OBJECTIVES: Immunohistochemistry (IHC) has been used for the diagnosis of indeterminate results in fine needle aspiration (FNA) of thyroid nodules. However, the role of IHC in core needle biopsy (CNB) is not clear and the efficacy of testing for molecular markers following CNB has not been evaluated. The aim of this study is to compare the role of IHC staining in CNB with that in FNA when examining thyroid nodules and to compare the sensitivity and usefulness of different molecular markers. METHODS: Consecutive cases of thyroid FNA and CNB accompanied by IHC from 2004 to 2014 were included in this study with retrospective review of medical record. The rate of remaining nondiagnostic result (unsatisfactory, atypia of undetermined significance or follicular lesion of undetermined significance [AUS/FLUS]) and rate of strong expression of each molecular marker according to the diagnosis were evaluated. RESULTS: IHC was more frequently performed in CNB with multiple molecular markers compared to FNA (38.1% vs. 2.8%, 3 or 4 markers [Gal-3, HBME-1, CK19, and CD56] vs. 1 marker [Gal-3]). In the CNB group, 11.3% remained as AUS/FLUS after IHC, and the rate remaining nondiagnostic was significantly less than in the FNA group (42.9%). Gal-3 and CK19 showed higher specificity and expressed mainly in conventional type of papillary carcinoma and HBME-1 showed higher sensitivity for the diagnosis of carcinoma with expression in both conventional type and follicular variant papillary thyroid carcinoma. CONCLUSION: With these data, we could conclude that IHC was more effective following CNB than following FNA.
Biopsy, Fine-Needle ; Biopsy, Large-Core Needle ; Carcinoma, Papillary ; Diagnosis ; Immunohistochemistry ; Medical Records ; Retrospective Studies ; Sensitivity and Specificity ; Thyroid Gland ; Thyroid Neoplasms ; Thyroid Nodule

No abstract available.
Adenocarcinoma

Most cases of congenital hyperthyroidism are autoimmune forms caused by maternal thyroid stimulating antibodies. Nonautoimmune forms of congenital hyperthyroidism caused by activating mutations of the thyrotropin receptor (TSHR) gene are rare. A woman gave birth to a boy during an emergency cesarean section at 33 weeks of gestation due to fetal tachycardia. On the 24th day of life, thyroid function tests were performed due to persistent tachycardia, and hyperthyroidism was confirmed. Auto-antibodies to TSHR, thyroid peroxidase, and thyroglobulin were not found. The patient was treated with propylthiouracil and propranolol, but hyperthyroidism was not well controlled. At 3 months of age, the patient had craniosynostosis and hydrocephalus, and underwent a ventriculoperitoneal shunt operation. Direct sequencing of the TSHR gene showed a heterozygous mutation of c.1899C>A (p.Asp633Glu) in exon 10. No mutations were discovered in any of the parents in a familial genetic study. We have reported a case of sporadic nonautoimmune congenital hyperthyroidism, by a missense mutation of the TSHR gene, for the first time in South Korea.
Cesarean Section ; Craniosynostoses ; Emergencies ; Exons ; Female ; Germ-Line Mutation ; Humans ; Hydrocephalus ; Hyperthyroidism* ; Immunoglobulins, Thyroid-Stimulating ; Iodide Peroxidase ; Korea ; Male ; Mutation, Missense ; Parents ; Parturition ; Pregnancy ; Propranolol ; Propylthiouracil ; Receptors, Thyrotropin ; Tachycardia ; Thyroglobulin ; Thyroid Function Tests ; Ventriculoperitoneal Shunt

Invasive fungal infections (IFIs) are common causes of mortality and morbidity in patients with hematologic diseases. Delayed initiation of antifungal treatment is related to mortality. Aspergillus sp. is the leading cause of IFI followed by Candida sp. Diagnosis is often challenging owing to variable conditions related to underlying diseases. Clinical suspect and prompt management is important. Imaging, biopsy, and non-culture-based tests must be considered together. New diagnostic procedures have been improved, including antigen-based assays and molecular detection of fungal DNA. Among hematologic diseases, patients with acute myeloid leukemia, myelodysplastic syndrome, recipients of hematopoietic stem cell transplantation are at high risk for IFIs. Antifungal prophylaxis is recommended for these high-risk patients. There are continuous attempts to achieve ideal management of IFIs. Scoring system for quality control has been developed with important recommendations of current guidelines. Higher adherence to guidelines is related to decreased mortality in IFIs.

