Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres

Abstract

SummaryIn bone marrow biopsies, stromal structural fibres are detected by reticulin and trichrome stains, routine stains performed on bone marrow biopsy specimens in diagnostic laboratories. Increased reticulin staining (reticulin fibrosis) is associated with many benign and malignant conditions while increased trichrome staining (collagen fibrosis) is particularly prominent in late stages of severe myeloproliferative diseases or following tumour metastasis to the bone marrow. Recent evidence has shown that the amount of bone marrow reticulin staining often exhibits no correlation to disease severity, while the presence of type 1 collagen, as detected by trichrome staining, is often associated with more severe disease and a poorer prognosis. It was originally thought that increases in bone marrow stromal fibres themselves contributed to the haematopoietic abnormalities seen in certain diseases, but recent studies suggest that these increases are a result of underlying cellular abnormalities rather than a cause. A growing body of evidence suggests that increased deposition of bone marrow stromal fibres is mediated by transforming growth factor-b and other factors elaborated by megakaryocytes, but it is likely that other cells, cytokines and growth factors are also involved. This suggests new avenues for investigation into the pathogenesis of various disorders associated with increased bone marrow stromal fibres.

Understanding deregulated cellular and molecular dynamics in the haematopoietic stem cell niche to develop novel therapeutics for bone marrow fibrosis

“…A number of haematological and non‐haematological disorders are associated with increased BM fibrosis, including myelodysplastic syndromes and myeloproliferative neoplasms (MPNs) 1.…”

Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era?

“…Importantly, although MF is an acquired clonal hematopoietic stem cell disorder, BM fibrosis represents a reactive phenomenon characterized by the presence of increased collagen fibers in a disorderly manner. 24 Histologically, this is best assessed by reticulin and collagen (trichrome) stains of the BM trephine biopsy, and graded by the four-grade semi-quantitative European consensus system. 25,26 A recent International and European LeukemiaNet effort has proposed a set of BM features that characterize therapy response by BM morphology.…”

High concordance in grading reticulin fibrosis and cellularity in patients with myeloproliferative neoplasms

“…[6][7][8][9][10][11][12] Bone marrow fibrosis is measured by reticulin and trichrome stains of the bone marrow trephine biopsy and is graded on a semiquantitative scale. 13 The classification proposed by the World Health Organization (WHO) and updated in 2008 employs the European Consensus System to grade bone marrow fibrosis, which has four possible grades (0, 1, 2, and 3); distinction between these levels is based on the number, density, and thickness of silver-stained reticulin fibers as assessed by the pathologist (Table 1). 14,15 Previous systems used to grade bone marrow fibrosis included the Manoharan and Bauermeister schemes.…”

“…14,15 Previous systems used to grade bone marrow fibrosis included the Manoharan and Bauermeister schemes. 13,14 Reticulin grade is not included among the factors used in primary myelofibrosis risk stratification systems, such as the Dynamic International Prognostic Scoring System 16,17 and shows variable correlation with clinical parameters of disease progression, such as splenomegaly. However, increased reticulin grade is an adverse prognostic factor in primary myelofibrosis, essential thrombocythemia, and polycythemia vera.…”