Fahir Ozkalemkas

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.

Diffuse involvement of the heart and great vessels in primary cardiac lymphoma

Primary cardiac lymphoma (PCL) is an extremely rare disorder. In this report, a 57-year-old male with diffuse large B-cell lymphoma involving the heart and great vessels is presented. Trans-thoracic echocardiography was the first modality used to establish the diagnosis. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showed diffuse increased metabolic activity of the heart walls and hypermetabolic lesions occupying cardiac chambers in some areas. The patient underwent systemic chemotherapy, and after 13 days, a marked regression of the tumour mass was evident based on echocardiographic examination. After completing six R-CHOP chemotherapy treatments, PET imaging was planned to control the residual mass, but the patient was intubated due to pneumonia that developed after the sixth chemotherapy session and subsequently died due to sepsis.

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.

Tuberculosis presenting as immune thrombocytopenic purpura.

BackgroundAlthough various hematologic abnormalities are seen in tuberculosis, immune thrombocytopenic purpura is a rare event.Case PresentationWe report a case of a 29 year-old male who was presented with immune thrombocytopenia-induced hemoptysis, macroscopic hematuria and generalized petechiae. The patient was found to have clinical, microbiological and radiological evidence of active pulmonary tuberculosis. The immune thrombocytopenic purpura was successfully treated with anti-tuberculous drugs combined with corticosteroids and high dose immune globulin therapy.ConclusionImmune thrombocytopenic purpura can be one of the hematological manifestations of tuberculosis which has a global prevalence with increasing incidence secondary to HIV infection.

Hairy cell leukemia presenting with Guillain-Barre syndrome.

Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder, which mainly infiltrates the bone marrow and the spleen, resulting in peripheral cytopenias and splenomagaly [1]. Unusual complications including autoimmune phenomena have been described in HCL [2 – 4]. Of these, to the best of our knowledge, Guillain-Barre syndrome (GBS) was reported only in two cases so far [5,6]. Here, we describe a HCL patient who presented with GBS at the time of diagnosis. A 61-year-old previously healthy male was referred to our department complaining of weight loss, night sweats, and pain, weakness and parasthesia progressing from distal to proximal limb muscles for the last 3 weeks. There was no preceding history of viral illness or vaccination or any medication. His physical examination revealed pale appearance, hepatomegaly (3 cm) and splenomegaly (3 cm). Precise neurological examination demonstrated second motor neuron type tetraparesis prominent in the lower extremities (20% muscle strength in lower, 80% in the upper extremities) with hypoactive deep tendon reflexes and loss of vibration sense. Blood picture showed Hb 10.9 g/dl, MCV 96 fl, WBC 10.66 10 l with 44% lymphocytes, 37% hairy cells, 17% PNL, and 2% band leukocyte differentiation, and a platelet count of 2126 10 l. Erythrocyte sedimentation rate was elevated (130 mm/h). Biochemistry tests were normal except for alkaline phosphatase. Serum cobalamin level was found in normal limits. Cytomorphological examination of the bone marrow demonstrated a normocellular marrow with hairy cells infiltration. Flow cytometry of the bone marrow cells revealed positivity for CD19 (64%), CD20 (96.1%), CD11c (98.8%), CD25 (99.1%), CD22 (98.9%), and CD103 (29.3%) and negativity for CD23 (8.5%) and CD5 (3.4%). Histopathological examination of the bone marrow established the diagnosis of HCL (Figure 1). Then, the patient was referred to the Neurology department for consultation. Whole spine magnetic resonance imaging was normal. Lumbar puncture was performed. Protein content of cerebrospinal fluid (CSF) was 201 mg/dl and CSF was acellular. Electroneuromyography (ENMG) was consistent with sensorymotor demyelinating polyneuropathy. The patient was diagnosed as GBS with albuminocytologic dissociation of CSF and ENMG findings reflecting demyelination in both sensory and motor nerves. He was treated with

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.