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Pseudoinvasion and squamous metaplasia/morules in colorectal adenomatous polyp: a case report and literature review 大肠腺瘤性息肉中的假性浸润和鳞状化生/小瘤:病例报告和文献综述
IF 2.6 3区 医学 Q2 PATHOLOGY Pub Date : 2024-09-17 DOI: 10.1186/s13000-024-01535-9
Li Shi, Huamin Li, Shulian Li, Songyan Lin, Ying Wu
Submucosal pseudoinvasion and squamous metaplasia (SM) are incidental and special morphological findings in colorectal adenomas, and both can mimic invasive carcinoma. The coexistence of these two findings further increases the risk of misdiagnosis, posing a great diagnostic challenge to pathologists. From 1979 to 2022, only 8 cases have been reported, which was extremely rare. In this report, we presented a case of sigmoid colon adenoma accompanied by pseudoinvasion and SM. Additionally, relevant literature was analyzed to summarize the clinical and pathological characteristics. A 51-year-old Chinese male patient presented with fresh blood after defecation. Electronic colonoscopy revealed multiple polyps, which were removed using a snare and subjected to high-frequency electrocoagulation resection. The largest polyp, located in the sigmoid colon, was a thick pedunculated and lobulated polyp with a maximum diameter of 2.8 cm. The surface of the polyp showed slight ruggedness and redness, and it was sent for pathological examination. Grossly, the polyp had a lobulated and slightly rough surface. Microscopically, it showed a tubulovillous adenoma with focal high-grade dysplasia and mucosal muscle hyperplasia. Glandular elements were observed in the submucosal layer, forming a well-defined lobular structure. Some of the glands displayed cystic change, and focal SM could be seen within the adenoma. SM could manifest as discrete solid cell nests of varying sizes or cribriform-morular-like structures. Immunohistochemical staining showed that SM cells were diffusely positive for cytokeratin 5/6 (CK5/6); p40, p63, and cytokeratin 20 (CK20) were negative; while caudal type homeobox 2 (CDX2) was weakly positive. β-catenin showed abnormal nuclear expression, and an extremely low Ki67 proliferation index was observed. Coexistence of SM and pseudoinvasion in colorectal adenomas is highly rare. It is more commonly observed in males and tends to occur in the sigmoid colon. It primarily manifests in tubulovillous adenoma and tubular adenoma, with a majority of cases exhibiting a pedicle. Histologically, it is similar to invasive lesions. The cystic dilation of the submucosal glands, hemosiderin deposition, and the presence of a lamina propria around the submucosal glands without adjacent desmoplastic reaction, suggest pseudoinvasion rather than cancer. The bland cytological morphology and Immunohistochemical markers play a crucial role in distinguishing SM from true invasive lesions.
