Diagnostic Sensitivity of the PCR for Antigen Receptor Rearrangement (PARR) Assay for Canine Plasma Cell Tumors.

Abstract

BACKGROUND: The PCR for Antigen Receptor Rearrangement (PARR) assay assesses clonality of a lymphoid population. Studies suggest PARR has decreased sensitivity for detecting clonality in canine plasma cell tumors (PCT) compared to lymphoma. OBJECTIVE: Assess sensitivity of PARR assays targeting the immunoglobulin heavy chain (IGH), immunoglobulin lambda light chain (IGL), and kappa deleting element (Kde) loci in canine PCT. METHODS: Canine cases included 35 PCTs (multiple myeloma and extramedullary, cutaneous or oral PCTs), 5 non-PCT foil cases, and 40 B-cell lymphoma cases. PCT diagnoses were confirmed via CD3, PAX5, and MUM1 immunolabeling, and some additionally had histopathology, serum or urine protein electrophoresis, or immunofixation. Nodal B-cell lymphomas were diagnosed by flow cytometry. Routine PARR (targeting IGH V-D-J and D-J rearrangements) and extended PARR (targeting additional IGH genes and IGL and Kde rearrangements) were performed on cytologic specimens (PCT and foil cases) and flow cytometry aspirates (lymphoma cases). Diagnostic sensitivity was calculated. RESULTS: Across both PARR assays, every PCT case with sufficient sample was interpreted as clonal and no foil cases were clonal. The routine PARR assay detected a clonal immunoglobulin rearrangement in 26/35 PCT cases (74.3%; 95% CI 56.7%-87.5%). The extended assay detected immunoglobulin gene clonality in 33/35 PCT cases (94.3%; 95% CI 80.8%-99.3%). 40/40 lymphoma cases were clonal in both the routine and extended PARR assays. CONCLUSION: The combined PARR assays used in this study, evaluating multiple IG loci, detected clonality in all PCTs tested, but routine PARR (targeting IGH) was less sensitive for detecting PCT clonality compared to B-cell lymphomas.