Investigations
1st investigations to order
FBC with differential
Test
Routine laboratory test for NHL.[70][71]
May show anaemia, 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., acute or chronic adult T-cell leukaemia/lymphoma [ATLL], T-cell prolymphocytic leukaemia [T-PLL]).[70]
Result
may show anaemia, thrombocytopenia, leukopenia, pancytopenia, or lymphocytosis
comprehensive metabolic panel (including liver function tests [LFTs])
serum lactate dehydrogenase (LDH)
Test
Routine laboratory test for NHL.[70][71]
An indirect measure of the proliferative rate of the lymphoma; an important diagnostic and prognostic factor.[74] See Criteria.
The degree of LDH elevation may affect urgency of treatment and intensity of tumour lysis syndrome prophylaxis. See Tumour lysis syndrome topic.
Result
may be normal or elevated
uric acid
Test
Routine laboratory test for NHL, particularly aggressive (high-grade) lymphomas.[70][71]
May be elevated due to high tumour cell turnover rate.
The degree of uric acid may affect urgency of treatment and intensity of tumour lysis syndrome prophylaxis. See Tumour lysis syndrome topic.
Result
may be normal or elevated
lymph node biopsy
Test
Excisional or incisional lymph node biopsy should be performed for diagnosis and grading of NHL, as this allows for optimal assessment of morphology (including lymph node architecture) and provides sufficient tissue for immunohistochemistry and molecular studies.[70][71][77]
Result
positive for lymphoma
biopsy (extranodal sites)
Test
Biopsy of extranodal sites may be required for diagnosing certain types of NHL.
Stereotactic biopsy of brain lesions for diagnosing primary CNS lymphoma.[79]
Fine-needle aspiration biopsy of periprosthetic effusion (>50 mL) and surgical biopsy (excisional, incisional, or core needle) of a breast mass for diagnosing breast implant-associated anaplastic large cell lymphoma (BIA-ALCL).[71]
Skin biopsy (punch, incisional, or excisional) should be performed diagnosing primary cutaneous lymphomas, or in cases of skin involvement by other lymphomas.[80]
Vitreous fluid biopsy for primary vitreoretinal lymphoma or primary CNS lymphoma ocular variant.[79]
Result
may be positive for lymphoma
bone marrow biopsy and aspiration
Test
May be helpful for evaluating unexplained cytopenias and establishing a diagnosis, depending on the type of NHL or the specific setting (e.g., when lymph node biopsy is not diagnostic and bone marrow involvement is suspected).[70][77]
Bone marrow may be the only site of disease.
Assessing bone marrow involvement is important for staging and guiding treatment (e.g., stem cell transplant).[81]
Bone marrow involvement usually signifies stage IV disease. See Criteria.
Result
may be positive for lymphoma
immunohistochemistry
flow cytometry
fluorodeoxyglucose (FDG)-PET/CT scan
Test
FDG-PET/CT scan or CT scan alone (of chest, abdomen, pelvis, head/neck [in some cases]) should be performed as part of the standard work-up (diagnosis, staging) and follow-up of NHL.[70][71][79][80]
FDG-PET/CT scan is the preferred imaging modality for staging and end-of-treatment response assessment in patients with FDG-avid lymphomas (e.g., diffuse large B-cell lymphoma [DLBCL], follicular lymphoma) as it is more accurate than CT scan alone in detecting nodal and extranodal lesions.[70][71][82][83][84]
FDG-PET/CT scan can also be used to identify biopsy sites with the highest diagnostic yield; detect histological transformation of an indolent lymphoma to aggressive lymphoma (FDG uptake is higher in aggressive lymphomas); and guide rebiopsy to confirm histological transformation if clinically suspected (e.g., elevated lactate dehydrogenase level; B symptoms present).[70][83][85][86][87][88][89][90][91][92][93]
Interim FDG-PET/CT scan may be useful for restaging and adapting treatment for certain NHLs (e.g., DLBCL, peripheral T-cell lymphomas); its role continues to be investigated.[70][71]
Result
may show involvement at nodal and extranodal sites (e.g., liver, spleen)
Investigations to consider
core needle biopsy
fine-needle aspiration (FNA) biopsy
Test
FNA biopsy alone is insufficient for diagnosis and grading of NHL.[70][71]
FNA biopsy may be used for the initial diagnostic work-up for certain lymphomas (e.g., breast implant-associated anaplastic large cell lymphoma [BIA-ALCL]).[13][71][78] FNA biopsy of a large volume of fluid (>50 mL) from around the breast may improve diagnostic yield.[71]
Result
may be positive for lymphoma
genetic testing
Test
Can detect genetic abnormalities associated with NHL, which can help establish a diagnosis (e.g., by confirming a malignant clone and determining the NHL subtype) and guide prognosis and treatment.
