Objective: To investigate the clinicopathological and genetic characteristics of mesenchymal tumors with GLI1 gene alterations. Methods: 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. Results: 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. Conclusions: 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. 目的： 探讨GLI1基因改变的间叶性肿瘤临床病理及遗传学特征。 方法： 回顾性收集华中科技大学同济医学院附属同济医院2021—2025年确诊的5例病例，复核HE及免疫组织化学染色切片，采用泛实体瘤468基因（116 DNA+352 RNA）检测试剂盒进行二代测序检测肿瘤相关基因变异，荧光原位杂交检测GLI1基因易位和扩增并收集临床资料及随访信息。 结果： 5例患者中女性3例，男性2例，年龄分别为48、16、47、47、37岁；肿瘤位于舌、小肠、卵巢及臀部。镜下观察，肿瘤细胞呈巢状、叶状分布，间质部分黏液变性、坏死及钙化，周围可见丰富纤维血管网，部分有假包膜；细胞以圆形、卵圆形为主，少数短梭形，轻至中度异型，核仁明显。免疫组织化学染色，肿瘤细胞不同程度表达CD56、S-100蛋白、平滑肌肌动蛋白，不表达广谱上皮标志物；GLI1弥漫强阳性（2例染色）；Ki-67阳性指数1%~30%。二代测序检测，3例检出PTCH1：：GLI1融合；2例检出GLI1拷贝数扩增。5例患者行肿瘤完整切除，术后未行放化疗。随访4~16个月，1例复发，4例无瘤生存。 结论： GLI1基因改变的间叶性肿瘤是一种具有潜在恶性潜能的肿瘤，为低级别肉瘤的生物学行为，目前WHO肿瘤分类无编码。手术切除为首选治疗。免疫表型缺乏特异性，GLI1免疫组织化学有助于诊断。确诊需结合特征性形态学表现，并依赖分子检测证实GLI1基因融合或扩增。.
Objective: To explore the clinicopathological features, immunophenotype, molecular characteristics, and prognosis of primary malignant solitary fibrous tumor (MSFT) of the kidney. Methods: The clinicopathological data of four renal MSFT cases diagnosed at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China and one case at the Ningbo Clinical Pathology Diagnostic Center, Ningbo, China between 2015 and 2025 were collected. The clinical features, histomorphology, and immunohistochemical characteristics were analyzed. Fluorescence in situ hybridization (FISH) and RNA-based next-generation sequencing were performed. Follow-up and review of relevant literature were conducted. Results: Among the five patients, three were male and two were female, aged 70(61,71) years. The tumors were all found during routine physical examinations. Four cases (cases 1, 3, 4, and 5) occurred in the left kidney, and one case (case 2) first occurred in the left kidney and recurred in the right kidney 5 years later. Four cases had a single lesion with a maximum diameter of 6.0-19.0 cm, and one case (case 5) had 2 lesions with maximum diameters of 2.0 cm and 4.0 cm, respectively. Histologically, three cases (cases 1, 2, and 5) were de novo MSFT, one case (case 5) was morphologically similar to synovial sarcoma with spindle cells arranged densely in bundles, one case (case 1) had sheets of epithelioid tumor cells, and one case (case 2) had alternating myxoid and spindle cell areas, with sparse tumor cells in the myxoid areas and dense tumor cells in the spindle cell areas. Two cases (cases 3 and 4) were classic solitary fibrous tumor (SFT) with dedifferentiation, and the dedifferentiated components were high-grade undifferentiated sarcoma. In the typical SFT areas, tumor cells were alternately dense and sparse, with collagenized areas and rare mitotic figures, while branching or hemangiopericytoma-like structures were also present. In the dedifferentiated areas, tumor cells were spindle-shaped or epithelioid with conspicuous nucleoli. Necrosis was seen in all three de novo MSFT cases (cases 1, 2, and 5) and one dedifferentiated case (case 4). The mitotic figures in three de novo SFT cases and two dedifferentiated areas were 4 to 10 per 10 HPF. No heterologous differentiation was found in any of the five cases. According to the Demicco risk classification, four cases were of moderate risk, and one case (case 4) was of high risk. Four cases showed diffuse expression of STAT6, while one case (case 3) showed partial expression. CD34 was diffusely positive in 3 cases, partially positive in one case (case 4) and negative in one case (case 1). Only one of the 5 cases expressed CKpan which was focally positive. PAX8, desmin, BCOR, S-100 protein, Melan A and HMB45 were all negative. H3k27Me3 expression was retained. FISH showed no SYT (SS18, 18q11) rearrangements in two cases (cases 4 and 5), and no MDM2 amplification in one case (case 5). RNA sequencing in four cases detected NAB2::STAT6 gene fusion, all of which were NAB2ex6::STAT6ex16 fusion subtypes. Follow-up data were available for four cases, with the follow-up period of 11-30 months. Among the 4 cases, one case had liver metastasis 3 months after surgery, and one case of left renal MSFT (moderate risk) had right renal recurrence 5 years after surgery. The other two had no recurrence or metastasis. Conclusions: Renal MSFT with moderate to high-risk is rare, shows a wide morphological spectrum and needs to be differentiated from various tumors. Extensive sampling, careful morphological observation, immunohistochemical staining and molecular detection of NAB2::STAT6 fusion are helpful for the diagnosis. It appears to have aggressive biological behaviors. 目的： 探讨原发性肾脏恶性孤立性纤维性肿瘤（MSFT）的临床病理特征、免疫表型、分子改变及预后。 方法： 收集2015—2025年上海交通大学医学院附属瑞金医院（4例）和宁波市临床病理诊断中心（1例）肾脏MSFT病例的临床病理资料，观察和分析其临床特征、组织形态学和免疫组织化学特点，进行荧光原位杂交检测和二代测序，随访及复习相关文献。 结果： 5例患者中男性3例、女性2例，年龄70（61，71）岁，均为体检发现肾脏占位。4例（例1，3，4，5）发生在左肾，1例（例2）初发于左肾、5年后右肾复发；4例为单一病灶，肿块最大径6.0~19.0 cm，1例（例5）为2灶病灶，最大径分别为2.0、4.0 cm。组织学上，3例（例1，2，5）为从头发生MSFT，1例（例5）形态类似于滑膜肉瘤，梭形细胞束状、密集排列，1例（例1）肿瘤细胞呈上皮样、弥漫排列，1例（例2）黏液变区域和梭形区域交替出现，黏液变区域肿瘤细胞稀疏，梭形区域肿瘤细胞密集。2例（例3，4）为经典型孤立性纤维性肿瘤（SFT）伴去分化，去分化成分均为高级别未分化肉瘤；典型SFT区域肿瘤细胞疏密交替、可见胶原化区域，并见分支状或血管外皮瘤样结构，核分裂象罕见。去分化区域肿瘤细胞呈梭形、上皮样，核仁明显，3例（例1，2，5）从头发生MSFT和1例（例4）去分化区域可见坏死。3例从头发生MSFT和2例去分化区域核分裂象4~10个/10 HPF。5例均未见异源性分化。Demicco危险度分级：4例中度危险，1例（例4）高度危险。免疫组织化学染色：4例肿瘤细胞弥漫表达STAT6、1例（例3）部分表达STAT6，3例弥漫表达CD34、1例（例4）部分表达CD34、1例（例1）不表达CD34。4例肿瘤细胞不表达CKpan、1例少量表达CKpan，PAX8、结蛋白、BCOR、S-100蛋白、Melan A、HMB45均不表达。H3k27Me3均未缺失表达。2例（例4，5）FISH检测SYT（SS18，18q11）断裂阴性，1例（例5）检测MDM2扩增阴性。4例RNA测序检测到NAB2：：STAT6基因融合，且均为NAB2ex6：：STAT6ex16融合亚型。4例获得随访资料，随访11~30个月，其中1例术后3个月伴肝转移，1例左肾MSFT（中危）术后5年右肾复发，其余均无复发和转移。 结论： 肾脏原发性中-高风险性MSFT罕见，形态学谱系广，需与多种肿瘤鉴别，广泛取材、仔细形态学观察、免疫组织化学染色及NAB2：：STAT6融合基因分子检测有助于诊断和鉴别诊断，具有侵袭性生物学行为。.
