Hee Yeon Woo

Clinical Significance of Serum Procalcitonin in Patients with Community-acquired Lobar Pneumonia

BACKGROUNDnCommunity-acquired pneumonia (CAP) is a common respiratory disorder in children, which necessitates hospitalization. Bacterial pneumonia, especially lobar pneumonia and parapneumonic effusions, is associated with considerably severe clinical course and extensive alveolar infiltrates. Serum procalcitonin (PCT) level has been used to distinguish bacterial from viral infections, but its usefulness is disputed. The diagnostic accuracy and usefulness of PCT, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count were determined by comparing their values in the patients with CAP with those in healthy controls.nnnMETHODSnThe serum PCT levels, as well as CRP level, ESR, and WBC counts, were measured in 76 hospitalized patients with CAP (lobar pneumonia, 16; bronchopneumonia, 60) and 18 healthy controls. Serum PCT level was measured using VIDAS BRAHMS PCT (Biomerieux, France), and ROC curve analysis was performed to evaluate its diagnostic accuracy.nnnRESULTSnSerum PCT levels were higher in the patients with CAP than in healthy controls, especially in the patients with lobar pneumonia than in those with bronchopneumonia. Serum CRP level was also significantly elevated in the patients with CAP, especially in those with lobar pneumonia. The diagnostic accuracy of serum PCT level for the diagnosis of lobar pneumonia was better than those of serum CRP level and ESR. The serum PCT level was significantly correlated with the CRP level, ESR, and WBC count.nnnCONCLUSIONSnSerum PCT level was a better marker than CRP level or ESR for the diagnosis of lobar pneumonia in children with CAP.

Molecular Cytogenetic Analysis of Gene Rearrangements in Childhood Acute Lymphoblastic Leukemia

The aims of this study were to estimate the incidences of BCR/ABL, MLL, TEL/AML1 rearrangements, and p16 deletions in childhood acute lymphoblastic leukemia (ALL), to identify new abnormalities, and to demonstrate the usefulness of interphase fluorescence in situ hybridization (FISH). We performed G-banding analysis and FISH using probes for BCR/ABL, MLL, TEL/AML1 rearrangements, and p16 deletions on 65 childhood ALL patients diagnosed and uniformly treated at a single hospital. Gene rearrangements were identified in 73.8% of the patients using the combination of G-banding and FISH, while the chromosomal abnormalities were identified in 49.2% using G-banding alone. Gene rearrangements were disclosed by FISH in 24 (72.7%) of 33 patients with normal karyotype or no mitotic cell in G-banding. Among the gene rearrangements detected by FISH, the most common gene rearrangement was p16 deletion (20.3%) and the incidences of others were 14.1% for TEL/AML1, 11.3% for MLL, and 1.8% for BCR/ABL translocations. Infrequent or new aberrations such as AML1 amplification, MLL deletion, ABL deletion, and TEL/AML1 fusion with AML1 deletion were also observed. We established the rough incidences of gene rearrangements in childhood ALL, found new abnormalities and demonstrated the diagnostic capability of interphase FISH to identify cryptic chromosome aberrations.

Higher Serum Direct Bilirubin Levels Were Associated with a Lower Risk of Incident Chronic Kidney Disease in Middle Aged Korean Men

