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Novel FOXL2 Mutation in an Ovarian Adult Granulosa Cell Tumor: Report of a Case With Diagnostic and Clinicopathologic Implications. 卵巢成人颗粒细胞瘤中的新型 FOXL2 基因突变:病例报告及诊断和临床病理学意义。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-02-19 DOI: 10.1097/PGP.0000000000001024
Agnes Nagy, Na Niu, Elena Ratner, Pei Hui, Natalia Buza

Adult granulosa cell tumor, the most common malignant ovarian sex cord-stromal tumor, harbors the characteristic mutation c.402C>G (p.C134W) in the FOXL2 gene in ~90% to 95% of cases. To date, no other variants of FOXL2 mutations have been identified in these tumors. Here we report the first case of an adult granulosa cell tumor with a novel FOXL2 point mutation c.398C>T (p.A133V) presenting in a 64-year-old postmenopausal woman. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy for atypical endometrial hyperplasia and gross examination revealed an incidental 3.2 cm right ovarian mass with a solid, bright yellow, homogeneous cut surface. Microscopically, ~30% of the tumor showed a nested growth pattern composed of uniform tumor cells with oval nuclei and a moderate amount of pale cytoplasm, while the remaining areas consisted of a bland storiform fibromatous stroma. Reticulin stain demonstrated loss of the individual pericellular network within the nested areas, while the pericellular staining pattern was retained in the background stromal component. FOXL2 sequencing analysis was performed in both components and revealed a c.398C>T (p.A133V) mutation in the nested component, whereas wild-type FOXL2 sequence was identified in the fibromatous stroma. Sections from the uterus showed a low-grade endometrioid endometrial adenocarcinoma with superficial myometrial invasion. The patient underwent adjuvant vaginal cuff brachytherapy for the endometrial carcinoma and is alive and well at 8 months follow-up. This case illustrates that new FOXL2 mutations may be detected in ovarian sex cord-stromal tumors with increasing use of routine molecular testing, adding to the complexity of the pathologic diagnosis. In the right morphologic and clinical context, a FOXL2 mutation-even if it is different from the dominant hotspot mutation c.402C>G (p.C134W)-can support the diagnosis of adult granulosa cell tumor.

成人颗粒细胞瘤是最常见的恶性卵巢性索间质瘤,约 90% 至 95% 的病例携带 FOXL2 基因的特征性突变 c.402C>G (p.C134W)。迄今为止,尚未在这些肿瘤中发现其他变异的 FOXL2 基因突变。在此,我们报告了第一例成人颗粒细胞瘤病例,患者是一名 64 岁的绝经后妇女,她的 FOXL2 基因出现了 c.398C>T (p.A133V) 点突变。患者因非典型子宫内膜增生症接受了全子宫切除术和双侧输卵管切除术,大体检查发现右侧卵巢偶然出现一个 3.2 厘米的肿块,切面呈实性、亮黄色、均质。显微镜下,约 30% 的肿瘤呈巢状生长,由均匀的瘤细胞组成,瘤细胞核呈椭圆形,有适量淡色胞质,其余区域由平淡的浆液状纤维瘤基质组成。网状纤维素染色显示,巢状区域内的单个细胞周围网络消失,而背景基质成分中保留了细胞周围染色模式。对这两种成分都进行了FOXL2测序分析,发现巢状成分中存在c.398C>T(p.A133V)突变,而在纤维瘤基质中发现了野生型FOXL2序列。子宫切片显示为低级别子宫内膜样腺癌,伴有浅表子宫肌层浸润。患者接受了子宫内膜癌的阴道袖带近距离辅助治疗,随访 8 个月后仍健在。该病例说明,随着常规分子检测的日益普及,卵巢性索间质瘤中可能会检测到新的FOXL2突变,从而增加了病理诊断的复杂性。在正确的形态学和临床背景下,FOXL2突变--即使不同于显性热点突变c.402C>G (p.C134W)--可支持成人颗粒细胞瘤的诊断。
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引用次数: 0
CXCR4 Expression and Cancer-associated Fibroblasts May Play an Important Role in the Invasion of Low-grade Endometrioid Carcinoma. CXCR4 表达和癌症相关成纤维细胞可能在低级别子宫内膜样癌的侵袭中发挥重要作用
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-01-22 DOI: 10.1097/PGP.0000000000001015
Chihiro Fukumitsu, Sakiko Sanada, Sachiko Ogasawara, Naotake Tsuda, Kenta Murotani, Mayuka Akao, Kimio Ushijima, Jun Akiba, Hirohisa Yano