粘膜下假性浸润和鳞状化生(SM)是结直肠腺瘤中偶然出现的特殊形态学发现,两者均可模拟浸润性癌。这两种发现的并存进一步增加了误诊的风险,给病理学家的诊断带来了巨大挑战。从 1979 年到 2022 年,仅有 8 例报道,极为罕见。在本报告中,我们介绍了一例伴有假性浸润和 SM 的乙状结肠腺瘤。此外,我们还分析了相关文献,总结了其临床和病理特征。一名 51 岁的中国男性患者在排便后出现鲜血。电子结肠镜检查发现多发性息肉,使用套管切除息肉并进行高频电凝切除。最大的息肉位于乙状结肠,是一个厚梗和分叶状息肉,最大直径为 2.8 厘米。息肉表面略有凹凸不平和发红,被送去进行病理检查。从外观上看,息肉呈分叶状,表面略微粗糙。显微镜下,息肉呈管状腺瘤,伴局灶性高度发育不良和粘膜肌肉增生。在粘膜下层观察到腺体成分,形成轮廓清晰的分叶状结构。部分腺体呈囊性改变,腺瘤内可见局灶性SM。SM可表现为大小不等的离散实心细胞巢或楔形瘤样结构。免疫组化染色显示,SM细胞的细胞角蛋白5/6(CK5/6)呈弥漫阳性;p40、p63和细胞角蛋白20(CK20)呈阴性;而尾型同源染色体2(CDX2)呈弱阳性。β-catenin的核表达异常,Ki67增殖指数极低。结直肠腺瘤中同时存在 SM 和假性浸润的情况非常罕见。这种情况更常见于男性,而且往往发生在乙状结肠。它主要表现为管状腺瘤和管状腺瘤,大多数病例有蒂。组织学上,它与浸润性病变相似。粘膜下腺体的囊性扩张、血色素沉积以及粘膜下腺体周围固有层的存在而无邻近的脱鳞反应,表明是假性浸润而非癌症。平淡的细胞学形态和免疫组化标记在区分 SM 和真正的浸润性病变中起着至关重要的作用。
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引用次数: 0
Model for detecting metastatic deposits in lymph nodes of colorectal carcinoma on digital/ non-WSI images 在数字/非 WSI 图像上检测结直肠癌淋巴结转移沉积物的模型
IF 2.6 3区 医学 Q2 PATHOLOGY Pub Date : 2024-09-16 DOI: 10.1186/s13000-024-01547-5
Talat Zehra, Sarosh Moeen, Mahin Shams, Muhammad Raza, Amna Khurshid, Asad Jafri, Jamshid Abdul-Ghafar
Colorectal cancer (CRC) constitutes around 10% of global cancer diagnoses and death due to cancer. Treatment involves the surgical resection of the tumor and regional lymph nodes. Assessment of multiple lymph node demands meticulous examination by skilled pathologists, which can be arduous, prompting consideration for an artificial intelligence (AI)-supported workflow due to the growing number of slides to be examined, demanding heightened precision and the global shortage of pathologists. This was a retrospective cross-sectional study including digital images of glass slides containing sections of positive and negative lymph nodes obtained from radical resection of primary CRC. Lymph nodes from 165 previously diagnosed cases were selected from Agha Khan University Hospital, from Jan 2021 to Jan 2022. The images were prepared at 10X and uploaded into an open source software, Q path and deep learning model Ensemble was applied for the identification of tumor deposits in lymph node. Out of the 87 positive lymph nodes detected by AI, 73(84%) were true positive and 14(16%) were false positive. The total number of negative lymph nodes detected by AI was 78. Out of these, 69(88.5%) were true negative and 9 (11.5%) were false negative. The sensitivity was 89% and specificity 83.1%. The odds ratio was 40 with a confidence interval of 16.26–98.3. P-value was < 0.05 (< 0.0001). Though it was a small study but its results were really appreciating and we encourage more such studies with big sample data in future.
