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Published in: Diagnostic Pathology 1/2015

Open Access 01-12-2015 | Research

Thrombosis in essential thrombocytemia and early/prefibrotic primary myelofibrosis: the role of the WHO histological diagnosis

Authors: Serena Rupoli, Gaia Goteri, Paola Picardi, Giorgia Micucci, Lucia Canafoglia, Anna Rita Scortechini, Irene Federici, Federica Giantomassi, Lidia Da Lio, Antonio Zizzi, Elisa Honorati, Pietro Leoni

Published in: Diagnostic Pathology | Issue 1/2015

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Abstract

Background

Vascular events represent the most frequent complications of thrombocytemias. We aimed to evaluate their risk in the WHO histologic categories of Essential Thrombocytemia (ET) and early Primary Myelofibrosis (PMF).

Methods

From our clinical database of 283 thrombocytemic patients, we selected those with available bone marrow histology performed before any treatment, at or within 1 year from diagnosis, and reclassified the 131 cases as true ET or early PMF, with or without fibrosis, according to the WHO histological criteria. Vaso-occlusive events at diagnosis and in the follow-up were compared in the WHO-groups.

Results

Histologic review reclassified 61 cases as ET and 72 cases as early PMF (26 prefibrotic and 42 with grade 1 or 2 fibrosis). Compared to ET, early PMF showed a significant higher rate of thrombosis both in the past history (22% vs 8%) and at diagnosis (15.2% vs 1.6%), and an increased leukocyte count (8389 vs 7500/mmc). Venous thromboses (mainly atypical) were relatively more common in PMF than in ET. Patients with prefibrotic PMF, although younger, showed a significant higher 15-year risk of developing thrombosis (48% vs 16% in fibrotic PMF and 17% in ET). At multivariate analysis, age and WHO histology were both independent risk-factors for thrombosis during follow-up; patients >60 yr-old or with prefibrotic PMF showed a significantly higher risk at 20 years than patients <60 yr-old with ET or fibrotic PMF (47% vs 4%, p = 0.005).

Conclusions

Our study support the importance of WHO histologic categories in the thrombotic risk stratification of patients with thrombocytemias.

