Benign extramedullary myeloid proliferations

Abstract

Extramedullary proliferations of bone marrow elements are infrequently encountered in routine pathology practice. On occasion, they can present diagnostic difficulties when seen in unusual or unanticipated sites. This review serves to cover aspects of underlying embryogenesis of myeloid elements, as well as sites and circumstance of benign proliferations of myeloid elements along with their occasional confusion with neoplastic myeloid proliferations. Benign proliferations associated with hematologic disorders and hematopoietic growth factors are discussed. Immunohistochemical evaluation of myeloid proliferations is considered as well. Modern Pathology (2007) 20, 405-415.

Extramedullary Hematopoiesis: A New Look at the Underlying Stem Cell Niche, Theories of Development, and Occurrence in Animals

“…16 However, high numbers of NRBCs, the presence of early or all stages of differentiation, and the presence of mitotic figures involving erythroid precursors would support erythroid EMH in cytologic specimens of spleen. Hepatic EMH is usually localized within the sinusoids (a site of fetal hematopoiesis) 78 but also is reported perisinusoidally, 64 in portal areas (eg, in acute myeloid leukemia), 113 and in larger portal veins. 64 Interestingly, hepatic EMH has been described in fine-needle aspiration specimens of transplanted livers in humans, which apparently have an altered microenvironment that is favorable for hematopoietic cell proliferation.…”

“…35,69,92,107 In neonatal mice, humans, dogs, cats, cattle, and pigs, persistent residual sites of fetal hematopoiesis are retained-mainly in spleen but also in liver and lymph nodes-that regress with growth and disappear prior to adulthood. 45,78,108,113 In mice (and, to a lesser extent, rats and hamsters), the spleen continues to play an active role in hematopoiesis throughout adulthood. 106 The shift of hematopoietic activity to spleen late in fetal development, with retention of minor residual hematopoiesis in other hemic organs (liver, lymph nodes), is consistent with the primary tissue distribution of EMH in adult animals.…”

“…However, EMH-and, therefore, presumably the requisite stem cell microenvironment-can occur in any tissue. 64,78 The activation of vascular niches appears to be important in establishing and sustaining hematopoietic activity in extramedullary sites such as the spleen and other tissues (and possibly neoplasms) in association with endothelium or vessels (Fig. 1).…”

“…78 Such bone marrow diseases include myelofibrosis, myelophthisis (replacement of hematopoietic bone marrow by abnormal tissue), myelodysplasia, drug or plant toxicities, radiation, immune-mediated disease, necrosis, infection, and metastatic neoplasia.…”

Implantable microenvironments to attract hematopoietic stem/cancer cells

“…The rationale of our approach was inspired by extramedullary hematopoiesis in which the body develops hematopoietic-inductive spaces for the ectopic growth of HSPCs during states of bone marrow failure. This compensatory process is a well-recognized clinical observation that occurs in a variety of nonosseous tissues including the spleen, liver, and skin (37)(38)(39). Although extramedullary sites do not have the same microenvironment as the endogenous bone marrow, they are assumed to retain the essential elements involved in HSPC migration and engraftment.…”