Choriocarcinoma

绒毛膜癌
  • 文章类型: Case Reports
    背景:绒毛膜癌是一种高度恶性的妊娠相关滋养细胞肿瘤,以早期转移到肺部为特征。因此,由于远处转移,患者可能会出现非神经系统症状。足月妊娠后绒毛膜癌的发生率非常罕见(1/160,000妊娠)。
    方法:我们报告一例20岁的伊朗妇女,gravida2para1活1流产1,她在分娩后第二天因突然发作的呼吸困难和左半胸疼痛而被转诊到我们的妇科。指数妊娠无任何并发症。在最初的检查之后,β-人绒毛膜促性腺激素(HCG)水平的升高(>1,000,000)以及远处转移的临床(阴道病变)和放射学证据(双侧肺结节)的鉴定指导我们对肺转移性绒毛膜癌的诊断。肿瘤学会诊后,依托泊苷,甲氨蝶呤,放线菌素D,环磷酰胺,并对患者开始长春新碱化疗方案。她对治疗反应良好,目前正在继续她的化疗过程。
    结论:如果按时开始治疗,绒毛膜癌的预后非常好。我们建议临床医生在产后并发症的鉴别诊断中应考虑妊娠滋养细胞瘤。尤其是在足月和非磨牙妊娠后。
    BACKGROUND: Choriocarcinoma is a highly malignant pregnancy-related trophoblastic neoplasm, characterized by early metastasis to the lungs. Therefore, patients may manifest nongynecological symptoms owing to distant metastases. The incidence of choriocarcinoma after a term pregnancy is really rare (1/160,000 pregnancies).
    METHODS: We report a case of a 20-year-old Iranian woman, gravida 2 para 1 live 1 abortion 1, who was referred to our gynecology department with sudden onset dyspnea and pain in the left hemithorax the day after her labor. The index pregnancy was without any complications. After the initial workup, the elevation of β-human chorionic gonadotropin (HCG) levels (> 1,000,000) along with the identification of clinical (vaginal lesions) and radiological evidence of distant metastases (bilateral pulmonary nodes) directed us toward pulmonary metastatic choriocarcinoma diagnosis. After the oncology consult, the etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy regimen was started for the patient. She responded well to the treatment and is currently continuing her chemotherapy process.
    CONCLUSIONS: The prognosis of choriocarcinoma is very good if the treatment is started on time. We suggest that clinicians should consider gestational trophoblastic neoplasia in their differential diagnosis of the post-natal period complications, especially after a term and nonmolar pregnancy.
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  • 文章类型: Case Reports
    原发性和继发性肿瘤很少涉及肺动脉。临床和影像学特征与PE相似,因此诊断具有挑战性。绒毛膜癌是一种恶性生殖细胞肿瘤,通常在女性生殖道。很少,它们可以表现为PA血栓。有磨牙妊娠史的女性患者,异位妊娠,流产或者在这种情况下是流产,妊娠滋养细胞疾病的风险更高,可以通过这种方式表现出来,尽管这是罕见的。在本报告中,我们描述了一名52岁女性的病例,该女性有1个月的呼吸困难和胸膜炎性下胸痛恶化的病史。CT肺动脉造影证实了肺栓塞(PE)的诊断,左肺动脉(PA)有大量血栓。她在标准抗凝治疗中未能改善,并被发现β-人绒毛膜促性腺激素升高>100,000。这导致广泛的恶性肿瘤发病。唯一相关的发现是PA血栓中氟脱氧葡萄糖(FDG)积累的增加。对血栓进行血管内活检,患者被诊断为PA绒毛膜癌。该病例强调了对PE抗凝治疗无效的患者进行进一步调查的重要性。它还说明了介入放射学在获得PA肿瘤血栓患者的组织学诊断中的作用。
    Pulmonary arteries may rarely be involved by primary and secondary tumors. Clinical and imaging features mimic those of PE making it challenging to diagnose. Choriocarcinoma is a malignant germ cell tumor, typically in the female genital tract. Rarely, they can present as PA thrombus. Female patients with a history of a molar pregnancy, ectopic pregnancy, abortion or in this case a miscarriage, are at a higher risk of gestational trophoblastic disease which can manifest in this way, albeit this is rare. In this report we describe the case of a 52-year-old female who presented with a 1 month history of worsening dyspnea and pleuritic lower thoracic pain. A diagnosis of pulmonary embolism (PE) was confirmed on CT pulmonary angiogram, with a large volume thrombus in the left pulmonary artery (PA). She failed to improve on standard anticoagulation therapy and was found to have a raised beta-human chorionic gonadotropin of >100,000. This leads to an extensive malignancy work-up. The only pertinent finding was that of increased fluorodeoxyglucose (FDG) accumulation in the PA thrombus. Endovascular biopsy of the thrombus was performed, and the patient was diagnosed with choriocarcinoma of the PA. This case highlights the importance of further investigation in patients failing to respond to anticoagulation therapy for PE. It also illustrates the role of interventional radiology in obtaining histological diagnosis in patient\'s presenting with PA tumor thrombus.
