T-cell Prolymphocytic Leukemia Frequently Shows Cutaneous Involvement and Is Associated With Gains of MYC, Loss of ATM, and TCL1A Rearrangement

Abstract

T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive mature T-cell leukemia with frequent cutaneous presentation, which has not been well characterized. Among the 25 T-PLLs diagnosed between 1990 and 2013 at our institution, 32% (8/25) showed cutaneous manifestations, presenting as rash, purpura, papules, and ulcers. The skin biopsies showed leukemia cutis with perivascular and periadnexal irregular, small to medium-sized lymphoid infiltrates without epidermotropism. The lymphoid infiltrates were composed of mature CD4+ T cells expressing other T-cell antigens, and a subset (48%) showed dual CD4+/CD8+ coexpression. Higher median absolute peripheral blood lymphocyte count (43.0 vs. 13.0 k/mm; P=0.031) and elevated lactate dehydrogenase levels (P=0.00018) at the time of diagnosis were significantly associated with T-PLLs with skin involvement compared with those without. The extent of bone marrow involvement (P=0.849) and overall survival (P=0.144) was similar in the 2 groups. Fluorescence in situ hybridization or karyotype revealed frequent gains of MYC (67%; n=9), loss of ATM (64%; n=11), and TCL1A rearrangement or inversion 14q (75%; n=12). Gains of TCL1A was also seen (78%; n=9), including in some cases that had concurrent TCL1A rearrangement, whereas TP53 loss was less common (30%; n=10). No correlation was seen between the immunophenotype and morphology versus the presence or absence of skin involvement. These data suggest that cutaneous involvement by T-PLL is relatively common and often associated with significant peripheral blood involvement. The frequent MYC, ATM, and TCL1A alterations identified support that these genes are integral to the pathogenesis of T-PLL.

T‐cell chronic lymphocytic leukemia or small‐cell variant of T‐cell prolymphocytic leukemia: a historical perspective and search for consensus

“…8p11.1 amplification results in aberrant expression of ankyrin‐1, probably contributing to the abnormal tendency of malignant T cells in T‐PLL to undergo transmigration into the extravascular cutaneous sites and peritoneal cavity. Finally, 8q gains result in MYC amplification and NBS1/nibrin gene overexpression , probably activating the Akt signaling pathway with a potential causal role in T‐PLL progression.…”

Sézary syndrome—clinical and histopathologic features, differential diagnosis, and treatment

“…ATLL can be excluded when serology is negative for human T-lymphotropic virus 1 (HTLV-1) , the virus that causes ATLL. T-PLL may also present with cutaneous involvement although, like ATLL, erythroderma is rare 37 ; patients with T-PLL often present with B symptoms, hepatomegaly, and a markedly elevated white blood count-features not commonly present in SS. Furthermore, cytogenetic studies of T-PLL usually reveal abnormalities in chromosome 14.…”

Pathogenesis and therapeutic targeting of aberrant MYC expression in haematological cancers

“…T‐prolymphocytic leukaemia (T‐PLL) is rare disorder caused by clonal expansion of post‐thymic T‐cells, commonly involving spleen, lymph nodes, bone marrow and peripheral blood. Apart from chromosomal alterations involving TCL1A (also termed TCL1 ), MTCP1 and the T‐cell receptor, MYC gains can also be found in T‐PLL (Tirado et al , ; Hsi et al , ). The exact role and prognostic implications of these signalling pathways in the pathogenesis of T‐PLL remain elusive.…”