CD5+ follicle center lymphoma. Immunophenotyping detects a unique subset of "floral" follicular lymphoma.

The "floral" variant of follicle center lymphoma (FCL) may be confused with progressive transformation of germinal centers or lymphocyte predominance Hodgkin lymphoma. Immunohistochemistry and gene rearrangement studies are usually sufficient to differentiate among these entities. We present 11 cases of floral FCL that were evaluated at our institution by flow cytometry, immunohistochemistry, or both and by polymerase chain reaction-based molecular analysis. In 4 cases, the neoplastic B cells coexpressed CD5 antigens; 3 of these 4 cases also were CD10+, and all demonstrated rearrangement within the bcl-2 locus. These findings demonstrate that a subset of floral FCL is CD5+. Recognition of this immunophenotype is important to avoid misdiagnosis of nodular variants of small lymphocytic lymphoma and mantle cell lymphoma. Studies suggest that expression of CD5 by neoplastic germinal center cells might result from alterations of the follicular microenvironment and/or inappropriate B-cell responses to cytokine networks.

[1]  R B Mann,et al.  Criteria for the cytologic subclassification of follicular lymphomas: A Proposed alternative method , 2007, Hematological oncology.

[2]  Paul J. Kurtin,et al.  Demonstration of distinct antigenic profiles of small B-cell lymphomas by paraffin section immunohistochemistry. , 1999, American journal of clinical pathology.

[3]  K. Rajewsky,et al.  B Cell Antigen Receptor Specificity and Surface Density Together Determine B-1 versus B-2 Cell Development , 1999, The Journal of experimental medicine.

[4]  G. Inghirami,et al.  Detection of Immunoglobulin κ Light Chain Rearrangements by Polymerase Chain Reaction: An Improved Method for Detecting Clonal B-Cell Lymphoproliferative Disorders , 1999 .

[5]  C. Caux,et al.  Toward a role of dendritic cells in the germinal center reaction: triggering of B cell proliferation and isotype switching. , 1999, Journal of immunology.

[6]  M. Nussenzweig,et al.  OCA‐B integrates B cell antigen receptor‐, CD40L‐ and IL 4‐mediated signals for the germinal center pathway of B cell development , 1998, The EMBO journal.

[7]  J. Rodríguez-Sánchez,et al.  B cells and monocytes are not developmentally affected in a case of reticular dysgenesis , 1997, Clinical and experimental immunology.

[8]  F. Herrmann,et al.  Concomitant manifestation of systemic lupus erythematosus and low-grade non-Hodgkin’s lymphoma , 1997, Leukemia.

[9]  Ernst Lindhout,et al.  Germinal center B cells rescued from apoptosis by CD40 ligation or attachment to follicular dendritic cells, but not by engagement of surface immunoglobulin or adhesion receptors, become resistant to CD95‐induced apoptosis , 1997, European journal of immunology.

[10]  F. Caligaris‐cappio.  B-chronic lymphocytic leukemia: a malignancy of anti-self B cells. , 1996, Blood.

[11]  H. Wortis,et al.  B-cell activation by crosslinking of surface IgM or ligation of CD40 involves alternative signal pathways and results in different B-cell phenotypes. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[12]  H Stein,et al.  A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. , 1994, Blood.

[13]  Carl T. Wittwer,et al.  Antigen expression and polymerase chain reaction amplification of mantle cell lymphomas , 1994 .

[14]  D. LeBrun,et al.  Floral Variant of Follicular Lymphoma: Immunological and Molecular Studies Support a Neoplastic Process , 1994, The American journal of surgical pathology.

[15]  N. Harris,et al.  Diffuse low-grade B-cell lymphomas. Four clinically distinct subtypes defined by a combination of morphologic and immunophenotypic features. , 1993, American journal of clinical pathology.

[16]  S. Hsu,et al.  Cytokines in malignant lymphomas: review and prospective evaluation. , 1993, Human pathology.

[17]  E. Cesarman,et al.  Detection of immunoglobulin gene rearrangement of B cell non-Hodgkin's lymphomas and leukemias in fresh, unfixed and formalin-fixed, paraffin-embedded tissue by polymerase chain reaction. , 1993, Laboratory investigation; a journal of technical methods and pathology.

[18]  V. Diehl,et al.  Immunophenotyping of low‐grade B‐cell lymphoma in blood and bone marrow: poor correlation between immunophenotype and cytological/histological classification , 1993, British journal of haematology.

[19]  M. Harigai,et al.  IL‐4 down‐regulates the surface expression of CD5 on B cells and inhibits spontaneous immunoglobulin and IgM‐rheumatoid factor production in patients with rheumatoid arthritis , 1992, Clinical and experimental immunology.