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  • 文章类型: Journal Article
    目的:很少有研究对生殖细胞肿瘤(GCT)的男性儿童和成人之间的组织学差异和生存意义进行量化。我们使用监测评估了这些差异以及与癌症特异性生存率(CSS)的关联,流行病学,和最终结果(SEER)癌症登记。
    方法:SEER(1988-2016)用于鉴定诊断为精原细胞瘤和非精原细胞瘤GCT(NSGCT)的0至40岁男性患者。按年龄组(0-4,12-18,19-40岁)比较了人口统计学和肿瘤特征以及组织学分布。在多变量Cox比例风险回归模型中评估CSS。
    结果:在确定的27,204名患者中,1,538(5.7%)为儿科(0-18岁)。Seminoma(54.3%)在成年患者(19-40岁)中占主导地位。在0到4岁之间,卵黄囊瘤(71.2%)和畸胎瘤(21.5%)最为常见。混合GCT(52.7%)在12至18岁精原细胞瘤中最普遍,胚胎,畸胎瘤的发生率分别为12%至15%。相对于儿科患者,在平均随访9年的Kaplan-Meier曲线上,成年患者精原细胞瘤的CSS相似,但NSGCT的CSS更差.绒毛膜癌和卵黄囊瘤相对于精原细胞瘤预后最差(分别为HR5.7和HR11.1,P<0.01)和成人(分别为HR4.6和HR4.6,两者P<0.01)针对阶段进行了调整。
    结论:GCT的组织学因年龄而异,卵黄囊瘤和畸胎瘤在0至4岁的男性患者中占优势,混合GCT12到18年,和精原细胞瘤19到40年。患有NSGCT的儿科患者的CSS高于成人患者。在研究期间,混合GCT占GCT的比例越来越高。年龄,舞台,和组织学影响CSS在儿童和成人人群。
    OBJECTIVE: Few studies have quantified differences in histology and implications for survival between male children and adults with germ cell tumors (GCT). We evaluated these differences and associations with cancer-specific survival (CSS) using Surveillance, Epidemiology, and End Results (SEER) cancer registries.
    METHODS: SEER (1988-2016) was used to identify male patients 0 to 40 years of age diagnosed with seminoma and nonseminomatous GCT (NSGCT). Demographic and tumor characteristics were tabulated with histology distributions compared by age group (0-4, 12-18, 19-40 years old). CSS was evaluated in multivariable Cox proportional hazards regression models.
    RESULTS: Among 27,204 patients identified, 1,538 (5.7%) were pediatric (0-18 years). Seminoma (54.3%) predominated in adult patients (ages 19-40). Among 0 to 4 years-old, yolk sac tumor (71.2%) and teratoma (21.5%) were most common. Mixed GCT (52.7%) was most prevalent among 12 to 18 years-old with seminoma, embryonal, and teratoma occurring in 12 to 15% each. Relative to pediatric patients, adult patients had similar CSS for seminoma but worse CSS for NSGCT on Kaplan-Meier curves with 9 years mean follow-up. Choriocarcinoma and yolk sac tumors carried the worst prognosis relative to seminoma for both children (HR 5.7 and HR 11.1, respectively, both P < 0.01) and adults (HR 4.6 and HR 4.6, respectively, both P < 0.01) adjusted for stage.
