Extramedullary Hematopoietic Tissue Research Articles

Compressive Myelopathy Caused by Arachnoid Cyst and Extramedullary Hematopoietic Tissue in a Patient with Thalassemia Major

AbstractThalassemias, inherited diseases of hemoglobin synthesis, are characterized by the presence of deficient hemoglobin chains that deposit in red blood cells, inducing hemolytic anemia. Extramedullary hematopoiesis represents a compensatory picture that usually affects the liver, the spleen, and lymph nodes. The involvement of the epidural space with spinal cord compression is extremely rare. Our objective was to describe the case of RMS, 31 years old, male, β-thalassemia major carrier, admitted with 2-month progressive paraparesis and urinary retention due to medullary compression by extramedullary hematopoietic tissue and thoracic arachnoid cyst, and to discuss therapeutic options. Magnetic resonance imaging (MRI) showed an extensive intraspinal and extramedullary lesion with homogeneous contrast enhancement of T3-T11 in addition to a T1-T3 cystic lesion isointense to cerebrospinal fluid (CSF). After the presumed diagnosis of spinal cord compression by proliferative hematopoietic tissue, a 10-session fractional radiotherapy treatment was immediately performed. After the radiotherapy treatment, the neurological deficits of the patient persisted despite the excellent image response with almost complete disappearance of the intraspinal mass. However, the MRI showed a persistent T1-T3 cystic lesion with significant mass effect on the spinal cord. The patient was submitted to microsurgery for total resection of this cystic lesion. In the postoperative period, the patient improved his sphincter control and motor deficits. Medullary compression by extramedullary epidural hematopoiesis is a rare complication in thalassemic patients and may be treated with surgery and/or radiotherapy. There are successful cases with the exclusive use of radiotherapy, especially in extensive lesions.

Alpha fetoprotein (AFP) participates in the build up of hematopoietic cells in the early embryonic stage: an abortion case observation

BackgroundAt the 3rd week of human embryo, some cell clumps are formed by the hyperplasia of mesenchymal cells at the germ layer of the yolk sac wall. These cell clumps are known as blood islands. The cells in the center of the blood islands further develop into primitive blood cells, such as hematopoietic stem cells. The blood island in the yolk sac further develops into the extramedullary hematopoietic tissue in 1 week at the 3rd to 4th week.Case presentationA 32-year-old pregnant woman who missed menstruation for 42 days discovered that her pregnancy required an abortion. The tissue collected after the abortion was a piece of gray-yellow and villus-like intrauterine tissue of a size of approximately 4 cm × 3 cm × 1.3 cm. The paraffin section stained with hematoxylin and eosin and observed under the light microscope showed a visible small embryo tissue in the early placental tissue. In the embryonic tissue, a large amount of extramedullary hematopoietic tissue was present, including myeloid, erythroid and megakaryocytic cells. The extramedullary hematopoietic cells were located in the blood vessels or naive liver sinus, were positive for alpha fetoprotein (AFP) and were without lymphocytes. The erythrocytes consisted of a large number of nucleated red blood cells. In addition, a neural tube and cystic structure were found. The final pathological diagnosis was as follows: Early embryonic tissue with a cystic structure formation in the embryo. After medical abortion the pregnant woman recovered well, without complications.ConclusionsOur case illustrates that AFP is an important structural protein of nucleated erythrocytes and myeloid hematopoietic cells, suggesting that it may participate in the build up of nucleated erythrocytes and myeloid hematopoietic cells. Furthermore, our case suggests that nucleated red blood cells can be detected from the 42nd day of pregnancy by a peripheral blood sample from the mother.

Detection of Extramedullary Hematopoietic Tissue in a Patient with Beta-Thalassemia Major on Tc99m-Sestamibi Parathyroid Scintigraphy.

A 50-year-old man with beta-thalassemia major underwent Tc-99m sestamibi parathyroid scintigraphy due to elevated parathyroid hormone and calcium serum levels. Single-photon emission computed tomography imaging of neck and thorax revealed a parathyroid adenoma, as well as increased tracer uptake in a paraspinal region in the right hemithorax, where X-ray and computed tomography of the thorax had shown previously a mass compatible with extramedullary hematopoietic tissue.

Extramedullary hematopoiesis presenting as spontaneous recurrent chronic subdural hematoma: Case report and review of the literature

Abstract Chronic subdural hematoma (CSDH) tends to be associated with elderly male, non-significant head trauma and anticoagulation therapy. The origin of the hematoma is believed to be a tear in a bridging vein. A CSDH rarely develops acute symptoms, but is rather characterized by progressive neuro-cognitive impairment and/or focal neurological deficits. Head trauma can be identified as the cause of a CSDH in about 60% of cases. We describe an unusual case of a spontaneous non-traumatic of CSDH in a middle aged female patient. This CSDH demonstrated a more therapy resistant behavior and more extensive surgical evacuation was necessary. The final pathology report revealed extramedullary hematopoietic tissue.

