Eva van der Slik1, Richard Feelders2, Andrew Hall3, Martyn Caplin 4, Krista Rombouts4, Johannes Hofland5, Wouter de Herder6, TuVinh Luong6, Leo Hofland7, Marie-Louise van Velthuysen 8
(1) Erasmus MC Cancer Institute/Department of Internal Medicine, sector Endocrinology, Rotterdam, Netherlands. (2) Erasmus MC Cancer Institute/Department of Internal Medicine, sector Endocrinology, Rotterdam, Netherlands. (3) Institute for Liver and Digestive Health, Royal Free Hospital/Regenerative Medicine and Fibrosis Group, London, United Kingdom. (4) ENETS Centre of Excellence, Royal Free London NHS Foundation Trust/Neuroendocrine Tumour Unit, London, United Kingdom. (5) Erasmus MC Cancer Institute/Department of Internal Medicine, sector Endocrinology, Rotterdam, Netherlands. (6) Erasmus MC Cancer Institute/Department of Internal Medicine, sector Endocrinology, Rotterdam, Netherlands. (7) Erasmus MC Cancer Institute/Department of Internal Medicine, sector Endocrinology, Rotterdam, Netherlands. (8) ENETS Centre of Excellence, Erasmus MC Cancer Institute/Department of Pathology, Rotterdam, Netherlands.
Objective:
Mesenteric fibrosis (MF) frequently develops around mesenteric metastasis in patients with small intestinal neuroendocrine tumors (SI-NET). Since MF is not always detected radiologically, histopathological examination is considered the gold standard. However, to date there is no uniform histopathological scoring system for diagnosing or grading MF, leading to variations in assessment. Our aim is to retrospectively validate a new MF scoring method to develop a more standardized scoring system linked to clinical data.
Methods:
FFPE blocks of mesenteric metastases from 49 operated SI-NET patients were collagen-stained. MF was graded by analyzing the width of the fibrotic capsule, the thickest intratumoral fibrotic band, and the collagen proportional area (CPA) of the tumor mass, both with and without the fibrotic capsule. Staining and digital analysis were performed at two institutions to investigate the reproducibility of the scoring systems. Additionally, two radiologists conducted a radiological scoring using pre-operative CT scans.
Results:
CPA measurements of the tumor mass, both with and without the fibrotic capsule, showed the least variability across institutions, with less than 20% difference in over 80% of cases. Spearman’s correlation coefficients were 0.522 (p < 0.001) and 0.739 (p < 0.001), respectively. Regression analysis identified CPA of the tumor mass without the fibrotic capsule as a significant predictor for tumor stage (p=0.04, OR 2.14 per 10% increase) and abdominal pain (p=0.015, OR 2.57 per 10% increase). CPA of the entire tumor mass correlated only with abdominal pain (p=0.022, OR 2.57 per 10% increase). Radiological fibrosis scoring was significantly associated with CPA intratumoral and capsule width measurements.
Conclusions:
Our results indicate that CPA measurements are more reproducible for scoring MF compared to other methods. CPA of the tumor mass without the fibrotic capsule correlated well with tumor grade and abdominal pain, suggesting it may be the most relevant metric for grading MF.