Objective: To investigate the clinicopathological features, diagnosis, and prognosis of Erdheim-Chester disease. Methods: 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. Results: 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. Conclusions: 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. 目的： 探讨Erdheim-Chester病的临床病理学特征、诊断与鉴别诊断及预后。 方法： 收集上海交通大学医学院附属第六人民医院病理科2002年8月至2025年7月诊断的16例Erdheim-Chester病患者的临床及影像学资料，对其病理学形态、免疫表型、分子病理特征及临床治疗随访情况进行回顾性分析，并复习相关文献。 结果： 16例患者中男性7例，女性9例；发病年龄38~70岁，年龄48.0（43.5，54.5）岁；2例合并朗格汉斯细胞组织细胞增生症；仅骨骼受累5例（以下肢长骨最多见），骨骼伴骨外系统（包括肺、垂体、泌尿系统、心包、大动脉）受累11例。骨内以双侧对称性、多灶弥漫性长骨骨干和干骺端的骨硬化为典型影像学表现，骨扫描见对称性摄取增高。MRI呈T1WI低信号，T2WI不均匀高信号，增强后可见明显强化。镜下见骨硬化，骨小梁间大量泡沫状、富含脂质的组织细胞或小型单核组织细胞浸润，细胞质均匀嗜酸性淡粉染，细胞核圆形或卵圆形，核仁不明显；伴有数量不等的Touton巨细胞及不同程度的纤维化。免疫组织化学均表达CD68、CD163、PGM1，不表达S-100蛋白和Langerin。5例检测到BRAF V600E基因突变。临床治疗包括骨内病灶刮除或联合激素/化疗/干扰素-α/BRAF V600E抑制剂治疗等。随访2~18年，死亡7例，带瘤生存6例，无病生存3例。 结论： Erdheim-Chester病罕见，以长骨多灶对称性受累多见，大部分患者合并系统性病变。病理结合影像有助于与炎症性病变及其他组织细胞增生性病变鉴别，整体预后差，尤其是多骨合并系统性病变患者病死率高。.
Objective: To study the clinicopathological features, immunophenotype, diagnosis, and prognosis of TSC/mTOR mutation-associated renal cell carcinoma with leiomyomatous stroma (M/TSC-RCC-LMS). Methods: Nine cases of molecularly confirmed M/TSC-RCC-LMS were collected at the Affiliated Hospital of Qingdao University (7 cases) and No. 971 Hospital of the People's Liberation Army, Qingdao, China (2 cases) between December 2011 and August 2024. Histological evaluation, immunohistochemical staining, and molecular analysis were performed, along with literature review. Results: Among the 9 patients, 1 was male and 8 were female, with their ages 48(35,55) years. Eight cases were detected during routine physical examinations, while 1 case presented with painless gross hematuria. All 9 cases were located within the renal parenchyma, presenting nodular masses with tumor diameters 2.0(1.4,2/7) cm. The lesions were well-circumscribed. The tumors were solid, grayish-white, grayish-yellow or grayish-red in color, and soft in consistency, while one case showed cystic-solid characteristics. All 9 cases exhibited thick fibromuscular pseudocapsules. In 8 cases, smooth muscle components within the capsule were observed extending into the tumor, dividing the neoplastic tissue into nodular and clustered patterns. The tumor cells were primarily arranged in tortuous, elongated branching tubular structures, with focal areas showing small amounts of delicate papillary structures containing fibrovascular cores. They also had abundant cytoplasm that was pale-staining or mildly eosinophilic, occasionally clear. The nuclei were round or irregular in shape, with some showing conspicuous nucleoli. All the 9 cases showed patchy to diffusely strong expression of CK7 (70%-100%). Carbonic anhydrase Ⅸ (CAⅨ, 6/9) and CD10 (membranous positivity, 8/9) demonstrated variable extent and intensity of expression. Glycoprotein nonmetastatic melanoma protein B (GPNMB) showed diffusely moderate to strong positivity in 7 of the 9 cases. The 9 cases were all negative for α-methylacyl-CoA racemase (AMACR), TFE3, TFEB, TCEB1, HMB45, and Melan A, with Ki-67 proliferative index ranging from 1% to 10%. Whole exome sequencing revealed mTOR gene mutations in 5 cases, concurrent TSC2 and mTOR mutations in 1 case, a TSC2 mutation in 1 case, and germline TSC1 mutations in 2 cases. Follow-up of the cases ranged from 6 to 159 months. All patients were alive at the end of the follow-up, with no recurrence or metastasis. Conclusions: M/TSC-RCC-LMS exhibits unique morphological and immunophenotypic characteristics. The tumor cells exhibit abundant pale or mildly eosinophilic cytoplasm, forming elongated, tortuous branching tubules accompanied by stromal smooth muscle components. These are typically morphological features of this renal cell carcinoma subtype. The contribute to the diagnosis and differential diagnosis of the tumor diffusely strong positivity of CK7 and the positivity of GPNMB. This type of renal cell carcinoma often demonstrates indolent biological behaviors with favorable prognosis and is expected to be newly classified as an independent subtype of renal cell carcinoma. 目的： 探讨TSC/mTOR突变相关伴有平滑肌瘤样间质肾细胞癌（TSC/mTOR mutation-associated renal cell carcinoma with leiomyomatous stroma，M/TSC-RCC-LMS）的临床病理特点、免疫表型、诊断及预后。 方法： 收集2011年12月至2024年8月青岛大学附属医院（7例）和中国人民解放军海军第九七一医院（2例）经分子学证实的M/TSC-RCC-LMS 9例，进行组织形态学观察、免疫组织化学染色及分子生物学分析，并复习相关文献。 结果： 9例患者中，男性1例，女性8例；年龄48（35，55）岁。8例因体检发现，1例因无痛性肉眼血尿就诊。大体检查：9例均位于肾实质内，结节状，肿瘤直径2.0（1.4，2.7）cm，边界清楚，除1例囊实性外，余均为实性，灰白、灰黄或灰红色，质软。镜下观察：9例均有厚的纤维肌性假包膜，8例可见包膜内平滑肌成分延伸至肿瘤内部将瘤组织分隔成结节状或片团状，瘤组织主要呈迂曲拉长的分支管状排列，局灶可见少量具有纤维血管轴心的纤细乳头状结构，瘤细胞胞质丰富，浅染或轻度嗜酸，偶尔透明，核圆形或不规则，部分可见核仁。免疫组织化学：9例CK7均呈斑片状至弥漫性强阳性表达（70%~100%），碳酸酐酶Ⅸ（CAⅨ，6/9）、CD10（膜阳性，8/9）呈范围不一、强弱不等阳性表达。糖蛋白非转移性黑色素瘤蛋白B（GPNMB）在7/9例呈弥漫性中至强阳性表达。9例α-甲酰基辅酶A消旋酶（AMACR）、TFE3、TFEB、TCEB1、HMB45和Melan A均阴性，Ki-67阳性指数1%~10%。全外显子测序：5例mTOR基因突变、1例同时发生TSC2和mTOR突变、1例TSC2突变、2例TSC1胚系突变。9例随访6~159个月，均存活，未见复发或转移。 结论： M/TSC-RCC-LMS具有独特的形态学及免疫表型特征，胞质丰富浅染或轻度嗜酸的瘤细胞形成迂曲拉长的分支管状伴间质内平滑肌成分是该类型肾细胞癌典型的形态学特征。CK7弥漫强阳性以及GPNMB阳性有助于该肿瘤的诊断和鉴别诊断。该类型肾细胞癌往往具有惰性的生物学行为，预后良好，并有望新增为独立的肾细胞癌亚型。.
