Myeloproliferative neoplasia

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Classification according to ICD-10
C92.1 Chronic myeloid leukemia
ICD-O 9875/3
D45 Polycythemia vera
ICD-O 9950/3
D47.3 Essential thrombocythemia
ICD-O 9950/3
D47.3 Primary myelofibrosis
ICD-O 9961/3
C92.7 Chronic neutrophil leukemia
ICD-O 9963/3
D47.5 Chronic eosinophilic leukemia /
hypereosinophilic syndrome
ICD-O 9880/3
D47.0 indolent systemic mastocytosis
ICD-O 9741/1
D47.0 systemic mastocytosis with associated clonal hematological non-mast cell disease
ICD-O 9741/3
C96.2 aggressive systemic mastocytosis
ICD-O 9741/3
C94.3 Mast cell leukemia
ICD-O 9742/3
C96.2 Mast cell sarcoma
ICD-O 9740/3
C94.6 Unclassifiable myeloproliferative neoplasia
ICD-O 9975/3
ICD-10 online (WHO version 2019)

The term myeloproliferative neoplasia ( MPN , from ancient Greek µυελός myelos , German 'marrow' , means the bone marrow , not the spinal cord , proliferation of the Latin proles 'offspring' , meaning cell growth and multiplication as well as neoplasia for 'new formation') summarized a number of chronic malignant blood diseases of the myeloid series. The term comes from the classification of the World Health Organization (WHO) from 2008 and has had a precisely defined meaning since then. In 2016, the diagnostic criteria were updated by the WHO.

Historical

In 1951, the American hematologist William Dameshek proposed that a group of malignant blood diseases should be summarized under the umbrella term Myeloproliferative Syndromes (MPS) due to various clinical similarities . Dameshek classified the following five diseases under this term:

Later, however, only the first four diseases were summarized under this term. The Di Guglielmo syndrome (the term is no longer in use today), on the other hand, was assigned to acute myeloid leukemia (AML) (AML FAB M6 ).

All four diseases have in common that they are based on a malignant degeneration of blood-forming cells of the myeloid series, which lead to increased proliferation (increased growth) of the cell series concerned. For example, in polycythemia vera there is an increased and uncontrolled formation of red blood cells, in essential thrombocythemia there is an increased formation of platelets, which in both cases results in symptoms of the disease. In addition to changes in the blood, splenomegaly (enlargement of the spleen ) and often also hepatomegaly (enlargement of the liver ) are typical . All four diseases carry the risk of developing into acute myeloid leukemia (or “ blast crisis ”), but with a significantly different probability. In osteomyelofibrosis, there is also a pronounced remodeling of connective tissue (fibrosis) of the bone marrow.

In the course of the decades, the above-mentioned diseases could be diagnosed better and better clinically and differentiated from other diseases, so that finally no more myeloproliferative syndromes (= symptom complexes ). Instead of (chronic) myeloproliferative diseases (CMPE / MPE or CMPD / MPD, myeloproliferative disease ). Further illnesses have been included under this heading (see the list below). The term Myeloproliferative Neoplasia (MPN) has been in official use since the World Health Organization (WHO) published the Classification of Haematological Diseases in 2008 . The term syndrome should no longer be used in this context as it is out of date.

The group of myeloproliferative neoplasms

The MPN in the sense of the WHO classification 2016 include:

Remarks

  1. The addition "NOS" refers to the fact that there are also other eosinophil diseases with specific genetic changes ( PDGFRA , PDGFRB , FGFR1 , PCM1-JAK2 , see table below), these are excluded here

The main changes compared to the WHO classification 2008 are the distinction between an early, “pre-fibrotic” stage from a late, “post-fibrotic” stage with bone marrow fibrosis in primary myelofibrosis, and the removal of mastocytosis from the MPN group. In the future, mastocytosis will form its own entity.

Differentiation from other myeloid diseases

The distinction between MPN and acute myeloid leukemia (AML) is somewhat arbitrary: by definition, AML is present from a blast percentage of 20% in the bone marrow. The differentiation from myelodysplastic syndromes (MDS) is sometimes difficult and there are smooth transitions. The basic characteristic of MDS is the maturation disorder of blood formation in the bone marrow , which leads to cytopenia ( anemia , thrombopenia , leukopenia ) in the peripheral blood. In myeloproliferations, however, the focus is on the proliferation of at least one cell row ( myelopoiesis , erythropoiesis , thrombopoiesis ) in the peripheral blood.

