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Background Complete blood count (CBC) results play an important role in peripheral blood smear (PBS) examinations. Many descriptions in PBS reports may simply be translated from CBC parameters. We developed a computer program that automatically generates a PBS draft report based on CBC parameters and age- and sex-matched reference ranges. Methods The Java programming language was used to develop a computer program that supports a graphical user interface. Four hematology analyzers from three different laboratories were tested: Sysmex XE-5000 (Sysmex, Kobe, Japan), Sysmex XN-9000 (Sysmex), DxH800 (Beckman Coulter, Brea, CA, USA), and ADVIA 2120i (Siemens Healthcare Diagnostics, Eschborn, Germany). Input data files containing 862 CBC results were generated from hematology analyzers, middlewares, or laboratory information systems. The draft reports were compared with the content of input data files. Results We developed a computer program that reads CBC results from a data file and automatically writes a draft PBS report. Age- and sex-matched reference ranges can be automatically applied. After examining PBS, users can modify the draft report based on microscopic findings. Recommendations such as suggestions for further evaluations are also provided based on morphological findings, and they can be modified by users. The program was compatible with all four hematology analyzers tested. Conclusions Our program is expected to reduce the time required to manually incorporate CBC results into PBS reports. Systematic inclusion of CBC results could help improve the reliability and sensitivity of PBS examinations.

Hereditary spherocytosis (HS) is a congenital disorder of the red blood cell membrane and is characterized by hemolytic anemia, variable jaundice, and splenomegaly. In neonates, the diagnosis of HS can be difficult in the absence of family history. Herein, we describe clinical and molecular genetic findings in a Korean neonate with HS. A one-month-old girl presented with severe anemia and jaundice. Spherocytes were frequently observed on peripheral blood smear, but the erythrocyte osmotic fragility test result was normal. Targeted next-generation sequencing (NGS) revealed the patient was heterozygous for a novel frameshift mutation, c.191_194del (p.Leu64Argfs*7), in exon 3 of

The present study was performed to evaluate the efficacy of circulating cystatin-C as a tumor monitoring biomarker at different clinical time points in patients with breast cancer over a long-term follow-up period. In addition, the secretory rate of circulating cystatin-C from cancer tissue was investigated by comparing the blood and tissue expression levels of cystatin-C. Blood samples from healthy volunteers (40 males and 40 females) were obtained at yearly health examinations if laboratory and imaging abnormalities were not detected. Blood samples from 34 patients with breast cancer were obtained at 205 different time points of clinical progression. Blood levels of cystatin-C were measured using ELISA and the tissue levels were measured using immunohistochemistry. No age-associated effect was observed in male and female blood cystatin-C levels. The positivity rate was 46% in patients (38/83) and 40% in samples collected at different time points (82/205). Blood cystatin-C levels were lowest following surgery compared with patients with systemic metastasis (P

The 2016 WHO diagnostic criteria for chronic myelomonocytic leukemia (CMML) require both absolute and relative monocytosis (≥1×109/L and ≥10% of white blood cell counts) in peripheral blood. Moreover, myeloproliferative neoplasm (MPN) features in bone marrow and/or MPN-associated mutations tend to support MPN with monocytosis rather than CMML. We assessed the impact of the 2016 WHO criteria on CMML diagnosis, compared with the 2008 WHO criteria, through a retrospective review of the medical records of 38 CMML patients diagnosed according to the 2008 WHO classification. Application of the 2016 WHO criteria resulted in the exclusion of three (8%) patients who did not fulfill the relative monocytosis criterion and eight (21%) patients with an MPN-associated mutation. These 11 patients formed the 2016 WHO others group; the remaining 27 formed the 2016 WHO CMML group. The significant difference in the platelet count and monocyte percentage between the two groups indicated that the 2016 WHO criteria lead to a more homogenous and improved definition of CMML compared with the 2008 WHO criteria, which may have led to over-diagnosis of CMML. More widespread use of molecular tests and more sophisticated clinical and morphological evaluations are necessary to diagnose CMML accurately.

As it is recommended that most assessments for treatment-free remission (TFR) in patients with chronic myeloid leukemia be conducted as prospective trials, we conducted a systematic review and meta-analysis to investigate which study-level factors affected the TFR rate. The MEDLINE, Embase, and Cochrane databases were systematically searched from inception to July 2018. A random effect model was used to estimate the overall mean TFR rate, subgroup differences, and regression coefficients with continuous variables. Overall, 12 tyrosine kinase inhibitor (TKI) stopping studies comprising 1699 chronic myeloid leukemia patients were included in this analysis. The overall mean TFR rate at 24 months after entering TFR phase was 55% [95% confidence interval (CI) 0.51–0.58]. Trials with molecular criteria of MR4.5 or better for stopping TKI reported higher TFR rates than those of MR4.0 (57.2% vs. 50.5%). Trials with eligible criteria for at least 24 months of deep molecular response (DMR) duration demonstrated higher TFR rates than those for 18 or 12 months (60.2% vs. 49.9%). Our results suggest that TKI stopping trials with sufficient duration of DMR and molecular criteria of MR4.5 or better may account for approximately 60% of the TFR rate at 24 months after stopping TKI.

