Publications by authors named "So Dug Lim"

67 Publications

Fatty acid synthetase expression in triple-negative breast cancer.

J Pathol Transl Med 2022 Mar 21;56(2):73-80. Epub 2022 Jan 21.

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Background: Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism-related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC.

Methods: Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0-1+ FASN staining were grouped as low-grade FASN and patients with 2-3+ FASN staining as high-grade FASN.

Results: FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups.

Conclusions: We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.
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http://dx.doi.org/10.4132/jptm.2021.10.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935000PMC
March 2022

Emerging glioneuronal and neuronal tumors: case-based review.

Brain Tumor Pathol 2022 Apr 20;39(2):65-78. Epub 2022 Jan 20.

Department of Pathology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.

Glioneuronal and neuronal tumors (GNTs) are rare heterogeneous central nervous system tumors characterized by slow growth and favorable outcomes, but are often associated with diagnostic difficulties. A thorough analysis of three rare and recently recognized GNTs was performed in the context of clinicopathological features and molecular genetic characterization. The current spinal diffuse leptomeningeal glioneuronal tumor (DLGNT) was characterized with oligodendroglioma-like tumor with chromosome 1p/19q codeletion without IDH mutations and KIAA1549:BRAF fusion. The current occipital multinodular and vacuolating neuronal tumor (MVNT) was characteristic of the variable-sized vague nodules consisted of gangliocytic tumor cells with intracytoplasmic and pericellular vacuolation and the next-generation sequencing (NGS) revealed MAP2K1 p.Q56_V60del. A diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) of the amygdala was characterized by oligodendroglia-like cells and nuclear clusters, and monosomy 14. From the current cases and literature review, we found that DLGNT commonly occurs in the spinal cord and can make mass and more commonly have KIAA1549:BRAF fusion; MVNT is a neoplasm rather than malformation and MAP2K1 deletion is one of the hallmarks of this tumor; although DGONC may require a methylation profile, we can reach a diagnosis through its unique histology, monosomy 14, and exclusion diagnosis without a methylation profile.
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http://dx.doi.org/10.1007/s10014-021-00420-3DOI Listing
April 2022

Concordance of Programmed Death-Ligand 1 Expression between SP142 and 22C3/SP263 Assays in Triple-Negative Breast Cancer.

J Breast Cancer 2020 Jun 1;23(3):303-313. Epub 2020 Jun 1.

Department of Pathology, Konkuk University School of Medicine, Seoul, Korea.

Purpose: Triple-negative breast cancer (TNBC) represents a major clinical challenge due to its aggressive and metastatic behavior and the lack of available targeted therapies. Therefore, therapeutic strategies are needed to improve TNBC patient management. Recently, atezolizumab and nab-paclitaxel chemotherapy has been approved by the Food and Drug Administration for the first-line treatment of patients with locally advanced and metastatic TNBC. The programmed death-ligand 1 (PD-L1) immunohistochemical SP142 assay was also approved as a companion diagnostic device for selecting TNBC patients for atezolizumab treatment. This study aimed to evaluate and compare the analytical performance of the PD-L1 22C3/SP263 assays in comparison with the SP142 assay for ≥ 1% immune cells (ICs).

Methods: Immunohistochemical expression for the PD-L1 22C3/SP263 assays, in comparison with the SP142 assay, was analyzed for the ≥ 1% ICs in 95 TNBCs.

Results: At the 1% cut-off value, the proportions of positive cases were 52.6% for the SP142 assay in infiltrating ICs and 50.5% and 52.6% for the 22C3 and SP263 assays in tumor cells, respectively. The PD-L1 SP263 assay had the highest while the PD-L1 22C3 assay had the lowest total positive expression rate at all cut-off values. The concordance rate between the assays was highest at a 1% cut-off value and decreased when the cut-off value increased. The concordance rate between the SP142 and SP263 assays at 1% cut-off was high, while in comparison, the concordance rate between the SP142 and 22C3 assays at 1% cut-off was relatively lower.

Conclusion: This study demonstrates that although the 22C3 assay at a 1% cut-off value compared with the PD-L1 SP142 assay at the clinically relevant cut-off shows comparable but not interchangeable analytical performance, the analytical performance of the SP263 assay at a 1% cut-off value shows interchangeable performance with the PD-L1 SP142 assay at the clinically relevant cut-off.
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http://dx.doi.org/10.4048/jbc.2020.23.e37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311361PMC
June 2020

Unusual clinicopathological presentation of nontraumatic cerebral fat embolism: Two-case report.

Medicine (Baltimore) 2020 Mar;99(12):e19574

Department of Pathology, Konkuk University School of Medicine, Seoul, Republic of Korea.

Rationale: Fat embolism syndrome (FES) is characterized by the classical triad of cerebral, respiratory, and cutaneous manifestations. In contrast, cerebral fat embolism (CFE), corresponding to incomplete pure type FES, is much rarer and usually follows trauma. CFE typically shows a "starfield" pattern on diffusion-weighted magnetic resonance imaging due to the involvement of multiple small arteries. We report 2 unusual cases of CFE that showed a nontraumatic etiology and the involvement of a single dominant cerebral artery.