Objective: To investigate the role of PTCH1 in epithelial-mesenchymal transition (EMT) and the development of chronic sinusitis with nasal polyps (CRSwNP). Methods: A total of 240 nasal polyps from CRSwNP patients were collected as experimental group, while nasal mucosa tissues from 30 patients with deviated nasal septum were collected as control group. They were all diagnosed at Beijing Chaoyang Hospital, Beijing, China from 2015 to 2023. Fifty-two CRSwNP samples were subjected to targeted next-generation sequencing. The effect of PTCH1 on the proliferation of nasal mucosal epithelial cells was detected using cell culture and the CCK8 assay. The expression of PTCH1, EMT markers (including E-cadherin, vimentin, and SMA) and the EMT-related transcription factor Snail/Slug were assessed using immunohistochemical staining. Results: Among the 240 cases of CRSwNP, 179 were male and 61 were female, with an average age of 49 (18, 72) years. Among the 30 cases of deviated nasal septum, 19 were male and 11 were female, age 42 (19, 75) years old. Targeted next-generation sequencing revealed that the mutation rate of PTCH1 in CRSwNP was 7.7% (4/52),which was significantly higher than the mutation frequency of less than 1% in the database of normal individuals. Cell culture and CCK8 assay showed that PTCH1 mutation could promote the proliferation of nasal mucosal epithelial cells. Immunohistochemical staining showed that 116 cases(116/240) CRSwNP were moderately to strongly positive for PTCH1, 114 cases (114/240) were weakly positive, and 10 cases (10/240) were negative. Two hundred and one of the 240 cases were weakly positive for E-cadherin, 4 cases (4/240) were moderately positive and 35 cases (35/240) were negative. Vimentin, SMA, Snail and Slug all showed various degrees of positive expression. Meanwhile, expression of PTCH1 was elevated in CRSwNP and correlated with the expression of Snail/Slug (r=0.776, P<0.01; r=0.767, P<0.01, respectively). Conclusions: PTCH1 mutation is an important genetic variant in CRSwNP. PTCH1 mutation activates the Hedgehog signaling pathway and promotes the EMT process by upregulating the expression of the transcription factor Snail/Slug, while PTCH1 mutation also directly promotes the proliferation of nasal mucosal epithelial cell. Both processes/pathways are involved in the development of CRSwNP and have the potential to become the targets for the future clinical therapy of CRSwNP. 目的： 探讨PTCH1诱导上皮间质转化（EMT）过程以及参与慢性鼻窦炎伴鼻息肉（CRSwNP）发生发展的作用及机制。 方法： 收集首都医科大学附属北京朝阳医院2015—2023年诊断的240例CRSwNP患者鼻息肉组织样本作为实验组；30例鼻中隔偏曲患者鼻黏膜组织作为对照组。对52例CRSwNP样本进行靶向二代测序检测基因变异。通过细胞培养及CCK8实验检测突变基因PTCH1对鼻黏膜上皮细胞增殖的影响。通过免疫组织化学染色检测突变基因PTCH1、EMT标志物（E-cadherin、波形蛋白、SMA）及EMT相关转录因子Snail/Slug在CRSwNP中的表达。 结果： 240例CRSwNP中男性179例，女性61例，年龄49（18，72）岁；30例鼻中隔偏曲中男性19例，女性11例，年龄42（19，75）岁。靶向二代测序发现CRSwNP中PTCH1的突变率为7.7%（4/52），对比正常人数据库中，该基因突变频率小于1%。细胞培养和CCK8实验显示PTCH1突变可以促进鼻黏膜上皮细胞增殖。免疫组织化学染色显示CRSwNP中116例（116/240）PTCH1呈中等及强阳性表达，114例（114/240）呈弱阳性表达，10例（10/240）阴性表达；201例（201/240）E-cadherin呈弱阳性表达，35例（35/240）呈阴性表达，4例（4/240）呈中等阳性表达。波形蛋白、SMA、Snail和Slug均呈现不同程度的阳性表达。同时，统计学分析显示PTCH1表达与转录因子Snail/Slug的表达呈正相关（r=0.776，P<0.01；r=0.767，P<0.01）。 结论： PTCH1突变是CRSwNP重要的基因变异。PTCH1突变激活Hedgehog信号通路，可能通过上调转录因子Snail/Slug的表达促进EMT过程，同时PTCH1突变促进鼻黏膜上皮细胞增殖，二者共同参与CRSwNP的发生发展，有可能成为未来临床治疗的靶点。.
Clinical pathology, as a core discipline of medical diagnosis, is experiencing unprecedented changes and challenges, with the growing acceptance of artificial intelligence in medicine, especially the introduction of foundation models in pathology. The emergence of these intelligent models will change the workflow of pathology, change the learning and diagnostic mode of pathologists, and also put forward new requirements and provide new paths for the training of clinical pathology residents. In this paper, the current status of the application of artificial intelligence in clinical pathology, its impact on residency training, the construction of the new paradigm, and the future development, will be discussed in this paper. 随着人工智能在医学领域的应用日益被接纳，尤其国内外病理大模型陆续推出，临床病理学作为医学诊断的核心学科，正经历着前所未有的变革与挑战。这些智能模型的出现将改变病理科工作流程，改变病理医师的学习和诊断模式，也对临床病理学住院医师培养提出了新要求，提供了新路径。本文将从人工智能在临床病理学中的应用现状、对住院医师培养的影响、新范式的构建以及未来发展等方面进行探讨。.
Objective: 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. Methods: 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. Results: 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. Conclusions: 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. 目的： 探讨荧光原位杂交（FISH）检测黏液样脂肪肉瘤（MLPS）DDIT3基因易位的临床应用价值并总结其中6例DDIT3隐匿性易位MLPS（CR-MLPS）的临床病理及分子遗传学特征。 方法： 收集四川大学华西医院2018年1月至2024年12月行DDIT3基因FISH检测的386例样本的临床病理信息和分子检测结果。其中6例DDIT3 FISH检测显示阴性，形态符合经典MLPS的病例加做FUS和EWSR1分离、EWSR1：：DDIT3、FUS：：DDIT3融合FISH检测，二代测序、逆转录聚合酶链反应（RT-PCR）进一步验证，总结其临床病理特征，并复习相关文献。 结果： 386例检测病例中，154例诊断为MLPS，其中DDIT3阳性病例148例，检出率96.1%。DDIT3阳性病例中，57例加做FUS和EWSR1基因易位，检出51例（51/57，89.5%）FUS易位，5例（5/57，8.8%）EWSR1易位，另1例未检出FUS和EWSR1基因易位。238例DDIT3阴性病例中，检出6例（6/238，2.5%）DDIT3 CR-MLPS，包括2例女性、4例男性，年龄32（14，55）岁，均位于四肢深部软组织。6例CR-MLPS具典型MLPS形态，呈结节状分布，富含黏液，可见分支状毛细血管。细胞呈圆形，中等大小，并见脂肪母细胞和脂肪分化细胞。肿瘤细胞S-100蛋白阴性或局灶阳性，p63（4/4）、CDK4（3/3）阴性表达。Ki-67阳性指数10%~15%。FISH检测显示3例（3/6）DDIT3呈不典型分离信号，1例（1/6）DDIT3着丝粒扩增，2例（2/6）DDIT3基因拷贝数增多。经验证4例（4/6）为EWSR1：：DDIT3融合，2例（2/6）为FUS：：DDIT3融合。6例患者均行手术切除后放疗，1例手术切除后4年复发，1例复发并转移。 结论： FISH法检测DDIT3基因易位对黏液样脂肪肉瘤的诊断具有重要价值，但仍有小部分病例因为隐匿性易位而漏检。隐匿性易位病例具有典型的黏液样脂肪肉瘤形态，其中EWSR1：：DDIT3融合亚型更为常见。.
