Purpose: Epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROSproto-oncogene 1 (ROS1) are ‘must-test’ biomarkers in the molecular diagnostics of advanced-stage lung cancer patients. Although single-gene assays are currently considered thegold standard for these genes, next-generation sequencing (NGS) tests are being introducedto clinical practices. We compared the results of current diagnostics and aimed to suggesttimely effective guidance for their clinical use. Materials and Methods: Patients with lung cancer who received both conventional single-gene assays and subsequenttargeted NGS testing were enrolled, and the results of their tests were compared. Results: A total of 241 patients were enrolled, and the EGFR real-time polymerase chain reaction,ALK fluorescence in situ hybridization (FISH), and ROS1 FISH assays exhibited 92.9%,99.6%, and 99.5% concordance with the NGS tests, respectively. The discordant cases weremostly false-negatives of the single-gene assays, probably due to technical limitation. Of158 cases previously designated as wild-type, EGFR, ALK, and ROS1 alterations were identifiedin 10.1%, 1.9%, and 1.3%, respectively, and other targetable alterations were identifiedin 36.1% of the cases. Of patients with additionally identified actionable alterations, 32.6%(31/95) received matched therapy with a clinical benefit of 48.4% (15/31). Conclusion Even though the conventional and NGS methods were concordant in the majority of cases,NGS testing still revealed a considerable number of additional EGFR, ALK, and ROS1 alterations,as well as other targetable alterations, in Korean advanced-stage lung cancer patients.Given the high frequency of EGFR and other targetable mutations identified in thepresent study, NGS testing is highly recommended in the diagnosis of Korean lung cancerpatients.

Esophageal duplication cysts are congenital anomalies of the foregut that are rarely found in the abdomen. An accurate preoperative diagnosis is not always possible, so the definitive diagnosis can be made by histologic examination of the surgical specimen. We experienced a case of Intra-abdominal esophageal duplication cyst in a 52-year-old female, who initially presented with an esophageal submucosal tumor on upper gastrointestinal endoscopy. She did not have any gastrointestinal symptoms. Barium esophagography, chest computed tomography scan and endoscopic ultrasonography demonstrated the cystic lesion in the intra-abdominal esophagus. Transhiatal enucleation of the lesion was performed successfully via the abdominal approach with no postoperative complications. Histologic study showed that the cyst wall contained a two-layered muscle coat and the surface of the lumen was lined by pseudo-ciliated columnar epithelium. The patient has been doing well without any complaints for 3 months of follow-up period.
Tomography, X-Ray Computed ; Radiography, Abdominal ; Middle Aged ; Humans ; Female ; Esophageal Cyst/*diagnosis/pathology/*surgery ; *Abdomen

PURPOSE: To investigate the etiology, pathologic finding, main symptom, and ideal age for operative correction, trigger thumb in children, without any residual symptom and complications. MATERIALS AND METHODS: 162 children (199 thumbs), who underwent operative treatment, formed the basis of this study. We investigate the main symptom, trauma history, other medical history, age of operation, relief of symptoms and complications after surgery. Two specimens were examined histolgically. RESULTS: Only four (2.5%) thumbs demonstrated triggering at birth. All patients had flexion contracture of the interphalangeal joint of the thumb. There were nodules in 50 thumbs (25.3%) and triggering in 38 thumbs (19.2%). The average age at the time of surgery was forty months. All patients, had complete resolution of triggering after surgery and at the time of follow-up examinations, except for one patient who demonstrated a prominent wound scar. In the histological analysis, proliferation of fibroblasts and dense collagen material without inflammation and degeneration were characteristic findings. CONCLUSION: Trigger thumb in children is a developmental condition caused by A1 pulley hypertrophy. The main symptom was flexion contracture. Therefore the term, developmental flexion contracture of the thumb, "rather than congenital trigger thumb, " is more appropriate. Surgical intervention is inexpensive, simple, safe and successful in preschool-aged children with persistent symptoms.
Child ; Cicatrix ; Collagen ; Contracture* ; Fibroblasts ; Follow-Up Studies ; Humans ; Hypertrophy ; Inflammation ; Joints ; Parturition ; Thumb* ; Trigger Finger Disorder* ; Wounds and Injuries