Virtual slides

The virtual slide(s) for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​2020211863144412​.
Literature
1.
go back to reference Visser O, Trama A, Maynadié M, Stiller C, Marcos-Gragera R, De Angelis R, et al. Incidence, survival and prevalence of myeloid malignancies in Europe. Eur J Cancer. 2012;48(17):3257–66.CrossRefPubMed Visser O, Trama A, Maynadié M, Stiller C, Marcos-Gragera R, De Angelis R, et al. Incidence, survival and prevalence of myeloid malignancies in Europe. Eur J Cancer. 2012;48(17):3257–66.CrossRefPubMed
2.
go back to reference Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011;29(23):3179–84.CrossRefPubMed Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011;29(23):3179–84.CrossRefPubMed
3.
go back to reference Spivak JL, Silver RT. The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal. Blood. 2008;112(2):231–9.CrossRefPubMed Spivak JL, Silver RT. The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal. Blood. 2008;112(2):231–9.CrossRefPubMed
4.
go back to reference Thiele J, Kvasnicka HM, Tefferi A, Barosi G, Orazi A, Vardiman JW. Primary myelofibrosis. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008. p. 44–7. Thiele J, Kvasnicka HM, Tefferi A, Barosi G, Orazi A, Vardiman JW. Primary myelofibrosis. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008. p. 44–7.
5.
go back to reference Thiele J, Kvasnicka HM, Orazi A, Tefferi A, Gisslinger H. Essential thrombocythaemia. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008. p. 48–50. Thiele J, Kvasnicka HM, Orazi A, Tefferi A, Gisslinger H. Essential thrombocythaemia. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008. p. 48–50.
6.
go back to reference Thiele J, Kvasnicka HM. 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. Histol Histopathol. 2003;18(1):93–102.PubMed Thiele J, Kvasnicka HM. 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. Histol Histopathol. 2003;18(1):93–102.PubMed
7.
go back to reference Florena AM, Tripodo C, Iannitto E, Porcasi R, Ingrao S, Franco V. Value of bone marrow biopsy in the diagnosis of essential thrombocythemia. Haematologica. 2004;89(8):911–9.PubMed Florena AM, Tripodo C, Iannitto E, Porcasi R, Ingrao S, Franco V. Value of bone marrow biopsy in the diagnosis of essential thrombocythemia. Haematologica. 2004;89(8):911–9.PubMed
8.
go back to reference Wilkins BS, Erber WN, Bareford D, Buck G, Wheatley K, East CL, et al. Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes. Blood. 2008;111:60–70.CrossRefPubMed Wilkins BS, Erber WN, Bareford D, Buck G, Wheatley K, East CL, et al. Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes. Blood. 2008;111:60–70.CrossRefPubMed
9.
go back to reference Brousseau M, Parot-Schinkel E, Moles MP, Boyer F, Hunault M, Rousselet MC. Practical application and clinical impact of the WHO histopathological criteria on bone marrow biopsy for the diagnosis of essential thrombocythemia versus prefibrotic primary myelofibrosis. Histopathol. 2010;56:758–67.CrossRef Brousseau M, Parot-Schinkel E, Moles MP, Boyer F, Hunault M, Rousselet MC. Practical application and clinical impact of the WHO histopathological criteria on bone marrow biopsy for the diagnosis of essential thrombocythemia versus prefibrotic primary myelofibrosis. Histopathol. 2010;56:758–67.CrossRef
10.
go back to reference Thiele J, Kvasnicka HM, Müllauer L, Buxhofer-Ausch V, Gisslinger B, Gisslinger H. Essential thrombocythemia versus early primary myelofibrosis: a multicenter study to validate the WHO classification. Blood. 2011;117(21):5710–8.CrossRefPubMed Thiele J, Kvasnicka HM, Müllauer L, Buxhofer-Ausch V, Gisslinger B, Gisslinger H. Essential thrombocythemia versus early primary myelofibrosis: a multicenter study to validate the WHO classification. Blood. 2011;117(21):5710–8.CrossRefPubMed
11.
go back to reference Buhr T, Hebeda K, Kaloutsi V, Porwit A, Van der Walt J, Kreipe H. European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis. Haematologica. 2012;97(3):360–5.CrossRefPubMedCentralPubMed Buhr T, Hebeda K, Kaloutsi V, Porwit A, Van der Walt J, Kreipe H. European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis. Haematologica. 2012;97(3):360–5.CrossRefPubMedCentralPubMed
12.
