Case 96-1

History/Physical Findings:

A 69-year-old male presented with weakness and splenomegaly.

Laboratory Findings:

Peripheral blood:

Immunophenotyping Studies:

Bit Map "B" Data

Discussion:

The peripheral blood smear reveals medium-sized lymphoid cells with delicate cytoplasmic projections. The nuclei are oval, slightly indented and the chromatin pattern has a "lacelike" appearance. The pale-blue cytoplasm has a "fluffy" texture and the cell border is irregular. The cytochemical stains demonstrate acid phosphatase activity resistant to inhibition by tartaric acid ("TRAP positivity"). These morphologic features and cytochemical findings are characteristics of Hairy Cell Leukemia (HCL).

Examination of the bone marrow biopsy reveals an infiltration of mononuclear cells with abundant clear to lightly eosinophilic cytoplasm, causing the individual nuclei to be evenly and widely spaced, imparting a "fried-egg" appearance. In HCL, mast cells are often prominent and lymphocytes and plasma cells may be admixed. Bone marrow reticulin is characteristically increased, which probably accounts for the high frequency of "dry taps" in patients with HCL. In the spleen, HCL is characterized by involving solely the red pulp, both the cords and sinuses.

The flow cytometry studies reveal a monoclonal population of cells that express the pan-B cell marker, CD 19, and also express CD 11c and CD 25. CD 11c was originally raised against "hairy cells," and recognizes a leukocyte adhesion molecule which is also present on monocytes and macrophages, granulocytes, some activated T cells and in T lymphoproliferative disorders. CD 11c is expressed strongly in virtually all cases of HCL and only occasionally on B lymphoproliferative processes other than HCL. CD 25 is the p55 receptor for interleukin 2 and is more specific for HCL than CD 11c. However, a minority of cases of HCL are CD 25 negative.

Included in the differential diagnosis of HCL are Splenic Lymphoma with Villous Lymphocytes (SLVL), Monocytoid B Cell Lymphoma (MBCL), and Prolymphocytic Leukemia (PLL). SLVL is morphologically very similar to HCL, expresses the HCL marker CD 11c, and sometimes demonstrates "TRAP" positivity. SLVL, however, is CD 25 negative and is confined to the white pulp in the spleen. MBCL may demonstrate the "fried egg" pattern similar to that of HCL is tissue sections. However, MBCL usually does not present with splenomegaly, peripheral blood or bone marrow involvement. In addition, MBCL is CD 25 and TRAP negative. PLL is sometimes included in the differential diagnosis because both peripheral blood and spleen are often involved. The prominent nucleoli of PLL and extremely high leukocyte count usually help to establish the diagnosis of PLL. Phenotypically, the CD 11c, CD 25 and TRAP negativity distinguish PLL from HCL.

HCL is an uncommon lymphoproliferative disorder that primarily affects elderly white men. Patients are often pancytopenic and have enlarged spleens are presentation. Peripheral lymphadenopathy is usually inconspicuous. The clinical course of HCL is indolent and treatment is usually not required until severe pancytopenia occurs. Most patients eventually will develop progressive disease, however. Following splenectomy, a minority of patients experience longlasting improvement without further treatment.

Diagnosis:

Hairy cell leukemia

References:

1. Chang KL et al: Hairy Cell Leukemia - Current Status. Am J Clin Pathol 97:719-738, 1992.
2. Hounieu H, Chittal S et al: Hairy Cell Leukemia. Am J Clin Pathol 98:26-33, 1992.

Contributors:

Beth B. Hewitt, M.D.
Department of Pathology
University of Virginia Health System.

Donald J. Innes, Jr., M.D.
Department of Pathology
University of Virginia Health System

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