Maturity-onset diabetes of the young (MODY) is caused by autosomal dominant pathogenic variants in one of 14 currently known monogenic genes. Characteristics of patients with MODY include early-onset clinical disease with a family history of diabetes and negative autoantibodies and may present with heterogeneous phenotypes according to the different subtypes. Here, we report a patient with early-onset diabetes who presented asymptomatic mild fasting hyperglycemia with the absence of autoantibodies. She was diagnosed with glucokinase (GCK)-MODY caused by a GCK variant, c.1289T>C (p.L430P), identified by targeted gene-panel testing, and the affected father had the same variant. We interpreted this rare missense variant as a likely pathogenic variant and then she stopped taking oral medication. This case highlights the usefulness of genepanel testing for accurate diagnosis and appropriate management of MODY. We also note the importance of familial genetic testing and genetic counseling for the proper interpretation of MODY variants.

We report a patient with massive eosinophilia and a complex karyotype that was initially misdiagnosed as chronic eosinophilic leukemia (CEL), but later diagnosed as anaplastic large cell lymphoma (ALCL) masked by massive eosinophilia. The complex karyotype observed at initial diagnosis remained unchanged later, after the evidence of bone marrow involvement of ALCL was obtained. At diagnosis, genetic aberrations corresponding to metaphase cytogenetics were not identified by interphase fluorescence in situ hybridization, although abnormal results were noted at follow-up. Together, these observations indicate that the complex karyotype at initial work-up has been derived from a low proportion of lymphoma cells with high mitotic ability that were not identified by microscopy, rather than from massive eosinophils. These findings suggest that our patient had ALCL with secondary eosinophilia rather than CEL since initial diagnosis.
Bone Marrow ; Cytogenetics ; Diagnosis ; Eosinophilia* ; Eosinophils* ; Fluorescence ; Follow-Up Studies ; Humans ; Hypereosinophilic Syndrome* ; In Situ Hybridization ; Interphase ; Karyotype* ; Lymphoma ; Lymphoma, Large-Cell, Anaplastic* ; Masks ; Metaphase ; Microscopy

A genomic instability called chromothripsis occurs as a single catastrophic event, generating massive complex genomic rearrangement with a possible characteristic pattern of copy number oscillations. Here, we report a case of secondary plasma cell leukaemia (PCL) showing chromothripsis identified by single nucleotide polymorphism array (SNP-A)-based karyotyping. A 53-year-old male patient was diagnosed as having secondary PCL four years after he was diagnosed with multiple myeloma, and he died four days later due to intracerebral haemorrhage. Chromosomal analysis and fluorescence in situ hybridization (FISH) revealed the deletions of 13q and 17p and an insertion of 1q. Further, genomic aberrations that were not detected by chromosomal analysis and FISH were identified by SNP-A. In particular, SNP-A revealed numerous alternating copy number state switches involving one, two, or three copy number states on chromosome 7q, suggesting the presence of chromothripsis. The present case suggests that chromothripsis may occur in secondary PCL and can be inferred from genomic copy number profiles identified by SNP-A.
Fluorescence ; Genomic Instability ; Humans ; In Situ Hybridization ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma ; Plasma Cells* ; Polymorphism, Single Nucleotide

Although neutrophilia can manifest from various causes, it is important to be able to distinguish chronic neutrophilic leukemia (CNL) from neutrophilic leukemoid reactions (NLR). In this paper, we describe four cases of leukocytosis with neutrophilia, including one case of CNL with a T618I mutation in colony stimulating factor 3 receptor (CSF3R) and three cases of NLR associated with malignancy or sepsis, which were initially suspected as CNL. Of the three NLR cases, one was associated with ovarian cancer, one with monoclonal gammopathy of undetermined significance and one with multiple myeloma with sepsis. This study demonstrated that confirming the clonality of myeloid cells with CSF3R T618I could contribute to making an accurate differential diagnosis between CNL and NLR in patients with solid cancers or plasma cell neoplasms caused by paraneoplastic syndromes and/or infection.
Colony-Stimulating Factors ; Diagnosis, Differential ; Humans ; Leukemia, Neutrophilic, Chronic* ; Leukemoid Reaction* ; Leukocytosis ; Monoclonal Gammopathy of Undetermined Significance ; Multiple Myeloma ; Myeloid Cells ; Neoplasms, Plasma Cell ; Neutrophils* ; Ovarian Neoplasms ; Paraneoplastic Syndromes ; Sepsis

The differential diagnosis of acute lymphoblastic leukemia (ALL) from other small round blue cell tumors in children is very important for proper treatment, but sometimes difficult. CD45 is expressed on almost all-human leukocytes and not expressed on other small round blue cell tumors. Moreover, CD19 is expressed on all stages of B lineage cells and loss of this antigen is very rare in precursor B-cell ALL. We report a case of ALL with atypical morphology and immunophenotype. A 6-yr-old girl presented with fever and weight loss. Many abnormal cells with variable sized, high nuclearcytoplasmic ratio and distinct nucleoli were counted 23% in bone marrow. The results of immunophenotyping were negative for CD45, CD19, CD10, CD20, CD3, CD5, CD7, CD56/16, CD13, and CD33 and positive for CD22, TdT, and CD34. The immunohistochemical staining of bone marrow biopsies was positive for CD79a, CD10, TdT and CD99. The cytogenetic study showed normal karyotype but amplification of MLL (myeloid/lymphoid or mixed lineage leukemia) gene was suggestive in the fluorescent in situ hybridization. The patient received the standard chemotherapy for acute lymphoblastic leukemia and reached complete remission.
Acute Disease ; Antigens, CD19/*analysis ; Antigens, CD45/*analysis ; Bone Marrow/*pathology ; Child ; Female ; Humans ; In Situ Hybridization ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/*pathology

