How is plasma cell percentage determined from bone marrow aspirations and cytology report?

How to Determine Plasma Cell Percentage from Bone Marrow Aspirations and Cytology Report

Primary Method: Morphological Assessment

Plasma cell percentage should be determined by morphological examination of Wright-stained bone marrow aspirate smears through manual differential counting by an experienced hematopathologist, as this remains the gold standard and is required by current diagnostic criteria. 1

Standard Counting Procedure

• Perform a 500-cell differential count on the bone marrow aspirate smear to calculate the percentage of plasma cells among all nucleated cells 1
• The cytologist counts plasma cells identified by their characteristic morphology: eccentric nucleus with clumped chromatin, perinuclear hof (Golgi zone), and basophilic cytoplasm 1
• Record both the total plasma cell percentage and the proportion showing atypical morphology, as >25% atypical forms predicts worse survival 2

Complementary Method: Bone Marrow Biopsy with Immunohistochemistry

You should always obtain both bone marrow aspirate and core biopsy, then use the highest plasma cell percentage from either method for diagnostic and prognostic purposes. 3, 2, 4

Biopsy Assessment Protocol

• Perform CD138 immunostaining on the trephine biopsy section to accurately identify and quantify plasma cells 3, 2
• The pathologist estimates plasma cell percentage by examining the overall cellularity and distribution pattern (focal, interstitial, diffuse, or nodular) 1
• Computer-assisted image analysis (CIA) can be used on CD138-stained sections for more objective quantification 2

Why Both Methods Matter

• Biopsy consistently yields higher plasma cell percentages (median 47.7%) compared to aspirate smears (median 30.6%) 2
• The highest estimate among all methods is the best predictor of complete response to treatment (P = 0.02) 4
• Combined assessment provides superior prognostic information for overall survival compared to either method alone 2

Common Pitfalls and How to Avoid Them

Sample Quality Issues

• Always use first-pull aspirate samples for laboratory studies, as secondary aspirates are diluted with peripheral blood and yield falsely low plasma cell counts 1
• Poor quality aspirate smears with hemodilution create the largest discrepancy between biopsy and aspirate results 2, 5
• If the aspirate is "dry tap" or poorly cellular, rely more heavily on the biopsy percentage 5

Biological Factors Affecting Recovery

• Plasma cells with malignant features are less likely to be recovered in aspirates, including those with:
  • High-grade cytologic atypia 5
  • CD56 expression 5
  • Multiple cytogenetic aberrations 5
  • MYC gene abnormalities 5
• Increased bone marrow fibrosis reduces plasma cell recovery in aspirates 5
• These biological properties can lead to aspiration failure and underestimation of disease burden 5

Flow Cytometry: Adjunctive Role Only

Flow cytometry consistently underestimates plasma cell percentage compared to morphological methods and should NOT be used as the primary method for determining plasma cell burden. 1, 6

When to Use Flow Cytometry

• Use flow cytometry to establish clonality through kappa/lambda light chain restriction, not for quantification 1, 3
• Flow identifies abnormal immunophenotype (CD19-, CD56+, CD38+, CD138+, CD45-) to distinguish clonal from reactive plasma cells 3
• Flow-based plasma cell percentages are typically 2-4 times lower than morphological counts due to:
  • Sample processing artifacts 6
  • Loss of plasma cells during preparation 6
  • Expression of adhesion molecules affecting cell recovery 1

Critical Distinction

• Flow cytometry blast percentages do NOT provide the same prognostic information as morphologic blast counts and should never substitute for morphological assessment 1
• Flow may have value for minimal residual disease detection after treatment, but not for initial diagnosis 1

Reporting Algorithm

Step 1: Document All Values

• Record plasma cell percentage from aspirate smear (cytologist count) 2
• Record plasma cell percentage from biopsy (pathologist count on CD138-stained sections) 2
• Note the pattern of infiltration on biopsy (focal, interstitial, diffuse, nodular) 1

Step 2: Identify Discrepancies

• If biopsy shows ≥50% higher plasma cells than aspirate, suspect poor aspirate quality or malignant cell properties 2, 5
• Document any factors affecting recovery: hemodilution, fibrosis, dry tap 5

Step 3: Report the Highest Value

• Use the highest plasma cell percentage obtained by any morphological method (aspirate or biopsy) for diagnostic classification and prognostic assessment 3, 4
• This approach provides the most accurate prediction of treatment response and survival 4

Step 4: Add Qualitative Details

• Describe plasma cell morphology: mature, immature, plasmablastic, or mixed 2
• Calculate percentage of atypical forms if >25% present (prognostic significance) 2
• Note distribution pattern from biopsy 1

Special Considerations for Specific Diagnoses

For Multiple Myeloma Diagnosis

• ≥10% clonal bone marrow plasma cells is required, but diagnosis also requires additional criteria (CRAB features or myeloma-defining events) 1, 7
• The plasma cell percentage must be determined by morphological assessment on aspirate or biopsy 1

For Complete Response Assessment

• <5% plasma cells on both aspirate and biopsy is required for complete response 1
• Biopsy confirmation is mandatory if monoclonal protein absence is sustained for 6 weeks 1
• For nonsecretory myeloma, repeat bone marrow after 6 weeks to confirm CR 1

For MDS Evaluation

• Bone marrow aspirate with Prussian blue stain evaluates plasma cells alongside assessment of dysplasia, blasts, and ringed sideroblasts 1
• Plasma cell percentage is less critical in MDS than in plasma cell disorders 1