Atypical presentations of eosinophilic fasciitis.

Eosinophilic fasciitis is an uncommon connective tissue disease that may mimic and overlap with other sclerosing disorders such as morphea and lichen sclerosus. Herein, we report four patients (two men and two women, aged 16-64 yeas) with eosinophilic fasciitis. There was overlap with both morphea and lichen sclerosus in 2 patients and with morphoea alone in 1 patient. Magnetic resonance imaging (MRI) was used for diagnosis in three patients and for assessing treatment response in one patient. Eosinophilic fasciitis may co-exist with morhoea and lichen sclerosus. In view of the overlapping clinical and histopathological features of these disorders, MRI may be helful in delineating the conditions by detecting involvement of fascia.

Myelodysplastic syndrome with t(9;22)(p24;q11.2), a BCR-JAK2 fusion: case report and review of the literature.

The human JAK2 gene is mainly targeted by two types of genetic lesions that play roles in the pathogenesis of hematologic malignancies: intragenic mutations and chromosomal translocations. Chromosomal translocations of JAK2 are typically associated with myeloid or lymphoid malignancies with an aggressive course and poor outcome. Here we report a t(9;22)(p24;q11.2) translocation, in a MDS patient and review results associated with BCR-JAK2 fusion reported in the literature.

Relationship of P-selectin glycoprotein ligand-1 to prognosis in patients with multiple myeloma.

BACKGROUND: Changes occur in adhesion molecules in the disease course of multiple myeloma. P-selectin glycoprotein ligand-1 (PSGL-1, CD162) works as the ligand of selectin-neutrophil adhesion molecules. The aim of the present study was to investigate the relationship between PSGL-1 expression in the bone marrow and the known prognostic factors for multiple myeloma disease, disease stage, and survival. MATERIALS AND METHODS: This research included 63 patients with multiple myeloma (26 women [41.3%]; 37 men [58.7%]). The bone marrow biopsy samples obtained at disease diagnosis for each patient were stained immunohistochemically in terms of CD162 expression using standard diagnostic immunohistochemical staining methods. The laboratory results, CD162 expression, overall survival, demographic characteristics of the disease, and the relationship between CD162 expression and the disease stage were evaluated. RESULTS: Among the 63 patients included in the present study, the survival rate was 82.3% for 1 year, 73.2% for 2 years, 63.4% for 3 years, 51.7% for 4 years, 40.3% for 5 years, and 33.6% for 6 and 7 years. A statistically significant difference was not detected between the CD162 staining ratio and disease survival (P = .232). A statistically significant difference was not detected between the CD162 staining degree and survival rate (P = .184). However, the overall survival of the patients with no CD162 expression in the bone marrow was lower than that for the patients whose CD162 was stained 1, 2, and 3 degrees (12.33 ± 11.49, 28.65 ± 31.44, 37.25 ± 29.32, and 47.92 ± 45.29 months, respectively; P < .001). CONCLUSION: In the present study, CD162 staining and the staining degree, with the other standard immunohistochemical stains, were shown to be beneficial in the diagnosis of multiple myeloma disease. However, the results did not provide information about the disease course. Studies of a larger number of patients to examine P-selectin and interleukin-6 levels are needed to investigate the disease course.

Newly diagnosed breast cancer in a patient receiving imatinib mesylate.

Imatinib mesylate is the standard treatment of chronic myeloid leukemia (CML). Despite imatinib is being used in the treatment of other malignancies as well, its potential role on de novo tumor growth is not known. Secondary malignancies are rarely seen in patients with CML and particularly in those receiving imatinib. Here, we present a CML patient taking imatinib therapy that was diagnosed to have breast cancer and received adjuvant chemo-and radiotherapy with imatinib. We tried to explain co-occurrence of these rare events by probable pathogenetic mechanisms.

Bortezomib in patients with renal impairment.

