Extramedullary Hematopoesis Research Articles

F-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Appearance of Extramedullary Hematopoesis in a Case of Primary Myelofibrosis.

A 44-year-old female with known primary myelofibrosis presented with shortness of breath. High Resolution Computed Tomography thorax revealed large heterogeneously enhancing extraparenchymal soft tissue density mass involving bilateral lung fields. F-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography revealed mildly FDG avid soft tissue density mass with specks of calcification involving bilateral lung fields, liver, and spleen. Subsequent histopathologic evaluation from the right lung mass was suggestive of extramedullary hematopoesis.

Poster 359 Role of Acute Inpatient Rehabilitation in Spinal Cord Injury due to Extramedullary Hematopoesis in Beta-Thalassemia: A Case Report

Poster 359 Role of Acute Inpatient Rehabilitation in Spinal Cord Injury due to Extramedullary Hematopoesis in Beta-Thalassemia: A Case Report

Significance of teardrop cells in peripheral blood smears

Abstract Teardrop erythrocytes (syn. dakryocytes) play a key role in the evaluation of peripheral blood smears in patients with anemia, especially as part of the “leukoerythroblastic picture”. Teardrop-shaped red blood cells can be seen in a wide range of diseases that lead to bone marrow fibrosis, which is often accompanied by extramedullary hematopoesis. The differential diagnoses encompass primary myelofibrosis (PMF), myelodysplastisc syndromes during the late course of the disease, rare forms of acute leucemias and myelophtisis caused by metastatic carcinoma. Rarely, MF associated with post-irradiation, toxins, autoimmune diseases, metabolic conditions, inborn hemolytic anemias, iron-deficient anemia or β-thalassaemia can lead to the formation of teardrops as visualized on peripheral blood smears.

Leveraging random forests for interactive exploration of large histological images.

The large size of histological images combined with their very challenging appearance are two main difficulties which considerably complicate their analysis. In this paper, we introduce an interactive strategy leveraging the output of a supervised random forest classifier to guide a user through such large visual data. Starting from a forest-based pixelwise estimate, subregions of the images at hand are automatically ranked and sequentially displayed according to their expected interest. After each region suggestion, the user selects among several options a rough estimate of the true amount of foreground pixels in this region. From these one-click inputs, the region scoring function is updated in real time using an online gradient descent procedure, which corrects on-the-fly the shortcomings of the initial model and adapts future suggestions accordingly. Experimental validation is conducted for extramedullary hematopoesis localization and demonstrates the practical feasibility of the procedure as well as the benefit of the online adaptation strategy.

Extramedullary hematopoiesis in the adrenal: Case report and review of literature

Extramedullary haematopoiesis (EMH) is common in the spleen, liver and lymph nodes, or in para osseus sites. EMH in the adrenal is rare, with fewer than 10 cases reported. We report the case of a 40-year-old male who underwent laparoscopic adrenalectomy for an incidentally detected adrenal mass. The histology showed extramedullary hematopoesis. In patients with a known history of haemolytic anaemia, an enlarged adrenal gland in an asymptomatic individual could represent extramedullary haematopoesis. A confirmatory biopsy would be all that is necessary to avoid adrenalectomy.

Spinal cord compression secondary to extramedullary hematopoiesis in a dog

An 11-year-old spayed female Siberian Husky was evaluated because of a 2-week history of progressive paraparesis. Results of neurologic examination were consistent with a T3-L3 myelopathy. There were no abnormalities on CBC, and hypercalcemia was noted on serum biochemical analysis. Several hypoechoic splenic nodules were evident on abdominal ultrasonography, and results of fine-needle aspiration cytology were consistent with splenic extramedullary hematopoiesis (EMH). Two compressive, extradural masses in the dorsal epidural space of the thoracolumbar region of the spinal cord were seen on MRI images. A dorsal laminectomy was performed to remove the extradural spinal masses. Results of histologic examination of tissue samples were consistent with EMH. Following surgery, clinical signs of paraparesis resolved, and there was no recurrence of the masses 24 months after surgery. Extramedullary hematopoesis should be considered as a differential diagnosis in dogs in which results of diagnostic imaging indicate a epidural mass. In human patients, spinal EMH usually occurs secondary to an underlying hematologic disease, but it can also occur spontaneously. Treatment options reported for humans include surgical decompression, radiation therapy, chemotherapy, and blood transfusion. The dog of this report responded favorably to surgical decompression and was clinically normal 2 years after surgery.