Pathogenesis ofFrog Virus 3(Ranavirus,Iridoviridae) Infection in Wood Frogs (Rana sylvatica)

Wood frogs ( Rana sylvatica) are highly susceptible to infection with Frog virus 3 (FV3, Ranavirus, Iridoviridae), a cause of mass mortality in wild populations. To elucidate the pathogenesis of FV3 infection in wood frogs, 40 wild-caught adults were acclimated to captivity, inoculated orally with a fatal dose of 104.43 pfu/frog, and euthanized at 0.25, 0.5, 1, 2, 4, 9, and 14 days postinfection (dpi). Mild lesions occurred sporadically in the skin (petechiae) and bone marrow (necrosis) during the first 2 dpi. Severe lesions occurred 1 to 2 weeks postinfection and consisted of necrosis of medullary and extramedullary hematopoietic tissue, lymphoid tissue in spleen and throughout the body, and epithelium of skin, mucosae, and renal tubules. Viral DNA was first detected (polymerase chain reaction) in liver at 4 dpi; by dpi 9 and 14, all viscera tested (liver, kidney, and spleen), skin, and feces were positive. Immunohistochemistry (IHC) first detected viral antigen in small areas devoid of histologic lesions in the oral mucosa, lung, and colon at 4 dpi; by 9 and 14 dpi, IHC labeling of viral antigen associated with necrosis was found in multiple tissues. Based on IHC staining intensity and lesion severity, the skin, oral, and gastrointestinal epithelium and renal tubular epithelium were important sites of viral replication and shedding, suggesting that direct contact (skin) and fecal-oral contamination are effective routes of transmission and that skin tissue, oral, and cloacal swabs may be appropriate antemortem diagnostic samples in late stages of disease (>1 week postinfection) but poor samples to detect infection in clinically healthy frogs.

Paraplegia due to Extramedullary Hematopoietic Tissue Compression of Thoracic Thecal Sac in a Patient with Thalassemia Treated Successfully with Surgical Decompression: A Case Report

Spinal cord compression due to extramedullary hematopoiesis (EMH) is a rare complication of thalassemia and generally presents as paraparesis with sensory impairment. Complete paraplegia is extremely rare in EMH due to thalassemia although it is known to occur in polycythemia vera and sickle cell anemia. Cases presenting with paraparesis have been treated with either surgery or radiotherapy with equal frequency and efficacy. Almost all reported cases with paraplegia have been treated with surgery with or without radiation therapy. As paraplegia secondary to EMH is rare, there is no consensus on treatment. We hereby report a case of thalassemia with paraplegia treated successfully with surgery. Treatment options for cord compression include primarily blood transfusion, surgery, and radiation therapy. Because of the extreme rarity of this condition, direct comparisons between various treatment modalities are not possible. The bias toward surgery is due to its immediate decompressing effect. EMH in thalassemia has also been treated with transfusion therapy with the rationale that correction of anemia would downregulate erythropoietin and lead to reversal of EMH. However, improvement with blood transfusion alone is usually incomplete and slow. Our patient did not improve after adequate blood transfusion and hence underwent surgical decompression after which he showed rapid and complete neurologic recovery. Therefore, we conclude that surgical decompression of EMH tissue has to be considered early in patients presenting with paraplegia if symptom shows no improvement after adequate blood transfusion.

Extramedullary Haematopoiesis Causing Spinal Cord Compression in a Thalassemia Intermedia Patient

