Ipek Yonal

The impact of platelet membrane glycoprotein Ib alpha and Ia/IIa polymorphisms on the risk of thrombosis in the antiphospholipid syndrome.

BACKGROUND Pathogenesis of thrombus formation in antiphospholipid syndrome (APS) is not clear. Platelet membrane glycoprotein (GP) receptors play important roles in development of thrombosis. OBJECTIVES We investigated the association between development of thrombosis in APS and polymorphisms of GPIb alpha variable number of tandem repeats (VNTR), Kozak, and GPIa C807T. Patients/Methods Sixty patients with APS (30 with proven thrombosis and 30 without thrombosis) and 63 controls were included. Presence of GPIa C807T polymorphism was determined with real-time PCR and GPIb alpha Kozak and VNTR polymorphisms by conventional PCR. RESULTS Frequency of C807T TT genotype was significantly higher in APS with thrombosis than APS without thrombosis (p=0.023) and also in APS with multiple thrombi compared to APS without thrombi (p=0.023). Frequency of Kozak TC genotype was higher in APS with arterial thrombosis compared to APS with venous thrombosis, controls, and APS without thrombosis (p=0.03, p=0.0007, and p=0.0024 respectively). D allele frequency and D allele carrier state for VNTR were significantly less in APS than controls (p=0.0018 and p=0.0046 respectively). CONCLUSIONS C807T TT genotype may confer a risk for thrombosis and Kozak TC genotype for arterial thrombosis. D allele of VNTR may protect from APS. No patients with C807T TT or Kozak TC genotypes carried the protective DD genotype of VNTR. These polymorphisms may increase risk for both arterial and venous thrombosis. The utility of prophylaxis with anti-platelet drugs in at least a subgroup of APS patients should be investigated with clinical trials.

Aleukemic Leukemia Cutis Manifesting with Disseminated Nodular Eruptions and a Plaque Preceding Acute Monocytic Leukemia: A Case Report

Aleukemic leukemia cutis (ALC), a discrete tumor of leukemic cells involving the skin, may be the first manifestation of acute myeloid leukemia, preceding the onset in marrow and blood by months and years. ALC is often difficult to diagnose and is associated with a dismal prognosis. A 63-year-old male presented with nodular swellings on the face, a plaque extending over the right shoulder and multiple enlarged cervical lymph nodes. The skin biopsy of the plaque lesion showed a diffuse neoplastic infiltration extending from the dermis to subcutaneous tissue with diffuse positivity for myeloperoxidase and focal positivity for CD34 on immunohistochemical staining. The diagnosis was leukemia cutis. One month later, acute monocytic leukemia (FAB AML-M5b) was diagnosed. The patient died on the seventh month of diagnosis.

A case of chronic lymphocytic leukemia with massive ascites.

An 81-year old woman with a history of chronic lymphocytic leukemia (CLL) was admitted with night sweats and abdominal distension. A complete blood count showed hemoglobin 5 g/dL, white blood cell (WBC) count 28.5×109/L and platelets 38.4×109/L. Peripheral blood smear examination showed a large number of smudge cells and lymphocytosis composed of mature-looking lymphocytes with clumped nuclear chromatin. Computed tomography scan demonstrated enlarged cervical, axillary, paraaortic, retroperitoneal and mesenteric lymph nodes with concomitant omental thickening and ascites. Also, the liver and the spleen were enlarged in the presence of multiple ill-defined hypoechoic areas in the latter. Histopathological analysis of the cervical lymph node biopsy was consistent with CLL. Bone marrow examination showed diffuse infiltration of the marrow with small lymphocytes. Analysis of the ascitic fluid revealed an exudate with WBC 1220 cells/mL. Cytocentrifuge preparation of the ascitic fluid showed small mature lymphoid cells containing hyperchromatic nuclei with coarsely granular chromatin. On flow cytometric analysis of the ascitic fluid, expression of CD5, CD19, CD20, CD22, CD23, CD45 and HLA-DR was compatible with a diagnosis of CLL, in accordance with the results of the peripheral blood analysis. The patient was treated with chemotherapy consisting of cyclophosphamide, vincristine and prednisolone but died within one month after development of non-chylous ascites.

