Chapter 12: Anemia Resulting from Marrow Infiltration

DEFINITIONS

Anemia or pancytopenia associated with extensive marrow infiltration is called myelophthisic anemia
Leukoerythroblastosis refers to anemia with schistocytes, teardrop-shaped red cells, nucleated red cells, megakaryocytic fragments, and immature myeloid cells (e.g., neutrophilic myelocytes) in the blood.

Table 12–1 lists the conditions that cause marrow infiltration.
Invasion is the essential component of cancer cell metastasis and often involves the loss of E-cadherin.
In most cases, the infiltration is focal, with surrounding areas of normal or hyperactive marrow.
Disruption of the microenvironment by infiltration with foreign cells leads to premature release of immature blood cells from the marrow.
Myelophthisic anemia is most often caused by humoral factors (e.g., cytokines) or injury to the marrow microenvironment.

TABLE 12–1CAUSES OF MARROW INFILTRATION

TABLE 12–1 CAUSES OF MARROW INFILTRATION

Fibroblasts and Collagen
1. Primary myelofibrosis (see Chap. 48)
2. Fibrosis of other myeloproliferative disorders (see Chaps. 43 and 44)
3. Fibrosis of hairy cell leukemia (see Chap. 57)
4. Metastatic malignancies
5. Sarcoidosis
6. Secondary myelofibrosis with pulmonary hypertension
Other Noncellular Material
1. Oxalosis
Tumor Cells
1. Carcinoma (e.g., lung, breast, prostate, kidney)
2. Sarcoma
Granulomas (inflammatory cells)
1. Miliary tuberculosis
2. Fungal infections
3. Sarcoidosis
Macrophages
1. Gaucher disease (see Chap. 38)
2. Niemann-Pick disease (see Chap. 38)
Marrow Necrosis
1. Sickle cell anemia (see Chap. 17)
2. Septicemia
3. Tumors
4. Arsenic therapy
Failure of Osteoclast Development
1. Osteopetrosis

Source: Williams Hematology, 8th ed, Chap. 44, Table 44–1, p. 614.

The clinical features of marrow infiltrative disorders are usually those of the underlying disease but the marrow replacement may also accentuate associated cytopenias.

Anemia is mild to moderate.
Leukocyte and platelet counts may be high or low depending on the nature and extent of marrow replacement.
Blood film may show anisocytosis and poikilocytosis, with schistocytes, teardrop cells, nucleated red cells, immature granulocytic cells, and megakaryocytic fragments.
Leukocyte alkaline phosphatase activity is normal or increased.
Clusters of cancer cells may rarely be found on the blood film (carcinocythemia).
Marrow biopsy is the most reliable diagnostic procedure. Marrow aspiration may also be of value. Aspiration or biopsy is more likely to be positive if taken from a tender area of bone.
Sites of marrow infiltration may be detected by technetium-99m sestamibi uptake, magnetic resonance imaging or fluorine-18 fluorodeoxyglucose with positron emission tomography.

Nucleated red cells and leukocytosis can be seen in overwhelming sepsis, primary myelofibrosis acute severe hypoxia (e.g., acute congestive heart failure), thalassemia major, and severe hemolytic anemia.
Primary myelofibrosis (see Chap. 48) may be confused with metastatic disease with focal fibrosis.
In the absence of a known primary site of cancer, it is important to rule out sarcoma of bone.

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