Bone Marrow Morphology in Myeloproliferative Neoplasms – Relevance in the Molecular Era
Keywords:
myeloproliferative neoplasm, LDH, bone marrow
Abstract
Background: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders. The mutation BCR-ABL is sine qua non for diagnosis of chronic myeloid leukemia and JAK2 V617F is present in majority of cases of polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MF). Recent 2016 classification consigns importance to BM morphology as mutations are not universal. Identification of specific features would aid diagnosis of JAK2V617F negative MPN. This study aims to assess utility of peripheral blood and bone marrow morphology in myeloproliferative neoplasms in correlation with BCR-ABL and JAK2V617F. Methods: A retrospective 7 years study of peripheral blood, bone marrow aspirate (BMA) and bone marrow biopsy (BMB) of 44 cases of myeloproliferative neoplasms with BCR-ABL and JAK2 V617F mutation analysis. Results: Forty four cases of MPNs including 24 (54.5%) cases of CML, 7 (15.9% ) cases of PV, 5 (11.3%) cases of MF, 3 (6.8%) cases of ET, and 5 (11.3%) cases of MPN-U. MPV and LDH were significantly higher in MF in comparison to PV and ET. Higher haemoglobin (Hb) and platelets were seen in PV and ET. Dwarf MKs with hypolobated, cloud like nuclei in CML (fig 1), large MKs with staghorn nuclei were seen in ET. normal sized MKs with cloud like hypolobated forms in PV(fig2) and cloud like atypical dysmorphic nuclei with dense clustering were seen in MF. Conclusion: Hb, mean platelet volume (MPV), and LDH in conjunction with MK morphology aids in the diagnosis of MPNs. These findings will enable accurate diagnosis in JAK2 negative MPNs and benefit low resource center.References
1. Campbell PJ, Green AR. The myeloproliferative disorders. N Engl J Med 2006; 335:2452-66
2. Arber AD, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM et al. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood 2016; 1:1-45
3. Swerdlow, S. H. et al. (eds). WHO classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edn, (International Agency for Research on Cancer, Lyon, France, 2017).
4. Koopmans SM, Bot FJ, Lam KH, Van Marion AMW, De Raeve H, Hebeda KM. Reproducibility of histologic classification in nonfibrotic myeloproliferative neoplasia. Am J Clin Pathol 2011;136:618-624.
5. Spivak JL, Silver RT. The revised World Health Organization diagnostic criteria for Polycythemia vera, Essential thrombocythemia, and Primary myelofibrosis: An alternative proposal. Blood 2008;112(2):231-9
6. Jameel A, Jamil SN. Clinico-pathological profile of chronic myeloid leukemia. JPMI 2006;20(3):235-238
7. Rumi, E, & Cazzola, M. (2017). Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms. Blood,129(6), 680-692.
8. Lelie Der JV, Borne Dem AK. Platelet volume analysis for differential diagnosis of thrombocytosis. J Clin Pathol 1986;39:129-133
9. Schelkar R, Florea A, Urean L, Patiu M, Petrov L. Differential diagnosis between chronic granulocytic leukemia, polycythemia vera and essential thrombocythemia using micro- and ultrastructural measurement data performed at the level of MKs. Romanian Journal of Morphology and Embryology 2009;50(4):595-603
10. Olteanu AL, Mihaila RG, Catana AC, Flucus O, Bus C, Mihalache M. Platelet indices in Philadelphia-negative chronic myeloproliferative neoplasms. Revista Romana de Medicina de Laborotor 2015;23(2):169-177
11. Thiele JM, Kvasnicka HM. Diagnosis of Polycythemia vera based on bone marrow pathology. Curr Hematol Rep 2005; 4(3):218-23
12. Philip AB, Campbell PJ , Green AR. Comparision of different criteria for the diagnosis of primary myelofibrosis reveals limited clinical utility for measurement of serum lactate dehydrogenese. Hematologica 2010 Nov; 95(11): 1960–1963
13. Hattori N, Fukuchi K, Nakashima H, Maeda T, Adachi D, Saito B et al. Megakaryocyte and platelet unction in polycythemia vera and essential thrombocythemia patients with JAK2 V617F mutation. Int J Hematol 2008; 88:181-188
