Bone marrow neoplastic
Bone marrow - neoplastic myeloid
Myeloproliferative neoplasms (MPN)
WHO classification - MPN
Author: Nikhil Sangle, M.D.
Last author update: 1 August 2011
Last staff update: 24 March 2022
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: MPN WHO classification
Table of Contents
World Health Organization classification | Diagrams / tables | Clinical features | Microscopic (histologic) description | Molecular / cytogenetics description | Additional referencesCite this page: Sangle N. WHO classification - MPN. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrowneoplasticMPNWHO.html. Accessed April 2nd, 2023.
World Health Organization classification
WHO 2008 - Myeloproliferative neoplasms (MPN)
WHO 2001 - Chronic myeloproliferative diseases
- Chronic myelogenous leukemia
- Polycythemia vera
- Essential thrombocythemia
- Primary myelofibrosis
- Chronic neutrophilic leukemia
- Chronic eosinophilic leukemia, not otherwise categorized
- Mast cell disease
- MPNs, unclassifiable
WHO 2001 - Chronic myeloproliferative diseases
- Chronic myelogenous leukemia (Philadelphia chromosome, t(9;22)(q34;q11), BCR-ABL positive)
- Chronic neutrophilic leukemia
- Chronic eosinophilic leukemia (and the hypereosinophilic syndrome)
- Polycythemia vera
- Chronic idiopathic myelofibrosis (with extramedullary hematopoiesis)
- Essential thrombocythemia
- Chronic myeloproliferative disease, unclassifiable
Diagrams / tables
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Drawing of JAK2 mutation
Drawing of c-Mpl mutation
Clinical features
- First described by William Dameshek in 1951 (Blood 1951;6:372)
- WHO 2001: termed chronic myeloproliferative diseases
- WHO 2008: termed myeloproliferative neoplasms, to emphasize the clonal evolution of these entities
- All have effective clonal myeloproliferation with no dyserythropoiesis, no granulocyte dysplasia and no monocytosis; their phenotypic diversity is due to different mutations affecting tyrosine kinases or related molecules, causing different patterns of abnormal signal transduction
- Initially hypercellular marrow with increased hematopoiesis, increased peripheral blood counts (often marked increase in all cell lines but with normal morphology) and extramedullary hematopoiesis in spleen with splenomegaly / other organomegaly; then spent phase with marrow fibrosis and cytopenia
- CML frequently progresses to acute myelogenous leukemia (AML) but other myeloproliferative neoplasms only rarely progress to AML
- There is considerable morphologic overlap among subtypes and with benign hyperplastic marrow conditions, requiring a multimodal diagnostic approach combining cytomorphology, cytogenetics and molecular methods for BCR-ABL negative cases (Ann Hematol 2008;87:1)
- 4 color flow cytometry is helpful in diagnosis (Arch Pathol Lab Med 2003;127:1140)
- Extramedullary hematopoiesis appears to be a clonal process (Hum Pathol 2007;38:1760) with JAK2 V617F mutation frequently present in splenic EMH cells (Mod Pathol 2007;20:929)
- Occasionally has coexisting monoclonal B cell infiltrate in bone marrow detectable by IgH PCR but not by morphology (Mod Pathol 2004;17:1521)
- May have nodal or extranodal tumor forming accumulations of plasmacytoid monocytes / interferon producing cells, which are clonal and related to underlying myeloid tumor (Am J Surg Pathol 2004;28:585)
- Associated with chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension (Respiration 2008;76:295)
- Usually prolonged survival
Microscopic (histologic) description
- May have emperipolesis (ingestion of blood cells by megakaryocytes or other cells)
- Rarely monocytic nodules similar to plasmacytoid monocyte nodules (Am J Clin Pathol 2003;120:874)
Molecular / cytogenetics description
- JAK2 V617F mutation (Janus kinase 2 gene) present in most non CML chronic myeloproliferative diseases ( > 85% of polycythemia vera, 65% of essential thrombocythemia, 65% of chronic idiopathic myelofibrosis, Am J Surg Pathol 2007;31:233), causes constitutive tyrosine kinase activity
- c-Mpl mutation (thrombopoietin receptor) occurs in essential thrombocythemia and idiopathic myelofibrosis (J Transl Med 2006;4:41)
- FLT3 mutations are occasionally seen (Am J Clin Pathol 2006;126:530)
Additional references
- WHO 2008: Leukemia 2008;22:14
- WHO 2001: Blood 2007;110:1092, Blood 2002;100:2292
