Figure 1: Peripheral blood findings
There is lymphocytosis with atypical cells. These are characterized by intermediate-sized cells with oval and slightly irregular nuclei, sometimes with nuclear indentation resembling “kidney beans”. There is a moderate amount of cytoplasm that often shows circumferential projections. Notably, monocytes are nearly absent.
Figure 2: Bone marrow H&E
Bone core biopsy shows a hypercellular marrow infiltrated by small lymphoid cells with oval nuclei placed centrally within abundant pale cytoplasm, imparting a “fried-egg” appearance. There is often a diffuse, interstitial infiltrate admixed with some small lymphocytes.
Figure 3: Bone marrow immunostains
Immunohistochemical stains on the core biopsy showed increased CD20+ B-cells with co-expression of TRAP (tartrate-resistant acid phosphatase) and Annexin A1. The latter is most sensitive and specific for hairy cell leukemia amongst other B-cell lymphomas. However, the marker is strongly positive in granulocytes, necessitating comparison with CD20 when interpreting the stain.
Figure 4: Flow cytometry
The bone marrow aspirate was submitted for flow cytometry analysis and within the lymphocyte gate (low side scatter with bright CD45) a monotypic B-cell population was identified showing expression of CD19, CD103, CD11c, and lambda light-chain. There is variable positivity for CD25. They are negative for CD5 and CD10.
Figure 5: Molecular studies
The peripheral blood smear was submitted to the molecular pathology lab to perform a melt-curve analysis for identification of BRAF V600E. Essentially all hairy cell leukemias harbor this missense mutation. This assay utilizes a FRET probe that takes advantage of the lower melting temperature of the DNA of mutated cases.
