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Uterine Neurotrophic Tyrosine Receptor Kinase Rearranged Spindle Cell Neoplasms: Three Cases of an Emerging Entity. 子宫神经营养酪氨酸受体激酶重排梭形细胞肿瘤:三例新发实体瘤。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-01 Epub Date: 2023-09-22 DOI: 10.1097/PGP.0000000000000988
Lucy Grant, William Boyle, Sarah Williams, Jennifer Pascoe, Raji Ganesan

Uterine sarcomas are rare; most are either smooth muscle or endometrial stromal in origin. Recent molecular advances have identified several, genetically defined entities with specific morphologic, clinicopathological associations, and therapeutic options. We report 3 cases of uterine neurotrophic tyrosine receptor kinase ( NTRK )-rearranged spindle cell neoplasms," currently classified as "emerging entities" in the WHO Classification of Female Genital Tract Tumors, 2020, Fifth Edition. The affected patients were 32, 34, and 42 years of age. Two patients presented with vaginal bleeding; the third presented with a cervical mass found incidentally during laparoscopy for an ectopic gestation. All 3 tumors were polypoid masses that distorted the cervix. Microscopically, they comprised cellular, fascicular, and storiform, plump spindle cells, with occasional rounded cells, and frequent mitoses (4-48/10 high power fields) in a myxoid stroma. All 3 cases showed entrapment of benign cervical glands. Inflammatory cell infiltrates, including plasma cells, were noted in all 3 tumors. One case had tumor cell necrosis, osteoid-like material, and osteoclast-like giant cells and showed lymphovascular invasion. Immunohistochemically, our cases showed patchy S100 (2/3) and CD34 (3/3) positivity. CD10 was positive in 2/3 cases. 3/3 cases showed pan-tropomyosin receptor kinase positivity (cytoplasmic). The NTRK -translocations demonstrated were: NTRK1::TMP3, NTRK1::TPR, and NTRK3::SPECC1L . Two of the patients had extensive disease and underwent chemotherapy. Larotrectinib was approved for one patient who demonstrated a striking reduction in tumor volume upon initiation of this treatment.

子宫肉瘤是罕见的;大多数起源于平滑肌或子宫内膜间质。最近的分子进展已经确定了几个具有特定形态学、临床病理学关联和治疗选择的基因定义实体。我们报告3例子宫神经营养酪氨酸受体激酶(NTRK)重排梭形细胞肿瘤,“目前被归类为”新兴实体“世界卫生组织女性生殖道肿瘤分类,2020,第五版。受影响的患者年龄分别为32岁、34岁和42岁。两名患者出现阴道出血;第三名患者出现宫外孕腹腔镜检查时意外发现的宫颈肿块。所有3个肿瘤都是扭曲宫颈的息肉样肿块。显微镜下,它们包括细胞、束状ar,黏液样间质中有储存状、肥大的梭形细胞,偶尔有圆形细胞,有频繁的有丝分裂(4-48/10高倍视野)。3例均表现为良性宫颈腺体包夹。在所有3个肿瘤中均发现炎症细胞浸润,包括浆细胞。1例出现肿瘤细胞坏死、类骨物质和破骨细胞样巨细胞,并显示淋巴管浸润。免疫组化显示,我们的病例显示斑片状S100(2/3)和CD34(3/3)阳性。CD10阳性2/3例。3/3例显示泛原肌球蛋白受体激酶阳性(细胞质)。证明的NTRK易位为:NTRK1::TMP3、NTRK1::TPR和NTRK3::SPECC1L。其中两名患者患有广泛的疾病,并接受了化疗。拉罗替尼被批准用于一名患者,该患者在开始该治疗时肿瘤体积显著减少。
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引用次数: 0
Synchronous Endometrial and Ovarian Carcinomas: Pathologic and Molecular Analysis Highlights the Monoclonal Origin of the Lesions. 子宫内膜和卵巢同步癌:病理学和分子分析强调病变的单克隆起源。
IF 2.4 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-01 Epub Date: 2023-09-08 DOI: 10.1097/PGP.0000000000000982
Angela Guerriero, Margherita Moro, Valentina Angerilli, Giada Munari, Luisa Santoro, Lara Alessandrini, Lara Favero, Giulia Tasca, Matteo Fassan, Angelo Paolo Dei Tos