Well-differentiated endometrioid carcinoma (EC) is a low-grade cancer with relatively indolent behavior. However, even with well-differentiated histology, it sometimes tends to invade extensively and shows metastatic potential, suggesting that this is a group of cancers with heterogeneous behavior. In contrast, due to its tendency for younger onset, the treatment strategy for EC frequently considers fertility preservation, highlighting the need for a more accurate evaluation of myometrial invasion through biopsy and imaging diagnostics. We previously reported the involvement of the CXCR4-CXCL12 and CXCL14 axes in EC invasion. Accordingly, we investigated whether CXCR4 expression could reflect invasive potential and explored its interaction with cancer-associated fibroblasts that produce chemokines in the tumor microenvironment. Immunohistochemical expression of CXCR4 was assessed in 71 cases of EC (14 of EC confined to the endometrium and 57 of myoinvasive EC), 6 cases of endometrial intraepithelial neoplasia, and 42 cases of noncarcinomatous conditions. CXCR4 expression was significantly higher in myoinvasive EC than in noncancerous conditions, endometrial intraepithelial neoplasia, and endometrium-confined EC. By univariate and multivariate analysis, CXCR4 expression significantly reflected myometrial invasion. CXCR4 expression in the biopsied and resected specimens correlated weakly positively. Invasion and wound-healing assays were performed culturing an EC cell line in a cancer-associated fibroblast-conditioned medium. The invasion and wound-healing potentials were dependent on CXCR4 and cancer-associated fibroblast. Our study demonstrated that CXCR4 expression is an independent factor in myometrial invasion and can support diagnostic evaluation before treatment in the biopsy sample.

分化良好的子宫内膜样癌(EC)是一种低分化癌症,症状相对较轻。然而,即使是组织学分化良好的子宫内膜样癌,有时也倾向于广泛浸润并显示出转移潜力,这表明这是一组行为异质性的癌症。相反,由于其发病年龄较小,EC的治疗策略通常会考虑保留生育能力,这就强调了通过活检和影像诊断对子宫肌层受侵情况进行更准确评估的必要性。我们以前曾报道过CXCR4-CXCL12和CXCL14轴参与了EC的侵袭。因此,我们研究了CXCR4的表达是否能反映侵袭潜力,并探讨了它与肿瘤微环境中产生趋化因子的癌症相关成纤维细胞的相互作用。对71例EC(14例局限于子宫内膜的EC和57例肌浸润性EC)、6例子宫内膜上皮内瘤变和42例非癌变病例中CXCR4的免疫组化表达进行了评估。肌层浸润性癌细胞中CXCR4的表达明显高于非癌性癌细胞、子宫内膜上皮内瘤变和子宫内膜封闭性癌细胞。通过单变量和多变量分析,CXCR4的表达明显反映了子宫肌层的侵袭情况。活检标本和切除标本中的CXCR4表达呈弱正相关。在癌症相关成纤维细胞条件培养基中培养了一个EC细胞系,进行了侵袭和伤口愈合试验。侵袭和伤口愈合潜能取决于 CXCR4 和癌相关成纤维细胞。我们的研究表明,CXCR4 的表达是子宫肌瘤侵袭的一个独立因素,可支持活检样本治疗前的诊断评估。
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引用次数: 0
A Novel EPC1 :: KDM2B Fusion in High-grade Endometrial Stromal Sarcoma. 高级别子宫内膜间质肉瘤中的新型 EPC1::KDM2B 融合体
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-03-11 DOI: 10.1097/PGP.0000000000001026
Katherine M Vroobel, Sana Khalid, Silvia Cavalchini, Ayoma D Attygalle

The spectrum of endometrial stromal sarcoma (ESS) has expanded substantially since the publication of the most recent World Health Organisation (WHO) Classification of Female Genital Tumours and the advent of widely available genomic testing. We describe a uterine mesenchymal tumor harboring a novel EPC1 :: KDM2B fusion, best classified within the umbrella of high-grade endometrial stromal sarcoma (HGESS). This tumor was composed of a uniform population of spindled cells with some myxoid stroma, a mitotic rate of up to 21/10 high-power fields, and a largely pushing margin with focal vascular invasion. Immunohistochemistry showed strong and diffuse cyclin D1 positivity while CD10, WT1, DOG1, CD117, CD34, CD99, S100, MelanA, SMA, desmin, and h-caldesmon were negative. The tumor was confined to the uterus and no recurrence has been detected thus far, albeit with a short follow-up interval of 9 mo.

自世界卫生组织(WHO)发布最新的《女性生殖器肿瘤分类》以及基因组检测广泛应用以来,子宫内膜间质肉瘤(ESS)的范围已大幅扩大。我们描述了一种携带新型EPC1::KDM2B融合体的子宫间质肿瘤,该肿瘤最好归类为高级别子宫内膜间质肉瘤(HGESS)。该肿瘤由均匀的纺锤形细胞群组成,伴有一些肌样基质,有丝分裂率高达 21/10 个高倍视野,边缘基本呈推移状,有局灶性血管侵犯。免疫组化显示细胞周期蛋白 D1 呈弥漫性强阳性,而 CD10、WT1、DOG1、CD117、CD34、CD99、S100、MelanA、SMA、desmin 和 h-caldesmon 阴性。肿瘤局限在子宫内,尽管随访时间只有短短的 9 个月,但迄今为止尚未发现复发。
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引用次数: 0
Coinactivation of the Switch/Sucrose Nonfermenting Complex SMARCA4/BRG1 and SMARCB1/INI1 in a Cervical Mixed Carcinoma: A Case Report. 宫颈混合型癌中开关/蔗糖不发酵复合物 SMARCA4/BRG1 和 SMARCB1/INI1 的共同活化:一个病例报告。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-02-19 DOI: 10.1097/PGP.0000000000001025
Yu Qi, Peng Qi, Qianlan Yao, Xiangjie Sun, Xiaoyan Zhou, Rui Bi

