Microscopic Polyangiitis Following mRNA COVID-19 Vaccination: A Case Report

Coronavirus disease 2019 (COVID-19) is one of the most widespread viral infections in human history. As a breakthrough against infection, vaccines have been developed to achieve herd immunity. Here, we report the first case of microscopic polyangiitis (MPA) following BNT162b2 vaccination in Korea. A 42-year-old man presented to the emergency room with general weakness, dyspnea, and edema after the second BNT162b2 vaccination. He had no medical history other than being treated for tuberculosis last year. Although his renal function was normal at last year, acute kidney injury was confirmed at the time of admission to the emergency room. His serum creatinine was 3.05 mg/dL. Routine urinalysis revealed proteinuria (3+) and hematuria. When additional tests were performed for suspected glomerulonephritis, the elevation of myeloperoxidase (MPO) antibody (38.6 IU/mL) was confirmed. Renal biopsy confirmed pauci-immune anti-neutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis and MPA was diagnosed finally. As an induction therapy, a combination of glucocorticoid and rituximab was administered, and plasmapheresis was performed twice. He was discharged after the induction therapy and admitted to the outpatient clinic 34 days after induction therapy. During outpatient examination, his renal function had improved with serum creatinine 1.51 mg/dL. We suggest that MPA needs to be considered if patients have acute kidney injury, proteinuria, and hematuria after vaccination.

Clinical Characteristics of Cervical Toxoplasma Lymphadenitis / 대한이비인후과학회지

Background and Objectives@#Toxoplasmosis is a disease caused by an intracellular parasite, Toxoplasma gondii. There has been only a few studies done on cervical toxoplasma lymphadenitis, and this study was performed to evaluate its clinical characteristics and outcomes.Subjects and Method We retrospectively reviewed the patients diagnosed with cervical toxoplasma lymphadenitis from January 2010 to December 2019. We investigated clinical pathologic findings, treatment and clinical outcomes. @*Results@#Enrolled in the study were 21 patients who were confirmed with typical pathologic findings in an excisional biopsy (16/21) and core needle biopsy (5/21). Nine patients were male and 12 patients were female, with the mean age of 46.1±13.59 (19-70). All patients complained of neck masses and 5 (23.8%) patients showed pain or tenderness. Only one (4.8%) patient had mild fever. Fine needle aspiration cytology was performed in 5 patients, with no resulting pathognomonic outcomes in any one of the patients. CT scan was performed in 15 patients, with 8 (53.3%) patients showing multiple nodal enlargements but 7 (46.6%) patients showing a single enlarged lymph node. The most frequently involved location was level I (53.3%), followed by level II (46.6%), level V (46.6%), level III (40.0%), and level IV (20.0%). The serologic test for toxoplasma revealed positive IgG (100%) and IgM (85.7%). Treatments were excision only (61.9%) and excision with pharmacologic treatment using sulfonamide or pyrimethamine (38.1%). There was no case of recurrence after treatment. @*Conclusion@#Cervical toxoplasma lymphadenitis can be diagnosed by biopsy but needle aspiration has little role. It shows favorable clinical outcomes after treatment.

Suppression of ARID1A associated with decreased CD8 T cells improves cell survival of ovarian clear cell carcinoma / 부인종양

Objective@#AT-rich interactive domain 1A (ARID1A) plays an important role as a tumor suppressor gene in ovarian clear cell carcinoma (OCCC), but the clinical application of ARID1A remains unclear. The aim of this study was to analyze clinicopathological parameters, molecular interactions and immune-infiltration in patients with low ARID1A expression and to provide candidate target drugs. @*Methods@#We investigated the clinicopathologic parameters, specific gene sets/genes, and immunological relevance according to ARID1A expression in 998 OCCC patients from 12 eligible studies (using meta-analyses); 30 OCCC patients from the Hanyang University Guri Hospital (HYGH) cohort; and 52 OCCC patients from gene set enrichment (GSE) 65986 (25 patients), 63885 (9 patients), and 54809 (6 patients and 12 healthy people) of the Gene Expression Omnibus (GEO). We analyzed network-based pathways based on gene set enrichment analysis (GSEA) and performed in vitro drug screening. @*Results@#Low ARID1A expression was associated with poor survival in OCCC from the metaanalysis, HYGH cohort and GEO data. In GSEA, low ARID1A expression was related to the tumor invasion process as well as a low immune-infiltration. In silico cytometry showed that CD8 T cells were decreased with low ARID1A expression. In pathway analysis, ARID1A was associated with angiogenic endothelial cell signaling. In vitro drug screening revealed that cabozantinib and bicalutamide effectively inhibited specific hub genes, such as vascular endothelial growth factor-A and androgen receptor, in OCCC cells with low ARID1A expression. @*Conclusions@#Therapeutic strategies making use of low ARID1A could contribute to better clinical management/research for patients with OCCC.

