Ahmet Tunali

The bone marrow aspirate and biopsy in the diagnosis of unsuspected nonhematologic malignancy: a clinical study of 19 cases.

BackgroundAlthough bone marrow metastases can be found commonly in some malignant tumors, diagnosing a nonhematologic malignancy from marrow is not a usual event.MethodsTo underscore the value of bone marrow aspiration and biopsy as a short cut in establishing a diagnosis for disseminated tumors, we reviewed 19 patients with nonhematologic malignancies who initially had diagnosis from bone marrow.ResultsThe main indications for bone marrow examination were microangiopathic hemolytic anemia (MAHA), leukoerythroblastosis (LEB) and unexplained cytopenias. Bone marrow aspiration was not diagnostic due to dry tap or inadequate material in 6 cases. Biopsy results were parallel to the cytological ones in all cases except one; however a meticulous second examination of the biopsy confirmed the cytologic diagnosis in this patient too. The most common histologic subtype was adenocarcinoma, and after all the clinical and laboratory evaluations, the primary focus was disclosed definitively in ten patients (5 stomach, 3 prostate, 1 lung, 1 muscle) and probably in four patients (3 gastrointestinal tract, 1 lung). All work up failed in five patients and these cases were classified as tumor of unknown origin (TUO).ConclusionOur series showed that anemia, thrombocytopenia, elevated red cell distribution width (RDW) and hypoproteinemia formed a uniform tetrad in patients with disseminated tumors that were diagnosed via bone marrow examination. The prognosis of patients was very poor and survivals were only a few days or weeks (except for 4 patients whose survivals were longer). We concluded that MAHA, LEB and unexplained cytopenias are strong indicators of the necessity of bone marrow examination. Because of the very short survival of many patients, all investigational procedures should be judged in view of their rationality, and should be focused on treatable primary tumors.

Maternal and fetal outcomes in pregnancy complicated with acute leukemia: a single institutional experience with 10 pregnancies at 16 years

The incidence of acute leukemia in pregnancy is low and the management of acute leukemia during pregnancy is difficult. We have observed a total of 10 pregnancies in 8 patients. Six of the patients had acute myeloblastic leukemia (AML) and two of them had acute lymphoblastic leukemia (ALL). Three of the pregnancies were diagnosed when the leukemia was in remission, six at the time of leukemia diagnosis and one at the time of leukemic relapse. Six of the pregnancies were found in first trimester, three in the second and one early in the third. Three pregnancies ended with spontaneous abortion, three with intrauterine death and three with medical termination. One of spontaneous abortions and one intrauterine death developed during combination chemotherapy (daunorubicin, cytarabine). Only 1 healthy baby survived from the 10 pregnancies and this child was the not exposed to chemotherapeutic agents. None of the cases had gynecologic and obstetric complications. Five of eight pregnant women with leukemia died because of the primary disease.

Tumor lysis syndrome as a contributory factor to the development of reversible posterior leukoencephalopathy

IntroductionReversible posterior leukoencephalopathy syndrome (RPLS) is a recently described clinical and radiological entity comprising headache, seizures, altered level of consciousness and visual disturbances in association with transient posterior cerebral white-matter abnormalities.MethodWe report a young woman with Burkitt’s lymphoma who developed RPLS after combined chemotherapy administered during the tumor lysis syndrome.ResultsThe symptoms in this patient fitted well with those of RPLS; they included abrupt alterations in mental status, seizures, headache, visual changes and characteristic neuroradiological findings. She was given further combination chemotherapy without any neurological complications, at which time she had already recovered from both RPLS and tumor lysis syndrome.ConclusionAlthough many etiological factors have been reported in the development of RPLS, the underlying mechanism is not yet well understood. With prompt and appropriate management, RPLS is usually reversible, and chemotherapy can be continued after complete recovery from RPLS. We suggest that tumor lysis syndrome should be considered as a contributory factor to the development of RPLS in patients for whom treatment with combined chemotherapy for hematological malignancies is planned.

