|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 24, No 12 (April 20), 2006: pp. 1950-a-1951 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.01.9141
Large B-Cell Lymphoma Masquerading As Acute LeukemiaHospital of the University of Pennsylvania, Philadelphia, PA A previously well 41-year-old man presented with a 1-week history of fevers, night sweats, lassitude, early satiety, and abdominal bloating. Physical examination revealed marked hepatosplenomegaly without palpable lymphadenopathy. Laboratory evaluation included a CBC with hematocrit at 35%, a platelet count of 122 x 109/L and a WBC count of 112.6 x 109/L with 89% large blastic appearing cells (Fig 1; peripheral blood smear: high-power view oil immersion, showing large [approximately 20 to 25 µm] blastic cells with variable amounts of agranular, pale basophilic cytoplasm with only rare vacuoles, and nuclei with open chromatin, irregular contours, and prominent nucleoli: original magnification x1,000). On the basis of these features, a diagnosis of an acute leukemia, possibly an acute monoblastic leukemia, was favored. However, flow cytometric analysis of these cells showed that they were neither "blastic" (absent CD34 and terminal deoxynucleotide transferase (TdT), bright CD45) nor myelomonocytic (Fig 2; flow cytometry showing a predominant population of high side-scatter, bright CD45+ cells that are CD19+, CD20+, CD10+, CD5+, CD34–, TdT–, SmIg– B-cells). Rather, they had a B-cell immunophenotype, expressing CD19, CD20, cCD79a, and human leukocyte antigen DR, as well as coexpressing both CD5 and CD10, but lacking surface immunoglobulin. Immunohistochemistry performed on an extensively infiltrated bone marrow biopsy and clot section confirmed the B-cell lineage of the cells, as well as the CD5 and CD10 coexpression (data not shown). Additionally, these studies revealed that the cells expressed BCL2 but neither cyclin D1 nor BCL6. Ki-67 was expressed by approximately 40% of the malignant cells. Thus, with these somewhat unanticipated immunophenotypic data, the initially favored diagnosis of an acute leukemia was revised to that of an aggressive, "mature" B-cell lymphoproliferative disorder with a leukemic phase. Indeed, computed tomography revealed quite extensive thoracic (confluent right and left paratracheal, subcarinal, right hilar, and right bronchopulmonary) and mild upper abdominal lymphadenopathy, in addition to the hepatosplenomegaly. Conventional karyotypic analysis performed on 25 cells revealed multiple abnormalities, but with a t(8;14)/CMYC-IGH translocation identified by fluorescence in situ hybridization (FISH) only (data not shown). There was no response to initial therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Following receipt of the cytogenetic and FISH results, therapy was switched to R-hyperCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone), which rapidly normalized the peripheral counts and decreased the lymphadenopathy. Unfortunately, the patient relapsed during his second cycle of hyperCVAD with recurrent hepatosplenomegaly, lymphadenopathy, and circulating lymphoma cells. These findings failed to normalize despite additional attempts at high-dose methotrexate and cytarabine-based chemotherapy. He developed acute renal failure, which was felt clinically to represent infiltration by lymphoma. After clinical deterioration while on dialysis, further aggressive care was withdrawn and the patient expired, 5 months following initial diagnosis.
Although the profound leukocytosis and morphology were initially interpreted to be most consistent with an acute leukemia, the immunophenotypic features indicated that this was a mature/nonblastic B-cell neoplasm, as evidenced by the expression of B-cell antigens, bright CD45, and absence of CD34 and Tdt. Furthermore, while the CD10 coexpression and FISH data might have suggested a Burkitt lymphoma/leukemia or variant thereof, there were a variety of morphologic (extremely large size of the neoplastic cells as well as lack of both the characteristically prominent cytoplasmic vacuoles and intense cytoplasmic basophilia), immunophenotypic (lack of surface immunoglobulin and BCL6, and presence of BCL2) and kinetic (relatively low proliferative index on Ki-67 analysis) data that militated against this consideration. Accordingly, this aggressive/"high-grade" B-cell lymphoproliferative disorder was given a (somewhat unusual) diagnosis of large B-cell lymphoma (LBCL), in leukemic phase. The presence of a CMYC translocation does not preclude this consideration; indeed, although t(8;14) is characteristically associated with Burkitt’s lymphoma, it is certainly not specific for this entity and has been described in approximately 5% to 10% LBCLs.1-3 LBCL typically presents in nodal or extranodal sites, with the florid leukemic presentation evident in this patient being rather unusual.4 The coexpression of CD5 in any aggressive B-cell lymphoma warrants some consideration of the possibility of large cell transformation of chronic lymphocytic leukemia (CLL) or mantle-cell lymphoma (MCL), perhaps blastoid variant thereof. However, since there was no antecedent history of CLL and cyclin D1 was negative, these diagnoses were considered most unlikely. Hence, a diagnosis of de novo CD5+ LBCL was favored. In general, de novo CD5+ LBCL, which appear to account for  10% of de novo LBCL, is characterized by numerous adverse prognostic features, as compared with CD5- DLBCL.5 These features include older age at presentation, poor performance status, higher LDH levels, more advanced stage, greater likelihood of B symptoms and more frequent extranodal involvement, with the most common location of the latter being the bone marrow. CD10 coexpression in CD5+ LBCL, as was evident in the presented patient, reportedly occurs in 5% of cases.5 Additionally, while the CD10 coexpression is suggestive of a germinal center histogenic origin of this LBCL, the absence of BCL6 and presence of BCL2 are more consistent with an "activated B-cell" origin,6 providing an additional adverse component to this disease. This case is instructive at a number of levels. First, the initial clinical presentation and morphology were rather deceptive; second, it highlights the fact that CD5 can be expressed on B-cell lymphoproliferative disorders other than CLL and MCL; and third, it confirms that the t(8;14) translocation is not specific for Burkitt lymphoma. Together, the features underscore the need to fully integrate morphologic, immunophenotypic, and genetic data in reaching specific diagnoses, even if they are rather unusual. Authors’ Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
REFERENCES 1. Rossi D, Gaidano G: Molecular heterogeneity of diffuse large B-cell lymphoma: Implications for disease management and prognosis. Hematology 7:239-252, 2002[Medline] 2. Akasaka T, Akasaka H, Ueda C, et al: Molecular and clinical features of non-Burkitt’s, diffuse large-cell lymphoma of B-cell type associated with the c-MYC/immunoglobulin heavy-chain fusion gene. J Clin Oncol 18:510-518, 2000 3. Fram RJ, Skarin AT, Rosenthal DS, et al: Clinical pathologic and immunologic features of patients with non-Hodgkin’s lymphoma in a leukemic phase. Cancer 52:1220-1228, 1983[Medline] 4. Bain B, Matutes E, Robinson D, et al: Leukaemia as a manifestation of large cell lymphoma. Br J Haematol 77:301-310, 1991[Medline] 5. Yamaguchi M, Seto M, Okamoto M, et al: De novo CD5+ diffuse large B-cell lymphoma: A clinicopathologic study of 109 patients. Blood 99:815-821, 2002 6. Hans CP, Weisenburger DD, Greiner TC, et al: Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103:275-282, 2004
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