Patient Concerns: Case 1 was a 33-year-old woman without a history of trauma who visited the emergency room due to hemiparesis and hemisensory deficits. She was a heavy smoker and had used oral contraceptives for several years. Most importantly, she had 2 experiences of autologous fat grafting 2 months previously. Magnetic resonance angiography (MRA) revealed acute occlusion of the right middle cerebral artery. Case 2 was an 80-year-old man suddenly presented with dizziness, ataxia, and left-sided sensorimotor dysfunction. He had a history of hypertension, untreated atrial fibrillation, and chronic alcoholism. MRA demonstrated the occlusion of the distal basilar artery.

Diagnosis: Case 1: Microscopic findings demonstrated variable sized fat vacuoles intermixed with moderate amounts of thrombi. Case 2: Histologically, mature adipocytes were intermingled with fibrin, blood cells, and a fragment of entrapped soft tissue resembling the vessel wall.

Intervention: Case 1 and 2 underwent aspirational thrombectomy guided by transfemoral cerebral angiography.

Outcome: Case 1 recovered well but Case 2 still suffers from gait ataxia.

Lessons: CFE can rarely occur in various nontraumatic conditions, with or without evident etiology. Furthermore, it may not show characteristic clinicopathological manifestations. Therefore, careful follow up of those who have undergone procedures that are likely to trigger FES or who have hemodynamic or hypercoagulable risk factors is needed.
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http://dx.doi.org/10.1097/MD.0000000000019574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220548PMC
March 2020

Genomic Landscape of Young-Onset Bladder Cancer and Its Prognostic Implications on Adult Bladder Cancer.

Cancers (Basel) 2020 Jan 28;12(2). Epub 2020 Jan 28.

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Due to the rare occurrence of young-onset bladder cancer (YBC), its genomic characteristics remain largely unknown. Twenty-nine biopsy-proven YBC cases were collected using a nation-wide search for bladder cancer diagnosed at 20 years or younger. Whole exome sequencing and RNA sequencing were carried out in 21 and 11 cases, respectively, and compared with those of adult bladder cancer (ABC) cases obtained from public databases. Almost all YBCs were low grade, non-invasive papillary tumors. YBC had a low mutation burden and less complex copy number alterations. All cases harbored putative driver mutations. Mutations were most commonly found in HRAS (10 cases), with a preference for exon 5. FGFR3 gene fusions were noted with various partner genes (7 cases). The alterations on HRAS and FGFR3 occurred in a mutually exclusive manner. Others included KRAS mutations (2 cases), chromosomes 4p and 10q arm-level deletions (1 case), and ERCC2 mutation (1 case). There were no point mutations in TP53 and FGFR3. The gene expression profiles of YBC were similar to those of the ABC group with good prognosis. None of the YBCs and ABCs with YBC-like mutations showed progression to muscle-invasive tumors. Our results suggest that bladder cancer with YBC-like mutations represents an indolent bladder tumor, regardless of age.
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http://dx.doi.org/10.3390/cancers12020307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073191PMC
January 2020

mRNA expressions of androgen receptor and its variants in matched hormone-sensitive and castration-resistant prostate cancer.

Scand J Urol 2019 Dec 6;53(6):365-371. Epub 2019 Dec 6.

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Androgen receptor splice variants (AR-Vs), especially androgen receptor splice variant 7 (AR-V7), are considered as important factors in developing castration-resistance of prostate cancer and also as candidate predictive factors. Our aim was to evaluate changes in the mRNA expression of full-length AR (AR-FL) and AR-Vs in the primary prostate cancers from the same patients before and after ADT. We compared morphologic differences and evaluated AR-FL, AR-V7, AR-V4, ARv567es, AR-V3 and AR8 mRNA expression in matched samples of primary hormone-sensitive and castration-resistant prostate cancer (CRPC) from 19 patients. mRNA expression of AR-FL, AR-V7, ARv567es and AR-V3 was present in hormone sensitive prostate cancer (HSPC) and was significantly increased in CRPC in 81.2% (13/16). There were strong positive correlations between AR-FL and AR-V7 ( = 0.93,  < .001), ARv567es ( = 0.72,  < .001) and AR-V3 ( = 0.81,  < .001) mRNA expression. AR-V7/AR-FL ratio was more significantly (>30%) increased after ADT in 25% (4/16) of the patients, who showed significantly ( < .001) worse overall survival. Neuroendocrine differentiation was seen in one patient (5.3%) and the Gleason score was increased in 10 (52.6%) patients. We demonstrated that the expression of AR-V7 is present at low levels in HSPC and is increased in CRPC and the increase is an active process possibly related to aggressive clinical course.
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http://dx.doi.org/10.1080/21681805.2019.1697359DOI Listing
December 2019

Gliadin intake induces oxidative-stress responses in Caenorhabditis elegans.

Biochem Biophys Res Commun 2018 09 7;503(3):2139-2145. Epub 2018 Aug 7.

Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea. Electronic address:

Clinical attention to gluten-related disorders, such as celiac disease and nonceliac gluten sensitivity, is on the rise. However, identifying the pathophysiological mechanisms of gluten-related disorders remains elusive. Gliadin, a component of gluten, is known to play a major role in gluten toxicity. Caenorhabditis elegans has been widely used as the predominant experimental animal model to study toxicity and stress response in biomedical research. We investigated the stress response induced by gliadin intake in C. elegans to evaluate its toxicity and found brood size, body bending, and pumping rates to be significantly altered in response to gliadin. Notably, reactive oxygen species (ROS) production and Pgst-4::GFP transgene expression, an indicator of the oxidative-stress response, were significantly increased after gliadin intake. Reduced pumping rates were most likely caused by gliadin-induced oxidative stress, since pumping rates in oxidative stress-sensitive mev-1 mutants were more severely reduced than in oxidative stress-resistant daf-2 mutants following gliadin intake. Our results indicated that gluten/gliadin intake in C. elegans triggered ROS production and induced an oxidative stress response that reduced pumping rates and decreased brood size. We suggest C. elegans to be a useful model system for studying gluten/gliadin toxicity.
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http://dx.doi.org/10.1016/j.bbrc.2018.08.002DOI Listing
September 2018

Mammographic and ultrasound findings in poroid hidradenoma of the breast mimicking intraductal papilloma and papillary carcinoma: A case report.

Medicine (Baltimore) 2018 Jun;97(25):e11154

Department of Radiology, Konkuk University School of Medicine, Seoul Department of Radiology, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon Department of Pathology, Konkuk University School of Medicine Department of Surgery, Konkuk University School of Medicine, Seoul, Korea.

Rationale: Poroid hidradenoma (PH) is a rare variant of benign sweat gland neoplasm without connection to the epidermis. This tumor presents clinically as a solitary lesion with a cystic component located in the subcutaneous layer abutting the skin. On ultrasound, it appears as a circumscribed complex cystic and solid mass abutting the dermis. The occurrence of PH in the breast is very rare. Its features overlap with intraductal papilloma and papillary carcinoma.

Patient Concerns: A 66-year-old woman presented with a palpable lump in her right breast.

Diagnoses: Clinical examination revealed dark bluish dome-shaped nodule which presented as circumscribed round isodense mass on mammography and oval complex cystic and solid mass abutting the dermis on ultrasound. Clinically, a papillary neoplasm was suspected.

Interventions: The patient underwent En bloc surgical excision including the overlying epidermis and the surrounding adipose tissue to prevent recurrence.

Outcomes: A well-demarcated, non-encapsulated grayish white mass composed of a partly solid and partly cystic area was completely removed and histopathologically confirmed as PH. At the 12-month follow-up, no recurrence was evident.

Lessons: PH should be considered in the differential diagnosis of a slowly growing breast mass that is bluish, cystic, and solid and abuts the dermis.
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http://dx.doi.org/10.1097/MD.0000000000011154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023949PMC
June 2018

Multiparametric MR imaging of peripheral zone prostate cancer: effect of postbiopsy hemorrhage on cancer detection according to Gleason score and tumour volume.

Br J Radiol 2018 Jun 9;91(1086):20180001. Epub 2018 Mar 9.

2 Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine , Seoul , Korea.

Objective: To evaluate effect of postbiopsy hemorrhage on detection of peripheral zone (PZ) prostate cancer by multiparametric MR imaging according to Gleason score and tumor volume.

Methods: This retrospective study included 54 biopsy-proven prostate cancer patients (median age, 67.0 years) who underwent multiparametric MR imaging. Two independent readers evaluated each sextant of the PZ using the PI-RADS v2. One reader recorded the presence or absence of hemorrhage per sextant on T weighted MR images. Areas under the receiver operating characteristic curves (AUCs) were used to evaluate cancer detection accuracy.

Results: Postbiopsy hemorrhage was noted in 122 (37.7%) of 324 sextants of all patients. There was no significant difference in the AUC for detection of cancer with Gleason score ≥3 + 4 or volume ≥0.5 ml between sextants with and without hemorrhage (with hemorrhage, reader 1, 0.83 for Gleason score ≥3 + 4, 0.84 for tumor volume ≥0.5 ml; reader 2, 0.74 for Gleason score ≥3 + 4, 0.77 for tumor volume ≥0.5 ml; without hemorrhage, reader 1, 0.86 for Gleason score ≥3 + 4, 0.88 for tumor volume ≥0.5 ml; reader 2, 0.79 for Gleason score ≥3 + 4, 0.83 for tumor volume ≥0.5 ml; p > 0.2 for all).

Conclusion: Postbiopsy hemorrhage did not negatively affect the detection of clinically significant PZ prostate cancer on multiparametric MR imaging. Advances in knowledge: Under influence of postbiopsy hemorrhage, multiparametric MR can be useful for the detection of clinically significant PZ prostate cancer.
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http://dx.doi.org/10.1259/bjr.20180001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223297PMC
June 2018

Ganglioneuroma of the Sacrum.

Korean J Spine 2017 Sep 30;14(3):106-108. Epub 2017 Sep 30.

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Presacral ganglioneuromas are extremely rare benign tumors and fewer than 20 cases have been reported in the literature. Ganglioneuromas are difficult to be differentiated preoperatively from tumors such as schwannomas, meningiomas, and neurofibromas with imaging modalities. The retroperitoneal approach for resection of presacral ganglioneuroma was performed for gross total resection of the tumor. Recurrence and malignant transformation of these tumors is rare. Adjuvant chemotherapy or radiation therapy is not indicated because of their benign nature. We report a case of a 47-year-old woman with a presacral ganglioneuroma.
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http://dx.doi.org/10.14245/kjs.2017.14.3.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642092PMC
September 2017

Level of mitoses in non-muscle invasive papillary urothelial carcinomas (pTa and pT1) at initial bladder biopsy is a simple and powerful predictor of clinical outcome: a multi-center study in South Korea.

