Bone Marrow - Fibrosis

Bone marrow fibrosis is a lesion characterized by an increase of reticulin fibers or reticulin and collagen fibers, and/or proliferating fibroblasts. It is a secondary change associated with such disorders as inflammation, bone marrow necrosis, bone marrow injury, and disorders of myeloproliferation (e.g., acute myeloid leukemia) and lymphoproliferation (e.g., lymphoma). Fibrosis can be focal, multifocal, or diffuse and range from a mild increase in fibroblasts, with the presence of scattered, loose eosinophilic collagen/reticulin fibers, to dense fibrosis tissue (Figure 1, Figure 2, and Figure 3). Modest increases in reticulin fibers can be difficult to appreciate but can be confirmed with a silver impregnation technique, such as Gomori stain. Collagen fibers are identified as eosinophilic fibers that may be in bundles and are confirmed with the use of a trichrome stain (e.g., Mallory’s or Masson’s).

While it is not clear in rodent toxicity or preclinical studies if there is a need to distinguish among fibrosis types, much has been recently learned in humans regarding this topic. In humans, increased reticulin fibers are associated with many benign and malignant conditions, while increased collagen is prominent in late stages of myeloproliferative diseases or following metastasis to the bone marrow. The amount of reticulin staining in the bone marrow often has no correlation with disease severity, while increases in collagen staining are associated with more severe disease and a poorer prognosis. In addition, reticulin fibrosis is more likely to reverse than is collagen fibrosis after removal or successful treatment of the causative disorder.

Although much about the pathophysiology of (secondary) bone marrow fibrosis remains to be elucidated, it is known that cytokines from bone marrow macrophages, megakaryocytes, and platelets appear to be necessary for fibrosis to occur. These include platelet-derived growth factor and transforming growth factor-β. Additionally, fibrosis has been induced in mice injected with high amounts of recombinant thrombopoietin.