The diagnosis of synchronous carcinomas, involving both the endometrium and ovaries, is not a rare finding in gynecologic pathology and represents a challenge with implications on tumor staging and therapeutic decision-making. A mono-institutional series of 11 metastatic and 6 paired synchronous endometrial and ovarian carcinomas were reviewed by 2 expert pathologists based on previously published histopathologic criteria. The series was investigated for DNA mismatch repair proteins, p53, and POLE status and was subject to DNA-based next-generation sequencing targeting 67 cancer-related genes. Out of 17 pairs, 16 featured the same histotype (10 endometrioid, 4 serous high-grade, and 2 clear cells). By using WHO 2020 criteria, 11 couples of tumors were confirmed as metastatic and 6 couples were confirmed as independent. Based on next-generation sequencing analysis, 16 of 17 cases (11 metastatic and 5 independent) of our series showed evidence of a clonal relationship between endometrial and ovarian carcinomas. In metastatic cases, the adverse outcome was associated with nonendometrioid/high-grade endometrioid histotype and with the p53-abnormal molecular subtype. Four cases originally fulfilling clinicopathological criteria of independent endometrial and ovarian carcinomas were clonally related, low-grade endometrioid histotype and POLE -mut, mismatch repair deficient, and no specific molecular profile molecular subtypes; no adverse event was recorded in this group. In summary, the molecular characterization of synchronous gynecologic carcinomas confirms their clonal origin in most cases. However, the results of our study point out that the clinical behavior of these tumors seems to be determined by the presence of high-risk WHO 2020 histologic criteria and molecular features (i.e. p53-abnormal), rather than the monoclonal origin.

同时涉及子宫内膜和卵巢的同步癌的诊断在妇科病理学中并不罕见,对肿瘤分期和治疗决策具有挑战性。2名专家病理学家根据先前发表的组织病理学标准,对11例转移性子宫内膜癌和6例同期子宫内膜癌及卵巢癌的单机构系列进行了审查。该系列研究了DNA错配修复蛋白、p53和POLE状态,并对67个癌症相关基因进行了基于DNA的下一代测序。在17对中,16对具有相同的组织类型(10个子宫内膜样,4个浆液性高级别,2个透明细胞)。根据世界卫生组织2020年标准,11对肿瘤被确认为转移性,6对被确认为独立性。基于下一代测序分析,我们系列的17例病例中有16例(11例转移,5例独立)显示出子宫内膜癌和卵巢癌之间存在克隆关系的证据。在转移病例中,不良结果与非子宫内膜样/高级子宫内膜样组织类型和p53异常分子亚型有关。4例最初符合独立子宫内膜癌和卵巢癌临床病理标准的病例为克隆相关、低度子宫内膜样组织型和POLE-mut、错配修复缺陷和无特定分子谱分子亚型;本组无不良事件记录。总之,同步性妇科癌的分子特征在大多数情况下证实了其克隆起源。然而,我们的研究结果指出,这些肿瘤的临床行为似乎是由世界卫生组织2020年高风险组织学标准和分子特征(即p53-异常)的存在决定的,而不是由单克隆来源决定的。
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引用次数: 0
SATB2 Cytoplasmic Expression is Characteristic of a Subset of Ovarian Stromal Cells and Sex Cord Stromal Tumors. SATB2 细胞质表达是卵巢间质细胞和性索间质瘤亚群的特征。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-01 Epub Date: 2023-08-25 DOI: 10.1097/PGP.0000000000000985
Maysa Al-Hussaini, W Glenn McCluggage

Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear transcription factor that shows consistent nuclear staining in colorectal adenocarcinoma and osteosarcoma. Following the observation of cytoplasmic staining with this marker in luteinized ovarian stromal cells, we studied the expression of SATB2 in ovarian stromal cells, various types of follicular cysts, and sex cord-stromal tumors. Eighty-five cases were stained for SATB2. Ovarian hilar Leydig cells (n = 12), luteinized stromal cells (n = 10), corpora lutea (n = 4), luteinized follicular cysts (n = 4), and stromal hyperthecosis (n = 6) exhibited consistent, usually diffuse, granular cytoplasmic staining. In addition, Leydig cell tumors (n = 1) and steroid cell tumors (n = 4) showed diffuse cytoplasmic staining. SATB2 also exhibited cytoplasmic staining in most Sertoli-Leydig cell tumors (n = 16) and gynandroblastomas (n = 3) confined to the Leydig cell component. Adult granulosa cell tumors (n = 14), juvenile granulosa cell tumors (n = 3), sex cord tumors with annular tubules (n = 3), cellular fibromas (n = 3), sclerosing stromal tumors (n = 1), and thecomas (n = 1) were negative apart from cytoplasmic staining in associated luteinized stromal cells. SATB2 cytoplasmic staining has not been previously described in these lesions but is characteristic of a variety of ovarian stromal cells and sex cord-stromal tumors, in particular, those exhibiting luteinization or a Leydig or steroid cell component. SATB2 staining may be of value in identifying luteinized or Leydig cells when these are morphologically inconspicuous.

