Objective: To investigate the clinicopathological features, immunophenotypic characteristics, molecular genetic profiles for an accurate diagnosis of renal tumors associated with Birt-Hogg-Dubé (BHD) syndrome. Methods: Clinicopathological data from 10 patients with BHD syndrome-associated renal tumors were collected from Ningbo Clinical Pathology Diagnosis Center (4 cases) and Ruijin Hospital, Shanghai Jiaotong University School of Medicine (5 in-house cases and 1 consultation case) from January 2015 to December 2025. Their clinical characteristics and histological features were studied and analyzed. Immunohistochemical staining and next-generation sequencing (NGS) were performed. Follow-up data were obtained and relevant literature was reviewed. Results: All 10 patients were adults, including 6 males and 4 females, with an age 57 (54, 67) years old. Seven patients had pulmonary bullae/pneumothorax and one patient had a right anterior chest wall fibroma. For the patients with renal tumor, 6 cases presented with a unilateral single tumor, 1 case with unilateral multiple tumors and 3 cases with bilateral multiple tumors (totaling 16 renal tumors). Four cases of the renal tumor were associated with multiple renal cysts. Histologically, among the 16 tumors, 10 were hybrid oncocytic/chromophobe tumors (HOCT) with the typical "mosaic" pattern, 4 with chromophobe renal cell carcinoma-like morphology, 1 with predominantly sarcomatoid morphology and focal areas of low-grade oncocytic renal tumor, and 1 renal angiomyolipoma. The immunophenotype of BHD-associated renal tumors was not specific. Immunohistochemistry revealed diffuse positive for GPNMB in all epithelial-derived renal tumors (15/15). CK7 and CD117 were focally expressed in 7/15 cases each, CD10 was focally expressed in 6/15 cases, and carbonic anhydrase Ⅸ (CAⅨ) was negative in all tumors (0/15). ALK, TFE3 and TFEB were negative. No loss of SDHB or FH expression was identified. DNA next-generation sequencing identified FLCN mutations in all cases, including 7 cases with germline FLCN mutations and 3 cases with somatic FLCN mutations. During a 9-120 months follow-up, the patient with sarcomatoid differentiation passed away 6 months after renal tumor identified, and another patient experienced relapse in the left kidney 6 years after bilateral nephron-sparing surgery. No relapse or metastasis was identified in the remaining 8 patients. Conclusions: Morphologically, BHD syndrome-associated renal tumors can mimic various low-grade oncocytic renal tumors. In addition to the classic HOCT morphology, they may also present with high-grade sarcomatoid differentiation. GPNMB is a highly sensitive marker for BHD-associated renal tumors. Molecular genetic analysis to detect FLCN mutation is the gold standard for definitive diagnosis. BHD syndrome-associated renal tumors typically show indolent biological behavior, with sarcomatoid differentiation as a morphological feature of poor prognosis.
