A common complication of myelofibrosis presenting as a rare finding in cerebrospinal fluid cytology

Herein, we present a rare case of intracranial extramedullary hematopoiesis (EMH) diagnosed by cerebrospinal fluid (CSF) cytology and describe the clinical presentation, radiologic, and pathologic findings. A 65 year‐old man with a history of progressing primary myelofibrosis was admitted for headaches and right facial numbness. A brain MRI revealed focal abnormalities that were suspicious for leptomeningeal involvement of acute leukemia. Cytologic examination of CSF demonstrated a hypercellular specimen composed of hematopoietic cells including few blasts, as well as maturing red blood cells and granulocytic cells. The integration of morphologic findings, peripheral blood and bone marrow counts, as well as flow cytometric analysis of CSF and bone marrow, excluded leptomeningeal involvement by leukemic blasts and helped establish the diagnosis of intracranial EMH. Inclusion of EMH in the differential diagnosis of intracranial pathology in patients with known conditions predisposing them to EMH is important because recognizing this rare event has implications for treatment and prognosis.     

Endoscopic ultrasound guided fine‐needle aspiration of a splenic hemangioma with extramedullary hematopoiesis

Extramedullary hematopoiesis (EMH) is the production of mature blood elements outside of the bone marrow and can occur as a compensatory result of a marrow replacing process or from marrow space occupying lesions such as tumor or marrow fibrosis. EMH can also be induced by factors elicited by neoplasms, such as vascular endothelial growth factor (VEGF). Usually, EMH is a diffuse process most commonly observed in lymph nodes, liver, and spleen. Rarely, EMH can form a mass lesion. Although the spleen is a common site for diffuse EMH, it is a rare location for a mass forming EMH. Hemangiomas are the most common benign tumors of the spleen. A case of a discrete, 8 cm lesion was noted incidentally on CT scan in a 59‐year‐old man with no significant past medical history. Endoscopic ultrasound guided fine‐needle aspiration (EUS FNA) biopsy was performed and cytologic examination revealed trilinear hematopoiesis, with the most distinctive elements being megakaryocytes and erythroid precursors. A diagnosis of EMH was made. On resection, the mass was a hemangioma with EMH. EUS guided FNA is a useful tool for diagnosing splenic masses. Awareness of EMH, both as a mass forming lesion and a feature associated with benign and malignant vascular lesions is important, especially in patients with hematologic malignancies or marrow replacing processes. Diagn. Cytopathol. 2013;41:1086–1090. © 2011 Wiley Periodicals, Inc.     

Chronic idiopathic myelofibrosis presenting as cauda equina compression due to extramedullary hematopoiesis: a case report

Extramedullary hematopoiesis (EMH) is occasionally reported in idiopathic myelofibrosis and is generally found in the liver, spleen, and lymph nodes several years after diagnosis. Myelofibrosis presenting as spinal cord compression, resulting from EMH tissue is very rare. A 39-yr-old man presented with back pain, subjective weakness and numbness in both legs. Sagittal magnetic resonance imaging showed multiple anterior epidural mass extending from L4 to S1 with compression of cauda equina and nerve root. The patient underwent gross total removal of the mass via L4, 5, and S1 laminectomy. Histological analysis showed islands of myelopoietic cells surrounded by fatty tissue, consistent with EMH, and bone marrow biopsy performed after surgery revealed hypercellular marrow and megakaryocytic hyperplasia and focal fibrosis. The final diagnosis was chronic idiopathic myelofibrosis leading to EMH in the lumbar spinal canal. Since there were no abnormal hematological findings except mild myelofibrosis, additional treatment such as radiothepary was not administered postoperatively for fear of radiotoxicity. On 6 month follow- up examination, the patient remained clinically stable without recurrence. This is the first case of chronic idiopathic myelofibrosis due to EMH tissue in the lumbar spinal canal in Korea.     

