Approach Considerations

Laboratory testing

Varying degrees of peripheral blood abnormalities may be present at diagnosis, and deviations from the normal ranges may be moderate or severe. Patients likely have one or more of the following changes: normocytic anemia, thrombocytopenia, or leukocytosis (with left shift).

Review of the peripheral blood smear is key and likely reveals several abnormalities. Dacryocytes (teardrop-shaped red blood cells) are common. Nucleated red blood cells and aniso-poikilocytosis are also frequently seen. Myelocytes and promyelocytes are present in small proportions in most patients; blasts may also be seen. Platelets may be large or unusually shaped. In rare cases, the platelet count may be elevated.^{[11, 36]}

Endocrinological testing may be indicated. Hyperparathyroidism (primary or secondary to vitamin D deficiency) has been described. In addition, hypoparathyroidism is sometimes observed. Bony abnormalities, including osteosclerosis, are reported.

In the appropriate clinical setting, a rheumatological evaluation is needed. Perform antinuclear antibody (ANA) testing because myelofibrosis occasionally complicates systemic lupus erythematosus. A low neutrophil alkaline phosphatase (LAP) score suggests chronic myeloid leukemia; a high level suggests chronic inflammation, as might be expected with systemic lupus erythematosus.

Megakaryocytes are present in the systemic venous blood. A characteristic finding is increased CD34⁺ cells in circulating blood.

Blood urea nitrogen (BUN)/creatinine testing should be performed to rule out renal dysfunction, which may suggest renal osteodystrophy as an underlying diagnosis.

A Coombs (direct antiglobulin) test can be ordered because myelofibrosis has been observed in association with autoimmune hematologic phenomena.

A purified protein derivative (PPD) test should also be performed because myelofibrosis has been described as a complication of tuberculosis.

Consider chromosomal analysis in any child with onset before age 2 years as trisomy 21, which is associated with marrow fibrosis, may be undiagnosed.

Imaging studies

Abdominal ultrasonography or computed tomography (CT) scanning often reveals hepatosplenomegaly, with or without adenopathy. Nephromegaly has also been described (secondary to myeloid metaplasia).^{[37, 38]}

Magnetic resonance imaging (MRI) scanning, if performed because of particular symptoms (eg, headache), often shows diagnostic changes in marrow signal. Osteosclerosis is a common finding. Also seen is marked radiodensity of superior and inferior margins of the vertebral body; this finding is known as “sandwich vertebrae.” Periosteal reactions are also seen.

Positron emission tomography (PET) scanning can identify osteosclerosis.

Other diagnostic considerations

The workup of children with myelofibrosis frequently leads to a diagnosis of acute myeloid (specifically, megakaryoblastic) leukemia or, less commonly, myelodysplastic syndrome.

Conditions to consider in the differential diagnosis include, along with those listed previously, osteopetrosis, gray platelet syndrome, and rickets.

Bone Marrow Aspirate and Biopsy

The biopsy demonstrates increased silver (reticulin) staining. Moreover, the aspirate is frequently hypocellular or shows insufficient cellularity ("dry"). An increased number of megakaryocytes that may be morphologically abnormal supports a diagnosis of primary myelofibrosis. Increased blasts are often observed, but the presence of more than 25% blasts is, by definition, more consistent with acute myelofibrosis.

Cytogenetic studies in myelofibrosis ensure diagnostic exclusion of myeloid neoplasms that are sometimes associated with bone marrow fibrosis (eg, BCR-ABL1).^[18]

Abnormalities may support a diagnosis of myelodysplasia (eg, monosomy 7) or acute megakaryoblastic leukemia (eg, t[1;21][p13;q13]).

Marrow biopsies typically exhibit marked fibrosis with pockets of cellularity that have fibroblasts and atypical megakaryoblasts. Less commonly, hyperplasia with predominance of megakaryocytic and erythroid precursors is observed, with only a slight increase in reticulin staining. The latter pattern is more typical of (adult) agnogenic myeloid metaplasia with myelofibrosis (AMMM) and may be observed in an older pediatric patient.

Treatment & Management

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Media Gallery

Photomicrograph of a peripheral smear of a patient with agnogenic myeloid metaplasia (idiopathic myelofibrosis) shows findings of leukoerythroblastosis, giant platelets, and few teardrop cells.

of 1

Author

Trisha Simone Natanya Tavares, MD Contract Clinical Hematologist and Oncologist, Department of Pediatric Hematology and Oncology, Presbyterian Healthcare; Volunteer Hematology/Oncology Physician, St Vincent de Paul Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

J Martin Johnston, MD Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Hematology/Oncology, The Children's Hospital at Memorial University Medical Center; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

J Martin Johnston, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, International Society of Paediatric Oncology

Disclosure: Nothing to disclose.

Chief Editor

Cameron K Tebbi, MD Director, Children's Cancer Research Group Laboratories

Cameron K Tebbi, MD is a member of the following medical societies: International Society of Pediatric Oncology

Disclosure: Nothing to disclose.

Acknowledgements

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children's Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.