目的:探讨原发中枢神经系统（CNS）ALK阳性组织细胞增生症（APH）的临床病理学特征。方法:对中山大学肿瘤防治中心病理科于2022—2024年间确诊的4例原发CNS APH病例（均以CNS为唯一受累部位）进行回顾性分析，包括其组织学形态、免疫表型、遗传学特征及预后，并复习相关文献。结果:例1~4患者年龄分别为2、6、14、14岁，例1和例4为男性，例2和例3为女性。组织学形态显示，在炎性细胞背景中见中等至大的肿瘤细胞，胞质丰富、淡嗜酸性，细胞核呈卵圆形或不规则折叠，染色质细腻，核仁不明显。免疫表型方面，4例肿瘤细胞均强阳性表达CD68、CD163及ALK（D5F3）。例1、3、4通过二代测序检出KIF5B：：ALK基因融合；例2、3经荧光原位杂交（FISH）检测出ALK基因断裂。4例患者术后接受了ALK抑制剂治疗，随访截至2025年9月，均恢复良好。结论:原发CNS APH少见，其多样的组织学形态易与其他原发CNS肿瘤/病变混淆。KIF5B：：ALK融合是最常见的分子事件。目前，以ALK抑制剂为核心的靶向治疗可获得显著疗效。病理医师需充分认识其组织学形态、免疫表型以及分子改变，对于实现精准诊断、指导临床治疗及改善患者预后至关重要。
Objective: To investigate the clinicopathological characteristics, molecular genetics, treatments and prognosis of aggressive B-cell lymphomas (ABCL) with MYC gene cluster amplification. Methods: Eight cases of ABCL with MYC gene cluster amplification were collected, including 6 cases from the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China and 2 consultation cases from outside hospitals. The histomorphology, immunohistochemical profiles, and molecular genetic characteristics were analyzed. Clinical follow-up and literature review were also conducted. Results: Among the eight patients, six were male and two were female, with an age 71.5 (61.7, 74.2) years. All six in-house patients presented with abdominal pain at onset, without B symptoms. Most cases were classified as Ann Arbor stage Ⅲ-Ⅳ. Extranodal involvement occurred in 5 of the 6 in-house cases, primarily affecting the gastrointestinal tract (4/5). All initial bone marrow biopsies showed no evidence of lymphoma. One patient had a history of immunosuppression following renal transplantation. Two cases exhibited diffuse large B-cell lymphoma (DLBCL) morphology. The other six showed high-grade features, while three of them showed Burkitt lymphoma-like morphology. Except for one case of blastoid variant mantle cell lymphoma, the remaining six cases (6/7) displayed a germinal center B-cell phenotype. None of the in-house cases harbored bcl-2 or bcl-6 rearrangements as shown by fluorescence in situ hybridization. 11q alterations were identified in all but one consultation case, including gain/loss type in five cases and 11q gain in two. 11q telomere loss of heterozygosity by chromosomal microarray analysis was not detected in one of the two cases with 11q gain that was subject to the test. The duration of follow-up ranged from 5.9 to 55.5 months, with 5 patients alive at the end of the study. Conclusions: ABCL with MYC gene cluster amplification often presents high-grade morphology and gastrointestinal involvement, which strongly suggests the alteration of 11q. It seems to have a favorable prognosis.
乳腺鳞状细胞癌（BSCC）是乳腺化生性癌中的罕见亚型。BSCC在临床上常表现为生长迅速、体积较大的肿块，多为三阴性表型，总体预后较差。目前研究提示其组织起源并非单一路径，可能源自良性囊性或增生性病变中鳞状化生区域发生恶变、非特殊型浸润性癌的克隆演化以及乳房植入物相关鳞状细胞癌。病理形态以典型鳞状分化为诊断要点，肿瘤内常伴成分与受体表达的空间异质性，故需充分取材并结合免疫表型综合评估。分子层面以TP53、PIK3CA等高频体细胞突变及PI3K/AKT相关通路异常为主要特征，部分病例可见PTEN失活、HRAS-PIK3R1共突变及TERT启动子突变等事件。鉴于BSCC需与转移性鳞状细胞癌、腺鳞癌、非特殊型浸润性癌伴鳞状分化及其他化生性肿瘤严格区分，本文在综述其临床病理与分子特征基础上，提出“排除转移、确认鳞状分化、界定化生性亚型”的三步法诊断路径，以期提高诊断一致性，并为分层治疗探索提供参考。
