Intracranial Extramedullary Hematopoiesis in β-thalassemia Major

A case of β-thalassemia major with a huge mass of hernatopoictic tissuc firmly attached tothe dura mater was reported This is the first case reported in China.

Intestinal obstruction caused by extramedullary hematopoiesis and ascites in primary myelofibrosis

Primary myelofibrosis(PMF) is a clonal hematopoietic stem cell disorder. It is characterized by bone marrow fibrosis, extramedullary hematopoiesis with hepatosplenomegaly and leukoerythroblastosis in the peripheral blood. The main clinical manifestations of PMF are anemia, bleeding, hepatosplenomegaly, fatigue, and fever. Here we report a rare case of PMF with anemia, small bowel obstruction and ascites due to extramedullary hematopoiesis and portal hypertension. The diagnosis was difficult to establish before surgery and the differential diagnosis is discussed.

Magnetic resonance imaging features of intrahepatic extramedullary hematopoiesis: Three case reports

BACKGROUND Extramedullary hematopoiesis rarely occurs within the liver alone,and is easily misdiagnosed.The radiological literature on this disease is exclusively case reports.There is a paucity of literature on the role of magnetic resonance imaging(MRI).The most common imaging modalities used are computed tomography and ultrasound.This report aims to provide more data on the appearance of extramedullary hematopoiesis using MRI to help radiologists establish the diagnosis.CASE SUMMARY Three patients(one male and two females)were incidentally found to have a hepatic mass or nodule,without hepatomegaly or splenomegaly.Laboratory tests including liver function,serum hepatic tumor markers,and hepatitis serologic markers were normal.On MRI scans,all lesions showed lower signal intensity on in-phase images than on out-phase images.One case showed changes in signal intensity on T2 weighted images(WI)and diffusion WI,which shifted from hyperintensity to hypointensity with size enlargement between two rounds of imaging examination.These lesions exhibited different enhancement patterns on dynamic contrast enhancement series.CONCLUSION The MRI signal change and in-/out-phase image might provide useful information and help radiologists establish the diagnosis of intrahepatic extramedullary hematopoiesis.

Bone-marrow derived cells participate in extramedullary hematopoiesis in a model of acetaminophen-induced acute liver failure in rats

Adult derived mononuclear bone marrow cells are a good alternative as cell therapy. These cells are capable of significantly improve survival rate of Wistar rats with acetaminophen (APAP) induced acute liver failure in ten days. However, long term of cell therapy is not deeply studied in the literature. Here, we report an extramedullary hematopoiesis process derived from transplanted mononuclear bone marrow cells in the liver of rats 10 days after APAP injection. This result indicates that liver maintains an adequate microenvironment for the occurrence of extramedullary hematopoiesis process. The consequence of this finding deserves more studies.

Extramedullary Hematopoiesis Mimicking a Neoplasm in a Goeldi＇s Monkey （Callimico goeldii）

Extramedullary hematopoiesis consists in the appearance and proliferation of hematopoietic cells outside the bone marrow. In this article, the authors describe a case of hepatosplenic hematopoiesis in a 9-year-old, male Goeldi＇s monkey concurrent with a Calodium hepaticum infestation, belonging to the Lisbon＇s Zoo primate collection （Portugal）. Lesions were identified upon necropsy after euthanasia due to the presence of an apparently non-excisable, metastatic aortic mass. Histopathological analysis of samples taken was carried out and immunohistochemical staining was used to characterize the cellular population involved, confirming the diagnosis of extramedullary hematopoiesis. To the best of the authors＇ knowledge, this is the first report of hepatosplenic extramedullary hematopoiesis in a Goeldi＇s monkey.

Clonal hematopoiesis:a shared risk factor for cardiovascular diseases and tumors

Clonal hematopoiesis(CH)is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoietic cells carrying markers of the clonal mutation.Genes integral to critical cellular processes such as epigenetic regulation,DNA damage response,and inflammation frequently carry these mutations.Clonal hematopoiesis becomes increasingly prevalent with age and is associated with an increased risk of hematological tumors and some nonhematological conditions.Recent insights have revealed that the mutations driving CH are not only implicated in hematologic neoplasms but also possess the potential to influence cardiovascular pathogenesis.Here,we reviewed up-to-date findings about the roles of CH in cardiovascular diseases and tumors and explored the clinical significance of CH,as well as look forward to future related studies,so as to provide valuable references for future research and clinical practice.

