0 5 Bcl-6 Bcl-6 NNP 6 16 expression expression NN 17 19 in in IN 20 28 reactive reactive JJ 29 39 follicular follicular JJ 40 51 hyperplasia hyperplasia NN 51 52 , , , 53 63 follicular follicular JJ 64 72 lymphoma lymphoma NN 72 73 , , , 74 77 and and CC 78 96 angioimmunoblastic angioimmunoblastic JJ 97 103 T-cell t-cell NN 104 112 lymphoma lymphoma NN 113 117 with with IN 118 130 hyperplastic hyperplastic JJ 131 139 germinal germinal JJ 140 147 centers center NNS 147 148 : : : 149 162 heterogeneity heterogeneity NN 163 165 of of IN 166 181 intrafollicular intrafollicular JJ 182 189 T-cells t-cell NNS 190 193 and and CC 194 199 their their PRP$ 200 207 altered altered JJ 208 220 distribution distribution NN 221 223 in in IN 224 227 the the DT 228 240 pathogenesis pathogenesis NN 241 243 of of IN 244 262 angioimmunoblastic angioimmunoblastic JJ 263 269 T-cell t-cell NN 270 278 lymphoma lymphoma NN 278 279 . . . 281 291 BACKGROUND background NN 291 292 : : : 293 296 The the DT 297 302 Bcl-6 Bcl-6 NNP 303 307 gene gene NN 308 315 product product NN 315 316 , , , 317 318 a a DT 319 326 nuclear nuclear JJ 327 341 phosphoprotein phosphoprotein NN 341 342 , , , 343 345 is be VBZ 346 355 expressed express VBN 356 369 independently independently RB 370 372 of of IN 373 378 Bcl-6 Bcl-6 NNP 379 383 gene gene NN 384 397 rearrangement rearrangement NN 397 398 . . . 399 401 In in IN 402 407 lymph lymph NN 408 413 nodes node NNS 413 414 , , , 415 425 expression expression NN 426 428 of of IN 429 434 Bcl-6 Bcl-6 NNP 435 442 protein protein NN 443 445 is be VBZ 446 456 restricted restricted JJ 457 459 to to TO 460 468 germinal germinal JJ 469 475 center center NN 476 477 ( ( ( 477 479 GC GC NNP 479 480 ) ) ) 481 488 B-cells B-cell NNP 489 492 and and CC 493 495 10 10 CD 495 496 % % NN 497 499 to to TO 500 502 15 15 CD 502 503 % % NN 504 506 of of IN 507 515 CD3/CD4+ cd3/cd4+ JJ 516 531 intrafollicular intrafollicular JJ 532 533 T t NN 534 539 cells cell NNS 539 540 . . . 541 556 Interfollicular interfollicular JJ 557 562 cells cell NNS 563 566 are be VBP 567 575 negative negative JJ 576 579 for for IN 580 585 Bcl-6 Bcl-6 NNP 586 593 protein protein NN 593 594 , , , 595 601 except except IN 602 605 for for IN 606 610 rare rare JJ 611 620 CD3+/CD4+ cd3+/cd4+ JJ 621 622 T t NN 623 628 cells cell NNS 628 629 . . . 630 638 Recently recently RB 638 639 , , , 640 642 we we PRP 643 651 reported report VBD 652 657 cases case NNS 658 660 of of IN 661 679 angioimmunoblastic angioimmunoblastic JJ 680 686 T-cell t-cell NN 687 695 lymphoma lymphoma NN 696 697 ( ( ( 697 701 AITL AITL NNP 701 702 ) ) ) 703 707 with with IN 708 720 hyperplastic hyperplastic JJ 721 724 GCs gc NNS 725 726 ( ( ( 726 733 AITL/GC AITL/GC NNP 733 734 ) ) ) 734 735 , , , 736 739 and and CC 740 748 observed observe VBD 749 753 that that IN 754 761 borders border NNS 762 764 of of IN 765 773 enlarged enlarged JJ 774 777 GCs gc NNS 778 782 were be VBD 783 786 ill ill RB 787 794 defined define VBN 794 795 , , , 796 800 with with IN 801 809 features feature NNS 810 820 suggestive suggestive JJ 821 823 of of IN 824 826 an an DT 827 834 outward outward JJ 835 844 migration migration NN 845 847 of of IN 848 850 GC GC NNP 851 856 cells cell NNS 857 859 to to TO 860 871 surrounding surround VBG 872 887 interfollicular interfollicular JJ 888 893 zones zone NNS 893 894 . . . 