Detection and Diagnosis of Circulating Plasma Cell Clones

Current Diagnostic Approaches for Circulating Plasma Cells

The International Society of Hematology recommends multiparametric flow cytometry as the established and preferred method for detecting and quantifying circulating plasma cells in peripheral blood 1, 2, 3
Flow cytometry can detect neoplastic plasma cells even when they represent as little as 0.01% of leukocytes, making it highly sensitive for early detection 2, 3
A minimum of 100 neoplastic plasma cell events should be acquired for accurate enumeration, with at least 1,000,000 total events required for a sensitivity limit of 0.01% 1, 3

The European Hematology Association suggests that CD38, CD138, and CD45 should be included in at least one tube for plasma cell identification and enumeration 4
The primary gating strategy should be based on CD38 vs. CD138 expression 4
For detection of abnormal plasma cells, a minimal panel should include CD19 and CD56 4, 5
A preferred panel would also include CD20, CD117, CD28, CD27, CD81, and cytoplasmic kappa and lambda light chains 5, 6

The World Health Organization proposes traditional criteria: ≥20% circulating plasma cells and/or an absolute count >2×10^9/L plasma cells in peripheral blood 7, 8
Newer proposed criteria: ≥5% circulating plasma cells and/or an absolute count ≥0.5×10^9/L, which should be recorded to prospectively analyze the biology and clinical course of these patients 8, 9
At least 200 circulating nucleated cells per smear should be systematically analyzed by an experienced hematologist 10, 9

The American Society of Clinical Oncology recommends careful morphological evaluation of peripheral blood smears by conventional microscopy in all patients with suspected plasma cell disorders 10, 8
Use multiparametric flow cytometry with CD38, CD138, CD19, CD56, CD45, and cytoplasmic kappa/lambda light chains 1, 5
Acquire at least 100 neoplastic plasma cell events for accurate enumeration 1, 3
Assess clonality through cytoplasmic κ/λ expression 2, 3

Relying solely on morphological examination without flow cytometry confirmation may miss cases with low levels of circulating plasma cells 8, 9
Using inadequate antibody panels that fail to distinguish between normal and neoplastic plasma cells 5, 6
Failing to acquire sufficient events (at least 1,000,000 total events) to achieve adequate sensitivity 1, 3
Not washing marrow samples twice in buffered saline solution prior to assessment of cytoplasmic immunoglobulin expression, which can lead to false results 2, 3