Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (377 page)

   
Serum free light chain immunoassay
: Normal κ:/λ is 0.26–1.65. The ratio is altered in nonsecretory myeloma, oligosecretory myeloma, and light chain myeloma. This assay is useful for diagnosis, monitoring during and after treatment, and perhaps prognosis of patients with multiple myeloma and an intact immunoglobulin.

   Cold agglutinins or cryoglobulins may be present.

   Serum calcium may be elevated due to osteolytic lesions.

   Hypercalciuria results from dehydration and renal tubular dysfunction.

   Serum uric acid is elevated in 50% of cases.

   ESR (is usually [90% cases]) markedly elevated.

   Serum β2 microglobulin can be elevated. A level >6 μg/mL portends poor prognosis.

   Renal function tests may be abnormal in the presence of monoclonal light chain proteinuria.

   
Immunophenotype
: The neoplastic plasma cells classically are CD138
⁺
, CD38
^high
, CD19
⁻
, CD56
⁺
(60–80%), and CD79a
⁺
and express monotypic cytoplasmic κ or λ. In addition, plasma cells may also aberrantly express CD117, CD20, CD52, CD10, and occasionally myeloid and monocytic antigens. Cyclin D1 expression may be seen in cases with t(11,14) translocation.

   
Genetics and cytogenetics
: New genetic technology now allows insight into the genetic aberrations in MM at a genome-wide scale and across different developmental stages in the course of an individual’s disease. Risk scores based on gene expression profiling have been recently presented as powerful prognostic predictors. While not yet applicable clinically, these advances will also lead to improved targeted therapies. At the cytogenetic level, the MM genome is recognized as being extremely complex. Nevertheless,
cytogenetic evaluation is mandatory
in all patients with newly diagnosed MM. Genetic abnormalities can be detected by interphase FISH in nearly 100% of cases. Cytogenetic abnormalities can be classified into two groups:
structural
(
translocations)
, involving the IGH locus, and
genomic imbalances, including gains and losses
. The most common IGH translocations are t(11;14)(q13;q32) CCND1-IGH (15–18%), t(14;16)(q32;q23) MAF-IGH (5%), t(4;14)(p16.3;q32) FGFR3-IGH (15%), and t(14;20)(q32;q12) MAB-IGH (2%). CCND1-IGH is considered a favorable finding with associated therapy; the other IGH partners are considered to be poor prognostic findings. Hyperdiploidy, typically with trisomy of chromosomes 3, 5, 7, 9, 11, 15, 19, and 21, is a favorable finding, while hypodiploidy is unfavorable. Hypodiploid clones often double and must be distinguished from hyperdiploid clones. Deletion of 13q or loss of 13 is common, and its prognostic impact, particularly as a sole abnormality, is unclear. Deletion of 17p (TP53) and MYC rearrangements represent progression of disease as do the molecular genetic findings of K or NRAS mutations (30–40%), FGFR3 mutation, and inactivation of RB1 or p18
^INK4c
.

   
Microbiology
: Repeated bacterial infections caused by
Diplococcus pneumoniae
,
Staphylococcus aureus
, and
Escherichia coli
.