Radiographic features in a rare case of sphenoid sinus extramedullary hematopoeisis in sickle cell disease

Sickle cell disease is a common hematologic disorder with some uncommon clinical manifestations. While there are an abundance of described disease manifestations of the head and neck, extramedullary hematopoesis within the paranasal sinuses is exceedingly rare. Here, we present a case of a young boy with known sickle cell disease who presented to hospital with headaches of new onset. Imaging demonstrated an expansile mass lesion occupying the sphenoid sinus and on biopsy was found to be active hematopoetic bone marrow. A description of the case and review of subtle but characteristic radiographic findings follow.

Splenectomy In Patients with MDS

AbstractAbstract 1879Splenectomy in patients with MDS is a treatment option that is beeing applied very rare [Steensma D., et al, Leuk Res.,2003; Bourgeosis E., et al, Leukemia, 2001]. There are anecdotal reports with very few patients demonstrating its efficacy. In most cases splenectomy was indicated for MDS patients with immune related thrombocytopenia.Here we would like to report the results of 33 splenectomies in patients with MDS who have been treated in our Center during 1994–2010. Within this period of follow-up totally 155 patients were diagnosed with different forms of MDS, 35% of them presenting with hypoplasia. The MDS treatment algorithm in our Center incorporates splenectomy as one of the options for pts with hypoplastic forms of MDS with bone marrow blast count less than 10%, refractory to initial cyclosporin A treatment or refractory to transfusions. Among patients who were splenectomised there were 20 females, 13 males with a median age of 40 years (range 18–74). Median time from diagnosis to splenectomy was 12 months (range 4–107). By WHO-classification there were 2 patients with RA, 22 – with RCMD, 2 – with MDS and del (5q), 6 - with RAEB, 1 - with AML after MDS. Cytogenetic analysis was available in 32 cases, and karyotype was normal in 15 patients (47%).The most common abnormalities were: del (5q) - 3, del (20q) - 2, trisomy 8 - 2, tetrasomy 8 - 1, monosomy 7 - 2, complex karyotype - 4. Bone marrow biopsy revealed hypoplasia in 25 patients (75%), myelofibrosis – in 7 (21%). The median WBC count was 2,6*109/L (range 0,6-8,7), hemoglobin 6,9 g/dL (47-119) and platelets 26*109/L (6-170). 27 pts (82%) were RBC transfusion dependent, 22 (67%) - platelets transfusion dependent. 13 pts had received immunosuppression therapy (ATG, cyclosporine A) before splenectomy, 2 - cytotoxic chemotherapy, 3 - decitabine. The majority of splenectomies were done by laparoscopic method - 26 (79%), in one case the convertion was done. In all cases we performed liver biopsy. Postoperative complications (hemorrhage) occurred in 1 patient but there were no deaths due to operation. One death occurred in 7 days after splenectomy due to fulminant progression to AML. Median spleen weight was 180 gms (range 70–930). Median intraoperative blood loss was 250 ml (range 50–9350).Histology was available in 30 patients. Extramedullary hematopoesis was revealed in 3 cases (10%), blast infiltration - in 2 (7%), massive lymphoid infiltration was detected in 5 cases and in one patient in was proved to be clonal (marginal zone lymphoma, MZL). Hemosiderin depositions in the macrophages were seen in half of the cases -16 (53%). One case was characterized by granulomatosis in spleen and liver with negative immunohistohemical staining to Mycobacteria tuberculosis.Splenectomy lead to sustained improvement of cytopenias in 16 cases (48%): decreased transfusion dependence in 14 (42%) and transfusion independence in 2 (6%).After splenectomy 5 patients were followed by “wait and see” approach, 17 continued with immunosuppressive therapy (ATG,CyA), 3 patients were treated with cytotoxic chemotherapy, 1 – with decytabine, 2 received EPO, 1- danazol, 2 - iron chelation therapy, 2 – only transfusions therapy. We did not noticed the infections rate augmentation after splenectomy. Transformation to AML was registered 6 (18%) at median 6 months (0,3 -9). 13 splenectomized patients (39%) died at a median 12 months (range 0,3-84) and the main death reasons were: AML progression, aplasia deterioration followed by infections and hemorrhage. 20 patients are alive with a median follow-up after splenectomy 33 months (2-108).Analysis of our 15-years study data give us a confidence to conclude that splenectomy still may be an adequate option for distinct forms of MDS (hypoplastic forms with bone marrow blast count less than 10%, refractory to initial immunosupressive treatment or refractory to transfusions), producing cytopenia improvement in half of the patients with decreasing transfusion dependance also in half of the patients, sometimes bringing a clear diagnosis (MZL). The mechanism of action is not very clear but we can speculate that splenectomy removes the “cell-destroying” organ, deminishes immune pathways of cytopenias due to large lymphoid compartment deletion, provides the resustainment of sensitivity to immunosupressive agents. Disclosures:No relevant conflicts of interest to declare.