目的:探讨儿童睾丸大细胞钙化型支持细胞瘤（LCCSCT）的临床病理学特征。方法:回顾性分析2012年1月至2025年6月徐州市儿童医院（2例）和首都医科大学附属北京儿童医院（2例）共4例儿童睾丸LCCSCT的临床资料，观察其病理组织学形态、免疫表型及分子遗传学特征，并复习相关文献。结果:例1~4均为男性患儿，无隐睾或假两性畸形，发病年龄分别为3岁3个月、6岁9个月、6岁6个月和6岁5个月。例1双侧睾丸相继受累，例2、例3和例4左侧单侧发病，均为单发病灶，肿瘤最大径分别为2.1 cm（左）/1.6 cm（右）、1.2 cm、1.8 cm、1.5 cm。临床表现为无痛性睾丸肿块，影像学检查示睾丸内混合回声伴钙化。大体观察见肿瘤切面灰黄实性、质地中等至硬、伴沙砾感。镜下观察见肿瘤细胞呈条索状、巢状或小管状排列，细胞呈卵圆形，胞质丰富且嗜酸性，核大空泡状，核仁清晰，伴钙化，局灶见黏液样间质及中性粒细胞浸润。免疫组织化学结果示4例均弥漫阳性表达α抑制素、钙视网膜蛋白及S-100蛋白，蛋白激酶A调节亚基1A（PRKAR1A）均为阴性。二代测序结果：1例检出PRKAR1A基因移码突变（p.Ser14fs）及无义突变（p.R42*），1例检出17q24.2区域杂合缺失性胚系突变（此例合并Carney综合征）。随访31~98个月，4例患儿均无病生存。结论:LCCSCT是儿童睾丸原发肿瘤中的罕见类型，多为散发，部分合并Carney综合征。组织学上存在钙化和PRKAR1A蛋白缺失表达有助于与其他类型支持细胞瘤鉴别，手术完整切除后患儿预后良好。
The pathological diagnosis of B-cell lymphomas is transitioning from traditional morphologic assessment to a multidimensional model that integrates histomorphology, immunophenotype, and genetic alterations. Establishing a standardized, stepwise clinical diagnostic pathway has become an urgent priority in precision medicine. This article systematically delineates a "four-step" integrated diagnostic pathway for B-cell lymphomas: step 1: initial screening and phenotyping, utilizing immunohistochemistry and flow cytometry to determine lineage and establish a preliminary classification; step 2: definitive diagnosis and differential diagnosis, employing gene rearrangement assays and in situ hybridization to verify clonality and identify characteristic genetic abnormalities; step 3: precision diagnostics, applying high-throughput sequencing for molecular subtyping, prognostic stratification, and targeted therapy guidance; and step 4: frontier exploration, leveraging single-cell and spatial multi-omics technologies along with artificial intelligence to address complex diagnostic challenges. It aims to help pathologists develop hierarchically structured and logically consistent molecular diagnostic approaches, promoting the translation of integrated lymphoma diagnosis from theory into clinical practice.
脉管畸形存在于多种先天性综合征中，无论是主要特征还是附加特征，都对临床和病理医师提出了重大挑战。由于其表型复杂多样，精确诊断往往较为困难，并可导致危及生命的并发症，且许多实体治疗仍不完善。为了便于识别，本文依据国际脉管异常研究学会（ISSVA）分类系统，对该类疾病进行梳理和总结，以期深化对脉管畸形相关综合征分类体系的认知。
原发性醛固酮增多症（PA）是继发性高血压最常见的病因之一，对于单侧优势PA，肾上腺切除术是首选治疗手段，术后肾上腺标本的病理诊断对确定病变功能性、评估术后疗效及指导随访管理等个体化治疗提供关键依据。目前国内PA术后病理诊断多停留于“肾上腺皮质腺瘤”或“结节性增生”等形态诊断层面，没有提供醛固酮生成病灶的功能特性，PA病理诊断应由单纯形态学描述转向以醛固酮合成功能定位为核心的规范化精准诊断。醛固酮合成酶（CYP11B2）免疫组织化学染色能够识别和确定功能性醛固酮生成病灶。HISTALDO国际共识建立了结合HE形态学和CYP11B2表达模式的标准化分型体系，将PA相关病变分为经典型病变和非经典型病变。经典型病变与较高的术后生化缓解率相关，具有明确的预后评估价值。
甲状旁腺功能亢进症是内分泌系统的常见疾病，分为原发性和继发性。在原发性甲状旁腺功能亢进症中，约5%~10%是由遗传性综合征所致。这些综合征不仅表现为甲状旁腺的病变，常累及多种内分泌器官和/或其他非内分泌器官，且具有家族遗传倾向。对于病理医师而言，准确识别这些遗传性综合征相关的甲状旁腺病变，不仅对患者的个体化治疗至关重要，也对家系筛查和遗传咨询具有指导意义。近年来，随着分子遗传学技术的发展，我们对这些疾病的认识不断深入，从传统的组织形态学观察，发展到免疫组织化学和基因测序相结合的精准诊断模式。本综述将探讨多发性内分泌腺肿瘤1型、多发性内分泌腺肿瘤2A型、多发性内分泌腺肿瘤4型、甲状旁腺功能亢进-颌骨肿瘤综合征、家族性孤立性甲状旁腺功能亢进症以及家族性低尿钙性高钙血症的分子发病机制、病理学特征及免疫组织化学表型，为临床病理诊断提供参考。
