title: Diagnosis and quantification of bone marrow fibrosis are significantly biased by the pre-staining processing of bone marrow biopsies.
abstract: OBJECTIVE
  Marrow fibrosis (MF) is an unfavourable, often lethal complication of haematological neoplasms. Although biopsy technique and staining procedure are standardized, the prestaining processing of bone marrow biopsies (BMBs) varies markedly without any existing data on its significance for the diagnosis of MF.
  
  
  RESULTS
  In this study on 712 BMBs from 296 patients with chronic idiopathic myelofibrosis (CIMF), chronic myeloid leukaemia (CML), or healthy bone marrow, MF was a characteristic complication of CML and CIMF. However, diagnosis and quantification of MF and detection of its prognostic significance were significantly biased by fixation, decalcification, embedding, marrow tissue shrinkage during biopsy processing and the thickness of marrow sections (P < 0.000005). The relevance of these influences was explained by their effect on the marrow volume to which the fibre content was related, whereas the stainability of fibres was not affected. Semiquantitative grading of fibrosis and measurements of fibre density could not be adjusted to various methods of processing of bone marrow biopsies (P < 0.003).
  
  
  CONCLUSIONS
  Evaluations of MF and its prognostic significance should consider the bias due to the prestaining processing of BMBs and the necessity of an adjustment to the thickness of tissue sections and the degree of marrow tissue shrinkage.
authors.affiliation: Department of Pathology, Medizinische Hochschule Hannover, Germany. guntram.buesche@arcor.de
authors.forename: G
authors.initials: G
authors.lastname: Buesche
authors.forename: A
authors.initials: A
authors.lastname: Georgii
authors.forename: H-H
authors.initials: HH
authors.lastname: Kreipe
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology*; D001856:Bone Marrow Examination / Q000592:standards; D005260:Female; D006651:Histocytochemistry / Q000379:methods / Q000592:standards; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D055728:Primary Myelofibrosis / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013194:Staining and Labeling / Q000379:methods / Q000592:standards*; D013997:Time Factors; D016610:Tissue Embedding; D016707:Tissue Fixation