Gastroparesis is a disorder of gastric motility that results in delayed gastric emptying. Up to 58% of patients with diabetes mellitus may have diabetic gastroparesis, a syndrome characterized by nausea, vomiting, early satiety, and bloating. The pathophysiology of this disorder is not completely understood, but it is believed to include fundic dysaccommodation, a decrease in gastroduodenal pressure gradient and antral hypomotility. In addition to antral and fundic dysfunction, patients with diabetes may typically have pyloric dysfunction or spasm. Treatment consists of a change in diet to small volume, frequent meals and the use of the prokinetic agents. This case report describes the four patients with severe diabetic gastroparesis whose symptoms persisted despite of dietary changes and the use of prokinetic agents in high doses. All of them were treated with pyloric injection of botulinum toxin and three had significant symptomatic and scintigraphic improvement.
Botulinum Toxins* ; Diabetes Mellitus ; Diet ; Gastric Emptying ; Gastroparesis* ; Humans ; Meals ; Nausea ; Pylorus ; Spasm ; Vomiting

BACKGROUND: This study was conducted to explore the effect of known risk factors, focusing on risk factors including age at menarche, age at menopause, number of children, family history of breast cancer, and age at first birth according to breast density, in consideration of interaction among East-Asian women. METHODS: Case-control study with 2,123 cases and 2,121 controls with mammographic density was conducted. Using the mammographic film, breast density was measured using Breast Imaging-Reporting and Data System. To identify the association of selected reproductive factors including age at menarche, age at menopause, number of children, family history of breast cancer, and age at first birth according to breast density, stratified analysis was conducted according to breast density groups and interaction effects was assessed. The results were presented with adjusted OR and 95% CIs. RESULTS: Significant interaction effect between age at first birth and breast density on breast cancer (P = 0.048) was observed. Women with age at first birth ≥ 28 years old showed increased breast cancer risk in extremely dense breast group (≥ 75%) (OR = 1.627, 95% CI = 1.190–2.226). However, women with fatty breast (< 50%) and heterogeneously dense breast (50%–75%) did not show an increased association. Age at menarche, age at menopause, number of children, and family history of breast cancer did not show significant interaction with breast cancer and similar risk patterns were observed. CONCLUSIONS: Age at first birth showed significant interaction with breast density on breast cancer risk. Further studies considering biologically plausable model between exposure, intermediate outcomes and breast cancer risk with prospective design need to be undertaken in East Asian women.
Asian Continental Ancestry Group ; Birth Order ; Breast Neoplasms ; Breast ; Case-Control Studies ; Child ; Female ; Humans ; Information Systems ; Menarche ; Menopause ; Prospective Studies ; Reproductive History ; Risk Factors

Background: Patients with hematologic diseases are at high risk of bloodstream infections (BSIs). This study aimed to analyze clinical features and distributions of microorganisms in patients with hematologic diseases presenting at a tertiary care university-affiliated hospital in Korea. Materials and Methods: We retrospectively reviewed all BSI episodes recorded in patient medical records at two hematologic wards of the Catholic Hematology Hospital from January to December 2020. Our aim was to analyze demographic and clinical characteristics relevant to BSIs. We also described the antimicrobial resistance patterns of the major pathogens identified in this study, and evaluated risk factors for extended-spectrum beta-lactamase (ESBL) production in Enterobacteriaceae isolates and for vancomycin resistance in enterococcal isolates. Results: A total of 380 BSI episodes were identified in 334 patients over the course of 1 year (monomicrobial BSI episodes, 86.1%; polymicrobial BSI episodes, 13.9%). Gram-negative bacteria accounted for 242 isolates (54.8%). The most frequently isolated Gram-negative bacteria isolates were Escherichia coli (107 [24.2%]) followed by Klebsiella spp. (72 [16.3%]), Pseudomonas spp. (21 [4.8%]), and Enterobacter spp. (12 [2.7%]). The most commonly identified Gram-positive bacteria were Enterococcus spp. (72 [16.3%]) followed by viridans streptococci (54 [12.2%]), coagulase-negative staphylococci (CoNS) (24 [5.4%]), and Corynebacterium spp. (22 [5.0%]). ESBL-producing Enterobacteriaceae accounted for 25.1% of the total distribution. Among 54 Enterococcus faecium isolates, 100.0% were resistant to ampicillin and 55.6% showed resistance to vancomycin, while 100.0% (n = 12) of Enterococcus faecalis isolates were susceptible to ampicillin and vancomycin, respectively. Use of ciprofloxacin prophylaxis (odds ratio: 5.20; 95% confidence interval: 1.11 - 24.34; P = 0.04) was an independent risk factor for ESBL production in Enterobacteriaceae BSIs. Conclusion Compared with the results of a previous study conducted at the same institution, our findings demonstrated that Gram-negative bacteria remained dominant pathogens in BSIs occurring in patients with hematologic diseases. Our findings also demonstrated a comparatively decreased prevalence of ESBL-producing Enterobacteriaceae in the evaluated BSIs. However, the prevalence of enterococcal BSIs had not decreased, and the proportion of vfancomycin-resistant Enterococcus isolates from E. faecium BSIs had increased. In addition, we found that ciprofloxacin prophylaxis was statistically significantly associated with ESBL production in Enterobacteriaceae BSIs. We conclude that, in order to avoid critical complications and to reduce the burden of antimicrobial-resistant organisms in patients with hematologic diseases, it is necessary to conduct periodic examinations evaluating changes in BSI epidemiology within a single medical center.

