Flow Cytometry Versus Immunoperoxidase Staining for Determination of Plasma Cell Clonality with Small Plasma Cell Numbers
Karen Moser, Mohamed E Salama, Jessica L Kohan, Sheryl R Tripp, David W Bahler, Sherrie L Perkins. Univ. of Utah Health Sciences Center, Salt Lake City, UT; ARUP Laboratories, Salt Lake City, UT
Background: Diagnosis of plasma cell (PC) myeloma requires demonstration of clonal PCs in the marrow, by 2008 WHO Classification and International Myeloma Working Group (IMWG) criteria. A recent update to the IMWG uniform response criteria defines stringent complete response as absent clonal PCs by immunoperoxidase staining (IPOX) or flow cytometry (FC), and IMWG diagnostic guidelines suggest IPOX or immunofluorescence for clonality assessment (Dimopoulos M 2011; Rajkumar SV 2011).
In our practice, we use IPOX for CD138 for PC quantitation and FC for PC light chain restriction. In this study, we review a pilot series of cases with low PC numbers and compare IPOX and FC performance, hypothesizing that FC can more accurately detect small mixed monoclonal and polyclonal PC populations, often seen in maintenance and early relapse cases.
Design: We retrospectively identified 24 cases examined 2/1-5/31/2011 with previously diagnosed PC myeloma, ≤10% PCs by CD138 IPOX staining, and both polyclonal and monoclonal PCs by FC. To test whether IPOX could also identify small clonal populations, IPOX staining for CD138, kappa and lambda light chains on core biopsies was reviewed when blinded to clinical and FC data.
Results: Patient age ranged from 48 to 81 years (mean= 65, median= 64), with 14 males and 10 females. Patients had 0-3 prior marrow transplants in the course of their treatment (1 in 9/24 cases).
Three hematopathologists (K.M., M.E.S., and S.L.P.) independently reviewed IPOX (CD138, kappa and lambda light chains). Excepting one case with inadequate tissue remaining, a consensus was reached in all cases. Eight of 24 cases (33%) were interpreted to have monoclonal PCs by IPOX (5 kappa and 3 lambda). Cases interpreted as monoclonal also had sheets/clusters of PCs and/or higher PC numbers. The remaining 15 cases (63%) had ≤5% PC and were interpreted to have polyclonal PCs by IPOX, despite clear monoclonal PCs by FC.
Conclusions: FC can better identify small mixed PC populations and is particularly useful in cases with ≤5% PC by IPOX and both monoclonal and polyclonal PCs. Despite the IMWG recommendations, IPOX alone may not be adequately sensitive to detect small monoclonal PC populations in previously treated patients, which are important to detect in the evaluation of ongoing treatment and remission. Our data show that FC is a superior tool for accurate detection of small monoclonal PC populations, and that FC should be used to monitor therapy in all cases of PC myeloma.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 224, Monday Morning