SMARCB1/SMARCA4-deficient malignancies of the female genital tract are rare entities, characterized by similar histologic features, such as sheet-like growth patterns and rhabdoid cells. Previous studies have shown mutually exclusive loss of SMARCA4/BRG1 and SMARCB1/INI1. Herein, we describe a unique cervical mixed carcinoma in a 77-year-old patient. The tumor consisted of 3 components, gastric-type adenocarcinoma, squamous carcinoma, and undifferentiated carcinoma. While the undifferentiated carcinoma was negtive for CK7, CK5/6 and p63, it was positive for pan-CK. DNA-based next-generation sequencing revealed a nonsense mutation in SMARCA4, copy number loss in SMARCB1, and a nonsense mutation in ARID1A. Different molecular alterations of the switch/sucrose nonfermenting complex subunits in the present case may provide further insights into the functions of the switch/sucrose nonfermenting complex in the progression of tumors.

女性生殖道SMARCB1/SMARCA4缺失性恶性肿瘤是一种罕见的实体肿瘤,具有类似的组织学特征,如片状生长模式和横纹状细胞。以往的研究表明,SMARCA4/BRG1 和 SMARCB1/INI1 的缺失是相互排斥的。在此,我们描述了一名 77 岁患者的独特宫颈混合癌。该肿瘤由胃型腺癌、鳞状癌和未分化癌三部分组成。虽然未分化癌的 CK7、CK5/6 和 p63 阴性,但泛 CK 阳性。基于DNA的新一代测序显示,SMARCA4存在无义突变,SMARCB1存在拷贝数缺失,ARID1A存在无义突变。本病例中开关/蔗糖不发酵复合体亚基的不同分子改变可能会让人们进一步了解开关/蔗糖不发酵复合体在肿瘤进展中的功能。
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引用次数: 0
Gynecologic Pathology Journal Club: A 2-year, Worldwide Virtual Learning Experience With a Focus on Mentorship and Inclusion. 妇科病理学期刊俱乐部:为期两年的全球虚拟学习体验,重点关注导师和包容。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-02-19 DOI: 10.1097/PGP.0000000000001022
Natalie Banet, Carlos Parra-Herran, Joseph T Rabban, Esther Oliva, Lora H Ellenson, Kay J Park, Naveena Singh, Kyle M Devins, Sameera Rashid, Karen L Talia

Journal clubs (JCs) are a common format used in teaching institutions to promote trainee engagement and develop skills in seeking out evidence-based medicine and critically evaluating literature. Digital technology has made JC accessible to worldwide audiences, which allows for increased inclusion of globally diverse presenters and attendees. Herein we describe the experience of the first 2 years of a virtual gynecologic pathology JC designed with the goal of providing mentorship and increasing inclusivity. JC began in a virtual format in April 2020 in response to the need for remote learning during the coronavirus disease 2019 pandemic. Each JC had 1 moderator, lasted 1 hour, featured up to 3 trainees/early-career pathologists, and covered articles on gynecologic surgical pathology/cytopathology. Trainees were recruited through direct contact with moderators and advertising through social media (eg, Twitter). A template was used for all presentations, and before presenting, live practice sessions were conducted with the moderator providing constructive feedback and evaluations were provided to presenters and attendees for feedback. Recordings of the meetings were made publicly available after the event through YouTube, a society website, and emails to registrants. Fifty-nine presenters participated, covering 71 articles. Most were trainees (53/59; 89%) from North America (33/59; 56%), with additional presenters from Asia (14/59; 24%), Australia/Oceania (5/59; 8%), Africa (4/59; 7%), and Europe (3/59; 5%). An average of 20 hours were spent per month by moderators on the selection of papers, meeting preparation, and provision of mentorship/feedback. Live events had a total of 827 attendees, and 16,138 interactions with the recordings were noted. Among those who self-identified on provided surveys, the attendees were most commonly from Europe (107/290; 37%) and were overwhelmingly practicing pathologists (275/341; 81%). The experience, including mentorship, format, and content, was positively reviewed by attendees and presenters. Virtual JC is an inclusive educational opportunity to engage trainees and early-career pathologists from around the world. The format allowed for the JC to be widely viewed by attendees from multiple countries, most being practicing pathologists. Based on feedback received, virtual JC appears to expand the medical knowledge of the attendees and empower presenters to develop their expertise and communication skills.

