Abducens Nerve Palsy and Optic Perineuritis Caused by Fungal Sphenoidal Sinusitis

PURPOSE: To report a case of abducens nerve palsy and optic perineuritis caused by fungal sphenoidal sinusitis. CASE SUMMARY: A 48-year-old male visited emergency department for retrobulbar pain, decreased vision, and horizontal diplopia for 3 days. He reported that previous medical history was non-specific, however, blood glucose level was 328 mg/dL (70–110). He had experienced severe headache for 7 days. The best corrected visual acuity was 20/20 at right eye and 20/25 at left eye. The pupil of left eye did not have relative afferent pupillary defect. Left mild proptosis was noted. The extraocular examination showed 30 prism diopters left esotropia at primary gaze and −4 abduction limitation of left eye. The left eye showed mild optic disc swelling and inferior field defect by field test. Brain magnetic resonance imaging showed enhancement of sphenoidal sinus, ethmoidal sinus, and around optic nerve at left eye. Three days after antibiotics treatment, the vision of left eye deteriorated to 20/40 and periorbital pain developed. The drainage and biopsy of sphenoidal sinus were performed. The histopathologic examination showed hyphae consistent with aspergillosis. The ocular symptoms were improved with anti-fungal treatment. Follow-up magnetic resonance imaging performed 1 month after treatment showed improvement of lesion at left orbit. Five months after surgery, the visual acuity of left eye was improved to 20/25. The patient showed orthotropia at primary gaze without limitation. CONCLUSIONS: The abducens nerve palsy and optic perineuritis can be caused by fungal sphenoidal sinusitis. The early diagnosis and appropriate treatment can lead to favorable outcome.

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.

CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway

The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular carcinogenesis mechanism was consolidated by the identification of the serrated neoplasia pathway, in which CIMP participates in the initiation and progression of serrated adenomas. Distinct clinicopathological and molecular features of CIMP-high (CIMP-H) CRCs have been characterized, including proximal colon location, older age of onset, female preponderance, and frequent associations of high-level microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or traditional serrated adenomas and thus tend to display the morphological characteristics of serrated adenomas, including epithelial serration, vesicular nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor prognosis and different responses of CRCs to adjuvant therapy depending on CIMP status indicate clinical implications. In this review, we present an overview of the literature documenting the relevant findings of CIMP-H CRCs and their relationships with the serrated neoplasia pathway.

Clinicopathological Significance of Elevated PIK3CA Expression in Gastric Cancer

PURPOSE: PIK3CA is often mutated in a variety of malignancies, including colon, gastric, ovary, breast, and brain tumors. We investigated PIK3CA expression in gastric cancer and explored the relationships between the PIK3CA expression level and clinicopathological features as well as survival of the patients. MATERIALS AND METHODS: We examined PIK3CA expression in a tissue microarray of 178 gastric adenocarcinomas by immunohisto-chemistry and reviewed patients' medical records. RESULTS: In our study, 112 of the 178 gastric cancer patients displayed positive PIK3CA expression. Overexpression of PIK3CA was correlated with low grade differentiation (P=0.001), frequent lymphatic invasion (P=0.032), and high T stage (P=0.040). Patients with positive PIK3CA staining were more likely to display worse overall survival rate than those with negative PIK3CA staining, as determined by Kaplan-Meier survival analysis with log-rank test (P=0.047) and a univariate analysis using the Cox proportional hazard model (hazard ratio=1.832, P=0.051). CONCLUSIONS: Elevated PIK3CA expression was significantly correlated with tumor invasiveness, tumor phenotypes, and poor patient survival.

CD9 Expression in Colorectal Carcinomas and Its Prognostic Significance

BACKGROUND: CD9, a member of the tetraspanin superfamily, is a tumor suppressor in many malignancies. The aim of this study was to evaluate the immunohistochemical expression of CD9 in colorectal carcinomas (CRCs) and determine clinicopathological and prognostic significance of its expression. METHODS: The CD9 expression status of 305 CRCs was evaluated using a semi-quantitative scoring system in tumor cells (T-CD9) and immune cells (I-CD9) by classifying the results as high and low expression. RESULTS: High T-CD9 (T-CD9 [+]) expression was detected in 175 samples (57.6%) and high I-CD9 (I-CD9 [+]) expression was detected in 265 samples (86.9%). Using Kaplan-Meier survival analysis, the T-CD9 (+) group showed a tendency for better disease-free survival (DFS) (p = .057). In left-sided tumors, DFS was significantly longer in the T-CD9 (+) group (p = .021) but no statistical significance was observed with right-sided tumors (p = .453). I-CD9 (+) CRCs significantly correlated with well/moderately differentiation (p = .014). In Kaplan-Meier analysis, the I-CD9 (+) group had a tendency towards worse DFS compared to the I-CD9 (–) group (p = .156). In combined survival analysis of T-CD9 and I-CD9, we found that the longest DFS was among patients in the T-CD9 (+)/I-CD9 (–) group, whereas the T-CD9 (–)/I-CD9 (+) group showed the shortest DFS (p = .054). CONCLUSIONS: High expression of T-CD9 was associated with a favorable DFS, especially in left-sided CRCs. Combined evaluation of T-CD9 and I-CD9 is required to determine the comprehensive prognostic effect of CD9 in CRCs.

