Human pathology最新文献_第5页

Continuous cast-like intrabiliary extension of biliary neoplasm associated with mass-forming invasive carcinoma may be a hitherto poorly-described progression of intraductal tubulopapillary neoplasm of the bile duct 胆道肿瘤的连续铸型胆道内延伸与肿块形成的浸润性癌相关，可能是迄今为止尚未描述的胆管内管状乳头状肿瘤的进展。

IF 2.6 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2025-12-01 DOI: 10.1016/j.humpath.2025.105908

Yasuni Nakanuma , Yuko Kakuda , Hiroyuki Matsubayashi , Takuma Oishi

引用次数: 0

Information for Authors 作者信息

IF 2.6 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2025-12-01 DOI: 10.1016/S0046-8177(25)00284-9

引用次数: 0

Inside front cover - Masthead 内前盖-报头

IF 2.6 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2025-12-01 DOI: 10.1016/S0046-8177(25)00278-3

引用次数: 0

Porto-sinusoidal vascular disease–like alterations in transplant liver biopsies: A clinicopathologic observation of transplant-associated portal vasculopathy 移植肝活检中门窦血管病变样改变：移植相关门静脉病变的临床病理观察

IF 2.6 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2025-11-24 DOI: 10.1016/j.humpath.2025.105984

Binny Khandakar, Albina Joldoshova, Xuchen Zhang

Objective

Non-cirrhotic portal hypertension (NCPH) encompasses hepatic vascular disorders without cirrhosis, now grouped under porto-sinusoidal vascular disease (PSVD). While PSVD features are well described in native livers, their significance in the liver transplant setting remains unclear and may present diagnostic challenges. This study aimed to investigate PSVD-like histologic alterations in liver allografts and their clinical relevance.

Design

We retrospectively analyzed 95 liver biopsies from 43 transplant recipients (2020–2022). Biopsies were reviewed for PSVD-specific features (obliterative portal venopathy [OPV], nodular regenerative hyperplasia [NRH], incomplete septal fibrosis) and nonspecific features (portal tract abnormalities, architectural disturbance, mild perisinusoidal fibrosis, non-zonal sinusoidal dilatation). Clinical data, including liver function tests (LFTs) and rejection status, were recorded.

Results

Among 95 biopsies, 37% showed OPV, 33% NRH, and 16% incomplete septal fibrosis. Nonspecific findings were frequent with portal tract abnormalities in 99%, sinusoidal dilatation in 68%, and architectural disturbance in 67%. PSVD alterations appeared more common at longer post-transplant intervals but showed no significant association with acute cellular rejection or abnormal LFTs.

Conclusions

PSVD-like histologic alterations are common in post-transplant biopsies which do not correlate with acute cellular rejection or liver function abnormalities. These findings suggest the presence of PSVD-like alterations is likely multifactorial and may be better characterized as transplant-associated poral vasculopathy rather than true PSVD. Recognizing these changes in the transplant setting is essential to avoid misinterpretation and ensure accurate diagnosis. An evidence-based terminology and well-defined criteria for the diagnosis of PSVD are needed.

目的非肝硬化门脉高压（NCPH）包括无肝硬化的肝血管疾病，现在归为门窦血管疾病（PSVD）。虽然PSVD的特征在原生肝脏中得到了很好的描述，但它们在肝移植环境中的意义尚不清楚，可能会给诊断带来挑战。本研究旨在探讨同种异体肝脏移植后psvd样组织学改变及其临床意义。我们回顾性分析了43名移植受者（2020-2022）的95份肝活检。活检检查psvd特异性特征（闭塞性门静脉病变[OPV]、结节性再生增生[NRH]、不完全性间隔纤维化）和非特异性特征（门道异常、结构紊乱、轻度窦周纤维化、非区域性窦扩张）。记录临床数据，包括肝功能检查（LFTs）和排斥反应状态。结果95例活检中，OPV占37%，NRH占33%，不完全性间隔纤维化占16%。非特异性表现常见，99%为门道异常，68%为窦状窦扩张，67%为结构紊乱。PSVD改变在移植后较长时间间隔内更为常见，但与急性细胞排斥反应或LFTs异常无显著相关性。结论spsvd样组织学改变在移植后活检中常见，与急性细胞排斥反应或肝功能异常无关。这些发现表明PSVD样改变的存在可能是多因素的，可能更好地表征为移植相关的门静脉病变，而不是真正的PSVD。认识到移植环境中的这些变化对于避免误解和确保准确诊断至关重要。需要一个基于证据的术语和明确的PSVD诊断标准。