期刊俱乐部(JCs)是教学机构常用的一种形式,旨在促进学员的参与,培养他们寻找循证医学和批判性评估文献的技能。数字技术使全世界的受众都能参与到期刊俱乐部中来,从而使全球不同的演讲者和参与者能够更多地参与其中。在此,我们将介绍虚拟妇科病理学联合会议头两年的经验,其目的是提供指导和提高包容性。为应对 2019 年冠状病毒疾病大流行期间的远程学习需求,JC 于 2020 年 4 月开始采用虚拟形式。每次 JC 有 1 名主持人,持续 1 小时,最多有 3 名学员/职业生涯初期的病理学家参加,内容涵盖妇科手术病理学/细胞病理学方面的文章。受训人员是通过与主持人直接联系和社交媒体(如推特)广告招募的。所有演讲均使用模板,演讲前进行现场练习,由主持人提供建设性反馈意见,并向演讲者和与会者提供评估反馈。会后通过 YouTube、学会网站和发送给注册者的电子邮件公开会议录音。59 位发言人参加了会议,涉及 71 篇文章。大多数发言人是来自北美的受训人员(53/59;89%)(33/59;56%),另外还有来自亚洲(14/59;24%)、澳大利亚/大洋洲(5/59;8%)、非洲(4/59;7%)和欧洲(3/59;5%)的发言人。主持人平均每月花费 20 个小时挑选论文、筹备会议和提供指导/反馈。现场活动共有 827 人参加,记录了 16138 次互动。在提供的调查问卷中,与会者大多来自欧洲(107/290;37%),绝大多数是执业病理学家(275/341;81%)。与会者和演讲者对包括指导、形式和内容在内的体验给予了积极评价。虚拟联合会议是一个包容性很强的教育机会,可吸引来自世界各地的受训人员和早期职业病理学家参与。通过这种形式,来自多个国家的与会者(其中大多数是执业病理学家)可以广泛观看联合会议。根据收到的反馈,虚拟联合会议似乎扩展了与会者的医学知识,并增强了演讲者发展专业知识和交流技能的能力。
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引用次数: 0
Adenoid Cystic Carcinoma of the Vulva and Vagina: A Clinicopathologic, Immunohistochemical, and Molecular Characterization of Five Cases. 外阴和阴道腺样囊性癌:五例病例的临床病理学、免疫组织化学和分子特征。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-01-22 DOI: 10.1097/PGP.0000000000001016
Delfim Doutel, Diana Venda, Fernanda Silva, Carmo Martins, Ana Félix, Joana Ferreira

Adenoid cystic carcinoma (ACC) is a rare neoplasm most frequently observed in the salivary glands, that can occur in other organs, including the vulva and vagina. Oncogenic mechanisms involving MYB, NFIB , and MYB-NFIB rearrangements have been described, but evidence in the vulva and vagina remains scarce. Our aim is to report the clinicopathologic features, immunohistochemical, and molecular findings in a series of vulvar and vaginal ACCs. Five cases were included. Medical records and slides were reviewed. Formalin-fixed paraffin-embedded material was available in 4 cases, where additional immunohistochemical and molecular studies were carried out. Fluorescence in situ hybridization using MYB, MYBL1 , and NFIB bacterial artificial chromosome-clones break-apart and MYB::NFIB BAC-clones fusion probes was performed. The patients' mean age at diagnosis was 52 years. Tumor size ranged from 0.5 to 5 cm. Microscopic examination revealed tubular, cribriform, and solid patterns. Perineural invasion was seen in 4 cases. Patients were treated with surgery, some with adjuvant radiation therapy. During follow-up (mean: 11 yr), 4 patients developed local recurrences. Recently, one of these patients developed pulmonary disease. Cam 5.2, CK5/6, CD117, and DOG-1 were positive in all 4 cases and S100 and calponin were positive in 3 cases. MYB rearrangement was present in 3 cases, including one with concurrent MYB amplification. There were no MYBL1 or NFIB rearrangements and no MYB :: NFIB fusions. Our findings corroborate that the histologic, immunohistochemical, and oncogenic background is similar between ACCs of the lower female genital tract and ACCs elsewhere, although the canonical MYB::NFIB fusion seems to be a less common finding in this location.

