ARTICLE IN PRESS JID: YDLD [m5G;September 28, 2020;17:0] Digestive and Liver Disease xxx (xxxx) xxx Contents lists available at ScienceDirect Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld Alimentary Tract Histological assessment of gastric pseudopyloric metaplasia: Intra- and inter-observer consistency Massimo Rugge a,b,c,∗ , Diana Sacchi a , Robert M. Genta c , Francesca Zanco a , Stefano Guzzinati b , Marco Pizzi a , Matteo Fassan a , Antonio Di Sabatino d , Hashem El-Serag c a Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy b Veneto Tumor Registry (RTV), Azienda Zero, Padova, Italy c Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine Houston, TX, USA d First Department of Medicine, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy a r t i c l e i n f o Article history: Received 20 July 2020 Accepted 6 September 2020 Available online xxx Keywords: Pseudopyloric metaplasia PPM SPEM Atrophic gastritis Autoimmune gastritis a b s t r a c t Background: The histological spectrum of oxyntic mucosal atrophy (a major determinant of gastric cancer risk) includes pseudopyloric metaplasia (PPM), which histological assessment has been regarded as unre- liable. PPM consistently expresses Trefoil-Factor 2 (TFF2), which is histochemically detecteble (TFF2-IHC). Aims: Intra- and inter-observer consistency in assessing PPM was examined using both hematoxylin & eosin (H&E) and TFF2-IHC. Materials and methods: Seventy-four oxyntic biopsy samples obtained from autoimmune gastritis were considered. Two serial histological sections obtained from the paraffin-embedded tissue-samples were stained with H&E and TFF2-IHC. Three pathologists (Alpha, Beta, Gamma) independently scored PPM by both staining and the Intra- and inter-observer consistency (H&E versus TFF2-IHC) was calculated using k-statistics and/or Spearman’s coefficient. Results: Based on H&E-stain versus TFF2-IHC, intra-observer consistency in PPM assessement was ranked as consistently “good” (k-values: Alpha=0.79; Beta=0.78; Gamma=0.75). Based on H&E, the overall PPM inter-observer consistency among the 3 observers was ranked as “good” (k=0.77) (the inter-observer con- sistency for pairs of observers was as follows: Alpha versus Beta k=0.88; Alpha versus Gamma k=0.87; Beta versus Gamma k=0.80). Based on TFF2-IHC, the overall PPM inter-observer agreement was ranked as “excellent” (k=0.91) (the inter-observer consistency for pairs of observers was as follows: Alpha versus Beta k=1; Alpha versus Gamma k=0.91; Beta versus Gamma k=0.91). Conclusion: Relying on either H&E staining or TFF2-IHC, pathologists assess PPM consistently. © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. 1. Introduction Gastric mucosa atrophy, a major determinant of gastric cancer (GC) risk, is defined as “loss of appropriate (i.e., native) glands” and the inter-observer variability in its assessment has been in- ternationally supported [1,2]. The histological spectrum of atrophy covers two phenotypic variants, one metaplastic and one not. Non- metaplastic atrophy occurs in mucosecreting (antral) and oxyntic (corpus and fundus) mucosa, where the glands that disappear are replaced by fibrosis. Metaplastic atrophy includes two histological variants: intestinal metaplasia (IM) [3]; and pseudopyloric meta- plasia (PPM) [4,5]. ∗ Corresponding author at: Surgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), University of Padova, Via A. Gabelli, 61, Padova 35121, Italy. E-mail address: massimo.rugge@unipd.it (M. Rugge). Irrespective of their topography, intestinalized glands are char- acterized by goblet cells alternating with columnar epithelium rich in acid mucins [6]. The reliability of histological IM scoring is well established [7,8], and several studies (particularly those applying high-definition endoscopy) have confirmed the consistency of en- doscopy in identifying IM-transformed glands [9,10]. By definition, PPM only affects the oxyntic gastric compartment. It used to be considered a part of atrophic changes in the gastric mucosa, and a metaplastic transformation carrying a greater neo- plastic risk [11]. The biological profile and the microscopic phe- notype of PPM (the stomach’s “version” of pyloric metaplasia in other glandular mucosal tissues [12]) both feature striking similar- ities with the ulcer-associated cell lineage (UACL), and the more recently described spasmolytic polypeptide-expressing metaplasia (SPEM) [4,13–15]. For the purposes of this study, PPM and SPEM can be considered equivalent: according to Goldering, “SPEM ap- pears to represent a more molecular representation of the histo- https://doi.org/10.1016/j.dld.2020.09.003 1590-8658/© 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Please cite this article as: M. Rugge, D. Sacchi and R.M. Genta et al., Histological assessment of gastric pseudopyloric metaplasia: Intra- and inter-observer consistency, Digestive and Liver Disease, https://doi.org/10.1016/j.dld.2020.09.003