Continuous quality improvement program and its results of Korean Society for Cytopathology

Since 1995, the Korean Society for Cytopathology has overseen the Continuous Quality Improvement program for cytopathology laboratories. The Committee of Quality Improvement has carried out an annual survey of cytology data for each laboratory and set standards for proficiency tests. Methods: Evaluations were conducted four times per year from 2008 to 2018 and comprised statistics regarding cytology diagnoses of previous years, proficiency tests using cytology slides provided by the committee, assessment of adequacy of gynecology (GYN) cytology slides, and submission of cytology slides for proficiency tests. Results: A total of 206 institutes participated in 2017, and the results were as follows. The number of cytology tests increased from year to year. The ratio of liquid-based cytology in GYN gradually decreased, as most of the GYN cytology had been performed at commercial laboratories. The distribution of GYN diagnoses demonstrated nearly 3.0% as atypical squamous cells. The rate for squamous cell carcinoma was less than 0.02%. The atypical squamous cell/squamous intraepithelial lesion ratio was about 3:1 and showed an upward trend. The major discordant rate of cytology-histology in GYN cytology was less than 1%. The proficiency test maintained a major discordant rate less than 2%. The rate of inappropriate specimens for GYN cytology slides gradually decreased. Conclusions: The Continuous Quality Improvement program should be included in quality assurance programs. Moreover, these data can contribute to development of national cancer examination guidelines and facilitate cancer prevention and treatment.

LGR5 and Downstream Intracellular Signaling Proteins Play Critical Roles in the Cell Proliferation of Neuroblastoma, Meningioma and Pituitary Adenoma

Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) has been reported to play critical roles in the proliferation of various cancer cells. However, the roles of LGR5 in brain tumors and the specific intracellular signaling proteins directly associated with it remain unknown. Expression of LGR5 was first measured in normal brain tissue, meningioma, and pituitary adenoma of humans. To identify the downstream signaling pathways of LGR5, siRNA-mediated knockdown of LGR5 was performed in SH-SY5Y neuroblastoma cells followed by proteomics analysis with 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE). In addition, the expression of LGR5-associated proteins was evaluated in LGR5-inhibited neuroblastoma cells and in human normal brain, meningioma, and pituitary adenoma tissue. Proteomics analysis showed 12 protein spots were significantly different in expression level (more than two-fold change) and subsequently identified by peptide mass fingerprinting. A protein association network was constructed from the 12 identified proteins altered by LGR5 knockdown. Direct and indirect interactions were identified among the 12 proteins. HSP 90-beta was one of the proteins whose expression was altered by LGR5 knockdown. Likewise, we observed decreased expression of proteins in the hnRNP subfamily following LGR5 knockdown. In addition, we have for the first time identified significantly higher hnRNP family expression in meningioma and pituitary adenoma compared to normal brain tissue. Taken together, LGR5 and its downstream signaling play critical roles in neuroblastoma and brain tumors such as meningioma and pituitary adenoma.

Coexistence of metastatic thyroid cancer and tuberculosis in a single neck lymph node: a rare association

No abstract available.

The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma

BACKGROUND: Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma. METHODS: Combined expression patterns based on Smad4+/– and PTEN+/– status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed. RESULTS: Smad4–/PTEN– status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p<.001). When Smad4–/PTEN– and Smad4+/PTEN+ groups were compared, Smad4–/PTEN– status was associated with high N stage (p=.018) and defective mismatch repair proteins (p=.006). Significant differences in diseasefree survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4–/PTEN+ or Smad4+/PTEN–, and Smad4–/PTEN–) (all p<.05). CONCLUSIONS: Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.

