Chen HR, Huang ZY, Ren ZR
… +6 more, Lu C, Ding YZ, Yu QQ, Lu LF, Cang SD, Liu QY
Zhonghua Bing Li Xue Za Zhi
· 2026 May · PMID 42103620
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To analyze the mutation status of the PIK3CA gene and the clinicopathological characteristics in lung adenocarcinoma. Lung adenocarcinoma cases that underwent next-generation sequencing (NGS) for the PIK3CA gene at the...To analyze the mutation status of the PIK3CA gene and the clinicopathological characteristics in lung adenocarcinoma. Lung adenocarcinoma cases that underwent next-generation sequencing (NGS) for the PIK3CA gene at the Department of Pathology, the Third People's Hospital of Henan Province and the Henan Provincial People's Hospital from January 1, 2020 to December 31, 2024 were collected. Clinicopathological indicators were recorded for statistical analysis, and follow-up was conducted. A total of 127 lung adenocarcinoma patients with PIK3CA mutations were detected. There was a slight female predominance (75/127, 59.1%), the majority were non-smokers (95/127, 74.8%), and age was 65.0(57.0, 71.0)years old. Most lung adenocarcinomas were moderately differentiated (56/127, 44.1%) or poorly differentiated (44/127, 34.6%), with clinical stage Ⅳ being the most common (60/127, 47.2%). Hotspot mutations in the PIK3CA gene were present in 77 cases (77/127, 60.6%), specifically manifesting as mutations in exon 9 (E9, p.E545K/Q, p.E542K) and exon 20 (E20, p.H1047R/L/Y). Compared with E9 mutations, E20 mutations were more frequently associated with lymph node metastasis, visceral pleural invasion, airspace dissemination, poorer differentiation, and higher staging, and had a worse prognosis. Multivariate Cox analysis showed that PIK3CA hotspot mutations did not significantly affect prognosis (=0.586,95%=0.343-1.002,=0.051). Co-existing mutations in other genes were found in 105 cases (105/127, 82.7%), with 72 cases (72/105, 56.7%) harboring concomitant EGFR mutations. Of the 62 cases receiving targeted therapy, 11 developed drug resistance, primarily due to secondary EGFR exon 20 mutations (9/11). Lung adenocarcinomas with PIK3CA mutations exhibit distinct clinicopathological characteristics in terms of gender, age, smoking history, differentiation degree, and clinical stage. Acquired drug resistance in lung adenocarcinoma may be accompanied by PIK3CA mutations, but PIK3CA mutation is not the main mechanism of targeted therapy resistance in lung adenocarcinoma patients.
Gao M, Wang LM, Xiong YL
… +4 more, Zhao LH, Hu ZL, Zhang XW, Teng LH
Zhonghua Bing Li Xue Za Zhi
· 2026 May · PMID 42103619
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To investigate the clinicopathological and molecular features of meningioma, and to analyze the characteristic molecular changes in high-grade meningioma (WHO grades 2-3). A total of 139 meningioma specimens from 134 pa...To investigate the clinicopathological and molecular features of meningioma, and to analyze the characteristic molecular changes in high-grade meningioma (WHO grades 2-3). A total of 139 meningioma specimens from 134 patients treated at Xuanwu Hospital, Capital Medical University from 2015 to 2020 were collected, including 49, 62 and 28 samples of WHO grades 1, 2 and 3 meningiomas, respectively. Clinical data and pathological diagnoses were reviewed. Next-generation sequencing (NGS) was conducted to analyze the associations of molecular biomarkers with clinicopathological features and prognosis. Among the 134 patients, 59 patients (44.0%) were male, and 75 (56.0%) were female, age 57 (49, 66) years old. The most common genetic alteration was NF2 mutation (43.2%, 60/139). In non-NF2 mutated meningiomas, the hotspot genes of detectable mutations were AKT1 (13.7%, 19/139), TRAF7 (9.4%, 13/139), KLF4 (5.7%, 8/139), SMO (5.7%, 8/139), and PIK3CA (1.4%, 2/139). Twelve of the 13 cases TRAF7 alterations co-occurred with other genetic changes. Some molecular alterations were associated with histological subtypes. For instance, NF2 mutations were most frequently detected in psammomatous meningiomas (2/2) and fibrous meningiomas (8/9), while all secretory meningiomas harbored KLF4 mutations (6/6). Some molecular alterations were associated with tumor grade and prognosis. JAK3 mutations (4.3%, 6/139), TERT promoter mutations (3.6%, 5/139), and homozygous deletion of CDKN2A/B (4.3%, 6/139) were exclusively found in high-grade meningiomas. TERT promoter mutations and CDKN2A/B homozygous deletion (versus normal) were both independently associated with poorer prognosis (<0.001 for both). JAK3 mutation was also associated with shorter overall survivals (=0.031). NF2 is the most frequently mutated gene in meningiomas. TERT promoter mutations and CDKN2A/B homozygous deletion occur exclusively in high-grade meningiomas, link to unfavorable prognosis, and can serve as independent diagnostic markers for WHO grade 3 meningioma. JAK3 mutation seems also to be associated with high-grade meningiomas and shorter survivals.