Unusual presentation of extramedullary blast crisis in chronic myeloid leukemia:A case report

BACKGROUND Extramedullary blast crisis in chronic myeloid leukemia(CML)is an uncommon occurrence of leukemic blast infiltration in regions other than the bone marrow.Malignant infiltration of the serosal membranes should be considered in cases where CML presents with ascites or pleural effusion.CASE SUMMARY A 23-year-old female with CML presented with progressively worsening ascites and pleural effusion despite first-line tyrosine kinase inhibitor treatment.Her blood work indicated leukocytosis with myelocyte bulge and 2%blasts.Analysis of the patient’s bone marrow confirmed the chronic phase of CML.Abdominal ultrasound revealed hepatosplenomegaly with ascites.The fluid investigation of both ascites and pleural effusion revealed a predominance of neutrophils with exudate.However,no acid-fast bacilli or growth was observed after culturing.Although hydroxyurea reduced cell counts,there was no observed effect on ascites or pleural effusion.Repeat investigation of the ascitic and pleural fluid revealed a polymorphous myeloid cell population consisting of myelocytes,metamyelocytes,band forms,neutrophils and a few myeloblasts.Extramedullary blast crisis was suspected,and mutation analysis was performed.We switched the patient to dasatinib.The patient’s symptoms were relieved,and ascites and pleural effusion diminished.CONCLUSION Serosal membrane involvement in CML is extremely rare.In this case,the patient responded well to dasatinib treatment.

一类Hematopoiesis模型的唯一正周期解的存在性

本文考虑了一类Hematopoiesis模型,利用减算子的一个不动点定理,得到该方程存在唯一正周期解的充分条件,改进了已有文献的相应结果。特别地,本文还给出了收敛于该周期正解的迭代数列,即给出了该周期正解的近似表示。进而使本文的结果具有较大的实际应用价值。

Paraparesis induced by extramedullary haematopoiesis

We describe a case of worsening paraparesis induced by spinal cord compression at T6-T7 levels associated with compensatory extramedullary haematopoiesis from a compound heterozygote for haemoglobin E and for β-thalassemia.An emergency T3-T9 laminectomy was performed with excision of the masses and complete rehabilitation of the patient.

Ossified thoracic spinal meningioma with hematopoiesis: A case report and review of the literature

Meningiomas account for 25% of spinal tumors, and they are often located in the thoracic spine. The ossified subtype is even rarer, and those with hematopoiesis are rarely described. The mechanism of bone formation has not yet been clarified. A case of ossified spinal meningioma with hematopoiesis occurring in a 78-year-old woman is described. Magnetic resonance imaging revealed a lesion with a dural tail sign at the T9 level located dorsal to the spinal cord. Computerized tomography revealed a high density lesion, as high as the bone signal. Total resection was performed, and the symptoms improved. Pathological findings revealed many psammoma bodies (PBs), bone formation, and bone marrow with hematopoiesis. Both PBs and bone seemed to be based on the same background of calcified structures. This report is the second dealing with ossified spinal meningioma with hematopoiesis. The hardness of the tumor can make the operation more difficult, so that the operation should be performed carefully to avoid injuring the spinal cord.

脉冲Hematopoiesis模型的概周期解（英文）

获得了脉冲Hematopoiesis模型Q(t)=-c(t)Q(t)-α(t)Q(t)1+Q(t)+β(t)∫τ0F(u)Q(t-u)1+Q(t-u)dsΔQ(t k)=a k(t)Q(t k)+b k(t{)概周期解的存在性与指数稳定性.

Regulation of hematopoiesis and the hematopoietic stem cell niche by Wnt signaling pathways

Hematopoietic stem cells （HSCs） are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal （in which the ability to function as HSCs is retained） and initiation of hematopoietic differentiation. Multiple signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. Wnt signaling pathways play a crucial role during embryogenesis and deregulation of these pathways has been implicated in the formation of solid tumors. Wnt signaling also plays a role in the regulation of stem cells from multiple tissues, such as embryonic, epidermal, and intestinal stem cells. However, the function of Wnt signaling in HSC biology is still controversial. In this review, we will discuss the basic characteristics of the adult HSC and its regulatory microenvironment, the ＂niche＂, focusing on the regulation of the HSC and its niche by the Wnt signaling pathways.

Gastrointestinal bleeding as initial presentation of extramedullary plasma cell neoplasms: A case report and review of the literature

BACKGROUND Plasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small number of cases with gastrointestinal involvement is reported in the literature and therefore high index of suspicion is essential for avoiding delays in diagnosis and treatment.CASE SUMMARY Our aim is to present our experience of a 70-year-old patient with a secondary presentation of plasmablastic myeloma manifesting as unstable upper gastrointestinal bleeding and to review the literature with the view to consolidate and discuss information about diagnosis and management of this rare entity. In addition to our case, a literature search(Pub Med database) of case reports of extramedullary plasma cell neoplasms manifesting as upper gastrointestinal bleeding was performed. Twenty-seven cases of extramedullary plasmacytoma(EMP) involving the stomach and small bowel presenting with upper gastrointestinal bleeding were retrieved. The majority of patients were males(67%). The average age on diagnosis was 62.7 years. The most common site of presentation was the stomach(41%), followed by the duodenum(15%). The most common presenting complaint was melena(44%). In the majority of cases, the EMPs were a secondary manifestation(63%) at the background of multiple myeloma(26%), plasmablastic myeloma(7%) or high-grade plasma cell myeloma(4%). Oesophagogastroscopy was the main diagnostic modality and chemotherapy the preferred treatment option for secondary EMPs.CONCLUSION Despite their rare presentation, upper gastrointestinal EMPs should be considered in the differential diagnosis of patients with gastrointestinal bleeding especially in the presence of systemic haematological malignancy.

