Series 4 : Diagnostic challenges in Plasma Cell Neoplasms . 📌Post 2 : Morphology Pitfalls in Plasma Cell Neoplasms- 2026 review. 📌Most myelomas are easy. The variants are not. ⏩Small cell / lymphoplasmacytic variant - 3-4% of cases - Looks like LPL or MZL - Frequently CD20+ and cyclin D1+ ( because of t(11;14)) - Key separators : CD138+ , usually CD45- , CD19-, clinical CRAB / lytic lesions , no MYD88. ⏩Plasmablastic variant - Large vesicular nuclei , prominent nucleoli - almost identical morphology & phenotype to Plasmablastic lymphoma . - Differentiate by clinical context , extent of marrow involvement , M- protein , FLC ratio and FISH ( gain 1q , del 1p , t(4;14) favour myeloma .) ⏩Anasplastic / pleomorphic variant - CaN express CD30 and mimic ALCL - Rare aberrant T cells markers ( CD3, CD4 ) occur. ⏩Myelomatous Effusion - can occur at initial diagnosis or during progression ( an ominous sign ). - Even when plasma cells become multinucleated or pleomorphic , the classic eccentric nucleus and perinuclear hof often persist. - When Morphology turns Plasmablastic , always Differentiate from primary effusion lymphoma , Plasmablastic lymphoma and fluid overload large B cell lymphoma . - Presence of M- protein + CRAB features strongly favours Myelomatous Effusion . ⏩Plasma Cells Leukemia - Defined by > 5% circulating plasma cells in peripheral blood ( WHO - HAEM5 / IMWG 2021 ) - Primary PCL ( de novo ) is highly aggressive. - Secondary PCL develops during relapse or progression . - Leukemic plasma cells are frequently CD56-negative. - Emerging data suggest even > 2% circulating neoplastic plasma cells may behave like occult primary PCL . Save this Post for quick reference #Hematopathology #Myeloma #Pathology #PlasmaCellLeukemia #DiagnosticPathology #MultipleMyeloma #Morphology