Primary bone lymphoma represents less than 1% of all malignant bone tumors and approximately 3% of extranodal lymphomas. Diffuse large B-cell lymphoma constitutes the most common histological subtype of primary bone lymphoma, typically affecting adults with a slight male predominance. The clinical presentation often mimics primary bone sarcomas, potentially leading to diagnostic delays. Double-expressor lymphomas, characterized by MYC and BCL2 protein co-expression, constitute 20-30% of DLBCL cases and are associated with inferior outcomes compared to standard DLBCL, requiring consideration of intensified treatment regimens.

A 29-year-old male presented with several months of progressive upper extremity pain, swelling, and limited range of motion involving the long bones and scapula. The clinical presentation initially raised suspicion for osteosarcoma or soft tissue sarcoma, prompting orthopedic evaluation and excisional biopsy.

Macroscopic examination revealed approximately 4 cm of grayish-white to brown tissue fragments submitted for histopathological analysis. Microscopic evaluation demonstrated cellular morphology consistent with lymphoproliferative disease rather than sarcomatous features, prompting comprehensive immunohistochemical evaluation.

Immunohistochemical analysis confirmed lymphoid origin with positive LCA (leukocyte common antigen) staining. B-cell lineage was established by strong, diffuse CD20 positivity (80-85% of cells). The tumor demonstrated germinal center B-cell phenotype with BCL6 expression in 80-85% of cells. Critically, MYC expression was present in 40-45% of tumor cells, suggesting double-expressor status pending BCL2 confirmation.

The proliferation index was extremely high with Ki-67 staining positive in 80-85% of cells, indicating highly aggressive biology. Negative staining for MyoD1, CD34, S100, and CD3 excluded sarcomatous differentiation and T-cell lymphoma.

Based on the constellation of findings, the diagnosis of high-grade diffuse large B-cell lymphoma with germinal center phenotype and suspected double-expressor features was established. The anatomical location involving upper extremity long bones and scapula confirmed primary bone lymphoma classification.

Additional molecular studies were recommended including FISH analysis for MYC, BCL2, and BCL6 rearrangements to distinguish between double-expressor and double-hit lymphoma. Comprehensive next-generation sequencing panel evaluation was suggested focusing on prognostically relevant genes including TP53, CDKN2A/B, NOTCH1/2, EZH2, and other lymphoma-associated mutations.

This case illustrates several important clinical and pathological considerations. Primary bone DLBCL in young adults is uncommon and may present diagnostic challenges due to clinical similarity to primary bone sarcomas. The initial clinical suspicion of sarcoma necessitated careful immunohistochemical evaluation to establish correct diagnosis.

The double-expressor phenotype with MYC and suspected BCL2 co-expression, combined with extremely high Ki-67 proliferation index (80-85%), indicates aggressive biology requiring intensive treatment approaches. While confirmation of BCL2 expression and FISH analysis for genetic rearrangements remain pending, the current findings suggest consideration of dose-adjusted EPOCH-R or similar intensified regimens rather than standard R-CHOP therapy.

The young age of the patient and localized bone involvement may offer favorable prognostic factors despite the aggressive biological features. However, the high proliferation index and suspected double-expressor status necessitate careful treatment planning with multidisciplinary input.

Primary bone DLBCL with double-expressor features in young adults represents a rare but aggressive entity requiring prompt recognition and intensive treatment. This case emphasizes the importance of comprehensive immunohistochemical evaluation in suspected bone malignancies and highlights the need for molecular characterization to guide optimal therapeutic approaches in high-grade B-cell lymphomas.