结直肠癌(CRC)约占全球癌症诊断和癌症死亡人数的 10%。治疗包括手术切除肿瘤和区域淋巴结。由于需要检查的切片数量越来越多,对精确度的要求越来越高,而且全球病理学家短缺,因此需要考虑采用人工智能(AI)支持的工作流程。这是一项回顾性横断面研究,包括从原发性 CRC 根治性切除术中获得的含有阳性和阴性淋巴结切片的玻璃载玻片的数字图像。2021 年 1 月至 2022 年 1 月期间,研究人员从阿迦汗大学医院选取了 165 个既往确诊病例的淋巴结。图像以 10 倍放大,上传到开源软件 Q path,并应用深度学习模型 Ensemble 来识别淋巴结中的肿瘤沉积物。在人工智能检测出的 87 个阳性淋巴结中,73 个(84%)为真阳性,14 个(16%)为假阳性。人工智能检测出的阴性淋巴结总数为 78 个。其中 69 个(88.5%)为真阴性,9 个(11.5%)为假阴性。灵敏度为 89%,特异性为 83.1%。几率比为 40,置信区间为 16.26-98.3。P值小于0.05(小于0.0001)。虽然这是一项小型研究,但其结果确实令人赞赏,我们鼓励今后开展更多此类大样本数据研究。
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引用次数: 0
Clinicopathological characteristics and genetic features of young and senior Ewing sarcoma patients 年轻和高龄尤文肉瘤患者的临床病理特征和遗传特征
IF 2.6 3区 医学 Q2 PATHOLOGY Pub Date : 2024-09-16 DOI: 10.1186/s13000-024-01548-4
Jiali Li, Yuan Ji
Ewing sarcoma (EwS) is a highly malignant and heterogeneous tumor. Exploring clinicopathological characteristics and genetic features of EwS is critical for prognosis and treatment regimen. Clinicopathological characteristics and genetic features of young (≤ 30y) and senior (> 30y) EwS patients were analyzed based on histology, phenotype, and next-generation sequencing (NGS) detection. The young group (18/36) presented nontypical EwS histological morphology, whereas the senior group (18/36) presented typical morphology. The prognosis of the young group was found to be worse compared with the senior group for patients without metastasis at the initial diagnosis. DNA- and RNA-based NGS was conducted on 20 extraosseous EwS patients. 16/20 samples demonstrated EWSR1-FLI1 fusion and 4/20 demonstrated EWSR1-ERG fusion. However, 13/16 EWSR1-FLI1fusions were detected both in DNA- and RNA-based NGS, 1/16 was detected only at the DNA level, and 2/16 were detected only at the RNA level. An analysis of the genetic profiles of the EWSR1-FLI1 cases revealed that the young group was inclined to couple with more copy number variations (CNV), such as CCND1, CDK4 amplification, and fusion variations, such as CHEK1-EWSR1, SLIT2-EWSR1, and EWSR1-FAM76B fusion. The senior group was more likely to have SNV or Indel mutations, such as EPHA3 and STAG2 mutations. Moreover, patients with more CNV abnormalities had a worse prognosis than those with predominantly SNP variants. In addition, compared with the senior group, the young group had significantly higher CyclinD1 protein expression. Clinicopathological characteristics and genetic features in young and senior EwS patients differed significantly. Targeting cell cycle dysregulation based on age subgroup may be a potential therapeutic strategy for Ewing sarcoma.
尤文肉瘤(EwS)是一种高度恶性的异质性肿瘤。探索EwS的临床病理特征和遗传学特征对预后和治疗方案至关重要。根据组织学、表型和新一代测序(NGS)检测结果,分析了年轻(≤30 岁)和高龄(>30 岁)EwS 患者的临床病理特征和遗传特征。年轻组(18/36)呈现非典型 EwS 组织学形态,而高龄组(18/36)呈现典型形态。对于初诊时没有转移的患者,年轻组的预后比年长组差。对 20 例骨膜外 EwS 患者进行了基于 DNA 和 RNA 的 NGS 研究。16/20 份样本显示 EWSR1-FLI1 融合,4/20 份显示 EWSR1-ERG 融合。然而,13/16 例 EWSR1-FLI1 融合在基于 DNA 和 RNA 的 NGS 中均被检测到,1/16 例仅在 DNA 水平被检测到,2/16 例仅在 RNA 水平被检测到。对EWSR1-FLI1病例遗传特征的分析表明,年轻组倾向于伴有更多的拷贝数变异(CNV),如CCND1、CDK4扩增,以及融合变异,如CHEK1-EWSR1、SLIT2-EWSR1和EWSR1-FAM76B融合。高龄组更有可能出现SNV或Indel突变,如EPHA3和STAG2突变。此外,与主要存在SNP变异的患者相比,有更多CNV异常的患者预后更差。此外,与高龄组相比,年轻组的CyclinD1蛋白表达量明显更高。年轻和高龄EwS患者的临床病理特征和遗传特征存在明显差异。针对年龄亚组的细胞周期失调可能是治疗尤文肉瘤的一种潜在策略。
