Extramedullary hematopoiesis

Extramedullary hematopoiesis (EMH or sometimes EH

Physiologic EMH occurs during embryonic and fetal development; during this time the main site of fetal hematopoiesis are liver and the spleen.

Pathologic EMH can occur during adulthood when physiologic hematopoiesis can't work properly in the bone marrow and the

Definitive hematopoiesis differs from the primitive phase through the production of hematopoietic stem cells.^[8] The formation of these cells occurs in the AGM (aorta-gonad-mesonephros) later in development. This occurs by conversion of endothelial cells to hematopoietic stem and progenitor cells (HPSCs) - a process called endothelial-to-hematopoietic transition or EHT. These hematopoietic stem cells are further closely associated with endothelial cells throughout human life. Later, they migrate to the fetal liver where the majority of physiologic EMH (extra-medullary hematopoiesis) takes place. They can also migrate to the spleen and lymph nodes where hematopoiesis can occur, but to a lesser degree. Finally, once the bone marrow has developed, they migrate there.^[9]

Pulmonary hematopoiesis

Pulmonary hematopoiesis also appears to play an important role in adults.^[5] In comparison to the bone marrow, where trilineage hematopoiesis occurs, the lungs preferentially contribute to the production of platelets through a resident population of megakaryocytes. This is supported by studies showing that blood leaving the lungs has more platelets and fewer progenitor cells than blood entering the lungs. It has been seen that in cases of severe thrombocytopenia, pulmonary megakaryocytes migrate out of lungs into the bone marrow, where they help to replenish the depleted bone marrow population.^{[citation needed]}

Pathologic EMH

In adults, the majority of hematopoiesis occurs in the bone marrow. Significant production in any other organ is usually the result of a pathological process. When red blood cell (RBC) numbers are low, the body induces a homeostatic mechanism aimed to increase the synthesis of RBCs, typically via the production of erythropoietin. If the loss of RBCs becomes severe, hematopoiesis will occur in the extramedullary spaces outside the bone.^[10]

The cause of pathologic EMH can be one of many hematological diseases, such as

Sites of EMH can be widespread however, most common localizations are in the spleen, liver, and lymph nodes. Other manifestations occur in the thymus, heart, breast, prostate, broad ligaments, kidneys, adrenal glands, pleura, retroperitoneal tissue, skin, peripheral and cranial nerves, and the spinal canal.[10]^[11]

Spleen

During the postnatal period, the spleen becomes a frequent site of EMH whereas, during the embryonic stages of hematopoiesis, it is only a minor factor. Despite the hypoxic/acidic conditions of the splenic microenvironment, supplied with a legion of macrophages making it inhospitable for HSCs, EMH usually occurs within the red pulp. Among the various organs associated with EMH, the spleen offers a unique site for evaluation of hematopoietic stem cell (HSC)/niche interactions.^[12][11]

Liver

It is normal for infants have hepatic EMH as they are developing up until roughly 5 weeks of age.^[13] On the other hand, hepatic EMH in adults can indicate a pathological state. This includes transplantation, hepatic tumors, hepatic disorders, or sepsis. Hepatoblastoma, adenomas and hepatocellular carcinomas can also lead to EMH in adults.^[14][15] Additionally, EMH is often observed within the hepatic sinusoids.

Lymph nodes

EMH in the lymph nodes is usually associated with underlying hematopoietic neoplasms. Myeloproliferative neoplasms (MPNs) tend to result in EMH.^[16] If EMH is identified in the lymph nodes of an adult or infant, a hematologic evaluation, including blood cell counts, peripheral blood smear and potentially a bone marrow biopsy should be performed.^[11]

Other sites

The following tissues may also be associated with EMH: