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Follicular lymphoma

Follicular lymphoma (FL) is the most common of the indolent non-Hodgkin's lymphomas. It is defined as a lymphoma of follicle center B-cells (centrocytes and centroblasts), which has at least a partially follicular pattern. more...

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Morphology

The tumor is composed of follicle center cells, usually a mixture of centrocytes (cleaved follicle center cells, "small cells") and centroblasts (large noncleaved follicle center cells, "large cells"). Centrocytes typically predominate; centroblasts are usually in the minority, but by definition are always present. Rare lymphomas with a follicular growth pattern consist almost entirely of centroblasts. Occasional cases may show plasmacytoid differentiation or foci of marginal zone or monocytoid B-cells.

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Transformation of follicular lymphoma to acute lymphoblastic leukemia
From Archives of Pathology & Laboratory Medicine, 8/1/02 by Sun, Xiaoping

In March 1994, a 56-year-old man underwent lobectomy of the upper lobe of the right lung and lymph node dissection for poorly differentiated adenocarcinoma. Malignant lymphoma, follicular, small cleaved was identified in multiple paratracheal and hilar lymph nodes. Hematoxylin-eosin-stained sections of the lymph nodes showed a follicular pattern and a predominance of small cleaved lymphoma cells (Figure, A). Bilateral bone marrow biopsies showed a single paratrabecular lymphoid aggregate that suggested involvement by the follicular lymphoma. During the next 6 years, the patient underwent 2 biopsies and 2 fine-needle aspiration biopsies of lymph nodes from different sites, and the results of all of these biopsies were consistent with the initial diagnosis. Flow cytometric immunophenotyping was performed on 3 of the lymph node specimens, and all contained CD10+ and CD5- clonal B cells (CD19+ and CD20+) with X surface immunoglobulin light chain restriction. In August of 1999, 5 years after the initial diagnosis, repeated bilateral bone marrow biopsies showed a normocellular bone marrow with 2 nonparatrabecular lymphoid aggregates; these findings were not diagnostic for lymphoma. Flow cytometry studies of the bone marrow showed no evidence of B-cell clonality. The patient's treatment included chlorambucil and radiolabeled rituximab.

In May 2001, nearly 7 years after the initial diagnosis, abnormal blastlike cells were noted in peripheral blood smears; these cells comprised 8% of white blood cells (Figure, B). No peripheral lymphadenopathy was noted. Bone marrow biopsies showed extensive diffuse infiltration of bilateral core sections by medium-sized lymphoid cells with immature chromatin and occasional prominent nucleoli (Figure, C). Mitotic figures were prominent. The aspirate smears contained cells with moderately basophilic cytoplasm and cytoplasmic vacuoles (Figure, D); these cells comprised 40% of nucleated bone marrow cells. Flow cytometry studies of the aspirate showed B cells (CD19+) that were positive for CD10 and dim positive for terminal deoxynucleotidyl transferase but negative for surface or cytoplasmic immunoglobulin expression. Polymerase chain reaction of the bone marrow biopsy revealed a bcl2-IgH gene rearrangement. A diagnosis of precursor B-- lymphoblastic leukemia arising from follicular lymphoma was rendered. The patient was treated with methotrexate and leukovorin calcium, and tumor lysis syndrome with acute renal failure occurred. The patient's condition subsequently stabilized, and chemotherapy was continued.

Follicular lymphoma usually has an indolent clinical course and may present with waxing and waning enlargement of the lymph nodes. The natural history of the disease is accrual of large cells and transformation to an aggressive lymphoma. Transformation occurs in approximately 60% of patients and is almost always transformation to a diffuse large B-cell lymphoma. Transformation to precursor B-lymphoblastic leukemia/lymphoma is extremely rare.1-3 In the current case, the patient had a 7-- year history of well-established low-grade follicular lymphoma that subsequently progressed to an aggressive lymphoid neoplasm with extensive involvement of the blood and bone marrow. This presentation together with the Mastic appearance of the tumor cells and the flow cytometric results (terminal deoxynucleotidyl transferase dim positive and surface immunoglobulin negative) led to the diagnosis of lymphoblastic leukemia. The bcl-2-IgH gene rearrangement in the leukemic cells suggests that the lymphoblastic leukemia most likely arose from the lowgrade follicular lymphoma.

The mechanism underlying transformation of follicular lymphoma is not known, although the transformed lymphoma cells may have genetic abnormalities in addition to the t(14;18) translocation. Transformation of follicular lymphoma is associated with a poor outcome. The use of high-dose chemotherapy and autologous stem cell transplantation in patients with relapsed disease is receiving increased attention.

References

1. Gauwerky CE, Hoxie J, Nowell PC, Croce CM. Pre-B-cell leukemia with a t(8;14) and a t(14;18) translocation is preceded by follicular lymphoma. Oncogene. 1988;2:431-435.

2. Fiedler W, Weh Hj, Zeller W, et al. Translocation (14;18) and (8;22) in three patients with acute leukemia/lymphoma following centrocytic/centroblastic nonHodgkin's lymphoma. Ann Hematol. 1991;63:282-287.

3. Kroft SH, Domiati-Saad R, Finn WG, et al. Precursor B-lymphoblastic transformation of grade I follicle center lymphoma. Am J Clin Pathol. 2000;113:411418.

Xiaoping Sun, MD, PhD; Leo I. Gordon, MD; LoAnn C. Peterson, MD

Accepted for publication March 1, 2002.

From the Department of Pathology, Northwestern University Medical School, Chicago, Ill.

Reprints: LoAnn C. Peterson, MD, Department of Pathology, Northwestern University Medical School, Feinberg Pavilion, Room 7-344, 251 East Huron St, Chicago, IL 60611 (e-mail: loannc@nwu.edu).

Copyright College of American Pathologists Aug 2002
Provided by ProQuest Information and Learning Company. All rights Reserved

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