特殊富AT序列结合蛋白2(SATB2)是一种核转录因子,在结直肠腺癌和骨肉瘤中显示出一致的核染色。继在黄体化卵巢基质细胞中观察到该标记物的细胞质染色后,我们研究了 SATB2 在卵巢基质细胞、各种类型的卵泡囊肿和性索间质肿瘤中的表达。85 个病例进行了 SATB2 染色。卵巢间质Leydig细胞(12例)、黄体化间质细胞(10例)、黄体(4例)、黄体化卵泡囊肿(4例)和间质肥大症(6例)表现出一致的、通常是弥漫性的颗粒状胞浆染色。此外,Leydig 细胞肿瘤(n = 1)和类固醇细胞肿瘤(n = 4)也表现出弥漫性胞浆染色。SATB2 在大多数 Sertoli-Leydig 细胞肿瘤(n = 16)和妇母细胞瘤(n = 3)中也表现出胞浆染色,但仅限于 Leydig 细胞部分。成人颗粒细胞瘤(14 例)、幼年颗粒细胞瘤(3 例)、环状小管性索瘤(3 例)、细胞纤维瘤(3 例)、硬化性基质瘤(1 例)和肉瘤(1 例)除相关黄体化基质细胞出现细胞质染色外,其他均为阴性。SATB2 细胞质染色以前未在这些病变中出现过,但它是各种卵巢基质细胞和性索间质肿瘤的特征,尤其是那些黄体化或具有莱地格或类固醇细胞成分的肿瘤。当黄体化或Leydig细胞在形态上不明显时,SATB2染色可能有助于鉴别这些细胞。
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引用次数: 0
PD-L1 Expression in HPV-associated Versus HPV-independent Invasive Vulvar Squamous Cell Carcinoma. PD-L1在HPV相关性外阴阴道鳞状细胞癌和HPV非相关性外阴阴道鳞状细胞癌中的表达。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-01 Epub Date: 2024-02-02 DOI: 10.1097/PGP.0000000000001003
Chau Minh Bui, Fabiola Medeiros, Mahzad Azimpouran, Mariza Venturina, Bonnie Balzer

Two etiological pathways have been implicated in the pathogenesis of vulvar squamous cell carcinoma (VSCC): a high-risk human papillomavirus (HPV)-associated route and an HPV-independent pathway characterized by TP53 mutations. Programmed cell death ligand 1 (PD-L1) has become increasingly useful in predicting the response to checkpoint inhibitor therapy in squamous cell carcinomas at various anatomical sites. This study aimed to assess the association between PD-L1 expression and the VSCC subtype to evaluate the utility of PD-L1 in prognostication and therapeutic selection based on HPV status. PD-L1 status was assessed using 3 separate metrics for the extent of PD-L1 staining in various cell types: immune cell score, tumor proportion score (TPS), and combined positive score. The study group consisted of 25 HPV-associated and 28 HPV-independent VSCCs. PD-L1 expression was positive in the majority of VSCCs according to all 3 scoring metrics (84.9% by immune cell score, 77.3% by TPS, and 90.6% by combined positive score). PD-L1 expression was observed in the majority of cases in both groups (60%-96.4%). PD-L1 expression using the TPS method was greater in HPV-independent tumors than in HPV-associated tumors ( P = 0.004), and high PD-L1 expression was also more common in the HPV-independent subtype ( P = 0.016 using the TPS method and P = 0.013 using the combined positive score method). Our findings contribute to the growing evidence that PD-L1 is expressed in the majority of invasive VSCCs, and thus may serve as an attractive therapeutic target. PD-L1 expression is higher in HPV-independent tumors, suggesting that this subtype may be more responsive to PD-L1 inhibitor therapy.

外阴鳞状细胞癌(VSCC)的发病机制涉及两种病因途径:一种是高危人乳头瘤病毒(HPV)相关途径,另一种是以TP53突变为特征的HPV无关途径。程序性细胞死亡配体1(PD-L1)在预测不同解剖部位的鳞状细胞癌对检查点抑制剂疗法的反应方面越来越有用。本研究旨在评估PD-L1表达与VSCC亚型之间的关联,以评估PD-L1在预后和基于HPV状态的治疗选择中的作用。PD-L1状态采用3种不同的指标来评估PD-L1在不同细胞类型中的染色程度:免疫细胞评分、肿瘤比例评分(TPS)和综合阳性评分。研究组包括25个HPV相关性VSCC和28个HPV非相关性VSCC。根据所有三种评分标准,大多数VSCC的PD-L1表达均为阳性(免疫细胞评分为84.9%,TPS评分为77.3%,综合阳性评分为90.6%)。两组中的大多数病例都观察到了 PD-L1 表达(60%-96.4%)。采用TPS法的PD-L1表达在HPV独立肿瘤中高于HPV相关肿瘤(P = 0.004),PD-L1高表达在HPV独立亚型中也更为常见(采用TPS法的P = 0.016,采用联合阳性评分法的P = 0.013)。越来越多的证据表明,PD-L1在大多数侵袭性VSCC中都有表达,因此可能成为一个有吸引力的治疗靶点。PD-L1在HPV依赖性肿瘤中的表达量更高,这表明该亚型可能对PD-L1抑制剂治疗反应更强。
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引用次数: 0
LINE-1 ORF1p is a Promising Biomarker in Cervical Intraepithelial Neoplasia Degree Assessment. LINE-1 ORF1p 是宫颈上皮内瘤变程度评估中一种有前途的生物标记物。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-06-26 DOI: 10.1097/PGP.0000000000001035
Réka Karkas, Khaldoon Sadiq Ahmed Abdullah, László Kaizer, Ádám Ürmös, May Raya, Lilla Tiszlavicz, Tibor Pankotai, István Nagy, Lajos Mátés, Farkas Sükösd

