Large granular lymphocyte leukaemia, T-LGL

Definition

There is a sustained (greater than six months) increase in the number of large granular lymphocytes in the peripheral blood.

Synonyms

Epidemiology

Accounts for 2-3% of cases of small lymphocytic leukaemia 

Clinical features

60% of patients are symptomatic at presentation. Moderate splenomegaly (20-50% of cases)¹, rheumatoid arthritis¹, circulating immune complexes and hypergammaglobulinaemia are common. Lymphadenopathy is uncommon¹. Severe neutropenia is common¹. Severe anaemia due to red cell hypoplasia may occur. The lymphocytosis usually exceeds 5.10⁹/l.

Histopathology

 The large granular lymphocytes in blood and bone marrow have abundant cytoplasm with azurophilic granules. The bone marrow involvement is often interstitial, rarely nodular.

The spleen, which may weigh up to 1.8 kg, shows preservation of the architecture, with a lymphocytic infiltrate within the red pulp. Neoplastic cells infiltrate the walls of blood vessels. The white pulp is preserved, with the marginal zone demarcated by granzyme-negative lymphocytes. Germinal centres are present and may be prominent. In one cases, non-caseating granulomas were observed¹.

Immunohistochemistry

CD2	positive
CD3	positive1
CD5	negative (normal red pulp lymphocytes are positive, as are circulating LGL cells in 75% of cases)1
CD11b	variable
CD16	positive
CD45RO	negative (normal red pulp lymphocytes are positive)1
CD56	variable
CD57	variable, more often in common type
TIA-1	usually positive, 5/51
Perforin	5/51
Granzyme B	3/41
bcl-2	negative1
MIB1	low expression1

The following variants exist:

	common variant	rare variants
TCRab	positive	positive	positive	negative
TCRgd	negative	negative	negative	positive
CD4	negative1	positive	positive	not defined
CD8	positive1	negative	positive	not defined

Differential diagnosis

• Cases resembling T-LGL but with an NK immunophenotype (CD3-, TCRab- and gd-) are classified with the NK disorders.

• benign NK-cell lymphoproliferative disorder

Management

Splenectomy is therapeutic in cases with hypersplenism¹.

References

⁰ World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

¹ Osuji N, Matutes E, Catovsky D, et al. Histopathology of the spleen in T-cell large granular lymphocyte leukemia and T-cell prolymphocytic leukemia: a comparative review. Am J Surg Pathol 2005; 29:935-41

This page last revised 24.9.2005.

©SMUHT/PW Bishop