Background To validate the clinical application of chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic test and to determine the impact of CMA results on patient clinical management, we conducted a multicenter prospective study in Korean patients diagnosed as having developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA). Methods We performed both CMA and G-banding cytogenetics as the first-tier tests in 617 patients. To determine whether the CMA results directly influenced treatment recommendations, the referring clinicians were asked to complete a 39-item questionnaire for each patient separately after receiving the CMA results. Results A total of 122 patients (19.8%) had abnormal CMA results, with either pathogenic variants (N=65) or variants of possible significance (VPS, N=57). Thirty-five well-known diseases were detected: 16p11.2 microdeletion syndrome was the most common, followed by Prader-Willi syndrome, 15q11-q13 duplication, Down syndrome, and Duchenne muscular dystrophy. Variants of unknown significance (VUS) were discovered in 51 patients (8.3%). VUS of genes putatively associated with developmental disorders were found in five patients: IMMP2L deletion, PTCH1 duplication, and ATRNL1 deletion. CMA results influenced clinical management, such as imaging studies, specialist referral, and laboratory testing in 71.4% of patients overall, and in 86.0%, 83.3%, 75.0%, and 67.3% of patients with VPS, pathogenic variants, VUS, and benign variants, respectively. Conclusions Clinical application of CMA as a first-tier test improves diagnostic yields and the quality of clinical management in patients with DD/ID, ASD, and MCA.

Acquired pure red cell aplasia (PRCA) can be induced by various factors such as viral infection, thymoma, connective tissue disease, lymphoma, and adverse drug reactions. PRCA has not been reported in an adolescent in Korea for the past several decades. We recently experienced a case of acquired PRCA in an adolescent. A 14-year-old girl presented with pallor, dizziness, and mild fever. She had isolated normocytic normochromic anemia with reticulocytopenia in the peripheral blood and erythroblastopenia in the bone marrow. She was diagnosed with secondary acquired PRCA presumably induced by Mycoplasma pneumoniae infection during her clinical course, and she experienced spontaneous remission 11 weeks after initial diagnosis. Her clinical and hematologic statuses were normal as far as 20 months after her diagnosis. pISSN 2233-5250 / eISSN 2233-4580 http://dx.doi.org/10.15264/cpho.2015.22.2.142 Clin Pediatr Hematol Oncol 2015;22:142∼145

Leukemic transformation of human cells is a complex process. Here we show that forced expression of MN1 in primitive human cord blood cells maintained on stromal cells in vitro induces a transient, but not serially transplantable, myeloproliferation in engrafted mice. However, cotransduction of an activated HOX gene (NUP98HOXD13) with MN1 induces a serially transplantable acute myeloid leukemia (AML). Further characterization of the leukemic cells generated from the dually transduced cells showed the activation of stem cell gene expression signatures also found in primary human AML. These findings show a new forward genetic model of human leukemogenesis and further highlight the relevance of homeobox transcription factors in the transformation process.

s Backgrounds Various studies have reported that the neutrophil-to-lymphocyte ratio in the serum (sNLR) may serve as a cost-effective and useful prognostic factor in patients with various cancer types. However, no study has reported the prognostic impact of the NLR in malignant pleural effusion (MPE). To address this gap, we investigated the clinical impact of NLR as a prognostic factor in MPE (mNLR) and a new scoring system that use NLRs in the serum and MPE (smNLR score) in lung cancer patients. Methods We retrospectively reviewed all of the patients who were diagnosed with lung cancer and who presented with pleural effusion. To maintain the quality of the study, only patients with malignant cells in the pleural fluid or tissue were included. The patients were classified into three smNLR score groups, and clinical variables were investigated for their correlation with survival. Results In all, 158 patients were classified into three smNLR score groups as follows: 84 (53.2%) had a score of 0, 58 (36.7%) had a score of 1, and 16 (10.1%) had a score of 2. In a univariate analysis, high sNLR, mNLR, and increments of the smNLR score were associated with shorter overall survival (p

Multivariate analyses of the factors that are predictive of overall survival in all patients apart from the new score, which use the neutrophil-to-lymphocyte ratios in the serum and malignant pleural effusion. (DOCX 16.8Â kb)

A 13-year old girl visited emergency medical center presenting with nasal bleeding and gross hematuria. She had no growth retardation, nor history of abnormal bleeding. Her initial blood test results showed normal platelet counts, normal liver enzyme level but prolonged prothrombin time and activated partial thromboplastin time. On admission, she showed massive but intermittent bleeding until the 15 hospital day. Evaluation including coagulation factor assay was done and the results were compatible with vitamin K deficiency. She was treated with vitamin K intramuscular injection 7 times and intermittent transfusion of red blood cells, platelets and fresh frozen plasma. After that, all of her blood test results returned to normal levels including coagulation tests concomitent with resolving symptoms. In that there were no proof of underlying diseases that can cause vitamin K deficiency, she was diagnosed as idiopathic transient vitamin K deficiency. pISSN 2233-5250 / eISSN 2233-4580 http://dx.doi.org/10.15264/cpho.2014.21.1.33 Clin Pediatr Hematol Oncol 2014;21:33∼36