Cervical intraepithelial neoplasia (CIN) represents a spectrum of preinvasive squamous lesions within the cervical epithelium, whose identification is a diagnostic challenge due to subtle histomorphological differences among its categories. This study explores ORF1p, a nucleic acid-binding protein derived from long interspersed nuclear element-1 (LINE-1), as a potential biomarker for enhancing CIN diagnosis. A comprehensive analysis of 143 cervical specimens, encompassing CIN I (n=20), CIN II (n=46), CIN III (n=14), invasive cancer (n=32), and nondysplastic cases (normal cervical epithelia (n=24) and atrophy (n=7) were conducted. ORF1p, Ki67, and p16 expressions were evaluated using immunohistochemistry. ORF1p immunopositivity was detected in the vast majority [110/112 (98.2%)] of dysplastic and neoplastic (CIN and invasive cancer) specimens, whereas 19/24 (79.2%) of normal cervical specimens lacked ORF1p expression. The observed pattern of ORF1p expression showed a progressively increasing extent and intensity with advancing CIN grades. CIN I exhibited mild ORF1p expression in the lower one or two-thirds of the cervical epithelium [14/16 (87.5%)], whereas CIN II demonstrated moderate to strong ORF1p expression spanning the lower two-thirds [29/46 (63.0%)]. Pronounced transepithelial ORF1p immunopositivity characterized CIN III cases [13/14 (92.8%)] and cervical cancer [30/32 (93.8%)]. These findings propose ORF1p as a valuable indicator even for detecting CIN I, effectively discerning them from normal cervical tissue (p < 0.0001). Our findings underscore the potential of ORF1p as an early diagnostic marker for cervical neoplasia.

宫颈上皮内瘤变(CIN)是宫颈上皮内的一种侵袭性前鳞状病变,由于不同类别的组织形态存在细微差别,其鉴别是一项诊断难题。本研究探讨了 ORF1p(一种核酸结合蛋白,来源于长穿插核元素-1(LINE-1)),将其作为一种潜在的生物标志物,以提高 CIN 诊断的准确性。研究人员对 143 例宫颈标本进行了全面分析,包括 CIN I(20 例)、CIN II(46 例)、CIN III(14 例)、浸润癌(32 例)和非增生病例(正常宫颈上皮(24 例)和萎缩(7 例))。采用免疫组化方法评估 ORF1p、Ki67 和 p16 的表达。绝大多数[110/112(98.2%)]发育不良和肿瘤(CIN 和浸润癌)标本都检测到 ORF1p 免疫阳性,而 19/24(79.2%)例正常宫颈标本缺乏 ORF1p 表达。观察到的 ORF1p 表达模式显示,随着 CIN 等级的提高,ORF1p 表达的范围和强度逐渐增加。CIN I 在宫颈上皮的下1/3或下2/3处有轻度 ORF1p 表达[14/16(87.5%)],而 CIN II 在下2/3处有中度至重度 ORF1p 表达[29/46(63.0%)]。CINⅢ病例[13/14(92.8%)]和宫颈癌[30/32(93.8%)]具有明显的经上皮ORF1p免疫阳性特征。这些研究结果表明,ORF1p 甚至可以作为检测 CIN I 的重要指标,有效区分 CIN I 与正常宫颈组织(p < 0.0001)。我们的研究结果凸显了 ORF1p 作为宫颈肿瘤早期诊断标志物的潜力。
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引用次数: 0
Prevalence of Occult Ovarian Cancer and Metastatic Breast Cancer in Ovarian Ablation Specimens of Patients With Hormone Receptor-Positive Breast Cancer: Implications for Tissue Sampling Strategies, Early Ovarian Cancer Detection and Resource Utilization. 激素受体阳性乳腺癌患者卵巢消融标本中隐匿性卵巢癌和转移性乳腺癌的发生率:组织取样策略、早期卵巢癌检测和资源利用的意义。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-06-26 DOI: 10.1097/PGP.0000000000001055
Anjali Walia, Nicholas R Ladwig, Julie S Mak, Joseph T Rabban

Bilateral oophorectomy is one method of hormone suppression for premenopausal patients with hormone receptor-positive breast cancer. Such specimens could, in theory, harbor occult early ovarian cancer and/or metastatic breast cancer but guidelines for tissue sampling for pathologic examination remain to be addressed. Therefore, we evaluated oophorectomy specimens from 166 patients who underwent ovarian ablation for hormone receptor-positive breast cancer. Results of germline genetic testing were documented by the surgeon in only 31.3% of the pathology specimen requisition forms, whereas that information was available for 81.3% of patients elsewhere in the electronic medical records. All but 5.2% tested negative for a hereditary ovarian cancer gene pathogenic variant before oophorectomy. Complete tissue sampling was performed in 77.1% of the cases and representative sampling in the remainder. No cases of ovarian cancer were observed. Ovarian metastasis of breast cancer was identified in 9.6% of patients, all of whom were already known to have advanced-stage disease. The number of tissue cassettes per ovary required for complete tissue submission was on average three times higher than that for representative tissue sampling (P < 0.01) and ranged up to 20 cassettes per ovary when multiple follicle cysts were present. We propose that guidelines for tissue sampling in this context be defined by a combination of hereditary risk and macroscopic examination; representative sampling is reasonable for macroscopically normal ovaries in hormone receptor-positive breast cancer patients whose germline genetic testing is negative. Positive genetic test results merit complete tissue submission even if macroscopically normal. This strategy balances the goals of early ovarian cancer detection and optimal resource utilization. However, it depends on clear documentation of genetic test results. Our study demonstrates that many opportunities remain to close gaps in the communication of genetic test results by clinicians submitting oophorectomy specimens for pathologic evaluation.