A 2-Week Steroid Trial for Differentiating Isolated IgG4-Related Sclerosing Cholangitis from Cholangiocarcinoma / 대한췌담도학회지

Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is rare disease which is steroid-responsive and often associated with IgG4 related systemic disease such as autoimmune pancreatitis. It is characterized by increased serum IgG4 and IgG4-positive lymphoplasmacytic infiltration in bile ducts. It is often difficult to distinguish IgG4-SC to hilar cholangiocarcinoma if it manifests as an isolated bile duct. We report a case of 79-year-old woman with IgG4-SC which was difficult to distinguish hilar cholangiocarcinoma due to similar clinical and radiologic findings, showing good therapeutic effect after a 2-week steroid trial.

Wnt7a Deficiency Could Predict Worse Disease-Free and Overall Survival in Estrogen Receptor-Positive Breast Cancer / 한국유방암학회지

PURPOSE: Wnt7a is a glycoprotein involved in embryonic development and the progression of different types of malignant tumors. This study aimed to detect the level of Wnt7a expression in breast cancer and explore its role in the disease progression and prognosis. METHODS: A total of 258 patients diagnosed with invasive ductal carcinoma of the breast were included in this study. Using tissue microarray and immunohistochemical staining, we evaluated the association between Wnt7a expression and clinicopathological parameters, and the prognostic value of Wnt7a. RESULTS: Wnt7a expression was significantly correlated with estrogen receptor (ER) expression (odds ratio, 3.95; 95% confidence interval [CI], 1.99–7.80; p < 0.001). On univariate and multivariate analyses, loss of Wnt7a expression was associated with poor disease-free survival (DFS) (multivariate hazard ratio [HR], 9.12; 95% CI, 1.80–46.09; p=0.008), but not with poor overall survival (OS). In the ER-positive group (n=114), loss of Wnt7a expression was an independent prognostic factor for shorter DFS (multivariate HR, 13.54; 95% CI, 1.11–165.73; p=0.042) and OS (multivariate HR, 4.76; 95% CI, 1.29–17.61; p=0.019) on univariate and multivariate analyses. However, in the ER-negative group, there was no significant difference in DFS and OS according to Wnt7a expression. CONCLUSION: The loss of Wnt7a expression might be a meaningful factor in assessing DFS and OS, especially in ER-positive breast cancer.

Thyroid Fine-Needle Aspiration Cytology Practice in Korea

We reviewed the current status of thyroid fine-needle aspiration cytology (FNAC) in Korea. Thyroid aspiration biopsy was first introduced in Korea in 1977. Currently, radiologists aspirate the thyroid nodule under the guidance of ultrasonography, and cytologic interpretation is only legally approved when a cytopathologist makes the diagnosis. In 2008, eight thyroid-related societies came together to form the Korean Thyroid Association. The Korean Society for Cytopathology and the endocrine pathology study group of the Korean Society for Pathologists have been updating the cytologic diagnostic guidelines. The Bethesda System for Reporting Thyroid Cytopathology was first introduced in 2009, and has been used by up to 94% of institutions by 2016. The average diagnosis rates are as follows for each category: I (12.4%), II (57.9%), III (10.4%), IV (2.9%), V (3.7%), and VI (12.7%). The malignancy rates in surgical cases are as follows for each category: I (28.7%), II (27.8%), III (50.6%), IV (52.3%), V (90.7%), and VI (100.0%). Liquid-based cytology has been used since 2010, and it was utilized by 68% of institutions in 2016. The categorization of thyroid lesions into “atypia of undetermined significance” or “follicular lesion of undetermined significance” is necessary to draw consensus in our society. Immunocytochemistry for galectin-3 and BRAF is used. Additionally, a molecular test for BRAF in thyroid FNACs is actively used. Core biopsies were performed in only 44% of institutions. Even the institutions that perform core biopsies only perform them for less than 3% of all FNACs. However, only 5% of institutions performed core biopsies up to three times more than FNAC.

Traumatic Bowel Perforation and Inguinal Hernia Masking a Mesenteric Calcifying Fibrous Tumor

No abstract available.

Imaging Mass Spectrometry in Papillary Thyroid Carcinoma for the Identification and Validation of Biomarker Proteins

Direct tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization and time-of-flight (MALDI-TOF) mass spectrometry has become increasingly important in biology and medicine, because this technology can detect the relative abundance and spatial distribution of interesting proteins in tissues. Five thyroid cancer samples, along with normal tissue, were sliced and transferred onto conductive glass slides. After laser scanning by MALDI-TOF equipped with a smart beam laser, images were created for individual masses and proteins were classified at 200-microm spatial resolution. Based on the spatial distribution, region-specific proteins on a tumor lesion could be identified by protein extraction from tumor tissue and analysis using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Using all the spectral data at each spot, various intensities of a specific peak were detected in the tumor and normal regions of the thyroid. Differences in the molecular weights of expressed proteins between tumor and normal regions were analyzed using unsupervised and supervised clustering. To verify the presence of discovered proteins through IMS, we identified ribosomal protein P2, which is specific for cancer. We have demonstrated the feasibility of IMS as a useful tool for the analysis of tissue sections, and identified the tumor-specific protein ribosomal protein P2.