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引用次数: 0

Immune profiling may improve risk stratification in early-stage colorectal carcinoma 免疫谱分析可能改善早期结直肠癌的风险分层

IF 2.6 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2025-11-23 DOI: 10.1016/j.humpath.2025.105987

Ruben Oganesyan , Berk Kaan Aktas , Soo Hyun Lee , Amaya Pankaj , Omer Yilmaz , Deepa Patil , Vikram Deshpande , Osman Yilmaz

Treatment decisions for pT1 colorectal cancer often rely on traditional histologic features, but these may incompletely predict metastatic risk. We evaluated whether features of the tumor immune microenvironment could enhance risk stratification, particularly in distinguishing indolent from aggressive disease. We analyzed 116 pT1 colorectal carcinomas, including 94 AJCC Stage I tumors (non-metastatic) and 22 AJCC Stage III/IV tumors (advanced/metastatic). Clinical, histologic, and molecular features, such as tumor grade, vascular invasion, perineural invasion, tumor budding, tumor deposits, and mismatch repair (MMR) status, were assessed. Immune profiling using tissue microarrays and digital image analysis included CD8, FOXP3, CD163, PD-L1, LAG3, HLA-I, HLA-II, and beta-2-microglobulin (B2M). Advanced-stage tumors (Stage III/IV) more frequently showed high-risk histologic features, including lymphovascular invasion (40.9 % vs. 8.6 %, p = 0.007), intramural venous invasion (27.3 % vs. 3.2 %, p = 0.0015), extramural venous invasion (13.6 % vs. 0 %, p = 0.0061), and tumor deposits (mean 0.23 vs. 0.00, p < 0.001). Cribriform morphology was also more common in advanced-stage tumors (38.5 % vs. 8.2 %, p = 0.015). Immune profiling revealed significantly higher densities of CD8⁺ T-cells (503.15 vs. 326.58 cells/mm², p = 0.010), PD-L1⁺ immune cells (90.79 vs. 12.68, p = 0.011), and higher tumor B2M expression (0.21 vs. 0.05, p = 0.020) in AJCC stage I tumors, while the other examined immune biomarkers revealed no significance. While the overall impact of the immune microenvironment remains unclear, this study suggests that combining immune profiling of CD8⁺ T-cell infiltration, PD-L1–positive immune cells, and tumor B2M expression may be useful as an adjunct to conventional histologic assessment to improve prognostic accuracy and guide management of early colorectal cancer.

pT1期结直肠癌的治疗决策通常依赖于传统的组织学特征，但这些特征可能不能完全预测转移风险。我们评估了肿瘤免疫微环境的特征是否可以增强风险分层，特别是在区分惰性和侵袭性疾病方面。我们分析了116例pT1结直肠癌，包括94例AJCC I期肿瘤（非转移）和22例AJCC III/IV期肿瘤（晚期/转移）。评估临床、组织学和分子特征，如肿瘤分级、血管侵犯、神经周围侵犯、肿瘤出芽、肿瘤沉积和错配修复（MMR）状态。使用组织芯片和数字图像分析的免疫谱包括CD8、FOXP3、CD163、PD-L1、LAG3、HLA-I、HLA-II和β -2微球蛋白（B2M）。晚期肿瘤（III/IV期）更多地表现出高危组织学特征，包括淋巴血管侵犯（40.9% vs. 8.6%, p = 0.007）、静脉内侵犯（27.3% vs. 3.2%, p = 0.0015）、静脉外侵犯（13.6% vs. 0%, p = 0.0061）和肿瘤沉积（平均0.23 vs. 0.00, p < 0.001）。筛状形态在晚期肿瘤中也更为常见（38.5%比8.2%,p = 0.015）。免疫分析显示，AJCC I期肿瘤中CD8+ t细胞密度（503.15 vs 326.58细胞/mm2， p = 0.010）、PD-L1+免疫细胞密度（90.79 vs 12.68, p = 0.011）和肿瘤B2M表达（0.21 vs 0.05, p = 0.020）较高，而其他检测的免疫生物标志物无显著性差异。虽然免疫微环境的总体影响尚不清楚，但本研究表明，结合CD8+ t细胞浸润、pd - l1阳性免疫细胞和肿瘤B2M表达的免疫谱分析，可能有助于作为常规组织学评估的辅助手段，提高早期结直肠癌的预后准确性和指导治疗。