Pleural fluid extramedullary hematopoiesis case report with review of the literature

Extramedullary hematopoiesis (EMH) is the trilineage formation of normal blood cells outside of the bone marrow. While predominantly seen in the spleen and liver, EMH rarely occurs in serous effusions. Accurate diagnosis requires recognition of megakaryocytes and other precursor hematopoietic elements. We present a case of pleural fluid EMH in a patient with primary myelofibrosis and developing leukemia, with a review of the literature, prognostic implications and diagnostic challenges. Diagn. Cytopathol. 2016;44:41–44. © 2015 Wiley Periodicals, Inc.     

Pleural mass forming extramedullary hematopoiesis masquerading as a malignant neoplasm

Extramedullary hematopoiesis (EMH) represents the presence of immature hematopoietic elements and their differentiation into mature blood components outside of the medullary bone and may be seen in a variety of circumstances in the postnatal period, but is most strongly associated with disorders of the hematopoietic system. Postnatally, EMH is typically identified at sites of fetal hematopoiesis, the spleen, and liver, but occasional reports have identified it in nearly every tissue of the body. We report a case of EMH presenting as pleural mass, initially suspected to represent a neoplastic process in a patient with multiple comorbidities, including history of carcinoma, but without co‐existing hematologic disorder. On‐site evaluation of the fine‐needle aspiration specimen was initially suspicious for a malignant neoplasm, but further evaluation revealed the lesion to be a mass forming focus of non‐hepatosplenic EMH. In the era of increasing utilization of imaging, mass forming EMH is increasingly detected. When unsuspected, EMH may present a diagnostic challenge for the pathologist and may be confused for a neoplastic process. Diagn. Cytopathol. 2015;43:996–999. © 2015 Wiley Periodicals, Inc.     

Extramedullary hematopoiesis in pyogenic granuloma

Extramedullary hematopoiesis (EMH) suggests the presence of hematopoietic stem cells (HSC) outside bone marrow. EMH has been reported, albeit rarely, in pyogenic granuloma (PG), a polypoid lobular capillary hemangioma. However, statistical data have hitherto been lacking on the actual incidence of EMH in PG. Therefore, we here reviewed 157 consecutive cases using routine diagnostic surgical slides and found unequivocal EMH in 17 (10.8%). This indicates that EMH is a rather common finding in PG, which could thus have strong potential to be an important resource for the study of HSC.     

Myocardial extramedullary hematopoiesis: a clinicopathologic study.

Extramedullary hematopoiesis (EMH) after fetal development is uncommon and is most often seen in patients who have hematologic disorders. EMH unassociated with hematologic disease is rare. After the recent observation of EMH in a myocardial infarct, we sought to determine the frequency and clinicopathologic setting of EMH in myocardial tissues submitted for pathologic examination. Hematoxylin and eosin (H&E)-stained sections from 805 consecutive myocardial samples (207 surgical specimens, 598 autopsy specimens) were examined retrospectively. The presence of immature erythroid or myeloid cell clusters in intramyocardial capillaries or stroma was considered sufficient for the diagnosis of EMH. Immunoperoxidase studies confirming the nature of the hematopoietic cell infiltrate were performed in selected cases. Foci of EMH (often multiple) were identified in 15 of 207 surgical hearts (7.2%) and in 22 of 598 autopsy hearts (3.7%). Patient ages (exclusive of premature infants) ranged from 2 weeks to 73 years (median, 13 years). Twenty-four of 37 (65%) EMH-positive cases were associated with infarcts in various stages of repair (accounting for 11 of 68 [16.2%] of all infarcts in surgical specimens and 13 of 86 [15.1%] of infarcts in autopsy specimens). Acute infarcts less than 72 hours old, excluding those with acute extension, were not associated with EMH. Viral myocarditis and myocardial hypertrophy with fibrosis accounted for primary diagnoses in the nonischemic, EMH-positive surgical cases, whereas seven of nine nonischemic, EMH-positive autopsy cases involved premature or term infants with no obvious myocardial disease. Another autopsy patient had sarcoidosis with myelophthisic involvement of her bone marrow and represented one of only two cases overall in which a hematopoietic disorder was coexistent or suspected. Myocardial EMH is relatively common after myocardial infarct but is rarely encountered in normal or nonischemic myocardium. Its presence in healing but not early acute stages of infarct suggests that EMH results from inflammation- or repair-associated trophic factors, not from ischemia itself.     