Tan SY, Zhang YY, Chen W
… +5 more, Li JN, Wei YR, Wang M, Fan LN, Wang Z
Zhonghua Bing Li Xue Za Zhi
· 2026 May · PMID 42103618
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To evaluate the performance of a deep learning framework based on the PathOrchestra pathology foundation model for predicting key driver gene mutations (VHL, PBRM1, BAP1, and SETD2) in clear cell renal cell carcinoma (cc...To evaluate the performance of a deep learning framework based on the PathOrchestra pathology foundation model for predicting key driver gene mutations (VHL, PBRM1, BAP1, and SETD2) in clear cell renal cell carcinoma (ccRCC), and to analyze the associations of these mutations with clinicopathological characteristics and prognosis using whole-exome sequencing data. Whole-slide images and matched whole-exome sequencing data were collected from 319 patients with pathologically confirmed ccRCC at the First Affiliated Hospital of Air Force Medical University between March 2018 and July 2023. Image features of the whole slide imaging were extracted using the PathOrchestra foundation model. An attention-based multiple-instance learning model was developed to predict gene mutations. Model performance was evaluated on an independent test set, with the UNI model serving as a baseline control. The associations of the mutation status with clinicopathological parameters and patient prognosis were also analyzed. On the independent test set, the PathOrchestra model achieved area under the receiver operating characteristic curve values of 0.87 for VHL, 0.84 for PBRM1, 0.95 for BAP1, and 0.88 for SETD2, showing higher predictive performances than the UNI baseline for BAP1 and SETD2. Clinicopathological correlation analysis based on whole-exome sequencing data revealed that BAP1 mutation was associated with higher WHO/ISUP grade (=17.694,=0.001), tumor relapse/metastasis (=4.257,=0.039), and shorter progression-free survival (=0.045). The PathOrchestra-based deep learning approach can effectively identify key driver gene mutations in ccRCC using whole slide images of HE-stained slides, providing a feasible method for inferring genetic alterations from pathological images. The association of BAP1 mutation in ccRCC with poor prognosis further supports its value in prognostications. Moreover, the model visualization reveals morphological signatures associated with gene mutations, offering preliminary insights into genotype-morphology relationships.
Zhonghua Bing Li Xue Za Zhi
· 2026 May · PMID 42103617
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To investigate the clinicopathological and genetic characteristics of mesenchymal tumors with GLI1 gene alterations. Five cases diagnosed at the Tongji Hospital, Tongji Medical College, Huazhong University of Science an...To investigate the clinicopathological and genetic characteristics of mesenchymal tumors with GLI1 gene alterations. Five cases diagnosed at the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China from 2021 to 2025 were collected. HE and immunohistochemical slides were reviewed. Tumor-associated genetic alterations were detected using a next generation sequencing (NGS) panel of pan-solid tumor genes (468 genes, 116 DNA+352 RNA). Fluorescence in situ hybridization (FISH) was performed to detect GLI1 gene translocation and amplification. Clinical and follow-up data were analyzed. There were 3 females and 2 males, aged 48, 16, 47, 47 and 37 years, respectively. The tumor locations were the tongue, small intestine, ovary, and buttock. Histologically, tumor cells arranged in nest and lobular arrangements; within a partially myxoid stroma with necrosis and calcification, surrounded by a rich fibrovascular network around and a pseudocapsule in some cases. The tumor cells were predominantly round to oval, with fewer short spindled forms, showing mild to moderate atypia and distinct nucleoli. Immunohistochemically, tumor cells variably expressed CD56, S-100, and smooth muscle actin, but were negative for broad-spectrum epithelial markers. GLI1 immunohistochemistry showed diffuse, strong positivity (2 cases stained). Ki-67 proliferation index ranged from 1% to 30%. NGS identified PTCH1::GLI1 fusions in three cases and GLI1 amplification in two. All patients underwent complete surgical resection without adjuvant therapy. During the follow-up (4-16 months), one case recurred, while four remained disease-free. Mesenchymal neoplasm with GLI1 gene alterations is a type of tumor with low malignant potential, representing the biological behavior of low-grade sarcoma. However, it is currently not recognized by the World Health Organization classification. Surgical resection is the preferred treatment. While immunophenotyping lacks specificity, and GLI1 immunohistochemistry could aid in its diagnosis. Definitive diagnosis and differential diagnosis of this tumor require characteristic morphological features combined with molecular confirmation of GLI1 gene fusion or amplification.
