scholarly journals The Classification of Myeloproliferative Neoplasms: Rationale, Historical Background and Future Perspectives with Focus on Unclassifiable Cases

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5666
Author(s):  
Marco Pizzi ◽  
Giorgio Alberto Croci ◽  
Marco Ruggeri ◽  
Silvia Tabano ◽  
Angelo Paolo Dei Tos ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Historical Background ◽  
World Health ◽  
Hematopoietic Stem ◽  
Chronic Eosinophilic Leukemia ◽  
History Of ◽  
Health Organization

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal hematopoietic stem cell disorders, characterized by increased proliferation of one or more myeloid lineages in the bone marrow. The classification and diagnostic criteria of MPNs have undergone relevant changes over the years, reflecting the increased awareness on these conditions and a better understanding of their biological and clinical-pathological features. The current World Health Organization (WHO) Classification acknowledges four main sub-groups of MPNs: (i) Chronic Myeloid Leukemia; (ii) classical Philadelphia-negative MPNs (Polycythemia Vera; Essential Thrombocythemia; Primary Myelofibrosis); (iii) non-classical Philadelphia-negative MPNs (Chronic Neutrophilic Leukemia; Chronic Eosinophilic Leukemia); and (iv) MPNs, unclassifiable (MPN-U). The latter are currently defined as MPNs with clinical-pathological findings not fulfilling the diagnostic criteria for any other entity. The MPN-U spectrum traditionally encompasses early phase MPNs, terminal (i.e., advanced fibrotic) MPNs, and cases associated with inflammatory or neoplastic disorders that obscure the clinical-histological picture. Several lines of evidence and clinical practice suggest the existence of additional myeloid neoplasms that may expand the spectrum of MPN-U. To gain insight into such disorders, this review addresses the history of MPN classification, the evolution of their diagnostic criteria and the complex clinical-pathological and biological features of MPN-U.

scholarly journals Update from the latest WHO classification of MPNs: a user’s manual

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 534-542 ◽  
Author(s):  
Francesco Passamonti ◽  
Margherita Maffioli
Keyword(s):  
Diagnostic Criteria ◽  
Who Classification ◽  
Triple Negative ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
World Health ◽  
Driver Mutations ◽  
Health Organization

Abstract The 2016 multiparameter World Health Organization (WHO) classification for Philadelphia-negative myeloproliferative neoplasms (MPNs) integrates clinical features, morphology, and genetic data to diagnose polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The main novelties are: (1) the reduction of the hemoglobin (Hb) level threshold to diagnose PV, now established at 16.5 g/dL for men and 16 g/dL for women (based on the identification of MPN patients with PV-consistent bone marrow [BM] features and a Hb level lower than that established in the 2008 WHO classification for PV); (2) the recognition of prefibrotic/early PMF, distinguishable from ET on the basis of BM morphology, an entity having a higher tendency to develop overt myelofibrosis or acute leukemia, and characterized by inferior survival; (3) the central role of BM morphology in the diagnosis of ET, prefibrotic/early PMF, PMF, and PV with borderline Hb values; megakaryocyte number and morphology (typical in ET, atypical in both PMF forms) accompanied by a new distinction of reticulin fibrosis grade in PMF (grade 1 in prefibrotic/early PMF and grade 2-3 in PMF) constitute diagnostic criteria; and (4) the inclusion of all mutually exclusive MPN driver mutations (JAK2, CALR, and MPL) as major diagnostic criteria in ET and PMF; 10% to 15% of these patients are triple negative, and in these cases the search for an additional clonal marker (eg, mutations in ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, and SF3B1) is warranted.

Haematopathology of classic myeloproliferative neoplasms

2020 ◽  
pp. 45-62
Author(s):  
Hans Michael Kvasnicka ◽  
Jürgen Thiele
Keyword(s):  
Continuous Improvement ◽  
Who Classification ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
World Health ◽  
Polycythaemia Vera ◽  
The World ◽  
Health Organization ◽  
Diagnostic Importance

