Chapter 57: Large Granular Lymphocytic Leukemia

DEFINITION

• T-cell large-granular lymphocytic (T-LGL) leukemia results from the clonal expansion of large granular lymphocytes (LGLs) with a T-cell (CD3+) phenotype and a clonal T-cell receptor gene rearrangement(s).

• Natural killer (NK)-LGL leukemia is a clonal expansion of LGL with a NK cell (CD3–) phenotype. It lacks convenient markers to determine clonality, such as antigen receptor rearrangements. (See Chap. 66.)

T-LGL LEUKEMIA

Etiology and Pathogenesis

• There is suggestive evidence of a role for human T lymphotropic virus (HTLV) retroviral infection in some patients.

• Most patients are not infected with either HTLV-I or HTLV-II.

• Cytomegalovirus implicated in rare cases of CD4+ T-LGL.

• Leukemic cells have features of antigen-activated cytotoxic T lymphocytes, suggesting a role for antigen in initial LGL expansion.

• Constitutive overexpression of the Fas ligand (CD178), which also is found at high levels in patients’ sera, may be a factor in many disease manifestations (eg, neutropenia, rheumatoid arthritis).

Clinical Features

• About half of patients have palpable splenomegaly. (Table 57–1)

• About one-third of patients have recurrent bacterial infections.

• “B symptoms” (eg, low-grade fevers, night sweats, and/or weight loss) (aggressive variant) are very infrequent.

• About one-fourth of patients have rheumatoid arthritis, often with features of “Felty syndrome.”

• Less than one-tenth of patients have lymphadenopathy.