Hairy Cell Leukaemia

Morphological features:

• Typically pancytopaenic
• Atypical lymphoid cells are larger than normal lymphocytes
• Abundant, weakly-basophilic cytoplasm with irregular projections which are thread-like
  • May be easier to see projections in the thicker part of the film
• Nuclear outline is typically regular – round or oval
  • Occasionally kidney, dumbbell or bi-lobed
• Generally absent nucleoli
• Monocytopaenia
• Anaemia (usually normocytic)
• There may be a leukoerythroblastic picture and teardrop cells from secondary marrow fibrosis.

Clinical features:

• Splenomegaly
• No lymphadenopathy
• Symptoms and signs of pancytopaenia

Differential diagnosis:

• Marginal zone lymphoma (less cytoplasm which is mor  basophilic, no monocytopaenia)
• Hairy cell leukaemia variant (often has prominent nucleoli, no monocytopaenia)

Disease	Immunophenotype	Other Features
Hairy cell leukaemia	20++/11c+/25+/103+/123+	Annexin A1 positive BRAF positive Monocytopaenia Pancytopaenia
Hairy cell variant	20+/11c+/103+/25-/123-	No monocytopaenia Generally high WBC May have prominent nucleoli BRAF mutation negative Annexin A1 and TRAP negative 50% have TP53 abnormalities and MAP2K1 mutations
Splenic marginal zone leukaemia / Splenic lymphoma with villous lymphocytes	Non-specific B cell phenotype. May be 11c+, occasionally 5+ or 103+.

Bone marrow aspirate features

• Typically aparticulate.
• In some cases where the secondary marrow fibrosis is not severe, aspirates may show the same atypical lymphoid cells seen in the peripheral blood.

Trephine features

• Variable extent of bone marrow effacement.
• Primary pattern is interstitial or patchy, usually some preservation of fat and haematopoietic elements.
• Characteristic infiltrate with widely-spaced lymphoid cells.
• Abundant cytoplasm and prominent cell borders produce a “fried egg” appearance.
• Mitotic figures are extremely rare.