go back to reference Thiele J, Orazi A, Kvasnicka HM, Franco V, Boveri E, Gianelli U, et al. European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis. Haematologica. 2012;97(3):360–55 – Comment. Thiele J, Orazi A, Kvasnicka HM, Franco V, Boveri E, Gianelli U, et al. European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis. Haematologica. 2012;97(3):360–55 – Comment.
13.
go back to reference Gianelli U, Bossi A, Cortinovis I, Sabattini E, Tripodo C, Boveri E, et al. Reproducibility of the WHO histological criteria for the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms. Mod Pathol. 2014;27:814–22.CrossRefPubMed Gianelli U, Bossi A, Cortinovis I, Sabattini E, Tripodo C, Boveri E, et al. Reproducibility of the WHO histological criteria for the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms. Mod Pathol. 2014;27:814–22.CrossRefPubMed
14.
go back to reference Cervantes F. Management of essential thrombocythemia. Hematology Am Soc Hematol Educ Program. 2011;2011:215–21.CrossRefPubMed Cervantes F. Management of essential thrombocythemia. Hematology Am Soc Hematol Educ Program. 2011;2011:215–21.CrossRefPubMed
15.
go back to reference Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90(8):1128–32.PubMed Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90(8):1128–32.PubMed
16.
go back to reference Arana Yi C, Jeyakumar G, Medinab P, Cortes J, Pierce S, Bueso-Ramos C, et al. Discrepancy in diagnosis of primary myelofibrosis between referral and tertiary care centers. Leuk Res. 2014;38(1):91–4.CrossRefPubMed Arana Yi C, Jeyakumar G, Medinab P, Cortes J, Pierce S, Bueso-Ramos C, et al. Discrepancy in diagnosis of primary myelofibrosis between referral and tertiary care centers. Leuk Res. 2014;38(1):91–4.CrossRefPubMed
17.
go back to reference Barosi G, Rosti V, Campanelli R, Catarsi P, Isgrò AM, Lupo L, et al. Prefibrotic Myelofibrosis (PreMF) Belongs to a Continuum of Epidemiological, Clinical and Histological Characteristics Featuring Primary Myelofibrosis (PMF). Blood. 2011;118:1743. ASH Annual Meeting Abstracts. Barosi G, Rosti V, Campanelli R, Catarsi P, Isgrò AM, Lupo L, et al. Prefibrotic Myelofibrosis (PreMF) Belongs to a Continuum of Epidemiological, Clinical and Histological Characteristics Featuring Primary Myelofibrosis (PMF). Blood. 2011;118:1743. ASH Annual Meeting Abstracts.
18.
go back to reference Barosi G. Essential Thrombocythemia vs. early/prefibrotic myelofibrosis: Why does it matter. Best Pract Res Clin Haematol. 2014;27:129–40.CrossRefPubMed Barosi G. Essential Thrombocythemia vs. early/prefibrotic myelofibrosis: Why does it matter. Best Pract Res Clin Haematol. 2014;27:129–40.CrossRefPubMed
19.
go back to reference Rosti V, Bonetti E, Bergamaschi G, Campanelli R, Guglielmelli P, Maestri M, et al. Frequency of endothelial colony forming cells marks a Non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis. PLoS One. 2010;5(12), e15277.CrossRefPubMedCentralPubMed Rosti V, Bonetti E, Bergamaschi G, Campanelli R, Guglielmelli P, Maestri M, et al. Frequency of endothelial colony forming cells marks a Non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis. PLoS One. 2010;5(12), e15277.CrossRefPubMedCentralPubMed
20.
go back to reference Barbui T, Carobbio A, Cervantes F, Vannucchi AM, Guglielmelli P, Antonioli E, et al. Thrombosis in primary myelofibrosis: incidence and risk factors. Blood. 2010;115(4):778–82.CrossRefPubMed Barbui T, Carobbio A, Cervantes F, Vannucchi AM, Guglielmelli P, Antonioli E, et al. Thrombosis in primary myelofibrosis: incidence and risk factors. Blood. 2010;115(4):778–82.CrossRefPubMed
21.
go back to reference Buxhofer-Ausch V, Gisslinger H, Thiele J, Gisslinger B, Kvasnicka HM, Müllauer L, et al. Leukocytosis as an important risk factor for arterial thrombosis in WHO-defined early/prefibrotic myelofibrosis: an international study of 264 patients. Am J Hematol. 2012;87:669–72.CrossRefPubMed Buxhofer-Ausch V, Gisslinger H, Thiele J, Gisslinger B, Kvasnicka HM, Müllauer L, et al. Leukocytosis as an important risk factor for arterial thrombosis in WHO-defined early/prefibrotic myelofibrosis: an international study of 264 patients. Am J Hematol. 2012;87:669–72.CrossRefPubMed
22.
