PMC9673799_01
Bone Marrow Biopsy Case #1. The initial bone marrow biopsy of case #1 revealed infiltrating large, atypical lymphocytes with open chromatin and prominent nucleoli (A, H&E stain x 40) which were positive for CD20 (B, IHC x 40). The black arrows in A and B indicate frequent mitosis. Three years later, repeat bone marrow biopsy with roll prep-smear demonstrated recurrent lymphoma (C, WG stain x 50; D, H&E x 40). The neoplastic lymphocytes were positive for PAX5 (E, IHC x 20) and showed a high proliferative rate with a Ki-67 of 60% (E and F, IHC x 40).
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The malignant cells were positive for CD20 (Figure 1A and B) and negative for CD5, CD25, CD30, CD34, BCL-1, and MUM-1. Immunohistochemistry (IHC) studies showed that the neoplastic B lymphocytes were positive for BCL-2 and negative for CD10 and MYC (Figure 1C-F).
Initial FDG PET-CT and Post-Treatment FDG PET-CT for Case #1. Composite FDG PET-CT images of case #1 at initial diagnosis (A and B) and after R-CHOP and high-dose MTX (C and D). Coronal view of fused FDG PET-CT MIP, CT, and PET (A) and sagittal fused FDG PET-CT, CT, and PET (B) demonstrates intense FDG accumulation in the bone marrow of the axial and appendicular skeleton at initial diagnosis without a specific focus of FDG accumulation, nor lytic or sclerotic lesions on CT. Reference L3 vertebral body SUVmax of 9.9 (red arrow). Physiologic FDG accumulation is seen in the liver (Orange arrow) and blood pool (magenta arrow) and spleen. No hypermetabolic lymph nodes or other soft tissue to suggest lymphomatous involvement. Post treatment fused FDG PET-CT MIP, CT, and PET (C) and sagittal fused FDG PET-CT, CT, and PET (D) demonstrate normalization of FDG accumulation in the bone marrow of the axial and appendicular skeleton (red arrow) with the L3 vertebrae (SUVmax of 2.3), and unchanged FDG accumulation in the liver (Orange arrow) and blood pool (magenta arrow).
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Epstein-Barr virus-encoded RNA (EBER) in situ hybridization (ISH) was also negative. 18F Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) demonstrated bone marrow involvement without evidence of other disease (Figure 2A and B). She achieved complete remission (CR) after four cycles (Figure 2C and D).
PMC9673799_02
Peripheral Smear and Bone Marrow Biopsy Case #2. For case #2, circulating atypical large lymphocytes (arrows) were present in the peripheral blood smear (A, WG stain, x 40; inset x 60). The roll prep smear and bone marrow biopsy revealed diffusely infiltrating lymphoma cells (B, WG stain x 40; C, H&E stain x 20). IHC showed the lymphoma cells were positive for CD79a and CD10 with a high proliferative rate by Ki-67 (80%) (D, E, F, x 20).
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There was an absolute lymphocytosis with 8% blastoid cells on peripheral smear (Figure 3A and Inset). IHC studies showed the neoplastic lymphocytes were positive for CD10, CD20, CD79a, PAX-5, BCL-2 (90%), and MYC (90%) (Figure 3B-F).
Peripheral Blood Flow Cytometry and FISH Testing for Case #2. For case #2, ancillary studies were performed on the peripheral blood as the bone marrow was a dry tap. Flow cytometry analysis identified two distinct B-cell populations (A-E). One B-cell population (red color) expressed CD19, CD5, and CD23 but was negative for CD10. The second B-cell population (pink color) was positive for CD10 but negative for CD5 and CD23. Both populations showed kappa light chain restriction (C and D). FISH break-apart probes showed MYC gene rearrangement and BCL2 gene rearrangement (F and G, green and red arrows indicate break apart signals) and identified deletion of 13q14.3 (H).
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PBFCM revealed two distinct B-cell populations (Figure 4A-E). Lymphoma fluorescence in situ hybridization (FISH) testing was consistent with HGBCL with BCL-2 and C-MYC rearrangements, the so-called "double hit" lymphoma (Figure 4F-G). CLL was positive for 13q deletion in 22% of cells (Figure 4H). Cerebrospinal fluid (CSF) cytology was negative for malignancy on 2 occasions.
FDG PET-CT of Case #2 After Cycle 1 of R-CHOP. Composite FDG PET-CT images of case #2 after cycle 1 of R-CHOP chemotherapy. Coronal view of fused FDG PET-CT MIP, CT, and PET (A) and sagittal fused FDG PET-CT, CT, and PET (B) demonstrates moderate intense FDG accumulation in the bone marrow of the axial and appendicular skeleton without a specific focus of FDG accumulation nor lytic or sclerotic lesions on CT. Reference L4 vertebral body SUVmax of 5.9 (red arrow). Physiologic FDG accumulation is seen in the liver (Orange arrow) and blood pool (magenta arrow) and spleen. No hypermetabolic lymph nodes or other soft tissue to suggest lymphomatous involvement.
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