FINAL DIAGNOSIS: HAIRY CELL LEUKEMIA
By WHO definition, hairy cell leukemia (HCL) is an indolent lymphoid neoplasm of small mature B lymphoid cells with oval nuclei and abundant cytoplasm with "hairy" projections involving peripheral blood (PB) and which diffusely infiltrates the bone marrow and splenic red pulp. It is a rare disease, comprising 2% of lymphoid leukemias. Patients are predominantly middle-aged to elderly adults.
Hairy cells are small to medium-sized lymphoid cells with hairy cytoplasmic projections. The diagnosis is best made on a bone marrow biopsy as an increase in reticulin fibers is present with hairy cell infiltrates in the bone marrow and often results in a "dry tap", as in this case. The extent of bone marrow effacement in hairy cell leukemia is variable. The primary pattern is interstitial or patchy with some preservation of fat and hematopoietic elements. The infiltrate is characterized by widely-spaced lymphoid cells with oval or indented nuclei, in contrast to the closely packed nuclei of most other indolent lymphoid neoplasms involving the bone marrow. In this case, the bone marrow biopsy demonstrated focal lymphoid infiltrates comprised of small to intermediate sized lymphoid cells with an oval or indented nucleus, abundant cytoplasm and a "fried-egg" appearance.
The classic immunophenotypic profile of hairy cell leukemia includes bright monotypic surface immunoglobulin, bright coexpression of CD20, CD22, and CD11c, and expression of CD103, CD25, CD123, Annexin A1, FMC-7 and cyclin D1 (usually weak). Most cases of hairy cell leukemia lack expression of both CD10 and CD5. However, it is not uncommon for HCL to display an unusual immunophenotype, including negativity for CD103 or CD25. Lack of CD103 expression, as in this case, has been reported in hairy cell leukemia[2,3] and these cases are morphologically and clinically similar to those of typical hairy cell leukemia. Recognizing the variability of immunophenotype and correlating with morphologic and clinical features are essential for establishing an accurate diagnosis of hairy cell leukemia. Cyclin D1 is a cell cycle protein that is overexpressed in MCL as a result of the translocation t(11;14)(q13;q32). Recent studies show that cyclin D1 is highly specific not only for mantle cell lymphoma but also for hairy cell leukemia. Cyclin D1 expression by immunohistochemistry is typically strong in the lymphoid cells of mantle cell lymphoma and can be weakly expressed in hairy cell leukemia. In this case, although the lymphoid cells lacked expression of CD103 by flow cytometry, the immunohistochemical stains along with the morphologic findings and results of flow cytometry studies were compatible with a diagnosis of hairy cell leukemia.
Hairy cell leukemia generally carries a relatively good prognosis. It is a rare disease for which there are multiple treatment options. Historically, the first treatment choices for hairy cell leukemia were splenectomy and alpha-interferon. Currently, purine nucleoside analogs (cladribine and pentostatin) are generally used for front-line treatment. Other active agents include interferon, rituximab and, rarely, splenectomy. A recent study evaluating the long-term outcome in patients with HCL from 1986 to 2008 with a median follow-up of 105 months, demonstrated that of 121 patients who received first line therapy (70% with purine analogues as front-line treatment) ,77% achieved complete remission, 18% achieved a partial response and 5% were nonresponders . Although retreatment with purine analogues is associated with high response rate, the relapse free survival curve does not appear to reach a platueau, and some patients become refractory to this class of agents.
The patient was treated with cladribine followed by maintenance Rituxan therapy and is currently in remission. The lack of CD103 expression in a small B-cell lymphoid neoplasm with hairy cell features of the lymphoid cells should not exclude a diagnosis of HCL. This case stresses the importance of ancillary studies, such as immunohistochemical staining with Annexin A1, in formulating this diagnosis. The relationship of prior radiation therapy and the development of hairy cell leukemia in this patient remains uncertain, although radiation exposure has been associated with HCL [7,8,9].
Contributed by Faye Gao, MD, PhD and Lydia C. Contis, MD -