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Journal of Clinical Oncology, Vol 25, No 16 (June 1), 2007: pp. 2326-2328 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.10.7896
Blastic Transformation of Low-Grade Follicular LymphomaDepartment of Pathology, University of Utah School of Medicine, Salt Lake City, UT
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT
Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI A 72-year-old woman with stage IV A follicular grade 2 lymphoma was referred to us in 2002 with a diagnosis of recurrent lymphoma. In the past, she was treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone leading to a complete response. She was in complete remission until 3 weeks before current presentation when she developed progressive weakness and malaise. Physical examination was remarkable for conjunctival pallor, cervical lymphadenoapthy, and mild pitting ankle edema. Laboratory data were notable for hematocrit of 23%, platelets 84 x 109/L, WBC 3 x 106/L, sodium 129 mmol/L, creatinine 3.4 mg/dL, calcium 7.8 mg/100 mL, albumin 3 gram percent, lactate dehydrogenase 1,409 U/L (normal range, 300-600 U/L). A computed tomography scan of the chest, abdomen, and pelvis without contrast revealed extensive axillary, mediastinal, and abdominal lymphadenopathy, splenomegaly, ascites, and right ureteral dilation. The scan suggested hydronephrosis secondary to obstruction by enlarged lymph nodes. Peripheral blood smear was remarkable for 22% of white cells being small to intermediate-size atypical lymphoid cells with a high nuclear-to-cytoplasmic ratio and fine chromatin consistent with the morphologic features of a lymphoblast (Fig 1, x100). A bone marrow aspiration demonstrated 90% cellularity, and more than 80% of the cells were small to intermediate-size atypical lymphocytes with blastic chromatin without a starry-sky pattern (Fig 2, x100). Flow cytometric analysis of the bone marrow aspirate specimen revealed a large population of CD10+ monoclonal B-cells, which expressed CD19, CD22, partial CD20, and kappa light chain, and were negative for terminal deoxynucleotidyl tranferase (TdT). However, a distinct population of paratrabecular lymphoid cells with the morphologic and immunophenotypic features of a low-grade follicular lymphoma was observed (as seen on low power in Fig 3, x40). The cytogenetic analysis of the aspirate revealed multiple cytogenetic abnormalities: 52,XX,+1,+add(1)(q11),del(1)(p32)x2, –5, +8, t(8;14)(q24.1;q32),add(9)(p24),+12,+ 12,-13,–13,add(14)(q32),+18,+3mar[cp2]/46,XX. Clinical and laboratory evaluation gave an impression of high-grade B-cell lymphoma with morphologic and immunophenotypic features of a blastic/blastoid transformation of a follicular lymphoma. The patient underwent a right ureteral stent placement and was transfused with packed RBC. Over the next 3 days, her weakness improved and serum creatinine decreased to 2.0 mg/dL. She was treated with rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin (RESHAP), which was complicated by tumor lysis syndrome. She also received intrathecal prophylaxis with methotrexate, though cerebrospinal fluid was negative for malignant cells. Her clinical condition improved markedly with normalization of blood counts and renal function, and the blasts in the peripheral blood disappeared. She received a total of four cycles of RESHAP, but immediately after the fourth cycle, rapid progression of disease was noted, and no further cytotoxic therapy was given. She died after 3 weeks of hospice care.
Follicular lymphoma (FL) is the most common type of indolent non-Hodgkin's lymphoma. The most common cytogenetic abnormality in follicular lymphoma is t(14;18)(q32;q21).1 This translocation results in the juxtaposition of the bcl-2 oncogene into the immunoglobulin heavy chain locus on chromosome 14, which leads to constitutive expression of the antiapoptotic protein bcl-2. 2 The median age for diagnosis of follicular lymphoma is 60 years with slight female preponderance. The disease course is characterized by initial partial or complete response to therapy, but eventual progression to treatment refractory disease or transformation to more aggressive forms. Median survival has been reported to be approximately 10 years after initial diagnosis and 22 months after histological transformation.3 The reported frequency of transformation of low-grade follicular lymphoma varies from 20% to 70%, depending on the duration of follow-up and whether histological transformation was documented by biopsies or autopsies.3,4 Progression and transformation of follicular lymphoma has been suggested to occur because of subclone selection (ie, the outgrowth of minor clones present at diagnosis that gain a growth advantage over time) or because of clonal evolution or a combination of both.2,5Though low-grade follicular lymphoma most commonly transforms to diffuse large B-cell lymphoma, blastic or blastoid transformation is known to occur rarely.6,7 The blastic/blastoid variant of follicular lymphoma has a highly aggressive disease course characterized by poor response to therapy and high mortality rate. Other morphologically similar lymphoproliferative disorders include blastic mantle-cell lymphoma and acute lymphoblastic leukemia. These can be distinguished from blastic transformation of FL using clinical and immunophenotypic characteristics. A patient with a previous diagnosis of FL with lymphoblast-like cells with a germinal center–type phenotype (bcl-2+, CD10+) would have blastic transformation of follicular lymphoma. Alternatively, a de novo diagnosis of blastic transformation of FL would be very rare, and mantle-cell lymphoma (CD20+, CD5+, CD23–, cyclin D1+) or acute lymphoblastic leukemia (CD20–, CD10–, TdT+, and so on) should be considered. To conclude, blastic transformation of low-grade follicular lymphoma is a rare entity and has a poor prognosis. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The authors indicated no potential conflicts of interest.
REFERENCES
1. The Non-Hodgkin's Lymphoma Classification Project: A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. Blood 89:3909-3918, 1997 2. Winter JN, Gascoyne RD, Van Besien K: Low-grade lymphoma. Hematology Am Soc Hematol Educ Program 203-220, 2004 3. Yuen AR, Kamel OW, Halpern J, et al: Long-term survival after histologic transformation of low-grade follicular lymphoma. J Clin Oncol 13:1726-1733, 1995[Medline] 4. Bastion Y, Sebban C, Berger F, et al: Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients. J Clin Oncol 15:1587-1594, 1997[Abstract] 5. Aarts WM, Bende RJ, Bossenbroek JG, et al: Variable heavy-chain gene analysis of follicular lymphomas: Subclone selection rather than clonal evolution over time. Blood 98:238-240, 2001 6. Natkunam Y, Warnke RA, Zehnder JL, et al: Blastic/blastoid transformation of follicular lymphoma: Immunohistologic and molecular analyses of five cases. Am J Surg Pathol 24:525-534, 2000[CrossRef][Medline] 7. Mohamed AN, Palutke M, Eisenberg L, et al: Chromosomal analyses of 52 cases of follicular lymphoma with t(14;18), including blastic/blastoid variant. Cancer Genet Cytogenet 126:45-51, 2001[CrossRef][Medline]
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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