Bone Marrow - Necrosis

Bone marrow necrosis is characterized by cytoplasmic vacuolization, indistinct cell borders, nuclear pyknosis, karyolysis, and karyorrhexis (Figure 1 and Figure 2). It is important to distinguish these changes from postmortem autolysis, which can have a similar appearance. With time, affected hematopoietic tissue is replaced with amorphous granular eosinophilic debris (Figure 3, Figure 4, and Figure 5) that should not be confused with fibrin deposition. In the acute stage, necrosis may be accompanied by acute inflammation or hemorrhage, while later stages or cases of subacute necrosis may be associated with increased numbers of macrophages in and around the necrotic area. Lesion distribution may be focal, multifocal, or diffuse and, in the case of ischemia, may be determined by the affected marrow blood supply. With time, necrotic marrow may eventually repopulate with hematopoietic cells, and in some cases, areas of previous necrosis may be replaced by fibrosis.

There are several known causes of bone marrow necrosis. It may occur as a direct result of compound administration (e.g.,cyclophosphamide) or may be secondary to severe infectious disease states (e.g., septicemia) or tissue ischemia caused by vascular injury, thrombosis, or vascular occlusion. Specific causes of the latter include neoplasia (e.g., tumor emboli, vascular occlusion), disseminated intravascular coagulation (thrombosis), and exposure to endotoxin (vascular injury). Necrosis caused by an obstruction of the blood supply (infarct) generally has well-delineated borders microscopically as a distinguishing feature (Figure 3 and Figure 4).

In a rat study to evaluate the effects of feed restriction on common toxicologic parameters, severe diet restriction (75% reduction) of only two weeks resulted in bone marrow necrosis and degeneration. Specific observations included vacuolated or necrotic-appearing stromal cells, necrosis of hematopoietic cells, remaining hematopoietic tissue <25% of concurrent controls, focal areas of hemorrhage, and readily observed emperipolesis of neutrophils within the megakaryocytes.