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引用次数: 0

Sarcomatoid carcinoma of the prostate – A single institution experience with emphasis on molecular genetic findings 前列腺肉瘤样癌-强调分子遗传学发现的单一机构经验。

IF 2.6 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2025-11-22 DOI: 10.1016/j.humpath.2025.105988

Burak Tekin , Lagnajita Datta , Ramin Zargham , William R. Sukov , John C. Cheville , Loren Herrera Hernandez , Stephen A. Boorjian , R. Jeffrey Karnes , Sounak Gupta , Rafael E. Jimenez

Objectives

Sarcomatoid carcinoma of the prostate (SCP) is a rare neoplasm known for its diagnostic difficulties and aggressive clinical course. Given the paucity of literature on its molecular landscape, we aimed to investigate a cohort of SCP, using a multi-modal approach.

Methods

Our surgical pathology archive was queried for patients diagnosed with SCP (2006–2022), followed by re-review of archived slides. For each case, a panel of immunohistochemical stains (including programmed death-ligand 1 [PD-L1] clones SP142, SP263, and 22C3) was performed on a representative block. Fluorescence in situ hybridization (FISH) was used to evaluate chromosomes 10 (including PTEN) and 17 (including TP53). All cases were evaluated using a next-generation sequencing (NGS) panel.

Results

Eight patients were included. Three (37.5 %) had a prior history of acinar adenocarcinoma, while a concomitant adenocarcinoma was present in five patients (62.5 %). The median duration of follow-up was 20.5 months. Seven patients (87.5 %) presented with or developed systemic metastases during follow-up. At last follow-up, 6 patients (75 %) were dead of disease. Three of the 7 cases (42.9 %) assessed for PD-L1 expression showed some staining. The most common pathogenic alterations identified by NGS involved TP53 (n = 5), followed by APC, BRCA2, CHECK2, CTNNB1, and RB1 (n = 1, each). On FISH testing, copy number changes involving chromosome 10 and 17 were found in 80 % and 60 % of the cases, respectively.

Conclusions

This study sheds light on the molecular landscape of SCP, which may be valuable to elucidate the prognostic and therapeutic implications for this uncommon disease.

目的：前列腺肉瘤样癌（SCP）是一种罕见的肿瘤，以其诊断困难和侵袭性临床过程而闻名。鉴于缺乏关于其分子景观的文献，我们旨在使用多模式方法调查SCP队列。方法：查询我院2006-2022年诊断为SCP的患者的手术病理档案，然后重新审查存档的切片。对于每个病例，在具有代表性的块上进行一组免疫组织化学染色（包括程序性死亡配体1 [PD-L1]克隆SP142， SP263和22C3）。采用荧光原位杂交技术（FISH）对10号染色体（包括PTEN）和17号染色体（包括TP53）进行鉴定。所有病例均采用下一代测序（NGS）面板进行评估。结果：纳入8例患者。3例（37.5%）既往有腺泡腺癌病史，5例（62.5%）合并腺癌。中位随访时间为20.5个月。7例（87.5%）患者在随访期间出现或发生全身转移。末次随访6例（75%）病死。7例患者中有3例（42.9%）的PD-L1表达出现染色。NGS发现的最常见的致病改变涉及TP53 (n=5)，其次是APC、BRCA2、CHECK2、CTNNB1和RB1（各n=1）。在FISH检测中，涉及10号染色体和17号染色体的拷贝数变化分别在80%和60%的病例中被发现。结论：本研究揭示了SCP的分子格局，这可能对阐明这种罕见疾病的预后和治疗意义有价值。

