Lymphoma and plasma cell neoplasms
B cell lymphoma subtypes
Hairy cell leukemia - variant type

Topic Completed: 1 February 2011

Revised: 13 March 2020

Copyright: 2001-2020,, Inc.

PubMed Search: hairy cell leukemia variant

Nikhil Sangle, M.D.
Page views in 2019: 1,796
Page views in 2020 to date: 460
Cite this page: Sangle N. Hairy cell leukemia - variant type. website. Accessed April 1st, 2020.
Definition / general
  • Uncommon variant of hairy cell leukemia (10% of cases) with more aggressive clinical course
  • Also called prolymphocytic variant, atypical hairy cell leukemia
  • A Japanese variant also exists (Rinsho Ketsueki 2004;45:405), and may respond better to treatment
Clinical features
  • Resembles classic hairy cell leukemia with the following differences: leukocytosis not leukopenia, cells have prominent nucleoli and blastic / convoluted nuclei; negative staining for CD25, Annexin A1 and TRAP on tumor cells; patients are resistant to conventional chemotherapeutic regimen
  • 60 - 75 new patients each year in U.S.
  • Older individuals (mean age 70 years)
  • Often men with massive splenomegaly, marked lymphocytosis without infection
  • Less marrow fibrosis so more successful marrow aspirates
  • No neutropenia, no monocytopenia
  • More aggressive than classic type
  • May be biologically different from classic hairy cell leukemia (Cancer Treat Rev 2011;37:3)
  • Rearrangement of VH4-34 gene is more common in variant than classic disease, and is associated with poorer survival (Blood 2009;114:4687)
Case reports
  • Poor response to initial cladribine
  • Shorter durations of response, and typically do not respond again to purine analogues after relapse
  • Addition of rituximab or antiCD22 immunotoxins may be helpful
Microscopic (histologic) description
  • Morphologic features are intermediate between hairy cells and prolymphocytes
  • Cells are large with abundant basophilic cytoplasm, circumferential stellate projections, round, occasionally bilobed nuclei and prominent nucleoli
  • Bone marrow: diffuse interstitial or sinusoidal patterns (Arch Pathol Lab Med 2005;129:395)
  • Spleen: expansion of red pulp with no / atrophic white pulp; lymphoid cells in sinusoids
Microscopic (histologic) images

Case of the Week #437

Images hosted on other servers:

Various images

Intrasinusoidal pattern

Cytology images

Images hosted on PathOut server:

Bone marrow aspirate - COW #437

Peripheral blood smear - COW #437

Flow cytometry images

Case of the Week #437

Images hosted on other servers:

Various images

B cells express
CD103 but not
CD25 in hairy cell
leukemia variant

Positive stains
Negative stains
Differential diagnosis
Board review style question #1
Which one of the following is not a shared feature of hairy cell leukemia and hairy cell leukemia - variant?

A. Affects adult patients
B. BRAF V600E mutation
C. CD103 positivity
D. Splenomegaly
Board review answer #1
B. Classical hairy cell leukemia is almost always positive for BRAF V600E mutation, but HCL-v is not
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