Grading of minor salivary gland immuno-histopathology post-allogenic hematopoietic cell transplantation

V Tollemar; H Arvidsson; H Häbel; N Tudzarovski; K Garming Legert; K Le Blanc; G Warfvinge; R V Sugars

doi:10.1016/j.heliyon.2023.e15517

Grading of minor salivary gland immuno-histopathology post-allogenic hematopoietic cell transplantation

Heliyon. 2023 Apr 15;9(4):e15517. doi: 10.1016/j.heliyon.2023.e15517. eCollection 2023 Apr.

Authors

V Tollemar¹, H Arvidsson¹, H Häbel², N Tudzarovski¹, K Garming Legert¹, K Le Blanc^{3

4}, G Warfvinge⁵, R V Sugars¹

Affiliations

¹ Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
² Medical Statistics Unit, Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden.
³ Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
⁴ Center of Allogeneic Stem Cell Transplantation and Cellular Therapy (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden.
⁵ Department of Oral Pathology, Faculty of Odontology, Malmö University, Malmö, Sweden.

Abstract

The oral cavity commonly displays mucosal lichenoid lesions and salivary gland dysfunction, which are considered different chronic Graft-versus-Host Disease (cGVHD) pathophysiology's. However, diagnostics of salivary gland (sg-)cGVHD are limited. The objectives of the current study are to evaluate the minor salivary gland (MSG) histo-immunopathological profiles post allogenic hematopoietic cell transplantation based on sg-cGVHD criteria. Design: Histopathology was characterized according to two published grading strategies. Firstly, the National Institute of Health (NIH) assessed peri-ductal/acinar infiltration, exocytosis, damage, and fibrosis, and a points-based grading scheme was established (0-16 points, Grade (G) 0 to IV). Second, a modified Sjögren's Syndrome focus-score with parenchymal damage was also adapted, (0-10 points, Score 0 to 2). 146 MSG biopsies from 79 patients were compared, using the histopathological specific criteria for sg-cGVHD pathology. Quantitative immunohistochemistry for T-cells (CD4, CD8), B-cells (CD19, CD20), monocytic cells (CD68) and dendritic cells (CD1a) were also assessed. Results: The large-scale cohort validated the use of both grading schemes. GIII-GIV and score 2 signified a histopathological diagnosis of "likely" sg-cGVHD. Immunopathological severity was associated with increased T-cells (CD4 and CD8) and monocytic (CD68) infiltrate, with minimal involvement of B-cells (CD19 and CD20), and Langerhans cells (CD1a). Conclusions: Both schemes were verified as being suitable for histological grading to improve assessment and diagnosis of sg-cGVHD. The NIH cGVHD grading appears to be more beneficial for research purposes, including final diagnostics of "no/inactive", "possible" or "likely" cGVHD. The study highlights the intricacies of sg-cGVHD pathology; and the need for standardized assessment to improve patient management associated to sg-cGVHD.

Keywords: Grading; Hematopoietic cell transplantation; Histopathology; Large cohort; Oral cGVHD.