    CONCLUSIONS: Histology of GCTs vary by age with yolk sac tumors and teratoma predominating for male patients 0 to 4 years, mixed GCT for 12 to 18 years, and seminoma for 19 to 40 years. Pediatric patients with NSGCT had higher CSS than their adult counterparts. Mixed GCT represented an increasing proportion of GCT over the study period. Age, stage, and histology impact CSS in both pediatric and adult populations.
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  • 文章类型: Journal Article
    甲氨蝶呤(MTX)通常作为妊娠滋养细胞肿瘤(GTN)的初始治疗,但MTX单药治疗可能对高危GTN和绒毛膜癌无效.MTX的细胞摄取对其药理活性至关重要。因此,本研究旨在探讨MTX在绒毛膜癌细胞中的细胞药代动力学和转运机制。为了定量细胞基质中的MTX浓度,建立并初步确认了液相色谱-串联质谱法。MTX在BeWo的积累,JEG-3和JAR细胞最小。此外,叶酸受体α(FRα)和乳腺癌耐药蛋白(BCRP)的mRNA水平在三种绒毛膜癌细胞系中相对较高,而质子偶联叶酸转运蛋白(PCFT),减少叶酸载体(RFC),有机阴离子转运蛋白(OAT)4较低。此外,其他转运蛋白的表达非常低或检测不到。值得注意的是,靶向FRα的抑制剂和小干扰RNA(siRNA)的应用,RFC,和PCFT导致BeWo细胞中MTX的积累显着减少。相反,多药耐药蛋白1(MDR1)和BCRP抑制剂的共同给药增加了MTX的积累。此外,OATs和有机阴离子转运多肽(OATPs)的抑制剂减少了MTX的积累,而肽转运蛋白抑制剂则没有效果。siRNA敲低实验和转运蛋白过表达细胞模型的结果表明,MTX不是核苷转运蛋白的底物。总之,结果表明,FRα和PCFT等多种转运蛋白,RFC,OAT4和OATPs可能参与了MTX的摄取,而MDR1和BCRP与MTX从绒毛膜癌细胞的流出有关。这些结果对预测转运蛋白介导的药物相互作用具有重要意义,并为进一步研究提高MTX敏感性提供了潜在的方向。
    Methotrexate (MTX) is commonly prescribed as the initial treatment for gestational trophoblastic neoplasia (GTN), but MTX monotherapy may not be effective for high-risk GTN and choriocarcinoma. The cellular uptake of MTX is essential for its pharmacological activity. Thus, our study aimed to investigate the cellular pharmacokinetics and transport mechanisms of MTX in choriocarcinoma cells. For the quantification of MTX concentrations in cellular matrix, a liquid chromatography-tandem mass spectrometry method was created and confirmed initially. MTX accumulation in BeWo, JEG-3, and JAR cells was minimal. Additionally, the mRNA levels of folate receptor α (FRα) and breast cancer resistance protein (BCRP) were relatively high in the three choriocarcinoma cell lines, whereas proton-coupled folate transporter (PCFT), reduced folate carrier (RFC), and organic anion transporter (OAT) 4 were low. Furthermore, the expression of other transporters was either very low or undetectable. Notably, the application of inhibitors and small interfering RNAs (siRNAs) targeting FRα, RFC, and PCFT led to a notable decrease in the accumulation of MTX in BeWo cells. Conversely, the co-administration of multidrug resistance protein 1 (MDR1) and BCRP inhibitors increased MTX accumulation. In addition, inhibitors of OATs and organic-anion transporting polypeptides (OATPs) reduced MTX accumulation, while peptide transporter inhibitors had no effect. Results from siRNA knockdown experiments and transporter overexpression cell models indicated that MTX was not a substrate of nucleoside transporters. In conclusion, the results indicate that FRα and multiple transporters such as PCFT, RFC, OAT4, and OATPs are likely involved in the uptake of MTX, whereas MDR1 and BCRP are implicated in the efflux of MTX from choriocarcinoma cells. These results have implications for predicting transporter-mediated drug interactions and offer potential directions for further research on enhancing MTX sensitivity.
