We compare 30 biopsies each of Pattern 1 angioimmunoblastic T-cell lymphoma (AITL1) and reactive lymphoid hyperplasia (RLH) by immunohistology, in-situ hybridization for Epstein-Barr virus-encoded RNA and T-cell receptor- (TRG)-clonality. AITL1 cases, more often than RLH controls, were older [median ages 61 (range 23-79) vs 46 (range 11-59) years, p<10(-4)], non-Chinese [16/30 (53%) vs 8/28 (29%), p=0.035], presented nodally [29/30 (97%) vs 23/30 (77%), p=0.024], showed: pan-T cell antigen attenuation [25/29 (86%) vs 5/21 (24%), p=1.0x10(-5)], CD4 predominance [25/28 (89%) vs 12/23 (52%), p=3.4x10(-3)], interfollicular lymphoid CD10-positivity [16/30 (53%) vs 1/29 (3%), p=1.5x10(-5)], TRG clonality [16/28 (57%) vs 1/20 (5%), p=1.4x10(-4)], higher maximum number of Epstein-Barr virus-encoded RNA+nuclei per 0.5-mm high-power field [median 6 (range 0-70) vs 1 (range 0-40), p=0.012] and interfollicular Ki-67 proliferation fraction [median 40% (range 10-80%) vs 20% (range 5-40), p<10(-4)], whereas their germinal centres (GCs) more often showed attenuation of CD10 [30/30 (100%) vs 11/29 (38%), p=5.3x10(-8)] and CD57 [18/25 (72%) vs 4/22 (18%), p=2.4x10(-4)] (respectively). GC-predominant PD-1 and ICOS immunoreactivity were more often seen in RLH [20/22 and 9/19 controls (91% and 47%)] than AITL1 [9/25 and 3/19 cases (36% and 16%), p=1.0x10(-4) and 0.033, respectively]. Significant independent predictors against AITL1 were: solid GC CD10 immunoreactivity {p=0.023, odds ratio (OR) for AITL1 0.01 [95% confidence interval (CI): 0.0002-0.529]}; lower interfollicular proliferation fraction [p=0.047, OR for AITL1 1.1 (95% CI: 1.001-1.209) per % rise in Ki-67]; younger presenting age [p=0.028, OR for AITL1 1.136 (95% CI: 1.014-1.272) per year older]. Hence, GCs and perifollicular zones in AITL1 are distinct from those in RLH. Copyright (c) 2013 John Wiley & Sons, Ltd.