Renal failure is a common manifestation of multiple myeloma (MM). Bortezomib is primarily metabolized by cytochrome p450 isoforms. It also has a cytochrome-independent metabolism by excretion through the bile and kidney. Based on our observations, we aimed to explore the efficacy and toxicity profiles of bortezomib in 56 patients with MM, 24 of which had moderate to severe renal failure. Overall response and complete response, as well as very good partial response rates, were comparable between patients with normal renal functions and renal impairment. The median overall survivals for patients with estimated glomerular filtration rates of <60 and ≥60 ml/minute were similar. Although there was a tendency for shorter overall survival along lower estimated glomerular filtration rates, this difference did not reach a statistical significance. Overall and severe adverse events, and dose modification and treatment discontinuation rates were higher in patients with renal impairment. Patients with renal failure had more thrombocytopenia and diarrhea. While thrombocytopenia was mild to moderate and manageable, diarrhea, which led to serious adverse events, was more severe in patients with renal failure who received bortezomib as monotherapy. Bortezomib appears to be active; however, when used alone, it may cause more frequent and severe adverse events in patients with MM and renal failure.

Aberrant expression of c-met and HGF/c-met pathway provides survival advantage in B-chronic lymphocytic leukemia.

BACKGROUND: B-chronic lymphocytic leukemia (B-CLL) is characterized by accumulation of CD5(+) B lymphocytes. Decreased VLA-4 (Cd49d/CD29) and CD11a expression and defective adhesion in B-CLL have been previously shown, although there was no substantial data about its importance in immunobiology of B-CLL. The hepatocyte growth factor (HGF) receptor, c-met, plays a role in adhesion by acting on VLA-4. c-met and VLA-4 share crucial signaling molecules in cell survival. In this study, relationship between expressions of c-met and CD49d, CD11a, and additional common signaling molecules in B-CLL was investigated. METHODS: White blood cells from 24 patients with CLL were studied by flow cytometry and/or western blotting prior to and after culturing with recombinant HGF. HGF level from sera was measured with a bead-based flow cytometric assay. RESULTS: c-metα and c-metß were expressed on B-CLL cells, while no expression was observed on normal donor CD19+ cells. This increase was inversely correlated with decreased expression of adhesion molecules. Serum level of HGF in B-CLL was found to be increased. In vitro experiments showed that HGF supported survival in B-CLL cells supporting the possible function of HGF/c-met pathway in B-CLL. Furthermore, expressions of critical signaling molecules shared by both VLA-4 and HGF/c-met systems including Bcl-XL, Akt, PI3K, and phospho-bad(136) following HGF stimulations of B-CLL cells have been found to be increased. CONCLUSION: Increased expression of c-met and HGF may bypass the importance of expression of critical adhesion molecules and support survival of B-CLL cells. c-met, being one of the surface tyrosine kinases, may serve as a target for future therapies in B-CLL meriting more attention.

Short and long term effects of granulocyte colony-stimulating factor during induction therapy in acute myeloid leukemia patients younger than 65: results of a randomized multicenter phase III trial.

This prospective multicenter phase III clinical trial was designed to assess efficacy and safety of G-CSF as an adjunct to de novo AML remission induction therapy (www.clinicaltrials.gov. NCT00820976). Patients' characteristics were similar in both arms. G-CSF improved severity and duration of leukopenia. Three-year OS were similar (25.6 ± 5.1% vs. 31.8 ± 5.6%) in both arms except for patients with myeloblastic features. Significant factors for better survival were the use of G-CSF (p=0.049), female sex (p=0.05) and single induction cycle (p<0.001) in multivariate analysis. Female patients performed better than male patients. Better survival obtained among female AML patients needs to be validated within the context of cytogenetic analysis.

Precursor B cell lymphoblastic lymphoma presenting as a solitary bone tumor: a case report and review of the literature.