In order not to over treat uterine leiomyoma and to avoid overlooking uterine leiomyosarcoma, a highly reliable diagnostic method has been thought. Occasionally, it is difficult to discriminate uterine leiomyoma from uterine leiomyosarcoma. Recently positron emission tomography/computed tomography (PET/CT) has been proved useful in assessing pelvic malignancies. We experienced a case of uterine leiomyoma showing increased F-18 fludeoxyglucose uptake on PET/CT in a postmenopausal woman. However, histological analysis demonstrated benign leiomyoma by the hysterectomy. Immunohistochemical analysis of glucose transporter-1 showed negative in leiomyoma. Our case indicates that uterine leiomyoma in a postmenopausal woman may show false positive result of PET/CT.

Retinal hemorrhage is a frequently observed sign in Plasmodium falciparum infection. In Plasmodium vivax infection, however, retinal hemorrhage is very rare; only five cases have been reported in the literature. In this case report, we review the literature and the case of 52-year-old man who had retinal hemorrhages in P. vivax infection. We analyzed the structural characteristics of the lesions using fluorescein angiography and spectral-domain optical coherence tomography. Physicians should be aware of the possibility of retinal hemorrhage in malaria patients, even those with P. vivax infection, and should consider a diagnosis of malaria in a patient with unexplained retinal hemorrhage and fever.

The in vivo skin prick test (SPT) or in vitro detection of allergen specific IgE in serum is commonly used for the diagnosis of allergic disease. In this study, we evaluated the usefulness of a new multiple allergen simultaneous test (MAST) immunoblot assay, Polycheck Allergy (Biocheck GmbH, Germany).A total of 100 patients with clinical findings of allergic diseases were tested by SPT and three different MAST assays: Polycheck Allergy (Biocheck GmbH, Germany), MAST CLA allergy system (Hitachi Chemical Diagnostics, USA) and Allergy Screen (R-biopharm, Germany). The results of MAST assays were compared with those of SPT.Concordance rates of MAST assays with SPT were 79-100% for Polycheck Allergy, 88.9-100% for MAST CLA and 72.7-98.3% for Allergy Screen. In ROC curve analysis, significant differences were observed in four of 25 allergens analysed: Alternaria, Birch, Hazelnut and D. farinae. For Alternaria and Birch, Polycheck Allergy (P0.001) and Allergy Screen (P=0.0075) showed significantly larger AUC (area under the curve) than MAST CLA. For Hazelnut, Polycheck Allergy (P=0.0021), and for D. farinae, MAST CLA (P=0.015) showed significantly larger AUCs than the other two tests. The ROC analysis for overall 16 food allergens showed better results in Polycheck Allergy (P0.001), and that for overall 21 inhalants did not show significant differences among three MAST assays (P0.05).Since Polycheck Allergy showed similar or superior result to the others, it can be used for the detection of allergen specific IgE antibodies.

This study investigated the relationship between the urine homocysteine/creatinine (uHcy/Cr) ratio and the levels of natural anticoagulants, proinflammatory cytokines, and nitric oxide (NOx) metabolites in cerebrovascular diseases. No significant differences were observed in protein C, protein S, and antithrombin III levels among subjects with serum Hcy (sHcy)15.0 μmol/L and ≤15.0 μmol/L. However, subjects with a uHcy/Cr ratio14.8 μmol/g Cr showed significant differences in the levels of the corresponding parameters than those with uHcy/Cr ratio ≤14.8 μmol/g Cr. The sensitivity and specificity of the sHcy level at a cutoff of 15.0 μmol/L were 32.6% and 85.7%, respectively, with a positive predictive value of 69.5%. In contrast, those values for the uHcy/Cr ratio at a cutoff of 14.8 μmol/g Cr were 55.1% and 91.4% with a positive predictive value of 86.5%. The uHcy/Cr ratio correlated more closely with protein C, antithrombin III, TNF-α, and NOx levels than did sHcy concentrations. In short, the uHcy/Cr ratio has a significant relationship with anticoagulation- and inflammation-related parameters. A measurement of the uHcy/Cr ratio may provide helpful information for assessing patients with cerebrovascular diseases.

Extensive molecular profiling of leukemias and preleukemic diseases has revealed that distinct clinical entities, like acute myeloid (AML) and T-lymphoblastic leukemia (T-ALL), share similar pathogenetic mutations. It is not well understood how the cell of origin, accompanying mutations, extracellular signals or structural differences in a mutated gene determine the phenotypic identity of leukemias. We dissected the functional aspects of different protein regions of the MN1 oncogene and their effect on the leukemic phenotype, building on the ability of MN1 to induce leukemia without accompanying mutations. We found that the most C-terminal region of MN1 was required to block myeloid differentiation at an early stage, and deletion of an extended C-terminal region resulted in loss of myeloid identity and cell differentiation along the T-cell lineage in vivo. Megakaryocytic/erythroid lineage differentiation was blocked by the N-terminal region. In addition, the N-terminus was required for proliferation and leukemogenesis in vitro and in vivo through upregulation of HoxA9, HoxA10 and Meis2. Our results provide evidence that a single oncogene can modulate cellular identity of leukemic cells based on its active gene regions. It is therefore likely that different mutations in the same oncogene may impact cell fate decisions and phenotypic appearance of malignant diseases.

