eMedicine Specialties > Hematology > Stem Cells and Disorders

Hairy Cell Leukemia: Differential Diagnoses & Workup

Author: Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Coauthor(s): Ulrich Woermann, MD, Consulting Staff, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland
Contributor Information and Disclosures

Updated: Nov 24, 2008

Differential Diagnoses

Agnogenic Myeloid Metaplasia With Myelofibrosis
Myelophthisic Anemia
Anemia
Myeloproliferative Disease
Aplastic Anemia
Chronic Lymphocytic Leukemia
Myelodysplastic Syndrome

Other Problems to Be Considered

Agnogenic myeloid metaplasia
Chronic lymphocytic leukemia
Low-grade lymphoma
Myelosclerosis
Pancytopenia and marrow fibrosis
Prolymphocytic leukemia
Splenic marginal zone lymphoma
Systemic mastocytosis

Workup

Laboratory Studies

  • The typical hairy cells of hairy cell leukemia are so named because of their characteristic cytoplasmic projections, which appear as fine (hairlike) microvilli when seen by light microscopy, phase-contrast microscopy, and electron microscopy. These are mononuclear cells with eccentric or centrally placed nuclei.
  • Hairy cells have a mature B-cell phenotype and typically express single or multiple immunoglobulin light chains and pan–B-cell antigens, such as CD19, CD20, CD22, and CD79b, but not CD21 (late B-cell marker). The cells also typically express CD103, CD11c, and CD25 but usually not CD5, CD10, or CD23. Hairy cells strongly express CD45, seen as a bright signal, with increased forward and side scatter resembling large lymphocytes and monocytes. Immunophenotypic analysis helps distinguish hairy cell leukemia from other low-grade B-cell malignancies.
  • Monoclonal BLy-7 has high sensitivity and specificity for HCL. CD22 stains at higher intensity in hairy cells than in normal B cells. Hairy cells can be identified immunophenotypically in 92% of cases, even when the cells represent less than 1% of the circulating lymphocytes.
  • Cytochemical evaluation is important for diagnostic confirmation of the morphologic findings. Hairy cells demonstrate strong positivity for tartrate-resistant acid phosphatase (TRAP) staining (see image below). A positive TRAP stain in conjunction with a characteristic bone marrow biopsy is essentially diagnostic of hairy cell leukemia.

    • Blood film at × 1000 magnification. This ima...

      Blood film at × 1000 magnification. This image demonstrates tartrate-resistant acid phosphatase (TRAP) activity of lymphocytes. Photographed by U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.

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      Blood film at × 1000 magnification. This ima...

      Blood film at × 1000 magnification. This image demonstrates tartrate-resistant acid phosphatase (TRAP) activity of lymphocytes. Photographed by U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.

  • The peripheral blood cell counts show pancytopenia with decreased cell counts in all 3 cell lines.
    • Anemia is usually severe and normochromic-normocytic in character.
    • Neutropenia and monocytopenia are usually present in hairy cell leukemia, but an elevated white blood cell count (hairy cells) is found in 20% of cases.
    • Thrombocytopenia is found in more than 80% of patients.
  • The bone marrow aspirate is usually unsuccessful due to a "dry tap." Infiltration of the bone marrow by hairy cell leukemia makes aspirating cells through a needle difficult.
    • Core biopsy of the bone marrow shows a pattern of hairy cell infiltration with a single round or oval nucleus separated by abundant cytoplasm in a fine fibrillar network.4
    • The cell appears separated, resulting in the characteristic fried-egg appearance.4
  • Clonal cytogenetic abnormalities are present in two thirds of patients, and the involvement of chromosomes 1, 2, 5, 6, 11, 14, 19, and 20 have been described. Chromosome 5 abnormality is most frequent (in 40% of patients) with trisomy 5 and pericentric inversions and interstitial deletions of band 5q13.

Imaging Studies

  • Most patients with hairy cell leukemia have massive splenomegaly such that imaging studies are unnecessary to appreciate its presence.
  • In milder forms, a liver and spleen scan or ultrasound measurement may detect some mild forms of organomegaly that may be missed by abdominal palpation.

Other Tests

  • Difficult cases can be confirmed by using immunophenotypic analysis of the buffy coat cells or by performing electron microscopy on suspected cells.
  • Soluble interleukin-2 receptor levels are elevated in patients with hairy cell leukemia and may provide additional supportive data for the diagnosis.

Histologic Findings

The findings of pancytopenia and splenomegaly in the presence of circulating cells that are TRAP positive and a dry bone marrow aspirate with biopsy material showing infiltration with a mononuclear cells that have a fried-egg appearance are diagnostic of hairy cell leukemia.