Precursor B cell lymphoblastic lymphoma (B-LBL) is quite uncommon and it usually manifests as an extranodal disease. Although B-LBL may present with bone involvement, it is a very rare manifestation of B-LBL as a primary solitary bone tumor. Here, we report a case of precursor B-LBL presenting with solitary bone tumor and a review of a total of seven adult patients reported previously in the literature. We described demographic and clinical characteristics of these patients with unique presentation and discussed treatment options. Unlike previous reports except one case, our patient underwent allogeneic stem cell transplantation (allo-SCT) due to refractory disease. She is alive without evidence of disease by the post-transplant 12th month. B-LBL has an aggressive clinical course in adult patients and allo-SCT may be the best treatment option.

Expression and prognostic significance of Cox-2 and p-53 in Hodgkin lymphomas: a retrospective study.

BACKGROUND: Cyclooxygenase (cox) is the rate-limiting enzyme, which catalyzes the conversion of arachidonic acid into prostaglandins and contributes to the inflammatory process. Cyclooxygenase-2 (cox-2), which is one of the two isoforms, plays a role in tumor progression and carcinogenesis. p53 contributes to apoptosis, DNA renewal and cell cycle. Studies concerning the relationship of cox-2 and p53 expressions and carcinogenesis are available, but the association between cox-2 and p53 in Hodgkin lymphoma (HL) is not exactly known.In our study, we examined the association of cox-2 and p53 expression, with age, stage, histopathological subtype, and survival in HL. We also examined correlation between cox-2 and p53 expression. METHODS: Cox-2 and p53 expressions in Hodgkin-Reed Sternberg cells (HRS) were examined in 54 patients with HL depending on cox-2 expression, stained cases were classified as positive, and unstained cases as negative. Nuclear staining of HRS cells with p53 was evaluated as positive. The classifications of positivity were as follows: negative if<10%; (1+) if 10-25%; (2+) if 25-50%; (3+) if 50-75%, (4+) if >75%. RESULTS: Cox-2 and p53 expressions were found in 49 (80%) and 29 (46%) patients, respectively. There were differences between histological subtypes according to cox-2 expression (p = 0.012). Mixed cellular (MC) and nodular sclerosing (NS) subtypes were seen most of the patients and cox-2 expression was evaluated mostly in the mixed cellular subtype.There were no statistically significant relationships between p53 and the histopathological subtypes; or between p53, cox-2 and the factors including stage, age and survival; or between p53 and cox-2 expression (p > 0.05). CONCLUSION: Considering the significant relationship between the cox-2 expression and the subtypes of HL, cox-2 expression is higher in MC and NS subtypes. However the difference between these two subtypes was not significant. This submission must be advocated by studies with large series.

Bortezomib: a new therapeutic option for POEMS syndrome.

OBJECTIVE: POEMS syndrome with its classical five findings (Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin changes) is a rare multisystem disease. Proinflammatory and proangiogenic cytokines play important roles in its pathogenesis. Treatment options are still debated. METHODS: We present a 65-year-old man with POEMS syndrome who was successfully treated with bortezomib. RESULTS: After seven cycles of this protocol, serum M protein level declined to normal range, and near-to-complete remission was achieved. His symptoms of polyneuropathy improved dramatically. CONCLUSION: Bortezomib may be an effective and safe therapeutic option for patients with POEMS syndrome.

Long-term culture-initiating cells (LTC-IC) produced from CD34+ cord blood cells with limiting dilution method.

OBJECTIVE: Even though much progress has been made in defining primitive hematologic cell phenotypes by using flow cytometry and clonogenic methods, the direct method for study of marrow repopulating cells still remains to be elusive. Long Term Culture-Initiating Cells (LTC-IC) are known as the most primitive human hematopoietic cells detectable by in vitro functional assays. METHODS: In this study, LTC-IC with limiting dilution assay was used to evaluate repopulating potential of cord blood stem cells. RESULTS: CD34 selections from cord blood were completed succesfully with magnetic beads (73,64%±9,12). The average incidence of week 5 LTC-IC was 1: 1966 CD34+ cells (range 1261-2906). CONCLUSION: We found that number of LTC-IC obtained from CD34+ cord blood cells were relatively low in numbers when compared to previously reported bone marrow CD34+ cells. This may be due to the lack of some transcription and growth factors along with some cytokines and chemokines released by accessory cells which are necessary for proliferation of cord blood progenitor/stem cells and it presents an area of interest for further studies.

Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma: report of a rare case and review of the literature.

A rare case of human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma: a report and review of the literature. APMIS 2009; 117:222-29. Primary effusion lymphoma (PEL) is a very rare type of lymphoma usually confined to the body cavities predominantly in immunosuppressed patients infected with human herpes virus 8 (HHV-8). The new term for HHV-8 independent PEL is HHV8-unrelated PEL-like lymphoma. We describe an 89-year-old human immunodeficiency virus (HIV)-negative male patient with HHV8-unrelated PEL-like lymphoma in the pleura. No hepatosplenomegaly or lymphadenopathy was detected. Chest radiography and computed tomography revealed right pleural effusion, but no evidence of tumor mass or lymph node enlargement. Cytological analysis of the pleural effusion revealed a high-grade lymphoma with round nuclei, prominent nucleoli and abundant cytoplasm with immunophenotypes positive for CD45, CD30, CD38, CD7 and CD71. Because of the advanced age, no chemotherapy was given. Effusion resolved spontaneously. One year after the diagnosis, a new pleural effusion developed at the left side. Following thoracentesis and pleurodesis, the patient remained in complete remission for 40 months. To date, 30 cases of HHV8-unrelated PEL-like lymphoma/HIV negative have been reported in the literature. The outcome of the HHV8-unrelated PEL-like lymphoma patients who were HIV negative seems to be better than HIV- and HHV-8-positive PEL.

A case of Cauda Equina syndrome in a leukemic patient due to intrathecal methotrexate.

The leukemias may cause neurologic dysfunction through either direct invasion of the nervous system or indirectly through cytopenias, or it may occur as a result of the necessarily vigorous treatment programs for leukemia. We report here a 24-year-old acute lymphoblastic leukemia patient who in her second cycle of hyper-CVAD chem therapy regimen (high-dose Ara-C and high-dose methotrexate) received intrathecal methotrexate and two days afterwards was diagnosed as having Cauda Equina syndrome (CES). A lumbo-sacral MRI imaging with gadolinium was performed and there was a remarkable enhancement in the Cauda Equina region, suggesting either leukemic involvement or a type of neurologic complication associated with intrathecal methotrexate treatment. To rule out leukemic involvement, a lumbar puncture was performed and the CSF was free of leukemic cells. There are cases of CES developing after spinal anesthesia reported in the literature, but this is the first report of CES due to intrathecal methotrexate.

Complete heart block in a neutropenic patient with invasive aspergillosis.

A patient with leukemia who developed complete heart block after the diagnosis of pulmonary aspergillosis is reported. The patient had probable invasive pulmonary aspergillosis with a sudden tachypnea, dyspnea, fever, bilateral pulmonary infiltrates and acute respiratory insufficiency after chemotherapy. On the sixth day of antifungal therapy, she developed complete atrioventricular block. Complete heart block has not been reported during liposomal amphotericin B (LAMB) therapy. Local or hematogenous involvement of the myocardium with aspergillosis may be the most likely explanation of the complete heart block.

Myelodysplastic syndrome with pseudoreticulocytosis.

A patient with myelodysplastic syndrome (MDS) with refractory anemia who had marked reticulocytosis in the absence of hemolytic anemia and/or blood loss is reported. Erythrocyte survival test showed that more than 50% of the patient's reticulocytes were still present on day seven. This should be due to the prolongation of reticulocyte maturation in MDS, and is known as pseudoreticulocytosis. This phenomenon which mimicks hemolytic anemia is an unusual presentation of myelodysplastic syndrome, with only 7 patients with pseudoreticulocytosis being reported previously.

