Applicability of the WHO grading for reticulin and collagen fibrosis in a routine diagnostic laboratory

Accurate grading of bone marrow fibrosis is essential for the diagnosis and prognostication of myeloproliferative neoplasms (MPNs). The 2017 World Health Organization (WHO) Classification recommends a trichrome stain be performed to evaluate collagen fibrosis when reticulin fibrosis grade is >1, but the inter-observer concordance in assessing collagen fibrosis in a routine diagnostic laboratory and the utility of this stain are unclear. This study assesses the inter-observer agreement in the grading of reticulin fibrosis and collagen fibrosis, and the concordance between reticulin and collagen fibrosis. Two pathologists assessed 174 consecutive bone marrow trephine biopsies with a diagnosis of an MPN at a tertiary referral centre. Reticulin fibrosis by silver impregnation and collagen fibrosis by Masson's trichrome stain were independently graded by the pathologists while blinded to clinical information. Discordant scores were reviewed to establish a final grade by consensus. Substantial inter-observer concordance was obtained for both reticulin [83%; Cohen's kappa 0.756, 95% confidence interval (CI) 0.69-0.84] and collagen fibrosis grading (81%; kappa 0.730, 95% CI 0.64-0.82). Using the final consensus scores, reticulin and collagen fibrosis grades were concordant in 60% of cases. Collagen fibrosis grade was higher than reticulin fibrosis score in 11% of cases. Inter-observer concordance in assessing the degree of collagen fibrosis using the trichrome stain is substantial. Reticulin (silver) staining alone may underestimate the degree of fibrosis. The prognostic significance where the degree of collagen fibrosis is greater than that of reticulin is uncertain and should be investigated in future studies.