More on Hairy Cell Leukemia

Overview: Hairy Cell Leukemia
Differential Diagnoses & Workup: Hairy Cell Leukemia
Treatment & Medication: Hairy Cell Leukemia
Follow-up: Hairy Cell Leukemia
Multimedia: Hairy Cell Leukemia
References
Further Reading
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References

  1. Bouroncle BA, Wiseman BK, Doan CA. Leukemic reticuloendotheliosis. Blood. Jul 1958;13(7):609-30. [Medline]. [Full Text].

  2. Cannon T, Mobarek D, Wegge J, Tabbara IA. Hairy cell leukemia: current concepts. Cancer Invest. Oct 2008;26(8):860-5. [Medline].

  3. Orsi L, Delabre L, Monnereau A, et al. Occupational exposure to pesticides and lymphoid neoplasms among men: results of a French case-control study. Occup Environ Med. Nov 18 2008;epub ahead of print. [Medline].

  4. Katayama I. Bone marrow in hairy cell leukemia. Hematol Oncol Clin North Am. Dec 1988;2(4):585-602. [Medline].

  5. Piro LD, Carrera CJ, Carson DA, Beutler E. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. N Engl J Med. Apr 19 1990;322(16):1117-21. [Medline].

  6. Goodman GR, Burian C, Koziol JA, Saven A. Extended follow-up of patients with hairy cell leukemia after treatment with cladribine. J Clin Oncol. Mar 1 2003;21(5):891-6. [Medline]. [Full Text].

  7. Chadha P, Rademaker AW, Mendiratta P, et al. Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA): long-term follow-up of the Northwestern University experience. Blood. Jul 1 2005;106(1):241-6. [Medline]. [Full Text].

  8. Zinzani PL, Magagnoli M, Bendandi M, et al. Long-term follow-up of hairy cell leukemia patients treated with 2-chlorodeoxyadenosine. Haematologica. Sep 2000;85(9):922-5. [Medline]. [Full Text].

  9. Ravandi F, Jorgensen JL, O'Brien SM, et al. Eradication of minimal residual disease in hairy cell leukemia. Blood. Jun 15 2006;107(12):4658-62. [Medline]. [Full Text].

  10. Flinn IW, Kopecky KJ, Foucar MK, et al. Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin. Blood. Nov 1 2000;96(9):2981-6. [Medline]. [Full Text].

  11. Au WY, Klasa RJ, Gallagher R, et al. Second malignancies in patients with hairy cell leukemia in british columbia: a 20-year experience. Blood. Aug 15 1998;92(4):1160-4. [Medline]. [Full Text].

  12. Kurzrock R, Strom SS, Estey E, et al. Second cancer risk in hairy cell leukemia: analysis of 350 patients. J Clin Oncol. May 1997;15(5):1803-10. [Medline].

  13. Glaspy JA, Baldwin GC, Robertson PA, et al. Therapy for neutropenia in hairy cell leukemia with recombinant human granulocyte colony-stimulating factor. Ann Intern Med. Nov 15 1988;109(10):789-95. [Medline].

  14. Monnereau A, Orsi L, Troussard X, Berthou C, et al. Cigarette smoking, alcohol drinking, and risk of lymphoid neoplasms: results of a French case-control study. Cancer Causes Control. Dec 2008;19(10):1147-60. [Medline].

  15. Ratain MJ, Golomb HM, Vardiman JW, et al. Relapse after interferon alfa-2b therapy for hairy-cell leukemia: analysis of prognostic variables. J Clin Oncol. Nov 1988;6(11):1714-21. [Medline].

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Keywords

hairy cell leukemia, hairy cell, leukemic reticuloendotheliosis, HCL, chronic lymphoid leukemia, lymphoproliferative disorders, B-cell disease, clonal B-cell lymphocyte, pancytopenia, anemia, thrombocytopenia, neutropenia, hepatosplenomegaly

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Contributor Information and Disclosures

Author

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Coauthor(s)

Ulrich Woermann, MD, Consulting Staff, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland
Disclosure: Nothing to disclose.

Medical Editor

Rodger L Bick, MD, PhD, FACP, Clinical Professor of Medicine, University of Texas Southwestern Medical Center; Director, Dallas and Pacific Thrombosis Hemostasis and Vascular Medicine Clinical Center
Rodger L Bick, MD, PhD, FACP is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Blood Banks, American Cancer Society, American College of Angiology, American College of Physicians, American Geriatrics Society, American Heart Association, American Medical Association, American Society for Clinical Pathology, American Society of Hematology, Association of Clinical Scientists, California Medical Association, California Thoracic Society, International College of Angiology, International Society of Hematology, International Society on Thrombosis and Haemostasis, New York Academy of Sciences, and Southwest Oncology Group
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Troy H Guthrie, Jr, MD, Director of Cancer Institute, Baptist Medical Center
Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Koyamangalath Krishnan, MD, FRCP, FACP, Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, Program Director, Hematology-Oncology Fellowship, James H Quillen College of Medicine at East Tennessee State University
Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians
Disclosure: Nothing to disclose.

 
 
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