The thalassemias are a heterogenous group of inherited disorders of hemoglobin (Hb) synthesis characterized by a lack of or decreased /defective synthesis of globin chains. The name Mediterranean anemia, which Whipple introduced, is misleading because the condition can be found in any part of the world. In ?-thalassemia, ?-globin chain synthesis is reduced, whereas in ?-thalassemia, ?-globin chain synthesis is defective. Their clinical severity varies widely, ranging from asymptomatic forms to severe or even fatal entities. Like most anemias, erythropoietin production and erythropoiesis is increased in thalassemia causing erythroid marrow hyperplasia as well as extramedullary haematopoiesis which is a common compensatory mechanism for chronic anemia found in patients with hemoglobinopathies such as thalassemia, sickle cell anemia, and hereditary spherocytosis. These patients are usually asymptomatic. Extramedullary hematopoiesis (EMH) usually manifests in the liver, spleen, kidneys and as paravertebral masses. Extramedullary hematopoietic tissue occurring within the spinal canal and causing cord compression is an unusual but well-described entity. Total surgical excision is usually not feasible because of the diffuse spread of extramedullary hematopoietic tissue and the possibility of recurrence, but acute neurological impairment does require emergency surgery. Extramedullary hematopoiesis is radiosensitive so radiation therapy is widely accepted as a very effective mode of therapy. Repeated blood transfusion and cytostatic agents are also recommended for treatment.We report a case of a 35-year-old man with underlying beta thalassemia intermedia who developed pain in lower back and progressive paresthesia and weakness of both lower limbs due to multifocal extramedullary epidural hematopoietic tissue occurring within the spinal canal with compression over the cord. Nepalese Journal of Radiology; Vol. 2; Issue 2; July-Dec. 2012; 81-85 DOI: http://dx.doi.org/10.3126/njr.v2i2.7692

The Spine in β-Thalassemia Syndromes

Literature review. To present a comprehensive overview of spinal involvement in patients with β-thalassemia, aiming to orient the spinal surgeon to these potentially disabling complications. β-thalassemia, an inherited disorder of hemoglobin synthesis, is the most common monogenetic disease worldwide. Patients with thalassemia major (TM) suffer a severe anemia that requires regular blood transfusions for survival and iron chelation therapy to control transfusional iron overload. Thalassemia intermedia is a phenotype of thalassemia with a milder course and anemia, wherein most patients remain transfusion independent. Spinal involvement related to disease course and treatment is common in patients with thalassemia syndromes, yet it has not been constructively reviewed in the literature. Potentially relevant studies were identified from an electronic search of MEDLINE (1966 to the second week of May 2010). In patients with TM, genetic and acquired risk factors lead to osteoporosis, pathologic fractures of the spine, and back pain. Osteoporosis in TM patients is progressive; thus, early diagnosis and treatment are recommended. Bisphosphonates are relatively safe and effective in this patient population. Characteristic intervertebral disc degeneration is also seen in patients with TM who have evidence of severe iron overload or those who receive the subcutaneous iron chelator deferoxamine. Spinal asymmetry and overt scoliosis are common in patients with TM. The prognosis seems favorable, with many patients showing spontaneous resolution without the need for intervention. In patients with thalassemia intermedia, ineffective erythropoiesis drives extramedullary hematopoietic tissue formation, which is mostly evident on magnetic resonance imaging. Paraspinal involvement is of greatest concern because of the associated spinal cord compression. Several treatment options have been described, including transfusion therapy, laminectomy, radiotherapy, and the use of fetal hemoglobin-inducing agents that decrease the hematopoietic drive. Current knowledge supports that spinal involvement in patients with β-thalassemia is common and diverse yet still requires further prospective evaluation.

Paraplegia treated with blood transfusion

Extramedullary hematopoiesis is a compensatory response in patients with thalassemia and other chronic anemia and can result in compressive myelopathy, if untreated. Two young adults with history of thalassemia presented with symptoms of spinal cord compression. Presence of extramedullary hematopoiesis was confirmed by magnetic resonance imaging. Both the patients were treated with blood hypertransfusion and showed improvement clinically and radiologically. Although there are various options in the management of such condition, including decompression surgery and radiation treatment, hypertransfusion can be very effective even in severe compression of the spinal cord. Hypertransfusion should be tried as the first line of management in patients with thalassemia presenting with compressive myelopathy to decrease the bulk of extramedullary hematopoietic tissue.

Beta-Thalassemia Presenting as an Acute Neurological Complication: A Case Report

Beta-thalassemia is an inherited defect in the rate of synthesis of one or more beta-globin chains of hemoglobin resulting in anemia, hemolysis and ineffective erythropoeisis. Extramedullary hematopoietic tumors may develop in extreme cases of dyserythropoiesis. Acute neurological complications in patients with beta-thalassemia have been reported in association with cerebral ischemia, spinal cord fractures and compression from extramedullary hematopoietic tumors. However extramedullary hematopeietic tumors in the setting of acute blood loss leading to neurological complications have never been reported. We report this case of a 27-year-old woman with beta-thalassemia who presented with acute neurological deficit during immediate postoperative period of cesarean section associated with significant drop in hemoglobin. The Magnetic Resonance Imaging of the thoracic and lumbosacral spine revealed compressive intra-spinal and para-spinal extra-medullary hematopoietic tissue. Patient’s symptoms improved dramatically with conservative management. doi:10.4021/jmc133w