We studied 14 adult patients presenting with fever and cytopenia of the peripheral blood and histiocytic hyperplasia with hemophagocytosis (HHH) in the bone marrow regarding an association of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) by using in situ hybridization (ISH) and also evaluated the clinical and laboratory findings according to the encountered organisms. ISH using a CMV RNA probe demonstrated infected cells in 6 out of 14 cases (43%), and ISH using an EBV EBER RNA probe demonstrated infected nuclei in 5 out of the same 14 cases (36%) of HHH. No cases showed a positive reaction with both probes. Three cases showed a negative reaction with both probes. The mean age of all patients was 29 years; and that of the CMV-positive patients was 27 years and that of the EBV-positive patients was 36 years. Organomegaly was found in 3 out of 6 CMV-positive patients (1 hepatomegaly, 1 splenomegaly, 1 hepatosplenomegaly), and 4 out of 5 EBV-positive patients (lymphadenopathy in all 4 cases, hepatosplenomegaly in 2 cases). One of the CMV-positive case had acute myeloblastic leukemia, and 2 EBV-positive cases had underlying malignancy (1 Hodgkin's disease, 1 non-Hodgkin's lymphoma). Seven out of the 14 HHH cases (50%) died within several months after diagnosis. Nucleic acid hybridization methods can be used for the routine examination of the association of CMV or EBV.

Objective Transcriptional control of hematopoietic lineage fate relies on the integration of many intra- and extracellular signals. To test whether the microenvironment impacts on leukemic phenotype, we exploited the MN1 model of acute myeloid leukemia under defined genetically modified microenvironmental conditions. Materials and Methods The requirement of both FLT3 and c-Kit signaling for MN1 leukemias was investigated using retroviral infection of bone marrow cells from wild-type, c-Kit –mutated (W41), and Flt3 -ligand knockout cells, and bone marrow transplantation into wild-type, c-Kit –mutated, or Flt3 -ligand knockout mice. Results Genetic disruption of both FLT3 and c-Kit signaling in the MN1-leukemia model was dispensable for MN1-induced leukemogenesis. However, it induced a switch from myeloid to erythroid phenotype that was preserved, when FLT3 signaling was restored by secondary transplantation of leukemic cells into wild-type recipients. Conclusions Our findings underscore the importance of microenvironmental signals for lineage choice in leukemia and identify signals that are important in myeloid-erythroid lineage decisions.

This study investigated the use of corrected 17-alpha-hydroxyprogesterone (17-OHP) values to detect congenital adrenal hyperplasia (CAH) in newborn infants. 17-OHP concentrations in blood spots from 913 neonates were measured using a neonatal screening test. A prematurity index was calculated using a scoring system based on gestational age and birth weight. Blood spot 17-OHP concentrations divided by the sum of prematurity scores were defined as the corrected 17-OHP values. Preterm infants (30 wk) and low birth weight infants (1.0 kg) showed 3.9- and 3.8-fold higher blood spot 17-OHP concentrations than normal full term infants. However, no significant differences were observed in the corrected 17-OHP values between the groups. Blood spot 17-OHP levels yielded significant correlations with the prematurity index (r = 0.42, p0.05). Positive results for CAH were obtained in 9.5% (n = 53) and 2.0% (n = 11) of 556 premature infants by the cutoffs of blood spot 17-OHP (15.0 ng/ml) and corrected 17-OHP values (13.0 ng/ml), respectively. Of the 53 positive subjects, 39 (73.6%) converted to negative after 1 to 5 mo without treatment. In summary, blood spot 17-OHP levels are influenced by the prematurity of newborns. Use of corrected 17-OHP values provide limited but helpful information in screening for CAH by reducing the rate of false-positive results, especially in premature infants.

Immunohistochemistry (IHC) is widely used in diagnostic practice and research, but it is limited due to its subjective nature and weakness in reproducibility. For successful interpretation, IHC requires an internal reference system that controls for procedural variables and provides a staining intensity reference. We investigated the feasibility of using mouse spleen tissue as an intensity reference in conventional IHC. Formalin-fixed, paraffin-embedded mouse (BALB/c) spleen tissue was stained with variable procedural conditions including primary antibody (Ab) types, antigen retrieval methods, chromogen exposure times, and secondary Ab concentrations. Mouse spleen tissue showed identical staining intensity regardless of primary Ab types, even without primary Ab, and showed minimal differences according to retrieval methods. However, it showed various staining intensities according to chromogen exposure time and secondary Ab concentration. When mouse spleen was included in tissue microarrays and compared with the c-erbB2 IHC scoring system, splenic B cells showed weak membrane staining compatible with score 1+, whereas splenic plasma cells showed strong staining intensity compatible with score 3+. These results show that mouse spleen tissue can serve as a staining intensity reference for the interpretation of IHC.