Erratum: Correction of Acknowledgments. ERG Immunohistochemistry as an Endothelial Marker for Assessing Lymphovascular Invasion

The Acknowledgments were marked incorrectly.

ERG Immunohistochemistry as an Endothelial Marker for Assessing Lymphovascular Invasion

BACKGROUND: ERG, a member of the ETS family of transcription factors, is a highly specific endothelial marker. We investigated whether the use of ERG immunostaining can help pathologists detect lymphovascular invasion (LVI) and decrease interobserver variability in LVI diagnosis. METHODS: Fifteen cases of surgically resected colorectal cancers with hepatic metastasis were selected and the most representative sections for LVI detection were immunostained with ERG, CD31, and D2-40. Eight pathologists independently evaluated LVI status on hematoxylin and eosin (H&E) and the corresponding immunostained sections and then convened for a consensus meeting. The results were analyzed by kappa (kappa) statistics. RESULTS: The average rate of LVI positivity was observed in 43% with H&E only, 10% with CD31, 29% with D2-40, and 16% with ERG. Agreement among pathologists was fair for H&E only (kappa=0.27), D2-40 (kappa=0.21), ERG (kappa=0.23), and was moderate for CD31 (kappa=0.55). Consensus revealed that ERG nuclear immunoreactivity showed better visual contrast of LVI detection than the other staining, with improved agreement and LVI detection rate (kappa=0.65, LVI positivity rate 80%). CONCLUSIONS: The present study demonstrated a superiority with ERG immunostaining and indicated that ERG is a promising panendothelial marker that might help pathologists increase LVI detection and decrease interobserver variability in LVI diagnosis.

The Glycolytic Phenotype is Correlated with Aggressiveness and Poor Prognosis in Invasive Ductal Carcinomas / 한국유방암학회지

PURPOSE: Glucose uptake and glycolytic metabolism are enhanced in cancer cells, and increased expression of glucose transporter 1 (GLUT1) has also been reported. The aim of this study was to investigate GLUT1 expression in human breast tissues and invasive ductal carcinomas. METHODS: We used tissue microarrays consisting of normal breast tissue, ductal hyperplasia, ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastases. We examined GLUT1 expression in the microarrays by immunohistochemistry, reviewed the medical records and performed a clinicopathological analysis. RESULTS: Membranous GLUT1 expression was observed in normal and tumor cells. GLUT1 expression was higher in ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastasis than in normal tissue and ductal hyperplasia (p=0.002). Of 276 invasive ductal carcinomas, 106 (38.4%) showed GLUT1 expression. GLUT1 expression was correlated with higher histologic grade (p<0.001), larger tumor size (p=0.025), absence of estrogen receptor (p<0.001), absence of progesterone receptor (p<0.001), and triple-negative phenotype (p<0.001). In univariate survival analysis, patients with GLUT1 expression had poorer overall survival and disease-free survival (p=0.017 and p=0.021, respectively, log-rank test). In multivariate survival analysis with the Cox proportional hazards model, GLUT1 expression was an independent prognostic factor of poorer overall survival and disease-free survival (p=0.017 and p=0.019, respectively). CONCLUSION: GLUT1 expression seems to play an important role in malignant transformation, and the glycolytic phenotype in invasive ductal carcinoma may indicate aggressive biological behavior and a worse prognosis.

Helicobacter pylori Infection is Associated with Elevated Low Density Lipoprotein Cholesterol Levels in Elderly Koreans

This study was conducted to investigate the association between Helicobacter pylori (H. pylori) infection and the lipid profile among elderly Koreans. A total of 462 subjects (mean age 66.2 +/- 7.6 yr, 84% males) who underwent health check-up were investigated. Each subject underwent gastroduodenoscopy with gastric mucosal biopsy, and H. pylori infection was determined by histopathological examination using the updated Sydney System score. The presence of H. pylori infection was significantly associated with the elevated serum levels of total cholesterol and low density lipoprotein (LDL) cholesterol (P 0.05 for each). After controlling confounders, multiple logistic regression analysis showed that the odds ratio of H. pylori infection for high LDL cholesterol level (> 140 mg/dL) was 3.113 (95% confidence interval, 1.364-7.018; P = 0.007). There were no significant associations between the presence of H. pylori infection and elevated total cholesterol levels (> 200 mg/dL) in this model (P = 0.586). The results of this study demonstrate that H. pylori infection is associated with the elevated serum LDL cholesterol levels in elderly Koreans, supporting the hypothesis that H. pylori plays a role in promoting atherosclerosis by modifying lipid metabolism.

