Genetic background of Richter transformation of atypical chronic lymphocytic leukemia to diffuse large B-cell lymphoma - a case study.
Sandra Przybysz, Anna Łojko-Dankowska, Magdalena Rakoczy et al.
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Case in brief
A 29-year-old woman with atypical chronic lymphocytic leukemia (aCLL) was initially treated with fludarabine, cyclophosphamide, and rituximab. Eight years later, disease progression led to ibrutinib treatment; after 5 months, her condition deteriorated. PET-CT suggested Richter transformation, and histopathology of nodal lesions confirmed diffuse large B-cell lymphoma (DLBCL). She was subsequently treated with DHAP-R and allogeneic hematopoietic stem cell transplantation. Whole-genome sequencing of lymphoma cells identified pathogenic variants in COL11A1 and MGME1 and likely pathogenic variants in ZMYM3, ALG6, UBA5, and ATG7.
What made this case unusual
Among the identified genes, only ZMYM3 was described as recurrently mutated in B-cell CLL; the other pathogenic or likely pathogenic variants point to a complex molecular background in this aCLL-to-DLBCL transformation.
Diagnostic / clinical pearl
In a patient with aCLL whose condition deteriorates, PET-CT may suggest Richter transformation, but nodal histopathology confirmed DLBCL in this case.
Why it matters
The authors suggest considering whole-genome variant assessment at B-CLL diagnosis, particularly when Richter transformation is suspected; the additional variants identified here require further study.