腺样囊性癌(ACC)是一种罕见的肿瘤,最常见于唾液腺,也可发生于其他器官,包括外阴和阴道。已有涉及 MYB、NFIB 和 MYB-NFIB 重排的致癌机制的描述,但在外阴和阴道中的证据仍然很少。我们的目的是报告一系列外阴和阴道 ACCs 的临床病理特征、免疫组化和分子研究结果。我们共纳入了五例病例。我们查阅了病历和切片。其中 4 例有福尔马林固定石蜡包埋材料,并进行了额外的免疫组化和分子研究。使用MYB、MYBL1和NFIB细菌人工染色体克隆断裂分离探针和MYB::NFIB BAC克隆融合探针进行了荧光原位杂交。患者确诊时的平均年龄为 52 岁。肿瘤大小从 0.5 厘米到 5 厘米不等。显微镜检查显示肿瘤呈管状、楔形和实性形态。4例患者出现了神经周围侵犯。患者接受了手术治疗,部分患者接受了辅助放射治疗。在随访期间(平均 11 年),4 例患者出现局部复发。最近,其中一名患者出现了肺部疾病。4例患者的Cam 5.2、CK5/6、CD117和DOG-1均呈阳性,3例患者的S100和钙蛋白呈阳性。3例出现MYB重排,其中1例同时伴有MYB扩增。没有 MYBL1 或 NFIB 重排,也没有 MYB::NFIB 融合。我们的研究结果证实,女性生殖道下段 ACC 与其他部位的 ACC 在组织学、免疫组化和致癌背景方面具有相似性,但 MYB::NFIB 融合在该部位似乎并不常见。
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引用次数: 0
Stromal p16 and SATB2 Expression Does Not Distinguish Atypical Polypoid Adenomyoma (APA) From its Benign Mimics. 基质 p16 和 SATB2 表达不能区分非典型多形性腺肌瘤 (APA) 和良性拟态腺肌瘤。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-05-29 DOI: 10.1097/PGP.0000000000001023
Chau Minh Bui, Mahzad Azimpouran, Bonnie Balzer, Horacio Maluf, Fabiola Medeiros

Atypical polypoid adenomyoma (APA) is a polypoid biphasic lesion of low malignant potential that arises in the lower uterine segment and uterine corpus. The diagnosis of APA is often challenging on biopsy and curettage specimens, and both benign and malignant processes need to be considered in the differential. Stromal expression of p16 and SATB2 have recently been shown to distinguish APA from myoinvasive endometrioid carcinoma. The authors hypothesized that p16 and SATB2 immunohistochemistry could also aid in the distinction of APA from benign adenomyomatous polyp and endometrioid adenomyoma. The study comprised 10 APAs, 7 adenomyomatous polyps, 11 endometrioid adenomyomas, and 10 myoinvasive endometrioid carcinomas. The majority of APAs showed moderate to strong, diffuse p16 and stromal expression. However, most adenomyomatous polyps and endometrioid adenomyomas also exhibited moderate to strong, focal to diffuse p16 stromal expression. SATB2 showed weak to moderate, focal to diffuse expression in the majority of APAs, adenomyomatous polyps and endometrioid adenomyomas. In contrast, p16 and SATB2 were negative to weak and focal in 90% of myoinvasive endometrioid carcinomas. Our findings demonstrate that p16 and SATB2 may be helpful in the differential diagnosis of myoinvasive endometrioid carcinoma and APA while not useful in separating APA from adenomyomatous polyp and endometrioid adenomyoma.

非典型多形性腺肌瘤(APA)是一种多形性双相病变,恶性程度较低,发生于子宫下段和子宫体。活检和刮宫标本对 APA 的诊断往往具有挑战性,在鉴别时需要考虑良性和恶性过程。最近有研究表明,p16 和 SATB2 的基质表达可将 APA 与肌浸润性子宫内膜样癌区分开来。作者假设 p16 和 SATB2 免疫组化也能帮助区分 APA 与良性腺肌瘤性息肉和子宫内膜样腺肌瘤。研究包括 10 例 APA、7 例腺肌瘤性息肉、11 例子宫内膜样腺肌瘤和 10 例肌浸润性子宫内膜样癌。大多数 APA 显示中度至高度弥漫性 p16 和基质表达。然而,大多数腺肌瘤性息肉和子宫内膜样腺肌瘤也表现出中度到高度、局灶性到弥漫性的p16基质表达。在大多数 APA、腺肌瘤性息肉和子宫内膜样腺肌瘤中,SATB2 表现为弱至中度、灶性至弥漫性表达。相反,在90%的肌浸润性子宫内膜样癌中,p16和SATB2呈阴性至弱表达,且呈局灶性表达。我们的研究结果表明,p16和SATB2可能有助于肌浸润性子宫内膜样癌和APA的鉴别诊断,但无助于将APA与腺肌瘤性息肉和子宫内膜样腺肌瘤区分开来。
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引用次数: 0
Morphomolecular Correlation and Clinicopathologic Analysis in Endometrial Carcinoma. 子宫内膜癌的形态分子相关性和临床病理学分析
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-08 DOI: 10.1097/PGP.0000000000001013
Göksenil Bülbül, Tekincan Çağri Aktaş, Anil Aysal Ağalar, Safiye Aktaş, Sefa Kurt, Bahadir Saatli, Emine Çağnur Ulukuş

