Sep 28, 2012 - teristic expression of CD5. these patients exhibited concurrent expression of CDl IC previously considered specific for hairy cell leukemia (HCL) ...
From bloodjournal.hematologylibrary.org by guest on September 28, 2012. For personal use only.
1992 80: 1095-1096
CD5+, CD11C+, trap-positive chronic lymphocytic leukemia/prolymphocytic leukemia [letter; comment] HM Prince, J Bashford and MB van der Weyden
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From bloodjournal.hematologylibrary.org by guest on September 28, 2012. For personal use only. CORRESPONDENCE
1095
CD5+, CDllC+, TRAP-POSITIVE CHRONIC LYMPHOCYTIC LEUKEMIA/PROLYMPHOCYTICLEUKEMIA To the Editor: We read with interest the two recent reports in Blood'.2 outlining a unique subset of the chronic lymphoproliferative disorders with morphologic features of chronic lymphocytic leukemia (CLL) and/or prolymphocytic leukemia (PLL). In addition to the characteristic expression of CD5. these patients exhibited concurrent expression of CDl IC previously considered specific for hairy cell leukemia (HCL). Both reports noted that tartrate-resistant acid phosphatase (TRAP) was negative in all patients tested. We report a CLL/PLL patient with CD5 and CDllc expression who also exhibited TRAP positivity. The patient is a 65-year-old Caucasian female who presented in 1987 with shoulder pain. There was no lymphadenopathy or organomegaly. The leukocyte count was 30.5 x 109/Lwith 90% lymphocytes. Limited immunophenotypic analysisof these lymphocytes showed CD19+,CD5+ and moderate intensity K light chain positivity. Over the next 4 years the patient was treated with intermittent coursesof low-dose chlorambucil,prednisolone,and cyclophosphamide. In May 1991, she had developed palpable splenomegaly (4 cm below left costal margin) with no lymphadenopathy. The leukocyte count was 300 x 10p/Lwith neutrophils of 3 x 109/L,
Fig 1. This photomicrograph(originalmagnification ~24,000)illustrates the electron microscopic features of the patient's peripheral blood prolymphocytic cells.
smear cells 69 x lo9& and lymphocytes 228 x IO9& 27% of which had characteristic prolymphocytic morphology with a regular cytoplasmic outline. The hemoglobin was 85 g/L and the platelet count was 167 x I09/L. Bone marrow aspirate displayed normal megakaryopoiesisand markedly reduced erythropoiesisand myelopoiesis with 80% small lymphocytes and 20% prolymphocytes. The trephine was 90% cellular with a diffuse infiltration of lymphocytes. Reticulin was mildly increased. TRAP staining of the peripheral blood and bone marrow was positive in the majority of prolymphocytes. Electron microscopy (EM) confirmed the presence of populations of mature lymphocytes and prolymphocytes(Fig I). lmmunophenotypicanalysis of peripheral blood and bone marrow displayed positivity for CD5, CD19, CD20, CD22. surface K 59% (moderate intensity), CDIlb, and CDllc with CDllICD19 coexpression. In addition, the cells were negative for CD25 and CD IO. With light microscopy and EM, the lymphoproliferativedisorder of the patient is consistent with CLL/PLL. The expression of CD5 together with the monoclonal light chain expression of moderate intensity concurs with this classification. CDl Ic and CDllcll9
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CORRESPONDENCE
coexpression was present, whereas CD25 was absent. Importantly, no cytoplasmic projections or ribosomal lamellar complexes characteristic of HCL were noted on EM. What is intriguing about the current patient is her TRAP positivity. Although TRAP positivity is classically associated with HCL, 10% of HCL are TRAP-negative: and up to 5% of PLL patients exhibit TRAP positivity: Although we partly agree with Hanson et al’s proposal2 that “CDllc-positive, Leu 8, CD25 and TRAP negative B-cell malignancy constitute a spectrum of disorders . . . intermediate between CLL and HCL,” we do not consider TRAP negativity an absolute criterion for phenotypic inclusion into this group of chronic lymphoproliferative disorders. It well may be that a specific
subgroup of these patients with CLL/PLL morphology and C D l l c and CDllc/l9 coexpression will, like our patient, exhibit TRAP positivity. The clinical significance of these findings remains to be determined.
