PROLIFERATION AND CELLULAR PHENOTYPE IN LYMPHOMATOID GRANULOMATOSIS

Pulmonary involvement by lymphomatoid granulomatosis (LYG) is characte rized by nodules of a polymorphous lymphoreticular infiltrate with nec rosis, angioinvasion, and variable numbers of large, atypical cells. U sing combined immunohistochemistry, the authors compared the expressio n of a marker of proliferation (DNA topoisomerase II alpha) between B cells, T cells, and histiocytes. Sixteen cases of LYG were stained by combined immunohistochemistry for DNA topoisomerase II alpha and CD-20 , CD-3, CD-68, and CD-57. A proliferation index was determined for B c ells, T cells, histiocytes, and natural killer cells by dividing the n umber of cells with coexpression of DNA topoisomerase II alpha: and CD -20, CD-3, CD-68, or CD-57 by the total number of CD-20(+), CD-3(+), C D-68(+), or CD-57(+) cells, respectively. A significantly higher proli feration 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 0.0 2 +/- 0.01 (range, 0.00-0.04), for histiocytes was 0.00 +/-. 0.01 (ran ge, 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 cas e of grade 1 LYG (0.00). The authors conclude that (1) there is a spec trum of B-cell proliferation in LYG that roughly correlates with histo logic grade, (2)T cells, histiocytes, and natural killer cells do not proliferate but are recruited, and (3) the average B-cell proliferatio n index in grade III LYG is similar to that observed in large cell non -Hodgkin's B-cell lymphomas. These observations provide a possible rat ionale for the use of chemotherapy for grade III LYG and observation o r immunologic adjuvants for LYG with grade I or grade II histology.