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Purpose: Recent development in perioperative treatment of resectable non-small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection., Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee., Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors., Conclusion: Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Objective: This study aims to determine whether the concurrent presence of tubulointerstitial inflammation (TII) and tubulointerstitial damage (TID) predicts the progression of chronic kidney disease (CKD) in patients with lupus nephritis (LN)., Methods: Data from 175 LN patients, collected at the time of renal biopsy, were analyzed. Patients were stratified into two groups based on the presence or absence of coexisting TII/TID. Uni- and multivariable Cox proportional hazard regression models were utilized to identify independent risk factors for CKD in LN patients., Results: Of 175 patients, 110 (62.9%) exhibited coexisting TII/TID, whereas 65 (37.1%) did not. Patients with coexisting TII/TID tended to be older and presented with higher levels of ESR and 24-h proteinuria, as well as lower levels of eGFR and hemoglobin compared to those without coexisting TII/TID. Over a mean follow-up period of 89.9 months, CKD and end-stage renal disease occurred more frequently in patients with coexisting TII/TID. Notably, the presence of coexisting TII/TID was associated with a higher risk of CKD progression, with adjusted hazard ratios of 2.667 (95% CI: 1.333, 5.335, p = 0.006) for all LN patients, 3.265 (95% CI: 1.451, 7.345, p = 0.004) for those with class III, IV, and V LN, and 3.045 (95% CI: 1.289, 7.195, p = 0.011) for those with class III, IV, V LN, and eGFR ≥ 30 mL/min/1.73 m 2 ., Conclusions: LN patients with coexisting TII/TID are at a heightened risk of kidney function deterioration at LN onset and subsequent development of CKD over the long term., (© 2024 The Author(s). International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Verrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma (SCC) characterized by its histological presentation as a low-grade tumor with no potential for metastasis, setting it apart from invasive SCC. However, distinguishing VC from its benign counterpart, verrucous hyperplasia (VH), is challenging due to their clinical and morphological similarities. Despite the importance of accurate diagnosis for determining treatment strategies, diagnosis of VH and VC relied only on lesion recurrence after resection. To address this challenge, we generated RNA profiling data from tissue samples of VH and VC patients to identify novel diagnostic markers. We analyzed differentially expressed (DE) mRNA and long non-coding RNA (lncRNA) in tissue samples from VH and VC patients. Additionally, ChIP-X Enrichment Analysis 3 (ChEA3) was conducted to identify the top five transcription factors potentially regulating the expression of DE mRNAs in VH and VC. Our analysis of mRNA and lncRNA expression profiles in VH and VC provides insights into the underlying molecular characteristics of these diseases and offers potential new diagnostic markers. The identification of specific DE genes and lncRNAs may enable clinicians to more accurately differentiate between VH and VC, leading to better treatment choices., Competing Interests: Declaration of competing interest No potential conflict of interest relevant to this article was reported., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Acral lentiginous melanoma (ALM) is the most common subtype of acral melanoma. Even though recent genetic studies are reported in acral melanomas, the genetic differences between in-situ and invasive ALM remain unclear. We aimed to analyze specific genetic changes in ALM and compare genetic differences between in-situ and invasive lesions to identify genetic changes associated with the pathogenesis and progression of ALM. We performed whole genome sequencing of 71 tissue samples from 29 patients with ALM. Comparative analyses were performed, pairing in-situ ALMs with normal tissues and, furthermore, invasive ALMs with normal and in-situ tissues. Among 21 patients with in-situ ALMs, 3 patients (14.3%) had SMIM14 , SLC9B1 , FRG1 , FAM205A , ESRRA , and ESPN mutations, and copy number (CN) gains were identified in only 2 patients (9.5%). Comparing 13 invasive ALMs with in-situ tissues, CN gains were identified in GAB2 in 8 patients (61.5%), PAK1 in 6 patients (46.2%), and UCP2 and CCND1 in 5 patients (38.5%). Structural variants were frequent in in-situ and invasive ALM lesions. Both in-situ and invasive ALMs had very low frequencies of common driver mutations. Structural variants were common in both in-situ and invasive ALMs. Invasive ALMs had markedly increased CN gains, such as GAB2 , PAK1 , UCP2 , and CCND1 , compared with in-situ lesions. These results suggest that they are associated with melanoma invasion., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aims: Bile reflux (BR) can influence the gastric environment by altering gastric acidity and possibly the gastric microbiota composition. This study investigated the correlation between bile acids and microbial compositions in the gastric juice of 50 subjects with differing gastric pathologies., Methods: This study included 50 subjects, which were categorized into three groups based on the endoscopic BR grading system. The primary and secondary bile acid concentrations in gastric juice samples were measured, and microbiota profiling was conducted using 16 S rRNA gene sequencing., Results: Significant differences were observed in each bile acid level in the three endoscopic BR groups (P < 0.05). The Shannon index demonstrated a significant decrease in the higher BR groups (P < 0.05). Analysis of the β-diversity revealed that BR significantly altered the gastric microbiota composition. The presence of neoplastic lesions and the presence of H. pylori infection impacted the β-diversity of the gastric juice microbiota. The abundance of the Streptococcus and Lancefielfdella genera exhibited positive correlations for almost all bile acid components(P < 0.05). In addition, the abundance of Slobacterium, Veillonella, and Schaalia showed positive correlations with primary unconjugated bile acids (P < 0.05)., Conclusion: Changes in microbial diversity in the gastric juice were associated with BR presence in the stomach. This result suggests that the degree of BR should be considered when studying the gastric juice microbiome., (© 2024. The Author(s).)

