Histopathological Grading of Oral Mucosal Chronic Graft-versus-Host Disease: Large Cohort Analysis.

Victor Tollemar,Gunnar Warfvinge,Robert Heymann,Mats Remberger,Nikcole Tudzarovski,Rachael V Sugars,Karin Garming Legert,Naom Yarom

doi:10.1016/j.bbmt.2020.06.031

Abstract

Graft-versus-host disease (GVHD) can manifest as acute or chronic complications in patients after hematopoietic cell transplantation (HCT). Oral chronic GVHD (cGVHD) occurs in approximately 70% of HCT recipients and includes lichenoid-like mucosal reactions, restricted mouth opening, and salivary gland dysfunction. However, the underlying histopathological presentation remains to be validated in large cohorts. We characterized the histopathological features of oral mucosal cGVHD and devised a scoring model in a large patient cohort (n=112). Oral mucosal biopsy sections (n=303) with and without oral cGVHD were identified from archived and current HCT recipients with additional healthy controls. Histological screening was performed on hematoxylin and eosin-stained and periodic acid-Schiff-stained sections. A points-based grading tool (0 to 19, grade 0 to IV) was established based on intraepithelial lymphocytes and band-like inflammatory infiltrate, atrophic epithelium with basal cell liquefaction degeneration, including apoptosis, as well as separation of epithelium and pseudo-rete ridges. Validation involved 62 biopsy specimens, including post-HCT (n=47) and healthy (n=15) specimens. Remaining biopsy specimens (n=199) were blindly graded by 3 observers. Histological severity was correlated with clinical diagnostic and distinctive features, demonstrating a spectrum of individual patient severity, including frequent signs of subclinical GVHD in healthy mucosa. However, oral cGVHD presented with significantly higher (P < .001) scores compared with HCT controls, with moderate to high positive likelihood ratios for inflammatory infiltrate, exocytosis, and basal membrane alterations. The grade II-IV biopsy specimens demonstrated a histopathological diagnosis of active mucosal lichenoid-like cGVHD, highlighting the importance of correlating clinical presentation with the dynamic histopathological processes for improved patient stratification. In addition, this tool could be used for assessing treatments, pathological processes, and immune cellular content to provide further insight into this debilitating disease.

Highlights

Allogeneic hematopoietic cell transplantation (HCT) is used worldwide for various conditions, mainly to treat leukemias [1]
Oral chronic GVHD (cGVHD) is proposed to present as a trio of separate diseases, highlighting the importance of assessing the diagnostic and pathological features for each to support clinicians and researchers with patient alignment [10]
This study focused on oral mucosal cGVHD across an extensive cohort of allogeneic HCT recipients and controls to assess distinctive histopathological features, resulting in an objective tissue grading tool

Summary

Introduction

Allogeneic hematopoietic cell transplantation (HCT) is used worldwide for various conditions, mainly to treat leukemias [1]. Improved transplantation technologies have facilitated the increased use of HCT, which in turn has led to an increased incidence of chronic graft-versus-host disease (cGVHD). This rise has been shown to be independent of associated. V. Tollemar et al / Biol Blood Marrow Transplant 26 (2020) 1971À1979 been stratified into organ-specific diagnostic and distinctive clinical signs by the National Institutes of Health (NIH) Consensus Development Project [5,6]. CGVHD in the oral cavity presents in approximately 70% of allogeneic HCT recipients and is considered one of most prevalent post-transplantation complications and, along with skin involvement, one of the earliest signs of cGVHD [3,7,8]. Salivary gland dysfunction, and limited mouth opening have been proposed as 3 different disease presentations and should be considered individually [10]

Methods

Results

Conclusion