Hepatosplenic γδ T‐cell lymphoma following seven malaria infections

Abstract

Hepatosplenic gammadelta T-cell lymphoma (HSTL) is a clinicopathological entity associated with an immunocompromised status in approximately 25% of patients. Herein is described a case of HSTL in a 53-year-old Brazilian man with seven previous malaria infections, initially misdiagnosed as a hyperreactive splenomegaly due to chronic malaria. A characteristic lymphoid infiltrate was observed in spleen, liver and bone marrow sinusoids/sinuses. Neoplastic cells had a CD45RO+, CD2+, CD7+, CD3+, CD5-, CD8+, CD56+, perforin+, FasL-negative, T-cell receptor (TCR)alphabeta-negative, TCRgammadelta+ profile. Analyses of gamma and delta TCR rearrangements confirmed diagnosis of gammadelta T-cell lymphoma by detecting VgammaI/Vdelta1-Jdelta1 clonal rearrangements. Sensitive polymerase chain reaction (PCR) for Plasmodium falciparum, Epstein-Barr virus and herpesvirus-8 failed to demonstrate infection. The disease progressed to a fatal outcome following cutaneous infiltration and leukemic proliferation. The authors also comment on the association of lymphoma and infection, focusing on PCR diagnosis of TCRgamma and delta clonal rearrangements and the presumed pathogenic events leading to HSTL in the context of chronic malaria infection. Initial lymphomagenic stages might not be direct consequences of antigenic stimulation of Vdelta1 T-cells, but might depend on interactions between gammadelta T and B cells during cooperative or regulatory responses to Plasmodium sp.

Malaria protection in β2‐microglobulin‐deficient mice lacking major histocompatibility complex class I antigens: essential role of innate immunity, including γδT cells

“…There was a polyclonal expansion of γδT cells using Vγ1, Vγ2, Vγ4 and Vγ6 in both B6 and β 2 m(–/–) mice. In early reports, the skewed usage of Vγ1Vδ6 or Vγ4Vδ4 (Vγ2Vδ4 Garman's classification) by γδT cells was seen after malarial infection 42–44 . Although Vγ1 + and Vγ2 + γδT cells seemed to expand in B6 and β 2 m(–/–) mice after malarial infection even in this study, the restriction to Vγ1 and Vγ2 was not seen in our experimental protocol.…”

Small B-cell lymphomas of the spleen: how to tell them apart

“…Some cases occur in the setting of immunosuppression due to prior transplantation or therapy with immunosuppressive agents for other reasons [58,59]. Similar to SMZL, rare cases have been reported in the setting of Plasmodium falciparum malaria infection, which is associated with an expansion of γδ-T cells in the peripheral blood and spleen [60]. Patients present with abdominal pain and often have fever, night sweats, or weight loss.…”

Intensive Induction Chemotherapy Followed by Early High-Dose Therapy and Hematopoietic Stem Cell Transplantation Results in Improved Outcome for Patients with Hepatosplenic T-Cell Lymphoma: A Single Institution Experience

“…5,12 Immunocompromised patients are overrepresented, with reports of HSTCL developing during long-term immunosuppression after solid-organ transplant 13–15 and in the setting of other immune dysregulation including malignancy and infection. 16,17 The importance of iatrogenic immunosuppression as a contributor to lymphomagenesis has become particularly relevant in light of increased incidence of HSTCL in patients with chronic inflammatory diseases after treatment with immunosuppressants, specifically agents blocking tumor necrosis factor (TNF)- α and/or thiopurine agents. 18–24 …”