What to know about rare B-cell malignancies in 2025

Rare B-cell malignancies pose a unique management challenge because of their rarity and aggressiveness. Given their low incidence, they require a high index of suspicion for diagnosis and necessitate specialized therapeutic approaches. Herein, we discuss 3 of those rare lymphomas: plasmablastic lymphoma, lymphomatoid granulomatosis, and intravascular lymphoma. Plasmablastic lymphoma is aggressive and often linked to immunosuppression, particularly in HIV- infected individuals. It is characterized by plasmablastic morphology lacking CD20 expression, extranodal disease, MYC rearrangement, and frequent Epstein-Barr virus infection. Recent advancements in treatment involve using novel agents like bortezomib, daratumumab, and B-cell maturation antigen-targeted therapy, which are improving outcomes; however, the prognosis for relapsed disease remains poor. Lymphomatoid granulomatosis is a rare, Epstein-Barr virus-driven B-cell disorder defined by angiocentric and angiodestructive infiltrates. It primarily affects the lungs but can also involve skin and the central nervous system, causing systemic symptoms. Treatment and prognosis vary by histologic grade; low-grade cases may be treated with immunomodulation, while high-grade cases generally require chemoimmunotherapy. Intravascular lymphoma involves malignant B cells proliferating in small blood vessels, leading to nonspecific clinical symptoms. Early diagnosis through tissue biopsy is crucial. The best remission chances come from rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy combined with central nervous system-directed treatment. New research is ongoing for relapsed cases.