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous and prevalent subtype of aggressive non-Hodgkin lymphoma that poses diagnostic and prognostic challenges, particularly in predicting drug responsiveness. In this study, we used digital pathology and deep learning to predict responses to immunochemotherapy in patients with DLBCL. We retrospectively collected 251 slide images from 216 DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), with their immunochemotherapy response labels. The digital pathology images were processed using contrastive learning for feature extraction. A multi-modal prediction model was developed by integrating clinical data and pathology image features. Knowledge distillation was employed to mitigate overfitting on gigapixel histopathology images to create a model that predicts responses based solely on pathology images. Based on the importance derived from the attention mechanism of the model, we extracted histological features that were considered key textures associated with drug responsiveness. The multi-modal prediction model achieved an impressive area under the ROC curve of 0.856, demonstrating significant associations with clinical variables such as Ann Arbor stage, International Prognostic Index, and bulky disease. Survival analyses indicated their effectiveness in predicting relapse-free survival. External validation using TCGA datasets supported the model's ability to predict survival differences. Additionally, pathology-based predictions show promise as independent prognostic indicators. Histopathological analysis identified centroblastic and immunoblastic features to be associated with treatment response, aligning with previous morphological classifications and highlighting the objectivity and reproducibility of artificial intelligence-based diagnosis. This study introduces a novel approach that combines digital pathology and clinical data to predict the response to immunochemotherapy in patients with DLBCL. This model shows great promise as a diagnostic and prognostic tool for clinical management of DLBCL. Further research and genomic data integration hold the potential to enhance its impact on clinical practice, ultimately improving patient outcomes., (© 2024 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Breslow thickness, ulceration, and mitotic rate are well-known prognostic factors for sentinel lymph node (SLN) metastasis in cutaneous melanoma. We investigated risk factors, including especially the degree of pigmentation, for SLN metastasis in Korean melanoma patients. We enrolled 158, composed of Korean 107 acral and 51 non-acral melanoma patients who underwent SLN biopsy. Clinicopathologic features such as Breslow thickness, ulceration, mitotic rate, and the degree of pigmentation were evaluated. The recurrence-free survival (RFS) rate and date of recurrence were determined. Fifty-four patients (34.2%) had a positive SLN biopsy result. In a multivariate analysis, Breslow thickness (odds ratio [OR] 1.93; 95% confidence interval [CI], 1.12-3.47; p = .022) and heavy pigmentation (OR 13.14; 95% CI, 2.96-95.20, p = .002) were associated with SLN metastasis. Positive SLN patients had a higher rate of loco-regional and/or distant recurrence (hazard ratio 6.32; 95% CI, 3.39-11.79; p < .001). Heavy pigmentation was associated with poor RFS. Heavy pigmentation is an independent predictor of SLN metastasis in both acral and non-acral melanoma. Our results suggest the need for in-depth SLN evaluation of cutaneous melanoma patients with heavy pigmentation and provide clinicians with important information for determining patient prognosis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Lymphovascular invasion (LVI) is one of the most important prognostic factors in gastric cancer as it indicates a higher likelihood of lymph node metastasis and poorer overall outcome for the patient. Despite its importance, the detection of LVI(+) in histopathology specimens of gastric cancer can be a challenging task for pathologists as invasion can be subtle and difficult to discern. Herein, we propose a deep learning-based LVI(+) detection method using H&E-stained whole-slide images. The ConViT model showed the best performance in terms of both AUROC and AURPC among the classification models (AUROC: 0.9796; AUPRC: 0.9648). The AUROC and AUPRC of YOLOX computed based on the augmented patch-level confidence score were slightly lower (AUROC: -0.0094; AUPRC: -0.0225) than those of the ConViT classification model. With weighted averaging of the patch-level confidence scores, the ensemble model exhibited the best AUROC, AUPRC, and F1 scores of 0.9880, 0.9769, and 0.9280, respectively. The proposed model is expected to contribute to precision medicine by potentially saving examination-related time and labor and reducing disagreements among pathologists.

We aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). This is a secondary study of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29-0.97). In multivariate analysis, patient age (p=0.014) and gross tumor volume (GTV, p=0.031) were significant factors associated with overall survival, while TLC reduction (p=0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p=0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. Immunohistochemical analysis of programmed death ligand 1 and CD8 expression on T cells was performed on 84 patients. CD8 expression was not significantly associated with the pretreatment lymphocyte count (p=0.673), and PDL1 expression was not significantly associated with OS or PFS. Univariate analysis revealed that high CD8 expression in TILs was associated with favorable OS and was significantly associated with favorable PFS (p=0.032). TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, in the era of immunotherapy, constraining the volume of the radiation dose to the whole heart must be prioritized for the better survival outcomes., Competing Interests: CONFLICT OF INTEREST STATEMENT: None declared., (© Chonnam Medical Journal, 2024.)

A definitive surgical resection is the preferred treatment for early-stage non-small cell lung cancer (NSCLC). Research on genetic alterations, including epidermal growth factor receptor (EGFR) mutations, in early-stage NSCLC remains insufficient. We investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutations and recurrence after a complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resections at a single regional cancer center in Korea were recruited. We retrospectively compared the clinical and pathological data between the recurrence and non-recurrence groups. Among the 659 enrolled cases, the median age was 65.86 years old and the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutations was 43% (194/451). Among them, L858R point mutations and exon 19 deletions were 52.3% and 42%, respectively. Anaplastic lymphoma kinase (ALK) rearrangement was found in 5.7% of patients (26/453) and ROS proto-oncogene 1 (ROS1) fusion was found in 1.6% (7/441). The recurrence rate for the entire population was 19.7%. In the multivariate analysis, the presence of EGFR mutations (hazard ratio (HR): 2.698; 95% CI: 1.458-4.993; p = 0.002), stage II (HR: 2.614; 95% CI: 1.29-5.295; p = 0.008) or III disease (HR: 9.537; 95% CI: 4.825-18.852; p < 0.001) (vs. stage I disease), and the presence of a pathologic solid type (HR: 2.598; 95% CI: 1.405-4.803; p = 0.002) were associated with recurrence. Among the recurrence group, 86.5% of the patients with EGFR mutations experienced distant metastases compared with only 66.7% of the wild type ( p = 0.016), with no significant difference in median disease-free survival (52.21 months vs. not reached; p = 0.983). In conclusion, adjuvant or neoadjuvant targeted therapy could be considered more actively because EGFR mutations were identified as an independent risk factor for recurrence and were associated with systemic recurrence. Further studies on perioperative therapy for other genetic alterations are necessary.

Spontaneous acute epidural hematoma (AEDH) co-occurring with metastatic hepatocellular carcinoma (HCC) of the skull is rare, with only 7 documented cases in existing literature. This report describes the case of a 42-year-old man who presented with decreased consciousness following intermittent headaches following minor head trauma. Computed tomography imaging revealed an AEDH, prompting surgical intervention. Despite preliminary assumptions linking the causes of the trauma, surgical exploration revealed no evidence of traumatic injury. Instead, an infiltrative soft-tissue mass within the skull was identified. Histopathological examination confirmed that the mass was a metastatic HCC. Despite the successful hematoma evacuation, the patient's neurological status did not improve. This case underscores the importance of considering metastatic disease in the differential diagnosis of AEDH, particularly in patients with a history of malignant tumors, irrespective of prior indications of bone metastasis. Furthermore, it emphasizes the need to enhance diagnostic and therapeutic strategies for such complex cases., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2023 Korean Neurotraumatology Society.)

Objectives: As a convenient and economical method of screening cervical cancer and precancerous pathologies, the Papanicolaou smear (Pap smear) has been most widely used. Nevertheless, it requires cytological changes for making diagnoses and reportedly has a high false-negative rate. In this study, the usefulness of the human papillomavirus (HPV) DNA chip test as a complementary method that can compensate for the defect of the Pap smear was investigated., Material and Methods: Of the 6516 patients who simultaneously underwent a Pap smear and an HPV DNA chip test at Chonnam National University Hospital between January 2015 and December 2016, 1897, an initial PAP smear-negative patients who had undergone an additional Pap smear during their 2-year follow-up period were selected for this study. Of the subject patients, 281 underwent a cervical biopsy., Results: The Pap smear follow-up of an initial Pap smear-negative subjects showed 53 (75.7%) HPV high-risk positive cases in the cytology low-grade lesion group (70 cases) and 46 (97.8%) HPV high-risk positive cases in the cytology high-grade lesion group (47 cases). The 281 biopsy cases included 67 biopsy low-grade lesion cases and 74 biopsy high-grade lesion cases, of which there were 45 (67.2%) and 67 (90.5%) HPV high-risk positive cases, respectively. The follow-up cytology on the high-risk HPV-positive subjects showed that the ratio of their high-grade lesions was 260.8 times greater than that of the high-risk HPV-negative subjects (OR = 260.8 and 95% CI: 36.1 and 1886.1); and their biopsy showed that the ratio of their high-grade lesions was 102.7 times greater than that of the HPV-negative subjects (OR = 102.7 and 95% CI: 14.0 and 753.3)., Conclusion: The complementary use of the HPV DNA chip test may be useful in increasing the accuracy of screening examinations for the early diagnosis of uterine cervix cancer when combined with the Pap smear., Competing Interests: The authors declare that they have no competing interest., (© 2023 Cytopathology Foundation Inc, Published by Scientific Scholar.)