Diagn Pathol 2017 Jul 24;12(1):54. Epub 2017 Jul 24.

Department of Pathology, Inje University Sanggye Paik Hospital, 1342, Dongilro, Nowon-gu, Seoul, South Korea.

Background: Histologic grade is the most important predictor of the clinical outcome of non-muscle invasive (Ta, T1) papillary urothelial carcinoma (NMIPUCa), but its ambiguous criteria diminish its power to predict recurrence/progression for individual patients. We attempted to find an objective and reproducible histologic predictor of NMIPUCa that correlates well with the clinical outcome.

Methods: A total of 296 PUCas were collected from the Departments of Surgical Pathology of 11 institutions in South Korea. The clinical outcome was grouped into no event (NE), recurrence (R), and progression (P) categories. All 25 histological parameters were numerically redefined. The clinical pathology of each case was reviewed individually by 11 pathologists from 11 institutions based on the 2004 WHO criteria and afterwards blindly evaluated by two participants, based on our proposed parameters. Univariate and multivariate logistic regression analyses were performed using the R software package.

Results: The level of mitoses was the most reliable parameter for predicting the clinical outcome. We propose a four-tiered grading system based on mitotic count (> 10/10 high-power fields), nuclear pleomorphism (smallest-to-largest ratio of tumor nuclei >20), presence of divergent histology, and capillary proliferation (> 20 capillary lumina per papillary core).

Conclusions: The level of mitoses at the initial bladder biopsy and transurethral resection (TUR) specimen appeared to be an independent predictor of the Ta PUCa outcome. Other parameters include the number of mitoses, nuclear pleomorphism, divergent histology, and capillary proliferation within the fibrovascular core. These findings may improve selection of patients for a therapeutic strategy as compared to previous grading systems.
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http://dx.doi.org/10.1186/s13000-017-0639-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525253PMC
July 2017

Molecular Profiling of Papillary Thyroid Carcinoma in Korea with a High Prevalence of BRAF Mutation.

Thyroid 2017 06 21;27(6):802-810. Epub 2017 Apr 21.

4 Department of Internal Medicine, Konkuk University School of Medicine , Seoul, Korea.

Background: The BRAF mutation in papillary thyroid carcinoma (PTC) is particularly prevalent in Korea, and a considerable number of wild-type BRAF PTCs harbor RAS mutations. In addition, subsets of other genetic alterations clearly exist, but their prevalence in the Korean population has not been well studied. Recent increased insight into noninvasive encapsulated follicular variant PTC has prompted endocrine pathologists to reclassify this entity as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). This study analyzed the genetic alterations among the histologic variants of PTC, including NIFTP.

Methods: Mutations of the BRAF and RAS genes and rearrangement of the RET/PTC1, NTRK1, and ALK genes using 769 preoperative fine-needle aspiration specimens and resected PTCs were analyzed.

Results: Molecular alterations were found in 687 (89.3%) of 769 PTCs. BRAF mutation (80.8%) was the most frequent alteration, followed by RAS mutation and RET/PTC1, NTRK1, and ALK rearrangements (5.6%, 2.1%, 0.4%, and 0%, respectively). The low prevalence of NTRK1 fusions and the absence of an ALK fusion detected in Korea may also be attributed to the higher prevalence of the BRAF mutation. There were significant differences in the frequency of the genetic alterations among the histologic variants of PTC. The prevalence of NIFTP in PTC was 2.7%, and among the NIFTPs, 28.6% and 57.1% harbored BRAF and RAS mutations, respectively. Clinicopathologic factors and mutational profiles between NIFTP and encapsulated follicular variant PTC with capsular invasion group were not significantly different.

Conclusions: Genetic alterations in PTC vary among its different histologic variants and seem to be different in each ethnic group.
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http://dx.doi.org/10.1089/thy.2016.0547DOI Listing
June 2017

BRAF-Mutated Colorectal Cancer Exhibits Distinct Clinicopathological Features from Wild-Type BRAF-Expressing Cancer Independent of the Microsatellite Instability Status.

J Korean Med Sci 2017 Jan;32(1):38-46

Department of Pathology, Konkuk University School of Medicine, Seoul, Korea.

