case_images: PMC11099200_01
case_images: 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).
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case_images: Sonography revealed an inhomogeneous tissue at the site of the swelling ( Figure 1A ). The scan visualized hypermetabolism in the right submandibular gland and an adjacent lymph node (2.6 x 3.3cm, SUVmax 14.9,  Figures 1B, C . The biopsy revealed an infiltration by medium-sized, monomorphic, and blastic CD20+ B-cells with basophilic cytoplasm accompanied by a significant number of mitotic figures ( Figures 1D, E ). The proliferation rate was very high (ki-67/MIB 95%,  Figure 1F ) and tingible body macrophages were interspersed ( Figure 1G ). TdT were negative within B-cells, whereas c-MYC positivity was abundant ( Figure 1H ). B-cell infection by EBV was negative ( Table 1 ). The pattern pointed to the differential diagnosis of Burkitt lymphoma. In October 2022, a bone marrow investigation revealed only 10% infiltration by CD20+ small lymphoid cells ( Figures 1I, J ). These small B-cells were low proliferative ( Figure 1K ). Remarkably, the malignant B-cells found in the submandibular gland and the bone marrow exhibited an identical monoclonal rearrangement of 108bp length in the framework region (FR3 region) of the immunoglobulin heavy chain (IGH) locus ( Figures 1L, M ), however an additional peak was noted in the Burkitt lymphoma sample ( Figure 1M ). IGL). IGH sequencing partially confirmed the results obtained suing fragment analysis: the SLL/CLL B-cells and the Burkitt lymphoma cells shared the same top rearrangement, with a frequency of 80.1% in the SLL/CLL sample and 40.5% in the Burkitt lymphoma sample ( Figure 1N ;  Table 2 , IGHV3-11).