Pilomatricomas are tumors originating from the matrices of hair follicles. Giant pilomatricomas, defined as pilomatricomas that are 5 cm or larger, are benign but may appear malignant clinically. We present the case of a 69-year-old man with a rapidly growing mass on his scalp. When he visited our department, the tumor measured 10.0×6.0×4.0 cm and showed inflammation and ulceration. Magnetic resonance imaging and 18 F-fluorodeoxyglucose positron emission tomography-computed tomography showed findings resembling lymph node metastasis from a malignant tumor. However, upon an incisional biopsy, the tumor was diagnosed as a pilomatricoma. Therefore, we performed an excisional biopsy instead of radical surgery and lymph node dissection. The tumor was ultimately diagnosed as a giant pilomatricoma based on the excisional biopsy, and the patient received reconstruction only at the site of the defect. A giant pilomatricoma can be mistaken for a malignant tumor due to its characteristics. In such uncertain cases, it can be helpful to first perform an excisional biopsy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: Cancer recurrence remains a significant problem, and most postoperative recurrences of non-small cell lung cancer (NSCLC) develop within 5 years after resection. We present a rare case of ultra-late recurrence of NSCLC accompanying choroidal metastasis with KIF13A-RET fusion 14 years after the definitive surgery., Case Description: A 48-year-old female patient who had never-smoked presented with decreased visual acuity. She had been treated with right upper lobe lobectomy followed by adjuvant chemotherapy 14 years prior. Fundus photographs revealed bilateral choroidal metastatic lesions. Positron emission tomography-computed tomography (PET-CT) scans showed extensive bone metastases and focal hypermetabolism in the left uterine cervix. An excision biopsy of the uterus showed primary lung adenocarcinoma with immunohistochemistry of TTF-1+. Plasma next-generation sequencing (NGS) identified the presence of KIF13A-RET fusion. After 6 months of selpercatinib therapy, PET-CT revealed a partial response for bone and uterine metastasis and stable disease for choroidal lesions., Conclusion: In this case report, we are reporting a rare case of ultra-late recurrence of NSCLC in a patient with choroidal metastasis. Furthermore, the diagnosis of NSCLC with RET fusion was based on liquid-based NGS rather than tissue-based biopsy. The patient showed a good response to selpercatinib, which supports the efficacy of selpercatinib as a treatment for RET -fusion-positive NSCLC with choroidal metastasis., Competing Interests: Author SJH is employed by Dxome Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Park, Park, Shin, Han, Ji, Oh, Kim, Lee, Choi and Oh.)

Primary mucosa-associated with a lymphoid tissue (MALT) lymphoma is a rare distinct subtype of non-Hodgkin's lymphoma that occurs in approximately 8% of all non-Hodgkin lymphomas. Primary gastrointestinal MALT lymphoma usually occurs in the stomach, but duodenal involvement is extremely rare. Therefore, the clinical manifestations, treatment, and prognosis of primary duodenal MALT lymphoma have not yet been validated because of its rarity. This paper reports a case of a 40-year-old male with primary duodenal MALT lymphoma who was treated successfully with radiation therapy alone. A 40-year-old male visited for a medical check-up. Esophagogastroduodenoscopy revealed whitish multi-nodular mucosal lesions in the second and third portions of the duodenum. Biopsy specimens from mucosal lesions in the duodenum were reported to be suspicious for MALT lymphoma of the duodenum. He received a total dose of 3,000 cGy in 15 fractions with external beam radiation therapy for three weeks. Three months after radiation therapy, an endoscopic examination revealed complete resolution of the duodenal lesions. The follow-up 12 months after radiation therapy showed no evidence of tumor recurrence.

Purpose: This study aimed to provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015., Materials and Methods: The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung Cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020., Results: We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with non-small cell lung cancer (NSCLC) and 345 (13.0%) were diagnosed with small cell lung cancer (SCLC), respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of epidermal growth factor receptor (EGFR) mutation (19% vs. 11%) or anaplastic lymphoma kinase (ALK) translocation (38% vs. 11%)., Conclusion: In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.

Primary pulmonary Hodgkin lymphoma (PPHL) is an extremely rare condition. Its clinicopathological characteristics remain unclear because of the limited number of patients with PPHL. The aim of this study was to comprehensively analyze the clinicopathological characteristics of PPHL. We reviewed the electronic medical records and pathology slides of our 10 PPHL patients. The female-to-male ratio was 6:4, and the mean age was 41 years. Although three patients had no symptoms, seven had localized or generalized symptoms, including cough, sputum, chest discomfort/pain, and weight loss. Some cases had not been diagnosed as PPHL in the initial needle biopsy. Four patients underwent surgical resection. With chemotherapy, eight patients achieved complete remission. We also conducted a thorough literature review on 105 previously reported PPHL cases. Among a total of 115 PPHL cases, the most common subtype was nodular sclerosis (37.4%). More than half of the cases (55%) were clinically suspected as infectious pneumonia. Of 61 patients whose biopsies were available, 27 (44.3%) were diagnosed correctly as Hodgkin lymphoma, whereas the misdiagnoses included tuberculosis, Langerhans cell histiocytosis, solitary fibrous tumor, and adenocarcinoma. We demonstrated that PPHL represents a diagnostic challenge on small biopsies. Recognizing that this rare tumor can mimic infectious and inflammatory diseases as well as malignancies is important because the accurate diagnosis of PPHL is essential for adequate clinical management.

Rationale: Myxoid pleomorphic liposarcoma (MPL) is a rare aggressive adipocytic tumor that mainly presents in children and adolescents. It is most frequently observed in the mediastinum and rarely in the head and neck, perineal region, or back. Herein, we report the first published case of MPL of the teres minor muscle., Patient Concerns: A 24-years-old woman presented with a painless palpable mass in her right shoulder., Diagnoses: Magnetic resonance imaging identified a 9.0 × 7.0 × 4.0 cm mass suspected to be a sarcoma in the teres minor muscle. Positron emission tomography/computed tomography revealed no evidence of distant metastasis. Histopathological examination revealed the mass to be an MPL, which was assigned a histologic grade of 3 according to the French Federation of Cancer Centers Sarcoma Group system. No tumor cells were observed along the resected margins., Interventions: Under general anesthesia, the right teres minor muscle containing the mass was excised en bloc and frozen biopsy confirmed that the tumor cells did not invade the surrounding tissues., Outcomes: The patient underwent radiotherapy and was followed up for 6 months without complications., Lessons: Although MPL in the teres minor muscle is rare, it should be considered in the differential diagnosis in patients with a mass in the teres minor muscle due to its poor prognosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Tracheal tumors are rare diseases. They can cause narrowing of a central airway, a severe respiratory distress, and death. The objective of this case series is to highlight the role of rigid bronchoscopy in diagnosing and treating carina masses which are difficult to remove surgically. Tumor excision was performed by the rigid bronchoscopic intervention. Additional treatment was administered according to the diagnosis of each individual patient. After the procedure, patients' symptoms were improved and stenotic central airways were reopened. Rigid bronchoscopy can be a good therapeutic option to reestablish airway patency and a bridge treatment for further definitive treatment., Competing Interests: The authors have no conflicts of interest to disclose., (© 2022 The Authors.)