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引用次数: 0

Conventional FLCN-mutated tumor: a retrospective study of 5 cases with emphasis on diagnostic challenges 常规flcn突变肿瘤：5例回顾性研究，重点是诊断挑战。

IF 2.6 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2025-11-22 DOI: 10.1016/j.humpath.2025.105986

Liangbin Wan , Bin Xie , Qi Li , Qiang Ma , Ying Huang , Zhongliang Hu , Junming Feng , Kuo Tong

Background

Conventional FLCN-mutated tumors (c-FMTs) occur in Birt-Hogg-Dubé syndrome (BHD), posing diagnostic challenges due to their overlapping histology with chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO).

Methods and results

Clinicopathological analysis, immunohistochemistry, fluorescence in situ hybridization, and whole exome sequencing (WES) were performed in this study. This cohort comprised 4 males and 1 female with ages from 31 to 69 years (median: 53 years) and tumor diameters from 0.8 to 3.5 cm (median: 2.6 cm). Four of 5 cases showed a solitary lesion macroscopically. These cases were initially diagnosed as ChRCC (n = 3), RO (n = 1), and eosinophilic vacuolated tumor (EVT, n = 1) and displayed variable nested, acinar, solid structures, and mixtures of oncocytic and pale/clear cells, lacking marked tubules, cysts, and papillae in nonconventional FMT. All tumors exhibited mutually exclusive FOXI1 and L1CAM staining. L1CAM was negative in ChRCCs (10/10) and most ROs (7/8), but positive in low grade oncocytic tumors (5/5) and EVT (1/1). WES identified (likely) pathogenic FLCN mutations in all cases and biallelic inactivation of FLCN was detected in 4 (80 %) of 5 cases. Copy number analysis revealed no characteristic chromosomal loss of ChRCCs. Although metachronous TFE3-traslocation RCC occurred in 1 of 4 patients, all patients remained disease-free, except for 1 patient alive with tumors.

Conclusions

Conventional FMTs are indolent tumors, harboring hybrids of likely multiple cell populations. These tumors are usually misdiagnosed as sporadic ChRCCs or ROs. The panel of CK7, CD117, FOXI1, and L1CAM is useful for the diagnosis of c-FMTs.

背景：传统的flcn突变肿瘤（c-FMTs）发生在birt - hogg - dub综合征（BHD）中，由于其与嫌色性肾细胞癌（ChRCC）和肾嗜癌细胞瘤（RO）的组织学重叠，给诊断带来了挑战。方法和结果：本研究采用临床病理分析、免疫组织化学、荧光原位杂交和全外显子组测序（WES）。该队列包括4名男性和1名女性，年龄从31岁到69岁（中位数：53岁），肿瘤直径从0.8到3.5厘米（中位数：2.6厘米）。5例中有4例在宏观上表现为单发病变。这些病例最初被诊断为ChRCC （n=3）、RO （n=1）和嗜酸性空泡瘤（EVT, n=1），并表现为不同的巢状、腺泡状、实体结构，以及嗜瘤细胞和苍白/透明细胞的混合物，在非常规FMT中缺乏明显的小管、囊肿和乳头状。所有肿瘤均表现出互斥的FOXI1和L1CAM染色。L1CAM在chrcc（10/10）和大多数ROs（7/8）中呈阴性，而在低级别癌细胞肿瘤（5/5）和EVT（1/1）中呈阳性。WES在所有病例中发现（可能）致病性FLCN突变，5例中有4例（80%）检测到FLCN双等位基因失活。拷贝数分析未发现chrcc的特征性染色体丢失。虽然4例患者中有1例发生了异时性tfe3易位性RCC，但除了1例存活的肿瘤患者外，所有患者均无疾病。结论：传统的FMTs是惰性肿瘤，可能包含多个细胞群的杂交。这些肿瘤通常被误诊为散发性chrcc或ROs。CK7、CD117、FOXI1和L1CAM的组合对c-FMTs的诊断是有用的。