Idiopathic thrombocytopenic purpura in pregnancy: a single institutional experience with maternal and neonatal outcomes

We observed 13 pregnant women of 70 females with idiopathic thrombocytopenic purpura (ITP) from January 1992 through September 2002. Thirteen mothers with ITP gave birth to twelve babies and two fetuses died. One of the pregnancies produced twins. Seven of the cases were diagnosed with ITP before pregnancy and six during pregnancy. One of the thirteen pregnancies was complicated by preeclampsia, one by ablatio placentae, and one by intrauterine death. Seven mothers received corticosteroid treatment, four high-dose immunoglobulin therapies, and one underwent splenectomy in the second trimester of gestation. At the time of delivery six mothers had normal platelet counts and seven had low platelet counts. Nine deliveries were by vaginal route and four were by cesarean section. Eleven infants were born with normal platelet counts and one was thrombocytopenic at the time of delivery. No infant showed any clinical signs of hemorrhage and there were no neonatal complications. Two fetuses died; one of them because of ablatio placentae and the other was intrauterine dead. In conclusion, ITP in pregnancy requires the management of two patients, the mother and her baby; hence, the close collaboration of a multidisciplinary group composed of a hematologist, obstetrician, anesthesiologist, and neonatologist is essential.

Invasive pulmonary aspergillosis: role of early diagnosis and surgical treatment in patients with acute leukemia

BackgroundAspergillus is a ubiquitous soil-dwelling fungus known to cause significant pulmonary infection in immunocompromised patients. The incidence of aspergillosis has increased during the past two decades and is a frequently lethal complication of acute leukemia patients that occurs following both chemotherapy and bone marrow transplantation. The diagnosis of invasive pulmonary aspergillosis (IPA) according to the criteria that are established by European Organization for the Research and Treatment of Cancer and Mycoses Study Group raise difficulties in severely ill patients. Despite established improvements in field of diagnosis (galactomannan antigen, quantitative PCR, real-time PCR for Aspergillus spp., and findings of computed tomography) and treatment with new antifungals, it is still a major problem in patients with acute leukemia. However, prompt and effective treatment of IPA is crucial because most patients will need subsequent chemotherapy for underlying hematologic disease as soon as possible.Case presentationWe report a 33-year-old male patient with acute promyelocytic leukemia diagnosed in 1993 that developed invasive pulmonary aspergillosis due to A. flavus at relapse in 2003. The patient was successfully treated with liposomal amphotericin B and underwent surgical pulmonary resection. The operative course was uneventful.ConclusionThis report emphasizes the clinical picture, applicability of recent advances in diagnostic and therapeutic approaches for IPA. For early identification of a patient infected with IPA, a high index of suspicion and careful clinical and radiological examinations with serial screening for galactomannan should be established. If aspergillosis is suspected, anti-aspergillosis drug should be administered immediately, and if a unique pulmonary lesion remains, surgical resection should be considered to prevent reactivation during consecutive chemotherapy courses and to improve the outcome.