Post-vaccination myocarditis after administration of the NVX-CoV2373 coronavirus disease 2019 (COVID-19) vaccine has been reported in a limited population. We report the first biopsy-proven case of myopericarditis after administration of second dose of NVX-CoV2373 COVID-19 vaccine (Novavax®) in Korea. A 30-year-old man was referred to emergency department with complaints of chest pain and mild febrile sense for two days. He received the second dose vaccine 17 days ago. Acute myopericarditis by the vaccination was diagnosed by cardiac endomyocardial biopsy. He was treated with corticosteroid 1 mg/kg/day for 5 days and tapered for one week. He successfully recovered and was discharged on the 12th day of hospitalization. The present case suggests acute myopericarditis as a vaccination complication by Novavax® in Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Bile acids have been linked to pathomechanism and prognosis in various types of cancers. The present study aimed to investigate the effect of bile acids on the molecular change in gastric epithelial cancer cells and to evaluate gastric bile acid concentration in patients with early gastric cancer (EGC). Human gastric cancer cells (AGS and NCI‑N87 cell lines) were treated with several bile acid types to determine their effect on molecular changes in the cells. Gastric levels of individual bile acids were measured (primary unconjugated or conjugated bile acids and secondary bile acids) in 39 participants (20 controls and 19 patients with EGC). Exposing gastric epithelial cancer cells to primary bile acids in vitro upregulated the expression of early growth response factor 1 (Egr‑1) and the oncogenes including c‑Jun, c‑Myc and Snail, whereas a p42/44 MAPK inhibitor exposure reduced their expression. There was a significant difference in age and presence of atrophic gastritis with intestinal metaplasia in background mucosa between controls and patients with EGC. There were significant differences in the levels of unconjugated or conjugated primary bile acids between controls and EGC patients except lithocholic acid. After adjustment of age and presence of atrophic gastritis with intestinal metaplasia, the levels of cholic acid [adjusted odds ratio (aOR) 4.3; 95% confidence interval (CI): 1.2‑16.2; P=0.029] and glycochenodeoxycholic acid [aOR 9.9; 95% CI: 1.3‑75.3; P=0.027] were significantly higher in patients with EGC compared with controls. In conclusion, bile acids upregulate Egr‑1 in gastric cancer cells via the MAPK signaling pathway, and higher gastric levels of primary bile acids are associated with EGC. Therefore, exposure of gastric cells to primary bile acids may play a role in gastric carcinogenesis.

Objectives: Amiodarone is widely used to treat arrhythmia. However, amiodarone is known for its severe toxicity to the liver, lungs, and thyroid. Amiodarone causes liver damage ranging from asymptomatic serum aminotransferase elevation to hepatic failure requiring liver transplantation. Although amiodarone toxicity has been reported, its simultaneous multi-organ toxicity is not well-known. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, lungs, thyroid, and eyes., Case Presentation: A 61-year-old woman visited the emergency room due to general weakness, nausea, visual disturbance, heat intolerance, and a non-productive cough. The patient had been using clopidogrel and amiodarone due to underlying atrial fibrillation. The total level of bilirubin was 0.71 mg/dL, aspartate aminotransferase was 358 U/L, alanine aminotransferase was 177 U/L, and prothrombin time was 27.1 s. Computed tomography showed diffuse increased liver intensity and scattered hyperattenuated nodular consolidations in both lungs. Transthoracic needle lung biopsy revealed fibrinoid interstitial inflammation with atypical change of type II pneumocytes and intra-alveolar foamy macrophages. In addition, the thyroid-stimulating hormone level was <0.008 μIU/mL, and free thyroxine was 4.67 ng/dL. The thyroid scan showed diffuse homogenous intake of technetium-99 m pertechnetate in both thyroid lobes. The ophthalmologic exam detected bilateral symmetrical corneal deposits in a vortex pattern. With these findings, we could diagnose amiodarone-induced hepatic, pulmonary, thyroid, and ophthalmologic toxicity. Liver function was restored after cessation of amiodarone, and thyroid function was normalized with methimazole administration. However, due to aggravated lung consolidations, systemic steroid treatment was administered, and improvement was seen 1 week after, at the follow-up exam. As her symptoms improved, she was discharged with a plan of steroid administration for 3 to 6 months., Conclusions: This case implies the possibility of multi-systemic amiodarone toxicity. Thus, the toxicity of amiodarone to multiple organs must be monitored. Prompt cessation of the drug should be considered upon diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 You, Yoon, Cho, Choi, Kim, Choi, Kang and Choi.)

