Extramedullary Hematopoiesis: Description, Causes and Risk Factors:
Extramedullary hematopoiesis (EMH) is defined as the presence of hematopoietic stem cells such as erythroid and myeloid lineage plus megakaryocytes in extramedullary sites like liver, spleen and lymph nodes and is usually associated with either bone marrow or hematological disorders. Mammary EMH is a rare condition either in human and veterinary medicine and can be associated with benign mixed mammary tumors.
EMH typically occurs in response to ineffective erythrocyte production or increased erythrocyte destruction. It is associated with severe congenital hemolytic anemias (e.g., thalassemia major, hereditary spherocytosis), polycythemia vera, lymphoproliferative disorders (e.g., myelofibrosis, chronic leukemia, lymphoma), and sickle cell disease. It has been proposed that mediastinal EMH results from paravertebral osseous extrusion of marrow elements through the thinned cortices of neighboring ribs and the vertebral column.
Extramedullary hematopoiesis is the production of blood elements outside the bone marrow cavity. Until 20 weeks of prenatal life, blood-cell production occurs in the yolk sac and in the reticuloendothelial (RE) system. Thereafter, the bone marrow is the primary site of hematopoiesis. Extramedullary hematopoiesis occurs in severe chronic anemia, which can arise from deficiency disorders such as vitamin B12 or folate deficiency or from disorders affecting pluripotent stem cells. The latter are classi?ed as: a) stem cell dysplasia, as in thalassemia, sickle cell hemoglobinopathy, and hereditary spherocytosis; b) stem cell failure resulting in aplastic anemia; c) uncontrolled stem cell proliferation, as in polycythemia vera; and d) malignant transformation and replacement, as in leukemia, lymphoma, multiple myeloma, and metastasis. Extramedullary hematopoiesis mainly involves the RE system (liver, spleen, and lymph nodes) but is also known to occur in every organ of the body, including the thyroid, prostate, pericardium, kidney, and lungs.
EMH occurs most often in the spleen and liver and occasionally in the lymph nodes. Involvement of other organs, such as the pleura, lungs, gastrointestinal tract, breast, skin, brain, kidneys, and adrenal glands, has been reported. Renal involvement can be parenchymal, intrapelvic, or perirenal. In the parenchymal type of renal involvement, the kidneys may be enlarged diffusely or have either single or multiple small focal lesions. Pelvic involvement is often an extension of parenchymal involvement but can be isolated, as was the case in our patient. In the perirenal type of renal involvement, a hypoattenuating mass or nodules are seen either around or encasing the kidneys. The intrapelvic and perirenal types of renal involvement are often bilateral but can also be unilateral.
Most often, it is microscopic and asymptomatic, but it can sometimes manifest as organomegaly and tumor-like masses. Rarely, it can cause spinal cord compression, pleural effusion, massive hemothorax, and respiratory failure. Intrathoracic EMH is a rare cause of paraspinal mass and should be differentiated from other common causes, such as neurogenic tumors, lymphoma, metastasis, paravertebral abscess, and lateral meningocele.
Bone changes are due to marrow expansion and reconversion. The latter is best seen by magnetic resonance imaging (MRI) examination. There is thinning of the cortices, underconstriction of long bones, and widening of ribs. The trabeculae are resorbed, giving the bones a coarse appearance. The tumor-like masses are usually slow-growing and do not cause bone erosion or pressure changes. Older, inactive masses may reveal iron deposits and/or fatty replacement and do not calcify. Radionuclide imaging with technetium-99m sulfur colloid may reveal extrahepatosplenic uptake of colloid. Fine-needle biopsy can con?rm the diagnosis.
Symptoms may include:
The diagnostic procedure of choice is magnetic resonance imaging (MRI) which characteristically shows an isointense mass with a high spinal intensity rim on T1-weighted images and a hyperintense mass on T2-weighted images.The diagnosis is based on strong clinical suspicion in the presence of diffuse bone marrow hyperplasia along with symmetric paraspinal and epidural masses. Most authors do not favor a tissue biopsy.
The role of Nuclear Medicine bone marrow imaging in theevaluation of EMH has not yet been clarified. Bone marrowimaging with indium 111 (111In) chloride (111InCl3) and99mTc-sulfur colloid has been useful in the evaluation of patientssuspected of having EMH. Bone marrow consistsof erythropoietic, myelopoietic, and reticuloendothelial elements.99mTc-sulfur colloid is used as a colloidal reticuloendothelialsystem imaging agent, and it is taken up by reticuloendothelialcells in bone marrow. InCl3 was initiallydeveloped as a pure erythropoietic agent to be used as a substitutefor iron, but reticuloendothelial cells also take upInCl3 when transferrin is saturated.
Treatment options for cord compression are surgery, radiation therapy, blood transfusions, hydroxyurea or various combinations thereof. Due to the extreme rarity of this condition, direct comparisons between various treatment modalities are not possible. Most reported cases of paraplegia due to EMH from any cause have been treated with surgical decompression with or without radiation therapy. The bias towards surgery in these cases is due to its immediate decompressing effect. Some authors also believe that radiation therapy may cause initial worsening of symptoms due to tissue edema. However, this can be easily prevented or controlled with concomitant steroid therapy. Hematopoietic tissue is extremely sensitive to radiation and low doses cause rapid shrinkage. In cases of EMH causing cord compression in thalassemia, improvement is clinically evident after an average of three fractions of radiotherapy and near complete recovery is generally observed by the end of treatment. Doses used have ranged from 750-3500 cGy (centigray). With these low doses, the only significant toxicity that may occur is a further decrease in blood cell counts which need to be frequently monitored. Excellent results have been obtained in cord compression due to EMH in thalassemia with radiotherapy alone. Recurrence rates of about 19% have been reported but these cases are amenable to treatment with further radiation.
In cases of paraplegia due to EMH, there seems to be a bias towards surgical decompression with the aim of causing rapid decompression. Surgery may be associated with various complications including bleeding, hemodynamic instability, spinal instability, etc. Radiation therapy is a simple, safe and effective approach for the treatment of spastic paraplegia consequent to spinal cord compression due to EMH. Fears of neurological deterioration due to radiation induced edema remain unfounded. Recovery of neurological function is rapid.
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