[20]  A. Kantor.  The development and repertoire of B-1 cells (CD5 B cells). , 1991, Immunology today.

[21]  H. Wortis,et al.  Treatment of murine CD5- B cells with anti-Ig, but not LPS, induces surface CD5: two B-cell activation pathways. , 1991, International immunology.

[22]  R. Braylan,et al.  Flow cytometric analysis of lymphomas. , 1989, Archives of pathology & laboratory medicine.

[23]  G. Freeman,et al.  Expression and regulation of CD5 on in vitro activated human B cells , 1989, European journal of immunology.

[24]  G. Gaidano,et al.  Human normal CD5+ B lymphocytes can be induced to differentiate to CD5- B lymphocytes with germinal center cell features. , 1989, Blood.

[25]  J. Banchereau,et al.  Human interleukin 4 down‐regulates the surface expression of CD5 on normal and leukemic B cells , 1989, European journal of immunology.

[26]  S. Korsmeyer,et al.  Thermostable DNA polymerase chain amplification of t(14;18) chromosome breakpoints and detection of minimal residual disease. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[27]  P. Lipsky,et al.  Inhibitory influence of IL-4 on human B cell responsiveness. , 1988, Journal of immunology.

[28]  D. Salter,et al.  Activation and differentiation antigen expression in B‐cell non‐Hodgkin's lymphoma , 1988, The Journal of pathology.

[29]  R. Warnke,et al.  "Well-differentiated" lymphocytic neoplasms. Immunologic findings correlated with clinical presentation and morphologic features. , 1987, The American journal of pathology.

[30]  M R Loken,et al.  Flow cytometric analysis of human bone marrow. II. Normal B lymphocyte development. , 1987, Blood.

[31]  H. Schuurman,et al.  Immunophenotyping of non-Hodgkin's lymphoma. Lack of correlation between immunophenotype and cell morphology. , 1987, The American journal of pathology.

[32]  B. Osborne,et al.  Follicular lymphoma mimicking progressive transformation of germinal centers. , 1987, American journal of clinical pathology.

[33]  R. Hardy,et al.  Development and Physiology of LY‐1 B and its Human Homolog, LEU‐1 B , 1986, Immunological reviews.

[34]  L. Herzenberg,et al.  The LY‐1B Cell Lineage , 1986 .

[35]  J. Nash,et al.  An immunohistochemical study of non‐Hodgkin's lymphomas: correlation of morphological appearances and immunophenotype in 148 cases , 1986, Histopathology.

[36]  S. Emerson,et al.  Leu-1+ (CD5+) B cells. A major lymphoid subpopulation in human fetal spleen: phenotypic and functional studies. , 1986, Journal of immunology.

[37]  R. Hardy,et al.  Progenitors for Ly-1 B cells are distinct from progenitors for other B cells , 1985, The Journal of experimental medicine.

[38]  S. Hsu,et al.  Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. , 1981, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[39]  E. Bruck,et al.  National Committee for Clinical Laboratory Standards. , 1980, Pediatrics.

[40]  R. Lukes,et al.  Immunologic characterization of human malignant lymphomas , 1974, Cancer.

[41]  C. Dunphy,et al.  Flow cytometric findings in the floral variant of follicular lymphoma , 1998, Journal of clinical laboratory analysis.

[42]  J. Binet,et al.  What do chronic B cell malignancies teach us about B cell subsets? , 1997, Chemical immunology.

[43]  M. Boiocchi,et al.  Cellular and molecular bases of B-cell clonal expansions. , 1996, Clinical and experimental rheumatology.

[44]  N. Harris,et al.  CD5+ extranodal marginal zone B-cell (MALT) lymphoma. A low grade neoplasm with a propensity for bone marrow involvement and relapse. , 1996, American journal of clinical pathology.

[45]  S. Asano,et al.  Clinical significance of serial measurement of the serum levels of soluble interleukin-2 receptor and soluble CD8 in malignant lymphoma. , 1995, Leukemia & lymphoma.

[46]  D. Jones,et al.  Correlation between histology and immunophenotype in a series of 322 cases of non‐Hodgkin's lymphoma , 1989, Hematological oncology.

[47]  R. Hardy,et al.  Immunoglobulin‐bearing B cells reconstitute and maintain the murine Ly‐1 B cell lineage , 1986, European journal of immunology.

[48]  K. Lennert,et al.  Immunohistological analysis of human lymphoma: correlation of histological and immunological categories. , 1984, Advances in cancer research.

[49]  H. Rappaport,et al.  Tumors of the hematopoietic system , 1966 .