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引用次数: 0
Navigating the diagnostic gray zone: a challenging case of pancreatic high-grade neuroendocrine neoplasm 探索诊断灰色地带:一例具有挑战性的胰腺高级别神经内分泌肿瘤病例
IF 2.6 3区 医学 Q2 PATHOLOGY Pub Date : 2024-09-12 DOI: 10.1186/s13000-024-01546-6
Brooke Mullen, Albert L. Sy, Priscila Dias Goncalves, M. Lisa Zhang
Grade 3 neuroendocrine tumor (G3 PanNET) and poorly differentiated neuroendocrine carcinoma (PanNEC) of the pancreas are considered distinct entities from a biological and prognostic perspective but may have overlapping features complicating a definitive diagnosis. A 52-year-old female presented with a pancreatic body mass and liver lesions. Initial biopsies showed variable lower- and higher-grade morphologies and modestly elevated Ki67 proliferation index up to 30%, leading to a diagnosis of G3 PanNET. The patient underwent everolimus treatment followed by surgical resection, revealing a complex tumor with features of both G3 PanNET and PanNEC, including admixed well- and poorly differentiated morphologies, modestly elevated hotspot Ki67 of 28%, retained ATRX/DAXX expression, and loss of RB expression. The final diagnosis rendered was “high-grade neuroendocrine neoplasm” with discussion of both entities in the differential. Post-operatively, the patient remains alive with stable metastases. This case highlights the diagnostic complexities of distinguishing G3 PanNET and PanNEC even with the support of ancillary immunohistochemical and molecular studies. In addition, such cases raise the possibility that G3 PanNET and PanNEC may lie on a spectrum of disease with potential biological overlap.
从生物学和预后角度来看,胰腺 3 级神经内分泌肿瘤(G3 PanNET)和分化不良神经内分泌癌(PanNEC)被认为是不同的实体,但它们可能有重叠的特征,从而使明确诊断变得复杂。一名 52 岁的女性因胰腺体块和肝脏病变就诊。最初的活检显示低级别和高级别形态不一,Ki67增殖指数略有升高,最高达30%,诊断为G3 PanNET。患者接受了依维莫司治疗,随后进行了手术切除,结果发现该肿瘤非常复杂,同时具有 G3 PanNET 和 PanNEC 的特征,包括好分化和差分化形态混杂、热点 Ki67 略微升高 28%、ATRX/DAXX 表达保留以及 RB 表达缺失。最终诊断为 "高级别神经内分泌肿瘤",并在鉴别中讨论了这两种实体。术后,患者仍然存活,转移情况稳定。该病例凸显了区分 G3 PanNET 和 PanNEC 的诊断复杂性,即使有辅助免疫组化和分子研究的支持。此外,此类病例还提出了一种可能性,即G3 PanNET和PanNEC可能处于一个疾病谱上,具有潜在的生物学重叠。
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引用次数: 0
Post-transplant lymphoproliferative disorders after allogeneic hematopoietic stem cell transplantation: a case report, meta-analysis, and systematic review. 同种异体造血干细胞移植后淋巴增生性疾病:病例报告、荟萃分析和系统综述。
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2024-09-07 DOI: 10.1186/s13000-024-01544-8
You-Yuan Su, Ya-Fei Yu, Zhen-Yu Yan, Ya-Jing Zhao, Jian-Wei Lou, Feng Xue, Miao Xu, Qi Feng, Xue-Bin Ji, Xiao-Yuan Dong, Wen Wang, Chuan-Fang Liu, Jun Peng, Xin-Guang Liu