Amifostine treatment in patients with myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a clonal disorder that is characterized by peripheral cytopenia and the induction of apoptosis is thought to be partially responsible for pathological haematopoiesis in MDS. Amifostine is a cytoprotective and antioxidant agent, and it may prolong the survival of progenitor cells in MDS by delaying apoptosis. The study has been carried out with 9 MDS cases. Four of them were diagnosed as refractory anemia (MDS-RA), two as refractory anemia with ring sideroblasts (MDS-RARS) and the remaining three as refractory anemia with excess blasts (MDS-RAEB) according to the French-American-British (FAB) classification. Amifostine was given in a dose of 400 mg/m2, as an IV infusion administered in 5-6 minutes, three times a week for 4 consecutive weeks. Three of the cases (33.3%), two with MDS RARS and one with MDSRA, showed a significant improvement in the number of total leukocyte, neutrophil and reticulocyte counts and a decrease in the requirement of erithrocyte transfusions. In clinically responsive cases, all hematological parameters returned back to pre-treatment values two weeks after the cessation of therapy. We conclude that Amifostine can be used in a selected group of patients with MDS-RA and MDS-RARS.

Bone marrow necrosis in a patient with non-Hodgkin lymphoma.

Bone marrow necrosis is a rare but ominous finding in various malignant and nonmalignant disorders. It is usually a postmortem diagnosis, but with the advent of modern imaging methods and clinical suspicion, bone marrow necrosis can be diagnosed as antemortem, especially in malignant disorders. We report a 60-years old man with newly diagnosed non-Hodgkin lymphoma presenting with anemia and very high level of alkaline phosphatase. On bone marrow biopsy, it was noted with extensive BMN characterized by cellular debris with indistinct cellular margin and abnormally eosinophilic staining cytoplasm. Despite the prompt institution of aggressive chemotherapy, one week later, liver function tests gradually deteriorated and the patient succumbed. Given the high mortality rate, when the bone marrow necrosis is suspected especially in a patient with malignancy, disease specific treatment and vigorous supportive measures should be immediately commenced.

Therapeutic Trial of Cobalamin in Patients with Normal Serum Cobalamin Levels and Predicted Cobalamin Deficiency.

Diagnosis of cobalamin deficiency can be difficult due to the variation in clinical presentation and lack of specificity of the laboratory findings. Although hypersegmentation and macrocytosis are important findings observed in cobalamin deficiency they are not sensitive and spesific. Additionally, cobalamin assays in commercial laboratories, being not reliable, makes the diagnosis more difficult. The metabolite assays, such as the total homocysteine and methylmalonic acid are costly, which restricts their widespread routine use. Our aim was to find out problems in diagnosis of cobalamin deficiency in general practice, and establish a better and cost-effective decision strategy for the diagnosis of this common clinical entity. Fifty patients with the diagnosis of cobalamin deficiency were retrospectively evaluated with respect to diagnosis. Normal cobalamin levels were observed at presentation in eight (16%) patients. Reticulocyte crisis was observed in all patients on the seventh day of cobalamin replacement therapy and all hematological parameters returned to normal at the end of three months of treatment. In anemic patients with clinical and biochemical findings suggestive of megaloblastic anemia, even though serum cobalamin level is normal, a therapeutic trial of cobalamin is cost effective and prevents delay in diagnosis.

Hairy cell leukemia in father and son.

Hairy cell leukemia (HCL) is an uncommon B cell disorder, and familial HCL is rarely encountered among the first degree relatives of HCL patients. A father and son, both of whom developed hairy cell leukemia, is presented in this report. The HLA haplotype shared by the father and son was A2, B18, BW6, CW7, DR3, DR10, and DQ8. Among these haplotypes, HLA A2 and Bw6 have previously been reported.