OBJECTIVE: In the era of potentially disease-modifying agents such as Janus kinase inhibitors, accurate grading and differentiation of bone marrow (BM) fibrosis has become more relevant to assess staging of disease and therapeutic effects. However, different fibrosis grading models have been used in the past without uniformity, including the proposal by the World Health Organization. Current scoring systems are based only on reticulin fibrosis. Therefore, additional assessment of collagen and the grade of osteosclerosis appear to be essential to discriminate all components of the complex BM fibrous matrix.
RESULTS: We evaluated problems and pitfalls regarding staining techniques and the interpretation of reticulin fibrosis on a total of 352 samples. Furthermore, we propose a minor modification of the current grading and separate scoring for collagen deposition and osteosclerosis. Reproducibility of gradings was tested among 11 haematopathologists in a blinded assessment. Overall, the inter-rater reliability of all three grading systems ranged between 0.898 and 0.926.
CONCLUSIONS: A standardized assessment of BM fibrosis with differentiation between reticulin, collagen and osteosclerosis is recommended to evaluate the various components of the fibrous matrix which may be delinked after therapy. In this regard, quality of staining and application of laboratory standards enable a highly reproducible scoring.

OBJECTIVE: Myelofibrosis (MF) implies an increase in the bone marrow (BM) fiber content without referring to quantity or quality (reticulin vs. collagen).
METHODS: This review on chronic myeloproliferative disorders is based on initial and sequential BM biopsies, clinical data and follow-up examinations. A semiquantitative grading system for MF approved by a panel of experts was applied.
RESULTS: In chronic myelogenous leukemia, minimal reticulin to advanced collagen MF is detectable at presentation in about 30% of patients. Significant correlations between BM and clinical features, but especially prognosis, are evident. Chronic idiopathic MF includes a prodromal stage showing no or little reticulin and no relevant MF with myeloid metaplasia (MMM). A stepwise evolution is demonstrable and associated with corresponding clinical data. Usually MMM is the diagnostic guideline for this disorder and consequently early stages with accompanying thrombocytosis may clinically mimic essential thrombocythemia. MF of various degrees may be observed in polycythemia vera depending on the progress of disease. Terminal stages (spent phase) reveal overt collagen corresponding with MMM. If diagnosis of essential thrombocythemia regards characteristic BM features, no relevant MF is seen at presentation and transformation into MMM is neglectable for many years.
CONCLUSIONS: To recognize dynamics of the disease process in chronic myeloproliferative disorders, an easily to reproduce scoring system for MF has been proposed. The clinical diagnosis of MMM does not include initial-early reticulin MF and therefore fails to detect prodromal stages.