Diagnostic Considerations

Primary myelofibrosis must be differentiated from conditions in which marrow fibrosis is a secondary development. For example, in patients with carcinoma or lymphoma, bone marrow involvement may be associated with marrow fibrosis, which reverses after effective treatment of the underlying disease. Similarly, in histoplasmosis and tuberculosis, marrow fibrosis may result in granulomatous involvement of the bone marrow.

Performing testing for bcr:abl gene rearrangements is important to exclude chronic myelogenous leukemia (CML). JAK2V617F mutation can be detected in approximately 50–60% of patients with primary myelofibrosis.^{[21, 22, 23]}

World Health Organization diagnostic criteria for primary myelofibrosis include three major criteria and four minor criteria. Diagnosis requires meeting all three major criteria and at least two minor criteria.^[6]The major criteria are as follows:

Megakaryocyte proliferation and atypia accompanied by reticulin and/or collagen fibrosis or, in the absence of reticulin fibrosis, the megakaryocyte changes accompanied by increased marrow cellularity, granulocytic proliferation and oftenndecreased erythropoiesis (ie, pre-fibrotic primary myelofibrosis)
Not meeting WHO criteria for chronic myeloid leukemioa, polycythemia vera, myelodysplastic syndrome, or other myeloid neoplasm
Demonstration of JAK2V617F or other clonal marker, or no evidence of reactive bone marrow fibrosis

Minor criteria are as follows:

Leukoerythroblastosis
Elevated serum lactate dehydrogenase level
Anemia
Palpable splenomegaly

The International Working Group for Myeloproliferative Neoplasm Research and Treatment (IWG-MRT) has established diagnostic criteria for post–polycythemia vera myelofibrosis (PPV-MF) and post–essential thrombocythaemia myelofibrosis (PET-MF).^[24]For both disorders, cases must meet the following two criteria:

Documentation of a previous diagnosis of PV or PET, as defined by the 2008 WHO criteria
Bone marrow fibrosis grade 2–3 (on a 0–3 scale) or grade 3–4 (on a 0–4 scale)

In addition, cases must meet at least two further criteria. For PVV-MF, the additional criteria are as follows:

Anemia or sustained loss of requirement for phlebotomy in the absence ofcytoreductive therapy
Leukoerythroblastic peripheral blood picture
Increasing splenomegaly - Either an increase in palpable splenomegaly of ≥5 cm from the left costal margin or the appearance of a newly palpable splenomegaly
Development of one or more constitutional symptoms (>10% weight loss in 6 months, night sweats, unexplained fever >37.5°C)

For PET-MF, the additional criteria are as follows:

Anemia and a decrease in hemoglobin level of 2 g/dL or more from baseline
Leukoerythroblastic peripheral blood picture
Increasing splenomegaly - Either an increase in palpable splenomegaly of ≥5 cm from the left costal margin or the appearance of a newly palpable splenomegaly
Development of more than one constitutional symptoms (>10% weight loss in 6 months, night sweats, unexplained fever >37.5°C)
Increased lactate dehydrogenase concentration

Differential Diagnoses

Workup

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Media Gallery

Primary myelofibrosis. Peripheral smear shows teardrop red blood cells (RBCs) and a leukoerythroblastic picture with nucleated RBC precursors and immature myeloid cells. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.
Bone marrow biopsy from a patient with primary myelofibrosis shows extensive fibrosis. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.
Reticulin stain on a bone marrow biopsy from a patient with primary myelofibrosis shows extensive fibrosis. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.
Extramedullary hematopoiesis in the spleen of a patient with primary myelofibrosis. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.

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Author

Asheesh Lal, MBBS, MD Physician, Department of Internal Medicine, Lexington Medical Center

Asheesh Lal, MBBS, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Acknowledgements

Author: Asheesh Lal, MBBS, MD, Physician, Department of Internal Medicine, Lexington Medical Center.

Asheesh Lal is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology.

Editors: Karen Seiter, MD, Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College; Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference; Emmanuel C Besa, MD, Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University.

Primary Myelofibrosis Differential Diagnoses

Diagnostic Considerations

Differential Diagnoses

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