Cold Agglutinin Disease

Differential diagnosis

• no B symptoms (may be difficult to separate from infx)
• no extramedullary disease (may push you toward MZL)
• CD5- (>50% CAD -ve for CD5), CD10- B cells: MZL vs IgM LPL (Waldenstrom)
• MYD88 L265P -ve (usu + in LPL)
• certain clusters of genomic and cytogenetic changes, e.g. KMT2D variant (69%) complete or partial gain of chromosome 3 (93%)
• WHO 2022: CAD is now a distinct lymphoid neoplasm (CAD-associated LPD) (hopefully, more diagnostic consensus will follow)