Hairy cell leukemia (HCL) is an uncommon (2% of lymphomas) but distinctive B-cell lymphoproliferative disease. Clinically, patients present with hepatosplenomegaly and pancytopenia usually with a marked moncytopenia. Classically, hairy cell leukemia has been difficult to differentiate from hairy cell variant (HCL-v) and splenic marginal zone lymphoma (SMZL). There has been significant morphologic, clinical and immunophenotypic overlap between these entities. An accurate diagnosis is critical as HCL is treated very differently (purine analogs) than other lymphomas with a high cure rate (>90%). Purine analog chemotherapy regimen is also much easier to tolerate than other chemotherapy protocols.
Morphology
HCL is characterized by small lymphoid cells with moderate to abundant cytoplasm (cells may be mistaken for erythroid precursors or other cells in the bone marrow trephine biopsy), which have an interstitial marrow pattern of involvement (morphologic estimate of involvement is often markedly underestimated compared to CD20 staining). Reticulin fibrosis is also characteristic, which often results in a “dry tap” (unable to obtain a bone marrow aspirate). Peripheral blood can show variable invovelemnt with characteristic “hair-like” cytoplasmic projections. It is very uncommon to have lymph node involvement.
Immunophenotype
- CD19/CD20 +
- CD25/CD103 + (CD25 co-expression with CD103 appears to be specific for HCL relative to the differential diagnosis with HCL-v and SMZL)
- Annexin A1 +
- CD11c +
- TRAP +
- DBA.44 + (thought to be specific for HCL when combined with TRAP +)
- CD5 – (rare cases <5% may be CD5+ by flow cytometry)
- CD10 -/+ (approximately 30% of cases may express CD10 by flow cytomtetry)
- BRAF VE1 (IHC) +
Molecular
- >90% found to have a BRAF V600E mutation. This can be identified by PCR or immunohistochemistry (IHC may be more sensitive than PCR). This appears to be relatively specific (relative to the usual differential diagnosis of HCL) with only rare cases of CLL/SLL, marginal zone lymphoma, and multiple myeloma found to express BRAF V600E IHC stain.
- MAP2K1 mutations (encodes MEK1 downstream of BRAF) in most BRAF negative HCL cases that use IgHV4-34. This mutation finding is not specific to HCL and may be seen in hairy cell variant (HCL-v).
References
Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127: 2375–2390. doi:10.1182/blood-2016-01-643569
Uppal G, Ly V, Wang ZX, Bajaj R, Solomides CC, Banks PM, et al. The Utility of BRAF V600E Mutation-Specific Antibody VE1 for the Diagnosis of Hairy Cell Leukemia. Am J Clin Pathol. 2014;143: 120–125. doi:10.1309/AJCPQLQ89VXTVWKN
Brown NA, Betz BL, Weigelin HC, Elenitoba-Johnson KSJ, Lim MS, Bailey NG. Evaluation of Allele-Specific PCR and Immunohistochemistry for the Detection of BRAF V600E Mutations in Hairy Cell Leukemia. Am J Clin Pathol. 2014;143: 89–99. doi:10.1309/AJCPDN4Q1JTFGCFC
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Robbins and Cotran Pathologic Basis of Disease. V Kumar, et al. 9th Edition. Elsevier Saunders. 2015. pp. 603-604.
Turakhia S, Lanigan C, Hamadeh F, Swerdlow SH, Tubbs RR, Cook JR. Immunohistochemistry for BRAF V600E in the Differential Diagnosis of Hairy Cell Leukemia vs Other Splenic B-Cell Lymphomas. Am J Clin Pathol. 2015;144: 87–93. doi:10.1309/AJCP5WVXJ2KTLODO
Andrulis M, Penzel R, Weichert W, Deimling von A, Capper D. Application of a BRAF V600E mutation-specific antibody for the diagnosis of hairy cell leukemia. Am J Surg Pathol. 2012;36: 1796–1800. doi:10.1097/PAS.0b013e3182549b50