Burkitt lymphomas (BLs) frequently show secondary chromosomal abnormalities. Here, the authors describe a case of BL with an unusual dual translocation of chromosome 14, t(8;14) and t(14;15), and partial duplication of 1q. This 5-yr-old female patient had several unfavorable prognostic factors including elevated serum lactate dehydrogenase activity and involvement of the central nervous system and bone marrow. Despite receiving CCG-106A chemotherapy, she was resistant to therapy and died on the 70th hospital day. To our knowledge, this is the first documented case report of BL harboring dual translocation of chromosome 14 involving chromosomes 8 and 15, which may be a factor associated with unfavorable clinical course.

We report a case of chronic myelogenous leukemia displaying a variant Philadelphia translocation t(11;22)(q25;q11.2). Breakpoint 11q25 has not previously been reported. Reverse transcriptase polymerase chain reaction and fluorescence in-situ hybridization demonstrated the BCR/ABL rearrangement.

We wanted to see whether the active inflammation in Behcet's disease (BD) can cause a thrombotic disorder by decreasing the protein S (PS) activity, and we evaluated the relationship between the decreased PS activity and the disease activity of BD. We included 122 patients with BD whose PS activity levels were measured. In 51 patients, the PS activity was measured again when there were changes in the number of items of "The Behcet's Disease Current Activity Form (BDCAF)". The thrombosis rate was 2.5% (3/122), and the PS activity was low in all three of the patients with thrombosis. The incidence of low PS activity in the total 122 BD patients was 27% (33/122). The incidence of the low PS activity in the active BD patients was 33.7% (31/92), and this was significantly more frequent than in the inactive BD patients, (6.7%, 2/30) (chi(2)-test, P value = 0.0038). The decrease of PS activity had good correlation with the increase of the number of BDCAF items (r = -0.351, P value = 0.012). The PS activity decrease is related to the BD activity. The low PS activity can be the risk factor for thrombotic disorder and also the activity marker for BD and other inflammatory diseases.

The plasma soluble interleukin-2 receptor (sIL-2R) level was higher in 137 patients with acute leukemia (1,489 +/- 1,798 U/ml, including 98 cases of acute myeloid leukemia (AML), 1,063 +/- 1,414 U/ml, and 39 cases of acute lymphoblastic leukemia (ALL), 2,561 +/- 2,194 U/ml), compared to 49 normal control subjects, 421 +/- 151 U/ml). The ALL patients showed elevated plasma sIL-2R levels more frequently than the AML patients (92.3% vs 44.9%). No patient with either hypoplastic AML or AML with multilineage dysplasia and only 1 of 13 patients with acute promyelocytic leukemia (APL) had an elevated plasma sIL-2R level. All the My+ ALL patients (15 cases) showed elevated plasma sIL-2R levels. Plasma sIL-2R levels were significantly lower after chemotherapy in the ALL patients, but were not significantly lower in the AML patients. IL-2R was expressed on the leukemic cells in 36 (53.7%) of 67 AML and in 9 (21.4%) of 42 ALL cases. None of the AML M3, M4, M5, M6, or M7 subgroups showed IL-2R expression. The My+ ALL patients (42.9%, 6/14) showed IL-2R expression more frequently than the other ALL subgroups (10.7%, 3/28) (p = 0.025). The plasma sIL-2R level was correlated with the proportion of leukemic cells expressing IL-2R in acute leukemia. However, there were many cases, particularly ALL cases, who had elevated plasma sIL-2R levels without IL-2R expression on their leukemic cells. These results suggest that the plasma sIL-2R level is a valuable marker for monitoring ALL after chemotherapy, particularly in My+ ALL cases, and that the T cell immune reaction to leukemia appears to be much higher in ALL patients than in AML patients.

The effectiveness of As2O3 treatment was studied in 3 carcinoma cell lines, LoVo, OVCAR-3, and PA-1, and in cancer cells obtained from ascites fluids of 8 patients with carcinomatosis peritonei. LoVo, OVCAR-3, and PA-1 cell lines, and cancer cells from the patients were cultured in As2O3 gradient media; As2O3 sensitivity was evaluated by trypan blue dye exclusion and by morphologic examination after Wright staining. PA-1 was the most sensitive cell line to As2O3; OVCAR-3 and LoVo were resistant to As2O3. Cancer cells from 2 of 8 patients were sensitive to As2O3. The in vivo tumoricidal effect of As2O3 (100 microg/day, i.p.) was studied in 30 BALB/c nude mice following i.p. implantation of PA-1 tumor cells. The 17 As2O3-injected mice died of extensive intratumoral hemorrhage, necrosis, and hemorrhagic ascites within 48 hr after initial treatment. In 10 As2O3-untreated tumor-bearing control mice, only focal intratumoral hemorrhage and necrosis were noted. In summary, solid tumor cell lines and cancer cells from patients showed various As2O3 sensitivities in vitro, and As2O3 had a marked tumoricidal effect on PA-1 cells in vivo. These results suggest that As2O3 treatment might possibly be beneficial in patients with carcinomatosis peritonei who are resistant to conventional therapy and whose tumors show in vitro sensitivity to As2O3. However, to minimize the life-threatening tumor lysis effect, it would be better to administer As2O3 after removal of the peritoneal tumor masses.

