Synchronous breast carcinoma and diffuse large B-cell lymphoma occurring as independent primary malignancies is exceptionally rare. Because these tumors differ markedly in histological origin, biological behavior, and treatment strategies, their coexistence can easily lead to diagnostic pitfalls and therapeutic dilemmas. Reporting such a case provides new insights into the clinical recognition and management of rare dual primaries. A 54-year-old woman presented with a painless left cervical (neck) mass. Imaging revealed a left breast lesion with multi-station lymphadenopathy (including cervical nodes), initially interpreted as metastatic breast carcinoma. Breast core biopsy confirmed HER2-overexpressing invasive ductal carcinoma with strong ER/PR positivity. Cervical (neck) lymph-node biopsy established diffuse large B-cell lymphoma (non-GCB/MCD) with TP53, MYD88, and CD79B mutations. The patient received rituximab-based therapy plus a Bruton tyrosine kinase inhibitor and underwent simple mastectomy. The breast carcinoma has remained controlled without evidence of recurrence, whereas the relapsing lymphoma ultimately determined the disease course. This case emphasizes the need for independent biopsies of suspicious lesions to avoid misclassification as metastatic disease. Management should follow a “lymphoma-first” approach with careful sequencing to balance treatments for both malignancies and to minimize overlapping toxicities. Prognosis is largely driven by the biological features of the lymphoma, particularly in high-risk molecular subtypes. A dual-track follow-up strategy, recording outcomes for each tumor separately, may improve clarity in assessing prognosis and guiding individualized care. This report underscores the importance of multidisciplinary collaboration and highlights potential directions for future research on the mechanisms and management of synchronous dual primaries.
Zhu et al. (2026) studied this question.