Typical genetic changes in myeloproliferative diseases

The MPN are often characterized by activating mutations in tyrosine kinase genes ( ABL , JAK2 , FGFR1 ) and can then be treated with specific tyrosine kinase inhibitors .

illness Gene alterations
CML BCR-ABL , very rarely BCR-JAK2 , BCR-FGFR1
PV JAK2 V617F, or (rarely) JAK2 exon 12 mutations
ET JAK2 V617F, calreticulin ( CALR ) exon 9 mutations, MPL mutations, less often others
PMF JAK2 V617F, calreticulin exon 9 mutations, MPL mutations, less often others
CNL CSF3R mutations
CEL heterogeneous, not exactly known
MPN, NOS heterogeneous, not exactly known

Remarks

  1. a b c d several dozen other genes were found mutated in MPN (but also in other myeloid neoplasms). These include B. ASXL1 , TET2 , SRSF2 , SF3B1 , RUNX1 , ...

The WHO classification from 2001, 2008 and 2016 in comparison

The following table compares the classification of chronic myeloid diseases in the WHO classifications from 2001, 2008 and 2016.

WHO classification 2001 WHO classification 2008 WHO classification 2016
  • Chronic myeloproliferative diseases (CMPD)
  • Myelodysplastic Syndromes (MDS)
  • MDS / MPN, i.e. H. Diseases with both myeloproliferative and myelodysplastic features
  • Mast cell diseases
  • Myeloproliferative Neoplasms (MPN)
  • Myelodysplastic Syndromes (MDS)
  • MDS / MPN hybrid forms
  • Myeloid neoplasms with eosinophilia and
    genetic abnormalities affecting the
    PDGFRA , PDGFRB , or FGFR1 genes
  • Myeloproliferative Neoplasms (MPN)
  • Mastocytosis
  • Myelodysplastic Syndromes (MDS)
  • MDS / MPN hybrid forms
  • Myeloid neoplasms with eosinophilia and
    genetic abnormalities that the genes
    PDGFRA , PDGFRB or FGFR1 concern, or the fusion gene PCM1-JAK2 have
  • Myeloid neoplasms with predisposing germline gene alterations

Explanations

  1. a b PDGFRA : platelet-derived growth factor receptor alpha , receptor alpha for growth factor from platelets
  2. a b PDGFRB : platelet-derived growth factor receptor beta , receptor beta for growth factor from platelets
  3. a b FGFR1 : fibroblast growth factor receptor 1 , receptor 1 for fibroblast growth factor

When the WHO classification was reformulated in 2008, the old name myeloproliferative syndromes or myeloproliferative diseases was deliberately not chosen. On the one hand, this was done in order to avoid confusion with the old meanings of these terms, on the other hand, it should be made clearer that the diseases so named are not " syndromes " (symptom complexes) in the narrower sense, but relatively well-defined malignant diseases ( Neoplasms).

Sometimes all diseases that are not CML are grouped together under the term Philadelphia Chromosome Negative MPN.

literature

  • SH Swerdlow, E. Campo, NL Harris, ES Jaffe, SA Pileri, H. Stein , J. Thiele, JW Vardiman (eds.): WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. 4th edition. IARC Press, Lyon 2008, ISBN 978-92-832-2431-0 . (the WHO classification from 2008)
  • E. Jaffe, NL Harris, H. Stein, JW Vardiman (Eds.): Pathology and Genetics of Tumors of Haemopoietic and Lymphoid Tissues. IARC Press, Lyon 2001. (the 2001 WHO classification)
  • AM Vanucchi, P. Guglielmelli, A. Tefferi: Advances in Understanding and Management of Myeloproliferative Neoplasms. In: CA Cancer J Clin . Vol 59, Number 3, 2009, pp. 171-191. PMID 19369682
  • A. Tefferi, JW Vardiman: Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. In: Leukemia . Volume 22, 2008, pp. 14-22. PMID 17882280 . (Review article on the WHO classification 2008)
  • W. Dameshek: Some speculations on the myeloproliferative syndromes. In: Blood. Volume 6, 1951, pp. 372-375. PMID 14820991 full text (historical article, term "Myeloproliferative Syndrome")

Web links

Individual evidence

  1. ^ W. Dameshek: Some speculations on the myeloproliferative syndromes. In: Blood. Volume 6, 1951, pp. 372-375. PMID 14820991 (full text)
  2. a b D. A. Arber, A. Orazi, R. Hasserjian, J. Thiele, MJ Borowitz, MM Le Beau, CD Bloomfield, M. Cazzola, JW Vardiman: The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia . In: Blood. Volume 127, No. 20, 2016, pp. 2391-2405. doi: 10.1182 / blood-2016-03-643544 PMID 27069254 .