The classification of the World Health Organization (WHO) continues to advocate the diagnostic importance of bone marrow (BM) morphology in the diagnostic workup of myeloproliferative neoplasms (MPN). In this regard, distinctive histological BM patterns characterize specific subtypes of MPN and are the key to a meaningful clinical and molecular-defined risk stratification of patients. In this regard, the morphological denominator includes a characteristic megakaryocytic proliferation along with variable changes in the granulopoiesis and erythropoiesis. Importantly, diagnosis of MPN requires absence of relevant dysgranulopoiesis or dyserythropoiesis. In terms of clinical practice, the concept of precursor stages provides the possibility of an early intervention by appropriate therapeutic regimens that might prevent fatal complications like thrombosis and haemorrhage, especially in early stages of polycythaemia vera or in primary myelofibrosis. However, the WHO classification is not aimed to capture all biological true cases of MPN or guarantee a complete diagnostic specificity and thus might be in need of continuous improvement following clinical experience.

scholarly journals Myeloid neoplasms with eosinophilia

Blood ◽  
2017 ◽  
Vol 129 (6) ◽  
pp. 704-714 ◽  
Author(s):  
Andreas Reiter ◽  
Jason Gotlib
Keyword(s):  
De Novo ◽  
Myeloproliferative Neoplasms ◽  
Disease Free Survival ◽  
World Health ◽  
Hematopoietic Stem ◽  
Chronic Eosinophilic Leukemia ◽  
Molecular Abnormalities ◽  
Myeloid Neoplasms ◽  
Variable Sensitivity ◽  
Health Organization

Abstract Molecular diagnostics has generated substantial dividends in dissecting the genetic basis of myeloid neoplasms with eosinophilia. The family of diseases generated by dysregulated fusion tyrosine kinase (TK) genes is recognized by the World Health Organization (WHO) category, “Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2.” In addition to myeloproliferative neoplasms (MPN), these patients can present with myelodysplastic syndrome/MPN, as well as de novo or secondary mixed-phenotype leukemias or lymphomas. Eosinophilia is a common, but not invariable, feature of these diseases. The natural history of PDGFRA- and PDGFRB-rearranged neoplasms has been dramatically altered by imatinib. In contrast, patients with FGFR1 and JAK2 fusion TK genes exhibit a more aggressive course and variable sensitivity to current TK inhibitors, and in most cases, long-term disease-free survival may only be achievable with allogeneic hematopoietic stem cell transplantation. Similar poor prognosis outcomes may be observed with rearrangements of FLT3 or ABL1 (eg, both of which commonly partner with ETV6), and further investigation is needed to validate their inclusion in the current WHO-defined group of eosinophilia-associated TK fusion-driven neoplasms. The diagnosis chronic eosinophilic leukemia, not otherwise specified (CEL, NOS) is assigned to patients with MPN with eosinophilia and nonspecific cytogenetic/molecular abnormalities and/or increased myeloblasts. Myeloid mutation panels have identified somatic variants in patients with a provisional diagnosis of hypereosinophilia of undetermined significance, reclassifying some of these cases as eosinophilia-associated neoplasms. Looking forward, one of the many challenges will be how to use the results of molecular profiling to guide prognosis and selection of actionable therapeutic targets.

scholarly journals Morphological Characteristics, Classifications and Difficulties in the Use of Diagnostic Criteria for Serrated Lesions of the Large Intestine

2021 ◽  
Author(s):  
Cesar de Souza Bastos Junior ◽  
Vera Lucia Nunes Pannain ◽  
Adriana Caroli-Bottino
Keyword(s):  
Diagnostic Criteria ◽  
Morphological Characteristics ◽  
World Health ◽  
Diagnostic Tools ◽  
Serrated Adenoma ◽  
The Past ◽  
The World ◽  
Serrated Lesions ◽  
Health Organization

Abstract Introduction Colorectal carcinoma (CRC) is the most common gastrointestinal neoplasm in the world, accounting for 15% of cancer-related deaths. This condition is related to different molecular pathways, among them the recently described serrated pathway, whose characteristic entities, serrated lesions, have undergone important changes in their names and diagnostic criteria in the past thirty years. The multiplicity of denominations and criteria over the last years may be responsible for the low interobserver concordance (IOC) described in the literature. Objectives The present study aims to describe the evolution in classification of serrated lesions, based on the last three publications of the World Health Organization (WHO) and the reproducibility of these criteria by pathologists, based on the evaluation of the IOC. Methods A search was conducted in the PubMed, ResearchGate and Portal Capes databases, with the following terms: sessile serrated lesion; serrated lesions; serrated adenoma; interobserver concordance; and reproducibility. Articles published since 1990 were researched. Results and Discussion The classification of serrated lesions in the past thirty years showed different denominations and diagnostic criteria. The reproducibility and IOC of these criteria in the literature, based on the kappa coefficient, varied in most studies, from very poor to moderate. Conclusions Interobserver concordance and the reproducibility of microscopic criteria may represent a limitation for the diagnosis and appropriate management of these lesions. It is necessary to investigate diagnostic tools to improve the performance of the pathologist's evaluation, for better concordance, and, consequently, adequate diagnosis and treatment.