In patients with colorectal cancer (CRC), the BRAF V600E mutation has been reported to be associated with several clinicopathological features and poor survival. However, the prognostic implications of BRAF V600E mutation and the associated clinicopathological characteristics in CRCs remain controversial. Therefore, we reviewed various clinicopathological features, including BRAF status, in 349 primary CRCs and analyzed the relationship between BRAF status and various clinicopathological factors, including overall survival. Similar to previous studies conducted in Eastern countries, the incidence of the BRAF V600E mutation in the current study was relatively low (5.7%). BRAF-mutated CRC exhibits distinct clinicopathological features from wild-type BRAF-expressing cancer independent of the microsatellite instability (MSI) status. This mutation was significantly associated with a proximal tumor location (P = 0.002); mucinous, signet ring cell, and serrated tumor components (P < 0.001, P = 0.003, and P = 0.008, respectively); lymphovascular invasion (P = 0.004); a peritumoral lymphoid reaction (P = 0.009); tumor budding (P = 0.046); and peritoneal seeding (P = 0.012). In conclusion, the incidence of the BRAF V600E mutation was relatively low in this study. BRAF-mutated CRCs exhibited some clinicopathological features which were also frequently observed in MSI-H CRCs, such as a proximal location; mucinous, signet ring cell, and serrated components; and marked peritumoral lymphoid reactions.
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http://dx.doi.org/10.3346/jkms.2017.32.1.38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5143296PMC
January 2017

Metastatic Intracranial Hemangiopericytoma to the Spinal Column: A Case Report.

Brain Tumor Res Treat 2016 Oct 31;4(2):128-132. Epub 2016 Oct 31.

Department of Pathology, Konkuk University Medical Center, Seoul, Korea.

Intracranial hemangiopericytoma (HPC) is a rare brain tumor with aggressive biologic behavior associated with high recurrence rate and often with extracranial metastasis. The most common sites of extracranial metastasis of the intracranial HPC are the long bones, lung, liver and abdominal cavity in the order of frequencies. Extracranial metastases usually occur long after the initial diagnosis of the primary tumor. Metastatic intracranial HPC to the vertebra has been rarely reported. We present a case of intracranial HPC metastasized to the L2 vertebral body 13 years after multiple surgical resections and radiotherapy of the primary intracranial HPC.
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http://dx.doi.org/10.14791/btrt.2016.4.2.128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114184PMC
October 2016

Palliative Resection of Metastatic Brain Tumors Previously Treated by Stereotactic Radiosurgery.

Brain Tumor Res Treat 2016 Oct 31;4(2):116-123. Epub 2016 Oct 31.

Department of Pathology, Konkuk University Medical Center, Seoul, Korea.

Background: Therapeutic approaches to brain metastases include surgery, whole-brain radiotherapy, stereotactic radiosurgery (SRS), and combination therapy. Recently, postoperative or preoperative SRS draws more attention to reduce postoperative recurrence in brain metastases. The goal of this study is to review surgical outcome of patients who had been treated by SRS, and to discuss the effectiveness of preoperative SRS.

Methods: From 2009 to 2015, 174 patients were treated by SRS for brain metastases, and among these 50 patients underwent surgery. Eighteen patients underwent surgery after SRS, and 14 had oligometastases. The patients' median age at the time of surgery was 56 years (range, 34-84 years). The median follow-up duration was 16.5 months (range, 4-47 months). Pathological findings were classified as follows; radiation necrosis (Group I, n=3), mixed type (Group II, n=2), and tumor-dominant group (Group III, n=9). We compared surgical outcome in respect of steroid, mannitol dosage, Karnofsky performance scale, and pathological subgroups.

Results: The median overall survival was 11 months (range, 2-40 months). Six, 12 and 24 months survival rate was 64.3, 42.9, and 28.6%, respectively. Improvement of Karnofsky performance score was achieved in 50% after surgery. The overall survival of Group I (26.6 months) was longer than the other groups (11.5 months). Additionally the patients were able to be weaned from medications, such as steroid administration after surgery was reduced in 10 cases, and mannitol dosage was reduced in 6 cases. Time interval within 3 months between SRS and surgery seemed to be related with better local control.

Conclusion: Surgical resection after radiologically and symptomatically progressed brain metastases previously treated with SRS seems to be effective in rapid symptom relief and provides an improvement in the quality of life. A short time interval between SRS and surgical resection seems to be associated with good local tumor control.
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http://dx.doi.org/10.14791/btrt.2016.4.2.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114182PMC
October 2016

Frequent somatic TERT promoter mutations and CTNNB1 mutations in hepatocellular carcinoma.

Oncotarget 2016 Oct;7(43):69267-69275

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Genetic alterations of TERT and CTNNB1 have been documented in hepatocellular carcinoma. TERT promoter mutations are the earliest genetic events in the multistep process of hepatocarcinogenesis related to cirrhosis. However, analyses of TERT promoter and CTNNB1 mutations in hepatocellular carcinoma tumor samples have not been performed in the Korean population, where hepatitis B virus-related hepatocellular carcinoma is prevalent. In order to identify the role of TERT promoter and CTNNB1 mutations in the hepatocarcinogenesis and pathogenesis of recurrent hepatocellular carcinoma, we performed the sequence analyses in 140 hepatocellular nodules (including 107 hepatocellular carcinomas), and 8 pairs of matched primary and relapsed hepatocellular carcinomas. TERT promoter and CTNNB1 mutations were only observed in hepatocellular carcinomas but not in precursor lesions. Of 109 patients with hepatocellular carcinoma, 41 (39.0%) and 15 (14.6%) harbored TERT and CTNNB1 mutations, respectively. TERT promotermutations were significantly more frequent in hepatocellular carcinomas related to hepatitis C virus infection (5/6; 83.3%) compared to tumors of other etiologies (P = 0.001). In two cases, discordance in TERT promoter mutation status was observed between the primary and the corresponding recurrent hepatocellular carcinoma. The two patients with discordant cases had early relapses. In conclusion, we identified TERT promoter and CTNNB1 mutations as the most frequent somatic genetic alterations observed in hepatocellular carcinoma, indicating its pivotal role in hepatocarcinogenesis. Furthermore, we suggest the possibility of intratumoral genetic heterogeneity of TERT promoter mutations in hepatocellular carcinoma as indicated by the discordance in TERT promoter mutations between primary and corresponding recurrent hepatocellular carcinoma.
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http://dx.doi.org/10.18632/oncotarget.12121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342476PMC
October 2016

Effect of low-dose valsartan on proteinuria in normotensive immunoglobulin A nephropathy with minimal proteinuria: a randomized trial.