Bortezomib in treatment of extramedullary plasmacytoma of the pancreas

BACKGROUND: Extramedullary pancreatic plasmacytoma treated with bortezomib is rarely reported. METHODS: We admitted a 53-year-old woman with an asymptomatic mass above the left clavicle for over three months, then an asymptomatic swelling of the pancreas was found. A biopsy on the mass and a fine needle aspiration of the pancreas were performed. The diagnosis of extramedullary plasmacytoma (EMP) was made. The patient was initially treated with combination chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD regimen). She progressed to painless jaundice during the chemotherapy. Then she was treated with bortezomib and hyper-dose dexamethasone. As a result, she had a near complete remission. RESULTS: The data demonstrated that the diagnosis was EMP of the pancreas. The patient responded very well to bortezomib, while failing to respond to the traditional chemotherapy regimen of VAD. CONCLUSION: EMP of the pancreas is rare. This case gives evidence for an excellent response of EMP of the pancreas to bortezomib. (Hepatobiliary Pancreat Dis Int 2009; 8: 329-331)

EFFECT OF RECOMBINANT MOUSE INTERLEUKIN-3 ON HEMATOPOIESIS IN NORMAL AND CYCLOPHOSPHAMIDE-TREATED MICE

Intraperitoneal injection of recombinant mouse IL-3 in normal mice for 6 days did not induce any significant changes in leukocyte and neutrophil counts. In comparison with saline controls, IL-3-treated mice experienced a 1.7-fold increase of bone marrow nucleated cells and 3.6-fold increase of CFU-GM colonies. Tritium thymidine incorporation of bone marrow cells significantly increased in IL-3-treated mice as compared with that in normal saline-treated mice. These results suggested that IL-3 expanded the number of granulocyte-macrophage progenitor cells but not the peripheral neutrophils. We examined the effect of IL-3 on hematopoietic reconstitution in a cyclophosphamide-treated mouse model. We found that the absolute neutrophil number of mice treated with IL-3 increased significantly on day 6 post injection when compared with the control mice (6.2± 4.1×109 / L versus 0.98± 1.4 × 109/ L, P【0.01) . The results demonstrated that IL-3 stimulated an early recovery of neutrophils after

Extramedullary plasmocytoma associated with a massive deposit of amyloid in the duodenum

We report a rare case of extramedullary plasmocytoma associated with a massive deposit of amyloid in the duodenum. A 72-year-old Japanese man was admitted to our hospital presenting with a 3-mo history of epigastric pain, vomiting and weight loss. On computed tomography （CT） a wall thickening of the fourth part of the duodenum was observed. Multiple biopsies obtained from the lesion showed infiltration of plasma cells and lymphocytes, but they were not conclusive. The patient underwent resection of the lesion and, on histopathological examination, the lesion consisted of a dense and diffuse infiltrate of plasma cells and a few admixed lymphocytes with reactive follicles extending to the muscular propria. An extensive deposition of amyloid was also observed. Immunohistochemical stains revealed that a few plasmacytoid cells showed λ light chain staining, though most were κ： light chain positive. These cells also were positive for CD138 and CD56 but negative for CD20 and CD79. The findings were consistent with extramedullary plasmocytoma associated with a massive deposit of amyloid in duodenum. A subsequent workup for multiple myeloma was completely negative. The patient showed no signs of local recurrence or dissemination of the disease after 12 mo follow-up. Because of the association of plasmocytoma and amyloidosis, the patient must be followed up because of the possible systemic involvement of the neoplasm and amyloidosis in future.

Ikaros in hematopoiesis and leukemia

Ikaros is a gene whose activity is essential for normal hematopoiesis.Ikaros acts as a master regulator of lymphoid and myeloid development as well as a tumor suppressor.In cells,Ikaros regulates gene expression via chromatin remodeling.During the past 15 years tremendous advances have been made in understanding the role of Ikaros in hematopoiesis and leukemogenesis.In this Topic Highlights series of reviews,several groups of international experts in this field summarize the experimental data that is shaping the emerging picture of Ikaros function at the biochemical and cellular levels.The articles provide detailed analyses of recent scientific advancements and present models that will serve as a basis for future studies aimed at developing a better understanding of normal hematopoiesis and hematological malignancies and at accelerating the application of this knowledge in clinical practice.