Research groups have identified 4 groups [polymerase epsilon (POLE) mutant, mismatch repair-deficient, p53-abnormal, and no specific molecular profile)] reflecting the Tumor Cancer Genomic Atlas Research Network subgroups in endometrial carcinomas, improving the clinical applicability of molecular classification. We have analyzed the histopathologic and prognostic characteristics of our cases based on the ProMisE classification, supported by growing data on recommended treatment regimens. The study included 118 cases of endometrial carcinoma diagnosed between 2016 and 2020, which underwent mismatch repair and p53 immunohistochemistry. Next-generation sequencing was performed for POLE mutation analysis, dividing the cases into 4 subgroups. The histopathologic and clinical characteristics of these groups were then analyzed statistically. Four cases(3.4%) were classified as POLE mutant, 31 (26.3%) as mismatch repair-deficient, 22 (18.6%) as p53 mutant, and 61 (51.7%) as no specific molecular profile. We categorized 118 patients with endometrial carcinoma into low (n=43), intermediate (n=28), high-intermediate (n=21), high (n=22), and advanced metastatic (n=4) risk groups regardless of the molecular subtypes of their disease. When we reclassified all cases according to the molecular subtypes of endometrial carcinoma only the risk group of 3 (2.5%) cases changed. Using the new algorithm we designed, after narrowing down the number of patients, the microcystic, elongated, and fragmented pattern of invasion was revealed as an independent prognostic factor that reduces overall survival time (hazard ratio: 16.395, 95% CI: 2.140-125.606, P =0.007). In conclusion, using the new algorithm we have designed, and by identifying patients for whom molecular classification could alter risk groups, we observed that molecular tests can be utilized more efficiently in populations with limited economic resources and, in doing so, we discovered a new morphologic marker with prognostic significance.

研究小组已在子宫内膜癌中确定了反映肿瘤基因组图谱研究网络亚组的 4 个组别[聚合酶ε(POLE)突变、错配修复缺陷、p53 异常和无特定分子特征],从而提高了分子分类的临床适用性。我们根据 ProMisE 分类分析了病例的组织病理学和预后特征,并辅以越来越多的推荐治疗方案数据。研究纳入了2016年至2020年间确诊的118例子宫内膜癌病例,对其进行了错配修复和p53免疫组化。研究人员进行了新一代测序以分析POLE突变,并将病例分为4个亚组。然后对这些分组的组织病理学和临床特征进行了统计分析。4例(3.4%)为POLE突变,31例(26.3%)为错配修复缺陷,22例(18.6%)为p53突变,61例(51.7%)无特定分子特征。我们将 118 名子宫内膜癌患者分为低危(43 人)、中危(28 人)、高危(21 人)、高危(22 人)和晚期转移(4 人),而不考虑其疾病的分子亚型。当我们根据子宫内膜癌的分子亚型对所有病例进行重新分类时,只有 3 例(2.5%)病例的风险组别发生了变化。使用我们设计的新算法,在缩小患者数量后,发现微囊状、拉长和碎裂的浸润模式是降低总生存时间的独立预后因素(危险比:16.395,95% CI:2.140-125.606,P=0.007)。总之,通过使用我们设计的新算法,并通过识别分子分类可改变风险组别的患者,我们观察到,在经济资源有限的人群中,分子检测可得到更有效的利用,同时,我们还发现了一种具有预后意义的新的形态学标志物。
{"title":"Morphomolecular Correlation and Clinicopathologic Analysis in Endometrial Carcinoma.","authors":"Göksenil Bülbül, Tekincan Çağri Aktaş, Anil Aysal Ağalar, Safiye Aktaş, Sefa Kurt, Bahadir Saatli, Emine Çağnur Ulukuş","doi":"10.1097/PGP.0000000000001013","DOIUrl":"10.1097/PGP.0000000000001013","url":null,"abstract":"<p><p>Research groups have identified 4 groups [polymerase epsilon (POLE) mutant, mismatch repair-deficient, p53-abnormal, and no specific molecular profile)] reflecting the Tumor Cancer Genomic Atlas Research Network subgroups in endometrial carcinomas, improving the clinical applicability of molecular classification. We have analyzed the histopathologic and prognostic characteristics of our cases based on the ProMisE classification, supported by growing data on recommended treatment regimens. The study included 118 cases of endometrial carcinoma diagnosed between 2016 and 2020, which underwent mismatch repair and p53 immunohistochemistry. Next-generation sequencing was performed for POLE mutation analysis, dividing the cases into 4 subgroups. The histopathologic and clinical characteristics of these groups were then analyzed statistically. Four cases(3.4%) were classified as POLE mutant, 31 (26.3%) as mismatch repair-deficient, 22 (18.6%) as p53 mutant, and 61 (51.7%) as no specific molecular profile. We categorized 118 patients with endometrial carcinoma into low (n=43), intermediate (n=28), high-intermediate (n=21), high (n=22), and advanced metastatic (n=4) risk groups regardless of the molecular subtypes of their disease. When we reclassified all cases according to the molecular subtypes of endometrial carcinoma only the risk group of 3 (2.5%) cases changed. Using the new algorithm we designed, after narrowing down the number of patients, the microcystic, elongated, and fragmented pattern of invasion was revealed as an independent prognostic factor that reduces overall survival time (hazard ratio: 16.395, 95% CI: 2.140-125.606, P =0.007). In conclusion, using the new algorithm we have designed, and by identifying patients for whom molecular classification could alter risk groups, we observed that molecular tests can be utilized more efficiently in populations with limited economic resources and, in doing so, we discovered a new morphologic marker with prognostic significance.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"535-556"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
"Uterine-type" Extra-uterine High-grade Sarcoma of the Rectovaginal Septum: Case Report and Review of Literature. 直肠阴道隔膜的 "子宫型 "子宫外高级别肉瘤:病例报告和文献综述。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-29 DOI: 10.1097/PGP.0000000000001019
Chirine Khaled, Nicky D'Haene, Jean-Christophe Noël

