The importance of central pathology review in international trials: a comparison of local versus central bone marrow reticulin grading

The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion

“…A central pathology review may be desirable in some clinical settings. Although BM fibrosis grading is considered a part of a standard BM biopsy examination report, low overall level of concordance of only 55.8% (range 33–100%) on 579 biopsy specimens between the local pathologists from various countries and a central review evaluation was demonstrated by a recent study 109 . This is in sharp contrast with central pathology review rates of 83–99.7%; these rates of > 80% are considered to represent excellent agreement according to the standards used to measure the strength of concordance 46 .…”

The international consensus classification of myeloid neoplasms and acute Leukemias: myeloproliferative neoplasms

“…Practical experience with the use of the WHO 2016/17 classification system 1,2 and published evidence have underscored the importance of meeting several prerequisites that are necessary to ensure an accurate classification: (i) Bone marrow (BM) smears and trephine biopsies should be collected at time of diagnosis, or within a short time‐frame thereafter, and in the absence of active therapy, especially with cytoreductive drugs; (ii) optimal biopsy specimens should be ≥1.5 cm in length, artifact‐free and performed at right angle to the cortical bone, and accompanied by BM aspirates and smears that are properly obtained and processed, and (iii) additional peripheral blood and BM samples should routinely be processed for cytogenetic and molecular studies, including screening for JAK2 (both exons 12 and 14), CALR and MPL 2,6 . A carefully processed specimen should allow accurate grading of fibrosis (3‐grade scoring system) as shown in Table 1 and assessment of age‐adjusted hematopoietic cellularity, both of which are crucially important diagnostic features 7–9 . Assessment of BM fibrosis must also include its quality (reticulin vs. collagen) 10 .…”

“…2,6 A carefully processed specimen should allow accurate grading of fibrosis (3-grade scoring system) as shown in Table 1 and assessment of age-adjusted hematopoietic cellularity, both of which are crucially important diagnostic features. [7][8][9] Assessment of BM fibrosis must also include its quality (reticulin vs. collagen). 10 A systematic approach that attends to specific details including total BM cellularity, notation of spatial distribution/ organization of the different hematopoietic cell lineages and their relative representation and morphologic hallmarks, generates unique histological patterns of significant diagnostic value (Table 2).…”

Rationale for revision and proposed changes of the WHO diagnostic criteria for polycythemia vera, essential thrombocythemia and primary myelofibrosis

“…Finally, concerning the still controversial differentiation between ET and prePMF 13 , 14 , 15 , 73 , 88 , 90 , 91 , 92 experts discuss that a more easy and precise definition of prePMF may be obtained by moving from a qualitative morphological description and a pattern recognition diagnostic process to a more quantitative evaluation of the morphological hallmarks and to follow a standardized procedural diagnostic pathway. 71 , 90 Although this is a very convincing proposal that has to be regarded, considering the overall poor results of fiber grading by local pathologists 100 in an international multicenter evaluation study, we should be aware that until now only few reference centers would be able to recognize and apply these key diagnostic features. All these shortcomings call for launching workshops and training sessions involving hematopathologists in reference centers to improve this unwanted situation we are still facing today.…”