{"title":"Conventional FLCN-mutated tumor: a retrospective study of 5 cases with emphasis on diagnostic challenges","authors":"Liangbin Wan , Bin Xie , Qi Li , Qiang Ma , Ying Huang , Zhongliang Hu , Junming Feng , Kuo Tong","doi":"10.1016/j.humpath.2025.105986","DOIUrl":"10.1016/j.humpath.2025.105986","url":null,"abstract":"<div><h3>Background</h3><div>Conventional FLCN-mutated tumors (c-FMTs) occur in Birt-Hogg-Dubé syndrome (BHD), posing diagnostic challenges due to their overlapping histology with chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO).</div></div><div><h3>Methods and results</h3><div>Clinicopathological analysis, immunohistochemistry, fluorescence in situ hybridization, and whole exome sequencing (WES) were performed in this study. This cohort comprised 4 males and 1 female with ages from 31 to 69 years (median: 53 years) and tumor diameters from 0.8 to 3.5 cm (median: 2.6 cm). Four of 5 cases showed a solitary lesion macroscopically. These cases were initially diagnosed as ChRCC (n = 3), RO (n = 1), and eosinophilic vacuolated tumor (EVT, n = 1) and displayed variable nested, acinar, solid structures, and mixtures of oncocytic and pale/clear cells, lacking marked tubules, cysts, and papillae in nonconventional FMT. All tumors exhibited mutually exclusive FOXI1 and L1CAM staining. L1CAM was negative in ChRCCs (10/10) and most ROs (7/8), but positive in low grade oncocytic tumors (5/5) and EVT (1/1). WES identified (likely) pathogenic FLCN mutations in all cases and biallelic inactivation of FLCN was detected in 4 (80 %) of 5 cases. Copy number analysis revealed no characteristic chromosomal loss of ChRCCs. Although metachronous TFE3-traslocation RCC occurred in 1 of 4 patients, all patients remained disease-free, except for 1 patient alive with tumors.</div></div><div><h3>Conclusions</h3><div>Conventional FMTs are indolent tumors, harboring hybrids of likely multiple cell populations. These tumors are usually misdiagnosed as sporadic ChRCCs or ROs. The panel of CK7, CD117, FOXI1, and L1CAM is useful for the diagnosis of c-FMTs.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"167 ","pages":"Article 105986"},"PeriodicalIF":2.6,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145587341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of gender and age on the histologic severity of metabolic syndrome associated steatohepatitis 性别和年龄对代谢综合征相关脂肪性肝炎组织学严重程度的影响

IF 2.6 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2025-11-22 DOI: 10.1016/j.humpath.2025.105985

Eesha K. Acharya , Robert Lam , Joseph K. Lim , Yanhong Deng , Dhanpat Jain

Background

Metabolic dysfunction–associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction–associated steatohepatitis (MASH), are leading causes of chronic liver disease. Although clinical studies suggest age and gender may influence disease severity, histologic data remain limited. We investigated the relationship between age, gender, and histologic features of MASH.

Methods

We retrospectively reviewed 407 liver biopsies (2012–2019) with histologic steatosis. Clinical, demographic, and laboratory data were collected. Biopsies were assessed for steatosis, inflammation, ballooning, and fibrosis, and the NAFLD activity score (NAS) was calculated. Patients were divided into four groups: women 18–50 years, men 18–50 years, women >50 years, and men >50 years. Statistical analyses included univariable and multivariable ordinal logistic regression.

Results

Younger patients (18–50 years) had higher steatosis and NAS irrespective of gender, while older patients (>50 years) had higher fibrosis scores. Fibrosis was most severe in older men (mean stage 2.41 ± 1.41), compared with younger men (1.21 ± 1.21) and younger women (1.52 ± 1.30). Severe ballooning and lobular inflammation were more frequent in women, particularly younger women. In multivariable regression, age > 50 years remained independently associated with higher fibrosis stage (OR 2.17), while gender was not significant. BMI did not differ between groups.

Conclusions

Older age is strongly associated with higher fibrosis in MASH, independent of BMI and other clinical covariates. Gender-related differences in histologic features contributed to NAS but were not statistically significant. These findings highlight age as a potentially important driver of fibrosis progression in MASH. Hormonal factors may play a role but further investigation is warranted.