Osteopetrosis due to Homozygous Chloride Channel ClCN7 Mutation Mimicking Metabolic Disease with Haematological and Neurological Impairment

We report on the fatal clinical course of a 3 year old male Turkish patient suffering from osteopetrosis caused by a homozygous mutation in the chloride channel gene ClCN7 with developing pancytopenia and severe neurological impairment. Hepatosplenomegaly due to extramedullary hematopoesis, severe transfusion-dependent anemia and growth failure initially suggested metabolic or oncologic disorder. Particular haematological parameters like tear drop cells basophilic punctation of the polymorphonuclear cells in the absence of haemolysis caused the diagnostic X-ray investigations of the skull and vertebral column. Raised serum creatinkinase-BB isoenzyme and genetic testing were in line with the diagnose of osteopetrosis at an age of 2(1/2) years. Osteopetrosis is a rare but considerable differential diagnose for unclarified change in haematopoetic cell lines combined with severe neurological symptoms mimicking metabolic or haematological disease. Because of this rare disease a consensus protocol for diagnostics, treatment and follow up of patients suffering from osteopetrosis is recently worked out from the European Group of Blood and Marrow Transplantation (EBMT) and the European Society for Immundeficiencies (ESID) to build up a central registry for this disease (available by ansgar.schulz@uniklinik-ulm.de).

Chronic idiopathic myelofibrosis with myeloid metaplasia presenting as refractory ascites

Chronic idiopathic myelofibrosis (CIM) with myeloid metaplasia is a myeloproliferative disorder characterized by leukoerythroblastosis, tear drop erythrocytes, extra-medullary hematopoesis (EMH), and varying degree of myelofibrosis. CIM, presenting as refractory ascites secondary to peritoneal hematopoesis, is extremely rare with only six adult cases reported in literature. This is a report of a child with CIM presenting as refractory ascites as a consequence of EMH in the peritoneum. The patient was treated with intermittent hydroxyurea with favorable response over 3 weeks. The patient was thereafter lost to follow up.

HYDROPS FETALIS IN A NEONATE WITH DOWN SYNDROME, TRANSIENT MYELOPROLIFERATIVE DISORDER AND HEPATIC FIBROSIS

Transient myeloproliferative disorder is a self limiting disorder characterized by leukocytosis with the presence of megakaryoblasts in the peripheral blood and bone marrow, anemia, thrombocytopenia, and organomegaly. It occurs in approximately 10% of newborn infants with Down syndrome. Hepatic fibrosis is seen in the severe form of transient myeloproliferative disorder with Down syndrome that is characterized by diffuse intralobular sinusoidal fibrosis and extramedullary hematopoesis. We describe a patient with hydrops fetalis, Down syndrome, and transient myeloproliferative disorder. We suggest that patients with the severe form of transient myeloproliferative disorder should be examined for hepatic fibrosis.

