Fibrosis

Fibrosis of the bone marrow is caused by a reactive (non-clonal) proliferation of fibroblasts which may occur in association with a variety of neoplastic and non-neoplastic conditions (McCarthy, 1985). Fibrosis is usually of the reticulin type, as detected by silver stains, in the early stages, but it may progress to a collagen fibrosis that is detectable by trichrome stains (Fig. 6.1). Normally, reticulin staining is minimal but increases slightly with age (Beckman et al., 1990). Extensive marrow fibrosis is typically associated with a leukoerythroblastic reaction in the peripheral blood that is characterized by the presence of immature granulocytes (usually myelocytes and metamyelocytes), late-stage erythroblasts, and teardrop-shaped red blood cells and enlarged platelets. Diffuse fibrosis usually results in the inability to aspirate the bone marrow. Bone marrow fibrosis is common in chronic myeloproliferative disorders, and extensive fibrosis with peripheral blood leukoerythroblastosis is typical of chronic idiopathic myelofibrosis with myeloid metaplasia. Patchy areas of fibrosis are also seen with bone marrow involvement by mast cell disease (Horny et al., 1985), which may accompany other hematologic malignancies at diagnosis or relapse. Many other neoplasms involving the marrow, including some acute leukemias, malignant lymphomas, and metastatic tumors, result in focal or diffuse marrow fibrosis (Table 6.1).

Marrow fibrosis may also be associated with non-neoplastic conditions, especially inflammatory diseases, reparative changes, or metabolic disorders. Among these reactive cases, a particularly severe degree of fibrosis can be seen in patients with autoimmune conditions (Bass et al., 2001) (Fig. 6.2).