Atypical “accelerated” chronic lymphocytic leukemia with abnormal lymphocyte chromatin clumping, bone involvement, and exceptional response to Imbruvica

Abstract

Background: The “accelerated” chronic lymphocytic leukemia (aCLL) is a relatively rare form of CLL progression. The expanded proliferation centers in aCLL have been associated with adverse prognostic features and propensity to more aggressive behavior with shorter survival. Case: An atypical case of aCLL with distinct features is described. A 66-year-old female presented with a marrow replacing process associated with multiple osseous metastases and trivial lymphadenopathy. Bone biopsy revealed an unspecified low-grade B cell lymphoproliferative disorder that demonstrated a suboptimal response to standard chemotherapy. Subsequent lymph node biopsy demonstrated findings consisted with aCLL. The distinguishing features of the case were, in addition to bone involvement, the lagging peripheral lymphocytosis and a striking pattern of the chromatin clumping with a prominent “shattered” appearance reminiscent of Pelger-Huet-like dysplastic anomaly. A targeted next-generation sequencing (NGS) assay detected pathogenic mutations in TP53 and SF3B1. In contrast to chemotherapy, the case demonstrated an excellent response to imbruvica. Conclusion: The noted peculiarities could potentially distinguish this case as a novel, rare variant of aCLL.