Activated STAT1 and STAT5 transcription factors in extramedullary hematopoietic tissue in a polycythemia vera patient carrying the JAK2 V617F mutation

The somatic V617F mutation in the Janus kinase (JAK) 2 gene, which causes a valine to phenylalanine substitution at position 617, has recently been found in the majority of patients with polycythemia vera and in many cases with essential thrombocythemia or idiopathic myelofibrosis. Here, we report on a 76-year-old female patient presenting with JAK2V617F-positive polycythemia vera and a pelvic mass with extramedullary hematopoiesis. Immunohistochemistry demonstrated tyrosine phosphorylation of JAK2 kinase as well as STAT1 and STAT5 transcription factors. However, only a minority of the total STAT1 pool was tyrosine-phosphorylated and, in contrast to its unphosphorylated counterpart, phospho-STAT1 clearly showed nuclear accumulation. While megakaryotes expressed virtually no phospho-STAT1, phosphorylated STAT5 was mainly restricted to megakaryocytes and rarely detected in non-megakaryocytes. Our data suggest that dysregulated STAT signal pathways are engaged in extramedullary hematopoiesis in polycythemia vera.

SPINAL CORD COMPRESSION DUE TO EPIDURAL EXTRAMEDULLARY HAEMATOPOIESIS IN ACUTE MYELOID LEUKEMIA: MRI FINDINGS

A 32 year-old-man with a history of acute myeloid leukemia on remission for one year presented with sudden back pain, weakness and reduced sensation in both legs, and urinary incontinence that had progressed over one weak. MRI of thoracic and lumbar spine was performed on a 1.5 T system using a body coil due to his neurological symptoms. T1-weighted sequence (TR/TE: 617/15 mse) and T2-weighted sequence (TR/TE: 4300/110 mse) on sagittal and axial images with 3 mm slice thickness were used. Gadolinium enhanced T1-weighted axial images were obtained. Magnetic resonance imaging (MRI) demonstrated spinal cord compression by epidural extramedullary hematopoietic tissue. Spinal epidural space is a very rare site for extramedullary hematopoiesis.

An Unusual Presacral Mass: Extramedullary Hematopoiesis

Presacral masses are a rare finding in the adult patient, confronting the physician with diagnostic and therapeutic challenges. We present an unusual case of a symptomatic presacral mass caused by extramedullary hematopoietic tissue in a thalassemic patient and review the unique aspects of this entity.

An etiologic model proposing that sporadic adult-onset carcinoma is extramedullary hematopoiesis

This model proposes that primary carcinomatous tumors and almost all metastases are extramedullary hematopoietic tissue formed to compensate for reduced hematopoietic activity in the bone marrow. These marrow lesions are currently considered to be metastatic in origin, but as fibrosis and sclerosis are identifying features they are here equated to myelofibrosis. Myelofibrotic marrow is characterized by an increase in the number and size of vascular sinusoids. The increased blood flow suggested by this morphology, and observed in myelofibrosis patients, causes a rise in marrow pressure which may trigger the fibrosis. Specific carcinoma morphologies are equated to stages in endochondral bone and marrow formation and, as such, cancer cell identity varies with morphology. For example, infiltrating carcinomas of the breast consist of collagen and mucoid secreting cells in single file formation. This morphology is equated to the cartilagenous stage of marrow formation, when mesenchymal stem cells proliferate and differentiate into chondroblasts. In this model "infiltrating" cells arise in situ from stem cells located in the connective tissue. Tubular breast carcinoma, with its single layer of osteoblast-like carcinoma cells encircling small lumens and long branching tubules, is equated to the trabecular stage of marrow formation during which osteoblasts surround small pieces of calcified cartilage and begin secreting osteoid that will form the trabeculae. Lobular carcinoma in situ consists of cancer cell clusters separated by narrow clear spaces that, under high magnification, appear vascular. This morphology is equated to hematopoietic tissue in which primitive hematopoietic cells lie between anastomosing sinusoids. Similar cartilagenous, trabecular and hematopoietic morphologies can be found in carcinomatous tumors of most organs, but the nomenclature is variable. The hematopoietic carcinomas share numerous features with hematopoietic tissue including a structure composed of intermingled normoxic and hypoxic regions and a metabolism characterized by elevated levels of glycolysis. They also contain similar proportions of clonal cells. If this model is correct it necessitates a change in the treatment of carcinoma. If cancer cells are not the enemy, but desperately needed immature blood cells, and the medical problem is not the presence of tumors, but the inefficiency of this extramedullary hematopoietic tissue, then treatment should focus on increasing marrow hematopoiesis. As evidence suggests that the marrow lesion is the result of increased hydrostatic pressure this could be done by reducing blood volume. One way to accomplish this may be through the ingestion of ephedrine, as it is hypothesized to increase vascular tone.

