title: Proliferation and cellular phenotype in lymphomatoid granulomatosis: implications of a higher proliferation index in B cells.
abstract: Pulmonary involvement by lymphomatoid granulomatosis (LYG) is characterized by nodules of a polymorphous lymphoreticular infiltrate with necrosis, angioinvasion, and variable numbers of large, atypical cells. Using combined immunohistochemistry, the authors compared the expression of a marker of proliferation (DNA topoisomerase IIalpha) between B cells, T cells, and histiocytes. Sixteen cases of LYG were stained by combined immunohistochemistry for DNA topoisomerase IIalpha and CD-20, CD-3, CD-68, and CD-57. A proliferation index was determined for B cells, T cells, histiocytes, and natural killer cells by dividing the number of cells with coexpression of DNA topoisomerase IIalpha and CD-20, CD-3, CD-68, or CD-57 by the total number of CD-20+, CD-3+, CD-68+, or CD-57+ cells, respectively. A significantly higher proliferation index was present in B cells compared to T cells, histiocytes, or natural killer cells (p < 0.002). The average proliferation index for B cells was 0.25+/-0.24 (range, 0.00-0.76), for T cells was 0.02+/-0.01 (range, 0.00-0.04), for histiocytes was 0.00+/-0.01 (range, 0-0.02), and for natural killer cells was 0.00+/-0.00 (range, 0.0-0.02). The average proliferation index of CD-20+ cells was greater in grade III LYG (0.36) than in grade II LYG (0.17) or the single case of grade I LYG (0.00). The authors conclude that (1) there is a spectrum of B-cell proliferation in LYG that roughly correlates with histologic grade, (2) T cells, histiocytes, and natural killer cells do not proliferate but are recruited, and (3) the average B-cell proliferation index in grade III LYG is similar to that observed in large cell non-Hodgkin's B-cell lymphomas. These observations provide a possible rationale for the use of chemotherapy for grade III LYG and observation or immunologic adjuvants for LYG with grade I or grade II histology.
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, USA. dgguinee@msscc.med.utah.edu
authors.forename: D G
authors.initials: DG
authors.lastname: Guinee
authors.forename: S L
authors.initials: SL
authors.lastname: Perkins
authors.forename: W D
authors.initials: WD
authors.lastname: Travis
authors.forename: J A
authors.initials: JA
authors.lastname: Holden
authors.forename: S R
authors.initials: SR
authors.lastname: Tripp
authors.forename: M N
authors.initials: MN
authors.lastname: Koss
mesh_terms: D000328:Adult; D000368:Aged; D018951:Antigens, CD20 / Q000032:analysis; D001402:B-Lymphocytes / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D018959:CD57 Antigens / Q000032:analysis; D002455:Cell Division; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology*; D008230:Lymphomatoid Granulomatosis / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D018951:Antigens, CD20; D015415:Biomarkers; D018959:CD57 Antigens; D004250:DNA Topoisomerases, Type II