Hairy Cell Leukemia

Epidemiology:

• Adults almost always
• Middle age to elderly males most commonly

Common sites:

• Spleen
• Bone marrow
• Liver
• Lymph nodes less commonly

Gross features:

o

Histologic features:

• hairy lymphocytes
• larger than normal lymphocytes (12-20um)
• N:C 4:1 to 2:1
• Oval to indented nucleus
• May be folded, bean-shaped, angulated, or dumbbell-shaped
• May be centrally or eccentrically placed
• Finer chromatin than usual lymphocytes – fine to slightly coarse
• Small single nucleolus often
• moderate to abundant pale blue to grayish blue cytoplasm (Wright)
• small vacuoles may be present giving a mottled appearance to the cytoplasm
• no granules in most cases
• cytoplasmic projections (hairy)
• indistinct cell borders
• not seen in some cases
• positive staining for tartrate resistant acid phosphatase (TRAP)
• BM:
• reticulin fibrosis of bone marrow (often gives “dry tap”)
• Spleen:
• Red pulp infiltration

Immunophenotype & Special Stains:

Marker:	Sensitivity:	Specificity:
Surface Ig (M, D, G, or A) (bright)
CD103		Good
CD11c (bright)		Good
CD25		Good
Pan B (CD19, 20, 22, 79a) (bright)
CD123
T-bet
Annexin A1 (ANXA1)		Most specific; not expressed in any other B-cell lymphoma; must distinguish from expression in myeloid cells and a proportion of T-cells
FMC7
Cyclin D1 (weak)
CD79b (neg)
DBA.44 (CD72)
CD5 (neg)	most
CD10 (neg)	most
CD23 (neg)
Tartrate resistant acid phosphatase (TRAP)

Molecular features:

• IgH and IgL gene rearrangements
• VH genes with somatic hypermutation (>85%)
• BRAF mutations (classic HCL) (>95% of classic HCL) (specific in the setting of low-grade B-cell neoplasms)
• V600E (exon 15)
• MEK-ERK pathway activation
• Not found in HCL-V

§ Not found in HCL expressing IGHV 4-34

§ Not found in rare classic HCL cases

§ Single cases with exon 11 mutations reported:

· F468C

· D449E

• No specific cytogenetic abnormalities
• Numerical abnormalities of chromosomes 5 and 7
• Translocations distinctly uncommon

Other features:

• B cell origin
• presents with splenomegaly (often massive) usually
• indolent course
• except pancytopenia due to splenomegaly
• overall 10 year survival > 90%
• uniquely sensitive to alpha-interferon or nucleosides (purine analogs)
• often “dry tap” bone marrow due to reticulin fibrosis

References:

• Swerdlow et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2008)
• Genetics and IHC sections
• Maevis V, Mey U, Schmidt-Wolf G, Schidt-Wolf IGH. Hairy cell leukemia: short review, today’s recommendations and outlook. Blood Cancer Journal (2014) 4, e184; doi:10.1038/bcj.2014.3
• British Journal of Haematology 2014;165:529-533.
• Dr. Fernandes