Prognostic and Clinicopathological Significance of Transducer-Like Enhancer of Split 1 Expression in Gastric Cancer

PURPOSE: Transducer-like enhancer of split 1 (TLE1) is a member of the Groucho/TLE family of transcriptional co-repressors that regulate the transcriptional activity of numerous genes. TLE1 is involved in the tumorigenesis of various tumors. We investigated the prognostic significance of TLE1 expression and its association with clinicopathological parameters in gastric cancer (GC) patients. MATERIALS AND METHODS: Immunohistochemical analysis of six tissue microarrays was performed to examine TLE1 expression using 291 surgically resected GC specimens from the Soonchunhyang University Cheonan Hospital between July 2006 and December 2009. RESULTS: In the non-neoplastic gastric mucosa, TLE1 expression was negative. In GC, 121 patients (41.6%) were positive for TLE1. The expression of TLE1 was significantly associated with male gender (P=0.021), less frequent lymphatic (P=0.017) or perineural invasion (P=0.029), intestinal type according to the Lauren classification (P=0.024), good histologic grade (P<0.001), early pathologic T-stage (P=0.012), and early American Joint Committee on Cancer stage (P=0.022). In the Kaplan-Meier analysis, the TLE1 expression was significantly associated with longer disease-free (P=0.022) and overall (P=0.001) survival rates. CONCLUSIONS: We suggested that TLE1 expression is a good prognostic indicator in GCs.

High EZH2 Protein Expression Is Associated with Poor Overall Survival in Patients with Luminal A Breast Cancer / 한국유방암학회지

PURPOSE: The enhancer of zeste homologue 2 (EZH2) is a catalytic subunit of the polycomb repressive complex 2, a highly conserved histone methyltransferase. EZH2 overexpression has been implicated in various malignancies, including breast cancer, where is associated with poor outcomes. This study aims to clarify nuclear EZH2 expression levels in breast cancers using immunohistochemistry (IHC) and correlate these findings with clinicopathologic variables, including prognostic significance. METHODS: IHC was performed on tissue microarrays of 432 invasive ductal carcinoma (IDC) tumors. Associations between EZH2 expression, clinicopathologic characteristics, and molecular subtype were retrospectively analyzed. The relationship between EZH2 protein expression in normal breast tissue and ductal carcinoma in situ (DCIS) was also assessed. RESULTS: High EZH2 expression was demonstrated in 215 of 432 tumors (49.8%). EZH2 was more frequently expressed in DCIS and IDC than in normal breast tissue (p=0.001). High EZH2 expression significantly correlated with high histologic grade (p<0.001), large tumor size (p=0.014), advanced pathologic stage (p=0.006), negative estrogen receptor status (p<0.001), positive human epidermal growth factor receptor 2 (HER2) status (p<0.001), high Ki-67 staining index (p<0.001), positive cytokeratin 5/6 status (p=0.003), positive epidermal growth factor receptor status (p<0.001), and positive p53 status (p<0.001). Based on molecular subtypes, high EZH2 expression was significantly associated with HER2-negative luminal B, HER2-positive luminal B, and HER2 type and triple-negative basal cancers (p<0.001). In patients with luminal A, there was a significant trend toward shorter overall survival for those with tumors having high EZH2 expression compared to those with tumors having low EZH2 expression (p=0.045). CONCLUSION: EZH2 is frequently upregulated in breast malignancies, and it may play an important role in cancer development and progression. Furthermore, EZH2 may be a prognostic marker, especially in patients with luminal A cancer.