To investigate the value of Tc-99m ciprofloxacin imaging in the differential diagnosis of chronic bacterial prostatitis.The study included 4 normal subjects as the negative controls, 2 patients with acute prostatitis or cystourethritis as the positive controls and 59 patients diagnosed as chronic bacterial prostatitis or chronic pelvic pain syndrome by traditional laboratory tests. In every subject, the single photon emission computerized tomography images were obtained 3 h after intravenous injection of Tc-99m Ciprofloxacin. The results of the imaging were compared with those of laboratory tests.On the images, negative uptake was observed in all normal subjects, while strong hot uptake, in the whole prostate of acute prostatitis patients and in the whole urethra of acute cystourethritis patients. In 13 (68%) of 19 patients categorized as chronic bacterial prostatitis by standard laboratory tests, hot uptake with less intensity than that of acute prostatitis was observed in the prostate area around the prostatic urethra. Negative uptake in the prostate was observed in 6 of 19 patients (32%) categorized as chronic bacterial prostatitis. Interestingly, hot uptake in the prostate was exhibited in 28 (70%) of the 40 patients categorized as chronic pelvic pain syndrome.Tc-99m ciprofloxacin imaging is helpful in the differential diagnosis of prostatitis syndrome.

Emphysematous pyelonephritis is an acute gas forming necrotizing infection of the renal parenchyma with high mortality, which shows non-specific clinical findings. Elderly patients with altered mentality and shock require careful monitoring and abdominal computed tomography scanning is thought to be beneficial in prompt detection of infection focus and management. We report on a patient with altered mentality who showed emphysematous pyelonephritis on abdominal computed tomography and provide a review of the literature.

Translocations involving chromosome 21q22 are frequently observed in hematologic malignancies including acute myeloid leukemia (AML), most of which have been known to be involved in malignant transformation through transcriptional dysregulation of Runt-related transcription factor 1 (RUNX1) target genes. Nineteen RUNX1 translocational partner genes, at least, have been identified, but not Homeobox A (HOXA) genes so far. We report a novel translocation of RUNX1 into the HOXA gene cluster in a 57-year-old female AML patient who had been diagnosed with myelofibrosis 39 months ahead. G-banding showed 46,XX,t(7;21)(p15;q22). The involvement of RUNX1 and HOXA genes was confirmed by fluorescence in situ hybridization.

Infection-associated plasmacytosis is not uncommon; however, marked plasmacytosis in both peripheral blood and bone marrow that mimicks plasma cell leukemia is a very rare condition. We encountered a case of extreme plasmacytosis associated with Klebsiella pneumoniae sepsis in an aplastic anemia patient. A 42-year-old man presented with high fever of 5 days' duration. Hematological analysis revealed severe neutropenia and thrombocytopenia; his white blood cell count was 900/mm(3), with 26% of plasma and plasmacytoid cells in peripheral blood. Bone marrow biopsy and aspiration showed 25% cellularity with marked plasmacytosis (80%), highly suggestive of plasma cell leukemia. On the eighth hospital day, K. pneumoniae was identified in blood and sputum cultures. Fever improved after switching antibiotics, although his hematological condition worsened. His bone marrow cellularity (plasma cell proportion) progressively decreased: the values were 25% (80%), 10% (26%), 10% (11%), and < 10% (< 4%) on the 8th, 30th, 60th, and 90th hospital day, respectively. His plasmacytosis was extremely severe but was confirmed to be reactive with polyclonality. The present case represents the first report of strong suspicion of K. pneumoniae sepsis-associated marked plasmacytosis in an aplastic anemia patient.

Anaerobiospirillum succiniciproducens is a spiral-shaped, gram-negative anaerobic bacterium. A. succiniciproducens is a rare cause of bacteremia in human, especially immunocompromised patients. This organism may be mistakenly identified when using an automated bacterial identification system, and may be mistaken for Campylobacter spp. when using Gram staining. We report a case of bacteremia caused by A. succiniciproducens, which was negative for catalase, oxidase, and urease and confirmed by 16S rRNA sequencing (analysis revealed a 99% similarity), in a 69-year-old patient who was undergoing chemotherapy for treatment of a malignancy. To the best of our knowledge, this is the first report of bacteremia caused by A. succiniciproducens in Korea. (Korean J Clin Microbiol 2012;15:74-77)

