Clinical and Prognostic Validation of the Reticulin, Collagen, Osteosclerosis (RCO) Score for Primary Myelofibrosis (PMF)

Introduction: Primary myelofibrosis (PMF) is hallmarked by stromal bone marrow (BM) changes that include reticulin fibrosis, collagen deposition, osteosclerosis, and microvascular proliferation. Accurate evaluation of BM fibrotic changes is key for MF diagnosis and deserves prognostic implications. Gianelli et al. ( Histopathol 2017;71:89) developed a comprehensive score, named reticulin (MF), collagen (Co), osteosclerosis (Ost) score (RCOs), which was prognostically informative and more accurate than the 2005 European Consensus on Grading of Bone Marrow Fibrosis (ECGMF) in identifying high-risk patients (pts). Aims&Methods: This retrospective, single-center study aimed to validate the RCOs and explore its clinical, genetic and prognostic correlates in a large cohort of clinically and molecularly annotated PMF pts diagnosed according to 2022 ICC criteria. The RCOs was assessed by two independent experienced histopathologists (U.G, R.S.). Results: The study included 222 pts with a diagnosis of PMF: 121 (55%) prefibrotic PMF (pre-PMF), 101 (45%) overt PMF. Median age was 66 years (range, 18-91), 127 (57%) were male. BM histological analysis according to the RCO algorithm provided the following results: MF-0 n=20 (9%), MF-1 n=102 (46%), MF-2 n=47 (21%), and MF-3 n=53 (24%); Co-0 n=130 (59%), Co-1 n=33 (15%), Co-2 n=31 (14%), and Co-3 n=28 (13%); Ost-0 n=146 (66%), Ost-1 n=45 (20%), Ost-2 n=18 (8%), and Ost-3 n=13 (6%). Next, we looked at the distribution of the Co and Ost variables according to MF grade and PMF diagnosis. Overall, morphological features evolved harmonically, with pre-PMF showing the less severe stromal changes and higher reticulin fibrosis being associated with the highest values of Co and Ost. Computation of the RCOs returned the following results: RCOs 0 n=20 (9%), RCOs 1 n=94 (42%), RCOs 2 n=15 (7%), RCOs 3 n=19 (9%), RCOs 4 n=9 (4%), RCOs 5 n=16 (7%), RCOs 6 n=13 (6%), RCOs 7 n=17 (8%), RCOs 8 n=11 (5%), and RCOs 9 n=8 (4%). Median RCOs for pts with pre- and overt PMF was 1 (range, 0-2) and 5 (range, 2-9), respectively. We investigated the correlations of RCOs with clinical and molecular variables. Higher RCOs was associated with overt PMF (median, 5 vs 1, P