Objective: To study the clinicopathological features and key differential diagnosis of clear cell adenocarcinoma (CCA) of the urinary tract. Methods: A retrospective analysis was performed on the clinicopathological data, immunophenotypes, and molecular test results of patients with pathologically confirmed primary CCA of the urinary tract at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China from December 2015 to September 2024. This study was supplemented by a review of the relevant literature. Results: Nine patients were included (1 male and 8 females), age 57.0 (44.5, 61.0) years old. The main symptoms were urinary tract irritation and hematuria. Th lesions were in the urethra of 5 patients and in the bladder in 4 patients. Macroscopically, the tumors were cauliflower-like, with edema and firm consistency. Microscopically, they showed mostly papillary/tubular-cystic structures, with solid sheet-like arrangements. The tumor cells showed clear or eosinophilic cytoplasm, moderate to high nuclear grade, prominent nucleoli, and frequent mitotic figures. The tumor cells also exhibited strong expression of PAX8, CK7, and HNF1-β, various positivity of Napsin A and P504s, and partial expression of SOX17, CK20, and GATA3. The Ki-67 index ranged from 30% to 70%, and p53 showed a heterogeneous expression pattern. The cells were negative for p63 and the renal cell carcinoma marker (RCC). Among the 7 cases subject to urine fluorescence in situ hybridization (FISH) testing, 5 cases showed abnormal centromeric signals. One case underwent next-generation sequencing (DNA-seq) and harbored a nonsense ARID1A mutation. Two patients underwent radical surgery, 3 total urethrectomy, and 4 palliative surgery. Four patients received postoperative chemotherapy. The follow-up ranged from 9 to 58 months: 3 patients had tumor recurrence while 2 died. Conclusions: CCA of the urinary tract is a rare and aggressive malignancy. Its histological morphology resembles that of ovarian CCA. The diagnosis should be based on a combination of morphological features and immunophenotype. It is recommended to use PAX8, CK7, HNF1-β, and Napsin A as a core immunohistochemical panel, while testing SOX17 can also help. 目的： 探讨原发于泌尿道的透明细胞腺癌（CCA）的临床病理学特征及鉴别诊断要点。 方法： 回顾性分析中山大学孙逸仙纪念医院2015年12月至2024年9月经病理确诊的原发于泌尿道CCA患者的临床病理资料、免疫表型及分子检测结果，结合相关文献进行复习；并纳入同期确诊的12例肾源性腺瘤（nephrogenic adenoma，NA）及12例原发于卵巢的CCA作为对照，比较SOX17标志物的表达差异。 结果： 共纳入9例患者（男1例，女8例），年龄57.0（44.5，61.0）岁。主要症状为泌尿道刺激症状和血尿；病灶位于尿道5例，膀胱4例。大体呈菜花状、黏膜粗糙僵硬或水肿；镜下以乳头状/管囊状结构为主，少数呈实性片状排列；肿瘤细胞胞质透亮或嗜酸性，细胞核级中-高级，核仁明显，核分裂象易见。免疫表型：肿瘤细胞强表达PAX8、CK7及HNF1-β，Napsin A与P504s呈不同程度阳性，部分表达SOX17、CK20及GATA3，Ki-67阳性指数30%~70%，p53呈强弱不等阳性表达；不表达p63及肾细胞癌标志物（RCC）。对照研究显示，SOX17在NA中呈阴性或弱阳性（12/12），在泌尿道CCA中部分呈高表达（6/9），在卵巢CCA中均呈强阳性（12/12）。分子特征：7例行尿液荧光原位杂交（FISH）检测，5例检测到染色体着丝粒位点（CSP）信号异常；1例行二代测序（DNA-seq）检出ARID1A无义突变。治疗与预后：2例行根治性手术，3例行尿道全切术，4例姑息性手术治疗；4例行术后化疗。随访9~58个月，3例复发，2例死亡。 结论： 原发于泌尿道的CCA是一种罕见的侵袭性恶性肿瘤，其组织学形态与卵巢CCA相似。诊断需结合形态学及免疫表型，推荐使用PAX8、CK7、HNF1-β及Napsin A作为核心免疫组织化学标志物组合，SOX17的表达情况也可为鉴别提供辅助参考。.
Objective: 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. Methods: 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. Results: 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 (χ2=17.694,P=0.001), tumor relapse/metastasis (χ2=4.257,P=0.039), and shorter progression-free survival (P=0.045). Conclusions: 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. 目的： 评估基于PathOrchestra病理大模型的深度学习框架预测透明细胞肾细胞癌（ccRCC）关键驱动基因（VHL、PBRM1、BAP1、SETD2）突变的性能，并基于外显子测序分析基因突变与临床病理特征和预后的关联。 方法： 收集2018年3月至2023年7月空军军医大学第一附属医院319例经病理确诊的ccRCC患者的HE染色全切片图像及配对的外显子组测序数据。基于PathOrchestra模型提取图像特征，构建注意力机制的多实例学习模型进行基因突变预测。以UNI模型作为基线对照，在独立测试集上评估性能。同时，基于测序鉴定的突变状态，分析其与患者临床病理参数及预后的关系。 结果： 在独立测试集上，PathOrchestra模型预测VHL、PBRM1、BAP1和SETD2突变的受试者工作特征曲线下面积分别为0.87、0.84、0.95和0.88，其中BAP1和SETD2的预测性能高于UNI基线模型。基于外显子测序数据的临床关联分析显示，BAP1突变与更高的WHO/ISUP分级（χ²=17.694，P=0.001）、肿瘤复发/转移（χ²=4.257，P=0.039）及更短的无进展生存期（P=0.045）显著相关。 结论： 该研究基于PathOrchestra病理大模型的深度学习方法能够有效识别ccRCC的关键驱动基因突变状态，为从病理图像推断基因变异提供了可行的方法。BAP1突变与不良预后显著相关，进一步支持该基因在ccRCC预后评估中的价值。此外，模型的可视化结果揭示了基因突变相关的形态学特征，为理解基因-形态关联提供了初步线索。.
Objective: To explore risk factors for colorectal adenoma (CRA) in non-smoking women, develop a simplified and efficient predictive model, and evaluate its performances with existing risk evaluation tools and in different time periods. Methods: Clinical data were collected from non-smoking women between November 2021 and April 2023. The positive case group included patients with colorectal polyps confirmed as CRA by pathology. Candidate variables were identified through single-factor logistic analysis (P<0.2), and prelimiarily screened using multivariate logistic regression. To obtain the optimal model, a stepwise regression method based on the AIC was employed for predictor selection, and the final prediction model was constructed with the selected predictors. A nomogram and model list were developed to visually demonstrate the contribution of each factor. The model's discrimination and calibration were evaluated and compared with existing risk assessment tools, including the Asia-Pacific Colorectal Screening (APCS) score, its modified version (MAPCS), and the "Colorectal Cancer Screening and Early Diagnosis and Treatment Program (2024 Edition)" of China. A temporal external test set was used to further evaluate the model's stability and predictive performance in a real-world clinical setting. Results: After analyzing data from 1 155 non-smoking women, the final model based on age (5 age groups) and BMI (≥24.0 kg/m²) as the main predictive factors was constructed. The model achieved area under the curve (AUC) values of 0.705 (95%CI: 0.672-0.738) in the training set (n=927) and 0.695 (95%CI: 0.629-0.762) in the validation set (n=228), with calibration curves and Hosmer-Lemeshow tests showing good fitness (P>0.05). A risk threshold of 0.400 was applied, with predicted probabilities ≥0.400 indicating high-risk and <0.400 indicating non-high-risk. The model achieved stable performance in the temporal external test set (n=272) with an AUC of 0.783 (95%CI: 0.730-0.836), further confirming the model's temporal stability and clinical utility. Compared with the existing risk evaluation tools, the values of the model in terms of discrimination are slightly higher than those of the high-risk groups in APCS, MAPCS and "Colorectal Cancer Screening and Early Diagnosis and Treatment Program (2024 Edition)", and the values in terms of specificity and accuracy are also higher. Conclusions: The simplified prediction model based on age and BMI can effectively evaluate CRA risk in non-smoking women, demonstrating high discriminatory power and temporal stability. It can provide more precise risk stratification guidance for early CRA screening with improved efficiency. 目的： 分析不吸烟女性结直肠腺瘤（CRA）的危险因素，构建简洁高效的预测模型，并评估其与现有风险评估工具的比较优势和在不同时间段人群中的效能。 方法： 收集2021年11月至2023年4月不吸烟女性资料，阳性病例组病理结果证实为CRA者。通过单因素logistic回归分析确定候选变量（P<0.2），采用多因素logistic回归分析初步筛选自变量；为得到最优模型采用最小赤池信息准则的逐步回归法进行预测变量筛选，最终筛选出预测变量构建预测模型。绘制nomogram图及建立列表，评估模型区分度及校准度，并与亚太地区结直肠肿瘤筛查评估（APCS）、其修订版（MAPCS）及《结直肠癌筛查与早诊早治方案（2024年版）》等现有风险评估工具进行比较。同时采用时间外部测试集进一步评估模型在实际临床环境中的稳定性和预测性能。 结果： 分析1 155名不吸烟女性的相关数据后，最终模型纳入年龄（分5个年龄段））和BMI（≥24.0 kg/m²）2个主要预测因素。模型在训练集（n=927）和验证集（n=228）的曲线下面积（AUC）分别为0.705（95%CI：0.672~0.738）和0.695（95%CI：0.629~0.762），校准曲线和Hosmer-Lemeshow检验均显示良好拟合性（P>0.05）。以0.400为风险阈值，预测概率≥0.400为高危组，<0.400为非高危组。模型在时间外部验证集（n=272）中表现同样稳定，AUC为0.783（95%CI：0.730~0.836），提示模型具有时间稳定性和临床实用价值。与现有风险评估工具相比，所构建模型在区分度方面的数值稍高于APCS、MAPCS和《结直肠癌筛查与早诊早治方案（2024年版）》等的高危组，且在特异度和准确度方面数值较高。 结论： 基于年龄和BMI的预测模型能有效评估不吸烟女性CRA发病风险，具有较高的区分能力和时间稳定性，可为CRA早期筛查提供更精准的风险分层指导，提高筛查效率。.
