Specific skin lesions as the presenting symptom of hairy cell leukemia

A 68-year-old Japanese man with a chief complaint of eczema-like dermatosis was diagnosed as having B-cell hairy cell leukemia (HCL) by demonstration of hairy cells in the skin lesions as well as in blood and bone marrow. He was treated with alpha-interferon, resulting in disappearance of skin lesions and reduction of his massive splenomegaly from 18 to 5 cm in about 14 months. Although specific skin lesions in HCL, shown by a review of the literature to occur in about 8% of cases, are not as uncommon as generally assumed, it is rare for HCL to present with specific skin lesions, the present case being only the second of its type mentioned in the literature.     

Atypical hairy cell leukemia

The morphologic differential diagnosis of mature B-cell neoplasms with cytoplasmic projections includes splenic lymphoma with villous lymphocytes and hairy cell leukemia. Although the classification of hairy cell leukemia is not universally recognized, 3 variants have been described, namely, classic, variant, and Japanese variant, each of which has different clinical and immunophenotypic features. Classic hairy cell leukemia is virtually always CD11c(+), CD25(+), and CD103(+). Variant and Japanese variant hairy cell leukemias are usually CD11c(+), always CD25(-), and occasionally CD103(+). Each variant is characteristically CD10(-). We present a case of hairy cell leukemia with a unique immunoprofile in that the cells were CD10(+), CD25(+), and CD103(-), and we review the criteria helpful in differentiating "hairy" B-cell neoplasms. This case emphasizes the variability of hairy cell leukemia and the need to correlate all clinical and pathologic data in reaching a diagnosis.     

Immunological studies in hairy cell leukemia.

Cytochemical and immunological studies were performed on tissues and mononuclear cell suspensions from ten patients with hairy cell leukemia. In all cases studied, tartrate-resistant acid phosphatase was noted within the cytoplasm of hairy cells (HCs). In two thirds of the cases, alpha naphthyl acetate esterase was observed in HCs. In addition, HCs did not form spontaneous rosettes with sheep erythrocytes. A variable number of HCs displayed complement receptors. The nonspecific binding of conjugated immunoglobulin to HCs probably reflected the presence of a high concentration of Fc receptors on the HCs surface. In three cases, the conjugated immunoglobulin reacted predominantly to one light chain, thus suggesting the presence of a monoclonal immunoglobulin. In four of six cases, mononuclear cell suspensions of HCs demonstrated latex phagocytosis. In one case, HCs displayed resynthesis of surface membrane immunoglobulin, the presence of B cell antigen, and phagocytosis of latex. These findings suggest that HCs are distinctive and contain properties of both B lymphocytes and monocytes.     

Coincidental hairy cell leukemia and large cell malignant lymphoma.

A 64-year-old man who had a two year history of hairy cell leukemia became feverish with night sweats. Splenomegaly and enlarged nodes in the neck and in the anterior mediastinum were detected. Splenectomy was performed and multiple white nodules on a dark-red background were seen in the spleen. The white nodules represented a large cell malignant lymphoma; other areas of the spleen contained mononuclear cells typical in hairy cell leukemia. One of the hilar lymph nodes of the spleen was involved by malignant lymphoma, and the other eight lymph nodes were involved by hairy cell leukemia. The coincidence of the two diseases tends to favor the view that hairy cells are of lymphocytic origin.     

Cytogenetic studies of hairy cell leukemia

Mononuclear cells from peripheral blood and spleen of four patients with hairy cell leukemia (HCL) were cultured for 1 to 10 days with and without phytohemagglutinin (PHA) stimulation. Blastogenesis and mitoses were not observed in the unstimulated cells cultured for up to 3 days. Prolonging the culture time of unstimulated cells to 7 days produced blastogenic response; a further increase in culture time to 10 days showed transformed cells but not mitoses. Poor PHA response was noted in the cultures stimulated for 3 days, but cells cultured for 7 days and then stimulated with PHA entered mitosis. Surface immunoglobulins were exhibited in 78–94% of the cells in the blood and spleen of patients. In addition, these cells had tartarate-resistant acid phosphatase and were able to phagocytize latex particles by which properties they were identified as hairy cell leukemia cells. Chromosome abnormalities were present in a proportion of cells of each patient, none of them, however, were clonal.     

Septic cutaneous lesions caused byMycobacterium malmoense in a patient with hairy cell leukemia

Patients with hairy cell leukemia seem to be prone to infections with mycobacteria. This report describes a patient with hairy cell leukemia and pulmonary infection as well as disseminated cutaneous infection caused byMycobacterium malmoense cultured from sputum and skin scrapings on Loewenstein-Jensen medium in eight weeks. Despite multiresistance of the causative strain, the infection was successfully treated with ethambutol, cycloserine and isoniazid.     

The hepatic sinusoid in hairy cell leukemia: an ultrastructural study of 12 cases

Ultrastructural lesions of the liver were studied in 12 cases of hairy cell leukemia, with the alterations of the sinusoidal barrier receiving special emphasis. Portal and sinusoidal tumoral infiltration was observed in all cases. It was associated with angiomatous lesions of the sinusoids in eight cases; these lesions consisted of randomly distributed cavities lined by hairy cells and containing hairy cells and erythrocytes. In addition to the attachment of hairy cells to the sinusoidal wall, other striking electron microscopic abnormalities of the sinusoids included 1) wide areas of communication between the sinusoidal lumen and Disse's space, allowing extravasation of blood cells; 2) focal disruption of the sinusoidal wall; and 3) replacement of the sinusoidal cell lining by tumor cells in close contact with hepatocytes. Most of these changes closely resembled those observed in peliosis hepatis. As in peliosis, sinusoidal alterations in hairy cell leukemia might be due to the destruction of the sinusoidal wall, and tumor cells could play a role in the pathogenesis of the lesions. The pattern of liver involvement in hairy cell leukemia, which is peculiar among hepatic localizations of blood malignancies, might reflect the unique phenotype of the tumor cells.     