Background: Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein-Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood.

Objectives: We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years.

Methods: We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI).

Results: The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47-0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15-0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83-0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56-0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31-0.87) and 49.0% (95% CI: 0.31-0.68), respectively.

Conclusions: This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.

背景:移植后淋巴增生性疾病(PTLD)是实体器官移植或异体造血干细胞移植(allo-HSCT)后出现的罕见但严重的并发症,病情发展迅速,死亡率高。原发性中枢神经系统(CNS)-PTLD 在组织病理学上很少被发现。此外,EBV DNA拷贝在CNS-PTLD中的诊断价值仍鲜为人知:目的:我们在此报告一例异基因造血干细胞移植后的单形性EBV相关中枢神经系统-PTLD(弥漫大B细胞淋巴瘤,DLBCL)病例,并进行荟萃分析以评估近年来PTLD治疗策略的疗效:我们提供了一份病例报告,内容包括一名原发性 CNS-PTLD 患者的临床表现、诊断、治疗和预后。此外,我们还对 431 例异体 HSCT 后 PTLD 患者的临床特征进行了系统回顾和荟萃分析。我们评估了PTLD治疗的主要治疗方案和结果,包括利妥昔单抗、化疗、自体或人类白细胞抗原(HLA)匹配的EBV特异性细胞毒性T淋巴细胞输注(EBV-CTLs)/供体淋巴细胞输注(DLI):荟萃分析显示,单用利妥昔单抗的总反应率为69.0%(95% CI:0.47-0.84),利妥昔单抗加化疗的总反应率为45.0%(95% CI:0.15-0.80),利妥昔单抗加EBV-CTLs/DLI的总反应率为91.0%(95% CI:0.83-0.96)。PTLD治疗后的完全应答(CR)率为67.0%(95% CI:0.56-0.77)。此外,6个月和1年总生存率(OS)分别为64.0%(95% CI:0.31-0.87)和49.0%(95% CI:0.31-0.68):该病例突出表明,中枢神经系统-PTLD急需有效、低毒的治疗方案。我们的荟萃分析表明,利妥昔单抗联合EBV-CTLs/DLI可能是治疗allo-HSCT后PTLD的有利策略。
{"title":"Post-transplant lymphoproliferative disorders after allogeneic hematopoietic stem cell transplantation: a case report, meta-analysis, and systematic review.","authors":"You-Yuan Su, Ya-Fei Yu, Zhen-Yu Yan, Ya-Jing Zhao, Jian-Wei Lou, Feng Xue, Miao Xu, Qi Feng, Xue-Bin Ji, Xiao-Yuan Dong, Wen Wang, Chuan-Fang Liu, Jun Peng, Xin-Guang Liu","doi":"10.1186/s13000-024-01544-8","DOIUrl":"10.1186/s13000-024-01544-8","url":null,"abstract":"<p><strong>Background: </strong>Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein-Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood.</p><p><strong>Objectives: </strong>We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years.</p><p><strong>Methods: </strong>We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI).</p><p><strong>Results: </strong>The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47-0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15-0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83-0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56-0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31-0.87) and 49.0% (95% CI: 0.31-0.68), respectively.</p><p><strong>Conclusions: </strong>This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.</p>","PeriodicalId":11237,"journal":{"name":"Diagnostic Pathology","volume":"19 1","pages":"122"},"PeriodicalIF":2.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TRPS1, a sensitive marker for different histological and molecular types of breast cancer. TRPS1,不同组织学和分子类型乳腺癌的敏感标记物。
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2024-09-06 DOI: 10.1186/s13000-024-01542-w
Change Kong, Baohua Yu, Rui Bi, Xiaoli Xu, Yufan Cheng, Wentao Yang, Ruohong Shui

Objectives: We explored Trichorhinophalangeal syndrome type 1 (TRPS1) expression in special types of breast carcinoma, and analyzed the correlation between TRPS1 and androgen receptor (AR) expression in triple-negative breast cancer (TNBC).

Methods: TRPS1 expression was analyzed in 801 patients with special types of breast carcinoma. A total of 969 TNBC were used to analyze the correlation between the expression of TRPS1 and AR. TRPS1 expression was evaluated in 1975 cases of breast cancer with different molecular types.

Results: A total of 801 special types of breast cancers were stained with TRPS1.TRPS1 was positive in 100% (63/63) of mucinous carcinoma, 100% (7/7) adenoid cystic carcinomas (4 classic adenoid cystic carcinomas and 3 solid-basaloid adenoid cystic carcinomas), 100% (4/4) tubular carcinomas, 100% (2/2) secretory carcinomas, and 99.59% (243/244) invasive lobular carcinomas, 99.26% (267/269) invasive micropapillary carcinomas, 97.44% (38/39) ER-positive neuroendocrine tumors, 94.44% (34/36) metaplastic breast carcinomas (MBCs), 63.73% (65/102) apocrine carcinomas. TRPS1 was negative in all triple-negative neuroendocrine carcinomas (0/7).TRPS1 was positive in 92.86% (26/28) of metastatic special types of breast cancer. TRPS1 and AR expression were analyzed in 969 cases of TNBC. 90.40% were positive for TRPS1, and 42.41% were positive for AR. A significant inverse correlation between TRPS1 and AR expression was shown in TNBC (p < .001). TRPS1 showed a higher positive rate (93.13%) in TNBC compared to GATA binding protein 3 (GATA3), gross cystic disease fluid protein 15 (GCDFP-15) and forkhead box transcription Factor C 1 (FOXC1).