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  • 文章类型: Journal Article
    新生儿和婴儿绒毛膜癌(N-CC)是一种极其罕见的,但是侵袭性癌症,经常观察到伴随的母亲疾病。回顾,在法国和波兰接受婴儿绒毛膜癌治疗的患者的双边研究分析了8例N-CC,中位年龄6周。所有肿瘤都是弥漫性的。六名患者接受了铂类药物治疗,5人推迟了对残留的远处肿瘤部位的手术。在后续行动结束时,4例患者完全缓解,4例死于该病.除了两种情况,母亲同时患有转移性绒毛膜癌.即使结果仍然很差,患者可以通过多模式治疗治愈。
    Choriocarcinoma in neonates and infants (N-CC) is an extremely rare, but aggressive cancer, frequently observed with concomitant maternal disease. A retrospective, bi-national study of patients treated in France and Poland for infantile choriocarcinoma analysed eight cases of N-CC, median age of 6 weeks. All tumours were diffuse. Six patients received a platinum-based regimen, and five had delayed surgery on residual distant tumour sites. At the end of follow-up, four patients were in complete remission and four had died of the disease. In all but two cases, mothers had simultaneous metastatic choriocarcinoma. Even if the outcome remains poor, patients could be cured with multimodal therapy.
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  • 文章类型: Case Reports
    一名65岁的呼吸困难和咯血的男性,在胸部计算机断层扫描(CT)上表现为右上叶肿块,伴有纵隔淋巴结肿大和双侧肺结节。疑似肺癌。支气管和CT引导活检显示低分化癌。在做出明确诊断之前,他的病情迅速恶化。尸检显示原发性纵隔绒毛膜癌。原发性纵隔绒毛膜癌罕见,难以早期诊断,预后不良。在肿瘤在肺和纵隔中扩展并表现出库分化癌的病理发现的患者中,我们应该考虑绒毛膜癌,评价血清β-人绒毛膜促性腺激素水平。
    A 65-year-old man with dyspnea and hemoptysis presented with a right upper lobe mass associated with enlarged mediastinal lymph nodes and bilateral pulmonary nodules on chest computed tomography (CT), suspected lung cancer. Bronchial and CT-guided biopsies revealed poorly differentiated carcinoma. His condition deteriorated rapidly before a definitive diagnosis could be made. Autopsy revealed primary mediastinal choriocarcinoma. Primary mediastinal choriocarcinomas are rare, difficult to diagnose early and have a poor prognosis. In patients with a tumor expanding across the lung and mediastinum and exhibiting pathologic findings of a pooly differentiated carcinoma, we should consider choriocarcinoma, evaluating the serum β-human chorionic gonadotropin levels.
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  • 文章类型: Journal Article
    背景:胎盘内绒毛膜癌(IC)是一种极为罕见的妊娠绒毛膜癌亚型。IC患者的长期随访和生殖结局仍不清楚。这里,我们报告了一系列14例病例,并进行了文献综述,以评估这种罕见疾病的生育力和复发结果。
    结果:本研究纳入了2002年1月至2022年7月在北京协和医院接受病理证实的14例IC患者。其中一半患有转移性IC,并通过有或没有手术的化疗进行治疗。只有1名患者患有化学耐药性疾病,但她在免疫疗法后完全缓解。中位随访时间为45.5个月(范围4-192),没有复发。一名化疗后缓解的转移性IC患者足月分娩。在有生育需求的5名患者中,3放弃了对怀孕的追求,因为\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\我们回顾了1963年至2022年的中英文文献中的89例IC,仅报道了5例随后的妊娠。所有病例均为非转移性IC.
