No abstract available.
Humans ; Multiple Myeloma ; Plasma Cells ; Plasma ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Axial mesodermal dysplasia complex (AMDC) arises in variable combinations of craniocaudal anomalies such as musculoskeletal deformities, neuroschisis, or rhombencephalic developmental disorders. To the best of our knowledge, the co-existence of AMDC with associated musculoskeletal anomalies, medullary neuroschisis with mirror movements, and cranial nerve anomalies has not yet been reported. Here, we report the case of a 4-year-old boy whose clinical features were suggestive of Goldenhar syndrome and Poland syndrome with Sprengel deformity. Moreover, he showed mirror movements in his hands suspected of rhombencephalic malformation, and infranuclear-type facial nerve palsy of the left side of his face, the opposite side to the facial anomalies of Goldenhar syndrome. After conducting radiological studies, he was diagnosed with medullary neuroschisis without pontine malformations and Klippel-Feil syndrome with rib anomalies. Based on these findings, we propose that clinical AMDC can be accompanied by a wide variety of musculoskeletal defects and variable degrees of central nervous system malformations. Therefore, in addition to detailed physical and neurological examinations, imaging studies should be considered in AMDC.
Central Nervous System ; Child, Preschool ; Congenital Abnormalities ; Cranial Nerves ; Facial Nerve ; Goldenhar Syndrome ; Hand ; Humans ; Klippel-Feil Syndrome ; Male ; Medulla Oblongata ; Mesoderm* ; Neurologic Examination ; Paralysis ; Poland Syndrome ; Rhombencephalon ; Ribs

Recent advances in chemotherapy have led to increased survival rates for patients with hematologic malignancies. However, standard chemotherapies, including alkylating agents for non-Hodgkin lymphoma, could induce therapy-related myeloid neoplasms (t-MNs), a group of disorders categorized by the World Health Organization in 2008. Here, we report a case of coexistence of bone marrow (BM)-involved refractory marginal zone B-cell lymphoma (MZL) and therapy-related myelodysplastic syndrome (t-MDS). Simultaneous presence of refractory lymphoma and t-MN in the BM is rare, and this is the first report in Korea. The patient received allogeneic hematopoietic stem cell transplantation (HSCT) to cure both the MZL and t-MDS. Since the HSCT, he has been stable for 21 months without any evidence of recurrence.
Alkylating Agents ; Bone Marrow ; Drug Therapy ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Korea ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone* ; Lymphoma, Non-Hodgkin ; Myelodysplastic Syndromes* ; Recurrence ; Survival Rate ; World Health Organization

Mutations in the calreticulin gene, CALR, have recently been discovered in subsets of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). We investigated Korean patients with ET and PMF to determine the prevalence, and clinical and laboratory correlations of CALR/JAK2/MPL mutations. Among 84 ET patients, CALR mutations were detected in 23 (27.4%) and were associated with higher platelet counts (P=0.006) and lower leukocyte counts (P=0.035) than the JAK2 V617F mutation. Among 50 PMF patients, CALR mutations were detected in 11 (22.0%) and were also associated with higher platelet counts (P=0.035) and trended to a lower rate of cytogenetic abnormalities (P=0.059) than the JAK2 V617F mutation. By multivariate analysis, triple-negative status was associated with shorter overall survival (HR, 7.0; 95% CI, 1.6-31.1, P=0.01) and leukemia-free survival (HR, 6.3; 95% CI, 1.8-22.0, P=0.004) in patients with PMF. The type 1 mutation was the most common (61.1%) type among all patients with CALR mutations, and tended toward statistical predominance in PMF patients. All 3 mutations were mutually exclusive and were never detected in patients with other myeloid neoplasms showing thrombocytosis. CALR mutations characterize a distinct group of Korean ET and PMF patients. Triple-negative PMF patients in particular have an unfavorable prognosis, which supports the idea that triple-negative PMF is a molecularly high-risk disease.
Adult ; Aged ; Aged, 80 and over ; Calreticulin/*genetics ; Disease-Free Survival ; Female ; Gene Frequency ; Genetic Association Studies ; Humans ; Janus Kinase 2/*genetics ; Male ; Middle Aged ; Mutation/genetics ; Primary Myelofibrosis/*genetics/mortality ; Receptors, Thrombopoietin/*genetics ; Republic of Korea ; Thrombocythemia, Essential/*genetics/mortality ; Young Adult

