High-Grade T-cell Lymphoma Complicating B-cell CLL: An Unusual Manifestation of Richter Transformation

Introduction/Background/Significance: Richter transformation (RT) typically involves transformation of chronic lymphocytic leukemia (CLL) into aggressive B-cell lymphoma. The transformation into high-grade T-cell lymphoma complicating underlying CLL is exceedingly rare, posing unique diagnostic and management challenges. We present two cases demonstrating the complexity in clinical presentation, progression, and therapeutic approaches for this unusual manifestation.

Materials and Methods/Case Presentation/Objective: Case 1: An 82-year-old man presented initially with cervical lymphadenopathy and was diagnosed with CD5+/CD20+ B-cell CLL/SLL. Further investigation revealed concurrent aggressive CD30-positive, ALK-negative anaplastic large cell T-cell lymphoma (Ki-67 >80%). Treatment with CHOP chemotherapy combined with Brentuximab vedotin led to significant gastrointestinal toxicity and severe pancytopenia, requiring extensive hospitalization. Despite temporary clinical stabilization, the patient experienced rapid disease progression involving widespread pulmonary nodules, pleural effusions, and skeletal metastasis. Given poor tolerance to treatment and disease severity, the patient transitioned to palliative and hospice care. Case 2: A 70-year-old man initially diagnosed with stage I CLL/SLL (CD5+/CD20+) presented with progressive lymphadenopathy. Biopsy confirmed the simultaneous presence of low-grade CD5-positive B-cell lymphoma (Ki-67 ~15%) and high-grade CD30-positive T-cell lymphoma (Ki-67 ~40%). Following six cycles of Rituxan-CHOP chemotherapy, the patient achieved an initial complete response. However, relapse occurred rapidly with aggressive T-cell lymphoma dominating the clinical picture. Brentuximab therapy was restarted, providing transient symptom control. Subsequent PET imaging demonstrated diffuse multifocal metabolic progression, complicating further therapeutic management.

Results/Description/Main Outcome Measures: These cases illustrate the rare but aggressive transformation of B-cell CLL/SLL into high-grade T-cell lymphoma. The clinical course in both cases was marked by rapid disease progression and significant treatment-related toxicities. CD30-directed therapies, while initially beneficial, showed limitations due to relapse and adverse effects. Therapeutic decisions must balance efficacy with patient tolerance, particularly in elderly or frail patients. Accurate histopathological and immunophenotypic characterization is vital for managing these complex presentations.

References:1. Amanda Lee, Milton E. Skelly, Douglas W. Kingma, L. Jeffrey Medeiros, B-Cell Chronic Lymphocytic Leukemia Followed by High Grade T-Cell Lymphoma: An Unusual Variant of Richter’s Syndrome, American Journal of Clinical Pathology, Volume 103, Issue 3, 1 March 1995, Pages 348–352, https://doi.org/10.1093/ajcp/103.3.3482. Hangping Ge, Xiangping Wu, Jianping Shen, Junfa Chen, Ying Chen, Yu Zhang, A case report of extranodal NK/T-cell lymphoma in patient with chronic lymphocytic leukemia. Medicine 97(30):p e11619, July 2018. | DOI: 10.1097/MD.0000000000011619

Conclusions: Transformation of B-cell CLL/SLL into aggressive T-cell lymphoma represents a unique and challenging Richter transformation variant. Prompt diagnosis, meticulous characterization, and tailored treatment strategies are crucial. Further research into targeted therapies is essential to improve clinical outcomes for this rare but aggressive disease manifestation.