CD44s and CD44v6 Are Predominantly Expressed in the Non-germinal Center B-Cell-like Type of Diffuse Large B-Cell Lymphomas

BACKGROUND: CD44 protein is known as a homing cellular adhesion molecule that is linked to diverse cellular functions such as adhesion, migration and invasion, which are all important in cancer progression and metastasis. The expression of CD44 standard and variant isoforms (CD44 standard isoform [CD44s] and CD44 splice variants containing exon v6 [CD44v6], respectively) is associated with an unfavorable clinical outcome in various neoplasms. METHODS: Forty patients who were diagnosed with diffuse large B-cell lymphoma (DLBCL) through biopsy at Hanyang University Hospital between 1996 and 2003 were included in this study. CD44 proteins expression was analyzed by immunohistochemical staining on a tissue microarray and the correlation of CD44 with the types of DLBCL and clinical parameters, including the factors defined by the International Prognostic Index, was evaluated. RESULTS: A high CD44s and intermediate to strong CD44v6 expression, including cytoplasmic membranous staining patterns, was present in 35% (14/40) and 25% (10/40) of DLBCL patients, respectively. High CD44s expression was correlated significantly with non-germinal center B-cell-like types (non-GCB, p=0.004) and patients with old age (p=0.041). CONCLUSIONS: High CD44s expression may be significantly associated with the non-GCB type compared to the GCB type and may be essential to the prediction of disease outcome in tumor stage III in DLBCL patients.

A Case of Gastric Carcinosarcoma with Neuroendocrine and Smooth Muscle Differentiation

Carcinosarcoma of the stomach is a rarely occurring malignant biphasic tumor that consists of both carcinomatous and sarcomatous components simultaneously in a single tumor. The common carcinoma component is tubular or papillary adenocarcinoma and the mesenchymal sarcomatous components are variable and these include leiomyosarcoma, rhabdomyosarcoma, osteosarcoma and chondrosarcoma. However, neuroendocrine carcinomatous differentiation in the carcinomatous component is extremely rare. We present here a rare gastric carcinosarcoma that demonstrated neuroendocrine carcinomatous and leiomyosarcomatous differentiation in a 47-year-old man.

Morsicatio Labiorum/Linguarum: Three Cases Report and a Review of the Literature

Morsicatio is a condition caused by habitual chewing of the lips (labiorum), tongue (linguarum), or buccal mucosa (buccarum). Clinically, it often produces a shaggy white lesion caused by pieces of the oral mucosa torn free from the surface. The condition is generally found among people who are stressed or psychologically impaired. Most patients with this condition are not even aware of their biting habit. Clinically, morsicatio mimics hairy leukoplakia, and sometimes, it may be confused with other dermatologic diseases involving the oral cavity. It is rarely described in pathologic and dermatological textbooks. Histological features are distinctive, however, being careful to make a correct diagnosis can help one avoid providing inappropriate treatment. In this report we describe three cases of morsicatio, one that developed in the lower lip and the others that developed on the side of the tongue.

Cystic Lymphangioma of the Breast in an Adult Woman

Cystic lymphangioma is also known as cystic hygroma, and this is a congenital malformation of the lymphatic system. Most lymphangiomas are present at birth and they are diagnosed by the age of 2. They are mostly located in the neck or axillary region. The breast as a site of origin is an extremely unusual location, and especially in adults. We report here on a case of cystic lymphangioma in a 36-year-old woman. Physical examination revealed a tender cystic mass in the upper outer quadrant of the right breast. Ultrasonography revealed an irregular hypoechoic mass lesion that was associated with irregular duct dilatation and several enlarged axillary lymph nodes. After the operation, the mass was revealed to be a cystic lymphangioma. Although it is very rare, cystic lymphangioma should be considered in the differential diagnosis of a breast mass in adults.