Nodular hematopoiesis of the liver diagnosed by fine-needle aspiration cytology

A case of tumor-like extramedullary hematopoiesis (EMH) of the liver diagnosed by fine-needle aspiration cytology guided by computer tomography (CT) is reported. The initial clinical diagnosis was metastatic carcinoma from an adrenal gland primary. Five other cases of tumor-like EMH diagnosed by FNA have been presented in the literature. In two of the cases, the primary clinical diagnosis was metastatic tumor. The most common location for tumor-like EMH is paravertebral and intrathoracic. Three such cases of paravertebral tumor-like EMH have been diagnosed by FNA. Nodular EMH can be found rarely in other organs as in the liver. Diagn. Cytopathol. 16:51–54, 1997. © 1997 Wiley-Liss, Inc.     

Transplantation studies in mice with congenital hemolytic anemia

Sphha/sphha anemic mice have an abnormality in the erythroid membrane protein, alpha spectrin, and exhibit multiple related clinical abnormalities, including spherocytosis, shortened red cell survival, chronic hemolysis, hemosiderosis, and extramedullary hematopoiesis. In addition, these mutant mice exhibit a granulocytosis and lymphocytosis, lymph node hyperplasia, elevated serum immunoglobulins, membranoproliferative glomerulonephritis, and decreased lifespan--abnormalities that are less clearly attributable to a spectrin defect. In order to further elucidate the mechanisms of disease in these animals, we undertook a series of bone marrow transplantation experiments. Transplantation of anemic marrow into lethally irradiated congenic +/+ mice resulted in chronic spherocytosis, hemolytic anemia, peripheral leukocytosis, and extramedullary hematopoiesis. Additionally, transplant recipients of anemic marrow which had received a higher radiation dose (12 Gy) had increased numbers of peripheral blood CD4+ and CD8+ lymphocytes, a hypocellcular thymus, and a severe pneumonitis characterized by nodular areas of consolidation and edema. Mice receiving congenic +/+ marrow and irradiated with the same radiation dose exhibited minimal pulmonary abnormalities. Anemic mice transplanted with congenic +/+ marrow usually died, but the survivors exhibited reversal of some clinicopathological changes. These results would suggest that the clinical abnormalities of sphha/sphha mice are in part attributable to abnormalities of hematopoietic stem cells but may also involve defects in other cell types. The pathogenesis of the accompanying lymphoid abnormalities observed in this mutant anemic mouse and any correlation with the erythroid spectrin defect are presently unknown. The pulmonary disease that develops in the transplant recipients of anemic marrow needs to be characterized further but may represent a unique model of lung injury.     

Extramedullary hematopoiesis presented as solitary renal mass: a case report with review of literature

In this article, we described a case of extramedullary hematopoiesis (EMH) in a 12-year-old boy with the clinical and hematological features of hemolytic anemia of unknown cause. The patient presented with a solitary well circumscribed mass in right kidney. Ultrasound guided fine-needle aspiration cytology showed myelocytes, metamyelocytes, megakaryocytes, and immature erythroid cells. A cytological diagnosis of EMH was made.     