Background: Dedifferentiated liposarcoma (DDLPS) is an extremely rare neoplasm that exhibits various morphologies. The tumor is characterized by immunoreactivity to MDM2 and CDK4 and can be confirmed by detecting MDM2 amplification via fluorescence in situ hybridization (FISH). Herein, we report an unusual case of DDLPS arising from the duodenum., Case Summary: A 64-year-old man presented with repeated abdominal pain and weight loss. Radiologic studies revealed a mass of the duodenum involving the pancreas. The patient was treated with pylorus-preserving pancreaticoduodenectomy. Histologically, the tumor showed a high-grade sarcoma. Immunohistochemistry demonstrated that the tumor cells were positive for MDM2 and CDK4 expression. MDM2 amplification was detected via FISH, leading to the final diagnosis of DDLPS. Following surgery, the patient was treated in the intensive care unit due to peritonitis, and died 60 d after surgery., Conclusion: To the best of the authors' knowledge, this is the first case of primary duodenal DDLPS in Korea and the third case in the English-language literature. Care must be taken not to misdiagnose DDLPS as another high-grade tumor. Liposarcoma should be in the differential diagnosis list., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Rationale: Apocrine carcinoma is a rare malignant sweat gland tumor that has been reported in approximately 200 cases. This tumor usually occurs in the axilla, but in rare cases, it can also develop in the scalp. In the present work, we report 2 cases of cutaneous apocrine carcinoma of the scalp., Patient Concerns: Two men visited our outpatient clinic with recurrence of tumor after undergoing surgery for scalp tumor at another hospital., Diagnoses: Brain magnetic resonance imaging of a 56-year old man showed the presence of a 5.0 × 4.5 × 4.4 cm scalp mass in the right parietal region, invading the skull and dura mater and a 2.2 × 2.0 × 0.7 cm bony mass without any skin lesions right next to the scalp mass. Neck magnetic resonance imaging of a 76-year-old man revealed the presence of a well-defined oval mass in the subcutaneous layer of the left occipital scalp and 2 enlarged lymph nodes in the left neck. Definite diagnoses were made postoperatively. The patients were diagnosed with cutaneous apocrine carcinoma. The diagnosis was confirmed through histopathological and immunohistochemical staining tests., Interventions: The tumors were removed with a wide safety margin and reconstructive surgery was performed., Outcomes: Additional radiotherapy or chemotherapy was performed. Follow-up more than 6 months revealed no recurrence or metastasis., Lessons: If accurate diagnosis and treatment had taken place at the initial stages of the primary cutaneous apocrine carcinoma, it would have been possible to prevent recurrence and intracranial invasion. As recurrent primary cutaneous apocrine carcinoma can become aggressive and difficult to treat, even a small mass on the scalp must be evaluated carefully and treated properly., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Extra-pulmonary neuroendocrine carcinoma is a rare and aggressive cancer. Although several biological and histological markers have been suggested as prognostic factors for this cancer, the prognostic importance of systemic inflammatory markers, including the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, is unclear. This study aimed to evaluate the association between systemic inflammatory markers and the prognosis of extra-pulmonary neuroendocrine carcinoma. We retrospectively analyzed the clinical data of 85 patients with unresectable or metastatic extra-pulmonary neuroendocrine carcinoma who received platinum-based chemotherapy as first-line chemotherapy from August 2007 to November 2019. We used time-dependent receiver operating characteristic curve analysis to determine the cut-off values. The cut-off values for the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 3.0 and 158.5, respectively. There was no significant difference in the Eastern Cooperative Oncology Group performance status score, Ki-67 index, or response to chemotherapy between groups. The high neutrophil-lymphocyte ratio group showed significantly worse overall survival (high vs. low, median 11.1 vs. 21.0 months, log-rank p=0.004) and shorter median progression-free survival, but the latter was not statistically significant. The high platelet-lymphocyte ratio group also showed significantly worse progression-free survival and overall survival than the low platelet-lymphocyte ratio group (high vs. low: median 5.6 vs. 9.8 months, log-rank p=0.047 and median 13.8 vs. 21.0 months, log-rank p=0.013, respectively). In multivariable analysis, a high neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival. The neutrophil-lymphocyte ratio is a potent and readily available prognostic factor for extra-pulmonary neuroendocrine carcinoma., Competing Interests: CONFLICT OF INTEREST STATEMENT: None declared., (© Chonnam Medical Journal, 2022.)

Scrub typhus is an acute zoonotic febrile illness caused by Orientia tsutsugamushi having a specific geographic endemic area. This infection could be complicated with multi-organ involvement including myocarditis with variable severity. Here, we report a rare case of scrub typhus with biopsy-proven acute fulminant myocarditis which progressed very rapidly to cardiac arrest and was treated successfully with extracorporeal cardiopulmonary resuscitation. Clinicians should be alert to possible rapid progression of scrub typhus myocarditis to fulminant form and be prepared for close monitoring and temporary mechanical support if indicated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Park, Lim, Kim, Kim, Jeong, Choi and Kim.)

The risk factors affecting acral melanoma metastasis and prognosis remain unclear. The study included 168 patients with invasive acral melanoma who were followed for ≥3 years. We evaluated patient demographics, stages, clinicopathological features, anatomic site of melanoma including nail versus volar surface, and degree of melanoma pigmentations, sentinel lymph node biopsy results, and the first metastasis sites. Of the 168 patients (mean age 64.5 years; 52.4% male), 43 (25.6%) had invasive melanoma without metastasis, 113 (67.3%) had invasive melanoma with a first lymph node metastasis, and 12 (7.1%) had invasive melanoma with invasive melanoma with a first distant metastasis. Advanced T stage, high mitotic rate, ulceration, and the degree of pigmentation were significant risk factors for metastasis. Amelanotic and mild pigmentation of acral melanoma was associated with first distant metastasis, whereas heavy pigmentation was associated with first lymph node metastasis. Advanced TNM stages, high mitotic rate, volar location (hazard ratio = 2.24, 95% confidence interval 1.18-4.26), and low-pigmentation (hazard ratio = 2.02, 95% confidence interval 1.17-3.49) were associated with melanoma-specific mortality., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recently, myocarditis following messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination has become an important social issue worldwide. According to the reports so far, myocarditis related to mRNA COVID-19 vaccination is rare and usually associated with a benign clinical course without intensive care or any sequelae of fulminant myocarditis. Here, we report a case of acute fulminant myocarditis and cardiogenic shock after the mRNA COVID-19 vaccination, requiring extracorporeal cardiopulmonary resuscitation. Clinicians should keep in mind the possibility of progression to fulminant myocarditis in patients who presented with suggestive symptoms or signs of myocarditis after the COVID-19 vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lim, Kim, Kim, Jeong, Cho, Choi and Lee.)

We report a patient with severe neurological deterioration due to leptomeningeal metastases involving brain and spinal cord from anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma, managed rapidly and successfully with lorlatinib therapy. A 48-year-old male patient presented with acute mental deterioration, severe headache, and weakness of both legs. The patient's previous medical history included cerebral metastases from ALK-positive lung adenocarcinoma, which had been successfully managed via whole brain radiation therapy and gamma knife radiosurgery one year and three months before, respectively. Physical examination revealed neck stiffness and paraparesis with motor grade I. Gadolinium-enhanced brain MRI showed newly developed leptomeningeal enhancement along cerebellar folia, and whole spine MRI revealed similar leptomeningeal metastasis along the whole spinal axis. Lorlatinib was started orally with a dose of 100 mg/day. The patient showed rapid clinical improvement after one week. The patient was alert and the headache disappeared, while the paraparesis improved to normal ambulatory status. Two months of lorlatinib treatment resulted in almost complete disappearance of previous leptomeningeal enhancement of brain and spinal cord, and absence of newly developed metastatic lesions in the central nervous system, based on MRI results. The patient had been regularly followed with ongoing lorlatinib therapy for 5 months without any systemic complications or neurological abnormality. Conclusively, lorlatinib could be a rapid and effective treatment for patients with central nervous system leptomeningeal metastases arising from ALK-positive lung cancer., Competing Interests: The author has no potential conflicts of interest., (Copyright © 2021 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Objectives: Little is known regarding the effect of hyperuricaemia on the progression of kidney function in patients with lupus nephritis (LN). Thus, we investigated the effect of uric acid (UA) on the long-term outcome of patients with biopsy-proven LN., Methods: Data were obtained from KORNET, a prospective longitudinal systemic lupus erythematosus registry in the Republic of Korea. All 137 patients with LN included in this study had undergone a kidney biopsy and were subsequently treated with immunosuppressants. The patients were divided into two groups: UA ≤7 mg/dL and >7 mg/dL; their sociodemographic, clinical, treatment-related data, and outcomes were compared. Cox-proportional regression analyses were performed to identify independent predictors of renal outcome in patients with LN., Results: Among the 137 patients, 37 (27.0%) had UA >7 mg/dL. This higher UA group included fewer women, but more patients with hypertension, proliferative type LN, and a chronicity index >12. The 24-h urinary protein excretion and the creatinine level were higher in this group; haemoglobin, platelet, and albumin levels were lower. During 85.0 months of follow-up, complete remission at 1 year was less frequent in the higher UA group, whereas chronic kidney disease (CKD) and end-stage renal disease were more prevalent. In the Cox proportional hazards regression analysis, UA >7 mg/dL was a signi cant predictor of progression to CKD in patients with LN (hazard ratio=2.437; p=0.020)., Conclusions: Our findings suggest that hyperuricaemia at LN onset is an independent risk factor that predicts the development of CKD in patients with LN.