Objective: To investigate the clinicopathological features of primary pulmonary epithelioid hemangioendothelioma (PEHE). Method: Forty cases of PEHE were diagnosed from October 2010 to June 2024 at the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. A retrospective analysis was conducted on their histological features, imaging findings, immunohistochemical characteristics and molecular phenotypes. Subsequently, the clinicopathological features were summarized. The patients were followed up. Result: Of the 40 cases, there were 19 males and 21 females, age 52.5 (43.0, 62.0) years old. Most patients were admitted for respiratory symptoms, mainly cough (25/40) and expectoration (14/40). Computed tomography findings mainly showed multiple intrapulmonary nodules (33/40) and solitary nodules in 7 cases (7/40). Tumor maximum diameters ranged from 3 to 70 mm, with a median of 19 (12, 35) mm. Grossly, all lesions appeared as grayish-white nodules with ill-defined margins and mucoid cut surfaces. Microscopically, tumor cells showed centrifugal distribution around blood vessels, arranged in irregular nests; local mucoid degeneration and chondroid matrix were noted. Intracytoplasmic vacuoles with red blood cells were noted in some tumor cells, indicating primitive vascular lumen differentiation. At the molecular level, WWTR1-CAMTA1 gene fusion was identified in 36 cases and YAP1-TFE3 fusion in 4 cases. Immunohistochemical results showed diffuse positivity for CD31 (38/38), CD34 (36/40), ERG (40/40) and Fli-1 (40/40), and focal positivity for TFE-3 (4/34). Therapeutic responses of 40 patients were assessed using the Response Evaluation Criteria in Solid Tumors criteria: complete response in 4 cases (10.0%), partial response in 5 (12.5%), stable disease in 7 (17.5%), and progressive disease in 24 (60.0%). Conclusions: PEHE is a rare vascular-derived tumor, radiologically characterized by multiple bilateral pulmonary nodules. It has non-specific clinical manifestations; combined use of highly sensitive and specific endothelial markers and genetic testing helps reach the definitive diagnosis. PEHE has an overall indolent course, with long-term survival in some patients. However, multiple lesions, pleural invasion, and distant metastasis may be linked to worse prognoses. 目的： 探讨原发肺上皮样血管内皮瘤（pulmonary epithelioid hemangioendothelioma，PEHE）的临床病理学特征及预后。 方法： 收集郑州大学第一附属医院2010年10月至2024年6月诊断为PEHE的病例40例，回顾性分析组织形态学特征、影像学、免疫组织化学及分子表型，总结临床病理特征，并随访患者生存情况。 结果： 40例PEHE患者中，男性19例，女性21例，年龄52.5（43.0，62.0）岁。40例患者中多数以咳嗽（25/40）、咳痰（14/40）等呼吸道症状为主要病因入院。CT主要表现为肺内的多发结节（33/40），也可表现为单发结节（7/40），肿瘤最大径19（12，35）mm。大体均表现为灰白色结节，界限不清，切面有黏液感。镜下见肿瘤细胞以血管为中心呈离心性分布，排列成大小不一的巢团状结构，局部区域可见黏液变性及软骨样基质。部分肿瘤细胞内可见含红细胞的空泡，提示原始血管腔分化。36例存在WWTR1-CAMTA1基因融合，4例为YAP1-TFE3基因融合的分子学特征。免疫组织化学结果显示CD31（38/38）、CD34（36/40）、ERG（40/40）及Fli-1（40/40）弥漫阳性，TFE-3（4/34）局灶阳性。40例PEHE患者依实体瘤疗效评价标准RECIST1.1标准评估，其中完全缓解4例（10.0%）、部分缓解5例（12.5%）、疾病稳定7例（17.5%）、疾病进展24例（60.0%）。 结论： PEHE是一种较为罕见的血管源性肿瘤，影像学以双肺多发结节为主要特征，临床表现缺乏特异性，联合应用灵敏度和特异度高的内皮标志物及基因检测有助于诊断。PEHE病程进展相对缓慢，部分患者可长期存活，但肿瘤多发、胸膜侵犯及远处转移可能影响预后。.
Objective: To score pheochromocytoma and paraganglioma (PPGL) by using the composite pheochromocytoma and paraganglioma grading system (COPPS), to analyze the correlations of COPPS, the pheochromocytoma of the adrenal gland scaled score (PASS), and the grading system for adrenal pheochromocytoma and paraganglioma (GAPP) with tumor metastasis or recurrence and to explore the relationship between gene mutations and metastasis or recurrence in some PPGL. Methods: Clinicopathological data of the 186 paragangliomas diagnosed from January 2012 to December 2022 at Beijing Friendship Hospital, Beijing, China, the Peking University Third Hospital, Beijing, China, and the First Affiliated Hospital of Shihezi University, Shihezi, China were collected and analyzed. Predictive values of the three systems for tumor metastasis or recurrence were evaluated. Immunohistochemistry was performed using the EnVision staining method. Whole-exome sequencing was used to detect gene mutations in 15 tumors. Results: Among the 186 PPGL patients, there were 93 females and 93 males, age 49 (47, 50) years old. Metastasis or recurrence occurred in 60 cases. 34 of the tumors were located in the retroperitoneum. The maximum tumor diameter was >7 cm in 42 cases. A COPPS score ≥3 was observed in 97 cases (52.2%, 97/186), among whom 53 cases (54.6%, 53/97) experienced metastasis or recurrence. The metastasis/recurrence rate in the COPPS score≥3 group was significantly higher than that in the <3 group (χ2=46.469,P<0.001). Tumor location in the retroperitoneum, presence of large nests of cells, pathological mitosis, spindle cells, capsular invasion, and fat infiltration were all associated with a COPPS score ≥3 (χ2=18.370, 51.730, 8.914,18.750, 62.481, 19.354, all P<0.05). The sensitivity of COPPS for predicting metastasis/recurrence was 88.3% (53/60), while the specificity was 65.1% (82/126). Negative expression of SDHB was observed in 50 cases, and negative expression of S-100 protein was observed in 96 cases. DNA extraction failed to produce qualified DNA in 3 cases; among the remaining 12 tumors that were subject to DNA extraction, 739 mutations (in 658 genes) were detected, including 300 germline mutations (in 265 genes) and 439 somatic mutations (in 408 genes). Related pathogenic germline mutation genes occurred on: SDHA, MDH2, MEN1, EGLN1, RET and SDHB. All 12 patients had more than four pathogenic germline mutations. Somatic pathogenic mutation genes included ATRX, KIF1B, EPAS1, HRAS, NF1, and MAML3. Conclusions: A higher COPPS score (≥3 versus <3) is associated with a higher metastasis/recurrence rate. Its sensitivity for predicting tumor metastasis/recurrence is higher than that of GAPP, while its specificity is higher than that of PASS. The combined use of negative SDHB and S-100 protein expression with COPPS could be used to stratify the risk of metastasis/recurrence in PPGL. 目的： 运用复合性嗜铬细胞瘤/副神经节瘤分级系统（COPPS）对嗜铬细胞瘤和副神经节瘤（pheochromocytoma and paraganglioma，PPGL）进行评分，并对比分析COPPS、肾上腺嗜铬细胞瘤评分系统（PASS）、肾上腺嗜铬细胞瘤和副神经节瘤分级系统（GAPP）与肿瘤转移或复发的相关性，初步探讨部分PPGL的基因突变与转移或复发的关系。 方法： 收集2012年1月至2022年12月北京友谊医院、北京大学第三医院、石河子大学医学院第一附属医院诊断的186例副神经节瘤的临床及病理资料，按照3种系统评估其对肿瘤转移或复发的预测能力；免疫组织化学采用EnVision法染色；采用全外显子测序方法检测15例肿瘤的基因突变情况。 结果： 186例PPGL包括女性93例，男性93例，年龄49（47，50）岁。60例发生转移或复发，34例位于腹膜后，42例肿瘤最大径>7 cm，COPPS评分≥3分者97例（52.2%，97/186），其中53例（54.6%，53/97）转移复发，转移复发率显著高于<3分组，差异有统计学意义（χ²=46.469，P<0.001）。肿瘤发生于腹膜后、出现大细胞巢、病理性核分裂象、梭形细胞、包膜侵犯、脂肪浸润均与COPPS评分≥3分相关（χ²=18.370、51.730、8.914、18.750、62.481、19.354；P均<0.05）。COPPS预测转移复发的灵敏度为88.3%（53/60），特异度为65.1%（82/126）。50例显示SDHB阴性表达，96例S-100蛋白阴性表达。3例DNA提取量不合格，余12例肿瘤共检测到739个突变（658个基因），包括胚系突变300个（265个基因）和体细胞突变439个（408个基因）。相关致病性胚系突变基因包括：SDHA、MDH2、MEN1、EGLN1、RET和SDHB，12例患者均出现4个以上的致病性胚系突变。体细胞致病突变基因包括ATRX、KIF1B、EPAS1、HRAS、NF1和MAML3。 结论： COPPS评分越高（≥3分者），转移复发率越高，其预测肿瘤转移复发的灵敏度高于GAPP，特异性高于PASS。SDHB和S-100蛋白阴性表达联合COPPS可更好地用于预测PPGL转移复发风险。.
