blood smear
Test
Nucleated red blood cells and left shift (early WBC precursors) from bone marrow involvement, abnormal lymphocytes and rarely circulating blasts (e.g., from rare blastic phase of mantle cell lymphoma).
Result
nucleated red blood cells, left shift
comprehensive metabolic panel (including liver function tests [LFTs])
Test
To assess kidney function, liver function, electrolytes, glucose; to evaluate organ involvement (e.g., liver) and organ dysfunction that may affect treatment, and need for tumor lysis syndrome prophylaxis.
Result
may be normal or abnormal
serum lactate dehydrogenase (LDH)
uric acid
Test
May be elevated due to high tumor cell turnover rate, particularly in aggressive (high-grade) lymphomas.
The degree of uric acid may affect urgency of treatment and intensity of tumor lysis syndrome prophylaxis.
Result
may be normal or elevated
lymph node biopsy
biopsy (extranodal sites e.g., brain, skin)
Test
Biopsy of extranodal sites may be required for diagnosis.
Brain biopsy is required for diagnosing primary CNS lymphoma.[53]
Skin biopsy may be helpful for diagnosing certain T-cell lymphomas (e.g., cutaneous T-cell lymphoma) or in cases of skin infiltration by other lymphomas.[49][54]
Result
may be positive for lymphoma
bone marrow biopsy and aspirate
Test
Helpful for establishing a diagnosis depending on the type of NHL or the individual case (e.g., when lymph node biopsy is not diagnostic and bone marrow involvement is suspected). Bone marrow may be the only site of disease.
Assessing the extent of bone marrow involvement is important for staging and guiding treatment (e.g., bone marrow transplant). Bone involvement by lymphoma usually signifies stage IV disease. See Criteria.
Result
may be positive for lymphoma
immunohistochemistry
Test
Performed on biopsy specimen.
Establishes the type of lymphoma and may be complementary to flow cytometry.
Result
positive for tumor markers for NHL
flow cytometry
Test
Performed on peripheral blood, bone marrow aspirate, lymph node suspensions, effusions, cerebrospinal fluid, and other body fluids.
Establishes the type of lymphoma and may be complementary to immunohistochemistry.
Result
positive for tumor cell surface markers for NHL
fluorodeoxyglucose (FDG)-PET/CT scan
Test
FDG-PET/CT scan or CT scan alone (of chest, abdomen, pelvis, neck [in some cases]) should be carried out as part of the standard workup (diagnosis, staging) and follow-up of NHL.[48][49]
FDG-PET/CT scan is more accurate than CT scan alone in detecting nodal and extranodal lesions.[55] FDG-PET/CT scan is the preferred imaging modality for staging and end-of-treatment evaluation in patients with FDG-avid lymphomas (e.g., diffuse large B-cell lymphoma [DLBCL], follicular lymphoma).[56]
FDG-PET/CT scan may be useful in identifying biopsy targets with the highest diagnostic yield, identifying disease transformation (i.e., from an indolent lymphoma to aggressive lymphoma), and guiding rebiopsy to confirm histologic transformation if clinically suspected (i.e., elevated LDH level; B symptoms).[48][56][57][58] FDG uptake is higher in aggressive lymphomas than low-grade (indolent) lymphomas.[56][59]
Interim FDG-PET/CT scan may be useful for restaging and adapting treatment for certain NHLs (e.g., DLBCL), but its role continues to be investigated.[48][60][61][62] [63]
Result
may show involvement at nodal and extranodal sites (e.g., liver, spleen)
Tests to consider
core needle biopsy
Test
A core needle biopsy is less optimal for diagnosis (excisional and incisional biopsy are preferred).[48][49] But it may be considered in certain situations (e.g., if surgery is not possible).
Combined core needle biopsy and fine-needle aspiration biopsy, with appropriate immunophenotyping and genetic studies, may be considered for diagnosis in certain cases (e.g., when a lymph node is not easily accessible).[48][49]
Result
may be positive for lymphoma
fine-needle aspiration (FNA) biopsy
Test
FNA biopsy alone is not optimal for diagnosis.[48][49]
Combined core needle biopsy and FNA biopsy, with appropriate immunophenotyping and genetic studies, may be considered for diagnosis in certain cases (e.g., when a lymph node is not easily accessible).[48][49]
Result
may be positive for lymphoma
genetic testing
Test
Genetic tests (including karyotype, fluorescence in situ hybridization [FISH], polymerase chain reaction [PCR], next-generation sequencing [NGS]) can be used to identify genetic abnormalities associated with NHL, for example: immunoglobulin (Ig) gene rearrangements (in B-cell lymphomas); chromosome translocations/rearrangements involving oncogenes such as BCL2 (e.g., t(14;18) in follicular lymphoma), CCND1 (e.g., t(11;14) in mantle cell lymphoma), MYC (e.g., t(8;14) in Burkitt lymphoma), and BCL6 (e.g., t(3;14) in DLBCL); T-cell receptor (TCR) gene rearrangements (in T-cell lymphomas); genetic mutations (e.g., TP53 in mantle cell lymphoma).[48][49]
These genetic abnormalities can help to establish the diagnosis (e.g., by confirming a malignant clone and determining NHL subtype) and guide prognosis and treatment.