895 899 This this DT 900 908 prompted prompt VBD 909 910 a a DT 911 916 study study NN 917 919 of of IN 920 930 follicular follicular JJ 931 938 borders border NNS 939 943 with with IN 944 949 Bcl-6 bcl-6 NN 950 958 staining staining NN 959 961 in in IN 962 970 reactive reactive JJ 971 981 follicular follicular JJ 982 994 hyperplasias hyperplasia NNS 995 998 and and CC 999 1009 follicular follicular JJ 1010 1019 lymphomas lymphoma NNS 1020 1022 to to TO 1023 1030 compare compare VB 1031 1035 with with IN 1036 1043 AITL/GC AITL/GC NNP 1043 1044 . . . 1045 1054 MATERIALS MATERIALS NNP 1055 1058 AND and CC 1059 1066 METHODS METHODS NNP 1066 1067 : : : 1068 1082 Formalin-fixed formalin-fixed JJ 1083 1091 paraffin paraffin NN 1092 1100 sections section NNS 1101 1105 were be VBD 1106 1110 used use VBN 1111 1114 for for IN 1115 1129 immunostaining immunostaining NN 1130 1132 of of IN 1133 1138 Bcl-6 Bcl-6 NNP 1138 1139 . . . 1140 1143 Six six CD 1144 1149 cases case NNS 1150 1152 of of IN 1153 1160 AITL/GC AITL/GC NNP 1160 1161 , , , 1162 1164 12 12 CD 1165 1176 nonspecific nonspecific JJ 1177 1185 reactive reactive JJ 1186 1196 follicular follicular JJ 1197 1208 hyperplasia hyperplasia NN 1209 1210 ( ( ( 1210 1212 FH FH NNP 1212 1213 ) ) ) 1213 1214 , , , 1215 1216 7 7 CD 1217 1220 HIV HIV NNP 1221 1231 adenopathy adenopathy NN 1231 1232 , , , 1233 1235 10 10 CD 1236 1246 follicular follicular JJ 1247 1255 lymphoma lymphoma NN 1256 1257 ( ( ( 1257 1259 FL FL NNP 1259 1260 ) ) ) 1260 1261 , , , 1262 1265 and and CC 1266 1267 8 8 CD 1268 1275 typical typical JJ 1276 1280 AITL AITL NNP 1281 1282 ( ( ( 1282 1284 ie ie FW 1284 1285 , , , 1286 1290 AITL AITL NNP 1291 1298 without without IN 1299 1301 GC GC NNP 1301 1302 ) ) ) 1303 1307 were be VBD 1308 1315 studied study VBN 1315 1316 . . . 1317 1323 Double double JJ 1324 1332 staining staining NN 1333 1336 for for IN 1337 1347 Bcl-6/CD20 Bcl-6/CD20 NNP 1347 1348 , , , 1349 1358 Bcl-6/CD3 Bcl-6/CD3 NNP 1358 1359 , , , 1360 1363 and and CC 1364 1374 Bcl-6/CD57 Bcl-6/CD57 NNP 1375 1378 was be VBD 1379 1388 performed perform VBN 1389 1391 in in IN 1392 1400 selected select VBN 1401 1406 cases case NNS 1406 1407 . . . 1408 1415 RESULTS results NNS 1415 1416 : : : 1417 1419 In in IN 1420 1422 FH FH NNP 1423 1426 and and CC 1427 1430 HIV HIV NNP 1431 1441 adenopathy adenopathy NN 1441 1442 , , , 1443 1451 staining stain VBG 1452 1455 for for IN 1456 1461 Bcl-6 Bcl-6 NNP 1462 1470 revealed reveal VBD 1471 1478 densely densely RB 1479 1488 populated populated JJ 1489 1492 GCs gc NNS 1493 1497 with with IN 1498 1510 well-defined well-defined JJ 1511 1514 and and CC 1515 1522 regular regular JJ 1523 1525 GC GC NNP 1526 1533 borders border NNS 1533 1534 , , , 1535 1542 whereas whereas IN 1543 1549 Bcl-6+ bcl-6+ JJ 1550 1555 cells cell NNS 1556 1560 were be VBD 1561 1565 rare rare JJ 1566 1568 in in IN 1569 1572 the the DT 1573 1588 interfollicular interfollicular JJ 1589 1594 areas area NNS 1594 1595 . . . 