Molecular analysis (e.g., PCR) can be used to detect immunoglobulin (Ig) gene rearrangements (in B-cell lymphomas) or T-cell receptor (TCR) gene rearrangements (in T-cell lymphomas).[70][71]
Cytogenetic analysis (e.g., karyotype; fluorescence in situ hybridisation [FISH]) can be used to detect chromosome translocations/rearrangements involving oncogenes, such as BCL2 (e.g., t(14;18) in follicular lymphoma and diffuse large B-cell lymphoma [DLBCL]), CCND1 (e.g., t(11;14) in mantle cell lymphoma), MYC (e.g., t(8;14) in Burkitt's lymphoma and DLBCL), and BCL6 (e.g., t(3;14) in DLBCL).[70]
Mutational analysis (e.g., gene sequencing; next-generation sequencing [NGS]) can be used to detect genetic mutations (e.g., TP53 in mantle cell lymphoma).[70]
Result
may be positive for: Ig gene rearrangements; TCR gene rearrangements; chromosome translocations/rearrangements involving oncogenes (e.g., BCL2, CCND1, MYC, BCL6); genetic mutations (e.g., TP53)
hepatitis B virus (HBV) serology
Test
HBV status should be determined prior to treatment because of the risk of HBV reactivation during chemotherapy and/or immunosuppressive therapy.[70][94]
All patients receiving anti-CD20 monoclonal antibody therapy (e.g., rituximab, obinutuzumab) should be screened for hepatitis B virus (HBV) prior to starting treatment.[70]
Result
may be positive for HBV
hepatitis C virus (HCV) serology
HIV testing
Test
HIV testing is required for certain lymphomas (e.g., primary central nervous system lymphoma, Burkitt's lymphoma) as it can inform management (e.g., use of antiretroviral therapy).[70][79]
NHL (particularly Burkitt's lymphoma) in a person living with HIV is an AIDS-defining condition.[96][97]
Burkitt's 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 hybridisation) can guide diagnosis and treatment, particularly for HIV-related B-cell lymphomas (e.g., diffuse large B-cell lymphoma, primary central nervous system lymphoma, Burkitt's lymphoma) and certain T-cell lymphomas (e.g., peripheral T-cell lymphoma, extranodal NK/T-cell lymphomas).[70][71]
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 leukaemia/lymphoma [ATLL]).[71]
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 [BIA-ALCL]).[71]
If imaging of the breasts shows periprosthetic effusion or an abnormal mass, then a biopsy (e.g., fine-needle aspiration [FNA] biopsy for effusion [>50 mL]; and/or excisional, incisional, or core needle biopsy for an abnormal mass) should be carried out for cytological and immunophenotypic evaluation.[13][71][78]
Result
may show periprosthetic effusion or mass
lumbar puncture
Test
May be 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 for patients with Burkitt's lymphoma, primary CNS lymphoma, or patients with neurological signs or symptoms suggesting CNS involvement.[70][79]
Lumbar puncture should 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.[70] 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
may show abnormal cells, low glucose, high protein, and/or high pressure
endoscopy
Test
May be useful for the diagnosis and staging of certain lymphomas (e.g., mantle cell lymphoma).[70]
Result
may show gastrointestinal lesions
serum protein electrophoresis with immunofixation
Test
Serum protein electrophoresis may be performed as part of the diagnostic work-up for follicular lymphoma and marginal zone lymphoma (particularly splenic).[70]
If a monoclonal immunoglobulin is detected or immunoglobulin level is elevated, further testing with immunofixation may be performed.[70]
Result
may detect a monoclonal immunoglobulin
quantitative immunoglobulins
serum beta-2 microglobulin
multigated acquisition (MUGA) scan
echocardiogram
ophthalmological examination (including slit lamp)
Test
May be performed to assess ocular involvement (primary vitreoretinal lymphoma) in a patient with primary CNS lymphoma.[79]
Result
may show lymphoma cell infiltration in the vitreous and/or retina
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