Hepatosplenic γδ T-cell lymphoma: ultrastructural, immunophenotypic, and functional evidence for cytotoxic T lymphocyte differentiation

Hepatosplenic T cell lymphoma. A review on 45 cases since the first report describing the disease as a distinct lymphoma entity in 1990

“…Lymphadenopathy has been reported only in a few patients at presentation of the disease. 10,18,23 The predominant laboratory findings are reduced peripheral blood cells ranging from isolated reduction of one lineage to pancytopenia, elevated lactate dehydrogenase, and pathologic liver parameters ( Table 2). The finding of pancytopenia and normal bone marrow has generated the hypothesis that cytokines produced by the malignant ␥␦ T cells may suppress bone marrow precursor cells, 8,17 however, data providing strong evidence for this hypothesis are missing.…”

“…For example, isolated thrombocytopenia which disappeared after splenectomy has been misinterpreted as idiopathic thrombocytopenic purpura, 15,16 circulating blast-like lymphoma cells were erroneously interpreted as acute lymphoblastic leukemia blasts, 18 or presentation with hepatosplenomegaly, jaundice, elevated liver parameters, thrombocytopenia, and fever have led to the assumption of a virus infection, which has usually not been confirmed. 5,21,26,29 Even more difficulties regarding the diagnosis of hepatosplenic ␥␦ T cell lymphoma may result from not considering this rare entity as a differential diagnosis.…”

“…Bone marrow involvement is seen in approximately two-thirds of the patients at diagnosis, more often in progressive course of disease, lymphadenopathy is rare 10,18 and sometimes associated with infiltration of other organs by malignant cells in the terminal stage of disease. 5,6 In the spleen, the red pulp is generally diffusely invaded and expanded by malignant ␥␦ T cells 3,15 resulting in an increased mass, whereas the white pulp can appear from normal to reduced to small residual areas.…”

“…[1][2][3]8,18,22,23,26 Besides peripheral cytopenia, this feature may be another indicator for active cytokine production by the tumor. 18 Tumor necrosis factor ␣ has been presumed to be responsible for histiocyte activation and subsequent erythrophagocytosis in EBV transformed T cell lymphomas. 43 However, hepatosplenic ␥␦ T cell lymphoma is generally not EBV associated.…”

“…[15][16][17][18]20 Malignant hepatosplenic ␥␦ T cells are usually of small to medium size with relatively regular or folded nuclei, mostly inconspicuous nucleoli, and with a mature dispersed chromatin and a pale blue, not granulated, somewhat abundant cytoplasm. Blast-like appearance at diagnosis is rare, 18 however, terminal transformation to blast-like cells with large nucleoli has been reported several times (Refs 6, 9, 11, 20 and case 45).…”