Osteomesopyknosis is a rare sclerosing bone disorder of autosomal dominant inheritance. We report a first case of osteomesopyknosis in Korea. A 16-year old girl complained of diffuse back pain for 1 year. We performed physical examination, biochemical investigations and imaging studies. A radiograph of spine revealed rugger-jersey vertebra and sandwich vertebra. Bone specific alkaline phosphatase, osteocalcin and C-terminal telopeptides of type I collagen were normal. Only an axial skeleton involvement was shown on the whole body bone scan. This patient was diagnosed to have osteomesopyknosis. Osteomesopyknosis is characterized by normal level of bone turnover marker and an axial bone involvement. Osteomesopyknosis can be occurred in Korea and needs to be considered when patients, especially young patients, suffer from back pain and have only axial osteosclerosis.
Alkaline Phosphatase ; Back Pain ; Bone Diseases ; Collagen Type I ; Female ; Humans ; Korea ; Osteocalcin ; Osteosclerosis ; Physical Examination ; Skeleton ; Spine ; Wills

BACKGROUND: The presence of significant dysplasia in bone marrow (BM) aspirates helps to distinguish between hypocellular myelodysplastic syndrome (hMDS) and aplastic anemia (AA). Occasionally, diluted BM aspirates make it difficult to recognize dysplastic changes and can also negatively affect the detection of cytogenetic abnormalities in hMDS. We evaluated the usefulness of CD34 and p53 immunoreactivity for discriminating between hMDS and AA and for estimating survival outcomes in hMDS patients. METHODS: BM clot section (BMC) or BM biopsy (BMB) specimens were obtained from 64 hMDS/AA patients (33 with hMDS and 31 with AA) and seven controls. Immunohistochemical (IHC) staining for CD34 and p53 was performed by using the EnVision detection system (Dako, Denmark). We compared the results of IHC staining, BM findings, and chromosomal analyses, and determined overall survival outcomes. RESULTS: The number of CD34- and p53-positive BM cells was higher among the patients with hMDS than among the patients with AA (P<0.001 and P=0.001, respectively). hMDS patients with increased CD34-positive cells had significantly poorer survival outcomes compared with those with normal number of CD34-positive cells (P=0.013). CONCLUSIONS: CD34 and p53 IHC stains of BMC or BMB provide useful information for differentiating between hMDS and AA. CD34 IHC staining of BMC or BMB also provides useful information for estimating survival outcomes in hMDS patients.
Adolescent ; Adult ; Anemia, Aplastic/*diagnosis ; Antigens, CD34/*metabolism ; Bone Marrow/metabolism/*pathology ; Child ; Chromosome Aberrations ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Myelodysplastic Syndromes/*diagnosis/mortality ; ROC Curve ; Tumor Suppressor Protein p53/*metabolism

BACKGROUND: Fms-like tyrosine kinase 3 internal tandem duplication (FLT3 ITD) mutation is related to poor prognosis in normal-karyotype acute myeloid leukemia (AML). However, the prognostic significance of the mutation at relapse has not been adequately investigated. We investigated the prognostic significance of the FLT3 ITD mutation at relapse in normal-karyotype AML patients. METHODS: We analyzed 69 normal-karyotype AML patients, in whom paired bone marrow samples taken at initial diagnosis and subsequent relapse were analyzed for the FLT3 ITD mutation at the Asan Medical Center between 1995 and 2009. RESULTS: Forty patients showed a persistent wild-type genotype, 11 showed the FLT3 ITD mutation at diagnosis and relapse, and 9 lost and another 9 acquired the mutation at relapse. The mutation status at relapse affected the overall survival (OS), with the mutation group showing shorter OS and survival after relapse than the wild-type group did (P<0.001 and P<0.001, respectively), despite having received more frequent stem cell transplantation after relapse than the wild-type group did. However, no difference was detected in the OS and survival after relapse with regard to the mutation status at diagnosis. CONCLUSION: The patients with FLT3 ITD mutation at relapse showed poorer prognoses than those without the mutation. However, mutation status at diagnosis did not affect the outcome. These results suggest that, in normal-karyotype AML patients with relapse, the prognostic significance of FLT3 ITD mutation at relapse is greater than that of the mutation status at diagnosis.
Bone Marrow ; fms-Like Tyrosine Kinase 3 ; Genotype ; Humans ; Leukemia, Myeloid, Acute ; Prognosis ; Recurrence ; Stem Cell Transplantation

