“Soccer ball” cells to “donut” cells: an unusual case of Richter syndrome Free

A 56-year-old man presented with relapsed chronic lymphocytic leukemia (CLL) with 90% bone marrow (BM) involvement, “soccer ball” morphology (panel A, hematoxylin and eosin stain; panel B, Wright-Giemsa stain), and the following immunophenotype: CD5⁺/CD19⁺/CD20dim⁺/CD38⁺/ZAP-70⁺/dim κ (panel C [APC, allophycocyanin; BV, brilliant violet]; panel D [FITC, fluorescein isothiocyanate; PE, phycoerythrin]). Fluorescence in situ hybridization (FISH) detected deletion D13S319 in both loci. The IGVH gene was unmutated and next-generation sequencing (NGS) showed SF3B1 mutation. He had a good response with venetoclax. Seven months later, he presented with pancytopenia, increased lactate dehydrogenase (1039 U/L), and multicompartmental lymphadenopathy. BM (panel E, hematoxylin and eosin stain) and subsequent lymph node biopsy showed large pleomorphic cells with “donut,” horseshoe, and Reed-Sternberg Hodgkin–like morphology (panel F [original magnification, ×1000; Wright-Giemsa stain]; inset [original magnification, ×1000; Wright-Giemsa stain]) expressing CD30 (panel G, immunostain), ALK-1 (panel H, immunostain), and CD2 (weak)/CD4/CD5/CD45 (LCA)/CD43; he was negative for CD3, CD7/CD8/CD15, and Pax-5. Flow cytometry detected a minute residual CLL population (0.2%). FISH detected ALK rearrangement. The FISH panel demonstrated extra copies of TP53 and D12Z3 and monosomy 13. NGS detected 2 TP53 gene mutations (TP53p.V216L and TP53p.L289fs) not identified previously.

Development of an aggressive neoplasm occurs in ∼5% of patients with CLL and is known as Richter syndrome, with diffuse large B-cell lymphoma being the most common subtype. In 80% to 90% of cases, aggressive neoplasm is clonally related to CLL; in 10% to 20%, the clones are unrelated. This case illustrates anaplastic large cell lymphoma, ALK⁺ as a rare subtype of Richter syndrome; ancillary studies suggest that the neoplasms are clonally unrelated.