1596 1598 An an DT 1599 1609 occasional occasional JJ 1610 1612 GC GC NNP 1613 1617 with with IN 1618 1620 an an DT 1621 1632 ill-defined ill-defined JJ 1633 1639 border border NN 1640 1643 was be VBD 1644 1654 invariably invariably RB 1655 1665 surrounded surround VBN 1666 1668 by by IN 1669 1670 a a DT 1671 1676 broad broad JJ 1677 1683 mantle mantle NN 1684 1688 zone zone NN 1688 1689 ; ; : 1690 1695 those those DT 1696 1700 with with IN 1701 1711 indistinct indistinct JJ 1712 1718 mantle mantle NN 1719 1724 zones zone NNS 1725 1728 had have VBD 1729 1741 well-defined well-defined JJ 1741 1742 , , , 1743 1750 regular regular JJ 1751 1758 borders border NNS 1758 1759 . . . 1760 1762 In in IN 1763 1765 FL FL NNP 1765 1766 , , , 1767 1776 follicles follicle NNS 1777 1781 were be VBD 1782 1789 densely densely RB 1790 1799 populated populate VBN 1799 1800 , , , 1801 1804 and and CC 1805 1810 their their PRP$ 1811 1818 borders border NNS 1819 1823 were be VBD 1824 1833 irregular irregular JJ 1833 1834 , , , 1835 1839 with with IN 1840 1844 some some DT 1845 1851 Bcl-6+ bcl-6+ JJ 1852 1857 cells cell NNS 1858 1860 in in IN 1861 1864 the the DT 1865 1880 interfollicular interfollicular JJ 1881 1886 zones zone NNS 1886 1887 . . . 1888 1890 In in IN 1891 1898 AITL/GC AITL/GC NNP 1898 1899 , , , 1900 1903 GCs GC NNP 1904 1908 were be VBD 1909 1913 less less RBR 1914 1919 dense dense JJ 1919 1920 , , , 1921 1923 GC GC NNP 1924 1931 borders border NNS 1932 1936 were be VBD 1937 1940 ill ill RB 1941 1948 defined define VBN 1949 1952 and and CC 1953 1962 irregular irregular JJ 1962 1963 , , , 1964 1967 and and CC 1968 1971 the the DT 1972 1978 number number NN 1979 1981 of of IN 1982 1997 interfollicular interfollicular JJ 1998 2004 Bcl-6+ bcl-6+ JJ 2005 2010 cells cell NNS 2011 2014 was be VBD 2015 2023 markedly markedly RB 2024 2033 increased increase VBN 2033 2034 . . . 2035 2041 Double double JJ 2042 2050 staining staining NN 2051 2059 revealed reveal VBD 2060 2064 that that IN 2065 2070 these these DT 2071 2086 interfollicular interfollicular JJ 2087 2093 Bcl-6+ bcl-6+ JJ 2094 2099 cells cell NNS 2100 2102 in in IN 2103 2110 AITL/GC AITL/GC NNP 2111 2115 were be VBD 2116 2138 Bcl6+/CD3+/CD20-/CD57- bcl6+/cd3+/cd20-/cd57- NN 2139 2140 T t NN 2141 2146 cells cell NNS 2146 2147 . . . 2148 2156 Moreover moreover RB 2156 2157 , , , 2158 2162 CD3+ cd3+ JJ 2163 2178 intrafollicular intrafollicular JJ 2179 2180 T t NN 2181 2186 cells cell NNS 2187 2191 were be VBD 2192 2200 depleted deplete VBN 2201 2203 in in IN 2204 2211 AITL/GC AITL/GC NNP 2211 2212 , , , 2213 2220 whereas whereas IN 2221 2225 they they PRP 2226 2230 were be VBD 2231 2239 abundant abundant JJ 2240 2242 in in IN 2243 2245 FH FH NNP 2245 2246 . . . 2247 2262 Intrafollicular intrafollicular JJ 2263 2268 CD57+ cd57+ JJ 2269 2274 cells cell NNS 2275 2278 did do VBD 2279 2282 not not RB 2283 2288 stain stain VB 2289 2292 for for IN 2293 2298 Bcl-6 Bcl-6 NNP 2298 2299 , , , 2300 2303 and and CC 2304 2308 were be VBD 2309 2313 also also RB 2314 2322 depleted deplete VBN 2323 2325 in in IN 2326 2333 AITL/GC AITL/GC NNP 2333 2334 . . . 2335 2337 In in IN 2338 2345 typical typical JJ 2346 2350 AITL AITL NNP 2350 2351 , , , 2352 2356 some some DT 2357 2367 neoplastic neoplastic JJ 2368 2373 cells cell NNS 2374 2378 were be VBD 2379 2387 positive positive JJ 2388 2391 for for IN 2392 2397 Bcl-6 Bcl-6 NNP 2397 2398 , , , 2399 2406 showing show VBG 2407 2415 variable variable JJ 2416 2423 degrees degree NNS 2424 2426 of of IN 2427 2435 staining staining NN 2435 2436 . . . 