Cyclin D1 expression as a diagnostic biomarker in lymphoid neoplasms

Cyclin D1 is a key regulator of cell cycle progression and a well-established diagnostic marker in mantle cell lymphoma (MCL). However, its expression has also been reported in a subset of other B-cell lymphoproliferative disorders, potentially creating diagnostic challenges. We performed a retrospective analysis of Cyclin D1-positive lymphoid neoplasms diagnosed between 2016 and 2025 at a single tertiary care centre. Expression patterns were evaluated according to tumour type, staining intensity, distribution, and co-expression with lineage-specific immunohistochemical markers. A total of 41 Cyclin D1-positive cases were identified, including MCL (65.85%), plasma cell neoplasms (19.51%), diffuse large B-cell lymphoma (DLBCL) (7.31%), hairy cell leukaemia (HCL) (4.88%), and chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) (2.43%). MCL cases demonstrated strong, diffuse nuclear expression with high concordance with CD5 and SOX11. In contrast, non-MCL neoplasms exhibited variable, frequently weaker, and more heterogeneous expression patterns. In CLL/SLL, Cyclin D1 positivity was minimal and restricted to proliferation centres, whereas HCL showed moderate and heterogeneous expression. DLBCL cases demonstrated moderate nuclear staining with limited overlap between Cyclin D1-positive and CD20-positive tumour cells. Although Cyclin D1 remains a highly sensitive marker for MCL, its expression in other B-cell neoplasms limits its diagnostic specificity. Accurate interpretation requires integration of morphological, immunophenotypic, and molecular findings to avoid diagnostic pitfalls, particularly when distinguishing MCL from other Cyclin D1-positive lymphoid neoplasms