T-cell large granular lymphocyte leukemia

T-cell large granular lymphocyte leukemia is a disease that exhibits a unexplained, chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood.^[1]

It is also known by the following terms: Proliferation of large granular lymphocytes (LGLs), LGL leukemia, Tγ-lymphoproliferative disorder, T-cell chronic lymphocytic leukemia^[1]

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Epidemiology

T-LGL is a rare form of leukemia, comprising 2-3% of all cases of small lymphocytic leukemias.^[1]

Clinical Features

Etiology

The postulated cells of origin are a transformed CD8+ T-cell with clonal rearrangements of β chain T-cell receptor genes for the majority of cases and a CD8- T-cell with clonal rearrangements of γ chain T-cell receptor genes for a minority of cases.^[1]

Clinical Presentation

This disease is known for an indolent clinical course and incidental discovery.^[1] The most common physical finding is moderate splenomegaly. B symptoms are seen in a third of cases, and recurrent infections due to the associated neutropenia are seen in almost half of cases.^[2][3][4][5] Rheumatoid arthritis is commonly observed in patients with T-LGL, leading to a clinical presentation similar to Felty's syndrome.^[6] Signs and symptoms of anemia are commonly found, due to the association between T-LGL and erythroid hypoplasia.^[7]

Laboratory Findings

The requisite lymphocytosis of this disease is typically 2-20x10⁹/L.^[7] Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen.^{[8][9][10][5]}

Sites of Involvement

The leukemic cells of T-LGL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.^[1][2]

Morphology

Peripheral blood

The neoplastic lymphocytes seen in this disease are large in size with azurophilic granules that contains proteins involved in cell lysis such as perforin and granzyme B.^[11]

Bone marrow

Bone marrow involvement in this disease is often present, but to a variable extent. The lymphocytic infiltrate is usually interstitial, but a nodular pattern rarely occurs.^[1]

Molecular Findings

Immunophenotype

The neoplastic cells of this disease display a mature T-cell immunophenotype, with the majority of cases showing a CD4-/CD8+ T-cell subset immunophenotype versus other permutations of those markers.^[3][4] Variable expression of CD11b, CD56, and CD57^[5] are observed. Immunohistochemistry for perforin, TIA-1, and granzyme B are usually positive.^[1]

Genetic Findings

Clonal rearrangements of the T-cell receptor (TCR) genes are a necessary condition for the diagnosis of this disease. The gene for the β chain of the TCR is found to be rearranged more often than the γ chain. of the TCR.^[9][12]

References