Toxicology and pharmacology of rho‐iso‐alpha acids (RIAA), hop‐derived inhibitors of prostaglandin E2 formation

Rho-iso-alpha acids (RIAA)—derived from hops (Humulus lupulus) strobiles by supercritical CO2 extraction and sodium borohydride reduction—is used as a flavoring agent in the beer industry. Recently, it was demonstrated that RIAA inhibits the formation of prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-activated mouse macrophage RAW264.7 cells. In a prelude to the development of RIAA as an anti-inflammatory agent, a 21-day study to assess the oral toxicity of RIAA was conducted in CD-1 mice. A total of 40 mice were orally administered RIAA by gavage at doses of 25, 75, and 250 mg/kg/day. The mice were evaluated for changes in clinical signs, food consumption, body weight and other parameters. Overall, it was observed that RIAA was well tolerated for 21 days, with the only notable treatment effects occurring in the liver (minimal centrilobular hepatocellular hypertrophy) and spleen (increased incidence and/or severity of extramedullary hematopoesis) at the highest dosage. Further, the effect of RIAA on the major human cytochrome (CYP) P450s involved in drug metabolism was investigated using recombinant singly expressed enzymes. RIAA displayed only weak interactions (IC50s > 10 μM) with CYP1A2, CYP2D6, CYP2E1 and CYP3A4, and moderate inhibition of CYP2C19 (IC50 6.13 μM). Significant inhibition was only observed for CYP2C9 (IC50 0.20 μM). These data suggest that RIAA is unlikely to alter the metabolic clearance of drugs that are primarily metabolized by these CYP isozymes, with the possible exception of CYP2C9. This study was supported by Metagenics, Inc.

MR IMAGING OF MEDIASTINAL MASSES

Although ongoing developments in MR imaging have resulted in improved image quality and decreased acquisition time, MR imaging is largely used as an adjunct to CT scanning in the evaluation of mediastinal abnormalities. In this role, MR imaging often provides additional information about the nature, location, and extent of disease. MR imaging is useful in confirming the cystic nature of mediastinal lesions that appear solid on CT and, by revealing small amounts of intralesional fat, can suggest the diagnosis of hemangioma, teratoma, or extramedullary hematopoesis. MR imaging is the preferred modality for imaging neurogenic tumors, because its multiplanar capability and high contrast resolution can best demonstrate the number and nature of the lesions (differentiating cysts from neoplasms), intraspinal extension, and craniocaudad extent. MR imaging is also especially useful for evaluating the mediastinum of patients for whom the administration of iodinated contrast material is contraindicated.

Fine-needle aspiration of the mediastinum: a clinical, radiologic, cytologic, and histologic study of 42 cases.

Forty-two fine-needle aspirates (FNA) of the mediastinum were reviewed from 1984-1995. The clinical, radiologic, pathologic, and cytologic material was studied. Twenty-five males and 17 females had an age range from 10-72 yr and a mean of 41 yr. Common complaints were chest pain, dyspnea, and cough. Thirty-eight tumors were in the anterior/superior mediastinum. Fifty-seven percent were primary neoplasms (Hodgkin's lymphoma, 7; non-Hodgkin's lymphoma, 6; thymoma, 3; germ-cell tumor, 3; thymic carcinoid and angiosarcoma, 1 each; and malignant not otherwise specified, 3). Twenty-four percent were metastatic tumors (carcinoma, 9; and sarcoma, 1). Twelve percent were benign conditions (granulomatous disease, 2; multinodular goiter, 1; extramedullary hematopoesis, 1; and one thymic cyst). Seven percent were inconclusive. FNA yielded adequate tissue for diagnosis in 83% and a correct diagnosis in 86%. There was one false-negative and no false-positive diagnosis. FNA is a useful tool for accurate tissue diagnosis of mediastinal masses.

Fine‐needle aspiration of the mediastinum: A clinical, radiologic, cytologic, and histologic study of 42 cases

Forty-two fine-needle aspirates (FNA) of the mediastinum were reviewed from 1984–1995. The clinical, radiologic, pathologic, and cytologic material was studied. Twenty-five males and 17 females had an age range from 10–72 yr and a mean of 41 yr. Common complaints were chest pain, dyspnea, and cough. Thirty-eight tumors were in the anterior/superior mediastinum. Fifty-seven percent were primary neoplasms (Hodgkin's lymphoma, 7; non-Hodgkin's lymphoma, 6; thymoma, 3; germ-cell tumor, 3; thymic carcinoid and angiosarcoma, 1 each; and malignant not otherwise specified, 3). Twenty-four percent were metastatic tumors (carcinoma, 9; and sarcoma, 1). Twelve percent were benign conditions (granulomatous disease, 2; multinodular goiter, 1; extramedullary hematopoesis, 1; and one thymic cyst). Seven percent were inconclusive. FNA yielded adequate tissue for diagnosis in 83% and a correct diagnosis in 86%. There was one false-negative and no false-positive diagnosis. FNA is a useful tool for accurate tissue diagnosis of mediastinal masses. Diagn. Cytopathol. 1998;19:428–436. © 1998 Wiley-Liss, Inc.

