ALOX15 Immunohistochemistry Aids in the Diagnosis of Eosinophilic Esophagitis on Pauci-eosinophilic Biopsies in Children

Abstract

Histologically, esophageal biopsies should have ≥15 intraepithelial eosinophils (IEEs) per high power field (HPF) to support a clinicopathologic diagnosis of eosinophilic esophagitis (EoE). Children with clinically apparent EoE may show pauci-eosinophilic biopsies due to patchy involvement. Immunostaining (Immunohistochemistry) for arachidonate-15 lipooxygenase (ALOX15) has been demonstrated to be a sensitive marker for EoE. We retrospectively assessed the expression of ALOX15 in 48 biopsies from 21 patients with established diagnosis of EoE and with tissue fragments below the threshold of 15 IEEs/HPF. Fragments were classified into pauci-eosinophilic and non-pauci-eosinophilic groups using cutoffs of 10 and 15 IEEs/HPF. Controls included patients with reflux and normal biopsies. Sixty-five (43.9%) fragments showed <10 IEEs/HPF and 83 (56.1%) showed ≥10 IEEs/HPF. Using a cutoff of 15 IEEs/HPF, 87 (58.7%) fragments showed <15 IEEs/HPF while 61 fragments (41.2%) had ≥15 IEEs/HPF. ALOX15 was positive in 53/65 (81.5%) of fragments with <10 IEEs/HPF versus 82/83 (98.8%) of fragments with ≥10 IEEs/HPF ( P < .001). For a cutoff of 15 IEEs/HPF, 75/87 (86.2%) of pauci-eosinophilic fragments were ALOX15-positive, while 60/61(98.4%) of biopsies meeting the threshold were positive ( P < .001). In 3/21 (14.3%) patients with EoE, all of the fragments (n = 7) were pauci-eosinophilic and all of them were positive for ALOX15. Two of 24 patients with reflux (one with 9 and one with 14 IEEs/HPF) were also positive. Fragments from normal controls (0 IEEs/HPF) were negative. Our results support the utility of ALOX15 immunohistochemistry in supporting the diagnosis of EoE in rare situations with strong clinical suspicion where no fragments reach 15 IEEs/HPF.

Guidelines for Regulated Cell Death Assays: A Systematic Summary, A Categorical Comparison, A Prospective

“…Some researchers have Karamitopoulou et al, 2007;Farnebo et al, 2011;Omori et al, 2011;Sen et al, 2015;Heng et al, 2016;Bani-Ahmad et al, 2018;Chen et al, 2019;Henrich et al, 2019;Moledina et al, 2019;Schiffmann et al, 2019 Prognostic Bcl-2, Bax, p53, Fas, FasL, caspase-2, caspase-3, caspase-7, caspase-8, caspase-9, TNF-α, DNA fragmentation, Bak, Bok, Bim, PUMA, PMAIP1, MCL1, BCL2L10, TRAIL, TRAIL-R1/2/3, c-FLIP, IAPs Feng et al, 2018;Huang K.H. et al, 2018 Necroptosis Diagnostic NLRP3, AUNIP, RIPK1/3 He et al, 2016;Lee et al, 2016;Yang Z. et al, 2019 Prognostic NLRP3, MLKL, RIPK1/3, TLR3/TICAM1, AURKA Yuan et al, 2015;Yao et al, 2017;Conev et al, 2019;Soleymani Fard et al, 2019;Sun et al, 2019;Malhotra et al, 2020 Autophagy Diagnostic LC3, Na+/K+-ATPase, mTOR Mijatovic et al, 2012;Mete et al, 2018;Sui et al, 2018 Prognostic LC3, ATG, BECN1, Na + /K + -ATPase, AMPK, mTOR Cao et al, 2016;Cheng et al, 2016;Schläfli et al, 2016;Gajate et al, 2018;Guo et al, 2019 Ferroptosis Diagnostic GPX4, ALOX15, SLC7A11, BAP1, HSP90, HSPB1, FANCD2, TP53 Kamal et al, 2004;Guerriero et al, 2015;Saif et al, 2016;Hui et al, 2017;Davidson et al, 2018;Xu et al, 2019Prognos...…”

An Update on Eosinophilic Esophagitis: Etiological Factors, Coexisting Diseases, and Complications

“…The literature by García-Rojo et al [40] reported that CD3-, CD4-, and CD8- marker analysis may be used to distinguish between GERD and EoE patients. In rare situations, for example, children with strong clinical suspicion where fragments do not reach 15 intraepithelial eosinophils/HPF, immunostaining for arachidonate-15 lipooxygenase has been found to be a sensitive marker for EoE [84]. Moreover, von Arnim et al [85] reported 10 characteristic marker set (atopy, food impaction, dysphagia, PPI-refractory symptoms, peripheral eosinophilia, IgE, weight loss, painful swallowing/odynophagia, age, and sex) which effectively distinguish GERD from EoE.…”