Chronic Lymphocytic Leukemia and Fatal Tissue Infiltration

Abstract

Chronic lymphocytic leukemia (CLL) is typically characterized as an indolent process that is most often a comorbid condition rather than an immediate cause of death. While it is well-known that CLL can infiltrate tissues and manifest as small lymphocytic lymphoma, diffuse parenchymal infiltration with perforation and hemorrhage is most often associated with more aggressive lymphomas, such as diffuse large B-cell lymphoma. Here we present a series of three cases of CLL in which fatal hemorrhage (two spontaneous and one procedure-related) resulted from tissue compromise due to infiltration of organ parenchyma by the patient's known CLL. In the first case, the patient died of spontaneous duodenal perforation and hemorrhage associated with CLL. This patient also had heart failure related to myocardial infiltration and diffuse hepatic infiltration. A second patient died of spontaneous pulmonary hemorrhage associated with CLL. The final case involved fatal pulmonary hemorrhage during bronchoscopy in a patient with unsuspected bronchial involvement by CLL. At autopsy, all three cases showed histologic and immunohistochemical features of typical CLL. None of the cases showed evidence of Richter transformation, and none of the patients had clinically evident coagulopathy. The literature contains few reports of parenchymal infiltration by CLL with fatal perforation or hemorrhage. This pattern may represent an under-appreciated mechanism of CLL contribution to morbidity and mortality. Further characterization of how CLL invades tissue and ultimately leads to compromise in the integrity of that tissue may be of clinical significance. In addition, continued research into the prevalence of CLL-related organ compromise, risk assessment, and disease progression monitoring is warranted to improve patient outcomes and quality of life.