Prognostic significance of a comprehensive histologic evaluation of reticulin fibrosis, collagen deposition and osteosclerosis in primary myelofibrosis patients

Aims: We aimed to evaluate whether a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis in bone marrow trephine biopsies (BMBs) of primary myelofibrosis (PMF) patients could have prognostic implication. Methods: According to the new grading system for the evaluation of Reticulin fibrosis, Collagen deposition and Osteosclerosis, proposed by Kvasnicka et al. in 2016, each of these morphological parameters was evaluated and graded from 0 to 3 in a series of 122 base-line BMBs of PMF patients. Then, a comprehensive score of the bone marrow stromal changes (RCO – score), obtained by summing the results of the three morphological parameters and thus ranging from 0 to 9 (grade of reticulin fibrosis+grade of collagen deposition+grade of osteosclerosis), was assigned to each case. Results: 88 out of 122 patients displayed a low-grade and 34 a high-grade RCO score. The latter was more frequently associated with anemia, thrombocytopenia, leukocytosis, peripheral blood blasts and increased lactate dehydrogenase levels. RCO score resulted strictly correlated with overall mortality (p=0.013) and International Prognostic Scoring System (IPSS) risk categories, and was able to discriminate the overall survival of both low- and high-grade patients (Log-Rank test: p<0.001). Moreover, it proved to be more accurate than the European Consensus on grading of bone marrow fibrosis (ECGMF grade) in identifying high-risk patients with poor prognosis. Finally, a combined analysis of RCO scores and IPSS risk categories in an integrated clinical-pathological evaluation was able to increase the positive predictive value (PPV) for mortality in high-risk patients. Conclusions: the comprehensive RCO score, obtained by histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis, resulted prognostically significant and more accurate than ECGMF grade in identifying high-risk PMF patients, and improved PPV when applied in addition to IPSS.