INTRODUCTION: Attention-deficit hyperactivity disorder (ADHD) was a newly coined term for a disease that existed prior to its naming in the mid 20th century. The issue about whether ADHD is a new disorder or merely a new name for an existing disorder is still controversial. The authors tried to find the clues to the answer for this question through reviewing historical documents for traces of ADHD. CONTENTS: We could find literatures and medical records that contain possible ADHD symptoms. In particular, in 1845, Heinrich Hoffmann's 'fidgety Philip' or 'Johnny Look-in-the-air' nearly satisfies today's criteria for ADHD. Methylphenidate was approved as a promising chemical for inattention in 1957 before the establishment of the concept of ADHD. In 1968, ADHD was first officially introduced as "Hyperactivity Reaction of Childhood" by DSM-II. In 1980, DSM-III, 'Attention Deficit Disorder (ADD)' was adopted as an official diagnostic term and changed to 'ADHD' since the creation of DSM-III-R in 1987. CONCLUSION: As stated above, ADHD has existed since long ago and became familiar via an advanced diagnostic system and therapeutic options.
Diagnostic and Statistical Manual of Mental Disorders ; Medical Records ; Methylphenidate ; Numismatics

BACKGROUND: The urinary albumin/creatinine ratio (ACR) is an important indicator of albuminuria. We aimed to estimate ACR uncertainty and its impact on test results and proposed imprecision quality goals based on the estimated uncertainty. METHODS: The combined ACR uncertainty was calculated using the individual uncertainties of urinary albumin and creatinine. ACR confidence intervals (CIs) were estimated based on the expanded uncertainty. When the CI contained the ACR category boundary (30 or 300 mg/g), the cases were considered ambiguous. Quality goals for ACR were suggested using the number of ambiguous cases among actual patient results. RESULTS: The number of ambiguous cases resulting from the combined ACR uncertainty was higher than expected based on biological variation (BV) quality goals. When the ACR met BV quality specifications, we estimated that 4.8–15.5% of the results may have been misclassified. To minimize the number of ambiguous results, the minimum, desirable, and optimum quality goals were set at 34.0%, 18.0%, and 4.5%, respectively. CONCLUSIONS: We expressed ACR uncertainty using the uncertainties of urinary albumin and creatinine and assessed the impact of this combined uncertainty on the test results. Subsequently, we proposed imprecision quality goals for ACR based on ambiguous results.
Albuminuria ; Creatinine ; Humans ; Uncertainty

BACKGROUND: For donor samples showing reactive results in a human T-cell lymphotropic virus (HTLV) antibody test along with indeterminate results in Western blot assay, HTLV nucleic acid amplification test using laboratory-developed polymerase chain reaction (PCR) was performed. It is necessary to construct an adequate internal control (IC) to evaluate the accuracy of the results since we did not use an IC in the laboratory-developed PCR. METHODS: As a competitive IC, plasmid DNA containing the primer recognition sequence for amplification of the HTLV pX region was constructed. We determined the adequate concentration of the IC, which was added to the samples to evaluate the accuracy of the test results. RESULTS: When the plasmid DNA was added to the HTLV-positive samples, the amplified product of IC (400 bp) was detected with the HTLV gene (230 bp). The adequate concentration of plasmid DNA added as an IC was 1 pg. CONCLUSION: The construction of plasmid DNA as a competitive IC is an efficient method to evaluate accuracy of the test results. However, the production process for the competitive IC must be further developed. Therefore, it is necessary to compare with the performance of a non-competitive IC.
Blotting, Western ; DNA ; Humans ; Methods ; Nucleic Acid Amplification Techniques ; Plasmids ; Polymerase Chain Reaction* ; T-Lymphocytes ; Tissue Donors

Aged ; Bone Marrow ; diagnostic imaging ; pathology ; Epidural Space ; diagnostic imaging ; pathology ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnostic imaging ; pathology ; Male ; Sarcoma, Myeloid ; diagnostic imaging ; pathology ; Spinal Cord Compression ; diagnostic imaging ; pathology

HBV core antibody and surface antibody test are currently conducted for those donors showing non-discriminated reactive (NDR) results on a nucleic acid amplification test (NAT) as a blood donor screening assay. It is necessary to investigate the relationship with HCV or HIV in the donors showing NDR results. From June 12th, 2012 to December 31st, 2018, 0.05% (9,020/17,798,461) donors showed NDR results on a NAT. Among the donors showing NDR results, 17 and 18 donors showed positive results on serological assay of HCV and HIV, respectively. 23 donors with NDR results showed positive results on the serological assay or NAT for HCV or HIV on the following donation. Further study and more accumulated data are required because it may be difficult to find the cause of NDR results by the current serological assay that is used for screening blood donors.
Blood Donors ; HIV ; Humans ; Mass Screening ; Nucleic Acid Amplification Techniques ; Tissue Donors