Zhonghua Bing Li Xue Za Zhi
· 2026 May · PMID 42103616
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To investigate the clinicopathological features, diagnosis, and prognosis of Erdheim-Chester disease. The clinical and imaging data of 16 patients with Erdheim-Chester disease diagnosed in the Department of Pathology, S...To investigate the clinicopathological features, diagnosis, and prognosis of Erdheim-Chester disease. The clinical and imaging data of 16 patients with Erdheim-Chester disease diagnosed in the Department of Pathology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from August 2002 to July 2025 were retrospectively analyzed. A comprehensive evaluation was conducted on histopathology, immunophenotype, molecular characteristics, clinical treatment and follow-up outcomes, supplemented by a review of relevant literature. There were 16 patients with Erdheim-Chester disease, including 7 males and 9 females. The age at onset ranged from 38 to 70 years, with an average age of 48.0 (43.5, 54.5) years. Two of the 16 cases were complicated by Langerhans cell histiocytosis. Isolated skeletal involvement was observed in 5 cases (most commonly affecting the long bones of the lower extremities), while skeletal involvement with extra-skeletal systemic manifestations (including pulmonary, pituitary, urinary system, pericardial, and aortic involvements) was identified in 11 cases. The characteristic imaging presentation consisted of bilateral symmetric, multifocal diffuse osteosclerosis predominantly involving the diaphyses and metaphyses of long bones. Bone scintigraphy revealed symmetrically increased radiotracer uptake. Magnetic resonance imaging showed hypointense signals on T1-weighted images and heterogeneously hyperintense signals on T2-weighted images, with significant enhancement observed after contrast administration. Histopathological examination revealed osteosclerosis accompanied by infiltration of abundant lipid-laden foamy histiocytes or small mononuclear histiocytes within the intertrabecular spaces. These cells exhibited uniformly eosinophilic, pale pink-stained cytoplasm and round to oval nuclei with inconspicuous nucleoli. The lesion was also characterized by variable numbers of Touton giant cells and varying degree of fibrosis. Immunohistochemical analyses demonstrated the expression of CD68, CD163, and PGM1, but no expression of S-100 or Langerin. BRAF V600E gene mutation was detected in five cases. Clinical management regimens encompassed curettage of intraosseous lesions, potentially combined with adjuvant therapies such as hormonal agents, chemotherapy, interferon-alpha, or BRAF V600E inhibitors. At the end of follow-up (ranging from 2 to 18 years), seven patients died of the disease, six survived with it, and three remained disease-free. Erdheim-Chester disease is a rare condition characterized predominantly by multifocal and symmetrical involvement of long bones, with the majority of patients presenting with systemic manifestations. Pathological examination combined with imaging studies aids in distinguishing it from inflammatory disorders and other histiocytic proliferative lesions. The overall prognosis is poor, especially in cases involving multiple bones and systemic involvement.