Conclusions: In conclusion, our study demonstrated that TRPS1 is a highly sensitive marker for most special types of breast carcinoma. TRPS1 was positive in 63.73% of apocrine carcinomas. TRPS1 and AR expression was inversely correlated in TNBC.

研究目的我们探讨了毛细血管畸形综合征1型(TRPS1)在特殊类型乳腺癌中的表达,并分析了TRPS1与三阴性乳腺癌(TNBC)中雄激素受体(AR)表达的相关性:方法:分析了801例特殊类型乳腺癌患者的TRPS1表达情况。方法:对801例特殊类型乳腺癌患者的TRPS1表达情况进行分析,其中969例TNBC患者的TRPS1表达与AR表达之间存在相关性。对1975例不同分子类型的乳腺癌进行了TRPS1表达评估:TRPS1在100%(63/63)粘液腺癌、100%(7/7)腺样囊性癌(4例典型腺样囊性癌和3例实基性腺样囊性癌)、100%(4/4)管状癌、100%(2/2)分泌性癌和99.59%(243/244)浸润性小叶癌、99.26%(267/269)浸润性微乳头状癌、97.44%(38/39)ER 阳性神经内分泌肿瘤、94.44%(34/36)变性乳腺癌(MBC)、63.73%(65/102)分泌性癌。在所有三阴性神经内分泌癌(0/7)中,TRPS1均为阴性;在92.86%(26/28)的转移性特殊类型乳腺癌中,TRPS1呈阳性。对969例TNBC进行了TRPS1和AR表达分析。90.40%的TRPS1阳性,42.41%的AR阳性。在 TNBC 中,TRPS1 和 AR 表达之间存在明显的反相关性(p 结论:TRPS1 和 AR 表达之间存在明显的反相关性:总之,我们的研究表明,TRPS1 是大多数特殊类型乳腺癌的高度敏感标记物。63.73%的分泌型乳腺癌中 TRPS1 呈阳性。在 TNBC 中,TRPS1 与 AR 表达呈反相关。
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引用次数: 0
Identification of HDAC10 as a candidate oncogene in clear cell renal carcinoma that facilitates tumor proliferation and metastasis. 确定 HDAC10 为透明细胞肾癌的候选癌基因,它能促进肿瘤增殖和转移。
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2024-09-05 DOI: 10.1186/s13000-024-01493-2
Luojia Yang, Qin Wei, Xinran Chen, Yang Yang, Qingbo Huang, Baojun Wang, Xin Ma

Background: Clear cell renal cell carcinoma (ccRCC) remains one of the most lethal urological malignancies even though a great number of improvements in diagnosis and management have achieved over the past few decades. Accumulated evidence revealed that histone deacetylases (HDACs) play vital role in cell proliferation, differentiation and apoptosis. Nevertheless, the biological functions of histone deacetylation modification related genes in ccRCC remains poorly understood.

Method: Bulk transcriptomic data and clinical information of ccRCC patients were obtained from the TCGA database and collected from the Chinese PLA General Hospital. A total of 36 histone deacetylation genes were selected and studied in our research. Univariate cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression, random forest (RF) analysis, and protein-protein interaction (PPI) network analysis were applied to identify key genes affecting the prognosis of ccRCC. The 'oncoPredict' algorithm was utilized for drug-sensitive analysis. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore the potential biological function. The ssGSEA algorithm was used for tumor immune microenvironment analysis. The expression levels of HDAC10 were validated by RT-PCR and immunohistochemistry (IHC). 5-ethynyl-2'-deoxyuridine (EdU assay), CCK-8 assay, cell transwell migration and invasion assay and colony formation assay were performed to detect the proliferation and invasion ability of ccRCC cells. A nomogram incorporating HDAC10 and clinicopathological characteristics was established to predict the prognosis of ccRCC patients.

