Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (344 page)

   Anemia and thrombocytopenia are common, in part due to bone marrow infiltration and in part to hypersplenism.

   WBC is usually decreased at presentation, but it may also be increased if the abnormal lymphocytes are elevated. Neutropenia and monocytopenia may be present.

   Usually from 10% to 90% of lymphocytes in the peripheral blood smear reveal lymphocytes with cytoplasmic projections (hairy). Nucleoli are not visible. Ten percent of patients present with marked leukocytosis and the HCL cells predominate.

   
Bone marrow
:

   Aspirate is difficult to obtain because of reticulin fibrosis.

   Biopsy shows a hypercellular marrow, with diffuse or interstitial infiltration by hairy cells in a characteristic loose, widely spaced, fashion, with a well-defined rim of cytoplasm leaving a clear zone around the cells, producing a “fried egg” appearance. The hairy projections are not clearly seen on the biopsy specimen. No nucleoli are seen. There is no paratrabecular involvement. In some patients, there may be a hypocellular marrow that may resemble aplastic anemia. Reticulin stain shows moderate to marked increase in reticulin fibers.

   
Spleen and lymph nodes
: The leukemic cells are found in the red pulp with infiltration of the cords and sinuses, whereas the white pulp is atrophic. Angiomatous lakes are formed.

   
Cytochemistry
: Tartrate-resistant acid phosphatase (TRAP) is invariably positive (see Table
9-3
) on involved white cells. It requires peripheral blood smear or bone marrow aspirate. Positivity appears as cytoplasmic granularity. It is rarely performed nowadays, having been replaced with the more specific flow cytometric studies.

   
Flow cytometry

   Flow cytometry (see Table
9-3
) is positive for CD19, CD20 (bright), CD22, CD25, CD11c, CD103, and often annexin A1, and CD123. Cyclin D1 is weakly positive. Hairy cells lack expression of CD10, CD5, CD21, and CD23. Surface immunoglobulin is positive.

   The hairy cell variant is negative for CD25 and CD123. This distinction is important therapeutically.

   
Molecular genetics
: Analysis of the immunoglobulin variable region genes shows somatic mutations in the majority of cases. Recent studies suggest that most cases demonstrate BRAF mutations. However, genetic studies have not been incorporated yet in the diagnostic criteria for HCL.