代谢功能障碍相关脂肪性肝病（MASLD）及其进行性形式代谢功能障碍相关脂肪性肝炎（MASH）是慢性肝病的主要原因。尽管临床研究表明年龄和性别可能影响疾病的严重程度，但组织学数据仍然有限。我们研究了年龄、性别和MASH的组织学特征之间的关系。方法回顾性分析2012-2019年407例组织学脂肪变性肝活检病例。收集临床、人口统计学和实验室数据。活检评估脂肪变性、炎症、水肿和纤维化，并计算NAFLD活动评分（NAS）。患者分为女性18 ~ 50岁、男性18 ~ 50岁、女性50岁、男性50岁四组。统计分析包括单变量和多变量有序逻辑回归。结果年轻患者（18-50岁）的脂肪变性和NAS评分较高，与性别无关，而老年患者（50岁）的纤维化评分较高。老年男性的纤维化最严重（平均分期2.41±1.41），而年轻男性（1.21±1.21）和年轻女性（1.52±1.30）。严重的球囊和小叶炎症在女性中更为常见，尤其是年轻女性。在多变量回归中，年龄和50岁仍然与较高的纤维化分期独立相关（OR 2.17），而性别不显著。BMI在两组之间没有差异。结论年龄与MASH患者较高的纤维化密切相关，独立于BMI和其他临床协变量。与性别相关的组织学特征差异导致NAS，但没有统计学意义。这些发现强调了年龄是MASH纤维化进展的潜在重要驱动因素。激素因素可能起作用，但需要进一步调查。

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引用次数: 0

Prevalence and distribution of human papillomavirus type 16 in esophageal squamous cell carcinoma and its association with p16INK4A expression: A large-scale study in Japan 16型人乳头瘤病毒在食管鳞状细胞癌中的流行和分布及其与p16INK4A表达的关系：日本的一项大规模研究

IF 2.6 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2025-11-12 DOI: 10.1016/j.humpath.2025.105983

Kaiyuan Jiang , Hirotaka Ishida , Yusuke Taniyama , Chiaki Sato , Hiroshi Okamoto , Yohei Ozawa , Yuto Yamazaki , Hironobu Sasano , Michiaki Unno , Takashi Suzuki , Takashi Kamei

The infection rate of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) varies widely (0 %–88.9 %), and the diagnostic utility of p16^INK4A as a surrogate marker remains controversial. Moreover, the distribution of HPV infection in ESCC has not been previously investigated. Patients with ESCC who underwent esophagectomy without neoadjuvant therapy between 2007 and 2022 were included in this study. Three formalin-fixed, paraffin-embedded blocks (oral side, tumor, and esophagogastric junction (EGJ)) were collected. p16^INK4A expression was assessed by immunohistochemistry (positivity defined as a labeling index of ≥10 %), whereas HPV type 16 DNA was detected by polymerase chain reaction. The distribution of HPV distribution was also assessed. In total, 158 patients were analyzed. p16^INK4A was detected in 19.0 % (30/158) and HPV DNA in 3.8 % (6/158) of tumor samples. The sensitivity and positive predictive value of p16^INK4A immunohistochemistry for detecting HPV DNA were 100 % and 20.0 %, respectively. HPV DNA was also detected in 3.6 % (5/137) of the oral side and 2.7 % (4/146) of EGJ samples. Infectious mapping revealed a random distribution pattern across the three anatomical regions. This large-scale study demonstrated a low prevalence of HPV infection in ESCC and indicated that p16^INK4A immunohistochemistry may aid in reducing the risk of missing patients with HPV-positive tumors. Notably, the random-like distribution of HPV DNA across the three anatomical sites suggests partial viral clearance by the host immune response. These findings underscore the potential for false-negative results in biopsy specimens obtained from non-infected regions in otherwise HPV-positive patients.

