Myeloid sarcoma in essential thrombocythemia that transformed into acute myeloid leukemia

A 72-year-old man was diagnosed with essential thrombocythemia (ET) and was treated with hydroxyurea for approximately 5 years. He was well until April 2007. In May 2007, a slight fall in hemoglobin levels was found. In June 2007, an upper endoscopy performed to investigate the cause of anemia showed multiple polypoid lesions in the body of the stomach. A gastric biopsy showed a diffuse infiltration of very immature cells. Several additional immunohistochemical staining showed that the cells were positive for CD13, CD34, CD117, and HLA DR, but negative for myeloperoxidase, CD42b, glycophorin, B cell marker, T cell marker, cytokeratin and desmin. We finally diagnosed the condition as myeloid sarcoma. Subsequently, the patient’s ET transformed into acute myeloid leukemia. To our knowledge, this is an exceedingly rare event involving a patient with essential thrombocythemia.     

Essential thrombocythemia that transformed to myelofibrosis after three years]

A 66-year-old man was presented with thrombocytosis in February, 1988. Laboratory examinations on admission revealed a white blood cell count of 17,700/microliters and a platelet count of 274.4 x 10(4)/microliters. Bone marrow aspirates showed an increase of megakaryocytes (1,294/microliters). There was no fibrosis or Ph1 chromosome. He was diagnosed as having essential thrombocythemia and was treated with thrombopheresis, carboquone and ranimustine (MCNU). Subsequently his platelet count was well controlled approximately for three years. He was readmitted because of pyrexia and left hypochondralgia in February 1991. Physical examination revealed hepatosplenomegaly. Peripheral blood revealed leukoerythroblastosis associated with the occurrence of tear drop cells. Bone marrow aspiration resulted in a dry tap and the biopsy specimen showed reticulin fibrosis. This is a fairly rare case of essential thrombocythemia that transformed to myelofibrosis.     

Essential thrombocythemia transformed to myelofibrosis with myeloid metaplasia after seven years

A 29-year-old male was diagnosed as having essential thrombocythemia (ET) in 1975. From that time, his platelet count gradually increased to more than 2 X 10(6)/microliter until 1979. However, his platelet count gradually decreased to less than 6 X 10(5)/microliter in 1985. Also, in 1982, erythroblasts and immature myeloid cells began to appear in the peripheral blood, and the liver and spleen became palpable in 1985. Bone marrow then revealed osteomyelosclerosis. These findings suggested that ET had transformed to myelofibrosis with myeloid metaplasia. Increased hepatosplenomegaly was accompanied by the appearance of ascites in June, 1988, and an esophageal varix ruptured in December of the same year. The varix was resected and the spleen was removed. After the operation, ascites did not recur and his condition became stable. Portal hypertension in this patient was considered to be due mainly to increased blood flow from the enlarged spleen.     

Essential thrombocythemia developing into refractory anemia and complicated by acute myeloid leukemia.

We report a case of essential thrombocythemia (ET) that climaxed in acute myeloid leukemia after developing into refractory anemia. The male patient had ET that was stable for 8 years on carboquone therapy. However, at the age of 72 years he developed an acute terminal illness that was characterized by severe pancytopenia, circulating myeloblasts, extensive bone marrow infiltration by myeloblasts, and an abnormal karyotype [46, XY, t(8q-; 20q+)]. He subsequently died of severe bilateral pneumonia and heart failure. This case suggests that ET may be similar to polycythemia vera; progression to leukemia is unusual except after chemotherapy. Therefore, treatment of patients with asymptomatic ET may not be advisable.     

Terminal deoxynucleotidyl transferase-positive acute myeloblastic leukemia

Terminal deoxynucleotidyl transferase (TdT) is a biochemical marker for acute lymphoblastic leukemia (ALL). In studies of ALL at diagnosis, there are usually greater than 40% TdT-positive cells by indirect immunofluorescence, whereas acute myeloblastic leukemia (AML) shows less than 1% TdT-positive cells. Rare cases of TdT-positive AML have been reported. We present here three AML patients with TdT in 15%, 45%, and 90% of the leukemic blasts. The diagnosis of AML was established on the basis of morphology and cytochemistry, and the cases included one patient with Auer rods. Myeloperoxidase was present respectively in 20%, 90%, and 5% of the blasts. There was no Philadelphia chromosome present in the three cases. These results may indicate the simultaneous presence of lymphoid and myeloid populations, or the presence of a blast cell with both lymphoid and myeloid markers.     