Korean J Intern Med 2016 Mar 15;31(2):335-43. Epub 2016 Feb 15.

Division of Nephrology, Department of Internal Medicine, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea.

Background/aims: Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day.

Methods: Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy.

Results: Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% ± 26.1% (p < 0.001) in the regular-dose group and -21.1% ± 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period.

Conclusions: Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.
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http://dx.doi.org/10.3904/kjim.2014.266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773712PMC
March 2016

Clinical Significance of Substaging and HER2 Expression in Papillary Nonmuscle Invasive Urothelial Cancers of the Urinary Bladder.

J Korean Med Sci 2015 Aug 15;30(8):1068-77. Epub 2015 Jul 15.

Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Korea.

The study aimed to verify the prognostic utility, therapeutic application and clinical benefits of tumor substaging and HER2 status in papillary non-muscle invasive bladder cancer (NMIBC). Select NMIBC transurethral resection specimens from 141 patients were used to construct tissue microarrays for assessing the substaging, HER2 protein expression by immunohistochemistry (HER2-IHC) and gene amplification by dual-color silver in situ hybridization (HER2-SISH). Substages were identified by the differing depth of tumor invasion (pTa / pT1a / pT1b / pT1c). HER2 protein expression was semiquantitatively analyzed and grouped into negative (score 0, 1+) and positive (score 2+, 3+). Other clinicopathological variables were also investigated. For NMIBC, HER2-IHC and HER2-SISH showed positive results in 6/141 (4.3%) and 4/141 (2.8%) respectively, which correlated well with tumor substaging. In multivariate analysis, substaging, HER2-IHC, and HER2-SISH were found to be independent predictors of progression-free survival (P < 0.001, P < 0.001, P = 0.031). HER2-IHC was the sole independent predictor of recurrent free survival in NMIBC (P = 0.017). It is suggested that tumor substaging and HER2 status are independent predictive markers for tumor progression or recurrence, and thus could be included in diagnostic and therapeutic management for NMIBC.
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http://dx.doi.org/10.3346/jkms.2015.30.8.1068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520937PMC
August 2015

Expression of Peroxisome Proliferator Activated Receptor gamma in Prostatic Adenocarcinoma.

J Korean Med Sci 2015 May 15;30(5):533-41. Epub 2015 Apr 15.

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Peroxisome proliferator-activated receptor gamma (PPAR-γ), a ligand-activated transcription factor has been investigated as the target for cancer treatment as well as metabolic disorders. Recent studies have demonstrated that PPAR-γ ligands are anti-tumorigenic in prostate cancer due to anti-proliferative and pro-differentiation effects. The aim of this study was to validate PPAR-γ expression in malignant and benign prostate tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). A total of 730 prostatic adenocarcinomas (PCAs) including 63 whole sections from radical prostatectomy specimens and tissue microarrays containing 667 PCAs were subject to immunostaining for two PPAR-γ antibodies. Twenty-five benign prostate tissues and PCAs were selected for investigating mRNA expression by quantitative real-time PCR. 10.7% of PCAs (78/730) showed cytoplasmic immunoreactivity of PPAR-γ and no nuclear immunoreactivity was noted in PCAs. Most benign prostatic glands showed negative immunoreactivity of PPAR-γ except for variable weak cytoplasmic staining in some glands. Nuclear immunoreactivity of PPAR-γ was noted some central zone and verumontanum mucosal epithelium. The constitutive PPAR-γ mRNA showed significantly lower level in PCAs compared to that in the benign tissues. There was no difference of PPAR-γ mRNA expression between low (≤7) and high (>7) Gleason score groups. There was no association of PPAR-γ mRNA level or cytoplasmic immunostaining with Gleason grade or pathologic stage. Our study supported the evidence of extra-nuclear localization and nongenomic actions of PPAR-γ. Further studies are needed to assess the functional role of PPAR-γ and to validate its therapeutic implication in prostate cancer.
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http://dx.doi.org/10.3346/jkms.2015.30.5.533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414635PMC
May 2015

Preoperative RAS mutational analysis is of great value in predicting follicular variant of papillary thyroid carcinoma.

Biomed Res Int 2015 12;2015:697068. Epub 2015 Jan 12.

Department of Surgery, Konkuk University School of Medicine, 120 Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.