生物标志物检测是实现胃癌精准诊疗的关键环节。为规范胃癌的生物标志物检测临床实践，胃癌相关领域多学科专家联合制定本指南，通过系统检索国内外循证证据，采用GRADE法进行证据分级，并经德尔菲法达成专家共识。指南系统梳理了HER2、CLDN18.2等分子靶向治疗，以及微卫星不稳定/错配修复、PD-L1等免疫治疗相关核心标志物的检测要点与推荐意见，明确界定了检测的适用人群、检测时机，同时规范了检测方法、检测顺序等关键临床操作。此外，指南还分析了当前胃癌生物标志物检测面临的挑战，指明了未来技术与临床应用的发展方向，并着重强调了检测全程质量控制与多学科协作诊疗的重要性，为胃癌的精准诊疗提供了科学、规范的生物标志物检测依据。
目的:总结分析特发性肠系膜静脉硬化（IMP）性结肠炎患者的临床病理学特征，提高活检病理识别率。方法:收集2019年10月至2025年10月北京大学第三医院诊断的IMP结肠炎病例，回顾性分析其临床、影像、内镜及活检组织病理学特点，并复习相关文献。结果:共纳入3例IMP结肠炎患者，均为女性；年龄分别为66、63和65岁，临床表现为腹痛和/或中-重度腹泻。影像学检查均显示肠系膜血管多发钙化、结肠肠壁增厚，内镜检查可见肠黏膜呈暗紫色，例1可见全结肠多发溃疡，部分溃疡深大、形态不规则，例2和例3回盲瓣/右半结肠可见浅溃疡。活检病理组织学特征：肠黏膜固有层、黏膜下层及小血管周围胶原沉积，静脉管壁纤维化。Masson染色显示沉积的胶原呈蓝色，刚果红染色阴性。例1巨细胞病毒染色阳性。经保守治疗，随访2~73个月，患者未再诉腹痛，腹泻程度均较前缓解。结论:IMP结肠炎是罕见的肠道缺血性疾病，肠黏膜活检组织学以小血管周围胶原沉积、管壁纤维化为主要特点，精准的病理诊断对于患者的及时治疗及预后有明确的指导意义。IMP结肠炎也可合并感染，需注意辨别，以免漏诊。
患者男，35岁。2025年8月因“发现右侧腋部肿物1年”就诊，彩超提示腋部皮下存在一椭圆形无回声区，考虑表皮样囊肿可能性大。患者行肿物切除术。病理检查示真皮和皮下组织内可见组织细胞样肿瘤细胞和散在分布的印戒细胞样肿瘤细胞弥漫浸润。免疫组织化学示肿瘤细胞雄激素受体、CK7及GCDFP-15阳性。二代测序分析提示存在CDH1、PIK3CA和ERBB2基因突变。诊断为腋部原发性皮肤印戒细胞/组织细胞样癌。
报道1例新生儿巨大型先天性黑色素痣伴增生性结节的病例。患儿出生时即见枕部、背部、臀部及四肢散在灰黑色斑块，随后枕部及颈背部出现皮下肿物。组织病理显示真皮内大量形态一致的痣细胞，可见成熟梯度，无病理性核分裂象或坏死；结节区细胞密度增高，呈膨胀性生长，核分裂象偶见。免疫组织化学染色提示黑色素细胞HMB45、S-100蛋白阳性；结节区Ki-67阳性指数约5%，PRAME部分阳性，p16部分缺失，H3K27me3未缺失。全基因测序检出NRAS c.181C>A（p.Gln61Lys）突变。术后随访11个月无进展。本例凸显了增生性结节与黑色素瘤在鉴别诊断上所面临的挑战，并提示通过综合分析其组织学、免疫表型及分子遗传学特征，可帮助判断生物学行为。
Objective: To investigate the clinicopathological characteristics of Zuska's disease of the breast. Methods: A total of 315 cases of breast Zuska's disease diagnosed from December 2018 to December 2025 were collected from the Seventh Medical Center of the People's Liberation Army General Hospital, Dongzhimen Hospital of Beijing University of Chinese Medicine, and the First Affiliated Laohekou Hospital of Hubei University of Arts and Science. HE staining was performed for the specimens, and the clinicopathological characteristics of these cases were analyzed and summarized. Results: Among the 315 patients, 306 were female and 9 were male, with an age of 31.0 (23.4,38.7) years. Clinically, viscous nipple discharge was often the initial symptom. Gross examination of the resected specimens of the breast lesion showed ulceration of skin. The cut surface of the lesion revealed significantly ductal dilatation, with secretions inside the ducts. Histologically, lactiferous ducts showed cystic dilatation with squamous metaplasia and hyperplasia. The lumens contained abundant acute, chronic inflammatory cells and keratin debris. There were extensive mixed inflammatory cell infiltration and fibrosis around the ducts. In later stages, the lactiferous duct centrically, subareolar abscess was developed. Conclusions: Mammary Zuska's disease is histopathologically characterized by squamous metaplasia of the lactiferous ducts, intraductal keratin accumulation, and periductal suppurative inflammation. A small subgroup of cases may be complicated by squamous cell carcinoma.
