Myelofibrosis
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Introduction
The Case of...
a simple case introducing clincial presentation and calling for a differential diagnosis to get students thinking.
Causes and Risk Factors
Primary myelofibrosis occurs following extensive collagen deposition by non-neoplastic fibroblasts in the marrow. The basis for this may be fibroblast growth factors, such as TGFb or PDGF, by neoplastic megakaryocytes.
Myelofibrosis can occasionally accompany the spent phase of proliferative conditions such as polycythemia vera or CML.
Metastatic carcinoma or infections with mycobacteria can also cause myelofibrosis.
Pathophysiology
Fibrosis progressively displaces hematopoietic elements, inculding stem cells, from the marrow. This leads to extramedullary hematopoiesis in the spleen, liver, and sometimes lymph nodes. In myelofibrosis, this hematopoiesis is disordered and ineffective, leading to cytopenias.
Signs and Symptoms
- history
- physical exam
History
Primary myelofibrosis often comes to attention due to either progressive anemia or marked splenic enlargement, producing a feeling of fullness in the upper left quadrant.
Increased mass of hematopoietic cells can increase metabolism, producing fatigue, weight loss, or night sweats.
High rates of cell turnover can induce hyperuricemia or secondary gout.
Physical Exam
Investigations
- lab investigations
- diagnostic imaging
Lab Investigations
Peripheral blood smears can display moderate to severe normochromic normocytic anemia with leukoerythroblastosis. White cell count is usually normal or reduced, but can be as high as 80-100 x 109/L.
Marrow biopsy must be done to diagnose myelofibrosis.
Early in myelofibrosis, the marrow is hypercellular due to increased maturing cells of all lineages. RBCs and granulocytes appear normal, but megakaryocytes are large, dysplastic, and abnormally clustered.
Marrow becomes progressively hypocellular and diffusely fibrotic, and late in the disease the marrow space can become converted to bone (osteosclerosis).
The spleen becomes larkedly enlarged, often up to 4000 gm, with subcapsular infarcts being common.
Peripheral blood smears reveal inappropriate release of nucleated erythroid cells and early granulocytes (leukoerythroblastosis), both from marrow distorted with fibrosis and from extramedullary sites. Tear drop cells (dacryocytes) can also be present due to RBC progenitor damage, and abdormally large platelets and basophilia can also result.
Diagnostic Imaging
Differential Diagnosis
Treatments
Consequences and Course
The course of the disease is difficult to predict.
Median survival is 3-5 years, with threats including infections, thrombosis, and hemorrhage due to platelet abnormalities.
In 5-20% of cases, transformation to AML occurs, potentially in extramedullary sites such as lymph nodes or soft tissues.
Resources and References
Topic Development
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