Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (345 page)

   
Karyotype
: No consistent karyotypic abnormalities are found. Abnormalities of 5q may be detected.

   
Hairy cell leukemia variant
is no longer considered a subtype of HCL, but a distinct lymphoproliferative entity. It is associated with extreme leukocytosis, with morphologic features between HCL and prolymphocytic leukemia.

Suggested Reading

Grever MR. How I treat hairy cell leukemia.
Blood.
2010;115:21–28.

T-CELL LARGE GRANULAR LYMPHOCYTIC LEUKEMIA (T-LGL)

   Definition

T-LGL is a clonal disease of large granular natural killer (NK) cells. It is characterized by a persistent (>6 months) increase in the number of clonal peripheral blood large granular lymphocytes (LGLs), usually between 2,000 and 20,000/μL (the absolute number of LGLs in normal subjects is 2–400), without a clearly identified cause, splenomegaly, and cytopenias. T-LGLs may be associated with other diseases, such as RA or other hematologic disorders.

   Who Should Be Suspected?

A middle age or elderly patient with neutropenia and/or anemia, together with peripheral blood lymphocytosis, and moderate splenomegaly. The patient may be asymptomatic for long periods of time or may suffer from repeated bacterial infections. If the total lymphocyte count is not elevated, the disease may be suspected if an increased number of LGLs are present on examination of the peripheral blood.

   Laboratory Findings

   
CBC

   RBC: Anemia is present in half the patients, occasionally with oval macrocytosis.

   WBC: Neutropenia is present in the majority of patients. LGLs are increased; they are large with abundant cytoplasm containing fine or coarse azurophilic granules and a reniform or round nucleus.

   Thrombocytopenia is present in approximately 20% of patients.

   
Bone marrow
may show diffuse infiltration with LGL, but the extent of bone marrow involvement is variable.

   
Immunophenotype
: Most T-LGL leukemias show a profile of cytotoxic T cells, with positive CD3, CD8, CD16, CD57, and the alpha/beta T-cell receptor (TCR). Diminished or lost expression of CD5 and/or CD7 is common. T-LGL cells can also express CD2, CD45RA, and IL-2 receptor beta (CD122).

   
Molecular studies
help define the disease by finding TCR gene rearrangement. Developing technology found a number of genes whose expression was active in LGL T cells, but silent in normal T cells.