Objective: To investigate the clinicopathological and molecular features of fibrolamellar hepatocellular carcinoma (FL-HCC). Methods: The clinicopathological and prognostic information of 9 FL-HCC cases diagnosed at the Fudan University Shanghai Cancer Center, Shanghai, China from January 2018 to December 2024 were collected and analyzed. The FL-HCC samples were examined with immunohistochemical staining, fluorescence in situ hybridization (FISH), and RNA-based next-generation sequencing (NGS). The related literature was also reviewed. Results: There were 3 males and 6 females. The patients' age was 18.0 (10.5, 26.0) years. One of the 9 patients had slightly elevated serum AFP level, and 2 patients had current infection of hepatitis B virus. Five cases occurred in the left lobe of the liver, 3 cases in the right lobe of the liver, and 1 case had multiple lesions involving both the left and right lobes. The tumor sizes ranged from 4.0 to 21.4 cm. Microscopically, neoplastic cells were mainly arranged in sheets or nests, separated by dense collagen bundles frequently arranged in cord-like or parallel lamellae. The tumor cells were large and polygonal, with abundant granular and eosinophilic cytoplasm, large vesicular nuclei, and prominent nucleoli. All tumor cells expressed CK7, HepPar-1, and Arg-1. Molecular analysis revealed that 6 cases harbored the DNAJB1::PRKACA gene fusion by NGS, while the other 3 cases showed PRKACA gene rearrangement by FISH using a break-apart probe. The follow-up period ranged from 7 to 80 months. One patient was lost to follow-up after diagnosis, 3 patients survived without recurrence, 1 patient relapsed with lung metastasis, and 4 patients died of the disease. Conclusion: FL-HCC is a rare type of hepatocellular carcinoma characterized by laminated intratumoral fibrous stroma and specific fusion (DNAJB1::PRKACA) or rearrangement of the PRKACA gene.
