Hepatosplenic α/β T-Cell Lymphoma with Polarized, Highly Motile Cytotoxic T Cells
Robert Willim, German A Pihan. Beth Israel Deaconess Medical Center, Boston, MA
Background: The α/β variant of hepatosplenic T-cell lymphoma (HSα/βTL) is an exceptionally rare lymphoma characterized by B symptoms, hepatosplenomegaly, and a very poor prognosis. Neoplastic cells classically infiltrate the sinusoids of the liver, and splenic red pulp and bone marrow sinuses. Unlike the γ/δ form, the α/β variant has a female predominance and a wider age distribution. We report two cases of HSα/βTL diagnosed at our institution during a one-year period with clinical, pathological, and immunophenotypic features similar to those described to date. However, unlike previous reports of HSα/βTL, we document the presence of prominent uropod and leading edge formation, and a characteristic live behavior, in HSα/βTL cells.
Design: The clinicopathological characteristics of two cases of HSTL diagnosed in 2012 were retrospectively reviewed. Time-lapse images of density-gradient isolated live lymphoma cells, taken at the time of diagnosis at 15 sec intervals, were also analyzed.
Results: Patient 1 (P1) was a 59 year-old male who presented with six months of B symptoms, jaundice, mild lymphadenopathy and massive hepatosplenomegaly. Patient 2 (P2) was a 67 year-old female who presented with a similar clinical picture; however, she developed a rash and ascites at the time of presentation. Both patients had liver biopsies showing sinusoidal infiltration by lymphoma cells, and peripheral blood involvement by flow cytometry. Circulating lymphoma cells with distinct uropod and leading-edge formation were identified in the peripheral blood of both patients. Biopsies confirmed bone marrow and lymph node involvement for P1. Neoplastic cells in both cases were medium in size, had irregular nuclei, and had scant to moderate amounts of cytoplasm. By immunohistochemistry, lymphoma cells were CD2+, CD3+, and CD4-/CD8-/+ TCR α/β+ T cells. In addition, P1 cells were CD5+, CD7+, CD56- and CD57-, while P2 cells were CD5-, CD7+, and CD56+. P1 and P2 lymphoma cells expressed TIA-1, granzyme and perforin. Both patients had clonally rearranged TCR-gamma in neoplastic cells. Live lymphoma cells exhibited prominent uropod formation and engaged in rapid leading-edge exploratory behavior captured by time-lapse photography. Cell movement and remodeling were highly dynamic occurring in time scales measured in seconds.
Conclusions: We demonstrate that HSα/βTL cells are highly activated cytotoxic T cells, which naturally exhibit cellular polarity and motility via distinctive uropod formation both in vivo and ex-vivo. It is likely that this behavior is tightly linked to the rapidly developing and severe end-organ damage characteristic of this rare form of lymphoma.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 241, Monday Morning