对于激素受体阳性的绝经前乳腺癌患者来说,双侧卵巢切除术是一种激素抑制方法。理论上,此类标本可能隐藏着隐匿性早期卵巢癌和/或转移性乳腺癌,但病理检查的组织取样指南仍有待制定。因此,我们对166名因激素受体阳性乳腺癌而接受卵巢消融术的患者的卵巢切除标本进行了评估。外科医生仅在 31.3% 的病理标本申请表中记录了种系基因检测结果,而 81.3% 的患者可在电子病历的其他地方获得该信息。除5.2%的患者外,其余患者在卵巢切除术前均未检测出遗传性卵巢癌基因致病变异。77.1%的病例进行了完整的组织取样,其余病例进行了代表性取样。未发现卵巢癌病例。在 9.6% 的患者中发现了乳腺癌的卵巢转移,这些患者都已是晚期患者。提交完整组织所需的每个卵巢的组织盒数量平均是代表性组织取样的三倍(P < 0.01),当存在多个卵泡囊肿时,每个卵巢的组织盒数量最多可达 20 个。我们建议,在这种情况下,组织取样的指导原则应结合遗传风险和宏观检查来确定;对于生殖系基因检测阴性的激素受体阳性乳腺癌患者的宏观正常卵巢,代表性取样是合理的。基因检测结果呈阳性的患者,即使宏观检查正常,也应提交完整的组织样本。这一策略兼顾了早期卵巢癌检测和资源优化利用的目标。不过,这取决于基因检测结果的清晰记录。我们的研究表明,临床医生在提交卵巢切除术标本进行病理评估时,仍有很多机会弥补基因检测结果沟通方面的不足。
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引用次数: 0
Mixed Gestational Trophoblastic Tumors-Challenging Clinicopathological Presentations. 混合型妊娠滋养细胞肿瘤--具有挑战性的临床病理表现。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-06-26 DOI: 10.1097/PGP.0000000000001044
Na Niu, Natalia Buza, Pei Hui

Mixed gestational trophoblastic tumors are exceptionally rare and have variable clinicopathological presentations. We report 3 such tumors with different combinations of choriocarcinoma (CC), placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). The patients' age ranged from 38 to 44 years. Mixed trophoblastic tumor was not considered at the initial diagnosis and all 3 tumors were proven of gestational origin by DNA genotyping. Patient #1 presented with serum human chorionic gonadotropin (hCG) of 97 mIU/mL and a 5.6-cm cervical mass that was initially interpreted as PSTT on biopsy. Hysterectomy revealed a mixed PSTT (60%) and ETT (40%) with extrauterine metastases of only the ETT component. The tumor recurred 15 months after a multiagent chemotherapy and was tested positive for programmed death-ligand 1. The patient received immune checkpoint inhibitor therapy and remained disease-free after 24 months. Patient #2 presented with vaginal bleeding and serum hCG of 46,458 mIU/mL. An endometrial biopsy was interpreted as CC. Recurrence developed in the uterus and lung after methotrexate-based chemotherapy. A mixed CC and ETT were eventually diagnosed upon consultation review. Patient #3 presented with a complete hydatidiform mole and serum hCG of 744,828 mIU/mL. Three months after methotrexate, followed by actinomycin D therapy, a uterine mass was found. Hysterectomy revealed a mixed CC and PSTT. In conclusion, the rarity, elusive presentation, and wide range of histology make the diagnosis of mixed trophoblastic tumors highly challenging. The clinical management and prognosis are dictated by each component of the tumor. CC component must be considered when the patient presents with a high serum hCG level.

