Case report: 'Atypical Richter transformation from CLL-type monoclonal B-cell lymphocytosis into Burkitt lymphoma in a treatment naïve patient'

Abstract

Background: Richter transformation refers to the progression of an initially slow-growing small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) into an aggressive lymphoma, typically diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma.

Case presentation: The patient presented with a rapid onset of localized cervical swelling, accompanied by monoclonal B-cell lymphocytosis displaying a CLL immunophenotype. The histopathological analysis identified a Burkitt lymphoma (BL) located in the submandibular gland and adjacent lymph node. The patient's bone marrow displayed a minor infiltration of monoclonal B-cells with a CLL immunophenotype (< 10%). Molecular analysis demonstrated the presence of the same monoclonal rearrangement in the framework region (FR3 region) of the immunoglobulin heavy chain (IGH) locus. High-throughput sequencing of the immunoglobulin heavy and light chains also confirmed the presence of the same rearrangement in SLL/CLL and in the Burkitt lymphoma sample, but also highlighted the presence of a second rearrangement in the Burkitt lymphoma cells, not shared with the SLL/CLL cells in the bone marrow. The patient was treated with DA-EPOCH-R, which lead to a complete metabolic response.

Conclusion: This report provides an exceptionally rare description of a CLL-type monoclonal B-cell lymphocytosis transforming into a very aggressive Burkitt lymphoma in a treatment naïve patient.

Keywords: Burkitt lymphoma; MBL; Richter transformation; SLL/CLL; state sequencing.

Figure 1

Atypical Richter transformation with localized presentation of Burkitt lymphoma in the submandibular gland. (A) Sonography of the cervical swelling, demonstrating inhomogeneous tissue. (B) The bone marrow displayed scarce nodular infiltrates of small lymphocytic cells which (C) stained positive for CD20⁺ and (D) presented a low proliferative activity (ki-67/MIB). (E) PET-CT scan axial plane of the patient, documented cervical consolidations with high metabolic activity. (F) Full body PET-CT scan with coronal plane visualizing the localized manifestation. (G) Submandibular gland specimen, stained with hematoxylin and eosin (H&E), demonstrating stroma with diffuse atypical lymphoid infiltrate composed of slightly pleomorphic configured cells with mitotic figures and interspersed scattered tingible body macrophages. (H) Submandibular gland lymphoid cells staining positive for the B-cell marker CD20. (I) Highly proliferative lymphoid cells (stained against ki-67) in the submandibular gland. (J) Submandibular gland B-cells being BCL2 negative and (K) c-MYC positive. (L, M) Multiplex PCR and high-resolution fragment analysis of the IGH locus. The numbers above designate fragment alignment by size distribution. A clear dominant peak was observed in the FR3 region of the IGH locus. This peak likely corresponds to the same clone, and is not visible in the submandibular gland sample due to higher DNA fragmentation caused by formalin-fixation (FR1 dominant peak fragment size > 360 bp). (N) BCR sequencing experiment. Top row) Depiction of the top IGH clones utilized by SLL/CLL cells vs. BL cells. Lower row) Depiction of the top IGKL clones utilized by SLL/CLL cells vs. BL cells. Gray shading depicts corresponding clones found in both tumors. (O) Heatmap illustrating the VJ gene usage in BL sequences not shared with the SLL/CLL B-cells and the overutilization of the V-segment V4-34. Frequency have been log10 transformed to reduce skewness of a measurement variable. Histology specimens are displayed with a 40x magnification (A-H) and 20x (I-K).