October 2001: 40-year-old Xhosa male with back pain and leg weakness

A 40-year-old Xhosa male presented with progressive upper lumbar back pain and weakness At examination he was emaciated and had enlarged lymph nodes in the groin and axilla. Both lower limbs were severely atrophic and weak. Sensation to touch and pain was decreased below L3 bilaterally. MR of the spine showed a discrete, contrast-enhancing epidural mass. A T10-T12 laminectomy revealed an soft, vascular extradural tumor dorsal to the cord. The mass was loosely applied to the dura and easy to remove. The operative specimen consisted of a sausage-shaped (3.5 x 2.0 x 1.2 cm), thinly-encapsulated mass of reddish-brown tissue. The cut surface had a mottled, vaguely nodular, yellowish-brown appearance. Microscopic examination revealed sheets of hematopoeitic elements, including myeloid, red cell and megakaryocytic lines, the latter showing Factor 8-related positivity. The final diagnosis was extramedullary hematopoiesis (EMH). A bone marrow biopsy performed as a result of the diagnosis showed a myeloproliferative disease and polycythemia vera. EMH in the spinal epidural space is a rare but treatable cause of progressive paraparesis in patients with a variety of hematological disorders. Since 1956 there have been more than 50 reported cases, most of which occurred in association with thalassaemia. In spinal cord compression secondary to EMH, the lesions are commonly localized to the mid-lower thoracic region.     

The role of Janus Kinase 2 V617F mutation in extramedullary hematopoiesis of the spleen in neoplastic myeloid disorders.

Extramedullary hematopoiesis (EMH) in the spleen is a characteristic feature of the chronic myeloproliferative disorders (CMPDs) and various other neoplastic or reactive myeloid conditions. However, the origin of these hematopoietic precursor cells and the molecular mechanisms underlying their development in the spleen is uncertain. The V617F mutation in the Janus Kinase 2 gene (JAK2(V617F)) was recently shown to be frequently and preferentially present in the peripheral blood and bone marrow cells of CMPD patients, and the resulting dysregulation of its downstream targets is important to CMPD pathogenesis. To determine the occurrence and potential role of JAK2(V617F) in splenic EMH cells, we studied splenectomy specimens from 47 patients with significant EMH. JAK2(V617F) was detected by real-time PCR melting curve analysis in 22 specimens, including 11/17 chronic idiopathic myelofibrosis, 7/7 polycythemia vera, 1/1 essential thrombocythemia, 1/3 CMPD unclassifiable, 1/5 chronic myelomonocytic leukemia, 0/5 chronic myelogenous leukemia, 1/3 myelodysplastic syndrome and 0/6 acute myeloblastic leukemia cases, whereas only the JAK2 wild-type allele was detected in the other 25. Nineteen of 20 cases with adequate bone marrow samples available for molecular examination demonstrated concordant JAK2 genotypes. Laser-capture microdissection was then used to enrich the EMH and non-EMH splenic cell fractions, confirming that the mutant alleles specifically originated from the EMH cells. Furthermore, megakaryocytes in the JAK2(V617F)-positive splenectomy specimens expressed higher levels of Bcl-xL, an antiapoptotic protein and downstream target of the JAK2/STAT5 pathway. Thus, JAK2(V617F) is frequently present in splenic EMH cells associated with CMPD, but it is rarely identified in splenic EMH cells associated with other myeloid disorders. Our results indicate that the precursor cells leading to extramedullary hematopoietic expansion in CMPD most likely originate from the transformed bone marrow clone. Also, dysregulation of downstream pathways such as Bcl-xL may be important to CMPD disease pathogenesis in the spleen.     

Fine-needle aspiration biopsy diagnosis of intrathoracic extramedullary hematopoiesis presenting as a posterior mediastinal tumor in a patient with sickle-cell disease: Case report

Extramedullary hematopoiesis (EMH) is a rare cause of an intrathoracic mass. Fine-needle aspiration biopsy (FNAB) has been only occasionally documented as a useful tool in diagnosing EMH tumor. We report a case of posterior mediastinal extramedullary hematopoietic mass in an 80-yr-old man with sickle-cell anemia. The mass was revealed incidentally on chest X-ray. The definitive diagnosis of this mass lesion was achieved by FNAB. The cytologic smears showed hematopoietic elements with erythroid hyperplasia. A correct cytologic diagnosis can thus help to avoid unnecessary surgical intervention, particularly in an asymptomatic patient.     