混合性妊娠滋养细胞肿瘤异常罕见,临床病理表现各不相同。我们报告了3例这样的肿瘤,它们分别是绒毛膜癌(CC)、胎盘部位滋养细胞肿瘤(PSTT)和上皮样滋养细胞肿瘤(ETT)的不同组合。患者年龄在 38 至 44 岁之间。最初诊断时未考虑混合型滋养细胞肿瘤,通过DNA基因分型,所有3种肿瘤均被证实为妊娠源性肿瘤。1 号患者的血清人绒毛膜促性腺激素(hCG)为 97 mIU/mL,宫颈肿块 5.6 厘米,活检初步诊断为 PSTT。子宫切除术发现了混合型 PSTT(60%)和 ETT(40%),只有 ETT 部分有宫外转移。患者接受了免疫检查点抑制剂治疗,24 个月后仍未复发。2 号患者出现阴道出血,血清 hCG 为 46,458 mIU/mL。子宫内膜活检被解释为 CC。甲氨蝶呤化疗后,子宫和肺部复发。经会诊复查,最终确诊为混合型 CC 和 ETT。3 号患者出现完全水样痣,血清 hCG 为 744 828 mIU/mL。在使用甲氨蝶呤和放线菌素 D 治疗三个月后,发现子宫肿块。子宫切除术发现了混合型 CC 和 PSTT。总之,混合型滋养细胞肿瘤的罕见性、难以捉摸的表现和广泛的组织学类型使其诊断极具挑战性。临床治疗和预后取决于肿瘤的各个组成部分。当患者出现高血清 hCG 水平时,必须考虑 CC 成分。
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引用次数: 0
The Prognostic Value of Tumor Cell Clusters in the Fallopian Tube Lumen in Stage I Endometrioid Carcinoma. I 期子宫内膜样癌输卵管腔内肿瘤细胞集群的预后价值
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-06-25 DOI: 10.1097/PGP.0000000000001054
Ye Jin Yoo, Yeon Joo Kim, Yong-Man Kim, Kyu-Rae Kim, Uiree Jo, Young Seok Kim

The aim of this study was to investigate the pathologic prognostic factors such as tumor cell clusters (TCCs) in the fallopian tube lumen, myometrial invasion patterns, and positive peritoneal cytology (PPC) in women with Stage I endometrial endometrioid carcinoma (EEC). From 2009 to 2020, consecutive patients with Stage I EEC who underwent hysterectomy and bilateral salpingectomy were included. The primary outcome was the recurrence-free survival (RFS) rate, and the clinicopathological factors affecting RFS were analyzed. A total of 765 patients were enrolled. Seventeen patients (2.2%) had TCC in the fallopian tube lumen, and 58 patients showed a microcystic elongated and fragmented pattern (7.6%). PPC was found in 19 patients (2.5%). The median follow-up period was 61.0 months (range: 2.0-149.7). The majority (88.6%) of patients had Stage IA EEC. The 5-year RFS and overall survival rates were 97.5% and 98.5%, respectively. In multivariate analysis for RFS, the significant prognostic factors were lymphovascular invasion (hazard ratio = 4.604; 95% CI: 1.387-15.288; P = 0.013) and grade (grade 2; hazard ratio = 4.949; 95% CI: 1.035-23.654; P = 0.045, and grade 3; hazard ratio = 5.469; 95% CI: 1.435-20.848; P = 0.013). Other pathologic factors including TCC in the fallopian tube lumen, myometrial invasion patterns, PPC, and hormonal status had no prognostic significance. TCC in the fallopian tube lumen, myometrial invasion pattern, PPC, and estrogen and progesterone receptor positivity were not significant prognostic factors in Stage I EEC. In contrast, lymphovascular invasion and grade were significant prognostic factors.

本研究旨在探讨I期子宫内膜样癌(EEC)女性患者的病理预后因素,如输卵管腔内的肿瘤细胞簇(TCC)、子宫肌层浸润模式和腹膜细胞学(PPC)阳性。研究纳入了2009年至2020年期间连续接受子宫切除术和双侧输卵管切除术的I期EEC患者。主要结果是无复发生存率(RFS),并分析了影响RFS的临床病理因素。共有 765 名患者入选。17名患者(2.2%)的输卵管腔内有TCC,58名患者(7.6%)的输卵管呈微囊状拉长和碎裂。19名患者(2.5%)发现了PPC。中位随访时间为 61.0 个月(2.0-149.7 个月)。大多数患者(88.6%)的EEC为IA期。5年RFS和总生存率分别为97.5%和98.5%。在RFS的多变量分析中,重要的预后因素是淋巴管侵犯(危险比=4.604;95% CI:1.387-15.288;P=0.013)和分级(2级;危险比=4.949;95% CI:1.035-23.654;P=0.045;3级;危险比=5.469;95% CI:1.435-20.848;P=0.013)。其他病理因素,包括输卵管腔内的TCC、子宫肌层侵袭模式、PPC和激素状况,均无预后意义。输卵管腔内的 TCC、子宫肌层侵袭模式、PPC 以及雌激素和孕激素受体阳性对 I 期 EEC 的预后无显著意义。相反,淋巴管侵犯和分级则是重要的预后因素。
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引用次数: 0
Comparison of PD-L1, VISTA, LAG-3, and GAL-3 Expressions and Their Relationships to Mismatch Repair Protein and p53 Expression in 529 Cases of Endometrial Carcinoma. 比较 529 例子宫内膜癌中 PD-L1、VISTA、LAG-3 和 GAL-3 的表达及其与错配修复蛋白和 p53 表达的关系。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-06-13 DOI: 10.1097/PGP.0000000000001049
Dilara Irem Arslan-Kahraman, Betul Ogut, Mehmet Arda Inan, Ferah Kazanci, Mehmet Anil Onan, Mehmet Erdem, Ozlem Erdem