OBJECTIVE: Large loop excision of transformation zone(LLETZ) is gaining popularity as an alternative to other ablative or cone methods for the treatment of cervical intraepithelial neoplasia(CIN). The optimal management of CIN after LLETZ, however, remains controversial and the reliable predictors of residual disease after LLETZ have not been consistently identified. This study was performed to identify factors to predict residual disease after LLETZ. METHODS: From August 1993 to July 1995, 133 patients who received subsequent hysterectomy after LLETZ in Department of Obstetrics and Gynecology at Seoul National University Hospital were retrospectively reviewed. Residual disease was defined as positive findings of CIN or further advanced findings in hysterectomy specimen. The age of patients, the severity of disease and the status of resection margin(RM) were analyzed for predictive values of residual disease. The Chi-square test, Fisher's exact test and Student t-test were used for statistical analysis. RESULTS: The residual disease after hysterectomy was negative in 85.7%(114/133) and positive in 14.3%(19/133). Among 19 cases with positive residual disease, 3 cases were revealed to be microinvasive cervical cancer. The mean age of patients with no residual disease was 42.5 years(range; 27-71) and that of patients with residual disease was 49.1 years(range; 33-72). Nine out of 94 cases(9.6%) with negative RM and 10 out of 39 cases(25.6%) with positive RM in LLETZ had residual disease. Two out of 14 cases(14.3%) with CIN II and 17 out of 119 cases(14.3%) with CIN III in LLETZ had residual disease. The success of LLETZ which means no residual disease was influenced by the age of patients(p=0.005) and the status of resection margin of LLETZ(p=0.032). CONCLUSION: The negative resection margin in LLETZ does not always guarantee that there is no residual disease. Close preoperative workup and more aggressive treatment plan(wide conization or hysterectomy) should be considered in patients who has higher possibility of positive residual disease such as old age and positive resection margin in LLETZ.
Cervical Intraepithelial Neoplasia* ; Conization ; Gynecology ; Humans ; Hysterectomy ; Obstetrics ; Retrospective Studies ; Seoul ; Uterine Cervical Neoplasms

Mucinous cholangiocarcinoma, characterized by large quantities of mucin production, is a rare subtype of peripheral cholangiocarcinoma and usually shows rapid progression and a fatal outcome. We report here a case of mucinous cholangiocarcinoma in a 69 year-old man, who was infected with Clonorchis sinensis. Histologically, the tumor was an adenocarcinoma with extensive intracellular and extracellular mucin production, up to 70% of the tumor mass and there was frequent lymphovascular invasion of the tumor cells. The liver adjacent to the mass contained eggs of Clonorchis sinensis in the bile duct lumen and showed ductal epithelial hyperplasia, mucinous metaplasia and adenomatous proliferation of intramural glands. The patient was treated with a right hepatectomy. Four months after the surgery, the tumor recurred in the soft tissue of the right flank.
Aged ; Bile Duct Neoplasms/*complications/secretion ; *Bile Ducts, Intrahepatic ; Cholangiocarcinoma/*complications/secretion ; Clonorchiasis/*complications ; English Abstract ; Humans ; Male ; Mucins/secretion

Calcifying fibrous pseudotumors (CFP) are rare soft tissue tumors that have unique histopathologic features characterized by a dense hyalinized collagenous tissue interspersed with benign spindle cells, lymphoplasmacytic infiltrate, and psammomatous or dystrophic calcifications. We report here on a case of calcifying fibrous pseudotumors in the pleura and provide a literature review.
Collagen ; Hyalin ; Pleura ; Pleural Diseases

Background/Aims: Intrahepatic cholangiocarcinoma (iCCA) with a ductal plate malformation (DPM) pattern is a recently recognized rare variant. The genomic profile of iCCA with DPM pattern needs to be elucidated. Methods: Cases of iCCA with DPM pattern were retrospectively reviewed based on the medical records, pathology slides, and magnetic resonance imaging (MRI) reports collected between 2010 to 2019 at a single center. Massive parallel sequencing was performed for >500 cancerrelated genes. Results: From a total of 175 iCCAs, five (2.9%) cases of iCCA with DPM pattern were identified. All cases were of the small duct type, and background liver revealed chronic B viral or alcoholic hepatitis. Three iCCAs with DPM pattern harbored MRI features favoring the diagnosis of hepatocellular carcinoma, whereas nonspecific imaging features were observed in two cases. All patients were alive without recurrence during an average follow-up period of 57 months. Sequencing data revealed 64 mutated genes in the five cases, among which FGFR2 and PTPRT were most frequently mutated (three cases each) including an FGFR2-TNC fusion in one case. Mutations in ARID1A and CDKN2A were found in two cases, and mutations in TP53, BAP1, ATM, NF1, and STK11 were observed in one case each. No IDH1, KRAS, or PBRM1 mutations were found. Conclusions iCCAs with DPM pattern have different clinico-radio-pathologic and genetic characteristics compared to conventional iCCAs. Moreover, FGFR2 and FGFR2 variants were identified. Altogether, these findings further suggest that iCCA with DPM pattern represents a specific subtype of small duct type iCCA.