2437 2448 CONCLUSIONS conclusions NNS 2448 2449 : : : 2450 2451 ( ( ( 2451 2452 1 1 LS 2452 2453 ) ) ) 2454 2457 GCs gc NNS 2458 2460 of of IN 2461 2468 AITL/GC AITL/GC NNP 2469 2477 differed differ VBD 2478 2482 from from IN 2483 2488 those those DT 2489 2491 of of IN 2492 2497 other other JJ 2498 2506 reactive reactive JJ 2507 2517 follicular follicular JJ 2518 2530 hyperplasias hyperplasia NNS 2531 2534 and and CC 2535 2545 follicular follicular JJ 2546 2555 lymphomas lymphoma NNS 2555 2556 , , , 2557 2560 and and CC 2561 2569 staining staining NN 2570 2573 for for IN 2574 2579 Bcl-6 Bcl-6 NNP 2580 2583 was be VBD 2584 2590 useful useful JJ 2591 2593 to to TO 2594 2601 discern discern VB 2602 2606 them them PRP 2606 2607 . . . 2608 2609 ( ( ( 2609 2610 2 2 LS 2610 2611 ) ) ) 2612 2627 Intrafollicular intrafollicular JJ 2628 2632 CD3+ cd3+ JJ 2633 2634 T t NN 2635 2640 cells cell NNS 2640 2641 , , , 2642 2646 many many JJ 2647 2649 of of IN 2650 2655 which which WDT 2656 2660 were be VBD 2661 2665 also also RB 2666 2674 positive positive JJ 2675 2678 for for IN 2679 2684 Bcl-6 Bcl-6 NNP 2684 2685 , , , 2686 2690 were be VBD 2691 2699 markedly markedly RB 2700 2708 depleted deplete VBN 2709 2711 in in IN 2712 2719 AITL/GC AITL/GC NNP 2719 2720 , , , 2721 2725 with with IN 2726 2735 increased increase VBN 2736 2751 interfollicular interfollicular JJ 2752 2763 Bcl-6+/CD3+ bcl-6+/cd3+ JJ 2764 2769 cells cell NNS 2769 2770 , , , 2771 2781 suggesting suggest VBG 2782 2784 an an DT 2785 2792 outward outward JJ 2793 2802 migration migration NN 2803 2805 of of IN 2806 2821 intrafollicular intrafollicular JJ 2822 2823 T t NN 2824 2829 cells cell NNS 2830 2832 in in IN 2833 2837 this this DT 2838 2847 condition condition NN 2847 2848 . . . 2849 2850 ( ( ( 2850 2851 3 3 LS 2851 2852 ) ) ) 2853 2868 Interfollicular interfollicular JJ 2869 2880 Bcl-6+/CD3+ bcl-6+/cd3+ JJ 2881 2886 cells cell NNS 2887 2889 in in IN 2890 2897 AITL/GC AITL/GC NNP 2898 2902 were be VBD 2903 2906 too too RB 2907 2915 numerous numerous JJ 2916 2918 to to TO 2919 2921 be be VB 2922 2931 accounted account VBN 2932 2935 for for IN 2936 2938 by by IN 2939 2948 migration migration NN 2949 2954 alone alone RB 2954 2955 , , , 2956 2966 suggesting suggest VBG 2967 2972 local local JJ 2973 2986 proliferation proliferation NN 2986 2987 . . . 2988 2989 ( ( ( 2989 2990 4 4 LS 2990 2991 ) ) ) 2992 3007 Intrafollicular intrafollicular JJ 3008 3013 CD57+ cd57+ JJ 3014 3019 cells cell NNS 3020 3024 were be VBD 3025 3033 negative negative JJ 3034 3037 for for IN 3038 3043 Bcl-6 Bcl-6 NNP 3043 3044 , , , 3045 3055 indicating indicate VBG 3056 3069 heterogeneity heterogeneity NN 3070 3072 of of IN 3073 3076 the the DT 3077 3092 intrafollicular intrafollicular JJ 3093 3099 T-cell t-cell NN 3100 3110 population population NN 3110 3111 . . . 3112 3113 ( ( ( 3113 3114 5 5 LS 3114 3115 ) ) ) 3116 3120 Some some DT 3121 3131 neoplastic neoplastic JJ 3132 3137 cells cell NNS 3138 3140 in in IN 3141 3145 AITL AITL NNP 3146 3153 stained stain VBN 3154 3157 for for IN 3158 3163 Bcl-6 Bcl-6 NNP 3163 3164 , , , 3165 3175 suggesting suggest VBG 3176 3189 up-regulation up-regulation NN 3190 3192 of of IN 3193 3198 Bcl-6 bcl-6 NN 3199 3209 expression expression NN 3210 3212 in in IN 3213 3217 this this DT 3218 3223 tumor tumor NN 3223 3224 . . .