Loss of ARID1A Expression in Gastric Cancer: Correlation with Mismatch Repair Deficiency and Clinicopathologic Features

PURPOSE: The AT-rich interactive domain 1A (ARID1A) gene encodes BRG1-associated factor 250a, a component of the SWItch/Sucrose NonFermentable chromatin remodeling complex, which is considered a tumor suppressor in many tumors. We aimed to investigate the prognostic significance of ARID1A expression in gastric cancers and explore its relationship with clinicopathologic parameters such as mismatch repair protein expression. MATERIALS AND METHODS: Four tissue microarrays were constructed from 191 resected specimens obtained at Soonchunhyang University Cheonan Hospital from 2006 to 2008. Nuclear expression of ARID1A was semiquantitatively assessed and binarized into retained and lost expression. RESULTS: Loss of ARID1A expression was observed in 62 cases (32.5%). This was associated with more frequent vascular invasion (P=0.019) and location in the upper third of the stomach (P=0.001), and trended toward more poorly differentiated subtypes (P=0.054). ARID1A loss was significantly associated with the mismatch repair-deficient phenotype (P=0.003). ARID1A loss showed a statistically significant correlation with loss of MLH1 (P=0.001) but not MSH2 expression (P=1.000). Kaplan-Meier survival analysis showed no statistically significant difference in overall survival; however, patients with retained ARID1A expression tended to have better overall survival than those with loss of ARID1A expression (P=0.053). In both mismatch repair-deficient and mismatch repair-proficient groups, survival analysis showed no differences related to ARID1A expression status. CONCLUSIONS: Our results demonstrated that loss of ARID1A expression is closely associated with the mismatch repair-deficient phenotype, especially in sporadic microsatellite instability-high gastric cancers.

Loss of Tumor Suppressor ARID1A Protein Expression Correlates with Poor Prognosis in Patients with Primary Breast Cancer / 한국유방암학회지

PURPOSE: Somatic mutations of the chromatin remodeling AT-rich interactive domain 1A (SWI-like) gene (ARID1A) have been identified in many human cancers, including breast cancer. The purpose of this study was to evaluate the nuclear expression of ARID1A in breast cancers by immunohistochemistry (IHC) and to correlate the findings to clinicopathologic variables including prognostic significance. METHODS: IHC was performed on tissue microarrays of 476 cases of breast cancer. Associations between ARID1A expression and clinicopathologic characteristics and molecular subtype were retrospectively analyzed. RESULTS: Low expression of ARID1A was found in 339 of 476 (71.2%) cases. Low expression of ARID1A significantly correlated with positive lymph node metastasis (p=0.027), advanced pathologic stage (p=0.001), low Ki-67 labeling index (p=0.003), and negative p53 expression (p=0.017). The ARID1A low expression group had significantly shorter disease-free and overall survival than the ARID1A high expression group (p<0.001 and p<0.001, respectively). Multivariate analysis demonstrated that low expression of ARID1A was a significant independent predictive factor for poor disease-free and overall survival in patients with breast cancer (disease-free survival: hazard ratio, 0.38, 95% confidence interval [CI], 0.20-0.73, p=0.004; overall survival: hazard ratio, 0.11, 95% CI, 0.03-0.46, p=0.003). In patients with luminal A type disease, patients with low ARID1A expression had significantly shorter disease-free and overall survival rates than patients with high ARID1A expression (p=0.022 and p=0.018, respectively). CONCLUSION: Low expression of ARID1A is an independent prognostic factor for disease-free and overall survival in breast cancer patients and may be associated with luminal A type disease. Although the biologic function of ARID1A in breast cancer remains unknown, low expression of ARID1A can provide valuable prognostic information.

Mediastinal Glomus Tumor: A Case Report and Literature Review

A glomus tumor in the mediastinum is very uncommon, and only five cases have been reported in the English literature. We recently encountered a 21-year-old woman with an asymptomatic mediastinal mass that measured 5.3 x 4.0 cm. Surgical excision was performed, and the tumor was finally diagnosed as mediastinal glomus tumor with an uncertain malignant potential. After reviewing this case and previous reports, we analyzed the clinicopathologic features associated with progression of such a tumor.

Intracranial Extracerebral Glioneuronal Heterotopia with Adipose Tissue and a Glioependymal Cyst: A Case Report and Review of the Literature

No abstract available.