Result: Two machine learning algorithms and PPI analysis identified four histone deacetylation genes that have a significant association with the prognosis of ccRCC, with HDAC10 being the key gene among them. HDAC10 is highly expressed in ccRCC and its high expression is associated with poor prognosis for ccRCC patients. Pathway enrichment and the experiments of EdU staining, CCK-8 assay, cell transwell migration and invasion assay and colony formation assay demonstrated that HDAC10 mediated the proliferation and metastasis of ccRCC cells and involved in reshaping the tumor microenvironment (TME) of ccRCC. A clinically reliable prognostic predictive model was established by incorporating HDAC10 and other clinicopathological characteristics ( https://nomogramhdac10.shinyapps.io/HDAC10_Nomogram/ ).

Conclusion: Our study found the increased expression of HDAC10 was closely associated with poor prognosis of ccRCC patients. HDAC10 showed a pro-tumorigenic effect on ccRCC and promote the proliferation and metastasis of ccRCC, which may provide new light on targeted therapy for ccRCC.

背景:透明细胞肾细胞癌(ccRCC)仍然是致死率最高的泌尿系统恶性肿瘤之一,尽管过去几十年来在诊断和治疗方面取得了很大进步。积累的证据表明,组蛋白去乙酰化酶(HDACs)在细胞增殖、分化和凋亡过程中发挥着重要作用。然而,组蛋白去乙酰化修饰相关基因在ccRCC中的生物学功能仍鲜为人知:方法:从TCGA数据库中获取ccRCC患者的大量转录组数据和临床信息,并从中国人民解放军总医院收集。研究共选择了36个组蛋白去乙酰化基因进行研究。应用单变量cox回归分析、最小绝对收缩和选择算子(LASSO)回归分析、随机森林(RF)分析和蛋白-蛋白相互作用(PPI)网络分析来确定影响ccRCC预后的关键基因。药物敏感性分析采用了 "oncoPredict "算法。基因组富集分析(Gene Set Enrichment Analysis,GSEA)和京都基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析用于探索潜在的生物学功能。ssGSEA算法用于肿瘤免疫微环境分析。通过RT-PCR和免疫组化(IHC)验证了HDAC10的表达水平。5-乙炔基-2'-脱氧尿苷(EdU检测法)、CCK-8检测法、细胞经孔迁移和侵袭检测法以及集落形成检测法用于检测ccRCC细胞的增殖和侵袭能力。结合HDAC10和临床病理特征,建立了预测ccRCC患者预后的提名图:结果:两种机器学习算法和PPI分析发现了四个组蛋白去乙酰化基因与ccRCC的预后有显著关联,其中HDAC10是关键基因。HDAC10在ccRCC中高表达,其高表达与ccRCC患者的不良预后有关。通路富集以及EdU染色、CCK-8检测、细胞经孔迁移和侵袭检测以及集落形成检测等实验表明,HDAC10介导了ccRCC细胞的增殖和转移,并参与了ccRCC肿瘤微环境(TME)的重塑。通过整合HDAC10和其他临床病理特征,建立了临床上可靠的预后预测模型 ( https://nomogramhdac10.shinyapps.io/HDAC10_Nomogram/ )。结论:我们的研究发现,HDAC10的表达增加与ccRCC患者的不良预后密切相关。HDAC10对ccRCC具有促肿瘤作用,可促进ccRCC的增殖和转移,这可能为ccRCC的靶向治疗提供新的思路。
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引用次数: 0
Correction: Utilizing deep learning model for assessing melanocytic density in resection margins of lentigo maligna. 更正:利用深度学习模型评估恶性白斑切除边缘的黑素细胞密度。
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2024-09-05 DOI: 10.1186/s13000-024-01545-7
Jan Siarov, Darshan Kumar, John Paoli, Johan Mölne, Martin Gillstedt, Noora Neittaanmäki
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引用次数: 0
The role of stathmin expression in the differential diagnosis, prognosis, and potential treatment of ovarian sex cord-stromal tumors. Stathmin表达在卵巢性索间质肿瘤的鉴别诊断、预后和潜在治疗中的作用。
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2024-08-30 DOI: 10.1186/s13000-024-01541-x
Adam Šafanda, Michaela Kendall Bártů, Romana Michálková, Marián Švajdler, Tetiana Shatokhina, Jan Laco, Radoslav Matěj, Gábor Méhes, Jana Drozenová, Jitka Hausnerová, Zuzana Špůrková, Jozef Škarda, Mária Hácová, Monika Náležinská, Pavel Dundr, Kristýna Němejcová

