Eun Kyung Kim

Objective: Gallbladder cancer (GBC) is a rare, aggressive malignancy with poor survival outcomes. The tumor microenvironment (TME), which includes stromal content, immune infiltration, and tumor budding, influences tumor progression and prognosis. ANXA1 is a multifunctional protein that mediates crosstalk within the TME to regulate cancer cell behavior and stromal dynamics; however, its prognostic role in GBC remains unclear. Patients and Methods: We retrospectively analyzed 131 patients who underwent surgery for primary GBC. Tumor–stroma ratio (TSR), local immune responses [Klintrup-Mäkinen (KM) grade, stromal tumor-infiltrating lymphocytes (TILs), and Crohn-like lymphoid reaction (CLR)], tumor budding, and ANXA1 expression were evaluated using hematoxylin and eosin-stained slides and immunohistochemistry. Associations with clinicopathological features, disease-specific survival (DSS), and progression-free survival (PFS) were assessed using Kaplan–Meier analysis and Cox regression models. Results: High-grade tumor budding was observed in 23% of tumors, and a stroma-high phenotype was identified in 29%. ANXA1 expression was positive in 80.9% of the tumors. Stroma high status and high-grade tumor budding were identified as independent predictors of poor DSS, whereas high-grade tumor budding independently predicted poor PFS. Low KM grade, stromal TILs, CLR, and ANXA1 expression were not independently associated with survival. Conclusions: High-grade tumor budding and stroma-rich phenotypes were independent adverse prognostic factors for GBC, whereas stromal TILs were associated with favorable outcomes. Although ANXA1 is expressed in GBC and linked to aggressive features, it does not independently predict survival. A comprehensive assessment of TME components may improve prognostic stratification and guide personalized management strategies for GBC.

Purpose In the modern era of precision medicine, next-generation sequencing (NGS) is employed for a variety of clinical purposes. The aim of this study was to investigate the trends and clinical characteristics of NGS testing in South Korea.Materials and Methods This nationwide, population-based, retrospective cohort study examined National Health Insurance Service claims data from 2017 to 2021 for NGS and from 2008 to 2021 for gene-targeted anticancer drugs.Results Among the total 98,748 claims, there were 51,407 (52.1%) solid cancer panels, 30,173 (30.5%) hereditary disease panels, and 17,168 (17.4%) hematolymphoid cancer panels. The number of annual claims showed a persistent upward trend, exhibiting a 5.4-fold increase, from 5,436 in 2017 to 29,557 in 2021. In the solid cancer panel, colorectal cancer was the most common (19.2%), followed by lung cancer (18.8%). The annual claims for targeted cancer drugs have increased 25.7-fold, from 3,932 in 2008 to 101,211 in 2020. Drugs for the treatment of lung cancer accounted for 488,819 (71.9%) claims. The number of patients who received non-hereditary NGS testing has substantially increased, and among them, the count of patients prescribed targeted anticancer drugs consistently rose from 508 (13.9%) in 2017 to 2,245 (12.3%) in 2020.Conclusion This study highlights the rising nationwide demand for comprehensive genetic testing for disease diagnosis and treatment following NGS reimbursement by the National Health Insurance in South Korea, in addition to the need for greater utilization of targeted anticancer drugs.

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.

We delved into the expression of amine oxidase family proteins and their potential significance in adrenal gland neoplasm. Tissue microarrays were prepared for 132 cases of adrenal cortical neoplasm (ACN) consisting of 115 cases of adrenal cortical adenoma (ACA), 17 cases of adrenal cortical carcinoma (ACC), and 163 cases of pheochromocytoma (PCC). Immunohistochemical stainings for MAOA, MAOB, LOX, and AOC3 were performed to evaluate the H-scores and compare them with clinicopathological parameters. The H-scores of MAOA (T; p = 0.005) and MAOB (T; p = 0.006) in tumor cells (T) were high in ACN, whereas LOX (T, S; p < 0.001) in tumor and stromal cells (S) and AOC3 (T; p < 0.001) were higher in PCC. In stromal cells, MAOA (S; p < 0.001) and AOC3 (S; p = 0.010) were more expressed in ACA than in ACC. MAOB (S) in PCC showed higher H-scores when the grading of adrenal pheochromocytoma and paraganglioma (GAPP) score was 3 or higher (p = 0.027). In the univariate analysis, low MAOA expression in stromal cells of ACN was associated with shorter overall survival (p = 0.008). In conclusion, monoamine oxidase proteins revealed differences in expression between ACN and PCC and also between benign and malignant cells.

Primary gastrointestinal T/NK cell lymphoma (GI-TNKL) is an uncommon and heterogeneous group of lymphoid malignancies. We aimed to investigate their subtype distribution, clinicopathologic characteristics, and clinical outcomes. A total of 38 GI-TNKL cases and their clinical and pathological characteristics were analyzed. GI-TNKL occurred in adults with a median patient age in the sixth decade of life and showed a slight male predominance. The most common histologic type was extranodal NK/T-cell lymphoma, nasal type (ENKTL; 34.2%), followed by monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL; 31.6%), intestinal T-cell lymphoma, NOS (ITCL, NOS, 18.4%), anaplastic large cell lymphoma, ALK-negative (ALCL, ALK-; 13.2%). The small intestine was the primary affected region. More than 90% of patients complained of various GI symptoms and cases with advanced Lugano stage, high IPI score, or bowel perforation that required emergent operation were not uncommon. GI-TNKL also showed aggressive behavior with short progression-free survival and overall survival. This thorough clinical and pathological descriptive analysis will be helpful for accurate understanding, diagnosis, and treatment.

Renal cell carcinoma (RCC) with clear cell morphology may show a prominent delicate vascularity. In this article, we report the morphologic and immunohistochemical features of a clear cell papillary RCC mimicking hemangioblastoma and a clear cell RCC mimicking hemangioma. Case 1 showed tubular and papillary growth of clear cells with distinctive areas of capillary proliferation and admixed stromal-like cells resembling a hemangioblastoma. Case 2 consisted of homogeneously delicate microvascular proliferations resembling a capillary hemangioma with scattered inconspicuous clear cells. The clear cells of Case 1 were PAX8(+), CK7(diffuse+), CA9(diffuse+, cup-shaped), and inhibin A(−). The hemangioblastoma-like areas were PAX8(+), CK7(−), CA9(diffuse+), and inhibin A(diffuse+). Case 2 showed PAX8(+), CK7(−), and CA9(diffuse+). They can be diagnostically challenging, and it is important to recognize that a pure hemangioma or hemangioblastoma of the kidneys is very rare, and that RCCs with clear cell morphology rarely exhibit hemangioma-like characteristics.

Background: The purpose of this study was to comprehensively characterize head and neck squamous cell carcinoma (HNSCC) arising in young patients (MET copy number gain, and lower pan‐Trk expression. PD‐L1 positivity in tumor cells and ICOS+ tumor infiltrating lymphocytes (TILs) were higher in the young age. Perineural invasion, PD‐L1 positivity, and higher ratio of CD163+ tumor infiltrating macrophages to CD8 + TILs were determined to be independent factors for poor progression‐free survival.Conclusion: Characterizing these features of young age HNSCC may help to identify the underlying pathogenesis and to improve patient outcome through different treatment strategies.