Indolent B-cell non-Hodgkin lymphoma (NHL) characterized by pancytopenia, splenomegaly, bone marrow fibrosis and the presence of atypical lymphoid cells with hairy projections in peripheral blood, bone marrow and spleen.
Represents approximately 2% of all leukaemias Median age of presentation: 50-55 years ♂:♀::4:1 All Non-Hodgkin’s lymphomas involve white pulp of spleen except:
Hairy cell leukaemia
Other B cell disorders with hairy projections on cells:
B-cell prolymphocytic leukaemia Atypical hairy cell leukaemia Splenic lymphoma with villous lymphocytes (SLVL)
Tumour cells share certain characteristics of memory B cells and can show monoclonal kappa light chain expansion (do not confuse with multiple myeloma)
Splenomegaly (involving red pulp) (M/C symptom, 96% cases) Hepatomegaly Pancytopenia: Anaemia Leukopenia → Infections Thrombocytopenia → Bleeding Cutaneous vasculitis No lymphadenopathy (seen in < 10% cases)
possibly related to frequent unexplained monocytopenia
Atypical mycobacterial infections: Mycobacterium avium– intracellulare infection (MAI) (UNIQUE FEATURE) Mycobacterium kansasii Toxoplasma gondii Legionella Listeria monocytogenes Pneumocystis jirovecii
Peripheral blood smear (PBS):
Hairy cells on Wright-stained peripheral blood smear:
Mononuclear cells (10-25 µm diameter) with abundant pale blue-grey agranular cytoplasm with elongated (hairy) projections. Stain positive for tartrate-resistant acid phosphatase (TRAP) stain (~95%)
(a) Peripheral blood-hairy cell with round nucleus, homogenous spongy chromation with abundant pale blue cytoplasm with circumferential hair like projections (Jenner Giemsastain, ×1000) (b) tartarate resistant acid phosphatase stain showing bright red granular cytoplasmic positivity in the leukemic cells.(tartrate-treated acid phosphatase stain, ×1000) | Somasundaram, V., Purohit, A., Aggarwal, M., Manivannan, P., Mishra, P., Seth, T., … Saxena, R. (2014). Hairy cell leukemia: A decade long experience of North Indian Hematology Center. Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology, 35(4), 271–275. doi:10.4103/0971-5851.144988
B markers: CD19, CD20, and CD22 Characteristic markers: CD11c, CD25, CD103, CD123
Flow cytometry dot plots in a case of hairy-cell leukaemia. The neoplastic cells co-express CD11c, CD25, CD103 with lambda light chain restriction. The cells also express FMC7 in most cases and CD 10 in some cases | Somasundaram, V., Purohit, A., Aggarwal, M., Manivannan, P., Mishra, P., Seth, T., Tyagi, S., Mahapatra, M., Pati, H. P., & Saxena, R. (2014). Hairy cell leukemia: A decade long experience of North Indian Hematology Center. Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology, 35(4), 271–275. https://doi.org/10.4103/0971-5851.144988
Bone marrow aspiration:
Dry tap: Due to HCL-induced marrow fibrosis and the interlocking cell borders of hairy cells Annexin A1 on paraffin-fixed bone marrow specimens (or acetone-fixed cytospins of peripheral blood): 100% sensitivity and specificity in differentiating hairy cell leukaemia from other B cell malignancies. Diffuse infiltration of tumour cells with honeycomb appearance. Fried egg appearance: Nucleus of each hairy cell surrounded by a halo of cytoplasm
Hairy cell leukemia. The marrow biopsy shows leukemic cells with abundant clear cytoplasm, oval or slightly indented nuclei, and the appearance of a “water-clear” rim separating each nucleus (hematoxylin and eosin, ×400 original magnification). | Golomb HM, Vardiman JW. Diagnosis of hairy cell leukemia. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003. Available from: https://www.ncbi.nlm.nih.gov/books/NBK13250/
Other tissue biopsies:
Spleen, lymph node and brain involvement by hairy cell leukemia-variant. a–d Hairy cell leukemia-variant diffusely infiltrates the red pulp of the spleen. Neoplastic cells display a fried egg appearance (a hematoxylin and eosin, ×200; b hematoxylin and eosin, ×1000). CD20 immunostain shows a diffuse replacement of the red pulp with scattered CD3-positive T-cells (c, d immunohistochemistry with hematoxylin counter stain, ×200). e–h Lymph node diffusely infiltrated by hairy cell leukemia-variant. The infiltrate is characterized by intermediate-sized lymphocytes with oval nuclei and moderately abundant clear cytoplasm, some of the leukemic cells show prominent nucleoli (arrowhead) (e hematoxylin and eosin, ×200; f hematoxylin and eosin, ×1000). Hairy cell leukemia-variant cells highlighted by immunohistochemical B-cell marker CD20 admixed with background small CD3-positive T-cells. (g, h immunohistochemistry with hematoxylin counter stain, ×200). i–k Involvement of the brain by hairy cell leukemia-variant (case #3): Multiple brain lesions by MRI (i). Brain biopsy specimen showing brain parenchyma with hemorrhages resembling blood lakes containing atypical lymphocytes (j hematoxylin and eosin, ×100). High-power showing blastoid morphology of hairy cell leukemia-variant cells highlighted by CD20 (inset) (k hematoxylin and eosin, ×400) | Angelova, E.A., Medeiros, L.J., Wang, W. et al. Clinicopathologic and molecular features in hairy cell leukemia-variant: single institutional experience. Mod Pathol 31, 1717–1732 (2018). https://doi.org/10.1038/s41379-018-0093-8
HCL is an incurable disease characterized by long periods of remission with eventual relapse and need for re-treatment in many patients.
Cladribine (DOC) Interferon α Pentostatin V600E BRAF mutation: BRAF inhibitors ( vemurafenib)
Treatment algorithm for HCL and HCLv: Both standard and investigational treatment options are shown for (1) patients with HCL without prior purine analogue therapy, (2) patients with HCL treated with 1 prior purine analogue, (3) patients with HCLv treated with 0 or 1 prior purine analogue, and (4) patients with multiply relapsed HCL/HCLv. | BR, bendamustine/rituximab; CDA, cladribine (2-chlorodeoxyadenosine); CDAR, cladribine/rituximab; DCF, pentostatin (2’-deoxycoformycin); DCFR, pentostatin/rituximab; HCL, hairy cell leukemia; HCLv, hairy cell leukemia variant; tx, therapy. | Kreitman, R. J., & Arons, E. (2018). Update on hairy cell leukemia. Clinical advances in hematology & oncology : H&O, 16(3), 205–215.