scholarly journals IMPORTANCE OF CLASSICAL MORPHOLOGY IN THE DIAGNOSIS OF MYELODYSPLASTIC SYNDROME

2015 ◽  
Vol 7 ◽  
pp. e2015035 ◽  
Author(s):  
Rosangela Invernizzi ◽  
Federica Quaglia ◽  
Matteo Giovanni Della Porta
Keyword(s):  
Molecular Techniques ◽  
Classification Systems ◽  
World Health ◽  
Hematopoietic Stem ◽  
Morphological Alterations ◽  
Diagnosis And Classification ◽  
The Moment ◽  
Health Organization ◽  
Selection Of

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders characterized by dysplastic, ineffective, clonal and neoplastic hematopoiesis. MDS represent a complex hematological problem: differences in disease presentation, progression and outcome  have necessitated the use of classification systems to improve diagnosis, prognostication and treatment selection. However, since a single biological or genetic reliable diagnostic marker has not yet been discovered for MDS, quantitative and qualitative dysplastic morphological alterations of bone marrow precursors and of peripheral blood cells are still fundamental for diagnostic classification. In this paper World Health Organization (WHO) classification refinements and current minimal diagnostic criteria proposed by expert panels are highlighted and related problematic issues are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies. Although in the future morphology should be supplemented with new molecular techniques, the morphological approach, at least for the moment, is still the cornerstone for the diagnosis and classification of these disorders.

A Study of Aetiological Factors at Critical Periods of Development in Autistic Children

1973 ◽  
Vol 7 (3) ◽  
pp. 163-168 ◽  
Author(s):  
Sara Williams ◽  
Juliet Harper
Keyword(s):  
Sensory Deprivation ◽  
Working Party ◽  
Infantile Autism ◽  
World Health ◽  
Critical Periods ◽  
Educational Placement ◽  
World Health Organization Classification ◽  
History Of ◽  
Health Organization

Ninety-seven children were diagnosed as suffering from infantile autism according to the nine points of the British Working Party and the World Health Organization classification of Mental Disorders in Childhood. Data on these cases were analyzed in terms of aetiology as known, social class of parents, year of onset, its relationship to the presence of an organic cerebral defect, and outcome in terms of the present educational placement of the child. Findings suggested that infantile autism was a disorder with a multiple aetiology and the causes, both organic and environmental, were interrelated. It was postulated that the most consistent effect present in the early backgrounds of these children was a history of sensory deprivation at a critical period of development.

The revised WHO diagnostic criteria for Ph-negative myeloproliferative diseases are not appropriate for the diagnostic screening of childhood polycythemia vera and essential thrombocythemia

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3384-3386 ◽  
Author(s):  
Luciana Teofili ◽  
Fiorina Giona ◽  
Maurizio Martini ◽  
Tonia Cenci ◽  
Francesco Guidi ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Diagnostic Criteria ◽  
Essential Thrombocythemia ◽  
Significant Proportion ◽  
Erythropoietin Receptor ◽  
World Health ◽  
Who Criteria ◽  
Myeloproliferative Diseases ◽  
History Of ◽  
Health Organization

Abstract In the proposed revised World Health Organization (WHO) criteria for the diagnosis of BCR-ABL− myeloproliferative diseases (MPDs), exclusion criteria have been replaced by the presence of JAK2 mutations. We applied these criteria to 45 children with MPDs: 13 with polycythemia vera (PV) and 32 with essential thrombocythemia (ET). Among these 45 patients, 12 with ET and 5 with PV had a familial history of MPD, and had been investigated for hereditary mutations of the erythropoietin receptor, thrombopoietin, or MPL genes. We found that the JAK2V617F mutation in children occurs less frequently than in adults, and that exon 12 JAK2 mutations are absent. On the basis of the revised WHO criteria, a significant proportion of childhood PVs were misdiagnosed. Furthermore, all familial ET, including patients carrying the hereditary MPLSer505Asn activating mutation, were erroneously diagnosed as MPDs. Our observations suggest that childhood MPDs require a set of specific diagnostic criteria.

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