Objective: To assess the utility of histopathological and immunohistochemical characteristics in identifying POLE-mutated (POLEmut) endometrial carcinoma (EC). Methods: A total of 1 541 EC cases that underwent molecular classification at Peking University Third Hospital from January 2018 to December 2024 were included. Cases were categorized into POLEmut and non-POLEmut groups (including p53-abnormal, mismatch repair-deficient, and no specific molecular profile subtypes). A comparative analysis of histopathological features, mismatch repair (MMR) protein expression, and p53 immunostaining patterns was performed. A multivariable logistic regression-derived prediction model for POLEmut status was developed and internally validated. Results: POLEmut tumors showed significantly higher frequencies of prominent peritumoral lymphocytes (PTLs) and tumor-infiltrating lymphocytes (TILs), high-grade nuclei, bizarre nuclei, clear cytoplasm, and ambiguous morphology compared with non-POLEmut tumors (all P<0.05). Multivariable analysis identified severe PTLs/TILs infiltration, high-grade nuclei, ambiguous morphology, and clear cytoplasm as independent positive correlates for POLE mutation status, while aberrant p53 expression and MMR protein loss were negative correlates. The scoring system showed robust discrimination, with an area under the curve (AUC) of 0.867 in the training set (n=1 319) and 0.873 in the test set (n=222). At the ≥3- point cutoff, it provided a sensitivity of 80.8%, specificity of 66.3%, and negative predictive value (NPV) of 96.3% in the test set. Calibration analysis indicated good overall performance (Brier score=0.045), though local miscalibration was observed in intermediate-and low-risk subgroups. Conclusions: This POLEmut scoring system achieves high sensitivity and high NPV for initial screening of POLEmut EC. Despite a relatively low positive predictive value requiring confirmatory sequencing, it effectively enriches candidates needing POLE gene sequencing in resource-limited settings. Future multicenter validation is warranted to assess its clinical utility. 目的： 评估利用子宫内膜癌（EC）病理形态及免疫组织化学特征识别POLE突变的可行性。 方法： 纳入2018年1月至2024年12月于北京大学第三医院完成分子分型的EC病例共1 541例。评估POLE突变组与非POLE突变组（含p53异常型、错配修复缺陷型、无特异分子谱型）病例的形态学、错配修复蛋白及p53表达特征。采用Logistic回归筛选POLE突变的独立相关因子，构建评分系统并进行内部验证。 结果： POLE突变组肿瘤周围淋巴细胞（PTLs）与肿瘤浸润淋巴细胞（TILs）的重度浸润、高级别核异型、奇异核、透明胞质及模糊的形态学发生率均显著高于非POLE突变组（均P<0.05）。多因素分析确定重度PTLs/TILs浸润、高级别核、模糊的形态学及透明胞质为POLE突变状态的独立正相关因子，而异常p53表达与错配修复蛋白缺失为其独立负相关因子。基于此建立的评分系统在训练集（n=1 319）中曲线下面积（AUC）为0.867，在独立测试集（n=222）中AUC为0.873。设定阈值为3分时，测试集灵敏度为80.8%，特异度为66.3%，阴性预测值达96.3%。校准分析显示整体识别性能良好（Brier分数=0.045），但中低风险区间存在局部校准偏差。 结论： POLE突变评分系统以高灵敏度和高阴性预测值，有效初筛POLE突变病例。尽管阳性预测值较低需测序验证，但该系统可显著富集需POLE基因检测人群，适用于资源有限场景，其临床适用性有待多中心研究进一步验证。.
Objective: To investigate the clinicopathological and molecular genetic features of micronodular thymoma (MNT) and micronodular thymic carcinoma (MNC) with lymphoid stroma. Methods: Seventeen cases of micronodular neoplasms with lymphoid stroma diagnosed at the Third Affiliated Hospital of Soochow University, Changzhou, China from March 2017 to October 2024 were collected (16 cases of MNT and 1 case of MNC). Their clinicopathological data were reviewed, and their paraffin-embedded sections were stained with immunohistochemistry (IHC). Three cases of MNT and one case of MNC were also examined using next generation sequencing (NGS). Results: Of the 17 patients with MNT or MNC, 7 were male and 10 were female, age 66 (63, 72)years old. Microscopically, tumor cells were scattered in the lymphoid stroma as solid epithelioid nests. The tumor nests were relatively regular in 16 cases, and the tumor cells were mainly short spindle or oval, with bland morphology. Tumor cells of MNC showed marked cytological atypia, conspicuous nucleoli, frequent mitotic figures, and fibrous stroma. IHC showed that tumor cells of all 17 cases diffusely expressed CKpan, CK19 and CK5/6. CD5, CD117 and Glut1 were diffusely positive in the MNC case, but negative in any of the 16 MNT cases. In contrast, there were a considerable number of immature T lymphocytes positive for CD99, TdT and CD1a in the lymphoid stroma around MNT tumor nodules, but not in the MNC. Among the 3 MNT cases subjected to NGS testing, 2 cases had missense mutations in GTF2I (p.L424H), and 1 had missense mutations in HRAS (p.G13V and p.L120P). In the MNC case subjected to NGS testing, gene alterations such as a frameshift mutation in BRCA2 (p.D1451Ifs*12) and a missense mutation in TP53 (p.I195T) were detected, but not GTF2I gene mutations. Conclusions: MNC cells are more atypical than MNT cells. CD5, CD117 and Glut1 are diffusely expressed in MNC, but not in MNT. The genetic alterations in MNC are more diverse than those of MNT, but MNC lacks the characteristic GTF2I mutation of MNT. 目的： 探讨伴淋巴样间质的微结节型胸腺瘤（MNT）及伴淋巴样间质的微结节型胸腺癌（MNC）的临床病理及分子遗传学特征。 方法： 收集2017年3月至2024年10月苏州大学附属第三医院诊断的伴淋巴样间质的微结节型胸腺肿瘤（MNN）共17例（MNT 16例，MNC 1例），复习其临床病理资料，并将其石蜡切片进行免疫组织化学（IHC）染色。对其中3例MNT及1例MNC进行二代测序检测。 结果： 17例MNN患者中，7例为男性，10例为女性，年龄66（63，72）岁。显微镜下可见肿瘤细胞呈散在的实性上皮样细胞巢分布在淋巴细胞样间质中，其中16例MNT的瘤细胞巢形状规则，肿瘤细胞主要为短梭形或卵圆形，形态温和，另外1例MNC具有显著异型性，核仁明显，核分裂象易见，可见纤维带穿插于瘤巢间。IHC染色显示17例MNN肿瘤细胞弥漫表达广谱细胞角蛋白（CKpan）、细胞角蛋白（CK）19及CK5/6，但16例MNT肿瘤细胞不表达CD5、CD117及Glut1，MNC肿瘤细胞弥漫表达CD5、CD117及Glut1。且MNT肿瘤结节周围的淋巴样间质中存在较多CD99、末端脱氧核苷酸转移酶（TdT）及CD1a阳性的未成熟T淋巴细胞，但MNC未见。二代测序检测，3例MNT中有2例检测到GTF2I错义突变（p.L424H），1例检测到HRAS的错义突变（p.G13V及p.L120P）。MNC中检测到了BRCA2移码突变（p.D1451Ifs*12）、TP53错义突变（p.I195T）等基因改变，但未检测到GTF2I基因突变。 结论： MNC肿瘤细胞的异型性比MNT更明显，且弥漫表达CD5、CD117及Glut1。MNC基因改变较多样但缺乏MNT具有的特征性GTF2I基因突变。.
