Ann Diagn Pathol.
It is possible that even experienced hematopathologists need special training to distinguish subtypes of ET. Photographs of trephine specimens were taken on an Olympus BX51 microscope (Olympus, Watford, United Kingdom) equipped with 10× super widefield eyepieces and Olympus U-PlanApo 40×/0.85 NA and UPlanFL N 100×/1.30 NA objectives using a Pixera Pro150ES digital camera and Pixera Viewfinder image acquisition software v.3.0.1 (Egham, Surrey, United Kingdom). Of the other criteria, there was little concordance as to which factors were independently informative. Interobserver agreement for each of the individual morphologic criteria was assessed using log-linear modeling of the second-order marginal tables from the 3 pairwise comparisons among the 3 hematopathologists, as described.25 The model controlled for the marginal distributions of each of the pathologists and fitted a linear-by-linear association term to measure the strength of interobserver agreement. Presence of unfavorable cytogenetic abnormalities is the strongest predictor of poor survival in secondary myelofibrosis. [18] CT imaging has somewhat better capacity for assessing the marrow cavity of bones, although with low sensitivity and specificity. Zhonghua Nei Ke Za Zhi. When there was disagreement, the median of the scores from the 3 hematopathologists was taken. These are multipotent stem cells that can differentiate into a variety of cell types.
NCI CPTC Antibody Characterization Program. However, we have been unable to reproduce these findings. J Trauma Acute Care Surg.
An alternative explanation for our results, and the one we favor, is that the current WHO histologic criteria are not sufficiently robust to define subtypes of ET. The normal bone marrow architecture can be damaged or displaced by aplastic anemia, malignancies such as multiple myeloma, or infections such as tuberculosis, leading to a decrease in the production of blood cells and blood platelets. HHS COVID-19 is an emerging, rapidly evolving situation. Diagnostic trephine specimens (n = 370) were studied independently by 3 experienced hematopathologists for 16 morphologic criteria (Table 1; Figure 1). Transplantation from one person to another is conducted for the treatment of severe bone marrow diseases, such as congenital defects, autoimmune diseases or malignancies. [4] Bone marrow comprises approximately 5% of total body mass in healthy adult humans, such that a man weighing 73 kg (161 lbs) will have around 3.65 kg (8 lbs) of bone marrow.[5]. The 5 most important morphologic features contributing to each factor are presented in Figure 4, and they suggest that the factors have relatively straightforward biologic interpretations.
This can be clinically variable, with myelofibrotic transformation, cytopenias, increased blasts, and increased white cells potentially present. In addition, they may put differing emphasis or weight on the relative importance of the various morphologic criteria. Our favored interpretation is also consistent with recent molecular genetic insights. This factor analysis suggests that 3 underlying processes describe many of the morphologic patterns evident in the bone marrow trephine histology of patients whose disease is diagnosed as ET (by PVSG criteria), namely cellularity, megakaryocyte clustering, and extent of fibrosis. [10], At the cellular level, the main functional component of bone marrow includes the progenitor cells which are destined to mature into blood and lymphoid cells. (2) In the bone marrow in slide #48, look for marrow sinuses and cords , which are expanded sinusoidal (discontinuous) capillaries characteristic of marrow. Principal component analysis and exploratory factor analysis. [30], The earliest fossilised evidence of bone marrow was discovered in 2014 in Eusthenopteron, a lobe-finned fish which lived during the Devonian period approximately 370 million years ago.
The cellularity factor shows significant correlation with JAK2 status, but the other 2 reflect unknown biologic mechanisms. Diagnostic differentiation of essential thrombocythaemia from thrombocythaemias associated with chronic idiopathic myelofibrosis by discriminate analysis of bone marrow features–a clinicopathological study on 272 patients. Epigenetic alterations complement mutation of JAK2 tyrosine kinase in patients with BCR/ABL-negative myeloproliferative disorders.
Shown for each factor are the 5 variables that contribute most heavily to each factor, with the y-axis representing their relative weight (contribution to the factor score).