Background The association between serum bilirubin levels and incident chronic kidney disease (CKD) in the general population is unknown. We aimed to examine the association between serum bilirubin concentration (total, direct, and indirect) and the risk of incident CKD. Methods and Findings Longitudinal cohort study of 12,823 Korean male workers 30 to 59 years old without CKD or proteinuria at baseline participating in medical health checkup program in a large worksite. Study participants were followed for incident CKD from 2002 through 2011. Estimated glomerular filtration rate (eGFR) was estimated by using the CKD-EPI equation. CKD was defined as eGFR <60 mL/min per 1.73 m2. Parametric Cox models and pooled logistic regression models were used to estimate adjusted hazard ratios for incident CKD. We observed 238 incident cases of CKD during 70,515.8 person-years of follow-up. In age-adjusted models, the hazard ratios for CKD comparing quartiles 2–4 vs. quartile 1 of serum direct bilirubin were 0.93 (95% CI 0.67–1.28), 0.88 (0.60–1.27) and 0.60 (0.42–0.88), respectively. In multivariable models, the adjusted hazard ratio for CKD comparing the highest to the lowest quartile of serum direct bilirubin levels was 0.60 (95% CI 0.41–0.87; P trendu200a=u200a0.01). Neither serum total nor indirect bilirubin levels were significantly associated with the incidence of CKD. Conclusions Higher serum direct bilirubin levels were significantly associated with a lower risk of developing CKD, even adjusting for a variety of cardiometabolic parameters. Further research is needed to elucidate the mechanisms underlying this association and to establish the role of serum direct bilirubin as a marker for CKD risk.

Establishment of Reference Intervals of Tumor Markers in Korean Adults

BACKGROUNDnThe sensitivity and specificity of tumor markers for detecting cancer could be significantly changed by the reference intervals of tumor markers. We established reference intervals of tumor markers in Korean adults and evaluated its importance, since the reference intervals recommended by the manufacturers were determined in the Caucasian population and have sometimes been adopted without verification.nnnMETHODSnWe established the reference intervals of alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA)125, carbohydrate antigen (CA)19-9, total prostate specific antigen (TPSA), cytokeratin fragment (Cyfra)21-1, and neuron specific enolase (NSE) according to the CLSI guideline in a maximum number of 1,364 healthy adults aged 20-60 yrs who visited a health promotion center from January to February 2007.nnnRESULTSnReference intervals of all tumor markers except for AFP were not in agreement with those recommended by the manufacturers. Reference intervals of CEA, TPSA, CA19-9, CA125, and Cyfra21-1 were age dependent. The mean reference values of NSE, CA125, and CEA were statistically different according to gender (11.72 vs 10.78 ng/mL), menopause status (18.89 vs 12.62 U/mL), and smoking status (2.60 vs 2.12 vs 1.80 ng/mL for smokers, past smokers, and non-smokers, respectively),respectively.nnnCONCLUSIONSnWith the verification and establishment of reference intervals of tumor markers in a Korean local population, we found the reference intervals significantly different by either age, gender, smoking or menopause status.

A Rare Case of Acute Leukemic Presentation of Blastic Plasmacytoid Dendritic Cell Neoplasm without Cutaneous Lesions