Skin Painting Studies in Mice with 14 Fd&c and D&c Colors: Fd&c Blue no. 1, Red No. 3, and Yellow No. 5, D&C Red No. 7, Red No. 9, Red No. 10, Red No. 19, Red No. 21, Red No. 27, Red No. 31, Red No. 36, Orange No. 5, Orange No. 10, and Orange No. 17

AbstractA series of 14 cosmetic colors were submitted to dermal toxicity testing in accordance with a protocol designed by the Food and Drug Administration and agreed upon with the Cosmetic, Toiletry and Fragrance Association (formerly the Toilet Goods Association). Dosage levels were based on lipstick use determinations made in a group of human female volunteers. The groups of lipstick colors were divided into three treatment series and painted on twice weekly to an area approximately 6 cm2. A total of 1400 mice were used comprising groups of 100 mice (50 per sex) plus additional positive control group of the same size and a vehicle control group of 300 mice (150 per sex). All colors were prepared at 1.0% suspensions in water. The positive control received 3.4–benzpyrene dissolved in acetone. Survival was approximately equivalent in all experimental groups except the positive controls who died earlier consistent with survival recorded by others for 3.4–benzpyrene treated mice. Extramedullary hematopoesis...

421 NEONATAL “HEPATIC RICKETS” IN PREMATURE INFANTS RECEIVING PARENTERAL ALIMENTATION (PA)

During a six month period, six premature infants (gestation 28-31 wks, weight 790-1180 gm) developed cholestasis and severe metabolic bone disease while receiving parenteral alimentation. Spontaneous long bone fractures occurred in 3/6. Infants received PA amino acid solutions for a mean of 4.5 wks (range 1-9); 4/6 received Intralipid. Hepatic dysfunction (direct hyperbilirubinemia, elevated transaminases) was first noted at a mean of 29 d (range 6-65) after initiation of PA. Osteopenia was evident by x-ray in all. Photon absorptiometry bone mineral analysis (BMA) was decreased in 3/4 infants (Steichen, A.J. Roent. 126: 1283). 25-OH vitamin D (25-OHD) was markedly reduced, < 10 ng/ml in 6/6; normal 20-80 ng/ml (Belsey's). Serum Ca was normal in all and P was 3.1-5.9 mg/dl. One of six infants died of non-hepatic causes. The liver showed cholestasis with extramedullary hematopoesis, canalicular and hepatocellular stasis and minimal inflammation in two cases examined. Surviving infants were treated with 2500 units vit. D3 p.o. and Ca 100 mg/kg/d. Fractures healed in 3/3; serum 25-OHD levels normalized in 2/4; serial BMA showed continued poor mineralization in 3/4. Decreased serum 25-OHD may relate to decreased intake, absorption and hydroxylation of vitamin D and decreased enterohepatic circulation of 25-OHD. “Hepatic Rickets” can occur in premature infants who develop cholestasis while receiving parenteral alimentation and should be anticipated by serial measurement of serum 25-OH vitamin D.

Portal hypertension in a patient with osteopetrosis. A case report with discussion of the mechanism of portal hypertension.

Portal hypertension without cirrhosis of the liver has been described in several hematological conditions.1-15Though there may be thrombosis of the portal, splenic, or hepatic veins in cases of the myeloproliferative syndromes,13-15many cases have been described in which these veins were patent.1-8,13The etiology of portal hypertension in these patients with patent venous systems has not been clearly elucidated. Alternative explanations include increased portal secondary to splenomegaly, the forward flow theory,2,3,8and increased hepatic resistance from infiltrative lesions in portal tracts and sinusoids.7,13 Portal hypertension without cirrhosis also occurs in tropical splenomegaly16and systemic-portal arteriovenous fistulae.17,18Investigations in these patients have also suggested that increased portal blood may cause portal hypertension in the absence of cirrhosis.16,17 The case described here represents an example of hematological portal hypertension. Bone marrow obliteration led to hepatosplenomegaly from extramedullary hematopoesis. Portal hypertension became obvious when a large epigastric collateral vein appeared.