Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + DEFINITIONS Download Section PDF Listen +++ ++ 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. + ETIOLOGY AND PATHOGENESIS Download Section PDF Listen +++ ++ 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 Graphic Jump LocationTABLE 12–1CAUSES OF MARROW INFILTRATIONView Table||Download (.pdf) TABLE 12–1 CAUSES OF MARROW INFILTRATION Fibroblasts and Collagen Primary myelofibrosis (see Chap. 48) Fibrosis of other myeloproliferative disorders (see Chaps. 43 and 44) Fibrosis of hairy cell leukemia (see Chap. 57) Metastatic malignancies Sarcoidosis Secondary myelofibrosis with pulmonary hypertension Other Noncellular Material Oxalosis Tumor Cells Carcinoma (e.g., lung, breast, prostate, kidney) Sarcoma Granulomas (inflammatory cells) Miliary tuberculosis Fungal infections Sarcoidosis Macrophages Gaucher disease (see Chap. 38) Niemann-Pick disease (see Chap. 38) Marrow Necrosis Sickle cell anemia (see Chap. 17) Septicemia Tumors Arsenic therapy Failure of Osteoclast Development Osteopetrosis Source: Williams Hematology, 8th ed, Chap. 44, Table 44–1, p. 614. + CLINICAL FEATURES Download Section PDF Listen +++ ++ 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 Download Section PDF Listen +++ ++ 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. + DIFFERENTIAL DIAGNOSIS Download Section PDF Listen +++ ++ 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. + TREATMENT AND PROGNOSIS Download Section PDF Listen +++ ++ The goal of treatment is to manage the underlying disease. Marrow infiltration may not always adversely affect the response to treatment of malignant disease. However, usually short-term survival is seen in patients with cancer metastatic to marrow. Patients with breast and prostate cancer metastatic to marrow have longer survival on average than those with lung cancer. ++ For a more detailed discussion, see Archana Agarwal and Josef T. Prchal: Anemia Associated with Marrow Infiltration. Chap. 44, p. 613 in Williams Hematology, 8th ed.