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Chapter 12: Anemia Resulting from Marrow Infiltration

DEFINITIONS

  • Anemia or pancytopenia associated with extensive marrow infiltration is called myelophthisic anemia.

  • Leukoerythroblastosis refers to the presence of nucleated red cells and myeloid precursor cells (eg, neutrophilic myelocytes) in the blood. These finding may be accompanied by schistocytes, teardrop-shaped red cells, and megakaryocytic fragments in patients with myelophthisic anemia.

ETIOLOGY AND PATHOGENESIS

  • Table 12–1 lists the conditions that cause marrow infiltration.

  • Invasion of blood vessels is the essential component of cancer cell metastasis and often involves the loss of E-cadherin.

  • In most cases, the marrow infiltration of metastatic cells 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 (eg, cytokines) and injury to the marrow microenvironment.

TABLE 12–1CAUSES OF MARROW INFILTRATION
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TABLE 12–1 CAUSES OF MARROW INFILTRATION

  1. Fibroblasts and Collagen

    1. Primary myelofibrosis (see Chap. 48)

    2. Fibrosis of other myeloproliferative neoplasms (see Chaps. 42, 43, 47)

    3. Fibrosis of hairy cell leukemia (see Chap. 57)

    4. Metastatic malignancies (eg, breast carcinoma)

    5. Sarcoidosis

    6. Secondary myelofibrosis with pulmonary hypertension

  2. Other Noncellular Material: Oxalosis

  3. Tumor Cells

    1. Carcinoma (eg, lung, breast, prostate, kidney, thyroid and neuroblastoma)

    2. Sarcoma

  4. Granulomas (inflammatory cells)

    1. Miliary tuberculosis

    2. Fungal infections

    3. Sarcoidosis

  5. Macrophages

    1. Gaucher disease (see Chap. 37)

    2. Niemann-Pick disease (see Chap. 37)

    3. Macrophage activation syndrome (MAS) (see Chap. 36)

  6. Marrow Necrosis

    1. Sickle cell disease (see Chap. 16)

    2. Solid tumor metastasis

    3. Septicemia

    4. Acute lymphoblastic leukemia (see Chap. 55)

    5. Arsenic therapy

  7. Failure of Osteoclast Development: Osteopetrosis

CLINICAL FEATURES

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

LABORATORY FEATURES

  • 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 rarely may be found on the blood film (carcinocythemia).

  • Marrow biopsy is the most reliable diagnostic procedure. Marrow aspiration may also be of value. Both are 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.

DIFFERENTIAL DIAGNOSIS

  • Nucleated red cells and leukocytosis can be seen in overwhelming sepsis, primary myelofibrosis, acute severe hypoxia (eg, acute congestive heart failure), thalassemia major, and severe hemolytic anemia.

  • Primary myelofibrosis (see Chap. 48) may be confused with metastatic disease with focal ...

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