The co-presence of deletion 7q, 20q and inversion 16 in therapy-related acute myeloid leukemia developed secondary to treatment of breast cancer with cyclophosphamide, doxorubicin, and radiotherapy: a case report

IntroductionTherapy-related acute myeloid leukemia occurs as a complication of treatment with chemotherapy, radiotherapy, immunosuppressive agents or exposure to environmental carcinogens.Case presentationWe report a case of therapy-related acute myeloid leukemia in a 37-year-old Turkish woman in complete remission from breast cancer. Our patient presented to our facility with fatigue, fever, sore throat, peripheral lymphadenopathy, and moderate hepatosplenomegaly. On peripheral blood and bone marrow aspirate smears, monoblasts were present. Immunophenotypic analysis of the bone marrow showed expression of CD11b, CD13, CD14, CD15, CD33, CD34, CD45 and human leukocyte antigen-DR, findings compatible with the diagnosis of acute monoblastic leukemia (French-American-British classification M5a). Therapy-related acute myeloid leukemia developed three years after adjuvant chemotherapy consisting of an alkylating agent, cyclophosphamide and DNA topoisomerase II inhibitor, doxorubicin and adjuvant radiotherapy. Cytogenetic analysis revealed a 46, XX, deletion 7 (q22q34), deletion 20 (q11.2q13.1) karyotype in five out of 20 metaphases and inversion 16 was detected by fluorescence in situ hybridization. There was no response to chemotherapy (cytarabine and idarubicin, FLAG-IDA protocol, azacitidine) and our patient died in the 11th month after diagnosis.ConclusionsThe median survival in therapy-related acute myeloid leukemia is shorter compared to de novo acute myeloid leukemia. Also, the response to therapy is poor. In therapy-related acute myeloid leukemia, complex karyotypes have been associated with abnormalities of chromosome 5, rather than 7. To the best of our knowledge, this is the first case of therapy-related acute myeloid leukemia showing the co-presence of deletion 7q, 20q and the inversion 16 signal.

Massive Ascites as the Initial Manifestation of Mantle Cell Lymphoma: A Challenge for the Gastroenterologist

Involvement of the serosa may be the presenting feature in a wide and complex variety of lymphoproliferative diseases, with differing clinical outcomes covering a spectrum of benign and malignant conditions. Effusions involving peritoneal and pericardial cavities are uncommon during the course of hematological malignancies. Obstructive and/or infiltrative tumor mass or vascular leakage due to stimulation by vascular endothelial growth factor contribute to the pathogenesis. In addition to clinical findings, cytomorphology and flow cytometric immunophenotyping of the serosal fluid yield valuable information in the differential diagnosis of lymphocytic infiltrates. Herein, we describe the case of primary mantle cell lymphoma in a 75-year-old man presenting with abdominal fullness and weight loss, suggesting a gastrointestinal pathology.

Leukemic ascites as an initial presentation of acute myelomonocytic leukemia with inversion of chromosome 16.

To the Editor: The inversion of chromosome 16, inv(16), a cytogenetic abnormality expressed in core binding factor acute myeloid leukemias (AML), is associated with myelomonocytic differentiation and eosinophilia.1 Even though inv(16) generally portends a good prognosis, accompanying mutations detected by molecular genetic methods, such as KIT and Ras mutations, alter their response to treatment.2 Infiltration of leukemic cells into serous effusions is unusual. To our knowledge, there are only a few reports of AML with inv(16) presenting with leukemic ascites.2 We present a 33-year-old woman with jaundice and massive ascites. The laboratory tests showed the following: hemoglobin 8.3 g/dL, hematocrit 25%, total leukocyte count 135 800/mm3, and platelet count 32 000/mm3, erythrocyte sedimentation rate 45 mm/hr, AST 597 U/L, ALT 111 U/L, ALP 417 U/L, GGT 191 U/L, lactate dehydrogenase 6515 U/L, total bilirubin 9 mg/dL and direct bilirubin 8.2 mg/dL. On peripheral blood smear, myeloblasts comprised 67% of the cells and the bone marrow analysis showed 57% myeloblasts with eosinophilic differentiation. Immunophenotypic analysis of the bone marrow was positive for CD13, CD14, CD45, CD33, CD34 and HLA-DR. FISH analysis of the bone marrow revealed an inv(16) signal. The final diagnosis was acute myelomonocytic leukemia (FAB Classification M4e) with inv(16). Abdominal computed tomography revealed massive ascites and multiple lympadenopathies with a maximal diameter of 1.5 cm at the mesenteric region. A diagnostic and therapeutic paracentesis was performed. Analysis of the ascitic fluid showed an exudate with a white blood cell count 3140 cells/ mL; red blood cell count 70000 cells/mL; monocyte count 1910 cells/mL. The ascitic total protein was 3.9 g/dL (serum, 7.1 g/dL), glucose 208 mg/dL (serum, 216 mg/ dL), lactate dehydrogenase 1918 U/L (serum, 2813 U/L) and albumin 2.4 g/dL (serum, 3.9 g/dL). Cytocentrifuge preparation of the patient’s ascitic fluid showed myeloblasts and monoblasts with irregular nuclei and prominent nucleoli (Figure 1). Flow cytometric analysis of the ascitic fluid showed the expression of CD13, CD14, CD33, CD34, CD45 and HLA-DR compatible with the diagnosis of acute

Plasmacytoma of the Nasolacrimal Duct Simulating Dacryocystitis: An Uncommon Presentation for Extramedullary Relapse of Multiple Myeloma