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a clinically aggressive phenotype arising from CD4/CD56-expressing plasmacytoid dendritic cell precursors [1]. BPDCN was categorized under AML and related precursor neoplasms by the 2008 WHO classification, with most cases having been previously classified as blastic natural killer (NK)-cell lymphoma/leukemia or agranular CD4+, CD56+ hematodermic neoplasm [2]. BPDCN cells generally express CD4, CD56, CD123, and TCL-1 but are negative for other T-, B-, NK-cell, or myeloid markers [3]. Clinically, patients with this disease typically present with a high incidence of cutaneous involvement described as generalized, localized, or solitary macules, plaques, and/or tumors, as the first manifestation, followed by involvement of bone marrow (BM), peripheral blood (PB), and lymph nodes (LNs). BM involvement usually occurs with leukemic progression of advanced or relapsed disease and is associated with a poor prognosis [4]. Diagnosis of leukemic BPDCN without cutaneous manifestation is rare. Here, we report a 41-yr-old man who was diagnosed with BPDCN in the absence of skin manifestation. n nThis patient was admitted for evaluation and management of palpable multiple neck lymphadenopathies that had developed a week previously. No improvement was noted despite antibiotic therapy, and the lymphadenopathies spread to the left axillary and inguinal LNs. The initial blood analysis revealed a white blood cell (WBC) count of 6.1×109/L (reference range, 4.1-10.2×109/L), an Hb level of 12.7 g/dL (reference range, 13.7-16.8 g/dL), and a platelet count of 329×109/L (reference range, 158-332×109/L). Approximately 25% of cells appeared atypical on PB smear. Other laboratory findings were not significant except for an increased lactate dehydrogenase (LDH) level of 719 IU/L (reference range, 252-458 IU/L). n nComputed tomography (CT) imaging revealed multiple enlargements of the supraclavicular, right interlobar, inguinal, and iliac LNs, with no evidence of hepatosplenomegaly. Right supraclavicular LN biopsy and BM examination were also performed to characterize the atypical cells in the PB. Microscopic examination of the LN biopsies revealed diffuse infiltration by uniform, medium-sized cells together with effacement of the normal LN architecture. The tumor cells exhibited round or polygonal nuclei, coarse chromatin, and prominent nucleoli. Analysis of the BM aspirate revealed that blastoid cells accounted for up to 61% of all nucleated cells and had a similar morphology to those tumor cells that had infiltrated the LN in the BM study (Fig. 1). n n n nFig. 1 n n(A) Peripheral blood smear (Wright-Giemsa stain, ×1,000): large atypical cells with high nuclear cytoplasmic (N/C) ratios, basophilic cytoplasm, and prominent nucleoli accounted for up to 25% of the leukocyte population. (B) In the bone marrow ... n n n nFlow cytometric analysis of the BM aspirate revealed 48% CD45dim positive cells within the blast gate, which were positive for CD33, CD7, CD56, CD117, HLA-DR, CD13 weak (w), CD11cw, and negative for myeloperoxidase (MPO), CD14, CD64, CD2, CD3, CD5, cytoplasmic CD3, CD10, CD19, CD20, CD22, CD79a, kappa and lambda light chain, terminal deoxynucleotidyl transferase (TdT), and CD34 (Fig. 2). Immunohistochemical staining of the BM section revealed it to be negative for MPO, non-specific esterase (NSE), and Periodic acid-Schiff (PAS) stain. The acute leukemic presentation and expression of myeloid lineage-associated markers with the exception of MPO was suggestive of AML with minimal differentiation. n n n nFig. 2 n nFlow cytometric analysis of the bone marrow aspirate. CD45dim cells within the blast gated cells were negative for CD34 and positive for CD56, CD33, and CD7 (red circles). n n n nThe neoplastic BPDCN cells are characterized as medium-sized cells with round nuclei and finely dispersed chromatin with absent or indistinct nucleoli, which thus resemble blasts. In addition, the cytoplasm is scant and has no granules [1]. Likewise, in this case, it could be confused with acute leukemia and the BPDCN could consequently be missed because the neoplastic BPDCN cells are similar to blasts that lack lineage-specific markers. Further evaluation is necessary for an accurate diagnosis. Therefore, we performed immunohistochemical staining of the LN biopsy and found that the tumor cells were positive for leukocyte common antigen (LCA), CD4, CD56 and bcl-2 (Fig. 3); negative for MPO, CD3, CD5, CD8, CD10, CD20, CD21, CD15, CD30, CD1a, CD34, TdT, multiple myeloma oncogene 1 (MUM1), anaplastic lymphoma kinase (ALK), and