Increased Incidence of T-Cell Malignancies in Patients with Chronic Lymphocytic Leukemia

Case Report

Ann Hematol Oncol. 2015;2(2): 1023.

Increased Incidence of T-Cell Malignancies in Patients with Chronic Lymphocytic Leukemia

Choi G1*, van den Broek EC3*, Stam OCG2, van Noesel CJM2, Tonino SH1 and Kater AP1

1Department of Hematology, University of Amsterdam, Netherlands

2Department of Pathology, University of Amsterdam, Netherlands

3Integraal Kankercentrum Zuid, Eindhoven, Netherlands

*Corresponding author: G Choi, University Medical Center Groningen, Department of Hematology (HPC DA21) Hanzeplein 1, 9713 GZ Groningen, The Netherlands

Received: December 04, 2014; Accepted: January 16, 2015; Published: January 19,2015


We present a patient with chemotherapy-refractory Chronic Lymphocytic Leukemia (CLL) in whom postmortem examination showed hepatosplenomegaly, with both multiple small-cellular CLL lesions and large-cellular, monoclonal T-cell infiltrates. Following this case, the co-incidence of T-cell malignancies and CLL was studied using Dutch and American cancer registry databases. Analysis showed an excess risk for T-cell malignancies in CLL patients, with increased standardized incidence ratios compared with the general population and all cancer survivors in the databases. We hypothesize that CLL cells interact with T-cells in the microenvironment, facilitating malignant transformation.

Keywords: Chronic lymphocytic leukemia; T-cell lymphoma; Neoplastic cell transformation; Cohort studies


Chronic Lymphocytic Leukemia (CLL) is a chronic lymphoproliferative disorder characterized by progressive accumulation of mature B-cells in peripheral blood and secondary lymphoid organs. Primary causes of death include infections and secondary malignancies [1], suggesting an immunodeficiency in CLL patients [2]. Recent epidemiological data demonstrated that the increased risk of other primary malignancies in CLL patients is independent of treatment or surveillance bias [3]. Most likely, CLL is not a disease limited to B-cells only, but also affects other components of the immune system due to extensive crosstalk between CLL cells and their microenvironment [4]. In this report, we present a patient with therapy-refractory CLL in whom post-mortem examination revealed the presence of a T-cell lymphoma. We further studied the coincidence of T-cell malignancies and CLL within two populationbased cancer registries, and found an excess risk of T-cell malignancies in patients with CLL.

Case Presentation

A 75-year-old male patient with therapy-refractory CLL was referred to our hospital. CLL had been diagnosed 7 years earlier (initially Rai 0) and during the last 3 years, he was intermittently treated with Chlorambucil. One month before admission, he had a painful cervical node, from which a biopsy revealed CD5 positive, cycline-D1 negative B-cells, compatible with CLL and without signs of transformation. Upon admission, patient presented with fever, dysphagia, and general malaise. His blood counts showed a pancytopenia with hemoglobin 7.9 g/dL (12.1 a month before), leukocytes 2,300/μl (50% lymphocytes), and platelets 10,000/μl (80,000 before). Without clinical signs of a specific infection, he was treated with broad-spectrum antibiotics. A bone marrow biopsy was performed, showing 80% CLL cells (positive for CD5/CD19/CD23/ CD20dim) and dysplasia in the myeloid and erythroid lineages. Within hours, he had progressive respiratory failure due to either sepsis or transfusion-related lung injury. Despite ventilatory support, patient’s condition rapidly deteriorated and he died within a few hours.

Post-mortem examination showed signs of multi-organ failure, including congested lungs without microbial infiltrates. There was hepatosplenomegaly and lymphadenopathy. Immunohistochemistry studies showed diffuse infiltrates of small, basophilic cells, positive for CD5, CD20 and CD23 (in liver, spleen, and bone marrow). Remarkably, the spleen contained, apart from CLL, areas with large cells with atypical nuclei positive for CD3, CD8, and Granzyme B, and negative for CD4, CD5, CD20, CD23, CD30, ALK1, CD79a, PAX-5, EBV, and keratin. Ki67 showed a high proliferation index in these areas. Altogether, this patient was found to have CLL and a high-grade peripheral T-cell lymphoma NOS (Figure 1). Molecular analyses of both spleen and liver lesions demonstrated clonal B-cell receptor and clonal T-cell receptor rearrangements, confirming both malignancies. Analysis was also performed on banked peripheral blood from 3 years earlier, excluding the presence of the malignant T-cell clone at an earlier stage of disease.

Citation: Choi G, van den Broek EC, Stam OCG, van Noesel CJM, Tonino SH and Kater AP. Increased Incidence of T-Cell Malignancies in Patients with Chronic Lymphocytic Leukemia. Ann Hematol Oncol. 2015;2(2): 1023. ISSN:2375-7965