Follicular variant of papillary thyroid carcinoma (FVPTC), particularly the encapsulated subtype, often causes a diagnostic dilemma. We reconfirmed the molecular profiles in a large number of FVPTCs and investigated the efficacy of the preoperative mutational analysis in indeterminate thyroid nodules. BRAF V600E/K601E and RAS mutational analysis was performed on 187 FVPTCs. Of these, 132 (70.6%) had a point mutation in one of the BRAF V600E (n=57), BRAF K601E (n=11), or RAS (n=64) genes. All mutations were mutually exclusive. The most common RAS mutations were at NRAS codon 61. FNA aspirates from 564 indeterminate nodules were prospectively tested for BRAF and RAS mutation and the surgical outcome was correlated with the mutational status. Fifty-seven and 47 cases were positive for BRAF and RAS mutation, respectively. Twenty-seven RAS-positive patients underwent surgery and all except one patient had FVPTC. The PPV and accuracy of RAS mutational analysis for predicting FVPTC were 96% and 84%, respectively. BRAF or RAS mutations were present in more than two-thirds of FVPTCs and these were mutually exclusive. BRAF mutational analysis followed by N, H, and KRAS codon 61 mutational analysis in indeterminate thyroid nodules would streamline the management of patients with malignancies, mostly FVPTC.
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http://dx.doi.org/10.1155/2015/697068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306358PMC
September 2015

Charcoal-induced granuloma that mimicked a nodal metastasis on ultrasonography and FDG-PET/CT after neck dissection.

Korean J Radiol 2015 Jan-Feb;16(1):196-200. Epub 2015 Jan 9.

Department of Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 143-729, Korea.

Charcoal can be used for preoperative localization of metastatic lymph nodes in the neck. Charcoal remains stable without causing foreign body reactions during as hort period. However, foreign body reactions may develop if charcoal is left in situ for more than 6 months. We reported a case of charcoal granuloma mimicking local recurrence on fluorodeoxyglucose-positron emission tomography/computed tomography and ultrasonography in a 47-year-old woman who had cervical lymph node dissection due to metastatic invasive ductal carcinoma of the breast.
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http://dx.doi.org/10.3348/kjr.2015.16.1.196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296270PMC
June 2015

Ileal mass-like lesion induced by Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in a patient with aplastic anemia.

APMIS 2015 Jan 22;123(1):81-6. Epub 2014 Sep 22.

Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening hyperinflammatory syndrome characterized by activated macrophages engulfing erythrocytes, leukocytes, platelets, and their precursor cells in bone marrow, liver, spleen, or lymph nodes. We report a case of Epstein-Barr virus (EBV)-associated HLH unusually presenting as an ileal mass. A 23-year-old man presented initially with persistent fever unresponsive to antibiotics and pancytopenia. A bone marrow aspiration and biopsy were used to diagnose the patient with aplastic anemia and HLH. A relatively well-defined low-density mass was radiologically noted in the terminal ileum, along with enlarged lymph nodes, and was suspected to be malignant lymphoma or an abscess. The ileocecectomy specimen revealed a transmural hemorrhagic infarction with numerous activated macrophages phagocytosing erythrocytes, plasma cells, and lymphocytes, and he was diagnosed with EBV-associated HLH. The patient received an allo-unrelated peripheral blood stem-cell transplantation and expired due to graft-versus-host disease following liver failure. The present case is very unique, in that EBV-associated HLH presented with an unusual ileal mass resulting from hemorrhagic infarction in a patient with aplastic anemia, suggesting variability in the biological behavior of EBV-associated disease.
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http://dx.doi.org/10.1111/apm.12308DOI Listing
January 2015

Imaging mass spectrometry in papillary thyroid carcinoma for the identification and validation of biomarker proteins.

J Korean Med Sci 2014 Jul 11;29(7):934-40. Epub 2014 Jul 11.

Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul, Korea.

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-µm 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.
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http://dx.doi.org/10.3346/jkms.2014.29.7.934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101781PMC
July 2014

Primary ductal adenocarcinoma of the lacrimal gland, associated with abundant intracytoplasmic lumens containing some eosinophilic hyaline globules: cytological, histological and ultrastructural findings.

Ultrastruct Pathol 2014 Oct 16;38(5):363-6. Epub 2014 Jun 16.

Department of Pathology, Konkuk University School of Medicine , Seoul , Korea.

A primary ductal adenocarcinoma (PDA) of the lacrimal gland is a rare distinct subtype of an epithelial tumor arising in the lacrimal gland. PDA is the counterpart of salivary duct carcinoma (SDC) resembling an invasive ductal carcinoma (IDC) of the breast. In our case, PDA revealed histopathological and immunohistochemical results corresponding to SDC. Interestingly, the tumor cells showed intracytoplasmic vacuoles containing dense eosinophilic hyaline globules at light microscopy. Ultrastructurally, the tumor cells exhibited microvilli-lined intracytoplasmic lumen containing homogenous electron-dense secretory products. A previous study demonstrated that numerous intracytoplasmic lumens of tumor cells are favored breast malignant tumor, similar to the histopathology of PDA, rather than benign lesion. This characteristic finding may be meaningful to diagnose high grade epithelial tumors including PDA.
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http://dx.doi.org/10.3109/01913123.2014.921656DOI Listing
October 2014

Extremely delayed brain metastasis from renal cell carcinoma.

Brain Tumor Res Treat 2013 Oct 31;1(2):99-102. Epub 2013 Oct 31.