Objective: AS is a rheumatic disease characterized by chronic inflammation and bony ankylosis. This study was to evaluate whether a signal transducer and activator of transcription 3 phosphorylation inhibitor (stat3-p Inh) could treat both chronic inflammation and bone formation in AS., Methods: Primary AS osteoprogenitor cells and spinal entheseal cells were examined for osteogenic differentiation. SF mononuclear cells (SFMCs) and lamina propria mononuclear cells (LPMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analysed using flow cytometry and ELISA. Female SKG mice were treated with stat3-p Inh, IL-17A blocker or vehicle. Inflammation and new bone formation were evaluated using immunohistochemistry, PET and micro-CT., Results: In the SKG mouse model, stat3-p Inh significantly suppressed arthritis, enthesitis, spondylitis and ileitis. In experiments culturing SFMCs and LPMCs, the frequencies of IFN-γ-, IL-17A- and TNF-α-producing cells were significantly decreased after stat3-p Inh treatment. When comparing current treatments for AS, stat3-p Inh showed a comparable suppression effect on osteogenesis to Janus kinase inhibitor or IL-17A blocker in AS-osteoprogenitor cells. Stat3-p Inh suppressed differentiation and mineralization of AS-osteoprogenitor cells and entheseal cells toward osteoblasts. Micro-CT analysis of hind paws revealed less new bone formation in stat3-p Inh-treated mice than vehicle-treated mice (P = 0.005). Hind paw and spinal new bone formation were similar between stat3-p Inh- and anti-IL-17A-treated SKG mice (P = 0.874 and P = 0.117, respectively)., Conclusion: Stat-3p inhibition is a promising treatment for both inflammation and new bone formation in AS., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Adventitial cystic disease (ACD) of the veins is a rare vascular disease. Most cases of venous ACD are located adjacent to the joint area, such as the common femoral, external iliac, and popliteal veins. To the best of our knowledge, 67 cases of venous ACD have been reported, and ACD of the superficial femoral vein (SFV) has never been reported. Herein, we report the case of a 57-year-old male who presented with swelling and discomfort in the left leg. Computed tomography venography revealed multiple cystic lesions in the left distal SFV. The patient underwent cyst excision, which relieved the compression in the vein, although mild stenosis prevailed in the SFV. After a week, thrombosis developed in the popliteal vein. The thrombosis resolved after three months of anticoagulant therapy, and the patient showed no recurrence of ACD during three years of follow-up.

Background: Traumatic events are thought to be a cause of acral melanoma. However, little is known about the role of mechanical trauma or physical stress in the development of acral melanoma., Objective: In our study, we evaluated the frequency of trauma, physical stress, and occupation in patients with acral melanoma and aimed to identify any pathological correlates of these factors., Methods: We conducted a retrospective study of 313 acral melanoma patients from Chonnam National University Hospital. We mapped melanoma-developed anatomical sites of acral areas and assessed patients' history of trauma, physical stress, and occupation., Results: Among the 313 acral melanoma patients, many reported a traumatic event (84 of 313; 26.8%) or physical stress (91 of 313; 29.1%) before the melanoma developed. The most common anatomical sites in these patients were on the borders of the foot (136 of 313; 43.5%). Trauma was more commonly associated with the fingernails and toenails than other sites. The frequency of each type of physical stress depended on the site of the lesion. Farmer and fisherman were the most common occupations (130 of 313; 41.5%) of the acral melanoma patients., Conclusion: Our results demonstrate that traumatic events, physical stress, and certain occupations are common in acral melanomas. Further studies are needed to establish whether these are risk factors for acral melanomas., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © 2021 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Rationale: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon and aggressive hematologic malignancy that arises from plasmacytoid dendritic cells. BPDCN typically presents with skin lesions with or without involvement of lymph nodes, peripheral blood, or bone marrow. However, breast involvement of BPDCN is rare and there has been no report describing the radiologic features of BPDCN within breast parenchyma., Patient Concerns: We report a case of a 47-year-old woman who presented with an incidentally detected hypermetabolic breast lesion on PET/CT with concurrent right cheek plaque., Diagnoses: Skin biopsy was performed for the right cheek plaque. Mammography and breast ultrasonography were performed to evaluate the breast lesion. The lesion was depicted as a 2.5 cm sized focal asymmetry on mammogram and an irregular heterogeneous echoic mass within the mammary zone of the right upper outer breast. Core needle biopsy was performed for the breast lesion. Histologic diagnosis of the two lesions was BPDCN., Interventions: The patient was treated with induction and consolidation chemotherapy and received allogenic peripheral blood stem cell transplantation., Outcomes: The patient remains in complete remission state without relapse at 34 months since initial diagnosis., Lessons: This is the first case of BPDCN manifested as a breast parenchymal mass and assessed by diagnostic breast imaging tools (mammography and ultrasonography). This case report is significant for BPDCN within the breast parenchyma and presenting rare radiologic description of BPDCN., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Solitary fibrous tumors (SFTs) are rare benign mesenchymal tumors that occur mainly in the pleura. We herein report the first case of a cellular SFT located in the mental region of the head and neck in a 46-year-old woman. Facial computed tomography revealed a mass measuring 0.8 cm with clear boundaries in the right mental region. After excision of the mass, expert pathologists diagnosed a cellular SFT. To our knowledge, this is the first case of a cellular SFT identified in the subcutaneous tissue of the mental region of the head and neck. Because the postsurgical prognosis of SFTs is unpredictable, long-term follow-up and further studies are necessary to determine the characteristics of cellular SFTs in the head and neck region.

Purpose: Osimertinib is a potent, irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for both EGFR-activating and T790M resistant mutation. The treatment efficacy of osimertinib was assessed in previously untreated patients with metastatic non-small cell lung carcinoma (NSCLC) harboring activating EGFR mutations in circulating tumor DNA (ctDNA) as well as tumor DNA., Materials and Methods: Patients with activating EGFR mutations in their tumor DNA underwent screening with ctDNA analysis using Mutyper and Cobas v2 assays. Enrolled subjects received osimertinib 80 mg, once daily. Primary endpoint was objective response rate (ORR) and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR), and safety., Results: Among 39 screened patients, 29 were ctDNA positive for activating EGFR mutations and 19 were enrolled (ex19del, n=11; L858R/L861Q, n=7; G719A, n=1). Median age was 70 and most patients had brain metastases (15/19, 79%). ctDNA test sensitivity for activating EGFR mutations was 74% using both methods and 62% (Mutyper) or 64% (Cobas v2) for individual methods. ORR was 68% (13/19), median PFS was 11.1 months (95% confidence interval [CI], 0.0 to 26.7), and median DoR was 17.6 months (95% CI, 3.5 to 31.7). ORR and median PFS were significantly superior with ex19del (91%; 21.9 months; 95% CI, 5.5 to 38.3) than with L858R/L861Q (43%; 5.1 months; 95% CI, 2.3 to 7.9). One patient discontinued the drug because of drug-related interstitial pneumonitis., Conclusion: Osimertinib had favorable efficacy in the first-line treatment of metastatic NSCLC harboring activating EGFR mutations in ctDNA as well as tumor DNA.