Background: Stathmin, a cytosolic microtubule-destabilizing phosphoprotein involved in the regulation of mitosis, is widely expressed in various malignancies and acts as an adverse prognostic factor. Our research analyzed its immunohistochemical expression on a large cohort of ovarian sex cord-stromal tumors, evaluating its potential utility in differential diagnosis, prognosis, and therapeutic application.

Methods: We examined 390 cases of ovarian sex cord-stromal tumors including 281 adult granulosa cell tumors (AGCT), 5 juvenile granulosa cell tumors (JGCT), 33 Sertoli-Leydig cell tumors (SLCT), 50 fibromas/thecomas (F/T), 11 Leydig cell tumors/steroid cell tumors (LCT/SterCT), 5 sex-cord stromal tumors NOS (SCST-NOS), 3 Sertoli cell tumors (SCT), and 2 sclerosing stromal tumors (ScST). Immunohistochemical analysis was performed using TMAs.

Results: Strong expression (> 50%) was observed in all cases of AGCT, JGCT, SLCT, SCST-NOS, SCT and 1 ScST. The other case of ScST exhibited mild expression (5-10%). The negative cases included exclusively F/T and LCT/SterCT, with F/T showing 24% of negative cases and LCT/SterCT comprising 64% of negative cases.

Conclusion: The results of our study indicate that stathmin is neither a prognostic marker nor suitable for the differential diagnosis of challenging cases of ovarian sex cord-stromal tumors. However, its predictive value may be theoretically significant, as a decrease in stathmin expression potentialy influences response to chemotherapy treatment.

背景:Stathmin是一种参与有丝分裂调控的细胞膜微管稳定磷蛋白,在各种恶性肿瘤中广泛表达,是一种不良预后因素。我们的研究分析了其在大量卵巢性索间质肿瘤中的免疫组化表达,评估了其在鉴别诊断、预后和治疗应用中的潜在作用:我们研究了 390 例卵巢性索-基质肿瘤,包括 281 例成人颗粒细胞瘤(AGCT)、5 例幼年颗粒细胞瘤(JGCT)、33 例绒毛膜-Leydig 细胞瘤(SLCT)、50 例纤维瘤/肉瘤、50个纤维瘤/肉瘤(F/T)、11个Leydig细胞瘤/类固醇细胞瘤(LCT/SterCT)、5个性索间质瘤NOS(SCST-NOS)、3个Sertoli细胞瘤(SCT)和2个硬化性间质瘤(ScST)。使用 TMA 进行了免疫组化分析:在所有 AGCT、JGCT、SLCT、SCST-NOS、SCT 和 1 例 ScST 中均观察到强表达(> 50%)。另一例 ScST 表现为轻度表达(5%-10%)。阴性病例仅包括 F/T 和 LCT/SterCT,其中 F/T 占阴性病例的 24%,LCT/SterCT 占阴性病例的 64%:我们的研究结果表明,stathmin既不是预后标志物,也不适合用于卵巢性索间质肿瘤疑难病例的鉴别诊断。然而,它的预测价值在理论上可能是有意义的,因为stathmin表达的减少可能会影响对化疗治疗的反应。
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引用次数: 0
Correction: Integrating bioinformatics and machine learning methods to analyze diagnostic biomarkers for HBV-induced hepatocellular carcinoma. 更正:整合生物信息学和机器学习方法,分析 HBV 诱导的肝细胞癌的诊断生物标志物。
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2024-08-29 DOI: 10.1186/s13000-024-01543-9
Anyin Yang, Jianping Liu, Mengru Li, Hong Zhang, Xulei Zhang, Lianping Wu
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引用次数: 0
期刊
Diagnostic Pathology
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