Bone Marrow - Inflammation

Granulomatous inflammation is sometimes observed in the bone marrow of rodents. This type of inflammation consists predominately of vacuolated or epithelioid macrophages that occur in relatively well-defined to organized aggregates (Figure 1 and Figure 2) or distinct compact granulomas (Figure 3 and Figure 4). Epithelioid macrophages have large amounts of eosinophilic cytoplasm and an oval to elongated nucleus with a dispersed chromatin pattern, several of which may fuse to form a multinucleated giant cell. Other cell types associated with granulomatous inflammation are lymphocytes, plasma cells, neutrophils, and fibroblasts, but they are not all constant features. Intracellularly, pigment (hemosiderin) or cholesterol clefts may be seen.

Occasionally, granulomatous inflammation is associated with lipid vacuoles that are usually smaller than the vacuoles of marrow adipocytes and are seen within macrophages and extracellularly. These lesions appear to be similar to the so-called lipid granulomas that have been described in human and canine bone marrow. Granulomatous inflammation may be associated with compound administration or infectious agents but is sometimes a nonspecific finding.

Suppurative inflammation, as occurs with bacterial sepsis, is rarely observed in the bone marrow of rodents involved in toxicologic studies. It consists of aggregates of nondegenerate and degenerate neutrophils (Figure 5 and Figure 6). Cell debris from the resident hematopoietic cells and the infiltrating leukocytes, as well as proteinaceous fluid, fibrin, and fewer lymphocytes, plasma cells, and macrophages, may also be present within the aggregates. Additional findings may include dilated sinusoids, interstitial edema, and/or hemorrhage.

In NTP studies, there are three other standard categories of inflammation: acute, chronic, and chronic-active. Briefly, in acute inflammation, the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. Lymphocytes predominate in chronic inflammation; lymphocytes also predominate in chronic-active inflammation, but there are also a significant number of neutrophils—both lesions may contain macrophages. These three other categories of inflammation are uncommon or are difficult to appreciate in the bone marrow because neutrophils are a resident population and lymphocytes are not easily identified—appearing very similar to erythroid precursors.