Rhabdomyosarcoma of the perianal region presenting as acute leukemia

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in adolescence and childhood, which becomes manifest by the locally destructive growth of the primary tumor or its metastases. Sometimes no discernible primary lesion can be detected despite widespread dissemination or in some rare cases the disease may be confined to the marrow. Although approximately 60% of soft tissue sarcomas of children are RMS, it constitutes only 2–5% of all soft tissue sarcomas in adults [1–3]. A 25-year-old female presented with pain and mass of the perianal region, fatigue, fever, and weight loss. Her history revealed that she had developed a papular lesion in her perianal region 4 months before her admittance, which enlarged and acquired a large mass with time. Concomitantly she had symptoms of anemia and weight loss. One month before her admittance, she underwent drainage of the mass as an abscess and had five erythrocyte transfusions at that time. Two weeks before admission, she developed dizziness, epistaxis, and 38°C fever and was referred to our unit with a diagnosis of acute leukemia. Physical examination revealed severe pallor, petechiae on the lower extremities, lymph node with dimension 2×2 cm in the right inguinal region, and a hyperemic, ulcerated, and infected mass with dimensions of 15×10 cm in the lower right gluteus. Her hematologic findings were: hemoglobin 5.3 g/dl, hematocrit 15.3%, mean corpuscular volume (MCV) 80 fl, mean corpuscular hemoglobin (MCHb) 28 pg, WBC 7.69×10/l with 53% polymorphonuclear cells, 16% bands, 18% lymphocytes, 9% monocytes, and 4% blasts, and platelets 107×10/l. Bone marrow smear showed that 90% of marrow cells were tumor cells. They were characterized by vacuolated cytoplasm and the propensity to form pairs, clusters, and multinucleated forms (Fig. 1a–c). Flow cytometric studies of the bone marrow cells revealed no lineage markers for B cells, T cells, or myeloid cells. Trephine biopsy showed complete replacement of marrow (Fig. 1d) and infiltration of the mass by small round cells (Fig. 1e), which stained positively for actin, desmin, and vimentin, but negatively for leukocyte common antigen (LCA) and cytokeratin. The diagnosis of alveolar rhabdomyosarcoma (ARMS) was established. Abdominopelvic computed tomography showed a mass with dimensions of 14×12×10 cm in the medial region of right gluteus and the other masses with 4×3 cm near the inferior ramus pubis and in the anterior part of the right piriform muscle (Fig. 1f). The patient underwent a combined regimen of chemotherapy. Initially the neoplasm responded to chemotherapy, but disease progressed after 4 months. The histological diagnosis of tumor often remains difficult in a variety of solid tumors characterized by round cell morphology including RMS, neuroblastoma, Ewing’s sarcoma, and some cases of non-Hodgkin’s lymphoma [3]. Relatively few conditions spuriously may mimic a hematological disease such as acute leukemia; one of these is ARMS. ARMS in cases of bone marrow involvement is easily confused with acute leukemia and also the clinical picture may mimic the similar systemic symptoms of acute leukemia. The cells of ARMS resemble hematologic blasts (particularly lymphoblasts) and are difficult to differentiate from leukemic cells [2, 4]. R. Ali (*) . F. Özkalemkaş . Ü. Ozan . T. Özçelik . V. Özkocaman . A. Tunalı Department of Internal Medicine, Division of Hematology, Uludağ University School of Medicine, Bursa, Turkey e-mail: ridvanali@uludag.edu.tr Tel.: +90-224-4428400 Fax: +90-224-4428060

Successful treatment of acquired haemophilia with prednisolone therapy

Summary.  Acquired hemophilia is a rare, life threatening coagulopathy in adults caused by the development of autoantibodies against to factor VIII. No general consensus exists on the best therapeutic approach. We report here a case that presented with extensive cutaneous and mucosal bleedings due to factor VIII inhibitors and treated successfully with steroid therapy alone but complicated with a life threatening thromboembolic attack during her follow up. In conclusion, corticosteroids are “cost effective therapy” associated with high inhibitor elimination rates and although recurrence of inhibitor in a patient with factor VIII inhibitor is an expected clinical situation thrombosis risk should also be considered.

Efficacy of bortezomib in combination chemotherapy on secondary plasma cell leukemia

