Laboratory findings in CD4(+) large granular lymphocytoses

Abstract

Large granular lymphocytic (LGL) leukemia is an uncommon disorder of mature T or natural killer (NK) cells. Most T-LGL proliferations are CD3(+)/CD8(+), although rare CD4(+) clonal T-LGL expansions have been reported. We report the clinicopathologic features of eight patients with aberrant CD4(+), cytotoxic T-cell lymphocytoses. Median follow-up was 29 months (range 8-100), during which all were alive without requirement for therapy. Four of eight patients had an additional malignancy; none had a history of rheumatoid arthritis, lymphadenopathy or hepatosplenomegaly. Morphologic expansions of granulated lymphocytes were evident in 6/8. All had immunophenotypically aberrant populations of CD4(+) T cells with uniform, moderate or bright CD56. Seven of eight expressed CD57, and four were CD8(partial dim +). Abnormal levels of expression of two or more T-cell antigens were seen in all cases. All tested cases were Tgamma PCR positive. Our results support that CD4(+) T-LGL lymphocytosis is a clonal disorder with clinicopathologic characteristics distinct from the more common CD8(+) variant.

High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia

“…Two cases were CD8 2 , 2 were weakly positive for CD8, and 2 were clearly positive for CD8 (supplemental Table 4). This is in accordance with the earlier reports [8][9][10] Figure 2). Fluorescence-activated cell sorter (FACS)-sorted CD4…”

“…However, in a small percentage of cases, the tumor cells have a CD4 1 phenotype. [8][9][10] Cytomegalovirus-derived stimulation and restricted use of the T-cell receptor (TCR)-Vb region has been associated with CD4…”

A unique CD4+ large granular lymphocytosis occurring in patients treated with tumor necrosis factor α inhibitors: report of 2 cases

“…In contrast to classic CD8 + T-LGL leukemia, there have been several case series describing an uncommon monoclonal CD4 + T-LGL lymphocytosis occurring in patients without cytopenias, underlying autoimmune disorders, or serologic abnormalities [1][2][3][4]. Interestingly, coexistence of a second malignancy was found in 29% and 50% of patients in 2 of these case series [1,2].…”

“…In contrast, rare cases of T-LGL proliferations composed of monoclonal CD4 + T cells with dim or no coexpression of CD8 (CD4 + T-LGL leukemia) are also described [1][2][3][4][5]. From 2 case series with a total 42 patients, CD4 + T-LGL lymphocytosis appears to have clinicopathological features that are distinct from classic CD8 + T-LGL leukemia, with almost all patients lacking the cytopenias or the association with autoimmune disease frequently seen in classic CD8 + T-LGL leukemia and with many patients harboring secondary malignancies [1,2].…”

Large granular lymphocytic leukaemia pathogenesis and management

“…Most LGL leukaemias (80-90%) are CD3 positive with co-expression of CD8, CD16 and CD57, with CD56 and CD28 being negative (Semenzato et al, 1997 an underlying non-haemopoietic malignancy (Olteanu et al, 2010). CD56 expression is thought to define a subgroup of CD3 + T-cell LGL leukaemia with younger age of onset, more aggressive disease evolution and shorter survival (Gentile et al, 1994;Macon et al, 1996;Tordjman et al, 1996;Passetto Falcao et al, 2000;Alekshun et al, 2007).…”