Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (379 page)

   Serum protein electrophoresis and immunofixation reveal a monoclonal protein (κ or λ) and identify preponderance of a specific immunoglobulin chain (IgG 70% of cases, IgA 12%, light chain 20%, IgM 15%, and biclonal 3%).

   Urine protein electrophoresis and immunofixation reveal M protein (Bence Jones protein) in one third of cases, reflecting urine light chains.

   Serum free light chain immunoassay. Normal κ-to-λ ratio is 0.26:1.65. Abnormal ratio in MGUS is a significant risk factor for progression to myeloma.

   Renal function tests may be abnormal in MGUS. Light chains and proteinuria may be present.

   Immunophenotype: Flow cytometry analysis frequently shows two populations of plasma cells: one with normal immunophenotype (CD38 bright+, CD19+, and CD56
⁻
) with polytypic cytoplasmic light chain expression and another with an aberrant phenotype (CD38+,
CD19
−,
CD56
+) with monotypic cytoplasmic light chain expression.

   Cytogenetics: The primary cytogenetic abnormalities can be divided into two, partially overlapping, entities: (1) hyperdiploidy in half the cases, with trisomies of chromosomes 3, 5, 7, 9, 11, 15, 19, and 21 and (2) nonhyperdiploid in the remaining 50% of cases, often associated with a translocation event at the IgH locus (on chromosome 14) with recurrent chromosomal patterns and oncogene deregulation. Dysregulation of a Cyclin D gene is found in all MGUS and plasma cell myeloma clones. Additional genomic events represent progression of MGUS to plasma cell myeloma.

Suggested Readings

Leung N, Bridoux F, Hutchinson CA, et al. Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant.
Blood.
2012;120:4292–4295.

Merlini G, Palladini G. Differential diagnosis of monoclonal gammopathy of undetermined significance.
Hematology Am Soc Hematol Educ Program.
2012;2012:595–603.

PLASMA CELL LEUKEMIA (PCL)

   Definition

PCL is an aggressive form of plasma cell myeloma consisting of clonal plasma cells circulating in the peripheral blood. PCL can occur de novo (primary PCL) or evolve as a late feature in the course of plasma cell myeloma (secondary PCL). It has a poor prognosis with a median survival of 7–11 months in treated cases.

   Who Should Be Suspected?

PCL is more common in men and in African Americans. The incidence is 0.02–0.03 cases/100,000 population. Secondary PCL occurs in 1–4% of plasma cell myeloma cases. Patients with PCL present with clinical features similar to those of plasma cell myeloma (PCM). Patients with primary PCL have smaller M-protein peak in serum, higher platelet count, younger age (55 vs. 65 for secondary PCL), and longer survival. In addition to peripheral blood and bone marrow, clonal plasma cells are found frequently in the spleen, liver, pleural effusions, ascites, and CNS.

   Laboratory Findings

   
CBC
: Leukocytosis with clonal plasma cells exceeding 2,000/μL or 20% of differential count. Mild anemia and/or thrombocytopenia can also be observed. The plasma cells have relatively scant cytoplasm and may resemble plasmacytoid lymphocytes. They may also have the morphology of plasmablasts.

   
Bone marrow
biopsy and aspirate are similar to that for PCM (see p. 432).