Objective: To investigate the clinicopathological, imaging, and molecular characteristics of mammary Rosai-Dorfman disease (RDD). Methods: A retrospective analysis was performed on four cases of primary RDD in the breast diagnosed at the First Affiliated Hospital with Nanjing Medical University from January 2018 to September 2025. Clinical, histopathological, and immunohistochemical features were reviewed, next-generation sequencing (NGS) was conducted, and the findings were discussed in the context of relevant literature. Results: Among the four cases, three were female and one was male, with ages of 54, 33, 67 and 62 years respectively. Ultrasound findings suggested inflammatory changes in one case, BI-RADS category 3 in one case, and BI-RADS category 4 in two cases. Microscopic examination revealed infiltration of lymphocytes, plasma cells, and histiocytes, with characteristic emperipolesis observed in some cases. Immunohistochemically, the lesional cells were positive for CD68, CD163, cyclin D1, S-100, and OCT2, and negative for Langerin and ALK. NGS performed in all four cases identified somatic mutations in homologous recombination repair-related genes-including RAD54L, RAD50, MRE11, and BRIP1-in three cases. One case showed somatic mutations in genes associated with signaling pathways and immune inflammation, such as AXIN2, FGF19, MYD88, NF2, and TSC2. Conclusions: RDD of the breast presents with non-specific clinical manifestations and radiologically misleading features. Its histopathological characteristics (especially the emperipolesis phenomenon) and typical immunohistochemical profile (CD68+, CD163+, cyclin D1+, S-100+, Langerin-, ALK-) may aid in differential diagnosis. The high frequency of DNA homologous recombination repair-related gene mutations in mammary RDD provides new insights into its pathogenesis and supports its classification as a clonal disease. 目的： 探讨原发性乳腺Rosai-Dorfman病的临床、影像、病理形态学及分子特征。 方法： 收集南京医科大学第一附属医院病理科2018年1月至2025年9月诊断的4例原发性乳腺Rosai-Dorfman病，分析其临床、组织病理和免疫组织化学特点，进行二代测序，并结合文献资料进行分析。 结果： 4例乳腺Rosai-Dorfman病患者中女性3例，男性1例，年龄分别为54、33、67和62岁。影像学BI-RADS分级4类2例，3类1例，提示炎性改变1例。镜下观察，淋巴细胞、浆细胞及组织细胞浸润，部分病例可见特征性的细胞内伸入现象，病变细胞免疫组织化学CD68、CD163、cyclin D1、S-100蛋白、OCT2阳性，Langerin、间变性淋巴瘤激酶（ALK）阴性。测序结果中3例检测出同源重组修复相关基因体系突变，包括RAD54L、RAD50、MRE11、BRIP1等；1例检测出AXIN2、FGF19、MYD88、NF2和TSC2等信号传导通路及免疫炎症相关基因突变。 结论： 乳腺Rosai-Dorfman病具有非特异性临床表现和影像学的迷惑性，组织学特征（尤其是细胞内伸入现象）及典型免疫组织化学表型（CD68阳性、CD163阳性、cyclin D1阳性、S-100蛋白阳性、Langerin阴性、ALK阴性）可能有助于鉴别诊断。DNA同源重组修复相关基因突变在乳腺Rosai-Dorfman病中高频出现，提示其可能为克隆性疾病，并为其发病机制提供了新视角。.
Objective: To investigate the diagnostic and prognostic value of CSPG4 and SFRP1 expression in esophageal basaloid squamous cell carcinoma (EBSCC). Methods: EBSCC cases in pathological diagnostic reports from Zhongshan Hospital, Fudan University from 2001 to 2023 were collected. Three senior pathologists independently reviewed the slides, and 81 cases of EBSCC and 55 conventional esophageal squamous cell carcinomas (ESCC) with consistent diagnoses were collected. Immunohistochemical staining for CSPG4 and SFRP1 was performed. The sensitivity and specificity of CSPG4 and SFRP1 expression in diagnosing EBSCC, as well as their correlation with prognosis, were analyzed. Results: Among the 81 EBSCC and 55 conventional ESCC cases, there were no significant differences in patient gender, age, or surgical resection time (P>0.05). The expression levels of CSPG4 and SFRP1 were significantly higher in EBSCC than in conventional ESCC (P<0.001), with no significant differences across different invasive layers (P>0.05). The receiver operating characteristic (ROC) curve for CSPG4 had an area under the curve (AUC) value of 0.952, with an optimal H-score cutoff of 75, showing a sensitivity of 92.6% and a specificity of 89.1% for diagnosing EBSCC. For SFRP1, the ROC curve had an AUC value of 0.880, with an optimal H-score cutoff of 1.5, showing a sensitivity of 81.5% and a specificity of 94.5%. When combined, CSPG4 and SFRP1 achieved a sensitivity of 80.2% and a specificity of 100% for diagnosing EBSCC. Among the 79 EBSCC cases with follow-up data, 17.7% showed high expression of both CSPG4 and SFRP1, 17.7% showed high CSPG4 but low SFRP1 expression, 13.9% showed low CSPG4 but high SFRP1 expression, and 50.6% showed low expression of both molecules. Compared to patients with low expression of both CSPG4 and SFRP1, those with high CSPG4 and low SFRP1 expression had the worst prognosis (disease-free survival: P=0.190; overall survival: P=0.031), particularly in stage Ⅰ-Ⅱ patients (disease-free survival: P=0.031; overall survival: P=0.013). Conclusions: CSPG4 and SFRP1 are primarily expressed in EBSCC. The combined application of immunohistochemical staining for these two markers can serve as a molecular indicator for the differential diagnosis and prognostic prediction of EBSCC. 目的： 探讨CSPG4和SFRP1在食管基底样鳞状细胞癌中的表达水平及其鉴别诊断和预后价值。 方法： 收集复旦大学附属中山医院2001—2023年病理诊断报告中诊断为食管基底样鳞状细胞癌的病例，3位高年资病理医师独立阅片，筛选诊断一致的基底样鳞状细胞癌81例和普通型鳞状细胞癌55例，进行CSPG4和SFRP1免疫组织化学检测，分析CSPG4和SFRP1表达对食管基底样鳞状细胞癌诊断的灵敏度和特异度以及预后的相关性。 结果： 在81例食管基底样鳞状细胞癌和55例普通型鳞状细胞癌中，患者的性别、年龄和手术切除时间差异无统计学意义（P>0.05）。基底样鳞状细胞癌中CSPG4和SFRP1的表达水平均显著高于普通型鳞状细胞癌（P<0.01），且在不同浸润层次病变中表达水平差异无统计学意义（P>0.05）。CSPG4的受试者工作特征（receiver operating characteristic，ROC）曲线下面积（area under the curve，AUC）值为0.952，最佳H-score=75，诊断基底样鳞状细胞癌的灵敏度为92.6%，特异度为89.1%。而SFRP1的ROC AUC值为0.880，最佳H-score=1.5，诊断基底样鳞状细胞癌的灵敏度为81.5%，特异度为94.5%。联合CSPG4和SFRP1，食管基底样鳞状细胞癌诊断的灵敏度为80.2%，特异度可达到100%。在79例获得随访的食管基底样鳞状细胞癌患者中，17.7% CSPG4和SFRP1均高表达，17.7% CSPG4高表达而SFRP1低表达，13.9% CSPG4低表达而SFRP1高表达，50.6%两分子均低表达。与CSPG4和SFRP1均低表达患者相比，CSPG4高表达而SFRP1低表达患者的预后最差（无病生存期：P=0.190，总生存期：P=0.031），主要表现在Ⅰ~Ⅱ期患者中（无病生存期：P=0.031，总生存期：P=0.013）。 结论： CSPG4和SFRP1主要在食管基底样鳞状细胞癌中表达，两者免疫组织化学的联合应用，可作为食管基底样鳞状细胞癌鉴别诊断和预后预测的分子指标。.
