To investigate the relationship between Ig class switch recombination (CSR) and mismatch repair (MMR) protein, microsatellite phenotype in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).

To analyze clinical characteristics and prognosis of B-cell acute lymphoblastic leukemia (B-ALL) patients with IKZF1 deletion.

To investigate the predictive value of morphology, immunology, and cytogenetics for isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation in newly diagnosed acute myeloid leukemia (AML) patients.

Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.

The incidence and mortality rates of lung cancer remain high, making it the leading cause of cancer-related deaths. In women, the predominant histological subtype is lung adenocarcinoma, commonly associated with epidermal growth factor receptor (EGFR) mutations, and EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can significantly improve patient prognosis. Metastasis of primary lung cancer to the endometrium is extremely rare and is often misdiagnosed as a primary reproductive system tumor, and its occurrence indicates poor prognosis. This article reports a case of an advanced lung adenocarcinoma patient with EGFR mutation, who developed abnormal vaginal bleeding after EGFR-TKIs treatment failure, and biopsy confirmed endometrial metastasis. A review of similar cases is also presented.
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Lung cancer remains the leading cause of cancer-related incidence and mortality worldwide. Among its histological subtypes, non-small cell lung cancer (NSCLC) accounts for the majority of cases, representing the predominant pathological type. Notably, in the elderly population, NSCLC continues to be a major contributor to cancer-related deaths. With the global ageing population, immunosenescence has emerged as a key factor influencing the occurrence, progression, and the efficacy of immunotherapy of NSCLC. Immunosenescence refers to the age-related decline in immune system function, which manifests as alterations in both the quantity and functionality of immune cells. These include thymic involution, T cell exhaustion, epigenetic modifications, weakened immune responses, and a chronic low-grade inflammatory state. This review comprehensively analyzes the role of immunosenescence in elderly patients with advanced NSCLC and proposes potential therapeutic strategies to intervene in the immunosenescence process. By targeting immunosenescence, these strategies aim to inhibit the progression of NSCLC and improve the effectiveness of immunotherapy.
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Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related mortality worldwide. In recent years, metabolomics has emerged as a key systems biology approach for analyzing small-molecule metabolites in cells, tissues and organisms. It provides new strategies for early diagnosis and metabolic profiling. Additionally, metabolomics plays a crucial role in studying resistance mechanisms in lung cancer. Tumor cell metabolic reprogramming is a key driving factor in the initiation and progression of lung cancer. Metabolomics studies have revealed how lung cancer cells regulate critical pathways such as energy metabolism, lipid metabolism, and amino acid metabolism to adapt to the demands of rapid proliferation and invasive metastasis. This review summarizes the latest advances in metabolomics research in lung cancer, focusing on the characteristics of metabolic reprogramming, the identification of potential metabolic biomarkers, and the prospects of metabolomics in early diagnosis and the elucidation of resistance mechanisms in lung cancer.
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Non-small cell lung cancer (NSCLC) ranks among the most lethal malignancies worldwide. The clinical application of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have successfully revolutionized the treatment paradigm for EGFR-mutant NSCLC, significantly prolonging progression-free survival and establishing EGFR-TKIs as the standard first-line therapy for advanced lung adenocarcinoma. However, acquired resistance remains a major obstacle to sustained clinical benefit, with mechanisms that are highly heterogeneous. A phenomenon of "oxidative stress compensation" is commonly observed in EGFR-TKIs-resistant cells, where in redox homeostasis, through the precise regulation of reactive oxygen species (ROS) generation and elimination, plays a pivotal role in maintaining the balance between tumor cell proliferation and apoptosis. This review aims to innovatively construct a theoretical framework describing how dynamic redox regulation influences resistance to third-generation EGFR-TKIs. It focuses on the multifaceted roles of ROS in both EGFR-dependent and EGFR-independent resistance mechanisms, and further explores therapeutic strategies that target ROS kinetic thresholds and antioxidant systems. These insights not only propose an innovative "metabolic checkpoint" regulatory pathway to overcome acquired resistance to third-generation EGFR-TKIs, but also lay a molecular foundation for developing the redox biomarker-based dynamic therapeutic decision-making systems, thereby facilitating a shift in NSCLC therapy from single-target inhibition toward multi-dimensional metabolic remodeling in the context of precision medicine.
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Small cell lung cancer (SCLC), a highly aggressive subtype of lung cancer that originates from pulmonary neuroendocrine cells, accounts for 10% to 15% of all lung cancers. It is characterized by a high rate of early metastasis and extremely poor prognosis, often accompanied by challenges such as drug resistance and recurrence. Related researches indicates that the Notch signaling pathway plays a crucial role in the occurrence and development of SCLC by regulating processes such as cell proliferation, differentiation, and apoptosis. In SCLC, abnormal Notch signaling may promote tumor malignancy and the occurrence of drug resistance. Additionally, the Notch pathway is involved in the epithelial-mesenchymal transition of SCLC and influences immune escape mechanisms through interactions with the tumor immune microenvironment. This article reviews the molecular mechanisms of Notch signaling in SCLC, including the roles of its receptors and ligands, signal transduction processes, and its role in tumorigenesis. It also discusses the research progress of Notch signaling as a potential therapeutic target and looks forward to future research directions in this field.
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Lung cancer remains one of the most prevalent and deadly malignancies worldwide, with persistently low five-year survival rates. This poor prognosis is primarily attributed to challenges such as difficulties in early diagnosis, high tumor heterogeneity, and strong therapeutic resistance. Although recent advances in targeted therapies and immune checkpoint inhibitors have significantly improved the prognosis of some patients, the majority still encounter primary or secondary resistance. Galectin-3, a multifunctional glycan-binding protein, is constitutively expressed in pulmonary tissues. Its expression encompasses bronchial and alveolar epithelial cells, the pulmonary vasculature, and resident immune cells. Galectin-3 plays a central role in lung cancer progression by regulating tumor cell proliferation, immune evasion, and angiogenesis. The complex immunosuppressive mechanisms within the tumor microenvironment not only facilitate tumor growth and metastasis but also partially limit the efficacy of cancer immunotherapies. Overcoming these barriers requires the exploration of novel regulatory targets to break through therapeutic bottlenecks. This review systematically elucidates the mechanisms by which galectin-3 interacts with immune cells (e.g., T cells, macrophages) in the tumor microenvironment and evaluates its potential as a therapeutic target, including inhibitor development and combination immunotherapy strategies. The findings aim to provide a theoretical foundation for advancing galectin-3 as a novel therapeutic target in lung cancer and offer new perspectives for overcoming current immunotherapy resistance.
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The proportion of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is relatively high in China. However, these patients currently lack significant benefits from available neoadjuvant treatment options. This study aims to explore the potential application value of neoadjuvant targeted therapy by evaluating its efficacy and safety in patients with EGFR-mutant resectable lung adenocarcinoma.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are important treatments for EGFR mutant non-small cell lung cancer (NSCLC). However, the first and second generation EGFR-TKI face clinical limitations due to acquired resistance, such as the T790M mutation. Irreversible EGFR-TKI can significantly prolong the survival of patients by enhancing the inhibition of drug-resistant mutations through the covalent binding mechanism. This article systematically reviews the mechanism of action, clinical research progress and future direction of irreversible EGFR-TKI, focusing on their potential to overcome drug resistance, combination treatment strategies and biomarker guided personalized treatment, in order to provide references for clinical practice.