14. Michiels JJ, Kutti J, Stark P, Bazzan M, Gugliotta L, Marchioli R et al. Diagnosis, pathogenesis and treatment of the myeloproliferative disorders essential thrombocythemia, polycythemia vera and essential megakaryocytic granulocytic metaplasia and myelofibrosis. Neth J Med 1999; 54(2):46-62
15. Michiels J, Thiele J. Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis (agnogenic myeloid metaplasia). Int J Hematol 2002; 76(2):133-45
16. Mesa RA, Silverstein MN, Jacobsen SJ, Wollan PC and Tefferi A. Population based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: An Olmsted county study, 1976-1995. Am J Hematol 1999;61:10-5
17. Vytrva N, Stacher E, Regitnig P, Zinke-Cerwenka W, Hojas S, Hubmann E et al. Megakaryocytic Morphology and Clinical Parameters in Essential Thrombocythemia, Polycythemia Vera, and Primary Myelofibrosis With and Without JAK2 V617F. Arch Pathol Lab Med 2014; 138;1203-09
18. Marchiolli R, Finazzi G, Landolfi R, Kutti J, Gisslinger H, Patrono C et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol 2005;23:2224-32
19. Thiele J, Kvasnicka HM, Zankovich R, Diehl V. Relevance of bone marrow features in the differential diagnosis between essential thrombocythemia and early stage idiopathic myelofibrosis. Haematologica 2000; 85(11):1126-34
20. Lan HF, Fang ZH, Zhang Y, Wang XY, Xue F, Zhang L et al. Clinical analysis of 438 patients with essential thrombocythemia. Zhonghua Xue Ye XUE Za Zhi 2008; 29(9):587-91
21. Thiele J, Kvasnicka HM, Zankovich R and Diehl V. Early-stage idiopathic (primary) Myelofibrosis – current issues of diagnostic features. Leuk Lymphoma 2002; 43(5):1035-41
22. Anastasi J, Vardiman JW. Chronic myelogenous leukemia and the Chronic myeloproliferative diseases. In: Knowles DM, editor. Neoplastic Hematopathology. 3rd ed. Philadelphia: Lippincott Williams and Wilkins; 2014. p. 1108-1136
23. Lichtman MA, Tefferi A. Primary Myelofibrosis. In: Kaushansky K, Lichtman MA, Beutler E, Kipps TJ, Seligsohn U, Prachal JT, editor. Williams Hematology. 8th ed. China: McGraw-Hill; 2010. p. 1381-1402
24. Holme S, Simmonds M, Ballek R, Murphy S. Comparative measurements of platelet size by coulter counter, microscopy of blood smears, and light transmission studies. J Lab Clin Med 1981;97:610-22
25. Small BM, Bettigole RE. Diagnosis of myeloproliferative disease by analysis of platelet volume distribution. Am J Clin Pathol 1981;76:685-91
26. Holme S, Murphy S. Studies on the platelet density abnormality in myeloproliferative disease. J Lab Clin Med 1984;103:373-83
27. Rudzki Z, Kawa R, Okon K, Szczygiel E, Stachura J. Objective, planimetry-based assessment of MKs histological pictures in Philadelphia-chromosome-negative chronic myeloproliferative disorders: a perspective for a valuable adjunct diagnostic tool. Virchows Archiv 2005; 448(1):59-67
28. Gianelli U, Lurlo A, Vener C. The significance of bone marrow biopsy and JAK2 V617F mutation in the differential diagnosis between the “early” prepolycythemic phase of polycythemia vera and essential thrombocythemia. Am J Clin Pathol 2008; 130(3):336-342
29. Gianelli U, Vener C, Rafaniello Raviele P, Alessia Moro, Savi F, Annaloro C et al. Essential thrombocythemia or chronic idiopathic myelofibrosis? A single center study based on hematopoietic bone marrow histology. Leuk Lymphoma 2006; 47(9):1774-81
2. Arber AD, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM et al. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood 2016; 1:1-45
3. Swerdlow, S. H. et al. (eds). WHO classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edn, (International Agency for Research on Cancer, Lyon, France, 2017).
4. Koopmans SM, Bot FJ, Lam KH, Van Marion AMW, De Raeve H, Hebeda KM. Reproducibility of histologic classification in nonfibrotic myeloproliferative neoplasia. Am J Clin Pathol 2011;136:618-624.
5. Spivak JL, Silver RT. The revised World Health Organization diagnostic criteria for Polycythemia vera, Essential thrombocythemia, and Primary myelofibrosis: An alternative proposal. Blood 2008;112(2):231-9