人乳头瘤病毒（HPV）在食管鳞状细胞癌（ESCC）中的感染率差异很大（0%-88.9%），p16INK4A作为替代标志物的诊断效用仍存在争议。此外，HPV感染在ESCC中的分布以前没有调查过。本研究纳入了2007年至2022年间接受食管切除术且未接受新辅助治疗的ESCC患者。收集三个福尔马林固定石蜡包埋块（口腔侧、肿瘤和食管胃交界处（EGJ））。p16INK4A的表达通过免疫组织化学检测（阳性定义为标记指数≥10%），而HPV 16型DNA通过聚合酶链反应检测。同时评估HPV的分布情况。总共分析了158例患者。在19.0%（30/158）的肿瘤样本中检测到p16INK4A，在3.8%（6/158）的肿瘤样本中检测到HPV DNA。p16INK4A免疫组化检测HPV DNA的敏感性为100%，阳性预测值为20.0%。口腔侧和EGJ侧分别有3.6%（5/137）和2.7%（4/146）检出HPV DNA。传染图谱显示了三个解剖区域的随机分布模式。这项大规模研究表明，ESCC中HPV感染的患病率较低，并表明p16INK4A免疫组化可能有助于降低HPV阳性肿瘤患者缺失的风险。值得注意的是，HPV DNA在三个解剖部位的随机分布表明宿主免疫反应部分清除了病毒。这些发现强调了从hpv阳性患者的非感染区获得的活检标本中假阴性结果的可能性。

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引用次数: 0

Integrating computational pathology and multi-transcriptomics to characterize glioblastoma heterogeneity and identify prognostic biomarkers 整合计算病理学和多转录组学表征胶质母细胞瘤异质性和确定预后生物标志物。

IF 2.6 2区医学 Q2 PATHOLOGY

Human pathology

Pub Date : 2025-11-11 DOI: 10.1016/j.humpath.2025.105982

Ying Dai , Chenglong Shi , Kai Zhao , Jinshan Tie , Kun Lian , Wenhu Li , Yan Li , Yuhao Wang , Ninghui Zhao

Background

Glioblastoma (GBM) remains a lethal brain cancer with median survival of 12–15 months, hindered by pronounced heterogeneity. Integrating histopathological, molecular, and microenvironmental data is critical for improving outcomes.

Methods

Pathological features from TCGA-GBM whole-slide images were combined with bulk RNA-seq (pan-apoptosis genes), scRNA-seq (monocytes), and spatial transcriptomics. A machine learning model (Lasso + plsRcox) was developed using 60 % training and 40 % validation data.

Results

The prognostic model achieved C-indices of 0.75 (training) and 0.616 (validation). High-risk patients had shorter median survival (14 vs. 28 months; HR = 3.87, P = 0.001). BCL2A1 was identified as a key risk gene (r = 0.42 with risk score) and correlated with poor survival (11 vs. 26 months, P = 0.004) and abnormal nuclear morphology. scRNA-seq revealed BCL2A1+ monocytes (12.3 % of cells) with high stemness and enriched angiogenesis pathways. Spatial analysis showed these monocytes localize at the invasive front (21.4 %) near endothelial cells, promoting VEGF signaling.

Conclusion

Integration of computational pathology and multi-transcriptomic data identified BCL2A1+ monocytes as drivers of angiogenesis and progression. This approach offers a prognostic tool and potential therapeutic targets for GBM.

背景：胶质母细胞瘤（GBM）仍然是一种致命的脑癌，由于明显的异质性，中位生存期为12-15个月。整合组织病理学、分子和微环境数据对于改善预后至关重要。方法：将TCGA-GBM全切片的病理特征与大体积RNA-seq（泛凋亡基因）、scRNA-seq（单核细胞）和空间转录组学相结合。使用60%的训练数据和40%的验证数据开发了机器学习模型（Lasso+plsRcox）。结果：预后模型的c指数分别为0.75（训练）和0.616（验证）。高危患者的中位生存期较短（14个月vs 28个月；HR = 3.87, P = 0.001）。BCL2A1被确定为关键风险基因（r = 0.42，风险评分），与生存差（11个月vs 26个月，P = 0.004）和核形态异常相关。scRNA-seq显示BCL2A1+单核细胞（12.3%的细胞）具有高干性和丰富的血管生成途径。空间分析显示，这些单核细胞定位于内皮细胞附近的侵袭前沿（21.4%），促进VEGF信号传导。结论：综合计算病理学和多转录组学数据，BCL2A1+单核细胞是血管生成和进展的驱动因素。这种方法为GBM提供了一种预后工具和潜在的治疗靶点。

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引用次数: 0