Management of extramedullary plasmacytoma: Role of radiotherapy and prognostic factor analysis in 55 patients

Objective： To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy（RT） in the management of extramedullary plasmacytoma（EMP）.Methods： Data from 55 patients with EMP between November 1999 and August 2015 were collected. The median age was 51（range, 22–77） years. The median tumor size was 3.5（range, 1.0–15.0） cm. The median applied dose was 50.0（range, 30.0–70.0） Gy. Thirty-nine patients（70.9%） presented with disease in the head or neck region. Twelve patients received RT alone, 9 received surgery（S） alone, 3 received chemotherapy（CT） alone, and 3 patients did not receive any treatment. Combination therapies were applied in 28 patients.Results：The median follow-up duration was 56 months.The 5-year local recurrence-free survival（LRFS）,multiple myeloma-free survival（MMFS）,progression-free survival（PFS）and overall survival（OS）rates were 79.8%,78.6%,65.2% and 76.0%,respectively.Univariate analysis revealed that RT was a favourable factor for all examined endpoints.Furthermore,head and neck EMPs were associated with superior LRFS,MMFS and PFS.Tumor size〈4 cm was associated with superior MMFS,PFS and OS;serum M protein negativity was associated with superior MMFS and PFS;age≥50 years and local recurrence were associated with poor MMFS.The dose≥45 Gy group exhibited superior 5-year LRFS,MMFS and PFS rates（94.7%,94.4%,90.0%,respectively）,while the corresponding values for the dose〈45 Gy group were 62.5%（P=0.008）,53.3%（P=0.036）and 41.7%（P〈0.001）.Conclusions：Involved-site RT of at least 45 Gy should be considered for EMP.Furthermore,patients with head and neck EMP,tumor size〈4 cm,age〈50 years and serum M protein negativity had better outcomes.

Coexistence of cervical extramedullary plasmacytoma and squamous cell carcinoma:A case report

BACKGROUND Extramedullary plasmacytoma(EMP),a variant form of myeloma,is a rare solid plasma cell tumor that originates from the bone marrow hematopoietic tissue and accounts for about 3%of all plasma cell tumors.EMP can affect various tissues and organs,about 90%of which is found in the head and neck.However,EMP in the reproductive organs is rare,and is difficult to be distinguished from other primary or metastatic genital tumors according to clinical symptoms and imaging findings.CASE SUMMARY Herein,we report a case with coexistence of EMP and squamous cell carcinoma in the cervix.The first histopathological report of neoplasms on the surface of the cervix and vagina showed an EMP.Both ultrasound and pelvic enhanced magnetic resonance imaging(MRI)indicated that there was a tumor in the cervix.Thus,another cervical biopsy and pathological examination were performed,which indicated EMP combined with squamous cell carcinoma.Then,the patient underwent extensive total hysterectomy(type C1)+systemic lymph node dissection and received 25 external pelvic irradiations with a dose of 50 Gy following surgery.During 2-year follow-up,no recurrence was reported.CONCLUSION In conclusion,EMP involving the reproductive system is relatively rare.In this case,MRI,B-ultrasound,and cervical canal scraping were used to further determine the diagnosis of EMP combined with squamous cell carcinoma.The patient had improved prognosis after appropriate treatments.

Non-secretory multiple myeloma expressed as multiple extramedullary plasmacytoma with an endobronchial lesion mimicking metastatic cancer:A case report

BACKGROUND Non-secretory multiple myeloma(MM)is a rare condition that accounts for only 3%of MM cases and is defined by normal serum and urine immunofixation and a normal serum free light chain ratio.Non-secretory MM with multiple extramedullary plasmacytomas derived from endobronchial lesions is extremely rare and can be misdiagnosed as metastasis of solid cancer.CASE SUMMARY A 36-year-old man presented with progressive facial swelling and nasal congestion with cough.Various imaging studies revealed an endobronchial mass in the left bronchus and a large left maxillary mass with multiple destructive bone metastatic lesions.He initially presented with lung cancer and multiple metastases.However,pathologic reports showed multiple extramedullary plasmacytomas in the left maxilla and the left bronchus.There was no change in the serum and urine monoclonal protein levels,and no abnormalities were observed in laboratory examinations,including hemoglobin,calcium,and creatinine levels.The bone marrow was hypercellular,with 13.49%plasma cells.The patient was diagnosed with non-secretory MM expressed as multiple extramedullary plasmacytomas with endobronchial lesions in a rare location.Radiation therapy for symptomatic lesions with high-dose dexamethasone was started,and the size of the left maxillary sinus lesion dramatically decreased.In the future,chemotherapy will be administered to control lesions in other areas.CONCLUSION We present a rare case of non-secretory MM with multiple extramedullary plasmacytoma with an endobronchial lesion.