The rectovaginal septum is an unusual location for neoplastic processes. The majority of these are extensions of tumors of the rectum or vagina. Masses arising primarily from the rectovaginal fascia are rare. Most primary rectovaginal malignant neoplasms are carcinomas that arise in the setting of endometriosis. Sarcomas in this location are exceedingly rare, with only few cases reported in the literature. We report a case of a 44-year-old lady who developed a high-grade sarcoma in the rectovaginal septum in the setting of endometriosis. We also discussed the differential diagnosis of this lady's challenging and unique lesion, which is most probably an extra-uterine "uterine-type" high-grade sarcoma that shows overlapping features of several entities. Moreover, we performed a literature review of sarcomas in this rare location. Given the fact that the rectovaginal septum is a common location for endometriosis, in the case of a rectovaginal neoplasm, a thorough sampling and a careful search for endometriotic lesions are important, as they may be a clue for the diagnosis. Although rare, sarcomas should always be considered in the differential diagnosis of rectovaginal neoplasms.

直肠阴道隔是一个不常见的肿瘤位置。其中大多数是直肠或阴道肿瘤的延伸。主要来自直肠阴道筋膜的肿块很少见。大多数原发性直肠阴道恶性肿瘤是在子宫内膜异位症的情况下发生的癌。该部位的肉瘤极为罕见,文献中仅有少数病例报道。我们报告了一例 44 岁女性因子宫内膜异位症在直肠阴道隔发生高级别肉瘤的病例。我们还讨论了对这位女士具有挑战性的独特病变的鉴别诊断,该病变很可能是子宫外 "子宫型 "高级别肉瘤,显示出多个实体的重叠特征。此外,我们还对这一罕见部位的肉瘤进行了文献综述。鉴于直肠阴道隔是子宫内膜异位症的常见部位,在直肠阴道肿瘤的病例中,彻底取样和仔细寻找子宫内膜异位症病灶非常重要,因为它们可能是诊断的线索。肉瘤虽然罕见,但在直肠阴道肿瘤的鉴别诊断中应始终予以考虑。
{"title":"\"Uterine-type\" Extra-uterine High-grade Sarcoma of the Rectovaginal Septum: Case Report and Review of Literature.","authors":"Chirine Khaled, Nicky D'Haene, Jean-Christophe Noël","doi":"10.1097/PGP.0000000000001019","DOIUrl":"10.1097/PGP.0000000000001019","url":null,"abstract":"<p><p>The rectovaginal septum is an unusual location for neoplastic processes. The majority of these are extensions of tumors of the rectum or vagina. Masses arising primarily from the rectovaginal fascia are rare. Most primary rectovaginal malignant neoplasms are carcinomas that arise in the setting of endometriosis. Sarcomas in this location are exceedingly rare, with only few cases reported in the literature. We report a case of a 44-year-old lady who developed a high-grade sarcoma in the rectovaginal septum in the setting of endometriosis. We also discussed the differential diagnosis of this lady's challenging and unique lesion, which is most probably an extra-uterine \"uterine-type\" high-grade sarcoma that shows overlapping features of several entities. Moreover, we performed a literature review of sarcomas in this rare location. Given the fact that the rectovaginal septum is a common location for endometriosis, in the case of a rectovaginal neoplasm, a thorough sampling and a careful search for endometriotic lesions are important, as they may be a clue for the diagnosis. Although rare, sarcomas should always be considered in the differential diagnosis of rectovaginal neoplasms.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"605-611"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Characteristics and Significance of Tertiary Lymphoid Structures Based on Molecular Subtypes in Endometrial Cancer. 基于分子亚型的子宫内膜癌三级淋巴结构的特征和意义
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-02-23 DOI: 10.1097/PGP.0000000000001027
Hui-Qing Jia, Shu-Ping Zhang, Yang Chen, Ye-Hua Qiao, Yi-Fan Yao, Xiang-Yan Zhang, Si-Yu Wu, Yao-Lin Song, Xiao-Ming Xing

