Diversity of leukaemic cell morphology in ATL correlates with prognostic factors, aberrant immunophenotype and defective HTLV‐1 genotype

Abstract

Summary.To investigate the diversity of morphology in adult T-cell leukaemia/lymphoma (ATL) and its possible association with the pathophysiology of ATL, we selected 36 acute cases and 14 chronic cases phenotypically confirmed to have >90% ATL cells in peripheral blood mononuclear cells. Prototype ATL cells were observed in all cases, although the percentage of all lymphoid cells varied considerably (48·9 Ϯ 23·8 in acute type, 29·6 Ϯ 18·9 in chronic type; P ¼ 0·015). Chronic lymphocytic leukaemia (CLL)-like morphology with round nuclei was more frequent in chronic type than in acute type (52·0 Ϯ 24·9% v 16·6 Ϯ 13·1%; P < 0·0001). Unusual morphology (UM; lymphoblastic, vacuolated, granular pleomorphic or large cells) was more frequent in acute type than in chronic type (20·1 Ϯ 18·7% v 2·7 Ϯ 3·2%; P < 0·0001). Furthermore, there were significant negative and positive correlations of % CLL-like cells and % UM cells respectively, with serum LDH level, hypercalcaemia, performance status, and total number of involved lesions. Cases with aberrant immunophenotype (n ¼ 6) or defective HTLV-1 integration (n ¼ 22) showed lower % CLL-like cells and higher % UM cells than other cases, respectively. Cases with >50% CLL-like cells (n ¼ 7; all chronic type) were younger (53·1 Ϯ 12·2 v 66·9 Ϯ 10·6 years; P ¼ 0·038) and showed longer acute-crisis free survival (mean: 16·7 v 3·0 years; P ¼ 0·012) than chronic cases with <50% CLL-like cells. These results suggest that diversity in genotype, phenotype, morphology and behaviour of ATL are closely associated, and that CLL-like morphology is a good prognostic factor for chronic type.

Pre-morbid human T-lymphotropic virus type I proviral load, rather than percentage of abnormal lymphocytes, is associated with an increased risk of aggressive adult T-cell leukemia/lymphoma

“…4,5 A further category of lymphocytes with 'unusual morphology', including lymphoblasts and lymphocytes with features including cytoplasmic granulation and vacuolation, has been described in ATLL. 6 The classification study reported 62.8% 4-year survival for smoldering ATLL. In another retrospective study, 11 of 26 (42%) smoldering ATLL transformed to aggressive ATLL after a median of 81 months.…”

Bone Marrow

“…Hyperlobated nuclei may be rare or absent in some cases, with small, uniform, CLL-like cells seen more commonly in the chronic or smoldering form of the disease. 392 The bone marrow is frequently normocellular with minimal and focal interstitial or diffuse involvement seen in approximately half of cases. 391,393 This bone marrow involvement is usually non-paratrabecular and may be subtle even with extensive peripheral blood involvement.…”

Adult T-cell leukemia/lymphoma

“…These cells are considered pathognomonic of ATL and enable diagnosis alone. 44 Other atypical cells may have the following morphologies: chronic lymphocytic leukemia, lymphoblastic type, and pleomorphic with granular or vacuolar cytoplasm. 44 Flow cytometry is an important test for the diagnosis of ATL.…”