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Pathology
Peripheral blood findings at diagnosis
Pancytopenia: 50%
“Leukemic” phase with a WBC >1000/mm3: 10–20%
Monocytopenia
Hairy cells identified in most patients, but the number is usually low and may be difficult to identify in the peripheral blood because of low numbers and staining technique
Bone marrow findings at diagnosis
Hypercellularity
Hairy cell infiltration: diffuse, patchy, or interstitial
Diffuse infiltration: Often results in complete effacement of bone marrow
Patchy infiltration: Subtle small clusters of hairy cells present focally or throughout the bone marrow
Interstitial Infiltration: Hairy cells do not form well-defined discreet aggregates, but merge almost imperceptibly with surrounding normal hematopoietic tissue
Hairy cell nuclei are usually round, oval, or indented, and are widely separated from each other by abundant, clear or lightly eosinophilic cytoplasm. Rarely hairy cells can be convoluted or spindle shaped
Extravasated blood cells create blood lakes in the bone marrow similar to those observed in the spleen
Mast cells are often numerous
Reticulin stain of the bone marrow almost always shows moderate to marked increase in reticulin fibers
Approximately 10–20% of patients show a hypocellular bone marrow
Immunophenotyping, cytogenetics, and molecular diagnostic studies
Cytochemical studies: Tartrate-resistant acid phosphatase (TRAP) stain. However, TRAP is not specific for HCL
Hairy cell immunophenotype: CD19(+), CD20(+), CD22(+), CD79B(+), CD5(−), CD10(−), CD11C(+), CD25 Sub(+), FMC(+), CD103(+), CD45(+)
Clonal cytogenetics: Abnormalities in approximately two-thirds of patients. Chromosomes 1, 2, 5, 6, 11, 14, 19, and 20 are most frequently involved. Chromosome 5 is altered in approximately 40%, most commonly as a trisomy 5, pericentric inversion, and interstitial deletions involving band 5q13. However, the identification of cytogenetic abnormalities in a patient with a definite diagnosis of HCL is usually not important as it does not influence, as far as is currently determined, prognosis or therapy
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Work-up
H&P
CBC with differential, serum electrolytes, BUN, creatinine, LFTs, and uric acid
Bone marrow aspirate and biopsy for tartrate-resistant acid phosphatase (TRAP) (although TRAP is not required for the diagnosis, has been largely abandoned, and has been supplanted by immunophenotyping) and morphologic review; immunophenotyping by flow cytometry with B-cell–associated antibodies, including CD20, CD79A, or DBA.44
Tallman MS et al. Hairy cell leukemia. In: Hoffman, ed. Hematology: Basic Principles and Practice, 3rd ed. Philadelphia, Churchill Livingstone, 2000:1363–1372
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Differential Diagnosis
Other small B-cell lymphoproliferative disorders associated with splenomegaly:
Prolymphocytic leukemia
Marked elevation in the WBC
Characteristic morphology of the prolymphocytes
Different immunophenotypic profile
Splenic marginal zone lymphoma (splenic lymphoma with villous lymphocytes)
Cells do not usually exhibit TRAP positivity
Bone marrow infiltrates are demarcated sharply
Different immunophenotypic profile; CD103(−)
HCL variant
Morphologic features between hairy cells and prolymphocytes
Usually associated with leukocytosis/lack of monocytopenia
Absence of CD25 expression
Systemic mastocytosis
Mast cells are negative for B-cell markers, and positive for tryptase
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A diagnosis of HCL by itself is not necessarily an indication to initiate treatment. If a patient is maintaining safe peripheral blood counts, the conservative approach is to “watch and wait” until counts decrease
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Treatment is indicated when a patient has developed life-threatening cytopenias (absolute neutrophil count <1000/mm3, hemoglobin <11 g/dL, or platelet count, <100,000/mm3), or in the presence of symptomatic splenomegaly or constitutional symptoms attributable to the disease
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There is no clear advantage to either purine analog as initial treatment for patients with previously untreated HCL with respect to long-term outcome. The ease of administration of cladribine, which requires only a single course of therapy, may offer some advantages
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Patients should be followed closely during treatment and for several months after completion of therapy, with special attention to appropriate surveillance and treatment for infection resulting from myelosuppression. An improvement in peripheral blood counts after purine nucleoside analog treatment may require weeks and sometimes months. Bone marrow biopsy to confirm a complete response is usually performed 3 months after the completion of therapy. However, if the peripheral blood counts return to normal, splenomegaly resolves and the patient is asymptomatic, one can argue not to carry out another bone marrow biopsy as the results will likely not influence further therapy. Even if the marrow demonstrates a small amount of HCL, further therapy is not indicated outside the context of a clinical trial exploring the potential benefits of additional therapy for residual disease
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For patients who do not respond to initial therapy with a purine analog, the suggested therapeutic option is treatment with a different purine analog. However, the lack of excellent response to one purine analog is exceedingly uncommon and would prompt a reevaluation of the diagnosis
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If relapse is suspected, the bone marrow should be reexamined before restarting therapy. In patients who achieved an initial, durable complete response to a purine analog lasting longer than 1 year, a reasonable course of action would be to retreat the patient either with the same agent or an alternative purine analog. If there was an initial remission of short duration (eg, <1 year), a repeated course of the original therapy is unlikely to result in a second remission of equivalent or longer duration. Retreatment with a second cycle of cladribine or pentostatin leads to a second complete remission in up to 70% of patients
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The anti-CD20 antibody rituximab has been evaluated in patients with relapsed/refractory HCL and should be considered in patients who are not eligible to enroll in a clinical trial. Clinical trials using the truncated Pseudomonas exotoxin-linked recombinant anti-CD22 antibody (BL22) have shown high response rates in patients with previously treated HCL
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