Richter’s Transformation in the Era of Targeted Therapy

Case Report

Ann Hematol Oncol. 2016; 3(5): 1093.

Richter’s Transformation in the Era of Targeted Therapy

Pierce L¹, Lally K², Phan R², Lewis M² and Sharma S³*

¹Department of Internal Medicine, VA Greater Los Angeles Healthcare System, USA

²Department of Pathology, VA Greater Los Angeles Healthcare System, USA

³Department of Hematology Oncology, West Los Angeles VA Medical Center, USA

*Corresponding author: Sanjai Sharma, Hematology Oncology, West Los Angeles VA Medical Center, Los Angeles, California, USA

Received: May 21, 2016; Accepted: July 18, 2016; Published: July 20, 2016


Transformation of Chronic lymphocytic leukemia (CLL) into an aggressive lymphoma is described as Richter’s transformation (Richter syndrome, RS). It has a very poor outcome and there are no effective therapies. We describe a case of Richter’s transformation in a CLL patient who had received multiple lines of treatment and was being treated with Bruton’s Tyrosine Kinase inhibitor, Ibrutinib. The CLL continued to respond to Ibrutinib while the patient developed an aggressive clonally related transformation lymphoma.

Keywords: Chronic lymphocytic leukemia; Richter’s transformation; BTK inhibitor

Case Presentation

A 69-year-old man with a 14-year history of chronic lymphocytic leukemia (CLL) was admitted to the medicine service with complaints of shortness of breath, drenching night sweats, and enlarging cervical lymph nodes. The neck nodes were progressively rapidly enlarging and were associated with cough. Computed tomography (CT) scan of neck was performed showing multiple bilateral enlarged cervical lymph nodes with the largest dominant node measuring 5.8 cm. Initial lab findings on admission were significant for a white blood cell (WBC) count of 5700/μL (80% lymphocytes) platelet count 63,000/ μL, hemoglobin 11 gm/dL and LDH of 1109 IU/L (normal 87-165 IU/L). He was a febrile but tachycardic and tachypneic with a chest radiograph suggestive of worsening paratracheal lymphadenopathy and other areas of mediastinal lymphadenopathy as well. He was treated for bacterial pneumonia based on his respiratory culture results and persistent cough. Despite treatment with antibiotics and supportive measures, the patient dyspnea did not improve during the hospital course. A Positron emission tomography (PET-CT) scan demonstrated a high SUV of 13.4 in one of the cervical lymph nodes that was biopsied. The pathology results from his lymph node biopsy were consistent with a diffuse large B-cell lymphoma (DLBCL) with a high proliferation rate (Ki-67 labeling index of 90%), indicative of Richter’s Transformation.

CLL leukemic cells in this patient co-expressed CD5 and CD23 markers, CD38 expression was absent. IgVH was mutated and FISH analysis showed only a 13q14 deletion. The neck lymph node biopsy demonstrated a diffuse proliferation of large cells with ovoid to irregular nuclear contours, vesicular chromatin, one to multiple prominent nucleoli and moderate cytoplasm (Figure 1). Lymphoma cells from the cervical lymph node biopsy were positive for CD20, BCL6, MUM1, BCL2, and CD5 with a high proliferation rate. Interestingly there was loss of CD23 expression in the Richter’s transformation DLBCL while the CLL cells were CD23 positive. Molecular analysis detected identical PCR-amplified dominant DNA bands corresponding to the clonal rearrangements of IGH gene from a lymph node biopsy done three years ago and from the neck node.

Citation: Pierce L, Lally K, Phan R, Lewis M and Sharma S. Richter’s Transformation in the Era of Targeted Therapy. Ann Hematol Oncol. 2016; 3(5): 1093. ISSN : 2375-7965