Differential Features of Microsatellite-Unstable Colorectal Carcinomas Depending on EPCAM Expression Status

BACKGROUND: Recent studies have revealed that a small subset of Lynch syndrome-associated colorectal carcinomas (CRCs) is caused by a germline EPCAM deletion-induced MSH2 epimutation. Based on the finding of this genetic alteration, we investigated the implications of EPCAM expression changes in microsatellite instability-high (MSI-H) CRCs. METHODS: Expression of EPCAM and DNA mismatch repair proteins was assessed by immunohistochemistry in 168 MSI-H CRCs. Using DNA samples of these tumors, MLH1 promoter methylation status was also determined by methylation-specific real-time polymerase chain reaction method (MethyLight). RESULTS: Among 168 MSI-H CRCs, complete loss (CL) and focal loss (FL) of EPCAM expression was observed in two (1.2%) and 22 (13.1%) cases, respectively. Both of the EPCAM-CL cases were found in MSH2-negative tumors without MLH1 promoter methylation. However, only nine of the 22 EPCAM-FL tumors had MSH2 deficiency. Of the 22 EPCAM-FL tumors, 13 showed MLH1 loss, and among them, nine cases were determined to have MLH1 methylation. EPCAM-FL was significantly associated with advanced stage (p=.043), distant metastasis (p=.003), poor differentiation (p=.001), and signet ring cell component (p=.004). CONCLUSIONS: Loss of EPCAM expression is differentially associated with clinicopathological and molecular features, depending on the completeness of the loss, in MSI-H CRCs.

Immunohistochemical Classification of Primary and Secondary Glioblastomas

BACKGROUND: Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification. METHODS: We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases. RESULTS: According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/p53(-), IDH-1(-)/EGFR(+)/p53(-), and EGFR(-)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(-)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(-)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(-) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(-) was best for identifying S-GBLs. CONCLUSIONS: We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.

Outcome of Glioblastoma Patients Treated with Surgery and Radiation Therapy / 대한방사선종양학회지

PURPOSE: To analyze the survival outcomes and prognostic factors in glioblastoma patients treated with surgery and radiation therapy. MATERIALS AND MEHTODS: One hundred twenty glioblastoma patients treated with postoperative radiation therapy from 1994 to 2003 at Samsung Medical Center were retrospectively reviewed. Surgical extents were gross total resection in 22 patients (18%), subtotal resection in 69 (58%), and biopsy only in 29 (24%). The median radiation dose was 60 Gy, ranging from 45 Gy to 72 Gy. The median follow-up period was 12 months ranging from 2 to 62 months. RESULTS: The overall 1- and 2-year survival rates were 52% and 14%, respectively, and the median survival duration was 13 months. Favorable prognostic factors by Uunivariate analyses of prognostic factors on 1-year survival rate wererevealed that age under 50 (p<0.01), ECOG performance status 0 or 1 (p=0.03), single lesion (p=0.02), and gross total resection (p=0.04), were the favorable prognostic factors. and by Mmultivariate analyses wererevealed that female (p<0.01), age under 50 (p<0.01), ECOG performance status 0 or 1 (p=0.05) and gross total resection (p=0.05) were the favorable prognostic factors. CONCLUSIONS: The results of our study were comparable with those previously reported. To improve treatment outcome, various modifications, including radiation dose escalation through newer radiation therapy techniques and use of effective chemotherapy regimen, should be further investigated. investigated. Also Furthermore, the application of individualized treatment strategy based on the patient's' prognostic factors might be needed.

Preliminary Results of Stereotactic Body Frame Based Fractionated Radiosurgery on Consecutive Days for Primary Lung Cancer or Metastatic Lung Tumors

To evaluate the feasibility and treatment outcomes of stereotactic radiosurgery (SRS) using a stereotactic body frame (Precision TherapyTM), we prospectively reviewed 34 tumors of the 28 patients with primary or metastatic intrathoracic lung tumors. Eligible patients included were 9 with primary lung cancer and 19 with metastatic tumors from the lung, liver and many other organs. A single dose of 10 Gy to the clinical target volume (CTV) was delivered to a total dose of 30~40 Gy with 3~4 fractions. Four to 8 coplanar or non-coplanar static fields were generated to adequately cover the planning target volume (PTV) as well as to exclude the critical structures as much as possible. More than 90% of the PTV was delivered the prescribed dose in the majority of cases (average; 96%, range; 74%~100%). The mean PTV was 41.4 cc ranging from 4.4 to 230 cc. Set-up error was within 5 mm in all directions (X, Y, Z axis). The response was evaluated by using a chest CT and or 18FDG-PET scans after SRS treatment, 11 patients (39%) showed complete response, 12 (43%) partial response (decrease of more than 50% of the tumor volume), and 4 patients showed minimally decreased tumor volume or stable disease, but 1 patient showed progressive disease. With a median follow-up period of 18 months, a median local disease progression free interval was 18 months ranging from 7 to 35 months. Although all patients developed grade 1 radiation pneumonitis within 3 months, none had symptomatic or serious late complications after completing SRS treatment. Given these observations, it is concluded that the stereotactic body frame based SRS is a safe and effective treatment modality for the local management of primary or metastatic lung tumors. However, the optimum total dose and fractionation schedule used should be determined after the longer follow-up of these results.