장우리·최종원·남정현·문연숙·김진주·김정희·임대현 Woo Ri Jang, M.D., Jong Weon Choi, M.D., Chung Hyun Nahm, M.D., Yeon Sook Moon, M.D., Jin Ju Kim, M.D., Jeong Hee Kim, M.D., Dae Hyun Lim, M.D. 인하대학교 의과대학 진단검사의학교실, 소아청소년과학교실 Departments of Laboratory Medicine and Pediatrics, College of Medicine, Inha University, Incheon, Korea 원저 Lab Med Online Vol. 2, No. 1: 20-27, January 2012 http://dx.doi.org/10.3343/lmo.2012.2.1.4 임상화학

Background: The identification of monoclonality has been widely used for making diagnoses of lymphoproliferative lesions. Awareness of the sensitivity and detection limit of the technique used would be important for the data to be convincing. Methods: We investigated the minimum requirement of cells and sensitivity of gel electrophoresis (GE) and laser-induced fluorescence capillary electrophoresis (LFCE) for identifying IgH gene rearrangement using BIOMED-2 protocols. DNA extracted from Raji cells were diluted serially with peripheral blood mononuclear cells (PBMNCs) DNA. DNA from mixtures of diffuse large B-cell lymphoma (DLBCL) and reactive lymph nodes were also serially diluted. Results: For Raji cells, the detection limit was 62 and 16 cell-equivalents for GE and LFCE, respectively. In the condition with PBMNCs mixture, 2.5% and 1.25% of clonal cells was the minimum requirement for GE and LFCE, respectively. In 23% of DLBCL cells in tissue section, the detection limit was 120 and 12 cell-equivalents for GE and LFCE, respectively. In 3.2% of DLBCL cells, that was 1,200 and 120 cell-equivalents for GE and LFCE, respectively. Conclusions: These results show that LFCE method is more sensitive than GE and the sensitivity of clonality detection can be influenced by the amount of admixed normal lymphoid cells.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease. The prognosis is poor in most cases with rapid progression despite administering chemotherapy. A 67-year-old man complained of skin rashes on his back and this spread to the trunk, face, arms and thighs, and he was initially diagnosed with cutaneous lupus erythematosus according to the skin biopsy. The skin rashes then became aggravated on a trial of low dose methylprednisolone for 3 months. Repeated skin biopsy revealed a diffuse infiltration of lymphoid cells with medium sized nuclei, positive for CD4 and CD56, negative for Epstein-Barr virus (EBV), indicating a diagnosis of BPDCN. Further workups confirmed stage IVA BPDCN involving the skin, multiple lymph nodes, the peripheral blood and the bone marrow. He was treated with six cycles of combination chemotherapy consisting of ifosphamide, methotrexate, etoposide, prednisolone and L-asparaginase, and he achieved a partial response. Herein we report on a rare case of BPDCN that was initially misinterpreted as cutaneous lupus erythematosus.

Intestinal TMA, a upcoming and serious problem after HSCT, usually manifests diarrhea, vomiting, GI bleeding and abdominal pain as initial clinical presentations similar to those of intestinal GVHD. But intestinal TMA should be distinguished from GVHD, because they needed to be treated in absolutely different way. Here we investigated the incidence of intestinal TMA and evaluated their clinical progressions in HSCT patients. We retrospectively reviewed 243 gastrointestinal mucosal biopsy slides obtained from HSCT patients having suffered from GI problems in the Catholic University Hospital, from 2000 to 2004. The collected cases were reviewed by two pathologists blindly and classified into TMA; showing microthrombi formation in the lumina of microvasculatures, GVHD; showing epithelial apoptosis and/or loss of glands, TMA+GVHD and non-specific inflammation. And next, their incidence and clinical outcomes were analyzed. On histopathological examination, 15 out of 243 cases (6.2%) showed luminal thrombi of microvasculature compatible with TMA, 58 cases (23.9%) showed findings compatible with GVHD, 3 cases (1.2%) showed both TMA and GVHD, and 173 cases (71.2%) showed nonspecific gastroenteritis. On peripheral blood smear examination, all 15 TMA cases showed less than 1% of fragmented RBC at the time of biopsy. But 2 out of 15 cases (13.3%) showed increase to 8% and 10% of fragmented RBC in follow-up, and they had been aggravated clinically and improved only after treatments including discontinuing immunosuppressant and plasma exchange. Among 58 GVHDs, 34 patients (75.9%) were improved with steroid pulse therapy, but 14 patients (24.1%) failed. These results show that intestinal TMA is not infrequent in HSCT patients and can be combined with intestinal GVHD. In conclusion, intestinal TMA should be recognized in pathological diagnosis of HSCT patients. It is important to differentiate intestinal TMA from GVHD in patients suffering from severe and refractory diarrhea after HSCT.

