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

Histopathology. 2017 Dec;71(6):897-908. doi: 10.1111/his.13309. Epub 2017 Sep 28.

Abstract

Aims: 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 may have prognostic implications.

Methods and results: Reticulin fibrosis, collagen deposition and osteosclerosis were graded from 0 to 3 in a series of 122 baseline BMBs. Then, we assigned to each case a comprehensive score [reticulin, collagen, osteosclerosis (RCO) score, ranging from 0 to 9] that allowed us to distinguish two groups of patients, with low-grade (RCO score 0-4) and high-grade (RCO score 5-9) stromal changes. Of 122 patients, 88 displayed a low-grade and 34 a high-grade RCO score. The latter was associated more frequently with anaemia, thrombocytopenia, peripheral blood blasts and increased lactate dehydrogenase levels. The RCO score was correlated strictly 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.

Conclusion: The comprehensive RCO score, obtained by histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis was prognostically significant and more accurate than ECGMF grade in identifying high-risk patients and improved PPV when applied in addition to IPSS.

Keywords: bone marrow morphology; collagen deposition; osteosclerosis; primary myelofibrosis; reticulin fibrosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Collagen / metabolism*
  • Female
  • Fibrosis / diagnosis*
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Humans
  • Male
  • Middle Aged
  • Osteosclerosis / diagnosis*
  • Osteosclerosis / metabolism
  • Osteosclerosis / pathology
  • Primary Myelofibrosis / diagnosis*
  • Primary Myelofibrosis / metabolism
  • Primary Myelofibrosis / pathology
  • Prognosis
  • Reticulin / metabolism*
  • Survival Analysis

Substances

  • Reticulin
  • Collagen