Fehmi Hindilerden

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.

Hairy Cell Leukemia Presenting with Isolated Skeletal Involvement Successfully Treated by Radiation Therapy and Cladribine: A Case Report and Review of the Literature

We describe an unusual case of hairy cell leukemia (HCL) in a 55-year-old male presenting with isolated skeletal disease as the initial manifestation without abnormal peripheral blood counts, bone marrow involvement, or splenomegaly. To the best of our knowledge, there have been only two previous reports of a similar case. The patient presented with pain in the right femur. Anteroposterior radiographs of both femurs revealed mixed lytic-sclerotic lesions. PET scan showed multiple metastatic lesions on axial skeleton, pelvis, and both femurs. Histopathological examination of the bone biopsy revealed an infiltrate of HCL. Localized radiation therapy to both proximal femurs and subsequently 4 weeks later, a 7-day course of 0.1 mg/kg/day cladribine provided complete remission with relief of symptoms and resolution of bone lesions. We addressed the manifestations and management of HCL patients with skeletal involvement.

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.

The Clinical Significance of IDH Mutations in Essential Thrombocythemia and Primary Myelofibrosis

Background Limited data exist regarding impact of IDH mutations in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs). Prognostic significance of IDH mutations was asessed in 184 Ph-negative MPN patients - 107 essential thrombocythemia (ET) and 77 primary myelofibrosis (PMF). Methods High-resolution melting (HRM) analysis was used to detect IDH1 and IDH2 mutations. Results PMF and ET patients showed no significant difference for prevalence of IDH mutations. Mutant IDH (IDH1 or IDH2) was documented in five of PMF (6.5%) and two of ET patients (1.9%). IDH mutations in ET patients included one IDH1 R132C and one IDH2 R140Q. Of the five IDH-mutated PMF patients, four (80%) displayed IDH1 (three IDH1 R132C and one IDH1 R132S) and one (20%) carried IDH2 (IDH2 R140Q) mutation. Sixty percent (three in five) of IDH-mutated PMF patients carried JAK2V617F with following allele burdens: 31-50%, 5-12.5% and 31-50%, respectively. Three of 77 PMF patients (3.9%) simultaneously harbored IDH and JAK2V617F mutations. IDH mutations in PMF showed a trend towards higher rate in females (100% and 52.8%, respectively). Bleeding complications were significantly higher in IDH-mutated PMF patients compared to IDH wild-type counterparts. Trend towards a lower prevalance of acetylsalicylic acid (ASA) use was present in IDH mutant PMF patients compared to wild-type counterparts (20% and 63.9%, respectively). Death rate was higher in IDH-mutated PMF patients compared to IDH wild-type PMF patients (60% and 15.3%). In univariate analysis, a significantly shorter leukemia-free survival (LFS) was observed in IDH-mutated PMF patients. Conclusions We conclude that IDH mutations indicate a risk for leukemic transformation in PMF.

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.

A Rare Cause of Unexplained Refractory Iron Deficiency Anemia: Unicentric Plasma-Cell Type Castleman’s Disease

Castleman’s disease (CD) is an uncommon benign lymphoproliferative disorder characterized by enlargement of hyperplastic lymph nodes with abnormal interfollicular vascular growth [1]. It is clinically categorized as unicentric disease or multicentric disease. Histopathologic variants of CD include hyaline-vascular type, plasma-cell (PC) type, and mixed form [2]. CD presents with features ranging from asymptomatic lymphadenopathy to systemic manifestations such as serious infections, anemia, and nerve damage [3]. In CD, hepcidin secretion induced by IL-6 is the main cause of anemia [4,5]. Anemia is more common in multicentric CD and is rarely reported in unicentric CD [3]. Few cases of unicentric PC type CD associated with iron deficiency anemia (IDA) have been reported [6,7,8,9]. To our knowledge, there is only one previous reported case of adult unicentric PC type CD located in the abdomen and presenting with IDA [9]. We describe an adult with occult unicentric PC type CD of the abdomen presenting with iron-refractory anemia (IRA) and achieving dramatic response to curative resection.

Primary B-Cell Mucosa-Associated Lymphoid Tissue Lymphoma of the Hard Palate and Parotid Gland: Report of One Case and Review of the Literature

A 61-year-old woman was admitted to our hospital with an ulcerated palate mass and swelling of the right parotid gland. Incisional biopsy from the hard palate revealed an extranodal marginal zone B-cell lymphoma, also called mucosa-associated lymphoid tissue (MALT) lymphoma. Final diagnosis was MALT lymphoma of the parotid gland with concomitant involvement of an extremely seldom site of involvement: the hard palate. To our knowledge, this report illustrates the first case of MALT lymphoma of the hard palate and parotid gland without an underlying autoimmune disease. Rituximab-based combination regimen (R-CHOP) provided complete remission with total regression of mass lesions at the hard palate and parotid gland. At 44-month follow-up, there is no disease relapse. We adressed the manifestations and management of MALT lymphoma patients with involvement of salivary gland and oral cavity.

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.