diagnosis of polycythemia vera

Polycythemia Vera: New Diagnostic Concept and Its Types

REVIEWS , , ,

AM Kovrigina1, VV Baikov2

1 Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

For correspondence: Alla Mikhailovna Kovrigina, DSci, Professor, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-61-12; e-mail: kovrigina.alla@gmail.com

For citation: Kovrigina AM, Baikov VV. Polycythemia Vera: New Diagnostic Concept and Its Types. Clinical oncohematology. 2016;9(2):115–22 (In Russ).

DOI: 10.21320/2500-2139-2016-9-2-115-122

ABSTRACT

Polycythemia vera (PV) is a clonal Ph-negative myeloproliferative disorder characterized by excessive myeloid proliferation of three hematopoietic cell lineages leading to ineffective myelopoiesis. According to WHO classification (2008), hemoglobin and hematocrit values are listed among the major diagnostic criteria. However, in many PV patients the levels may be below the diagnostic level, thus leading to underdiagnosis of PV. At present, three clinical types of the disease are recognized: 1) masked (latent/prodromal), 2) classic (overt), and 3) PV with progression/transformation into myelofibrosis. The masked form is most difficult for diagnosis, being highly heterogeneous with regard to clinical manifestations, laboratory data, medical history, and the course of the disease. It includes early stages, some of them with very high platelet count, imitating essential thrombocythemia, cases with abdominal thrombosis, and latent PV. Bone marrow trephine biopsy appears to be the most reliable method for diagnosis of masked PV. Findings typical for PV are readily visible, including hypercellular bone marrow with three-lineage myeloid proliferation, excess of megakaryocytes with mild to moderate cellular atypia and polymorphism. Gradi

 

ng of reticulin fibrosis has impact on prognosis and reflects the risk of progression into myelofibrosis. In revised edition of WHO classification (2016), the typical bone marrow histopathology will be included among the major criteria for the diagnosis of PV, meaning that bone marrow trephine biopsy is a mandatory diagnostic procedure in patients with borderline levels of hemoglobin and hematocrit.

Keywords: polycythemia vera, myeloproliferative disorder, diagnosis of polycythemia vera, types of polycythemia vera.