Objective: To investigate the clinicopathological characteristics of early gastric cardia adenocarcinoma from the tissue specimens obtained by endoscopic submucosal dissection (ESD). Methods: A retrospective study was designed on 133 patients with early cardiac gastric cancer (cardiac group) and 142 patients with early non-cardiac gastric cancer (non-cardiac group) who underwent ESD procedure at Xiangcheng County People's Hospital in Henan Province and the Pingdingshan Medical District of the 989th Hospital of the Joint Logistic Support Force from January 2012 to June 2025. The clinical, endoscopic, pathological, immunophenotypic data and prognostic factors of the two groups were systematically compared. Results: The patients in the cardiac group were older [(64.6±8.9) years vs. (62.3±9.3) years; t=2.086, P=0.038] and had tumor of a larger size, with diameters [16.0 (10.0, 26.0) mm vs. 14.0 (8.0, 22.0) mm; Z=-2.041, P=0.041] compared with those in the non-cardiac group; endoscopically, type 0-Ⅱc lesions accounted for a higher proportion in the cardiac group than in the non-cardiac group [(92/133, 69.2%) vs. (75/142, 52.8%); χ²=7.896, P=0.019]. Predominate histopathological type was well-to-moderately differentiated tubular adenocarcinoma in both groups; however, the cardiac group showed significantly higher proportions of cases with concomitant papillary adenocarcinoma [(21/133, 15.8%) vs. (11/142, 7.7%); χ²=4.321, P=0.038], mild cellular atypia [(43/133, 32.3%) vs. (30/142, 21.1%); χ²=4.421, P=0.035], surface coverage by normal epithelium [(50/133, 36.1%) vs. (21/142, 14.8%); χ²=16.580, P<0.001], surface coverage by mild atypical epithelium [(39/133, 29.3%) vs. (19/142, 13.4%); χ²=10.489, P=0.001], and coexistence with gastritis cystica profunda [(25/133, 18.8%) vs (11/142, 7.7%); χ²=7.371, P=0.007] compared with the non-cardiac group. Immunohistochemically, the cardiac group showed a higher rate of aberrant p53 protein expression than the non-cardiac group [(42/69, 60.9%) vs. (30/100, 30.0%); χ²=15.911, P<0.001]. Within the cardiac group, the MUC5AC positive rate was significantly higher in cases with aberrant p53 expression than in those with normal p53 expression [(40/42, 95.2%) vs. (19/27, 70.4%); χ²=8.201, P=0.004]. Multivariate regression analysis confirmed that aberrant p53 protein expression was independently associated with MUC5AC positivity (OR=12.22, P=0.032). Short-term follow-up [cardiac group: 36.0 (25.0, 45.5) months, non-cardiac group: 37.0 (25.8, 49.3) months] showed no statistically significant difference between the two groups (Z=1.455, P=0.146), and no recurrence or metastasis was observed in either group. Conclusions: Early cardiac gastric cancer shows the coexistence of occult histology and highly aberrant p53 protein expression, closely coupled with the gastric phenotypic marker MUC5AC, suggesting that early cardiac gastric cancer may represent a distinctive tumor subtype.
患者女，75岁。2025年12月因“左下腹疼痛伴肉眼血尿4个月”入院。泌尿系CT尿路造影（平扫+增强）提示左侧输尿管中下段管壁增厚伴强化、上尿路扩张积水，左肾实质强化减低，局部见肿瘤强化灶。患者行腹腔镜下左侧根治性肾输尿管切除术。病理示肾盂、输尿管见两枚独立肿物，相距5.0 cm；镜下见肿瘤细胞呈巢团状、实性片状浸润性生长，可见2种细胞成分：嗜碱性基底样细胞和影细胞。免疫组织化学示肿瘤细胞CKpan、β-catenin、LEF-1、CDX2、SATB2、p63、高相对分子质量细胞角蛋白（CK-H）阳性。分子检测证实存在CTNNB1基因第3外显子的突变。诊断为伴影细胞形态的浸润性高级别尿路上皮癌。
患者男，35岁。2025年12月因“发现头皮肿物1年余”就诊。患者行肿物活检术，倾向为恶性肿瘤，遂行肿物切除术。病理示肿瘤细胞呈胖梭形，多呈席纹状、编织状排列；细胞稀疏区域肿瘤细胞呈多角形，伴有硬化的背景及增生的薄壁血管。免疫组织化学示肿瘤细胞ALK弥漫阳性，CKpan、EMA、SMA、CD34、S-100蛋白、SOX-10、Stat6均为阴性。二代测序检测到CARS：：ALK基因融合。诊断为皮肤炎性肌纤维母细胞肿瘤。
确定肿瘤组织来源是肿瘤病理诊断的核心，但通过详细的常规检查后仍有少部分肿瘤无法明确原发部位，称之为不明原发肿瘤。不明原发肿瘤仅占所有肿瘤的1%~2%，但病死率高居肿瘤相关死亡第4位，是目前临床诊疗面临的重大挑战。随着人工智能技术的突破性发展与在医学中的广泛应用，它为预测肿瘤组织来源提供了创新路径。本文系统综述了基于分子数据（基因组、转录组、表观遗传组、多组学及循环分子）和基于医学图像（影像图像、病理图像）的人工智能模型在该领域的研究现状与新近进展，并讨论了当前研究面临的局限与挑战，最后对未来发展方向进行了展望。