Result
may be positive for: Ig gene rearrangements; chromosome rearrangements involving oncogenes (e.g., BCL2, CCND1, MYC, BCL6); TCR gene rearrangements; genetic mutations (e.g., TP53)
hepatitis B and C serology
Test
Hepatitis B and C status needs to be determined prior to treatment because of the risk of virus reactivation during chemotherapy and/or immunosuppressive therapy.[48][65]
All patients receiving anti-CD20 monoclonal antibody therapy (e.g., rituximab, obinutuzumab) should be screened for hepatitis B virus (HBV) prior to starting treatment.[48]
Result
may be positive for hepatitis B or hepatitis C
HIV testing
Test
HIV testing is required for certain lymphomas (e.g., primary central nervous system lymphoma, Burkitt lymphoma) as it can inform management (e.g., use of antiretroviral therapy).[48][53]
NHL (particularly Burkitt lymphoma) in a person with HIV is an AIDS-defining condition.[66][67]
Burkitt lymphoma may be the presenting sign of HIV/AIDS.
Result
may be positive for HIV
Epstein-Barr virus (EBV) testing
Test
EBV testing (e.g., PCR, in situ hybridization) can guide diagnosis and treatment, particularly for HIV-related B-cell lymphomas (e.g., diffuse large B-cell lymphoma) and certain T-cell lymphomas (e.g., peripheral T-cell lymphoma, extranodal NK/T-cell lymphomas).[48][49]
Result
may be positive for EBV
human T-cell lymphotropic virus (HTLV) testing
Test
HTLV testing can guide diagnosis for certain T-cell lymphomas (e.g., adult T-cell leukemia/lymphoma [ATLL]).[49]
Result
may be positive for HTLV
MRI (brain, spine)
ultrasound (breast, axilla)
Test
Performed if there are signs or symptoms suggesting breast implant involvement (breast implant-associated anaplastic large cell lymphoma).[49]
If imaging of the breasts shows periprosthetic effusion or an abnormal mass, then a biopsy (e.g., fine-needle aspiration [FNA] biopsy for effusion; and/or excisional, incisional, or core needle biopsy for an abnormal mass) should be carried out for cytologic and immunophenotypic evaluation.
FNA biopsy of a large volume of fluid (>50 mL) from around the breast may improve diagnostic yield.[49]
Result
may show periprosthetic effusion or mass
lumbar puncture
Test
Performed to assess central nervous system (CNS) involvement and for administration of intrathecal CNS prophylaxis.
Lumbar puncture with cerebrospinal fluid analysis (including flow cytometry) is indicated in Burkitt lymphoma, primary CNS lymphoma, and other HIV-related B-cell lymphoma, or if there are neurologic signs or symptoms suggesting CNS involvement.[48][53]
Lumbar puncture may be considered for patients with diffuse large B-cell lymphoma (DLBCL) who have high-risk disease, including those with: high-risk score on the CNS-International Prognostic Index (CNS-IPI 4-6); kidney or adrenal gland involvement; testicular lymphoma; primary cutaneous DLBCL, leg type; or stage IE DLBCL of the breast.[48] See Criteria.
How to perform a diagnostic lumbar puncture in adults. Includes a discussion of patient positioning, choice of needle, and measurement of opening and closing pressure.
Result
presence of abnormal cells, low glucose, high protein, and high pressure
endoscopy and colonoscopy
Test
May be useful for the diagnosis of certain lymphomas (e.g., extranodal marginal zone lymphoma, mantle cell lymphoma).[48]
Result
micropolyps, erythema, erosions, ulcerations
serum protein electrophoresis with immunofixation
Test
Useful for diagnosis in suspected cases of splenic marginal zone lymphoma or lymphoplasmacytic lymphoma (Waldenström macroglobulinemia), where a monoclonal immunoglobulin may be detected.[48]
Result
may detect a monoclonal protein
quantitative immunoglobulins
Test
Useful for diagnosis in suspected cases of splenic marginal zone lymphoma or lymphoplasmacytic lymphoma (Waldenström macroglobulinemia), where a monoclonal immunoglobulin may be detected.[48]
Result
may show elevated immunoglobulin levels
serum beta-2 microglobulin
Helicobacter pylori testing
Test
Indicated if gastric mucosa-associated lymphoid tissue (MALT) lymphoma is suspected.[48]
See MALT lymphoma.
Result
may be positive for H pylori
multigated acquisition (MUGA) scan
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