go back to reference Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Randi ML, et al. Brief report Initial bone marrow reticulin fibrosis in polycythemia vera exerts an impact on clinical outcome. Blood. 2012;119:2239–41.CrossRefPubMed Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Randi ML, et al. Brief report Initial bone marrow reticulin fibrosis in polycythemia vera exerts an impact on clinical outcome. Blood. 2012;119:2239–41.CrossRefPubMed
23.
go back to reference Vannucchi AM. Insights into the pathogenesis and management of thrombosis in polycythemia vera and essential thrombocythemia. Intern Emerg Med. 2010;5(3):177–84.CrossRefPubMed Vannucchi AM. Insights into the pathogenesis and management of thrombosis in polycythemia vera and essential thrombocythemia. Intern Emerg Med. 2010;5(3):177–84.CrossRefPubMed
24.
go back to reference Tefferi A. Polycythemia vera and essential thrombocythemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol. 2012;87(3):285–93.PubMed Tefferi A. Polycythemia vera and essential thrombocythemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol. 2012;87(3):285–93.PubMed
25.
go back to reference Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29(6):761–70.CrossRefPubMed Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29(6):761–70.CrossRefPubMed
26.
go back to reference Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood. 2012;120(26):5128–33.CrossRefPubMed Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood. 2012;120(26):5128–33.CrossRefPubMed
27.
go back to reference Gangat N, Wassie E, Lasho T, Finke C, Ketterling R, Hanson C, et al. Mutations and thrombosis in essential thrombocythemia: prognostic interaction with age and thrombosis history. Eur J Haematol. 2015;94(1):31–6.CrossRefPubMed Gangat N, Wassie E, Lasho T, Finke C, Ketterling R, Hanson C, et al. Mutations and thrombosis in essential thrombocythemia: prognostic interaction with age and thrombosis history. Eur J Haematol. 2015;94(1):31–6.CrossRefPubMed
28.
go back to reference Barosi G, Vannucchi AM, De Stefano V, Pane F, Passamonti F, Rambaldi A, et al. Identifying and addressing unmet clinical needs in Ph-neg classical myeloproliferative neoplasms: a consensus-based SIE, SIES, GITMO position paper. Leukem Res. 2014;38(2):155–60.CrossRef Barosi G, Vannucchi AM, De Stefano V, Pane F, Passamonti F, Rambaldi A, et al. Identifying and addressing unmet clinical needs in Ph-neg classical myeloproliferative neoplasms: a consensus-based SIE, SIES, GITMO position paper. Leukem Res. 2014;38(2):155–60.CrossRef
29.
go back to reference Hasselbalch HC. Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer? Blood. 2012;119(14):3219–25.CrossRefPubMed Hasselbalch HC. Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer? Blood. 2012;119(14):3219–25.CrossRefPubMed
30.
go back to reference Landolfi R, Di Gennaro L. Prevention of thrombosis in polycythemia vera and essential thrombocythemia. Haematologica. 2008;93(3):331–5.CrossRefPubMed Landolfi R, Di Gennaro L. Prevention of thrombosis in polycythemia vera and essential thrombocythemia. Haematologica. 2008;93(3):331–5.CrossRefPubMed
31.
go back to reference Patrono C, Rocca B, De Stefano V. Platelet activation and inhibition in polycythemia vera and essential thrombocythemia. Blood. 2013;121(10):1701–11.CrossRefPubMed Patrono C, Rocca B, De Stefano V. Platelet activation and inhibition in polycythemia vera and essential thrombocythemia. Blood. 2013;121(10):1701–11.CrossRefPubMed
32.
go back to reference Alvarez-Larrán A, Cervantes F, Pereira A, Arellano-Rodrigo E, Pérez-Andreu V, Hernández-Boluda JC, et al. Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood. 2010;116(8):1205–10. Alvarez-Larrán A, Cervantes F, Pereira A, Arellano-Rodrigo E, Pérez-Andreu V, Hernández-Boluda JC, et al. Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood. 2010;116(8):1205–10.
Metadata
Title
Thrombosis in essential thrombocytemia and early/prefibrotic primary myelofibrosis: the role of the WHO histological diagnosis
Authors
Serena Rupoli
Gaia Goteri
Paola Picardi
Giorgia Micucci
Lucia Canafoglia
Anna Rita Scortechini
Irene Federici
Federica Giantomassi
Lidia Da Lio
Antonio Zizzi
Elisa Honorati
Pietro Leoni
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2015
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-015-0269-1

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