Hairy Cell Leukemia Variant With Features of Intrasinusoidal Bone Marrow Involvement

Archives of Pathology & Laboratory Medicine, Mar 2005 by Ya-In, Charin, Brandwein, Joseph, Pantalony, Dominic, Chang, Hong

Hairy cell leukemia variant (HCL-V) is a rare lymphoproliferative disorder. We report a case of HCL-V with an intrasinusoidal pattern of bone marrow involvement without interstitial or diffuse infiltration that is typical of HCL and its variant. The peripheral blood and bone marrow aspirates demonstrated abnormal lymphoid cells with cytoplasmic projections that were weakly positive for tartrate-resistant acid phosphatase cytochemical staining. Immunostaining of the bone marrow biopsy specimen showed that these cells were strongly positive for CD20, located within bone marrow sinusoids, and weakly positive for DBA44. By flow cytometry, these cells were positive for CD19, CD20, CD11c, and CD103, exhibited λ light chain restriction, and were negative for CD25. The patient was initially diagnosed as having splenic lymphoma with villous lymphocytes (SLVL) or splenic marginal zone lymphoma (SMZL) (World Health Organization designation) and treated with fludarabine followed by splenectomy with simultaneous liver biopsy. The pathologic analysis of the spleen revealed infiltration of red pulp by the critical cells without white pulp involvement, which is characteristic of HCL and HCL-V but not of SLVL (SMZL). This case illustrates an atypical marrow presentation of HCL-V and emphasizes the need to correlate all clinical and pathologic data, including tissue biopsy, in reaching a diagnosis.

(Arch Pathol Lab Med. 2005;129:395-398)

Hairy cell leukemia (HCL) was first described in 1958 by Bouroncle et al' and was called lenkemic reticuloendothcliosis. Classic HCL (HCL-C) comprises 2% of lymphoid leukemias, with a median patient age at onset of 55 years. The male-female ratio is 5:1.1,2 It has been frequently characterized by pancytopenia, monocytopenia, splenomegaly, absence of peripheral lymphadenopathy, and marrow fibrosis, which typically contribute to an unsuccessful bone marrow aspiration. A bone marrow core biopsy specimen contains patchy interstitial infiltrates of enlarged lymphoid cells with a low nuclear-cytoplasmic ratio, reticular chromatin, and cytoplasmic projections.

A variant form of HCL (HCL-V) was recognized by Cawley et aP in 1980. It is an uncommon disorder that accounts for approximately 0.4% of chronic lymphoid malignancies and represents 10% of all HCL cases.4 The variant form of HCL is a distinct clinicopathologic entity with intermediate features between HCL-C and B-cell prolymphocytic leukemia,5,6 with a median patient age of onset of 71 years. Frequently, HCL-V is characterized by splenomegaly and a high white blood cell count without neutropenia or monocytopenia and has hypercellular marrow that can be aspirated.7

Splenic lymphoma with circulating villous lymphocytes (SLVL) was first described by MeIo et al8 in 1987 and was defined as the leukemic form of splenic marginal zone lymphoma (SMZL), with a median patient age of onset of 69 years.9 Splenic marginal zone lymphoma seems to affect both sexes equally."1 The patients usually have leukocytosis and splenomegaly with successful bone marrow aspiration.h In addition, HCL-C, HCL-V, and SMZL have some common features, including splenomegaly, peripheral blood and bone marrow infiltration by villous lymphoid cells, and B-lymphocyte immunophenotype.6 Also, SMZL has characteristic intrasinusoidal bone marrow involvement that is considered a prominent and fairly reliable pattern of bone marrow involvement." n However, this type of marrow involvement is not specific and is also found in HCL-C but usually seen in association with other types of bone marrow involvement, such as interstitial, diffuse, or nodular patterns.12,13 We herein report a case of HCL-V with an exclusive intrasinusoidal pattern of bone marrow involvement. To our knowledge, the solely intrasinusoidal infiltrates of the marrow have not been described for HCL-V, which can be confused with SMZL.

REPORT OF A case

A 68-year-old woman presented with significant splenomegaly (5 cm below the left costal margin, 23 cm on ultrasound) and hepatomegaly. There was no lymphadenopathy on physical examination or abdominal ultrasound. She had night sweats but no fever. At presentation, the hemoglobin level was 12.5 g/dL, white blood cell count was 35800/µL (neutrophils, 9%; lymphocytes, 88%; monocytes, 1%; and eosinophils, 2%), and platelet count was 146 × 10^sup 3^/µL. Bone marrow aspiration and biopsy were performed, and the findings were interpreted as consistent with SLVL based on the characteristics of the blood and bone marrow lymphocytes, the pattern of the lymphoid infiltration, immunohistochemical stains, and flow cytometry profiles. She had no response to chlorambucil and only a transient response to fludarabine chemotherapy, with recurrence in her blood 4 months after treatment; therefore, she subsequently underwent splenectomy.

PATHOLOGIC FINDINGS

Blood smear at the time of diagnosis revealed lymphocytosis, which was composed of 75% of the white blood cells. They were medium in size with a moderate amount of cytoplasm, some with nucleoli, and a few with cytoplasmic projections. Bone marrow aspiration showed 28% of lymphoid cells, similar to the blood smear, with a reticular chromatin pattern, cytoplasmic projections, and indistinct nucleoli (Figure 1, A). Tartrate-resistant acid phosphatase (TRAP) cytochemical stain was weakly positive in the marrow cells but negative in those of the peripheral blood. The bone marrow biopsy specimen showed normal cellularity for the patient's age. The architectural features were intact with no evidence of paratrabecular aggregates of lymphoid cells. The section showed a distinct intrasinusoidal population of CD20^sup +^ lymphocytes (Figure 1, B). The lymphocytes had abundant cytoplasm and indistinct nucleoli. Mitotic activity was normal. DBA44 was weakly positive in atypical lymphoid cells. The remainder of the marrow showed a good hematopoietic reserve and slightly increased reticulin.