Cytogenetic studies in hairy cell leukemia

Cytogenetic analyses were performed on cells from 17 patients with hairy cell leukemia stimulated with polyclonal B-cell activators (in 155 different cultures). No mitosis was obtained in samples from four cases (23.5%). Of 14 bone marrows, four (28.6%) showed mitoses, two with clonal abnormalities. All four samples from the spleen had mitoses with four clonal changes; eight of 13 (37.5%) blood samples had mitoses with three clonal changes. Of the polyclonal B-cell activators (PBA), lipopolysaccharide and protein A seemed to be effective for the detection of clonal abnormalities in hairy cell leukemia. Among the clonal aberrations, chromosomes #3, #10, and #17 were affected in two cases each; frequent numerical changes were monosomies of #10 and #17 and structural changes were deletions at band 3p21 (two cases), 6q-, and der(9)t(9;?)(p22;?). The chromosomal bands involved in structural changes were close to accepted constitutive fragile sites.     

Immunophenotypic variations in hairy cell leukemia

Hairy cell leukemia (HCL) exhibits a characteristic immunophenotypic profile that is strongly positive for pan-B-cell markers; positive for CD103, CD11c. and CD25; and usually negative for CD5, CD10, and CD23. We evaluated 35 HCL cases and identified atypical immunophenotypes in 12 cases (34%), including CD103- in 2 (6%), CD25- in 1 (3%), CD10+ in 5 (14%), and CD23+ in 6 (17%) cases. Among these cases one was CD103-/CD10+ and one was CD10+/CD23+. All available specimens from the 12 cases were reviewed and showed morphologic features characteristic for HCL. The initial clinical information was reviewed and showed no significant differences with that reported for typical HCL. Of the 12 cases, 11 patients received purine analogue therapy and achieved complete remissions. Our study indicates that it is not uncommon for HCL to display an unusual immunophenotype, including negativity for CD103 or CD25. Recognizing the variability of immunophenotype and correlating with morphologic and clinical features are essential for establishing an accurate diagnosis of HCL.     

Analysis of CD10+ hairy cell leukemia

Hairy cell leukemia (HCL) has been reported to sometimes express CD10. However, the reported frequencies have been quite variable and the significance of CD10 expression has not been addressed. Cases of HCL submitted to our flow cytometry service during a 2-year period were evaluated for CD10 expression. Information regarding demographics, clinical manifestations, tissue morphologic features, and response to treatment was reviewed. Of the 97 HCL cases identified, 10 expressed CD10. The level of CD10 staining was typically well above control levels and also could be detected easily by immunohistochemical analysis. All cases analyzed were negative for bcl-6. Our study suggests that approximately 10% of otherwise typical cases of HCL show aberrant CD10 expression. CD10+ HCL cases seem to be morphologically and clinically similar to CD10-HCL cases. Appreciating that HCL can express CD10 may be especially important when evaluating specimens with suboptimal morphologic features and/or limited immunophenotyping panels.     

Ultrastructural localization of immunoglobulins in hairy cell leukemia

Neoplastic cells from 13 cases of hairy cell leukemia were investigated for immunoglobulin production and lysozyme activity by an electron-immunoperoxidase technique. In 10 cases cytoplasmic immunoglobulins were found, but lysozyme activity was absent in all cases. Immunoglobulins were detected in the perinuclear space and endoplasmic reticulum and at the surface of hairy cells. Of the cases in which immunoglobulins were detected in hairy cells, nine were positive with IgM antiserum and one with IgG antiserum. The immunoglobulins were monoclonal in all cases; six were positive with lambda antiserum and three with kappa antiserum. The class and type of surface immunoglobulins were identical to those of cytoplasmic immunoglobulins in the hairy cells. These results support the conclusion that hairy cells are commonly derived from immunoglobulin-producing B cells at an earlier stage of differentiation than plasma cells.     

Disseminated atypical mycobacterial infection in hairy cell leukemia

The clinical features are described of disseminated atypical mycobacterial infection of the subcutaneous tissues occurring in a patient 3 yr after the diagnosis of hairy cell leukemia. Skin biopsy identified the causative organism as an atypical mycobacterium of the M. avium-intracellulare-scrofulaceum (MAIS) complex. In vitro studies showed that the patient had impaired mononuclear cell phagocytosis. These findings, lend support to the hypothesis of a specific defect of immunity in hairy cell leukemia.     

Central nervous system involvement in hairy cell leukemia

Summary A patient with central nervous system involvement by hairy cell leukemia is reported. Hairy cells were identified in the cerebrospinal fluid by electron microscopy and by tartrate-resistant acid phosphatase positive staining. Intrathecal treatment with methotrexate resulted in neurologic improvement, but was complicated by Cryptococcus neoformans meningitis. The leukemic phase of the disease was later successfully controlled by treatment with alpha interferon. Surface marker studies indicated a B- and T-cell phenotype of the hairy cells.