Identification of patients with myeloproliferative neoplasms (MPNs)

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An Interview With
Jamile M. Shammo, MD, FASCP, FACP
Associate Professor of Medicine and Pathology
Rush University Medical Center

Introduction to MPNs

MPNs are neoplastic disorders of hematopoietic stem cells, characterized by proliferation of myeloid lineages in the bone marrow. They include primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocythemia (ET).1,2

The importance of an accurate diagnosis

An accurate diagnosis for MPNs is important because proper identification of a disease entity has prognostic implications, allows determination of appropriate interventions to prevent complications, improves the patient’s quality of life, and ultimately, optimizes outcomes.3,4

Diagnostic considerations for MPNs

The diagnosis of MPNs is based on clinical, morphologic, and genetic information outlined by the World Health Organization (WHO).1,5 With regard to the diagnosis of MPNs:

  • It is important to rule out other conditions that could have a similar clinical presentation. The various MPNs have signs and symptoms that not only overlap with each other, but also overlap with those of nonneoplastic conditions.1,6-8 Autoimmune or inflammatory diseases, for example, can result in laboratory parameters that may be observed in MPNs, such as leukocytosis or thrombocytosis1,2
  • Advances in diagnostic testing offer the ability to identify molecular lesions, such as the JAK2 mutation, which aids in diagnosis of MPNs1,5,8
  • Evaluation of the bone marrow histology helps distinguish among conditions such as ET and prefibrotic MF1

Bone marrow histology of myelofibrosis

Photomicrograph of a bone marrow biopsy from a patient with PMF.
Photos courtesy of Jamile M. Shammo, MD, FASCP, FACP.
Reticulin stain showing an extensive fibrotis response.

The role of bone marrow biopsy

Bone marrow biopsy is an important tool for the identification and classification of MPNs.1 The results of a bone marrow biopsy help distinguish among overlapping diseases with similar clinical presentation, especially early in the disease process.1,9

  • For example, a bone marrow biopsy can help distinguish ET from prefibrotic MF.10 Both entities can present with isolated thrombocytosis.1,11 In biopsies from patients with ET, minimal or absent reticulin fibrosis, along with proliferation of mature and enlarged megakaryocytes with no dysplastic features, can be observed1,9
  • In prefibrotic MF, also characterized by minimal or no reticulin fibrosis, megakaryocytic clustering and atypia may be identified, along with neutrophilic proliferation1,9
  • The combination of the JAK2 V617F mutation and a bone marrow biopsy may be helpful in diagnosing early PV if a red cell mass determination is unavailable12

Bone marrow biopsy in disease progression

Understanding disease progression and the timing of bone marrow biopsy is important. ET and PV can result in a fibrotic phase that can be difficult to distinguish histologically from PMF.10 Therefore, patients with ET and PV who may be evolving to MF should undergo a bone marrow biopsy to confirm the presence of features consistent with disease progression to MF.10

According to the 2008 WHO diagnostic criteria for post–PV MF or post–ET MF, a bone marrow biopsy represents one of the two major criteria, both of which are required to make such a diagnosis.10 Key features include clustering of megakaryocytes, extent of dysplasia, and the presence of significant reticulin and/or collagen fibrosis.1,10 Thus, performing a bone marrow biopsy is important in making an appropriate initial diagnosis, as well as identifying disease progression and evolution to myelofibrosis.1,10

References
  1. Vardiman JW, Thiele J, Arber DA, et al. Blood. 2009;114(5):937-951.
  2. Emanuel RM, Dueck AC, Geyer HL, et al. J Clin Oncol. 2012;30(33):4098-4103.
  3. Kalala F, Mamara A, Ioannou M, et al. Hematol Rep. 2012;4(2):e12. doi:10.4081/hr.2012.e12.
  4. Bonicelli G, Abdulkarim K, Mounier M, et al. Br J Haematol. 2013;160(2):251-254.
  5. Barbui T, Barosi G, Birgegard G, et al. J Clin Oncol. 2011;29(6):761-770.
  6. Andrikovics H, Krahling T, Balassa K, et al. Haematologica. 2014;99(7):1184-1190.
  7. Geyer HL, Scherber RN, Dueck AC, et al. Blood. 2014;123(24):3803-3810.
  8. Vannucchi A, Guglielmelli P, Tefferi A. CA Cancer J Clin. 2009;59(3):171-191.
  9. Thiele J, Kvasnicka HM, Vardiman J, et al. Best Pract Res Clin Haematol. 2006;19(3):413-437.
  10. Barosi G, Mesa RA, Thiele J, et al; International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Leukemia. 2008;22(2):437-438.
  11. Tefferi A, Vardiman JW. Leukemia. 2008;22(1):14-22.
  12. Silver RT, Chow W, Orazi A, et al. Blood. 2013;122(11):1881-1886.