Purpose: Despite advances in treatment, lung cancer remains the leading cause of cancer mortality. This study aimed to characterise genome-wide tumorigenesis events and to understand the hypothesis of the multistep carcinogenesis of lung adenocarcinoma (LUAD) Materials and Methods: We conducted multiregion whole-exome sequencing of LUAD with synchronous atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ, or minimally invasive adenocarcinoma of 19 samples from three patients to characterize genome-wide tumorigenesis events and validate the hypothesis of the multistep carcinogenesis of LUAD. We identified potential pathogenic mutations preserved in preinvasive lesions and supplemented the finding by allelic variant level from RNA sequencing. Results: Overall, independent mutational profiles were observed per patient and between patients. Some shared mutations including epidermal growth factor receptor (EGFR , p.L858R) were present across synchronous lesions. Conclusion Here, we show that there are driver gene mutations in AAH, and they may exacerbate as a sequence in a histological continuum, supporting the Darwinian evolution model of cancer genome. The intertumoral and intratumoral heterogeneity of synchronous LUAD implies that multi-biomarker strategies might be necessary for appropriate treatment.

Background: Alopecia areata (AA) is common non-scarring hair loss disease. Sleep distrubance has been regarded as a triggering or aggravating factor for AA. However, objective evaluation of sleep disturbance and its clinical effect on AA has not been clearly demonstrated. Objective: This study investigated objective sleep evaluation tool for AA patients and their clinical correlation. Methods: Patients presenting with new-onset AA or recurrences of pre-existing AA were included, and those who reported sleep disturbance in the preliminary survey were designated as the sleep disturbance group (SD group). Sleep quality was investigated for them using three self-administered questionnaires: Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Epworth Sleep Scale (ESS). Demographic information and clinical features of AA were analyzed according to sleep quality. Results: A total of 400 participants were enrolled, and 53 were categorized into the SD group. The incidence of stressful events was significantly higher in the SD group (54.7%) than in the non-SD group (25.1%) (p<0.001). Based on the PSQI, 77.3% of participants were objective poor sleepers (score of 5 or more), and they showed a significantly higher incidence of stressful events compared to good sleepers (p=0.019). The proportion of poor sleepers was significantly lower in patients with mild AA (S1) than in those with moderate to severe AA (S2~S5) (p=0.045). Conclusion This study demonstrated a positive correlation among stress, SD, and AA. The degree of SD was objectively represented by the PSQI score, showing different scores according to AA severity.

After anaplastic large-cell lymphoma (ALCL) was first described by Stain in 1985, there have been several histological variants of ALCL reported. There are classified histological subtypes of ALCL, such as lymphohistiocytic, small cell, Hodgkin-like, composite pattern, and other less common variants including neutrophil-rich ALCL. A 63-year-old male patient presented with erythematous exophytic mass on the left lower leg. In the past, his condition had been diagnosed as abdominal primary cutaneous ALCL (pcALCL), which recurred as systemic ALCL (sALCL) in the left bronchus. After treatment, he achieved complete remission. Histopathologic examination showed large-sized pleomorphic, anaplastic mitotic tumor cells, several neutrophils, and a few lymphocytes. Neutrophil-rich ALCL is a rare histological variant of ALCL. It is characterized by the presence of CD30-positive anaplastic tumor cells with numerous neutrophil infiltrations. Neutrophil-rich ALCL responds well to treatment but tends to recur. There were four cases reported to have recurrent neutrophilrich ALCL. All cases were diagnosed with neutrophil-rich pcALCL prior to recurrence.Three cases had local recurrence, and only one case relapsed as sALCL. Herein, we present the first case of neutrophil-rich ALCL recurring as sALCL twice.