The purpose of this study is to investigate the characteristics and significance of tertiary lymphoid structures (TLSs) in endometrial cancer (EC) based on molecular subtypes. A total of 220 patients with EC were retrospectively enrolled, including 20 with polymerase epsilon ultramutated (POLE-mut), 63 with mismatch repair deficient, 32 with p53 abnormal, and 105 with no specific molecular profile. The presence and maturity of TLSs were determined by immunohistochemical markers (CD3, CD20, CD21, and Bcl6). Disease-free survival served as the endpoint event. TLSs were found in 91 out of 220 patients (41.1%), with 68 located in peritumoral tissues and 37 exhibiting well-formed germinal center structures. The presence and different maturity of TLSs were closely associated with tumor-infiltrating lymphocytes and the programmed cell death ligand-1 expression. Moreover, TLSs displayed heterogeneity across different molecular subtypes. Notably, the TLSs, tumor-infiltrating lymphocytes, and expression of the programmed cell death ligand-1 were significantly enriched in POLE-mut EC. Multivariate logistic regression analysis showed the presence of TLSs (odds ratio: 3.483, 95% CI: 1.044-11.623, P = 0.042) as a potential predictor of POLE-mut EC. Kaplan-Meier survival curves revealed that molecular subtypes significantly stratified prognosis in patients with EC (P = 0.002), whereas TLSs did not. Multivariate Cox regression analysis indicated that The International Federation of Gynecology and Obstetrics stage and Ki-67 expression were independent prognostic factors affecting disease-free survival in patients with EC, and TLSs were not included. In conclusion, TLSs in EC exhibit heterogeneity based on molecular subtypes, necessitating further exploration to determine their clinical application value.

本研究旨在根据分子亚型研究子宫内膜癌(EC)中三级淋巴结构(TLS)的特征和意义。研究共回顾性地纳入了220例子宫内膜癌患者,包括20例聚合酶ε超突变(POLE-mut)患者、63例错配修复缺陷患者、32例p53异常患者和105例无特定分子特征的患者。TLS的存在和成熟度通过免疫组化标记(CD3、CD20、CD21和Bcl6)来确定。无病生存作为终点事件。在220例患者中,有91例(41.1%)发现了TLS,其中68例位于瘤周组织,37例表现为形成良好的生殖中心结构。TLS的存在和不同成熟度与肿瘤浸润淋巴细胞和程序性细胞死亡配体-1的表达密切相关。此外,TLS在不同分子亚型中表现出异质性。值得注意的是,TLSs、肿瘤浸润淋巴细胞和程序性细胞死亡配体-1的表达在POLE-mut EC中明显富集。多变量逻辑回归分析显示,TLSs的存在(几率比:3.483,95% CI:1.044-11.623,P = 0.042)是POLE-突变EC的潜在预测因子。卡普兰-梅耶生存曲线显示,分子亚型对EC患者的预后有显著的分层作用(P = 0.002),而TLS则没有。多变量Cox回归分析表明,国际妇产科联盟分期和Ki-67表达是影响EC患者无病生存的独立预后因素,而TLS不包括在内。总之,根据分子亚型,TLSs在EC中表现出异质性,因此有必要进一步探讨以确定其临床应用价值。
{"title":"Characteristics and Significance of Tertiary Lymphoid Structures Based on Molecular Subtypes in Endometrial Cancer.","authors":"Hui-Qing Jia, Shu-Ping Zhang, Yang Chen, Ye-Hua Qiao, Yi-Fan Yao, Xiang-Yan Zhang, Si-Yu Wu, Yao-Lin Song, Xiao-Ming Xing","doi":"10.1097/PGP.0000000000001027","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001027","url":null,"abstract":"<p><p>The purpose of this study is to investigate the characteristics and significance of tertiary lymphoid structures (TLSs) in endometrial cancer (EC) based on molecular subtypes. A total of 220 patients with EC were retrospectively enrolled, including 20 with polymerase epsilon ultramutated (POLE-mut), 63 with mismatch repair deficient, 32 with p53 abnormal, and 105 with no specific molecular profile. The presence and maturity of TLSs were determined by immunohistochemical markers (CD3, CD20, CD21, and Bcl6). Disease-free survival served as the endpoint event. TLSs were found in 91 out of 220 patients (41.1%), with 68 located in peritumoral tissues and 37 exhibiting well-formed germinal center structures. The presence and different maturity of TLSs were closely associated with tumor-infiltrating lymphocytes and the programmed cell death ligand-1 expression. Moreover, TLSs displayed heterogeneity across different molecular subtypes. Notably, the TLSs, tumor-infiltrating lymphocytes, and expression of the programmed cell death ligand-1 were significantly enriched in POLE-mut EC. Multivariate logistic regression analysis showed the presence of TLSs (odds ratio: 3.483, 95% CI: 1.044-11.623, P = 0.042) as a potential predictor of POLE-mut EC. Kaplan-Meier survival curves revealed that molecular subtypes significantly stratified prognosis in patients with EC (P = 0.002), whereas TLSs did not. Multivariate Cox regression analysis indicated that The International Federation of Gynecology and Obstetrics stage and Ki-67 expression were independent prognostic factors affecting disease-free survival in patients with EC, and TLSs were not included. In conclusion, TLSs in EC exhibit heterogeneity based on molecular subtypes, necessitating further exploration to determine their clinical application value.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":"43 6","pages":"595-604"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
期刊
International Journal of Gynecological Pathology
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