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WHO Classification of Tumours
Myeloproliferative neoplasm, unclassifiable
Tumours of haematopoietic and lymphoid tissues


Definition

The designation myeloproliferative neoplasm, unclassifiable (MPN, U) should be applied only to cases that have definite clinical, laboratory and morphological features of an MPN but that fail to meet the criteria for any of the specific MPN ­entities, or that present with features that overlap two or more of the MPN categories. Most cases of MPN, U, will fall into one of three groups:
1) Early stages of polycythemia vera (PV), primary myelofibrosis (PMF) or essential thrombocythemia (ET) in which the characteristic features are not yet fully developed;
2) Advanced stage MPN, in which pronounced myelo­fibrosis, osteo­sclerosis, or transformation to a more aggressive stage (i.e. increased blasts and/or dysplasia) obscures the ­underlying disorder

Click to access Pubmed
Georgii A, Buesche G, Kreft A (1998)
The histopathology of chronic myeloproliferative diseases.
Baillieres Clin Haematol 11: 721-49




Click to access Pubmed
Kvasnicka HM, Thiele J (2007)
Classification of Ph-negative chronic myeloproliferative disorders--morphology as the yardstick of classification.
Pathobiology 74: 63-71




Click to access Pubmed
Thiele J, Kvasnicka HM (2007)
Myelofibrosis--what's in a name? Consensus on definition and EUMNET grading.
Pathobiology 74: 89-96




Click to access Pubmed
Thiele J, Kvasnicka HM, Orazi A (2005)
Bone marrow histopathology in myeloproliferative disorders--current diagnostic approach.
Semin Hematol 42: 184-95




Click to access Pubmed
Thiele J, Kvasnicka HM, Vardiman J (2006)
Bone marrow histopathology in the diagnosis of chronic myeloproliferative disorders: a forgotten pearl.
Best Pract Res Clin Haematol 19: 413-37



; or,
3) Patients with convincing evidence of an MPN in whom a coexisting neoplastic or inflammatory disorder obscures some of the diagnostic clinical and/or morphological features.

> Exclusion criteria
The presence of a Philadelphia (Ph) chromosome, BCR-ABL1 fusion gene or rearrangement of PDGFRA, PDGFRB or FGFR1 genes ­excludes the diagnosis of MPN,U. Further, the diagnosis of MPN,U should not be used when clinical data necessary for proper classification are insufficient or not available, when the bone marrow (BM) specimen is of inadequate quality or size for accurate evaluation

Click to access Pubmed
Kvasnicka HM, Thiele J (2007)
Classification of Ph-negative chronic myeloproliferative disorders--morphology as the yardstick of classification.
Pathobiology 74: 63-71




Click to access Pubmed
Thiele J, Kvasnicka HM, Orazi A (2005)
Bone marrow histopathology in myeloproliferative disorders--current diagnostic approach.
Semin Hematol 42: 184-95




Click to access Pubmed
Thiele J, Kvasnicka HM, Vardiman J (2006)
Bone marrow histopathology in the diagnosis of chronic myeloproliferative disorders: a forgotten pearl.
Best Pract Res Clin Haematol 19: 413-37



, or when there has been recent cytotoxic or growth factor therapy —problems that account for the majority of the unclassifiable cases ­encountered in routine practice. In such cases it is often preferable to describe the morphological findings, and to suggest additional clinical and laboratory procedures that are needed to further classify the process, including adequate peripheral blood (PB) and BM biopsy and aspirate specimens. When a diagnosis of MPN, U is made, the report should summarize the reason for the difficulty in reaching a more specific diagnosis, and, if possible, specify which of the MPN can be excluded from consideration.

> Differential diagnosis
If a case does not have the features of one of the well-defined entities, the possibility that it is not an MPN must be strongly considered. A reactive BM response to infection and inflammation, toxins, chemotherapy, and administration of growth factors, cytokines and immunosuppressive agents may closely mimic MPN and must be excluded. Furthermore, a number of other haematopoietic and non-haematopoietic neoplasms, such as lymphoma or metastatic carcinoma, may infiltrate the marrow and cause reactive changes, including dense fibrosis and ­osteosclerosis that can be misconstrued as an MPN

Click to access Pubmed
Thiele J, Kvasnicka HM (2007)
Myelofibrosis--what's in a name? Consensus on definition and EUMNET grading.
Pathobiology 74: 89-96



.

Detection of a clonal cytogenetic abnormality, a JAK2 V617F or other functionally similar JAK2 mutation, or an MPL (MPL W515K/L) mutation will distinguish an MPN from such reactive conditions, although not all cases of MPN, U express a currently recognized genetic marker

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Tefferi A, Lasho TL, Gilliland G (2005)
JAK2 mutations in myeloproliferative disorders.
N Engl J Med 353: 1416-7; author reply 1416-7




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Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA, Barosi G, Verstovsek S, Birgegard G, Mesa R, Reilly JT, Gisslinger H, Vannucchi AM, Cervantes F, Finazzi G, Hoffman R, Gilliland DG, Bloomfield CD, Vardiman JW (2007)
Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel.
Blood 110: 1092-7



. In addition, the defining characteristics of each MPN must be considered with the realization that, as with any other biological process, variations do occur, and they may progress through ­different stages so that the clinical and morphological manifestations of the disease will change with time
Click to access Pubmed
Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA, Barosi G, Verstovsek S, Birgegard G, Mesa R, Reilly JT, Gisslinger H, Vannucchi AM, Cervantes F, Finazzi G, Hoffman R, Gilliland DG, Bloomfield CD, Vardiman JW (2007)
Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel.
Blood 110: 1092-7




Click to access Pubmed
Thiele J, Kvasnicka HM, Orazi A (2005)
Bone marrow histopathology in myeloproliferative disorders--current diagnostic approach.
Semin Hematol 42: 184-95



.