The most common site for localized forms of plasma cell neoplasms (extramedullary plasmacytoma; EMP) is the upper respiratory tract, including the oropharynx, nasal cavities, sinuses and larynx. A 50-year-old woman with a history of myeloma in complete remission after autologous stem cell transplantation complained of two weeks of epiphora of the left eye with subsequent diplopia, bloody nasal discharge and progressive swelling around the nasolacrimal sac. A solitary mass in the left sinonasal area, extending to the nasolacrimal duct (NLD) was detected on MRI, whose histopathological examination was consistent with plasmacytoma. Further clinical investigation ruled out multiple myeloma (MM). The patient underwent debulking surgery and adjuvant chemotherapy followed by local radiotherapy in an attempt to achieve complete response. Despite being a rare entity, EMP of the NLD should be considered in the differential diagnosis of epiphora and dacryocystitis. To our knowledge, this is the first case of a plasmacytoma of the NLD presenting as isolated extramedullary relapse of MM. The follow-up in EMPs should include appropriate imaging studies, a systemic workup to rule out MM.

Primary Mediastinal large B-Cell Lymphoma as an incidental finding: report of a case.

A 21-year-old female was examined for an incidentally detected left parahilar mass on chest radiograph which was taken at the time of job application (Figure 1a). Thoracic computed tomography revealed a mass of 10x9x5 cm with irregular lobulated borders in the anterior mediastinum invading the pericardium (Figure 1b). Histopathological examination of the anterior mediastinotomy material revealed large neoplastic B cells staining positive for CD20 and MUM-1, negative for CD10, and with a high Ki-67 proliferation index (80%-90%) (Figure 2). On positron-emission tomography scan, only the mediastinal mass showed increased fludeoxyglucose uptake (SUVmax: 18) (Figure 1c). Final diagnosis was stage 1A primary mediastinal large B-cell lymphoma (PMBCL). After 6 cycles of R-CHOP, PET scan showed partial anatomical and metabolic response. R-CHOP was completed to 8 cycles followed by mediastinal radiation. She has now been disease-free for 2 years.

Impact of JAK2V617F Mutational Status on Phenotypic Features in Essential Thrombocythemia and Primary Myelofibrosis.

Objective: The JAK2V617F mutation is present in the majority of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF). The impact of this mutation on disease phenotype in ET and PMF is still a matter of discussion. This study aims to determine whether there are differences in clinical presentation and disease outcome between ET and PMF patients with and without the JAK2V617F mutation. Materials and Methods: In this single-center study, a total of 184 consecutive Philadelphia-negative chronic myeloproliferative neoplasms, 107 cases of ET and 77 cases of PMF, were genotyped for JAK2V617F mutation using the JAK2 Ipsogen MutaScreen assay, which involves allele-specific polymerase chain reaction. Results: ET patients positive for JAK2V617F mutation had higher hemoglobin (Hb) and hematocrit (Hct) levels, lower platelet counts, and more prevalent splenomegaly at diagnosis compared to patients negative for the JAK2V617F mutation, but rates of major thrombotic events, arterial thrombosis, and venous thrombosis were comparable between the groups. At presentation, PMF patients with JAK2V617F mutation had significantly higher Hb and Hct levels and leukocyte counts than patients without the mutation. Similar to the findings of ET patients, thromboembolic rates were similar in PMF patients with and without theJAK2V617F mutation. For ET and PMF patients, no difference was observed in rates of death with respect to JAK2V617F mutational status. Moreover, leukemic transformation rate was not different in our PMF patients with and without JAK2V617F mutation. Conclusion: We conclude that JAK2V617F-mutated ET patients express a polycythemia vera-like phenotype and JAK2V617F mutation in PMF patients is associated with a more pronounced myeloproliferative phenotype.

Tüylü hücreli lösemi tanılı iki olguda birinci dizi ve nükste kladribin uygulaması

Tuylu hucreli losemi (THL) birinci dizi ve nukste purin nukleozid analogu olan kladribin (2-klorodeoksiadenozin) ile tedavi edilebilen nadir gorulen kronik seyirli lenfoproliferatif hastaliktir. Bu yazida THL tanisi ile kladribin uygulanarak tam remisyon (TR) elde edilmis ve taninin 6. yilinda nuks nedeniyle tekrar kladribin uygulanmasi sonrasi 3. ayda kemik iligi biyopsisinde retikulin liflerinin kayboldugu, tuylu losemi hucrelerinin de saptanmadigi (tekrar TR elde edilen) bir olgu ve THL tanisi ile kladribin uygulanarak TR elde edilen, taninin 14. yilinda nuks THL tanisiyla kladribin uygulanmasinin 23. gununde notropenik ates, candida pnomonisi ve septik sok sonucu eks olan ikinci bir olgu bildirilmektedir.