Large granular lymphocytic leukaemia

Keywords: LGL, GLL, Granular lymphocytic leukaemia

   

T-cell granular lymphocytic leukemia (T-GLL)

Associations with pure red cell aplasia and rheumatoid arthritis are recognised.

LGL leukaemias are characterized by clonal large granular lymphocytes (LGL) involving peripheral blood, bone marrow and spleen. Cytopenias are common. They comprise:

  • T cell lineage (85% of cases).
  • NK lineage (15%).

Causes of non-clonal granular lymphocytosis include :

  • Viral infections (EBV, HBV, HCV, HIV, CMV)
  • Connective tissue disorders
  • Immune thrombocytopenia
  • Lymphoma (non-Hodgkin)
  • Skin disorders
  • Haemophagocytosis syndromes
  • MDS/solid tumours

See also: Lymphocytosis, Splenomegaly, Neutropenia, Lymphocytosis and Cell immunophenotyping.

Full blood count and Blood film: neutropenia is a common association.

Bone marrow examination

Flow cytometry / immunophenotyping of lymphocytes: The pathological cell population expresses CD3 with the common variant co-expressing CD8 and CD57. Other rare variants are recognised that co-express CD4 or both CD4 and CD8. CD56 may also be expressed. Aberrant loss of other pan T-cell markers and/or over expression of CD16 may be seen.

T-cell receptor (TCR) gene rearrangement studies: May confirm clonality.

Aggressive NK-cell leukaemia:

This condition commonly presents with fever, hepatosplenomegaly and lymphadenopathy with a leukaemia blood film.

Full blood count and Blood film: anaemia, neutropenia and thrombocytopenia are common.

Bone marrow examination

Flow cytometry / immunophenotyping of lymphocytes: The pathological cell population expresses CD2 and CD56 in the absence of CD3. CD11b and CD16 may be expressed. CD57 is often negative.

Assessment of KIR antigen status may assist in establishing clonality.

TCR gene rearrangement studies: TCR genes are not rearranged.

Indolent NK-cell lymphoproliferative disorder: aka chronic NK-cell lymphocytosis / NK-cell large granular lymphocytosis.

Cases are typically asymptomatic, although co-existing vasculitis or nephrotic syndrome may rarely be seen.

Full blood count and Blood film: anaemia, neutropenia and thrombocytopenia are common.

Flow cytometry / immunophenotyping of lymphocytes: The pathological cell population expresses CD2, CD16 and CD56 and CD57 in the absence of CD3.

TCR gene rearrangement studies: TCR genes are not rearranged.

Reference:

Swerdlow et al. World Health Organisation Classification of Tumors - Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC Press, 2008.