Chen M, Jing WY, He X
… +4 more, Peng H, Peng R, Lu Y, Zhang HY
Zhonghua Bing Li Xue Za Zhi
· 2026 May · PMID 42103615
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To investigate the clinical application of DDIT3 gene rearrangement using fluorescence in situ hybridization (FISH) in myxoid liposarcoma (MLPS) and to analyze the cases with atypical signal pattern. A total of 386 case...To investigate the clinical application of DDIT3 gene rearrangement using fluorescence in situ hybridization (FISH) in myxoid liposarcoma (MLPS) and to analyze the cases with atypical signal pattern. A total of 386 cases were examined for DDIT3 gene rearrangement using FISH in the West China Hospital, Sichuan University, Chengdu, China from January 2018 to December 2024. The clinicopathologic data and molecular detection results were collected. Six MLPS with DDIT3 cryptic rearrangement (CR-MLPS) were identified and subject to FISH testing of FUS and EWSR1 break, EWSR1::DDIT3 and FUS::DDIT3 fusion, next-generation sequencing (NGS), reverse-transcriptase polymerase chain reaction and Sanger sequencing. Among the 386 successfully tested cases, 154 cases were histologically diagnosed as MLPS, of which 148 (148/156, 96.1%) were positive for DDIT3 gene rearrangements. In the positive cases, 57 cases were further subject to FUS and EWSR1 break-apart examination. Among them, 51 cases (51/57, 89.5%) showed FUS rearrangements, 5 cases (5/57, 8.8%) displayed EWSR1 rearrangements and 1 case was negative for FUS and EWSR1 rearrangement. DDIT3 gene rearrangements were negative in 238 cases (238/386, 59%). Six CR-MLPS were identified, including two females and four males, with an average age of 32 (14, 55) years, all located in the deep soft tissues of the extremities. All six cases of CR-MLPS presented typical MLPS morphology, with nodular distribution, abundant mucin, and visible branched capillaries. The cells were round and of medium size. Adipoblasts and cells with adipocyte-differentiation were also observed. The tumor cells in all six cases of CR-MLPS were negative or focally positive for S-100, and negative for p63 (4/4) and CDK4 (3/3). The Ki-67 index was 10% to 15%. Three of the six DDIT3 CR-MLPS showed small gap of DDIT3 break, one case revealed centromeric amplifications of DDIT3 gene, and two cases displayed 1 to 3 yellow/fusion signals. Subsequent FISH fusion test, reverse-transcriptase polymerase chain reaction and NGS confirmed that four cases had EWSR1::DDIT3 variants and two cases had FUS::DDIT3 variants. All six patients underwent surgical resection followed by radiotherapy. Among them, one patient had a recurrence 4 years after surgery, and another had recurrence and metastasis. FISH detection of DDIT3 gene rearrangements is important for the diagnosis of MLPS, whereas a small number of cases may still be missed due to cryptic rearrangement. The CR-MLPS cases present typical morphology, among which the EWSR1::DDIT3 variants are more commonly detected than the others.
Zhonghua Bing Li Xue Za Zhi
· 2026 May · PMID 42103614
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In conjunction with the new 2025 ISSVA classification, this article interprets the classification of this group of diseases one by one and elaborates on clinical and pathological issues related to the new classification....In conjunction with the new 2025 ISSVA classification, this article interprets the classification of this group of diseases one by one and elaborates on clinical and pathological issues related to the new classification. It aims to provide a reference for the accurate classification and diagnosis of vascular anomalies diseases from a pathological perspective and further enhance pathologists' in-depth understanding.
Zhonghua Bing Li Xue Za Zhi
· 2026 May · PMID 42103613
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In August 2025, an updated International Multidisciplinary Classification of Interstitial Pneumonias was released by the European Respiratory Society (ERS) and American Thoracic Society (ATS). For the first time, the "id...In August 2025, an updated International Multidisciplinary Classification of Interstitial Pneumonias was released by the European Respiratory Society (ERS) and American Thoracic Society (ATS). For the first time, the "idiopathic-only" paradigm has been transcended through the integration of secondary interstitial lung diseases (ILD) into a unified framework. Grounded in recent advances in ILD research, major changes have been introduced to disease patterns, diagnostic terminology, subcategories, and diagnostic approach. Actual histopathologic findings are more accurately represented by the new schema, and clearer, more actionable guidance for patient management is provided to clinicians. The pathological dimensions of the update are highlighted herein, with key innovations outlined, newly introduced subcategories, terminologies, and categorization systems elucidated, and a systematic overview of the histological characteristics of major patterns offered. Additionally, the opportunities and challenges that the new classification presents to pathologists are discussed.