The term ‘bone marrow’ (BM) refers to the tissue occupying the cavities under the cortex within the honeycomb of trabecular bone. A gain-of-function mutation of JAK2 in myeloproliferative disorders. Diffuse marrow T1 hypointensity without contrast enhancement or cortical discontinuity suggests red marrow conversion or myelofibrosis. Reticulin grade was the dominant independent predictor of WHO diagnostic category for all 3 hematopathologists. Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia. contributed to collection of patient samples. We start with the third factor, because it has the most straightforward interpretation. It is composed of hematopoietic cells, marrow adipose tissue, and supportive stromal cells.In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis. Patients entered a higher risk study if they developed appropriate features. *Higher scores for strength of association represent stronger interobserver reliability, with a score of 1 indicating no agreement beyond chance. An activating mutation in MPL occurs in approximately 10% of this subgroup,34 but the molecular mechanisms responsible for the rest remain unclear. However, neither is available in routine diagnostic practice, and it is hard to see the general use of criteria, the application of which is so difficult even for experienced hematopathologists. Similarly, there were no differences between true ET and prefibrotic myelofibrosis in age, sex, or rates of splenomegaly, leukoerythroblastic blood film, and cytogenetic abnormalities for any of the hematopathologists (P > .1 all variables). Many measures of interobserver agreement, such as Cohen κ score, fail to correct for differences in the pattern of scores for each observer. In keeping with this concept, histologic features of bone marrow in ET, as defined by PVSG criteria, show substantial variability. Across the 3 hematopathologists, the frequency of patients with true ET ranged from 10% to 48%, prefibrotic myelofibrosis from 9% to 28%, and higher levels of fibrosis from 37% to 76%. The study protocol was approved by institutional ethics committees in all centers, and written informed consent was obtained from all patients in accordance with the Declaration of Helsinki. Clipboard, Search History, and several other advanced features are temporarily unavailable. Initial (prefibrotic) stages of idiopathic (primary) myelofibrosis (IMF): a clinicopathological study. This underscores the difficulty of combining multiple morphologic features into a single diagnosis without explicit guidance as to which factors are most significant or characteristic.
Bone marrow is a semi-solid tissue found within the spongy or cancellous portions of bones. The statistical analysis therefore included a core set of 370 trephine specimens more than 5 mm in length, for which all criteria could be assessed by all 3 hematopathologists. 2007;74(2):97-114. doi: 10.1159/000101709. Conflict-of-interest disclosure: The authors declare no competing financial interests. In humans, marrow is colloquially characterized as "red" or "yellow" marrow (Latin: medulla ossium rubra, Latin: medulla ossium flava, respectively) depending on the prevalence of hematopoetic cells vs fat cells. Not all paraffin-embedded sections were of sufficient length or quality to enable all parameters to be assessed. Factor 3, in picking out the cellularity criteria, correlates significantly with JAK2 V617F status (P < .001). Normal "red" marrow is typically equivalent or brighter than skeletal muscle or intervertebral disc on T1-weighted sequences. [16], Bone marrow derived stem cells have a wide array of application in regenerative medicine.
Bone Marrow Smear – The differential Practical advices • Always do your differential with 1,000x magnification. We cannot exclude the possibility that prolonged follow-up or greater numbers of patients might reveal differences in outcome. Follow-up examinations including sequential bone marrow biopsies in essential thrombocythemia (ET): a retrospective clinicopathological study of 120 patients. It proved possible to make the diagnosis of MDS on the basis of bone-marrow biopsies. The JAK2(V617F) tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. World Health Organization Classification of Tumours Pathology and Genetics of Tumours of Haemopoietic and Lymphoid Tissues. There were no differences in the rates of thrombosis, major hemorrhage, myelofibrotic transformation, or survival between prefibrotic myelofibrosis and true ET as labeled by any of the hematopathologists. For instance, they generate colony stimulating factors, which have a significant effect on hematopoiesis. Finally, we were unable to identify any distinguishing diagnostic clinical or laboratory features even when subsets of patients identified as prefibrotic myelofibrosis by any 2 or all 3 hematopathologists were considered (data not shown). and P.J.C. thymus) in order to complete maturation. Tissue with increased cellular composition, such as normal "red" marrow or cancer cells within the medullary cavity will measure variably higher in density.[19]. For clinical outcome, we used a composite clinical end point of time to first arterial or venous thrombosis; major hemorrhage; myelofibrotic, leukemic, or myelodysplastic transformation; or death. Marisavljević D, Rolović Z, Cemerikić V, Bosković D, Colović M. Med Oncol. For example, normal fatty "yellow" marrow in adult long bones is of low density (-30 to -100 Hounsfield units), between subcutaneous fat and soft tissue. WHO bone marrow features and European clinical, molecular, and pathological (ECMP) criteria for the diagnosis of myeloproliferative disorders. Bone marrow examination is the pathologic analysis of samples of bone marrow obtained via biopsy and bone marrow aspiration.
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