Essential thrombocythemia

Significant progress in our understanding of the molecular pathogenesis of essential thrombocythemia (ET) and the other Philadelphia (Ph) chromosome-negative myeloproliferative disorders (MPDs) has recently been achieved. Unfortunately, the diagnosis of ET still relies on a set of exclusion criteria developed years ago, as recent advances have yet to be evaluated for this purpose. The clinical course of ET is characterized by an increased incidence of thrombotic and hemorrhagic complications and an inherent tendency to progress into myelofibrosis or acute myeloid leukemia (AML). There is concern about undesirable effects of cytoreductive therapy given to prevent vascular events, particularly the risk of accelerating the rate of hematologic transformation. Thus, management involves modification of reversible vascular risk factors and further stratification according to the thrombotic risk. Myelosuppressive agents are not recommended in low-risk patients, whereas controlled studies support the therapeutic value of hydroxyurea (HU) plus aspirin in high-risk cases. Anagrelide or interferon-alpha (IFN-alpha) could be considered as second-line therapy in patients refractory or intolerant of HU. IFN-alpha is preferred in pregnant women.     

Takayasu's arteritis associated with acute myeloblastic leukemia

INTRODUCTION: We present one patient with acute myeloblastic leukemia diagnosed two months after the onset of Takayasu's arteritis.EXEGESIS: A 21-year old woman with a previous history of erythema nodosum and episcleritis was admitted for a left cervical mass. Diagnostic imaging showed an aneurism of the left extracranial internal carotid and a stenosis of the left subclavian artery. Histological findings of the carotid aneurism revealed a granulomatous giant cell arteritis consistent with Takayasu's arteritis. Two weeks after, she was discharged, elevated white cell count (440.000/mm3 ) was disclosed. A bone marrow aspirate documented an acute myeloid leukemia. The patient died of intracerebral hemorrhage. CONCLUSION: Leucocytoclastic vasculitis and polyarteritis nodosa occur in acute myeloid leukemia, but the association with Takayasu's arteritis is new. In our knowledge, only two documented cases of Takayasu's arteritis in association with acute myeloblastic leukemia have been published.     

Gastric myeloid sarcoma without acute myeloblastic leukemia

Myeloid sarcomas(MS)involve extramedullary blast proliferation from one or more myeloid lineages thatreplace the original tissue architecture,and these neoplasias are called granulocytic sarcomas,chloromas or extramedullary myeloid tumors.Such tumors develop in lymphoid organs,bones(e.g.,skulls and orbits),skin,soft tissue,various mucosae,organs,and the central nervous system.Gastrointestinal(GI)involvement is rare,while the occurrence of myeloid sarcomas in patients without leukemia is even rare.Here,we report a case of a 38-year-old man who presented with epigastric pain and progressive jaundice.An upper GI endoscopy had shown extensive multifocal hyperemic fold thickening and the spread of nodular lesions in the body of the stomach.Biopsies from the gastric lesions indicated myeloid sarcoma of the stomach.However,concurrent peripheral blood and bone marrow examinations showed no evidence of acute myeloid leukemia.For diagnosis,the immunohistochemical markers must be checked when evaluating a suspected myeloid sarcoma case.Accurate MS diagnosis determines the appropriate therapy and prognosis.     

Unusual intracytoplasmic inclusions in acute myeloblastic leukemia

Unusual intracytoplasmic inclusions within early granulocyte precursor cells from a patient with acute myeloblastic leukemia (AML) are described. Based upon their staining characteristics and electron- and light-microscopic appearance, the inclusions are distinctly different from any previously described. The inclusions display a variety of shapes, including rectangles, squares, circles, ovals, and irregular, globular forms. Most of the inclusions are refractile and crystal-like. The possible composition of these inclusions is discussed. They are compared with inclusions previously described within leukemic and granulocytic cells.     

