ICD-O 9831/3 | MeSH D054066 | |
Large granular lymphocytic (LGL) leukemia is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood.
Contents
- History
- Epidemiology
- Etiology
- Clinical presentation
- Laboratory findings
- Sites of involvement
- Prognosis
- Peripheral blood
- Bone marrow
- Immunophenotype
- Genetic findings
- Treatment
- References
It is divided in two main categories: T-cell LGL (T-LGL) leukemia and natural-killer (NK)-cell LGL (NK-LGL) leukemia. As the name suggests, T-cell large granular lymphocyte leukemia is characterized by involvement of cytotoxic-T cells).
It is also known by the following terms: proliferation of large granular lymphocytes (LGLs), LGL leukemia, Tγ-lymphoproliferative disorder, and, in common with other T cell leukemias such as T-cell prolymphocytic leukemia, T-cell chronic lymphocytic leukemia.
History
LCLL was discovered in 1985 by Thomas P. Loughran Jr. while working at Fred Hutchinson Cancer Research Center. Specimens from patients with LCLL are banked at the University of Virginia for research purposes, the only bank for such purposes.
Epidemiology
T-LGL is a rare form of leukemia, comprising 2-3% of all cases of chronic lymphoproliferative disorders.
Etiology
The postulated cells of origin of T-LGL leukemia are 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.
Clinical presentation
This disease is known for an indolent clinical course and incidental discovery. 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.
Rheumatoid arthritis is commonly observed in patients with T-LGL, leading to a clinical presentation similar to Felty's syndrome. Signs and symptoms of anemia are commonly found, due to the association between T-LGL and erythroid hypoplasia.
Laboratory findings
The requisite lymphocytosis of this disease is typically 2-20x109/L.
Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen.
Sites of involvement
The leukemic cells of T-LGL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.
Prognosis
The 5 year survival has been noted as 89% in at least one study from France of 201 patients with T-LGL leukemia.
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.
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.
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. Variable expression of CD11b, CD56, and CD57 are observed. Immunohistochemistry for perforin, TIA-1, and granzyme B are usually positive.
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.
Treatment
Alemtuzumab has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.