The aim of this study is to evaluate the expressions of programmed death-ligand 1 (PD-L1), V-domain Ig suppressor of T-cell activation (VISTA), lymphocyte activation gene-3 (LAG-3), and galectin-3 (GAL-3), in mismatch repair-deficient (MMRd)/MMR-proficient and abnormal p53 expressing endometrial carcinomas and their relationship with clinical-histopathological features. Patients who underwent surgery for endometrial carcinoma between January 2008 and December 2018 were included in the study. Immunohistochemical analysis of MLH1, PMS2, MSH2, MSH6, p53, PD-L1, VISTA, LAG-3, and GAL-3 was performed on the tissue samples of microarray. A total of 529 patients were included. MMRd and p53-mutant tumors accounted for 31.5% and 11.5% of cases, respectively. PD-L1 and LAG-3 expressions in the MMRd and p53-mutant groups were higher than in the MMR-proficient group (P < 0.001). GAL-3 expression in the MMR-proficient group was statistically higher than in the MMRd and p53-mutant groups (P < 0.001). Mean age, grade, International Federation of Gynecology and Obstetrics stage, lymphovascular invasion, and lymph node metastasis were significantly higher in the p53-mutant group (P < 0.001). In the group with PD-L1 expression, nonendometrioid histologic type, tumor grade, and lymphovascular invasion were significantly higher (P < 0.001). Tumor grade, lymphovascular invasion, lymph node metastasis, and microcystic, elongated and fragmented pattern of invasion were significantly higher in the group with high VISTA expression (P < 0.05). Tumor grade was significantly higher in the group with LAG-3 expression (P < 0.001). Immunohistochemically determined subgroups and PD-L1, VISTA, LAG-3, and GAL-3 expression levels may be useful indicators of molecular features, and clinical outcomes also may have important implications for the development of targeted therapies in endometrial carcinoma.