We aimed to examine the usefulness of serum glutathione peroxidase 3 (GPx3) as a biomarker of lung cancer recurrence after complete resection. We prospectively collected serial serum samples at the baseline, as well as 3, 6 and 12 months after surgery from complete resection cases in 2013. GPx3 levels were measured by enzyme-linked immunosorbent assay. Statistical tests including t-tests and Cox proportional hazard regression analyses were performed. Totally, 135 patients were enrolled, and 39 (28.9%) showed relapse during the median follow-up period (63.60 months; range, 0.167-81.867). The mean GPx3 change was significantly higher in the recurrence group at 6 months (0.32 ± 0.38 vs. 0.15 ± 0.29, p = 0.016) and 12 months (0.40 ± 0.37 vs. 0.13 ± 0.28, p = 0.001). The high GPx3 change group showed significantly higher 60-months recurrence rates than the low group (48.1% vs. 25.2% at 3 months, p = 0.005; 54.5% vs. 28.9% at 6 months, p = 0.018; 38.3% vs. 18.3% at 12 months, p = 0.035). High GPx3 change at 3 months were independent risk factors of recurrence (hazard ratio (HR) 3.318, 95% confidence interval (CI), 1.582-6.960, p = 0.002) and survival (HR 3.150, 95% CI, 1.301-7.628, p = 0.011). Therefore, serum GPx3 changes after surgery may be useful predictive biomarkers for recurrence in lung cancer. Larger-scale validation studies are warranted to confirm these findings.

Air embolism is a rare, fatal complication of computed tomography (CT)-guided transthoracic needle biopsy (TTNB) of the lung. Here, we report a patient who developed an air embolism after CT-guided TTNB, which led to ST-elevation myocardial infarction and acute cerebral ischemia. The patient recovered completely without critical sequelae and was diagnosed with adenocarcinoma harboring activating epidermal growth factor receptor (EGFR) mutation. The patient responded to subsequent treatment with gefitinib. KEY POINTS: SIGNFICANT FINDINGS OF THE STUDY: Air embolism is a rare, fatal complication of CT-guided transthoracic lung biopsy. Only a few cases have been previously reported where myocardial and cerebral infarction occurred after TTNB, demonstrated not only on CT scan, but also electrocardiogram and electroencephalogram. WHAT THIS STUDY ADDS: Detection of driver gene mutation is crucial for planning lung cancer treatment. Despite the need for tissue biopsy, air embolism propagation to vital organs could result in severe end-organ damage and multidisciplinary approaches are needed to improve initial outcomes., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

An inflammatory myofibroblastic tumor originating from the aorta is extremely rare. Here, we report a case involving a 41-year-old female patient with an aortic inflammatory myofibroblastic tumor. Although preoperative imaging showed a mediastinal mass indicative of invasive thymoma, surgical findings revealed that this mass originated from the aorta. The patient underwent partial resection of the aorta, including the mass with patch angioplasty. Based on the postoperative histological findings, the patient was diagnosed with an aortic inflammatory myofibroblastic tumor and is currently under outpatient follow-up.

Background: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor that exhibits an epithelioid and spindle cell morphology. The tumor is characterized by immunoreactivity for melanocytic and myogenic markers but can be misdiagnosed as more common tumors with similar characteristics, including gastrointestinal stroma tumors or leiomyosarcomas. Recently, a subset of PEComas has been reported to harbor a transcription factor binding to TFE3 fusion. Herein, we report a rare case of TFE3 -expressing malignant PEComa arising from the mesentery., Case Summary: A 50-year-old woman presented with abdominal discomfort for 3 months. Results of laboratory tests were all within the normal ranges, and the patient had no notable medical history. Magnetic resonance imaging revealed a large tumor on the right side of the pelvic floor, which was originally suspected to be a primary ovarian tumor. However, during surgery, the tumor was revealed to have originated from the mesentery. Histologically, the tumor was composed of bundles of spindle cells and sheets of epithelioid cells. Extensive coagulative necrosis and numerous mitotic figures were observed. Immunohistochemistry revealed that the tumor cells were positive for smooth muscle actin, HMB-45, and TFE3 expression. Tumor involvement of the rectal serosa was identified, leading to a final diagnosis of malignant PEComa of the mesentery. Surgical resection was followed by adjuvant chemotherapy. No recurrence or metastasis was observed over a 6-month follow-up period., Conclusion: Malignant PEComa of the mesentery is extremely rare and should be distinguished from morphological mimics through differential diagnosis and immunohistochemistry., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Backgrounds: The present study evaluated Korean women with lung cancer and compared the clinical characteristics of ever-smoker and never-smoker groups using the National Lung Cancer Registry., Methods: In affiliation with the Korean Central Cancer Registry, the Korean Association for Lung Cancer constructed a registry into which 10% of the lung cancer cases in Korea were registered. Female lung cancer patients with valid smoking history were evaluated., Results: Among 735 female lung cancer patients, 643 (87.5%) were never-smokers and 92 (12.5%) were smokers. The median survival was significantly longer in the never-smoker group (28 vs. 14 months; P<0.001). Among 683 patients with non-small cell lung cancer (NSCLC), the never-smoker group showed significantly longer median survival (29 vs. 14 months; P=0.002) and a higher proportion of stage I cancer (40.3% vs. 25.7%; P<0.001). Survival analysis of the NSCLC patients showed that smoking status, receiving only supportive care, EGFR mutation status, lung cancer stage, and forced vital capacity (FVC) (%) were significantly associated with mortality in the multivariate analysis (P=0.025, HR 2.39, 95% CI: 1.12-5.11; P=0.017, HR 3.14, 95% CI: 1.22-8.06; P=0.033, HR 0.63, 95% CI: 0.41-0.96; P<0.001, HR 11.88, 95% CI: 5.79-24.38; P=0.002, HR 0.98, 95% CI: 0.96-0.99, respectively)., Conclusions: In Korean women with NSCLC, smoking status, not receiving active anticancer treatment, EGFR mutation status, lung cancer stage, and pulmonary function were significantly associated with mortality., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1671). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: Extraosseous Ewing sarcoma (EES) usually has a pseudocapsule and high vascularity, making it well circumscribed and focally dense with contrast enhancement on magnetic resonance imaging (MRI). Consequently, it is difficult to diagnose and distinguish from other spinal tumors, based on pretreatment radiologic findings alone. Here, we present a case of EES involving the thoracic spinal column, which was suspected to be spinal schwannoma through pretreatment radiologic findings., Case Description: A 54-year-old woman was admitted to our hospital with upper back and left-sided chest pain. Contrast-enhanced MRI of the thoracolumbar spine showed a 17- × 12-mm-sized mass in the epidural region and left neural foramen at the T6-7 level. Our preliminary diagnosis was spinal schwannoma. The patient underwent T6 hemilaminectomy. Intraoperatively, the lesion appeared as gray-colored soft mass with high vascularity, which seemed to have originated from the left T6 nerve root. The tumor was excised with en bloc resection. Histopathologic examination of the lesion revealed classical Ewing sarcoma with high cellularity of small round cells. Immunohistochemistry revealed strong positivity for cluster of differentiation 99 and FLI-1. Intensity-modulated radiation therapy was performed. The patient did not receive chemotherapy. Five years after surgery, follow-up spinal MRI and positron emission tomography computed tomography scan revealed no recurrence of the tumor or new lesions., Conclusions: Clinicians should consider EES in the differential diagnosis of other neural foraminal spinal tumors, such as schwannoma. If clinicians are confident that EES has been removed completely and there are no other lesions, radiotherapy is sufficient and additional chemotherapy may not be necessary., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) pathway have significantly improved outcomes for patients with a variety of malignancies, including non-small cell lung cancer (NSCLC). In contrast, the incidence of immune-related cutaneous adverse events such as vitiligo have been on the rise because of the increasing use of ICIs. Vitiligo-like depigmentation has been reported in only 2.0% to 8.3% of patients with melanoma and is considered a favorable prognostic factor. However, it has been rarely reported in patients with non-melanoma malignancies. We describe a case of vitiligo-like skin depigmentation after pembrolizumab use in a patient with stage IV NSCLC. Multiple ill-defined painless and non-pruritic depigmented patches appeared on the patient's hands, scrotum, and lower lip after five months of pembrolizumab. We continued treatment with pembrolizumab 2 mg/kg for 14 months with close monitoring of vitiligo lesions until the progression of brain metastasis, but the vitiligo-like depigmentation did not improve by the combined excimer laser and topical corticosteroid therapy. Clinicians should be aware that immune-related cutaneous adverse events such as vitiligo-like depigmentation are not limited to cases of melanoma but arise as a direct result of anti-PD-1 therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-386). The authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

Objectives: Bronchial brushing (BB) is often used to obtain supplementary samples for diagnosing lung cancer. We examined the possibility of epidermal growth factor receptor (EGFR) testing on BB samples and compared them with bronchial biopsy samples., Material and Methods: We used 150 BB samples with non-small cell carcinoma submitted to our department within 2 years. Biopsy samples were concurrently submitted for histologic diagnosis. We used the peptide nucleic acid clamping method for EFGR mutation test. Histologic diagnosis identified 137 cases of adenocarcinomas and 13 cases of non-small cell lung carcinoma, not otherwise specified. Each sample was assessed for adequacy and DNA content for EGFR mutation test., Results: Among BB samples, 28 had exon 19 deletion, 21 had mutations in exon 21, 99 were wild type, and analysis of two failed. The EGFR mutation rate in BB samples was 33.1% (49/148). Among bronchial biopsy samples, 26 had exon 19 deletion, 20 had mutations in exon 21, 92 were wild type, and analysis of 12 failed. The EGFR mutation rate using biopsy sample was 33.8% (46/136). The mutation detection results were nearly identical in both groups of samples (131/138, 94.9%). However, in two cases, an exon 21 mZutation was detected in biopsy samples but not in BB samples. In five cases, exon 19 deletion (two cases) and exon 21 mutation (three cases) were detected in BB but not in biopsy samples. The median DNA content was 58.83 ng for BB samples and 48.47 ng for biopsy samples. The failure rate for BB samples was lower than for biopsy samples. Overall, the BB samples were comparable to bronchial biopsy samples in terms of DNA quantity and mutation detection results., Conclusion: We conclude that in case of inadequate biopsy samples, BB samples can be used as a substitute material for EGFR mutation test., Competing Interests: All authors declare that this study was supported by a grant (CRI 14028-1) from the Chonnam National University Hospital Biomedical Research Institute., (©2020 Cytopathology Foundation Inc, Published by Scientific Scholar.)

Background: IBM Watson for Oncology (WFO) is a cognitive computing system helping physicians quickly identify key information in a patient's medical record, surface relevant evidence, and explore treatment options. This study assessed the possibility of using WFO for clinical treatment in lung cancer patients., Methods: We evaluated the level of agreement between WFO and multidisciplinary team (MDT) for lung cancer. From January to December 2018, newly diagnosed lung cancer cases in Chonnam National University Hwasun Hospital were retrospectively examined using WFO version 18.4 according to four treatment categories (surgery, radiotherapy, chemoradiotherapy, and palliative care). Treatment recommendations were considered concordant if the MDT recommendations were designated 'recommended' by WFO. Concordance between MDT and WFO was analyzed by Cohen's kappa value., Results: In total, 405 (male 340, female 65) cases with different histology (adenocarcinoma 157, squamous cell carcinoma 132, small cell carcinoma 94, others 22 cases) were enrolled. Concordance between MDT and WFO occurred in 92.4% (k=0.881, P<0.001) of all cases, and concordance differed according to clinical stages. The strength of agreement was very good in stage IV non-small cell lung carcinoma (NSCLC) (100%, k=1.000) and extensive disease small cell lung carcinoma (SCLC) (100%, k=1.000). In stage I NSCLC, the agreement strength was good (92.4%, k=0.855). The concordance was moderate in stage III NSCLC (80.8%, k=0.622) and relatively low in stage II NSCLC (83.3%, k=0.556) and limited disease SCLC (84.6%, k=0.435). There were discordant cases in surgery (7/57, 12.3%), radiotherapy (2/12, 16.7%), and chemoradiotherapy (15/129, 11.6%), but no discordance in metastatic disease patients., Conclusions: Treatment recommendations made by WFO and MDT were highly concordant for lung cancer cases especially in metastatic stage. However, WFO was just an assisting tool in stage I-III NSCLC and limited disease SCLC; so, patient-doctor relationship and shared decision making may be more important in this stage., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr.2020.04.11). The authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

Pancreatic cancer is the worst exocrine gastrointestinal cancer leading to the highest mortality. Recent studies reported that aberrant expression of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is involved in uncontrolled cell growth. However, the molecular mechanism of APE1 biological role remains unrevealed in pancreatic cancer progression. Here, we demonstrate that APE1 accelerates pancreatic cancer cell proliferation through glial cell line-derived neurotrophic factor (GDNF)/glial factor receptor α1 (GFRα1)/Src/ERK axis-cascade signaling. The proliferation of endogenous APE1 expressed-MIA PaCa-2, a human pancreatic carcinoma cell line, was increased by treatment with GDNF, a ligand of GFRα1. Either of downregulated APE1 or GFRα1 expression using small interference RNA (siRNA) inhibited GDNF-induced cancer cell proliferation. The MEK-1 inhibitor PD98059 decreased GDNF-induced MIA PaCa-2 cell proliferation. Src inactivation by either its siRNA or Src inhibitor decreased ERK-phosphorylation in response to GDNF in MIA PaCa-2 cells. Overexpression of GFRα1 in APE1-deficient MIA PaCa-2 cells activated the phosphorylation of Src and ERK. The expression of both APE1 and GFRα1 was gradually increased as progressing pancreatic cancer grades. Our results highlight a critical role for APE1 in GDNF-induced pancreatic cancer cell proliferation through APE1/GFRα1/Src/ERK axis-cascade signaling and provide evidence for future potential therapeutic drug targets for the treatment of pancreatic cancer.