Antithymocyte globulin treatment of retrovirus-induced feline erythroid aplasia: in vivo and in vitro studies

The Kawakami-Theilen strain of feline leukemia virus (FeLV-KT) was used experimentally to produce erythroid aplasia in cats. The in vivo effects of goat anti-feline-thymocyte globulin (ATG) on hematopoiesis were investigated in FeLV-negative normal and FeLV-positive anemic cats. Treatment was initiated in anemic cats between 4 and 6 weeks postinoculation (PI) when erythroid progenitors were reduced to 10% of normal levels. During the first 2 weeks of treatment, ATG significantly increased the numbers of erythroid precursors in bone marrow from 15 to 35% in anemic cats and from 28 to 43% in normal cats. ATG stimulated a twofold increase of CFU-E and a threefold increase of CFU-GM in normal cats between 2 and 4 weeks after initiation of treatment but had no effect on CFU-E or CFU-GM in anemic cats. The in vivo effects of ATG were transient despite weekly treatment. Cats treated with normal globulin were not significantly different from untreated anemic control cats. In vitro treatment of low density bone marrow mononuclear cells with ATG plus complement increased CFU-E and BFU-E of bone marrow from cats prior to inoculation but not from viremic cats. These results indicate that, although ATG stimulates erythropoiesis and granulopoiesis in normal cats, it does not reverse retrovirus-induced erythroid aplasia.     

Extramedullary hematopoiesis mimicking acute appendicitis: a rare complication of idiopathic myelofibrosis

Extramedullary hematopoiesis (EMH) is rarely found in the gastrointestinal tract. To our knowledge, EMH involving the appendix was not described. We report a case with a previous history of idiopathic myelofibrosis, which presented with clinical findings of acute appendicitis that necessitate appendectomy after the relief of his anemia. Microscopic examination and immunohistochemistry revealed foci of EMH throughout the mucosa and the submucosa. In the latter, small clusters of hematopoietic cells were also detected in a few dilated vascular structures. The histopathological features of acute appendicitis were not observed. Our case supports that EMH might develop in organs that are not involved in hematopoiesis. Although in gastrointestinal system, obstruction and bleeding are the most common symptomatic manifestations, this case emphasizes that EMH might also present clinically as acute appendicitis. The absence of histopathological features of acute appendicitis raises the possibility that local production of some mediators from hematopoietic precursor cells might contribute to this clinical presentation.     

Mass-forming extramedullary hematopoiesis diagnosed by fine-needle aspiration cytology

Extramedullary hematopoiesis (EMH) is usually a microscopic finding. However, it may present as a mass-forming lesion making it amenable to fine-needle aspiration biopsy (FNAB). When mass-forming EMH occurs, it can simulate a neoplasm clinically and radiologically. Additionally, the megakaryocytes can mimic malignant neoplastic cells, particularly if EMH is not a considered diagnosis. We report six cases of mass-forming EMH diagnosed by FNAB and evaluate the utility of FNAB in diagnosing EMH. Four patients had prior diagnoses of hematologic disorders, one patient had malignant mastocytosis who presented with lymphadenopathy and one patient had a history of carcinoma. The patients' ages ranged from 46 to 78 yr with an equal sex distribution. Aspirate smears showed trilineage hematopoiesis. The cytomorphologic differential diagnosis included metastatic carcinoma, Hodgkin lymphoma and myeloid sarcoma. No special stains were necessary due to the classic cytologic findings and prior hematologic history.     

