title: Aberrant immunoarchitecture distinguishes hyperplastic germinal centres in pattern 1 angioimmunoblastic T-cell lymphoma from reactive follicles.
abstract: 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-γ (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 = 1.0 × 10(-5)], CD4 predominance [25/28 (89%) vs 12/23 (52%), p = 3.4 × 10(-3)], interfollicular lymphoid CD10-positivity [16/30 (53%) vs 1/29 (3%), p = 1.5 × 10(-5)], TRG clonality [16/28 (57%) vs 1/20 (5%), p = 1.4 × 10(-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 = 5.3 × 10(-8)] and CD57 [18/25 (72%) vs 4/22 (18%), p = 2.4 × 10(-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 = 1.0 × 10(-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.
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Leonard Hwan-Cheong
authors.initials: LH
authors.lastname: Tan
authors.forename: Soo-Yong
authors.initials: SY
authors.lastname: Tan
mesh_terms: D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D018858:Germinal Center / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D008221:Lymphoid Tissue / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019310:Pseudolymphoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers
keywords: Angioimmunoblastic T-cell lymphoma; CD10; CD57; Germinal centres; ICOS; PD-1; Pattern 1; TFH; immunoarchitecture