BACKGROUND: It has been demonstrated that flow cytometric detection of minimal residual disease (MRD) has a prognostic significance in the treatment of patients with acute leukemia. We investigated the significance of flow cytometric MRD detection for the first time in Korea. METHODS: We analyzed the results of MRD detection in morphologically complete remission bone marrow aspirates from 89 patients with newly-diagnosed or relapsed acute leukemia, in which leukemic cells had cross-lineage antigen expression. Patients were grouped based on MRD frequencies: > or =1.0%, high MRD; <1.0%, low MRD. RESULTS: Forty-seven ALL patients consisted of 10 with high and 37 with low MRD levels. Patients with high MRD levels showed a tendency of more frequent relapse than those with low MRD levels (40.0% and 13.5%, respectively) (P=0.08). High MRD group showed a tendency of short relapse-free survival (RFS) and overall survival (OS), although the differences were not statistically significant. Forty-two AML patients consisted of 16 with high and 26 with low MRD levels. There were no correlations between the MRD levels and relapse rate, RFS or OS. AML patients with high MRD levels showed significantly higher rate of unfavorable cytogenetic risk categories and lower rate of favorable risk categories (P=0.03). CONCLUSIONS: MRD detection by flow cytometric assay of cross-lineage antigen expression would be useful in predicting treatment outcome in patients with ALL rather than AML. We expect that the establishment of the standardization of methods, time to test or antibody combination would be achieved through further trials in this country.
Acute Disease ; Adolescent ; Adult ; Aged ; Antigens/*metabolism ; Antigens, CD/metabolism ; Bone Marrow/metabolism ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; *Flow Cytometry ; Humans ; Infant ; Leukemia, Myeloid, Acute/*diagnosis/mortality/therapy ; Male ; Middle Aged ; Neoplasm, Residual/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/mortality/therapy ; Recurrence ; Survival Rate

PURPOSE: This study was designed to investigate differences in ultrasonographic findings between malignant and benign mammary duct ectasia. METHODS: From January 2003 to June 2005, 54 surgically proven mammary duct ectasia lesions depicted on sonograms were included in this study. We evaluated the ultrasonographic (US) findings in terms of involved ductal location, size, margin, intraductal echogenicity, presence of an intraductal nodule, calcification, ductal wall thickening and echo changes of the surrounding breast parenchyma. The US findings were correlated with the pathological features. RESULTS: Of the 54 lesions, 46 lesions were benign and eight lesions were malignant. Benign lesions included an inflammatory change (n=7), ductal epithelial hyperplasia (n=7), fibrocystic change (n=18), intraductal papilloma (n=11), atypical ductal hyperplasia (n=2) and sclerosing adenosis (n=1). Malignant lesions included ductal carcinoma in situ (DCIS) (n=6), infiltrating ductal carcinoma (n=1) and mucinous carcinoma (n=1). On US images, the peripheral ductal location, an ill-defined margin, ductal wall thickening and a hypoechoic change of the surrounding parenchyma were features significantly associated with malignant duct ectasia. CONCLUSION: For ill-defined peripheral duct ectasia with ductal wall thickening and surrounding hypoechogenicity as depicted on US, the possibility of malignancy should be considered and radiologists should not hesitate to recommend a prompt biopsy.
Adenocarcinoma, Mucinous ; Biopsy ; Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Dilatation, Pathologic ; Hyperplasia ; Papilloma, Intraductal ; Ultrasonography, Mammary

BACKGROUND: Therapy-related myeloid neoplasm (t-MN) is a distinct class of acute myeloid leukemia (AML) in the World Health Organization (WHO) classification. Both AML and acute lymphoblastic leukemia (ALL) may develop after treatment for primary cancer. Topoisomerase inhibitors are commonly used to treat breast cancer patients and are well-known for their effect on leukemogenesis of therapy-related acute leukemias (t-AL). METHODS: We retrospectively evaluated bone marrow test results, chromosomal findings, and clinical characteristics of 12 patients who received topoisomerase inhibitors for breast cancer treatment and later developed acute leukemia. RESULTS: Fourteen patients (0.2%) developed t-AL after treatment for breast cancer. Topoisomerase inhibitors were administered to 12 patients. Among them, 9 patients (75%, 9/12) were diagnosed with therapy-related AML (t-AML) and 3 patients (25%, 3/12) with therapy-related ALL (t-ALL). Eight patients (67%, 8/12) showed translocation involving 11q23 and 3 different partner genes, 19p13.1 (37.5%, 3/8), 9p22 (37.5%, 3/8), and 4q21 (25%, 2/8). The median interval between completion of chemotherapy for breast cancer and occurrence of t-AL was 25 months. Patients with 11q23 translocation showed markedly poorer event-free survival than the group without involvement of 11q23. CONCLUSION: The incidence rate of t-AL after treatment for breast cancer was 0.2% in a tertiary hospital in Korea. Translocation involving the MLL gene was frequently found in t-AL caused by a topoisomerase inhibitor and was related to poor prognosis.
Bone Marrow ; Breast ; Breast Neoplasms ; Disease-Free Survival ; Humans ; Incidence ; Korea ; Leukemia ; Leukemia, Myeloid, Acute ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Retrospective Studies ; Tertiary Care Centers ; Topoisomerase Inhibitors ; World Health Organization