Extramedullary hematopoiesis in breast after neoadjuvant chemotherapy for breast carcinoma

We report incidental extramedullary hematopoiesis (EMH) in breasts of 2 patients following neoadjuvant chemotherapy for locally advanced breast cancer. Neither of the patients had a history of hematologic disorders. After chemotherapy, one of the patients had a complete pathologic response and the other had residual carcinoma. In both cases, EMH was mostly seen as myelopoiesis in a background of chemotherapy-induced changes. In the patient with residual carcinoma, EMH was observed in the contralateral prophylactic mastectomy specimen. EMH should be considered a diagnostic pitfall in the differential diagnosis of unusual cellular infiltrates in breast after neoadjuvant chemotherapy. To our knowledge, the association of EMH and neoadjuvant chemotherapy has not been previously reported.     

多发性骨髓瘤患者骨髓间充质干细胞冻存前后的生物学特性

背景：多发性骨髓瘤患者的骨髓间充质干细胞具有多向分化、免疫调节和支持造血作用,但是这些功能是否受冻存的影响目前尚不清楚。 目的：探讨冻存对多发性骨髓瘤患者骨髓间充质干细胞生物学特性的影响。 方法：采用细胞贴壁法获取多发性骨髓瘤患者骨髓间充质干细胞,将传代后的细胞用IMDM细胞冻存液(含10%的二甲基亚砜和体积分数40%的胎牛血清)保存在-196 ℃液氮中。检测短期(1个月)和长期(12个月)冻存复苏后间充质干细胞的活性和增殖能力;将冻存后多发性骨髓瘤患者骨髓间充质干细胞作为滋养层,应用甲基纤维素半固体培养,检测其支持造血的能力;混合淋巴细胞反应检测冻存后多发性骨髓瘤患者骨髓间充质干细胞调控免疫能力。 结果与结论：经过短、长期冻存后多发性骨髓瘤患者骨髓间充质干细胞的细胞活性分别为(92.9±7.5)%和(86.7±9.2)%;短、长期冻存后细胞的增殖能力与冻存前间充质干细胞相似;冻存后多发性骨髓瘤患者骨髓间充质干细胞仍具有支持造血祖细胞生长的作用和抑制T淋巴细胞增殖的能力,与冻存前相比,没有明显差别。说明冻存可以降低多发性骨髓瘤患者骨髓间充质干细胞的细胞活性,但是并不影响间充质干细胞的增殖、支持造血和免疫调节的能力。     

Janus kinase 2 V617F mutation is detectable in spleen of patients with chronic myeloproliferative diseases suggesting a malignant nature of splenic extramedullary hematopoiesis

Extramedullary hematopoiesis occurs in patients with a variety of hematologic diseases, and the spleen is a common site. Extramedullary hematopoiesis is very common in chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The pathogenesis of extramedullary hematopoiesis is unknown. Using JAK2 V617F mutation as a molecular marker, we assessed paired spleen and bone marrow samples of 15 patients with various types of chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The diagnosis was chronic idiopathic myelofibrosis (n=8), polycythemia vera (n=3), and chronic myelomonocytic leukemia (n=4). DNA was extracted from fixed, paraffin-embedded tissue and assessed for JAK2 V617F by real-time polymerase chain reaction assay followed by melting curve analysis. Concordant JAK2 mutation was detected in the paired samples in 7 patients. A discordant result with JAK2 V617F found in the spleen but not bone marrow was noted in 1 patient. These results indicate that extramedullary hematopoiesis in patients with chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases is a clonal process and lend support to the theory that the cells of extramedullary hematopoiesis are carried from the bone marrow.     

Complete regression of bone marrow fibrosis following allogeneic peripheral blood stem cell transplantation in a patient with idiopathic myelofibrosis

The authors present a case of a 47-year-old man with idiopathic myelofibrosis. The diagnosis of myelofibrosis was made in 1981. Because of progression of the disease and failure of hematopoiesis in 2002, allogeneic peripheral blood stem cell transplantation was performed; the donor was an HLA identical relative. Six months after transplantation, trephin biopsies were made and a complete regression of bone marrow fibrosis was documented. It is the first case of this treatment for idiopathic myelofibrosis in the University Hospital in Hradec Králové.