Department of Pathology, Konkuk University Medical Center, Seoul, Korea.

Brain metastasis occurs in 3.9-24% of patients with renal cell carcinoma (RCC), with an average interval from nephrectomy to brain metastasis of 1 to 3 years. A few cases have been reported where brain metastasis occurred after a delay of more than 10 years from the initial onset of renal cell carcinoma. This long interval for central nervous system metastasis from the primary cancer has been recognized as an indicator of better prognosis. Histopathological confirmation and aggressive treatment must be considered in these delayed brain metastases cases, since the patients usually show long survival and good prognosis. We present a case of a 76-year-old woman who developed extremely late multiple brain metastases 18 years after a nephrectomy for RCC.
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http://dx.doi.org/10.14791/btrt.2013.1.2.99DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027107PMC
October 2013

Primary intracranial fibrosarcoma presenting with hemorrhage.

Brain Tumor Res Treat 2013 Oct 31;1(2):91-4. Epub 2013 Oct 31.

Department of Pathology, Konkuk University Medical Center, Seoul, Korea.

Primary intracranial fibrosarcomas (PIFs) are extremely rare and the origin of these tumors is still controversial. The rarity of primary intracranial fibrosarcomas makes it difficult to diagnose them correctly and establish a standard treatment. The pathologic diagnosis is made by distinguishing findings from light microscopic and immunohistochemistry analysis. PIFs have been known to be very aggressive neoplasms. The extra-axial location of the tumor could provide an opportunity to perform a total resection even if it does not mean a cure. We present a case of PIFs mimicking a falx meningioma in a 17-year-old man.
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http://dx.doi.org/10.14791/btrt.2013.1.2.91DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027100PMC
October 2013

Neuroendocrine dysplasia combined in a tubular adenoma of rectum: a case report.

Korean J Pathol 2013 Oct 25;47(5):495-8. Epub 2013 Oct 25.

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.4132/KoreanJPathol.2013.47.5.495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831001PMC
October 2013

Rhabdoid colorectal carcinomas: reports of two cases.

Korean J Pathol 2013 Aug 26;47(4):372-7. Epub 2013 Aug 26.

Department of Pathology, Research Center, Aerospace Medical Center, Republic of Korea Air Force, Cheongju, Korea.

Rhabdoid colorectal carcinomas are very rare and only 10 cases have been previously reported. We report two cases of rhabdoid colorectal carcinoma, one arising in the sigmoid colon of a 62-year-old man and another in the rectum of an 83-year-old woman. In both cases, the patients had advanced tumors with lymph node metastases. The tumors mostly showed a diffuse arrangement with rhabdoid features and small glandular regions were combined. Transitional areas from the adenocarcinomas to the rhabdoid tumors were also noted. Adenocarcinoma cells were positive for mixed cytokeratin (CK), CK20 and epithelial membranous antigen (EMA), but focal positive for vimentin. The rhabdoid tumor cells were positive for mixed CK, but focal positive or negative for CK20 and EMA. In addition, they were diffusely positive for vimentin, but negative for desmin. The histological and immunohistologial findings of these two cases suggest that the rhabodid tumor cells originated from dedifferentiated adenocarcinomas.
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http://dx.doi.org/10.4132/KoreanJPathol.2013.47.4.372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759637PMC
August 2013

ERG Immunohistochemistry as an Endothelial Marker for Assessing Lymphovascular Invasion.

Korean J Pathol 2013 Aug 26;47(4):355-64. Epub 2013 Aug 26.

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

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 (κ) 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 (κ=0.27), D2-40 (κ=0.21), ERG (κ=0.23), and was moderate for CD31 (κ=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 (κ=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.
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http://dx.doi.org/10.4132/KoreanJPathol.2013.47.4.355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759635PMC
August 2013

Surgical corner. Evaluation of the wound healing response after deep dermal heating by fractional micro-needle radiofrequency device.

J Drugs Dermatol 2013 Sep;12(9):1044-9

Background: Fractional Radiofrequency Microneedles (FRM) are minimally invasive devices that use inserting bipolar radiofrequency for deep dermal heating, has been introduced. We investigated the tissue response after FRM according to different energy levels in porcine skin.

Methods: Porcine back skin was used in the study. A FRM device was composed of 49 insulated needles. Needles were vertically inserted with 1.5mm depth and four different energy levels were used to examine wound healing response chronologically. Histologic evaluation was done by hematoxylin & eosin (H&E) and heat shock proteins (HSP) 47 staining for immediately after, 2 days after, 14 days after, 28 days after and 10 weeks after the procedure. RT-PCR was done for various cytokines including HSP47, HSP72, metalloproteinase (MMP), and extracellular matrix (ECM) proteins.

Results: FRM treatment generated a thermally coagulated zone localized in the reticular dermis, without damaging the epidermis. The coagulation necrosis zone in H&E staining was replaced by new collagen tissue over 10 weeks. RT-PCR studies revealed an increase in HSP, MMPs, and ECM proteins. In the high energy level procedure, an increased number of fibroblasts were found.

Conclusion: FRM treatment induced a dermal remodeling process including neocollagenesis in the deep dermis. From this result, FRM is expected to provide a good and positive efficacy for skin rejuvenation.
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September 2013
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