title: Problems and pitfalls in grading of bone marrow fibrosis, collagen deposition and osteosclerosis - a consensus-based study.
abstract: 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.
authors.affiliation: Senckenberg Institute of Pathology, University of Frankfurt, Frankfurt, Germany.
authors.forename: Hans Michael
authors.initials: HM
authors.lastname: Kvasnicka
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Beham-Schmid
authors.affiliation: Berlin Reference and Consultation Centre for Lymphoma and Hematopathology, Pathodiagnostik Berlin, Berlin, Germany.
authors.forename: Roshanak
authors.initials: R
authors.lastname: Bob
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Dirnhofer
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Kais
authors.initials: K
authors.lastname: Hussein
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.affiliation: Institute of Pathology, Staedtisches Klinikum Muenchen, Muenchen, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Kremer
authors.affiliation: Institute of Surgical Pathology, University Hospital, Freiburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Schmitt-Graeff
authors.affiliation: Department of Pathology, University Medical Centre Erlangen, Erlangen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schwarz
authors.affiliation: Institute of Pathology, University of Cologne, Cologne, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Thiele
authors.affiliation: Institute of Surgical Pathology, University Hospital, Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.affiliation: Berlin Reference and Consultation Centre for Lymphoma and Hematopathology, Pathodiagnostik Berlin, Berlin, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
mesh_terms: D001853:Bone Marrow / Q000473:pathology*; D003094:Collagen / Q000032:analysis*; D005355:Fibrosis / Q000473:pathology; D006651:Histocytochemistry; D006801:Humans; D009196:Myeloproliferative Disorders / Q000473:pathology*; D010026:Osteosclerosis / Q000473:pathology*; D015203:Reproducibility of Results; D012155:Reticulin / Q000032:analysis*
chemical_list: D012155:Reticulin; D003094:Collagen
keywords: bone marrow fibrosis; collagen; osteosclerosis; reticulin fibres