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Laboratory Tests and Ancillaries
Urinalysis
24-hour urine analysis for total protein, urine
protein electrophoresis (UPEP), and urine immunofixation electrophoresis
(UIFE) should be requested.
Bone Marrow Aspiration and Trephine
Biopsy (BMAT)
Bone marrow aspiration and trephine biopsy is the main
procedure used to obtain bone marrow specimens for confirmation and
quantification of abnormalities in the BMPCs using
immunophenotyping, cytogenetic studies, and fluorescence in situ hybridization
(FISH).
Multiple Myeloma_DiagnosticsImmunophenotyping
Examples: Immunohistochemical staining, immunofluorescent studies, flow cytometry
Immunophenotyping is used to detect the presence of either λ or κ chains in BMPC cytoplasm. The distinguishing feature in patients with multiple myeloma is the presence of CD19, CD56, CD38, CD45, and κ and λ light chains.
Serum Free Light-Chain (FLC) Assay
Serum FLC assay quantifies serum κ and λ light Ig chains unbound to heavy chains. The abnormal FLC ratio is present in 90% of patients with multiple myeloma.
Serum FLC assay is used in screening for plasma cell abnormalities, especially for the detection and prognostication of monoclonal gammopathy of undetermined significance, smoldering myeloma, active myeloma, Ig light-chain amyloidosis, and solitary plasmacytoma. It is used alongside serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE). It is also used for the assessment of prognosis, quantitative monitoring of patients with light-chain amyloidosis, and oligosecretory myeloma. A normal FLC ratio is a required criterion for a stringent complete response.
Serum Immunofixation Electrophoresis (SIFE) Test
SIFE determines the type of abnormal immunoglobulins. It is done together with a serum protein electrophoresis (SPEP) test to measure the amount of abnormal serum Ig present.
Serum Protein Electrophoresis (SPEP)
SPEP is used to identify the monoclonal protein (myeloma protein, serum M-protein) used in the diagnosis and clinical response to treatment. It determines the quantity of monoclonal protein.
Cytogenetic Studies
Fluorescence in situ Hybridization (FISH)
FISH uses the specimen obtained in bone marrow aspiration for the detection of chromosomal abnormalities. The chromosomal aberrations identified in multiple myeloma patients include del(13), del17p13, IGH gene rearrangement at 14q32, 14q32 translocations [t(11;14)(q13;q32), t(4;14)(p16;q32), t(14;16)(q32;q23), t(14;20)(q32;q12)], and chromosome 1 abnormalities. Examination for del(13), del(17p13), t(4;14), t(11;14), t(14;16), 5(14;20), 1q21 gain or 1q21 amplification, 1p deletion is recommended to determine biological subtype, for prognostication and to determine candidacy for clinical trials.
Karyotyping (Conventional Cytogenetics)
Karyotyping is used to detect the presence of chromosomal abnormalities including 13q14 deletion, chromosome 13 monosomy, and hypodiploidy.
Other Laboratory Examinations
Other laboratory requests that may be requested in patients with multiple myeloma include complete blood count (CBC) with differential and platelet count, peripheral blood smear examination, blood urea nitrogen (BUN), serum creatinine and creatinine clearance, serum electrolytes including serum calcium, serum uric acid, liver function tests (LFTs), albumin, lactate dehydrogenase (LDH), beta-2 microglobulin, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP/BNP).
Single nucleotide polymorphism (SNP) array on bone marrow and/or next-generation sequencing (NGS) panel on bone marrow may also be requested as it helps identify additional abnormalities, which allows for further categorization and prognostication.
Imaging
The International
Myeloma Working Group (IMWG) recommends at least 1 imaging modality to be done
in patients with smoldering multiple myeloma, depending on availability and
cost.
Computed Tomography (CT)
CT scan is used to assess tumor load and for the
assessment of symptoms.
Whole-body low-dose CT (WBLD-CT)
is one of the recommended imaging modalities for the detection and for baseline assessment of bone involvement. It is statistically significantly superior in terms of sensitivity
compared to conventional skeletal survey for the detection of osteolytic
lesions, with shorter procedure time, and better positional comfort. It is superior
to a skeletal survey for the detection of lesions in areas that are difficult
to visualize such as ribs and skulls. It
is recommended for patients with suspected high-risk non-IgM monoclonal
gammopathy of undetermined significance.
Magnetic Resonance Imaging (MRI)
MRI should be considered for patients with negative
results on skeletal survey and those with possible spinal cord compression and other
central nervous system (CNS) involvement. It is the preferred modality for
patients with newly diagnosed solitary bone plasmacytoma. It is used to
distinguish smoldering myeloma from multiple myeloma if WBLD-CT or positron
emission tomography with CT (PET/CT) is negative. It is also preferred in
patients suspected to have smoldering multiple myeloma if without bone lesions
on CT and no symptoms of end-organ damage.
Whole-body MRI is preferred but may be limited to
the spine and pelvis if not possible. It is recommended for patients negative
on WBLD-CT and without any other myeloma-defining signs and symptoms. Spinal and
pelvic MRI is recommended if a focal bone marrow lesion is highly likely.
Positron Emission Tomography with
CT (PET-CT)
PET-CT is used to evaluate
bone lesions that cannot be confirmed with plain CT or MRI imaging. It is superior
to MRI when assessing focal lesion viability. Fluorodeoxyglucose
(FDG)-PET/CT scan is the preferred recommended imaging modality for the initial
work-up of patients suspected with multiple myeloma or solitary plasmacytoma. It is the preferred modality for patients suspected of having
extramedullary disease and as baseline imaging for treatment response
assessment. It may be used for the early detection of bone marrow involvement
in patients with solitary plasmacytoma.
Skeletal Survey
A skeletal survey is an imaging modality option used
for the determination of lytic lesions. It is inferior to WBLD-CT and should
not be used for the initial evaluation of bone disease in multiple myeloma. It
should include the spine, pelvis, skull, humeri, and femurs.