Background: Next-generation sequencing (NGS) is an approved test to select patients for BRAF V600E targeted therapy in Korea. However, the high cost, long turnaround times, and the need for sophisticated equipment and skilled personnel limit the use of NGS in daily practice. Immunohistochemistry (IHC) is a rapid and relatively inexpensive assay available in most laboratories. Therefore, in this study, we evaluate the usefulness of BRAF VE1 IHC in terms of predictive value and interobserver agreement in non–small cell lung cancers (NSCLCs). Methods: A total of 30 cases with known BRAF mutation status were selected, including 20 cases of lung adenocarcinomas, six cases of colorectal adenocarcinomas, and four cases of papillary thyroid carcinomas. IHC for BRAF V600E was carried out using the VE1 antibody. Fifteen pathologists independently scored both the staining intensity and the percentage of tumor cell staining on whole slide images. Results: In the lung adenocarcinoma subset, interobserver agreement for the percentage of tumor cell staining and staining intensity was good (percentage of tumor cell staining, intraclass correlation coefficient = 0.869; staining intensity, kappa = 0.849). The interobserver agreement for the interpretation using the cutoff of 40% was almost perfect in the entire study group and the lung adenocarcinoma subset (kappa = 0.815). Sensitivity, specificity, positive predictive value, and negative predictive value of BRAF VE1 IHC were 80.0%, 90.0%, 88.9%, and 81.8%, respectively. Conclusions BRAF VE1 IHC could be a screening test for the detection of BRAF V600E mutation in NSCLC. However, further studies are needed to optimize the protocol and to establish and validate interpretation criteria for BRAF VE1 IHC.

Purpose: Neuregulin 1 (NRG1) gene fusion is a potentially actionable oncogenic driver. The oncoprotein binds to ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic approach for inhibiting ERBB3/ERBB2. However, the frequency and clinicopathological features of solid tumors harboring NRG1 fusions in Korean patients remain largely unknown. Materials and Methods: We reviewed archival data from next-generation sequencing panel tests conducted at a single institution, specifically selecting patients with in-frame fusions that preserved the functional domain. The clinicopathological characteristics of patients harboring NRG1 fusions were retrospectively reviewed. Results: Out of 8,148 patients, NRG1 fusions were identified in 22 patients (0.27%). The average age of the patients was 59 years (range, 32 to 78 years), and the male-to-female ratio was 1:1.2. The lung was the most frequently observed primary site (n=13), followed by the pancreaticobiliary tract (n=3), gastrointestinal tract (n=2, stomach and rectum each), ovary (n=2), breast (n=1), and soft tissue (n=1). Histologically, all tumors demonstrated adenocarcinoma histology, with the exception of one case of sarcoma. CD74 (n=8) and SLC3A2 (n=4) were the most frequently identified fusion partners. Dominant features included the presence of fewer than three co-occurring genetic alterations, a low tumor mutation burden, and low programmed death-ligand 1 expression. Various clinical responses were observed in patients with NRG1 fusions. Conclusion Despite the rarity of NRG1 fusions in Korean patients with solid tumors, identification through next-generation sequencing enables the possibility of new targeted therapies.

Purpose: We investigated the clinical impact of genomic and pathway alterations in stage I epidermal growth factor receptor (EGFR)–mutant lung adenocarcinomas, which have a high recurrence rate despite complete surgical resection. Materials and Methods: Out of the initial cohort of 257 patients with completely resected stage I EGFR-mutant lung adenocarcinoma, tumor samples from 105 patients were subjected to analysis using large-panel next-generation sequencing. We analyzed 11 canonical oncogenic pathways and determined the number of pathway alterations (NPA). Survival analyses were performed based on co-occurring alterations and NPA in three patient groups: all patients, patients with International Association for the Study of Lung Cancer (IASLC) pathology grade 2, and patients with recurrent tumors treated with EGFR–tyrosine kinase inhibitor (TKI). Results: In the univariate analysis, pathological stage, IASLC grade, TP53 mutation, NPA, phosphoinositide 3-kinase pathway, p53 pathway, and cell cycle pathway exhibited significant associations with worse recurrence-free survival (RFS). Moreover, RPS6KB1 or EGFR amplifications were linked to a poorer RFS. Multivariate analysis revealed that pathologic stage, IASLC grade, and cell cycle pathway alteration were independent poor prognostic factors for RFS (p=0.002, p < 0.001, and p=0.006, respectively). In the grade 2 subgroup, higher NPA was independently associated with worse RFS (p=0.003). Additionally, in patients with recurrence treated with EGFR-TKIs, co-occurring TP53 mutations were linked to shorter progression-free survival (p=0.025). Conclusion Genomic and pathway alterations, particularly cell cycle alterations, high NPA, and TP53 mutations, were associated with worse clinical outcomes in stage I EGFR-mutant lung adenocarcinoma. These findings may have implications for risk stratification and the development of new therapeutic strategies in early-stage EGFR-mutant lung cancer patients.