Am J Clin Pathol. 2026 Jul 6;166(1):aqag080. doi: 10.1093/ajcp/aqag080.
ABSTRACT
OBJECTIVES: Plasma cell neoplasms (PCNs) harboring IGH::CCND3 (t(6;14)) are rare (<1% of PCNs). We sought to study these cases, as they have not been studied as a distinct entity, and their clinicopathologic features are not well characterized.
METHODS: Cytogenetics databases were searched for positive IGH::CCND3 interphase fluorescence in situ hybridization (FISH) results in plasma cell neoplasms. We analyzed the clinical, morphologic, immunophenotypic, and cytogenetic features of these cases and evaluated the utility of cyclin D3 immunohistochemistry (IHC) for identifying these neoplasms.
RESULTS: Sixteen patients were identified, presenting with multiple myeloma (n = 9), monoclonal gammopathy of undetermined significance (n = 3), smoldering myeloma (n = 2), plasma cell leukemia (n = 1), and amyloid light chain amyloidosis (n = 1). Median age at diagnosis was 68.9 years. Most cases showed lymphoplasmacytoid morphology (63%, 10/16), with frequent CD20 expression (53%, 8/15) and aberrant expression of CD56 (71%, 10/14) and CD117 (69%, 9/13). Monosomy 13 was the most frequent concurrent cytogenetic abnormality (50%, 7/14). Cyclin D3 IHC showed nuclear expression in plasma cells in all tested patients (11/11). Background erythroid precursors and megakaryocytes also showed variable positivity. When performed as a dual immunostain with CD138, cyclin D3 served as a highly sensitive and specific method for detecting these neoplastic plasma cells.
CONCLUSIONS: IGH::CCND3 PCNs frequently exhibit lymphoplasmacytoid features and CD20 expression, resembling the more common t(11;14) PCNs. Cyclin D3 IHC is an effective surrogate for the t(6;14) translocation in PCNs. We recommend using cyclin D3 IHC in the workup of PCNs with lymphoplasmacytoid morphology but negative cyclin D1 to appropriately trigger reflex FISH testing in positive cases and rescue them from the "partner-negative" category.
PMID:42418658 | DOI:10.1093/ajcp/aqag080