Autocrine secretion of GM-CSF in acute myeloblastic leukemia

Three cases of acute myeloblastic leukemia (AML) were identified in which clonogenic cells proliferated autonomously in vitro. Cells from two of these cases were found to secrete a colony-stimulating factor (CSF) that was immunologically and molecularly related to GM-CSF. Growth of AML-CFU could be blocked by the addition of a neutralizing antiserum to GM-CSF. Northern blot hybridization of leukemic cell mRNA with a cDNA probe for the GM-CSF gene revealed a 1-kb message identical in size to the normal GM-CSF message in stimulated T cells. No GM-CSF message was detected in the third case. These results indicate that constitutive expression of the GM-CSF gene, apparently by leukemic cells, can result in autonomous in vitro proliferation of AML-CFU in some cases of AML.     

Sensitivity to 5-azacytidine of blast progenitors in acute myeloblastic leukemia

In a previous study, we showed that the blast stem cells of acute myeloblastic leukemia (AML) were more sensitive to cytosine arabinoside (ara-C) when growing in suspension culture than during colony formation in methylcellulose. We suggested that the difference might be explained by considering the cellular mechanisms responsible for growth in suspension and colony formation. In the former, the clonogenic cells increase in number (self-renewal); in the latter, most of the divisions are terminal. The increased sensitivity to ara-C in suspension might then be attributed to its ability to inhibit self-renewal to a greater degree than cell division generally. A test of this hypothesis would be to compare the survival curves in suspension and in methylcellulose using a drug that spared or stimulated self-renewal. Such an agent is 5- azacytidine (5-aza) and has the additional advantage that its analogue, 6-azacytidine (6-aza) has no effect on self renewal. The data supported the hypothesis, since clonogenic AML blasts were much less sensitive to 5-aza in suspension than in methylcellulose. The effect of 6-aza, while qualitatively similar, was much less marked. Controls showed that the difference in survival curves could not be explained on a kinetic basis or by the secretion of growth factors by 5-aza-treated cells. We suggest that a comparison of the effects of drugs in suspension and in methylcellulose may be useful in preclinical screening of putative anti- AML compounds.     

Evolution to acute myeloblastic leukemia from chronic neutrophilic leukemia with dysplastic features in granulocytic lineage

We experienced the case of an 82-year-old man with chronic neutrophilic leukemia (CNL) with dysplastic features in the granulocytic lineage which subsequently progressed to acute myeloblastic leukemia (AML) with myelofibrosis. The patient had hepatosplenomegaly, but there was no evident cause of neutrophilic leukocytosis. The cytogenetic study showed that he had a normal karyotype. Concentrations of the serum granulocyte colony-stimulating factor (G-CSF) were not detectable. Two years after the diagnosis of CNL, blastic transformation to AML occurred with myelofibrosis and significant morphological abnormalities in neutrophils. The blasts were positive for myeloperoxidase, CD33, CD34, and HLA-DR, and the presence of dysplasia within the granulocytic lineage suggested that he had an abnormality at the level of the granulocyte-committed progenitors. Heterogeneous origins of CNL might lead to various clinicopathological features in each case.     

Essential thrombocythemia in transformation from myelodysplastic syndrome to acute myeloid leukemia with inv(3) after treatment for gastric cancer

In March 1990, a 61-year-old man was given a diagnosis of essential thrombocythemia with a normal karyotype and subsequently treated with hydroxyurea. In November 1995, he underwent surgery for gastric cancer with thereafter received tegafur/uracil for 2 years. Refractory anemia with excess of blasts in transformation and chromosomal abnormalities including -5, -7, 20q-developed in August 1998. Combined chemotherapy with daunorubicin, cytarabine, mercaptopurine, and prednisolone, had only limited effectiveness. Acute myeloid leukemia was finally diagnosed in October 1998, and chromosomal analysis disclosed inv(3) in addition to -5 and -7. The appearance of inv(3) might be related to leukemic transformation of hematopoietic stem cell disease with an increase in the number of megakaryocytes and platelets.     

Acute myeloblastic leukemia presenting as apparent acute otitis media

Three cases of acute myeloblastic leukemia of FAB-M2 type revealed by an isolated otitis media are reported. This mean of revelation is valuable for early diagnosis and treatment of the disease. A karyotype was performed in two cases and showed an 8;21 translocation. As far as we know, these are the first acute myeloblastic leukemia cases with otitis media reported in which an 8;21 translocation was detected.