Objective: To investigate the clinicopathological features, genetic characteristics, and differential diagnosis of glomangiomatosis with uncertain malignant potential. Methods: Two cases of glomangiomatosis with uncertain malignant potential were collected at Henan Provincial People's Hospital from 2013 and 2023. Immunohistochemistry and next generation sequencing (DNA-seq) were used to detect the related protein and gene variation. Patients were followed up. Results: Case 1 was male, 34 years old; and case 2 was female, 28 years old. Both had tumor recurrence in the original site. There were multiple nodules at right calf and ankle, involving superficial subcutaneous tissue and deep interfascicular muscles; some nodules were borderless and painful. Microscopically, the tumor was nodular with fibrous pseudocapsule, some had indistinct borders and diffuse infiltration to the surrounding adipose tissue. The tumor cells were round to ovoid with inconspicuous nucleoli, partly surrounding small irregularly dilated thin-walled blood vessels. The recurrent tumors showed epithelioid morphology in some of the tumor cells, with eosinophilic cytoplasm, some apparent nucleoli, mild to moderate nuclear atypia, and brisk mitotic figures. Focally, perimuscular cell differentiation was noted. The small lesion showed intravascular tumor thrombus. NGS revealed BRAF V600E mutation in case 1, and BRAF V600E mutation combined with PDGFRB gene amplification in case 2. Conclusions: Glomangiomatosis with uncertain malignant potential is a rare variant of glomus tumor. It has a unique growth pattern morphologically, BRAF V600E mutation, and invasive biological behavior.

