Combined evaluation of bone marrow aspirate and biopsy is superior in the prognosis of multiple myeloma

Abstract

Background: Estimation of plasma cell infiltrates in bone marrow aspirates (BMA) and bone marrow biopsy (BMB) is a standard method in the diagnosis and monitoring of multiple myeloma (MM). Plasma cell fraction in the bone marrow is therefore critical for the classification and optimal clinical management of patients with plasma cell dyscrasias. The aim of the study was to compare the percentage of plasma cells obtained by both methods with the patient clinical parameters and survival.

Methods: This retrospective study included BMA and BMB of 59 MM patients. The conventional differential count was determined in BMA to estimate the percentage and cytologic grade of plasma cells. The pattern of neoplastic infiltration and percentage of plasma cells were estimated on CD138 immunostained BMB slides microscopically and by computer-assisted image analysis (CIA).

Results: Significantly higher values of plasma cell infiltrates were observed in pathologist (47.7 +/- 24.8) and CIA (44.1 +/- 30.6) reports in comparison with cytologist analysis (30.6 +/- 17.1; P < 0.001 and P < 0.0048, respectively). BMB assessment by pathologist counting and using CIA showed strongest correlation (r = 0.8; P < 0.0001). Correlation was also observed between the pathologist and cytologist counts (r = 0.321; P = 0.015) as well as comparing the percentage of plasma cells in BMA and CIA (r = 0.27; P = 0.05). Patients with clinical stage I/II had a significantly lower CIA plasma cell count than those with clinical stage III (P = 0.008). Overall survival was shorter in patients with more than 25% of atypical plasma cell morphology estimated in BMA (P = 0.05) and a higher percentage of tumor cell infiltrates estimated by the pathologist and CIA (P = 0.0341 and P = 0.013, respectively).

Conclusion: Study results suggested the combined analyses to be useful as a routine procedure to achieve more accurate and informative diagnostic data.

Figure 1

Computer-assisted image analysis. Screen shoots of scanned sample, with detailed histology images of (a) interstitial, (b) nodular and (c) diffuse type of bone marrow infiltration showing color based sample analysis.

Figure 2

Analysis of plasma cell count in bone marrow aspirate (BMA) and bone marrow biopsy (BMB). (a) Box and whisker plot (T-test) showing significant difference in plasma cell count between BMA and BMB analysis. Higher values were observed in pathologist (BMB) (mean 47.712 ± 24.8) and computer image analysis (CIA) (mean 44.113 ± 30.6) as compared with (BMA) cytologist report (mean 30.649 ± 17.1) (P < 0.001 and P < 0.0048, respectively). (b) Scatter plots showing correlation between CIA and BMB; BMA and BMB; CIA and BMA. Correlation of BMB assessment: pathologist and CIA counting (r = 0.8; P < 0.0001), pathologist and cytologist counting (r = 0.321; P = 0.015), and percentage of plasma cells in BMA and CIA (r = 0.27; P = 0.05).

Figure 3

Kaplan-Meier survival analysis (months) showing difference in patients survival (when plasma cell count divided in high and low groups according the median) obtained by (a) pathologist report (BMB) (P = 0.0341), (b) computer-assisted (CIA) report (P = 0.013), and (c) cytologist (BMA) report (P = 0.05), when cut off for atypical plasma cell count was set at 25%.