6. Jameel A, Jamil SN. Clinico-pathological profile of chronic myeloid leukemia. JPMI 2006;20(3):235-238
7. Rumi, E, & Cazzola, M. (2017). Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms. Blood,129(6), 680-692.
8. Lelie Der JV, Borne Dem AK. Platelet volume analysis for differential diagnosis of thrombocytosis. J Clin Pathol 1986;39:129-133
9. Schelkar R, Florea A, Urean L, Patiu M, Petrov L. Differential diagnosis between chronic granulocytic leukemia, polycythemia vera and essential thrombocythemia using micro- and ultrastructural measurement data performed at the level of MKs. Romanian Journal of Morphology and Embryology 2009;50(4):595-603
10. Olteanu AL, Mihaila RG, Catana AC, Flucus O, Bus C, Mihalache M. Platelet indices in Philadelphia-negative chronic myeloproliferative neoplasms. Revista Romana de Medicina de Laborotor 2015;23(2):169-177
11. Thiele JM, Kvasnicka HM. Diagnosis of Polycythemia vera based on bone marrow pathology. Curr Hematol Rep 2005; 4(3):218-23
12. Philip AB, Campbell PJ , Green AR. Comparision of different criteria for the diagnosis of primary myelofibrosis reveals limited clinical utility for measurement of serum lactate dehydrogenese. Hematologica 2010 Nov; 95(11): 1960–1963
13. Hattori N, Fukuchi K, Nakashima H, Maeda T, Adachi D, Saito B et al. Megakaryocyte and platelet unction in polycythemia vera and essential thrombocythemia patients with JAK2 V617F mutation. Int J Hematol 2008; 88:181-188
14. Michiels JJ, Kutti J, Stark P, Bazzan M, Gugliotta L, Marchioli R et al. Diagnosis, pathogenesis and treatment of the myeloproliferative disorders essential thrombocythemia, polycythemia vera and essential megakaryocytic granulocytic metaplasia and myelofibrosis. Neth J Med 1999; 54(2):46-62
15. Michiels J, Thiele J. Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis (agnogenic myeloid metaplasia). Int J Hematol 2002; 76(2):133-45
16. Mesa RA, Silverstein MN, Jacobsen SJ, Wollan PC and Tefferi A. Population based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: An Olmsted county study, 1976-1995. Am J Hematol 1999;61:10-5
17. Vytrva N, Stacher E, Regitnig P, Zinke-Cerwenka W, Hojas S, Hubmann E et al. Megakaryocytic Morphology and Clinical Parameters in Essential Thrombocythemia, Polycythemia Vera, and Primary Myelofibrosis With and Without JAK2 V617F. Arch Pathol Lab Med 2014; 138;1203-09
18. Marchiolli R, Finazzi G, Landolfi R, Kutti J, Gisslinger H, Patrono C et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol 2005;23:2224-32
19. Thiele J, Kvasnicka HM, Zankovich R, Diehl V. Relevance of bone marrow features in the differential diagnosis between essential thrombocythemia and early stage idiopathic myelofibrosis. Haematologica 2000; 85(11):1126-34
20. Lan HF, Fang ZH, Zhang Y, Wang XY, Xue F, Zhang L et al. Clinical analysis of 438 patients with essential thrombocythemia. Zhonghua Xue Ye XUE Za Zhi 2008; 29(9):587-91
21. Thiele J, Kvasnicka HM, Zankovich R and Diehl V. Early-stage idiopathic (primary) Myelofibrosis – current issues of diagnostic features. Leuk Lymphoma 2002; 43(5):1035-41
22. Anastasi J, Vardiman JW. Chronic myelogenous leukemia and the Chronic myeloproliferative diseases. In: Knowles DM, editor. Neoplastic Hematopathology. 3rd ed. Philadelphia: Lippincott Williams and Wilkins; 2014. p. 1108-1136
23. Lichtman MA, Tefferi A. Primary Myelofibrosis. In: Kaushansky K, Lichtman MA, Beutler E, Kipps TJ, Seligsohn U, Prachal JT, editor. Williams Hematology. 8th ed. China: McGraw-Hill; 2010. p. 1381-1402
24. Holme S, Simmonds M, Ballek R, Murphy S. Comparative measurements of platelet size by coulter counter, microscopy of blood smears, and light transmission studies. J Lab Clin Med 1981;97:610-22
25. Small BM, Bettigole RE. Diagnosis of myeloproliferative disease by analysis of platelet volume distribution. Am J Clin Pathol 1981;76:685-91
26. Holme S, Murphy S. Studies on the platelet density abnormality in myeloproliferative disease. J Lab Clin Med 1984;103:373-83
27. Rudzki Z, Kawa R, Okon K, Szczygiel E, Stachura J. Objective, planimetry-based assessment of MKs histological pictures in Philadelphia-chromosome-negative chronic myeloproliferative disorders: a perspective for a valuable adjunct diagnostic tool. Virchows Archiv 2005; 448(1):59-67
28. Gianelli U, Lurlo A, Vener C. The significance of bone marrow biopsy and JAK2 V617F mutation in the differential diagnosis between the “early” prepolycythemic phase of polycythemia vera and essential thrombocythemia. Am J Clin Pathol 2008; 130(3):336-342
29. Gianelli U, Vener C, Rafaniello Raviele P, Alessia Moro, Savi F, Annaloro C et al. Essential thrombocythemia or chronic idiopathic myelofibrosis? A single center study based on hematopoietic bone marrow histology. Leuk Lymphoma 2006; 47(9):1774-81
Published
2018-09-27
Issue
Section
Original Article
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access at http://opcit.eprints.org/oacitation-biblio.html).