Follicular dendritic cell neoplasm(FDCN), a rare tumor exhibiting a broad histopathological spectrum and unpredictable biologic behavior, has been classified into follicular dendritic cell tumor(FDCT) and follicular dendritic cell sarcoma(FDCS) regarded as borderline lesion and malignant tumor, respectively, by World Health Organization. But still no definite diagnostic criteria distinguishing FDCT from FDCS was established. Here in, as an approach to the differential diagnostic criteria, we performed clinicopathological analysis for 146 cases of FDCN, documented in English literature from January 1986 to May 2006. Through PubMED search with key words of FDC or dendritic cell tumor, we collected and reviewed 73 articles out of more than six thousands candidates, which contained 146 FDCNs with clinicopathological informations. We analyzed the carefully selected cases with parameters including age, gender, tumor location, tumor size, tumor margin, EBV association, mitosis, nuclear atypism, hemorrhage, necrosis and Castleman’s disease association. Recurrence, metastasis and death of disease were referred as event. Kaplan-Meier model was used for overall event-free survival analysis and the log-rank test was used to assess statistical significance. Mitotic Index (MI, ≥ 5/10HPF vs

Purpose: We wanted to determine whether inflammation and bacterial infection, as tested for by the traditional 4-glass test or Tc-99m ciprofloxacin imaging, correlate with the symptom severity in men with chronic prostatitis. Materials and Methods: The study included 256 patients with symptoms of prostatitis. The Korean version of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) was used to measure the symptoms of each patient. To diagnose bacterial infection, four-glass tests were performed that included culture for general bacteria, Mycoplasma hominis and Ureaplasma urealyticum, and polymerase chain reaction was performed for Chlamydia trachomatis. The patients with established uropathogens localized to the expressed prostatic secretion or the voided urine 3 were classified as having chronic bacterial prostatitis (CBP). To further localize the infection, the single photon emission computerized tomography images were obtained 3 hours after intravenous injection of Tc-99m ciprofloxacin. Associations between the symptoms and the inflammation and infection were evaluated. Results: Based on the 4-glass tests, the patients were classified as CBP (n=16) or as chronic pelvis pain syndrome (CCPS) (the inflammatory type, n=94; non-inflammatory type, n=146). The CBP patients had a higher pain score than did the CPPS patients and there were no significant differences in the subscores for voiding symptoms and the quality of life between the groups. No significant differences were found in the total score or the subscores of the NIH-CPSI based on the presence or location of infection on the Tc-99m ciprofloxacin imaging. Conclusions: These findings suggest that bacterial infection, not inflammation, as determined by traditional laboratory tests contribute to the symptoms, especially pain, in men with chronic prostatitis. (Korean J Urol 2006; 47:870-875)

Forty two people (men 22, women 20) diagnosed as Durie-Salmon stage IIIA or B multiple myeloma were treated with a combination chemotherapy consisting of cyclophosphamide at 400mg and dexamethasone at 40mg (CHD) regardless of body surface for 4 or 5 consecutive days every 3 or 4 weeks from August 1996 through July 2005. The treatment was repeated as long as the patient could tolerate or until disease progressed. The chemotherapy was given to 36 chemo-naïve patients as primary therapy and to 6 patients exposed to VAD (vincristine, doxorubicin, dexamethasone) as salvage therapy. Palliative loco-regional radiotherapy was also given to 20 of 44 patients. A total of 433 cycles (mean 10.3, range 2~28 per individual) of chemotherapy were given and the response evaluation was made in accordance to the criteria of Dr. Blade. SD (stable disease) was defined as reduction or increase of myeloma protein within 25%. Six of 36 chemo-naïve patients who did not respond to CHD received salvage therapy consisting of VAD or MP (melphalan plus prednisone). Eleven patients (26%) attained CR (complete remission) at a median of 7 cycles (range 4~10), 15 (36%) achieved PR (partial remission) at a median of 3 cycles (range 2~16), 12 (28%) stayed at SD, and 4 patients (10%) showed PD (progressive disease). The measurement of survival duration was started at the beginning of the CHD chemotherapy. The measurement was censored in 6 patients at the time of stem cell transplant, 5 autologous (one was disease free at 108 months after transplant), and 1 allogeneic. On a mean follow-up period of 15.1 months (range 3~59), 15 people remained alive at 3, 3, 3, 4, 6, 6, 8, 10, 14, 15, 16, 16, 16, 26, and 37 months. The mean response duration and OS (overall survival) of the patients who entered CR were 7 (range 2~18) and 31.3 (range 6+~59) months respectively. The correspondent durations of the patients in PR were 7.9 (range 2+~28) and 15 (range 3+~37+). The corresponding durations of the patients in SD were 8.3 (range 2~26) and 13.5 (3+~48). The mean OS duration of the patients in PD was 5.3 (range 3~8). The difference in OS durations between patients in PR and those in SD was not statistically meaningful. Five of 6 patients exposed to VAD responded to CHD, whereas one of 5 patients exposed to CHD did to VAD. Two of 4 patient exposed to CHD responded to MP. Adverse effect was minimal with non-fatal events including 5 febrile episodes of unknown origin, 3 cases of pneumonia, 2 cases of urinary tract infection, 1 case of peritonitis, 1 case of herpes zoster, and 1 case of intractable nausea during the 433 chemotherapy courses. There were 2 cases of fatal septicemia and 1 case of fatal pneumonia during the period. CHD combination chemotherapy seems an active and less toxic regimen in the treatment of multiple myeloma.