Objective: To investigate the clinicopathological features of SMARCA4-deficient uterine sarcoma. Methods: Five cases of SMARCA4-deficient uterine sarcoma at the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from 2018 to 2024 were collected. The morphological and immunohistochemical features were observed and analyzed. A follow-up study was also carried out. Results: Five female patients, aged 24, 54, 56, 61, and 41 years, respectively, presented with vaginal bleeding or abdominal pain. All patients had imaging findings of intracavitary lesion in the uterus, with tumor sizes ranging from 3.0 cm to 8.8 cm. The patients were followed up for 2 to 14 months. Case 1 died 9 months after surgery, whereas the remaining four patients were still alive. Histologically, the tumor cells exhibited a diffuse growth pattern, with an infiltration depth involving more than half of the myometrium. Portions of the interstitium appeared sclerosed. Benign endometrial glandular structures were observed in a leaf-like or fissured pattern, resembling those of uterine adenosarcoma. The tumor cells were large epithelioid with abundant or faintly eosinophilic cytoplasm, and the nuclei were moderately to markedly atypia with prominent nucleoli and brisk mitosis. Rhabdoid cells were seen. Some areas showed small round blue cells, with occasional spindle cells and myxoid stroma. Additionally, widespread or focal lymphovascular space invasion was observed within the myometrium. All five cases exhibited absence of SMARCA4 (BRG1) expression and retained SMARCB1 (INI1). Claudin4 expression was negative. There was no deficient expression of mismatch repair proteins MLH1, PMS2, MSH2 and MSH6. p53 showed wild-type expression. Ki-67 index ranged from 30% to 60%. CKpan, CK7, ER, PR, and PAX8 were negative. Conclusions: SMARCA4-deficient uterine sarcoma is rare, highly aggressive, and has a poor prognosis. The tumor exhibits a broad morphological spectrum, with rhabdoid cells and adenosarcoma-like structures serving as important diagnostic clues. The absence of BRG1 expression lends support to a definitive diagnosis.

Objective: To explore the clinicopathological and molecular genetic characteristics of anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (RCC), including a rare case with the TPM1-ALK gene subtype. Methods: Three cases of ALK-rearranged RCC diagnosed in the Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from January 2020 to December 2024 were collected. Their clinical pathological and next-generation sequencing (NGS) data were analyzed. Relevant literature was also reviewed, and follow-ups were carried out. Results: Among the three patients, there were 1 female (case 1) and 2 males (cases 2 and 3), with the ages of 29,41 and 44 years, respectively. All of them were presented with space-occupying renal lesions. Case 1 (KIAA1217-ALK RCC) showed mixed cystic and solid components under the microscope, with tubular, papillary, and cribriform arrangements. The tumor cells had clear boundaries, and were cubic or low columnar, arranged in a single layer, pseudostratified or in sheets. The cytoplasm was abundant and eosinophilic, and part of the cytoplasm was vacuolated, as if there was accumulation of mucoid substances. The tumor cell nuclei were oval with prominent nucleoli. A large amount of mucus and inflammatory cell infiltration were noted in the stroma. Case 2 (TPM1-ALK RCC) showed a papillary growth pattern, with small, slender papillae accompanied by branches. The cells were arranged in a single layer, and the cytoplasm was either eosinophilic or clear. Foamy cells were aggregated in the stroma, accompanied by psammoma body-like calcifications. Case 3 (EML4-ALK RCC) was characterized by papillary and tubulocystic structures. The cytoplasm was abundant and eosinophilic. The tumor cell nuclei were large, with prominent nucleoli. There was conspicuous infiltration of lymphocytes and neutrophils in the fibromuscular stroma. The tumor cells all expressed epithelial markers, PAX8, GATA3, P504s and FH. ALK (5A4) staining showed diffuse strong expression in the cytoplasm, while TFE-3 was positive (nuclear stain) only in case 1 and case 3. The fluorescence in situ hybridization showed that ALK gene rearrangement was present in all three cases, while TFE-3 gene rearrangement/mutation was not detectable in case 1 and case 3. NGS showed the KIAA1217::ALK fusion (the fusion site in the exon 11 of KIAA1217 and exon 18 of ALK) in case 1, the TPM1::ALK fusion (the exon 8 of TPM1 and exon 20 of ALK) in case 2, and the EML4::ALK fusion (the exon 2 region of EML4 and the exon 20 region of ALK) in case 3. Conclusions: ALK-rearranged RCC has unique molecular characteristics. Its histological morphology is easily confused with that of papillary RCC and TFE3-rearranged RCC. Both immunohistochemistry and gene rearrangement tests should be used to confirm the diagnosis.