We read with great interest the article by Finnegan et al. [1] in a recent issue of Leukemia & Lymphoma, describing the results of primary plasma cell leukemia (PPCL) treated with bortezomib. We would like to describe and share our experience in a patient with secondary plasma cell leukemia (SPCL), who was successfully treated with a combination of one dose of bortezomib, doxorubicin and dexamethasone, and in whom complete remission was maintained with the administration of a single dose of bortezomib every 3 weeks. A 59-year-old man was diagnosed with IgAk multiple myeloma (MM), stage IA, in April 2001. The management decision was to perform autologous stem cell transplantation following three cycles of combination chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD), but he did not respond to the therapy, and autologous stem cell transplantation could not be performed because of an inadequate stem cell collection. Therefore, from April 2001 to September 2004, he received successive treatments with six cycles of VAD, thalidomide alone, thalidomide plus dexamethasone, and melphalan plus prednisone, respectively. But he did not achieve complete remission. His treatment was complicated with peripheral sensory neuropathy and deep venous thrombosis during the treatment with thalidomide, and he was found to be homozygous for factor V Leiden abnormality. Moreover, he needed treatment for two pneumonia episodes. In September 2004, he presented with fatigue, loss of appetite, and multiple purpuric spots. On physical examination, he had no lymphadenopathy or hepatosplenomegaly. The peripheral blood counts showed hemoglobin 8.14 g/dl; platelets 326 10/l; and white cells count 13.16 10/l. Peripheral blood smear revealed 91% plasma cells. Bone marrow aspirate and trephine biopsy showed 90% plasma cells and plasmablasts. Flow cytometry of the bone marrow aspirate revealed intense positivity for CD38 and intracytoplasmic CD79a. Cytogenetic analysis was normal. The biochemical tests were normal except for calcium (8 mg/dl), total protein (9 g/dl) and albumin (2 g/dl). b2-microglobulin level was 5706 mg/l. Serum protein electrophoresis and immunofixation studies revealed IgAk paraprotein. Upon establishing the diagnosis of SPCL and obtaining the patient’s informed consent, treatment with bortezomib (1.3 mg/m, bolus injection, Day 1), doxorubicin (9 mg/m cont. inf., Days 1 – 4) and dexamethasone (40 mg p.o., Days 1 – 4, 9 – 12, 17 – 20) was commenced. At the end of the first cycle, circulating plasma cells disappeared from peripheral blood. His hemoglobin level and platelet count increased, and he became transfusion-independent. At the end of the 3rd cycle, peripheral blood counts returned to normal with a normal differential, and the percentage of plasma cells in the bone marrow decreased from 90% to 10%. At the end of the 6th cycle, he was in complete remission which was demonstrated both by pathological and serological studies. Afterwards, bortezomib 1.3 mg/m and zolendronic acid 4 mg every 3 weeks were employed as maintenance treatment. In March 2006, 12

Incidence of aplastic anemia in Turkey: A hospital-based prospective multicentre study

The incidence of aplastic anemia among hospitalized adult patients was prospectively determined in this first study in Turkey. New cases of aplastic anemia among patients 14 years and older who were admitted to the study centers were included in a 3 year survey. Seventy-three patients fulfilled the diagnostic criteria, yielding a mean annual incidence rate of 1.14 cases in 10(3) admissions. The male-to-female ratio of the cases (1.6:1) differed from the almost equal ratio of the larger population of Turkey. The median age was 30 years and females were younger at diagnosis. The age distribution of the cases was different from that of the population; showing two incidence peaks in both sexes. The majority of the patients (89%) had severe disease.

Extramedullary Plasmacytoma Involving the Abdominal Vessels and Pancreas

To the Editor: We read with great interest the article by Attwell and colleagues [1] in a recent issue of Digestive Diseases and Sciences that described a case of IgA multiple myeloma (MM) involving two unusual extramedullary sites: the porta hepatis and peritoneum. The involvement of abdominal vessels and pancreas by plasma cell neoplasms is very rare and usually diagnosed at autopsy [1–3]. We would like to describe and share our experience in a patient with known MM who developed plasmacytoma on the chest wall and in the abdomen involving the abdominal vessels and pancreas, without concurrent relapse of the disease, and to add some points concerning the treatment of extramedullary plasmacytomas (EMP). A 64-year-old-man was diagnosed to have stage II MM of the IgA(λ) subtype in 2001. He was given a chemotherapy regimen with six courses of melphalan and prednisolone and achieved a plateau phase. In 2002, at the sixth month of the