H. MILES PRINCE JOHN BASHFORD MARTIN B. VAN DER WEYDEN Department of Haematology Alfred Hospital Prahran, Kctoria Australia
REFERENCES
1. Wormsley SB, Baird SM, Gadol N, Rai KR, Sobol RE: Characteristics of CDllc+, CD5+ B cell leukemias and the identification of novel peripheral blood B cell subsets with chronic lymphoid leukemia immunophenotypes. Blood 76:123,1990 2. Hanson CA, Gribbin TE, Schnitzer B, Schlegelmilch JA, Mitchell BS, Shoolman LM: C D l l c (LeuM5) expression characterizes a B-cell chronic lymphoproliferative disorder with features of
both chronic lymphocytic leukemia and hairy cell leukemia. Blood 762360,1990 3. Buskard NA, Catovsky D, Okos A, Goldman JM, Galton DAG: Prolymphocytic leukemia: Cell studies and treatment by leucapheresis. Hamatol Bluttransf 18:237,1976 4. Catovsky D: Hairy cell leukemia and prolymphocytic leukemia. Clin Haematol6:245, 1977
RESPONSE Prince et a1 describe an interesting case of a CLL in apparent prolymphocytoid transformation that exhibited TRAP positivity with an immunophenotype showing expression of CD5, CD19, CD20, CD22, CDllc, and monoclonal K Ig. We appreciate their recognition that the distinction between CLL and HCL can sometimes be blurred and that a spectrum of intermediate chronic lymphoproliferative disorders probably exists. Their case brings up two points of interest worth further discussion. One of the main contentions of our report was the problem of relying on a single laboratory test (eg, CD5, CDllc, etc) as the “gold standard” for the diagnosis of a specific disease entity, such as CLL or HCL.’ Prince et a1 point out that TRAP staining is neither an absolutely specific or sensitive test for HCL, which is a well-established fact in the literature? Rather, HCL is a disease diagnosed on clinical findings, nuclear and cytoplasmic features of leukemic cells in blood and bone marrow smears, bone marrow histologic sections, and, finally, TRAP cytochemical ~taining.~ All these components are necessary in the evaluation of HCL, but are not essential for the diagnosis of HCL. The finding of TRAP positivity in this case of CLL in prolymphocytoid transformation is certainly within the known spectrum of TRAP staining, which has been reported in some cases of PLL? The second point relates to the biologic role of the CDllc/CD18 complex in chronic lymphoproliferative disease. C D l l c is one of the a chain components of the CDllc/CD18 leukocyte adhesion
complex.’ Its role in leukocyte biology involves cell-cell and cell-surface interaction. Our data and those of others suggest that this molecule, undoubtedly in association with other lymphocyte migration and adhesion complexes, may selectively promote migratiodadhesion to extranodal sites, such as the ~ p l e e n . ’ ,The ~ , ~ case described by Prince et a1 had many similarities to the cases described in our study, including the presence of splenomegaly without lymphadenopathy. Unfortunately, C D l l c was not evaluated at the initial presentation and we cannot tell from their letter whether CDllc was expressed in the majority or a minority (ie, just the prolymphocytes) of cells. Anecdotally, we have also observed two cases of PLL with moderate to marked splenomegaly, in which the leukemic cells uniformly expressed CD1lc, again raising questions as to whether this adhesion complex may mediate the splenic enlargement, which appears to be characteristic of these lymphoproliferative disorders. CURTIS A. HANSON BERTRAM SCHNITZER Department of Pathology BEVERLY S . MITCHELL THOMAS E. GRIBBIN Department of Internal Medicine University of Michigan Hospitals Ann Arbor, MI
REFERENCES
1. Hanson CA, Gribbin TE, Schnitzer B, Schlegelmilch JA, Mitchell BS, Stoolman LM: C D l l c (Leu-M5) expression characterizes a B-cell chronic lymphoproliferative disorder with features of both chronic lymphocytic leukemia and hairy cell leukemia. Blood 762360,1990 2. Catovsky D Hairy cell leukemia and prolymphocytic leukemia. Clin Haematol6:245,1977 3. Change KL, Stroup R, Weiss LM: Hairy cell leukemia: Current status. Am J Clin Pathol97:719,1992
4. Wormsley SB, Baird SM, Gadol N, Rai KR, Sobol RE: Characteristics of CDllc+CD5+ chronic B-cell leukemias and the identification of novel peripheral blood B-cell subsets with chronic lymphoid leukemia immunophenotypes. Blood 76:123, 1990 5. Heimann PS, Vardiman JW, Stock W, Platanias LC, Golomb HM: CD5+, CDllc+, CD20+ hairy cell leukemia. Blood 77:1617, 1991 (letter)