Neoadjuvant therapy has become one of the standard treatment modalities for various solid tumors. Accurate assessment of pathological response after neoadjuvant therapy is crucial to the guidance of subsequent treatment strategies and the determination of patient prognosis. Currently, expert consensus on pathological evaluation of neoadjuvant therapy efficacy has been well-established for tumors such as breast cancer and non-small cell lung cancer. However, the significant heterogeneity and multifocality of prostate cancer pose unique obstacles to establishing a standardized system for the pathological assessment for neoadjuvant hormonal therapy (NHT), The current status and challenges of pathological assessment for NHT response in prostate cancer are reviewed in this article, and the clinical value of predictive biomarkers is explored. The overarching goals are the optimize of patient stratification and the advance of precision medicine for prostate cancer. 新辅助治疗已经成为当前多种实体肿瘤的标准治疗模式之一，与之相关的病理反应评估对后续治疗策略的制订和患者预后判定至关重要。目前，针对乳腺癌、非小细胞肺癌等肿瘤已经形成较为成熟的新辅助治疗疗效病理评估专家共识。然而，前列腺癌因其显著的异质性和多灶性，使得新辅助内分泌治疗的病理反应评估面临独特挑战，迄今尚未建立标准化体系。本文旨在阐述前列腺癌新辅助内分泌治疗病理反应评估的现状与挑战，并探讨疗效预测性标志物的临床应用价值，以期筛选最大获益人群，推动前列腺癌的精准治疗。.
The traditional paradigm of pathology diagnosis faces challenges like data fragmentation and inefficiency in the era of big data and artificial intelligence, necessitating a digital transformation built upon high-quality, standardized databases. This article reviews global efforts in digital pathology database construction and details our team's pilot practice in developing a specialized breast pathology database. We share our approach to case enrollment, systematic data collection, and standardized slide digitization. Key issues, including data schema design, multi-center integration, scanning protocols, and collaborative models, are discussed to inspire industry-wide standardization and support the sustainable development of digital pathology and artificial intelligence in China. 传统病理学诊断范式在大数据与人工智能技术飞速发展的背景下，正面临数据整合困难、分析效率不足等现实挑战，其数字化转型亟需以高质量标准化数据库作为底层支撑。本文在梳理国内外数字病理库建设现状的基础上，系统介绍了本课题组在乳腺数字病理专病库构建中的初步实践经验，涵盖病例入组策略、结构化与非结构化数据的系统采集，以及数字化切片扫描的规范化流程探索。文中进一步对数据库建设中的若干关键问题，如信息条目设计、多中心数据整合路径、切片扫描策略与未来协作模式等进行了初步探讨，旨在引发对行业数据标准化与治理规范的深入思考，为我国数字病理与人工智能领域的规范化建设和可持续发展提供参考。.
Objective: To investigate the prognostic stratification value of MLH1 promoter methylation in a mismatch repair deficiency (dMMR)-type endometrioid endometrial carcinoma (EEC). Methods: A total of 338 patients with confirmed diagnosis of dMMR EEC at Third Hospital of Peking University Health Science Center, from July 2005 to June 2023 were analyzed. Based on the promoter methylation, they were classified into a dMMR methylated (dMMR MET) group (177 cases) and a dMMR nonmethylated (dMMR nonMET) group (127 cases). Somatic mutations were analyzed by targeted sequencing (196/425-gene panel), and transcriptomic differences were assessed by RNA sequencing (Master panel). We compared the clinicopathological characteristics, gene mutation/expression profiles, and molecular pathway activities systematically between the two groups. Results: Compared with the dMMR nonMET group, patients of the dMMR MET group were older significantly [(56.89±8.85) vs. (53.76±9.45) years, P=0.003] and had tumor size of larger diameters [(3.39±1.78) vs. (2.71±1.31) cm, P=0.014]. The menopausal proportion (66.9% vs. 48.8%, P=0.002) and the proportion with tumor buddings (47.5% vs. 30.4%, P=0.036) were higher. No significant differences were identified in FIGO stage, histologic grade, depth of myometrial invasion, lymphovascular invasion, or rate of lymph node metastasis (P>0.05). Mutational profiling revealed that the nonMET group had significantly higher mutation frequencies in CHD4, NF1, SMARCA4, and RET (P<0.05). Transcriptomic analysis demonstrated upregulation of immune-related genes (CCL21, CXCL2) in the MET group, and downregulation of epithelial-mesenchymal transition (EMT)-associated genes (SOX2, FOXA1). Both GO and KEGG enrichment analyses of different gene expression in the MET group demonstrated an association with the MAPK pathway. However, Hallmark pathway analysis showed no significant differences in overall pathway activity between the two groups. Survival analysis revealed no significant differences in progression-free survival (P=0.206) or overall survival (P=0.813) between the groups. Conclusions: The methylation status of the MLH1 promoter has limited value in predicting the prognosis of dMMR EEC. Molecular pathways heterogeneity between the methylated and nonmethylated subgroups suggests the necessity of integrate multi-dimensional indicators to optimize stratification strategies, instead of relying on a single epigenetic marker. 目的： 探讨MLH1启动子甲基化在错配修复缺陷（mismatch repair deficiency，dMMR）型子宫内膜样癌（endometrioid endometrial carcinoma，EEC）中的预后分层价值。 方法： 收集北京大学第三医院2005年7月至2023年6月338例经严格分子分型验证的dMMR型EEC患者，根据MLH1启动子甲基化状态分为dMMR甲基化组（177例）和dMMR非甲基化组（127例）。采用靶向测序（196/425基因Panel）分析体细胞突变，并基于RNA测序（Master panel）评估转录组差异，系统比较两组病例的临床病理、基因突变/表达谱特征及分子通路活性的差异。 结果： 甲基化组患者相较于非甲基化组患者，年龄［（56.89±8.85）岁比（53.76±9.45）岁，P=0.003］及肿瘤最大径［（3.39±1.78）cm比（2.71±1.31）cm，P=0.014］更大，绝经比例（66.9%比48.8%，P=0.002）及伴有肿瘤出芽比例（47.5%比30.4%，P=0.036）更高，两组在FIGO分期、组织学分级、肌层浸润深度、淋巴血管间隙侵犯及淋巴结转移率方面差异无统计学意义（P>0.05）。基因突变谱显示，非甲基化组CHD4、NF1、SMARCA4及RET突变频率显著升高（P<0.05）。转录组分析表明，甲基化组上调免疫调节基因（CCL21、CXCL2），下调EMT相关基因（SOX2、FOXA1）；根据差异表达基因对甲基化组行GO及KEGG富集分析均显示与MAPK通路相关。Hallmark通路分析显示两组间各通路活性差异无统计学意义。生存分析显示两组无进展生存期（P=0.206）及总生存期（P=0.813）差异无统计学意义。 结论： MLH1启动子甲基化状态对dMMR EEC预后预测价值有限。甲基化与非甲基化亚组的分子通路异质性提示需整合多维度指标优化分层策略，而非依赖单一表观遗传标志。.
Objective: To analyze the mutation status of the PIK3CA gene and the clinicopathological characteristics in lung adenocarcinoma. Methods: 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. Results: 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 (HR=0.586,95%CI=0.343-1.002,P=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). Conclusions: 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. 目的： 分析PIK3CA基因在肺腺癌中的变异情况及临床病理特征。 方法： 收集2020年1月1日至2024年12月31日经河南省直第三人民医院和河南省人民医院病理科对PIK3CA基因进行下一代测序的肺腺癌病例，收集临床病理学指标，行统计学分析，并随访。 结果： PIK3CA突变的肺腺癌患者127例，其中女性稍多（75/127，59.1%）、不吸烟者为主（95/127，74.8%），发病年龄65.0（57.0，71.0）岁；多数肺腺癌组织学分化程度呈中分化（56/127，44.1%）和低分化（44/127，34.6%），临床分期Ⅳ期多见（60/127，47.2%）。77例（77/127，60.6%）存在PIK3CA基因热点区突变，具体为第9号外显子（E9，p.E545K/Q、p.E542K）及第20号外显子（E20，p.H1047R/L/Y）；与E9突变相比，E20突变多见于淋巴结转移、脏层胸膜侵犯、气腔播散、较低分化、较高分期的人群，其预后亦较差。多因素Cox分析结果显示PIK3CA热点突变对预后无显著影响［HR=0.586，95%置信区间（CI）=0.343~1.002，P=0.051］。105例（105/127，82.7%）共存其他基因突变，其中72例（72/105，56.7%）伴EGFR突变，62例靶向治疗后，11例发生耐药，耐药机制多为继发EGFR基因第20号外显子突变（9/11）。 结论： PIK3CA突变的肺腺癌在性别、年龄、吸烟史、分化程度及临床分期方面具有独特的临床病理学特征，获得性耐药的肺腺癌可伴随PIK3CA基因突变，但PIK3CA突变并非肺腺癌患者靶向耐药的主要机制。.