Received: January 19, 2015

Accepted: February 1, 2016

Read in  PDF( RUS) pdficon

REFERNCES

  1. Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J. 2015;5(11):e366. doi: 10.1038/bcj.2015.95.
  2. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17):1779–90. doi 10.1056/nejmoa051113.
  3. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7(4):387–97. doi: 10.1016/j.ccr.2005.03.023.
  4. Chloe J, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144–8. doi: 10.1038/nature03546.
  5. Baxter EJ, Scott LM, Campbell PJ, et al. Cancer Genome Project. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. The Lancet. 2005;365(9464):1054–61. doi: 10.1016/s0140-6736(05)71142-9.
  6. Wang YL, Vandris K, Jones A, et al. JAK2 Mutations are present in all cases of polycythemia vera. Leukemia. 2008;22(6):1289. doi: 10.1038/sj.leu.2405047.
  7. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379–90. doi: 10.1056/NEJMoa1311347.
  8. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391–405. doi:  10.1056/NEJMoa1312542.
  9. Broseus J, Park JH, Carillo S, et al. Presence of calreticulin mutations in JAK2-negative polycythemia vera. Blood. 2014;124(26):3964–6. doi: 10.1182/blood-2014-06-583161.
  10. Fairbanks VF, Klee GG, Wiseman GA, et al. Measurement of Blood volume and Red Cell Mass: re-examination of 51Cr and 125I methods. Blood Cells Mol Dis. 1996;22(15):169–86. doi: 10.1006/bcmd.1996.0024.
  11. Lorberboym M, Rahimi-Levene N, Lipszyc H, et al. Analysis of Red Cell Mass and Plasma Volume in Patients With Polycythemia. Arch Pathol Lab Med. 2005;129:89–91.
  12. Murphy S. Diagnostic criteria and prognosis in polycythemia vera and essential thrombocythemia. Semin Hematol. 1999;36(1 Suppl 2):9–13.
  13. Alvarez-Larran A, Ancochea A, Angona A, et al. Red cell mass measurement in patients with clinically suspected diagnosis of polycythemia vera or essential thrombocythemia. Haematologica. 2012;97(11):1704–7. doi: 10.3324/haematol.2012.067348.
  14. Tefferi A. Polycythemia vera and essential thrombocythemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol. 2012;87(3):285–93. doi: 10.1002/ajh.23135.
  15. Johansson PL, Safai-Kutti S, Kutti J. An elevated venous haemoglobin concentration cannot be used as a surrogate marker for absolute erythrocytosis: a study of patients with polycythaemia vera and apparent polycythaemia. Br J Haematol. 2005;129(5):701–5. doi: – 10.1111/j.1365-2141.2005.05517.x.
  16. Thiele J, Kvasnicka HM, Orazi A, et al. Polycythaemia vera. In: Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. Lyon: IARC Press; 2008. pp. 40–43.
  17. Silver RT, Chow W, Orazi A, et al. Evaluation of WHO criteria for diagnosis of polycythemia vera: a prospective analysis. Blood. 2013;122(11):1881–6. doi: 10.1182/blood-2013-06-508416.
  18. Berk PD, Wasserman LR, Fruchtman SM, et al. Treatment of polycythemia vera: a summary of clinical trials conducted by the polycythemia vera study group. In: Wasserman LR, Berk PD, Berlin NI, eds. Polycythemia Vera and the Myeloproliferative Disorders. Philadelphia: WB Saunders; 1995. pp. 166–94.
  19. McMullin MF, Bareford D, Campbell P, et al. Guidelines for the diagnosis, investigation and management of polycythaemia/erythrocytosis. Br J Haematol. 2005;130(2):174–95. doi: 10.1111/j.1365-2141.2005.05535.x.
  20. McMullin MF, Reilly JT, Campbell P, et al. Amendment to the guideline for diagnosis and investigation of polycythaemia/erythrocytosis. Br J Haematol. 2007;138(6):821–2. doi: 10.1111/j.1365-2141.2007.06741.x.
  21. McMullin MF. The classification and diagnosis of erythrocytosis. Int J Lab Hematol. 2008;30(6):447–59. doi: 10.1111/j.1751-553X.2008.01102.x.
  22. Shih LY, Lee CT. Identification of masked polycythemia vera from patients with idiopathic marked thrombocytosis by endogenous erythroid colony assay. Blood. 1994;83(3):744–8.
  23. Thiele J, Kvasnicka HM, Diehl V. Initial (latent) polycythaemia vera with thrombocytosis mimicking essential thrombocythaemia. Acta Haematol. 2005;113(4):213–9. doi: 10.1159/000084673.
  24. Thiele J, Kvasnicka HM. Diagnostic impact of bone marrow histopathology in polycythemia vera (PV). Histol Histopathol. 2005;20:317–28.
  25. Kvasnicka HM, Thiele J. Prodromal myeloproliferative neoplasms: The 2008 WHO classification. Am J Hematol. 2010;85(1):62–9. doi: 10.1002/ajh.21543.
  26. Barbui T, Thiele J, Gisslinger H, et al. Masked polycythemia vera (mPV): results of an international study. Am J Hematol. 2014;89(1):52–4. doi: 10.1002/ajh.23585.
  27. Barbui T, Thiele J, Carobbio A, et al. Discriminating between essential thrombocythemia and masked polycythemia vera in JAK2 mutated patients. Am J Hematol. 2014;89(6):588–90. doi: 10.1002/ajh.23694.
  28. Barbui T, Thiele J, Vannucchi AM, et al. Rethinking the diagnostic criteria of polycythemia vera. Leukemia. 2014;28(6):1191–5. doi: 10.1038/leu.2013.380.
  29. Barbui T, Thiele J, Carobbio A, et al. Masked polycythemia vera diagnosed according to WHO and BCSH classification. Am J Hematol. 2014;89(2):199–202. doi: 10.1002/ajh.23617.
  30. Chu D, Cho Y-U, Jang S, et al. Straightforward Identification of Masked Polycythemia Vera Based on Proposed Revision of World Health Organization Diagnostic Criteria for BCR-ABL1-Negative Myeloproliferative Neoplasms. Ann Lab Med. 2015;35(6):651–3. doi: 10.3343/alm.2015.35.6.651.
  31. Barbui T, Thiele J, Vannucchi AM, Tefferi A. Rationale for revision and proposed changes of the WHO diagnostic criteria for polycythemia vera, essential thrombocythemia and primary myelofibrosis. Blood Cancer J. 2015;5(8):e337. doi: 10.1038/bcj.2015.64.
  32. Harrison CN, Campbell PJ, Buck G, et al. United Kingdom Medical Research Council Primary Thrombocythemia 1 Study. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005;353(1):33–45.
  33. Gisslinger H, Gotic M, Holowiecki J, et al. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013;121(10):1720–8. doi: 10.1182/blood-2012-07-443770.
  34. Thiele J, Kvasnicka HM. Chronic myeloproliferative disorders with thrombocythemia: a comparative study of two classification systems (PVSG, WHO) on 839 patients. Ann Hematol. 2003;82(3):148–52.
  35. Ковригина А.М., Байков В.В. Патоморфологическая дифференциальная диагностика первичного миелофиброза. Учебное пособие для врачей-патологоанатомов. М., 2014. 64 с.
    [Kovrigina AM, Baikov VV. Patomorfologicheskaya differentsial’naya diagnostika pervichnogo mielofibroza. Uchebnoe posobie dlya vrachei-patologoanatomov. (Pathomorphological differential diagnosis of primary myelofibrosis. Manual for pathologists.) Moscow; 2014. 64 p. (In Russ)]
  36. Thiele J, Kvasnicka HM, Zankovich R, Diehl V. The value of bone marrow histology in differentiating between early stage polycythemia vera and secondary (reactive) polycythemias. Haematologica. 2001;86(4):368–74.
  37. Gianelli U, Iurlo A, Vener C. et al. The Significance of Bone Marrow Biopsy and JAK2V617F Mutation in the Differential Diagnosis Between the “Early” Prepolycythemic Phase of Polycythemia Vera and Essential Thrombocythemia. Am J Clin Pathol. 2008;130(3):336–42. doi: 10.1309/6BQ5K8LHVYAKUAF4.