本研究旨在评估程序性死亡配体1(PD-L1)、V-domain Ig抑制T细胞活化(VISTA)、淋巴细胞活化基因-3(LAG-3)和galectin-3(GAL-3)在错配修复缺陷(MMRd)/MMR-pficient和p53表达异常的子宫内膜癌中的表达及其与临床病理特征的关系。研究纳入了2008年1月至2018年12月期间接受子宫内膜癌手术的患者。对芯片组织样本进行MLH1、PMS2、MSH2、MSH6、p53、PD-L1、VISTA、LAG-3和GAL-3的免疫组化分析。共纳入了 529 例患者。MMRd和p53突变肿瘤分别占31.5%和11.5%。PD-L1和LAG-3在MMRd组和p53突变组的表达高于MMR-proficient组(P < 0.001)。MMR缺陷组的GAL-3表达在统计学上高于MMRd组和p53突变组(P < 0.001)。p53突变组的平均年龄、分级、国际妇产科联盟分期、淋巴管侵犯和淋巴结转移均显著高于p53突变组(P < 0.001)。PD-L1表达组中,非子宫内膜组织学类型、肿瘤分级和淋巴管侵犯明显高于P53突变组(P<0.001)。VISTA 高表达组的肿瘤分级、淋巴管侵犯、淋巴结转移以及微囊状、拉长状和碎裂状侵犯模式均明显高于对照组(P<0.05)。LAG-3表达组的肿瘤分级明显更高(P < 0.001)。免疫组化确定的亚组和PD-L1、VISTA、LAG-3和GAL-3表达水平可能是分子特征的有用指标,临床结果也可能对子宫内膜癌靶向疗法的开发具有重要意义。
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引用次数: 0
Folate Receptor Immunohistochemical Staining and Gynecologic Tumors: Initial Experience With 216 Cases. 叶酸受体免疫组化染色与妇科肿瘤:216 例病例的初步经验
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-06-12 DOI: 10.1097/PGP.0000000000001053
Barrett C Lawson, Mario L Marques-Piubelli, Shannon N Westin, Anais Malpica
<p><p>Folate receptor alpha has been shown to have possible mechanisms of tumorigenesis in malignancies, becoming a potential target for therapy. Mirvetuximab soravtansine is an antifolate receptor alpha monoclonal antibody, with an approved FOLR1-2.1 immunohistochemical biomarker. After IRB approval, a retrospective review of gynecologic pathology cases was performed to identify cases in which FOLR1 immunohistochemistry (IHC) was performed at our institution over a period of 9 months as part of clinical care for therapy eligibility. Clinical data collected included patients' age, tumor histotype, tumor grade, primary tumor site, FIGO stage, dates of recurrence/progression, and use of mirvetuximab therapy. FOLR1 IHC data were recorded, including the date specimen obtained, date IHC was performed, site tested, case type, percentage tumor staining, and intensity. Cases were deemed positive or negative according to current recommendations (75%, 2-3+intensity). Two hundred sixteen cases were identified. Patient ages ranged from 25 to 83 years old (median: 59 yr). Staining intensity was reported as 0 in 15 (6.9%) cases, weak (1+) in 8 (3.7%), moderate (2+) in 27 (12.5%), strong (3+) in 27 (12.5%), weak-to-moderate (1-2+) in 15 (6.9%), and moderate-to-strong (2-3+) in 99 (45.8%); intensity was not provided in 25 (11.6%). Percentage of tumor staining ranged from 0 to 100, with a median of 60. The IHC was overall deemed positive in 98 (45.4%) cases and negative in 118 (54.6%). By histotype, 5 of 17 (29.4%) low-grade serous carcinomas, 88 of 162 (54.3%) high-grade serous carcinomas, 3 of 5 (60%) of carcinosarcomas, and 2 of 6 (33.3%) of mixed carcinomas were positive. No case of clear cell CA, endometrioid CA, Mullerian CA NOS, serous borderline, mucinous CA, or granulosa cell tumor was positive. The primary site of disease was tubo-ovarian in 192 (88.9%) cases, peritoneal in 8 (3.7%) cases, uterine in 3 (1.4%) cases, and unknown in 13 (6%) cases. By site on which immunohistochemical stain was performed: primary site positive in 53 of 96 (55.2%) cases, metastatic site at time of diagnosis/debulking positive in 23 of 41 (52.1%) cases, and metastatic/recurrent cases positive in 22 of 79 (27.8%) cases. There was a statistically significant correlation when comparing the positivity rates between these sites (P = 0.0004). Survival data were examined with high-grade serous carcinoma, with no statistically significant difference between positive and negative cases in overall survival (P = 0.622) or progression-free survival (P = 0.711). Biopsy specimens were positive in 17 (25%) cases, while negative in 51 (75%), whereas resection specimens were positive in 81 (54.7%) and negative in 67 (45.3%), a statistically significant difference (P < 0.0001). Cases that were <19 months old had 38 (36.2%) positive and 67 (63.8%) negative, compared with cases ≥19 months old that had 60 (54.1%) positive and 51 (45.9%) negative, a statistically significant difference (P = 0.008
叶酸受体α在恶性肿瘤中被证明具有可能的肿瘤发生机制,成为潜在的治疗靶点。Mirvetuximab soravtansine是一种抗叶酸受体α单克隆抗体,其FOLR1-2.1免疫组化生物标志物已获批准。在获得 IRB 批准后,我们对妇科病理病例进行了回顾性审查,以确定本机构在 9 个月内进行过 FOLR1 免疫组化 (IHC) 分析的病例,作为治疗资格临床护理的一部分。收集的临床数据包括患者的年龄、肿瘤组织型、肿瘤分级、原发肿瘤部位、FIGO 分期、复发/进展日期以及使用米韦单抗治疗的情况。记录的 FOLR1 IHC 数据包括标本获取日期、IHC 进行日期、检测部位、病例类型、肿瘤染色百分比和强度。根据目前的建议(75%,2-3+强度),病例被视为阳性或阴性。共鉴定出 216 例病例。患者年龄从 25 岁到 83 岁不等(中位数:59 岁)。染色强度为 0 的有 15 例(6.9%),弱(1+)的有 8 例(3.7%),中等(2+)的有 27 例(12.5%),强(3+)的有 27 例(12.5%),弱到中等(1-2+)的有 15 例(6.9%),中等到强(2-3+)的有 99 例(45.8%);未提供强度的有 25 例(11.6%)。肿瘤染色的百分比从 0 到 100 不等,中位数为 60。98 例(45.4%)的 IHC 结果为阳性,118 例(54.6%)为阴性。按组织类型划分,17 例低度浆液性癌中有 5 例(29.4%)呈阳性,162 例高级别浆液性癌中有 88 例(54.3%)呈阳性,5 例癌肉瘤中有 3 例(60%)呈阳性,6 例混合型癌中有 2 例(33.3%)呈阳性。没有一例透明细胞癌、子宫内膜样癌、Mullerian CA NOS、浆液性边界癌、粘液腺癌或颗粒细胞瘤呈阳性。192例(88.9%)患者的原发部位为输卵管,8例(3.7%)患者的原发部位为腹膜,3例(1.4%)患者的原发部位为子宫,13例(6%)患者的原发部位不明。按进行免疫组化染色的部位划分:96 个病例中有 53 个(55.2%)原发部位阳性,41 个病例中有 23 个(52.1%)诊断时/清扫时转移部位阳性,79 个病例中有 22 个(27.8%)转移/复发病例阳性。在比较这些部位的阳性率时,存在统计学意义上的显著相关性(P = 0.0004)。对高级别浆液性癌的生存数据进行了研究,发现阳性和阴性病例的总生存期(P = 0.622)或无进展生存期(P = 0.711)差异无统计学意义。活检标本阳性病例有 17 例(25%),阴性病例有 51 例(75%);切除标本阳性病例有 81 例(54.7%),阴性病例有 67 例(45.3%),差异有统计学意义(P < 0.0001)。病例
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引用次数: 0
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International Journal of Gynecological Pathology
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