Hematopoietic Remodeling in Interferon-γ–Deficient Mice Infected With Mycobacteria

Control of intracellular bacterial infections requires interferon-gamma (IFN-gamma) both for establishing a Th1 T-cell response and for activating macrophages to kill the bacteria. Exposure of mice deficient in IFN-gamma to mycobacterial infection produces an immune response characterized by a Th2 T-cell phenotype, florid bacterial growth, and death. We report here that IFN-gamma-deficient mice infected with mycobacteria also undergo a dramatic remodeling of the hematopoietic system. Myeloid cell proliferation proceeds unchecked throughout the course of mycobacterial infection, resulting in a transition to extramedullary hematopoiesis. The splenic architecture of infected IFN-gamma-deficient mice is completely effaced by expansion of macrophages, granulocytes, and extramedullary hematopoietic tissue. These features coincide with splenomegaly, an increase in splenic myeloid colony-forming activity, and marked granulocytosis in the peripheral blood. Systemic levels of cytokines are elevated, particularly interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF). These results suggest that in addition to its central role in cellular immunity, IFN-gamma may be a key cytokine in coordinate regulation of immune effector cells and myelopoiesis. This model should be valuable for deciphering the cross-talk between the immune response and hematopoiesis during bacterial infection and for improving our understanding of the mechanisms that control chronic infections.

Combined Radiotherapeutic and Surgical Management of a Spinal Cord Compression by Extramedullary Hematopoiesis in a Patient with Hemoglobin E Beta-Thalassemia

A 22-year-old male with a history of hemoglobin E beta zero-thalassemia presented with thoracic spinal cord compression due to extramedullary hematopoietic tissue in the epidural space. Following decompressive laminectomy, this epidural mass was irradiated to 20.4 Gy in 12 fractions. The patient made a complete recovery from his neurological symptoms following treatment. Follow-up radiographs showed significant reductions in size of the extradural tumor. Results from this case supported by review of the literature suggest that radiation therapy, with or without decompressive surgery, is an effective therapy in treatment of patients with spinal cord compression due to epidural extramedullary hematopoietic tissue.

Massive Hemothorax Associated with Intrathoracic Extramedullary Hematopoiesis Involving the Pleura

Intrathoracic extramedullary hematopoiesis rarely involves the pleura and is usually asymptomatic. We report a 73-year-old woman with myelofibrosis who had pleural involvement with extramedullary hematopoietic tissue that produced a massive hemothorax. Before the diagnosis of extramedullary hematopoietic tissue was established, sclerosis with tetracycline was attempted, which accelerated pleural bleeding and required surgical evacuation. The bleeding was ultimately controlled by low-dose radiation therapy.

Spinal extradural hematopoiesis in adolescents with thalassemia

Extramedullary hematopoietic tissue occurring within the extramedullary space and causing cord compression is an unusual occurrence in childhood and adolescence, and only four cases have been reported during the first two decades of life. We had the opportunity to treat a 16-year-old girl and a 14-year-old boy with paraparesis secondary to extradural extramedullary hematopoiesis. Findings in these cases are discussed, and an attempt is made to stress once more the possibility of congenital hematopoietic rests as the origin of such hyperplastic tissue. The various modes of therapy are discussed and related literature is reviewed.

Roentgen findings in extramedullary hematopoiesis.

ROENTGEN FINDINGS IN EXTRAMEDULLARY HEMATOPOIESISPAUL ROSS, M.B., B.S. and WENDE LOGAN, M.D.Audio Available | Share

Roentgen Manifestations of Thoracic Extramedullary Hematopoiesis

Intrathoracic masses of extramedullary hematopoietic tissue present a diagnostic problem for the clinician and the radiologist. The diagnosis should be considered especially in cases of spherocytic anemia. The pathologic findings in bone marrow and roentgenographic changes in bones due to marrow replacement or abnormal proliferation of marrow are important indicators of the diagnosis. The roentgenographic demonstration of well defined masses in the paravertebral gutter, enlarged spleen, bone changes, and a history of a severe anemia are a tetrad toward a preoperative diagnosis of extramedullary hematopoiesis. Three cases of extramedullary hematopoiesis presenting as masses in the thorax are described. Two of the cases demonstrate mediastinal masses in association with congenital hemolytic anemia. The third case was in association with myelosclerosis and the extramedullary hematopoietic mass compressed the thoracic spinal cord. This is the first known case with such a manifestation to be reported.