<aside> 💡 CD5-, CD10-, CD11c+, CD20+ (bright), CD22+, CD25+, CD103+, CD123+, cyclin D1+, annexin A1+, and CD200+ (bright).

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Clinical Presentation

• A male:female ratio of 4:1 and a peak incidence at 40–60 years.
• Patients typically present with infections, anemia or splenomegaly.
• Lymphadenopathy is uncommon.
• Pancytopenia is usual at presentation and the lymphocyte count is rarely over 20000/μL.
• Monocytopenia is a distinctive feature.
  • The defects in monocyte production and function may account for the unusual susceptibility of these patients to atypical mycobacterial and fungal infections.
  • Lymphocyte functional studies reveal impaired delayed-type hypersensitivity to recall antigens, as well as near-absent antibody-dependent cellular cytotoxicity.
• Clinical manifestations secondary to various autoimmune disorders are being recognized with increasing frequency in patients with HCL.
  • These complications were second only to infection as a cause of morbidity.
  • The onset may occur at any time during the course of the disease and is not related to tumor burden.
• The blood film reveals a variable number of unusual large lymphocytes with villous cytoplasmic projections.

Diagnosis

• The tumor cells usually have mutations of the variable region of the immunoglobulin heavy chain gene (IGHV-mutated), and are unique memory B cells in expressing multiple immunoglobulin (Ig) isotypes.
• A mutation in exon 15 of the gene for the protein kinase *BRAF*V600E underlies the disease.
• The bone marrow trephine shows a characteristic appearance of mild fibrosis and a diffuse cellular infiltrate.