bcl-6; and had a ki-67 labeling index of 60%. Based on these findings, the initial differential diagnosis included leukemic infiltration of acute leukemia, T cell lymphoma, myeloid leukemia/sarcoma, or acute leukemia presenting as BPDCN. We examined the whole body for skin involvement, but found no skin lesions in this patient. Nonetheless, the leukemic presentation with strong positivity for CD4 and CD56, combined with the absence of lineage-specific markers in blastoid cells were indicative of BPDCN. We additionally confirmed immunohistochemical positivity for CD4 and CD123 in BM and CD123 in the LN biopsy. Taken together, the diagnosis was most consistent with the current WHO category of BPDCN within the AML and related precursor neoplasms group of malignancies. n n n nFig. 3 n nImmunohistochemical staining of the right supraclavicular lymph nodes biopsy. (A) CD4+, (B) CD56+, (C) leukocyte common antigen (LCA)+, and (D) CD123+. n n n nIn a cytogenetic study, complex structural abnormalities were observed and the karyotype was found to be 45,XY,der(3;7)(q10;q10),t(6;19)(p21.1;p13.3),t(8;18)(q24.1;q21.1) in 16 out of 20 analyzed metaphase cells. Leroux et al. [5] reported that chromosomal alterations in BPDCN seemed to occur most frequently at 6 chromosomal sites: 5q (72%), 12p and 13q (each 64%), 6q (50%), 15q (43%), and 9 (28%). However, the malignant cells in this case did not show aberrations at any of these chromosomal sites. BPDCN might be linked to genetic disorders that involve CDKN1B, CDKN2A, ARF, CDKN2, RB1, and MLL-ENL rearrangement, although the etiology and prognosis of BPDCN remains unclear [6-8]. n nBPDCN is initially highly sensitive to chemotherapy, with complete response rates ranging from 47% to 86%. However, the prognosis is poor even for patients who achieve a complete response, with a median survival period of 14 months (range, 10-18 months), and 2- and 5-yr overall survival rates of 33% and 6%, respectively [9, 10]. In leukemic BPDCN patients without cutaneous manifestations, the median survival was even lower at only 10 months. However, this survival data should be interpreted with caution because the therapeutic management of the patients was inhomogeneous and often not optimal [11]. It was recently suggested that patients with BPDCN should be treated with chemotherapy similar to that used for AML, followed by allogeneic stem cell transplantation (SCT) on complete response [12]. We performed further molecular studies of prognostic markers such as NPM1, cKIT, and FLT3-ITD, but detected no mutations. Induction chemotherapy with cytarabine and daunorubicin was administered, and a follow-up BM biopsy at day 14 after the start of chemotherapy revealed a marrow hypocellularity of 15% with no residual leukemic cells. The patient was transferred to another hospital for allogenic stem cell transplantation. n nAlthough a few case reports and literature reviews of BPDCN without cutaneous lesion have been reported worldwide [9, 11], there has been no report in Korea. We describe, to our knowledge, the first Korean case of acute leukemic presentation of BPDCN without cutaneous lesion. Even in the absence of characteristic cutaneous manifestations of BPDCN, patients with leukemic presentation and an absence of lineage-specific markers should undergo immunophenotyping including CD4, CD56, and CD123 to exclude this malignancy. Cytogenetic molecular analysis is necessary to further investigate the pathogenesis and genetic background of BPDCN.

Necrotizing Pneumonia and Empyema in an Immunocompetent Patient Caused by Nocardia cyriacigeorgica and Identified by 16S rRNA and secA1 Sequencing

Nocardiosis is a rare and potentially life-threatening infection. Nocardia species are a group of aerobic actinomycetes, which are filamentous, branching, gram-positive, and acid-fast bacilli [1]. Worldwide, respiratory and disseminated infections are most often due to N. asteroids complex, which is increasingly recognized as an opportunistic infection in immunocompromised hosts with underlying HIV infection, neoplastic disease, or long-term high-dose corticosteroid therapy [2]. Recently, infection of N. cyriacigeorgica was reported in an immunocompromised patient in Korea, which was identified by 16S rRNA sequencing analysis and additional biochemical tests combined to draw a conclusion [3]. Here, we describe a case of necrotizing pneumonia and empyema caused by N. cyriacigeorgica in a 77-yr-old Korean male patient who was immunocompetent. This case was diagnosed by DNA amplification and sequence analyses of the 16S rRNA and secA1 genes.