Evaluation of an open-source machine-learning tool to quantify bone marrow plasma cells

Abstract

Aims: The objective of this study was to develop and validate an open-source digital pathology tool, QuPath, to automatically quantify CD138-positive bone marrow plasma cells (BMPCs).

Methods: We analysed CD138-scanned slides in QuPath. In the initial training phase, manual positive and negative cell counts were performed in representative areas of 10 bone marrow biopsies. Values from the manual counts were used to fine-tune parameters to detect BMPCs, using the positive cell detection and neural network (NN) classifier functions. In the testing phase, whole-slide images in an additional 40 cases were analysed. Output from the NN classifier was compared with two pathologist's estimates of BMPC percentage.

Results: The training set included manual counts ranging from 2403 to 17 287 cells per slide, with a median BMPC percentage of 13% (range: 3.1%-80.7%). In the testing phase, the quantification of plasma cells by image analysis correlated well with manual counting, particularly when restricted to BMPC percentages of <30% (Pearson's r=0.96, p<0.001). Concordance between the NN classifier and the pathologist whole-slide estimates was similarly good, with an intraclass correlation of 0.83 and a weighted kappa for the NN classifier of 0.80 with the first rater and 0.90 with the second rater. This was similar to the weighted kappa between the two human raters (0.81).

Conclusions: This represents a validated digital pathology tool to assist in automatically and reliably counting BMPC percentage on CD138-stained slides with an acceptable error rate.

Keywords: bone marrow neoplasms; computer-assisted; image processing; multiple myeloma; pathology; surgical.