    结论:IC对化疗敏感,长期缓解良好,复发率低。转移性或非转移性IC患者治疗后可取得良好的妊娠效果。医生应该多关注这些患者的心理。
    背景:不适用。
    BACKGROUND: Intraplacental choriocarcinoma (IC) is an extremely rare subtype of gestational choriocarcinoma. The long-term follow-up and reproductive outcomes of IC patients remain unclear. Here, we report a series of 14 cases and conduct a literature review to assess the fertility and recurrence results of this rare disease.
    RESULTS: Fourteen patients with pathologically confirmed IC treated in Peking Union Medical College Hospital between January 2002 and July 2022 were included in this study. Half of them had metastatic IC and were treated by chemotherapy with or without surgery. Only 1 patient had chemoresistant disease, but she achieved complete remission after immunotherapy. The median follow-up time was 45.5 months (range 4-192), and no recurrence occurred. One metastatic IC patient who achieved remission after chemotherapy had a full-term delivery. Among the 5 patients with fertility demands, 3 abandoned their pursuit of pregnancy because of \"fear and worry about choriocarcinoma recurrence\". We reviewed a total of 89 cases of IC in English and Chinese literature from 1963 to 2022, and only 5 cases with subsequent pregnancy were reported, all of them were nonmetastatic IC cases.
    CONCLUSIONS: IC is sensitive to chemotherapy and has good long-term remission and a low recurrence rate. Patients with metastatic or nonmetastatic IC can have good pregnancy results after treatment. Doctors should pay more attention to the psychology of these patients.
    BACKGROUND: N/A.
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  • 文章类型: Journal Article
    合胞体滋养层是由单核细胞滋养层融合产生的多核结构。覆盖胎盘绒毛并调节跨母胎界面的运输。这里,我们问绒毛发育过程中必须产生的动态机械力是否会影响融合,并利用体外绒毛膜癌滋养细胞模型探讨这一问题。我们证明了机械应力模式出现在细胞单层的局部融合位点周围,符合绒毛形态发生的计算预测的模式。然后,我们将这些机械应力模式从外部施加到细胞单层,并证明等双轴压缩应力(但不是单轴或等双轴拉伸应力)增强了syndecan-1的表达和E-cadherin的损失,作为融合的标记。这些发现表明,有助于雕刻胎盘绒毛的机械应力也可能影响发育组织的融合。然后,我们将此概念扩展到3D文化,并证明可以通过对球体模型施加低等距压缩应力来增强融合。即使没有诱导剂。这些结果表明,机械刺激是细胞融合的有效激活剂,提出改进实验性生殖模型的新途径,胎盘组织工程,了解妊娠发育障碍。
    The syncytiotrophoblast is a multinucleated structure that arises from fusion of mononucleated cytotrophoblasts, to sheath the placental villi and regulate transport across the maternal-fetal interface. Here, we ask whether the dynamic mechanical forces that must arise during villous development might influence fusion, and explore this question using in vitro choriocarcinoma trophoblast models. We demonstrate that mechanical stress patterns arise around sites of localized fusion in cell monolayers, in patterns that match computational predictions of villous morphogenesis. We then externally apply these mechanical stress patterns to cell monolayers and demonstrate that equibiaxial compressive stresses (but not uniaxial or equibiaxial tensile stresses) enhance expression of the syndecan-1 and loss of E-cadherin as markers of fusion. These findings suggest that the mechanical stresses that contribute towards sculpting the placental villi may also impact fusion in the developing tissue. We then extend this concept towards 3D cultures and demonstrate that fusion can be enhanced by applying low isometric compressive stresses to spheroid models, even in the absence of an inducing agent. These results indicate that mechanical stimulation is a potent activator of cellular fusion, suggesting novel avenues to improve experimental reproductive modelling, placental tissue engineering, and understanding disorders of pregnancy development.
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  • 文章类型: Case Reports
    绒毛膜癌综合征是一种罕见的肿瘤溶解综合征,主要发生在转移性生殖细胞肿瘤患者中。特别是那些出现广泛肺转移的患者。我们报告了一例先前健康的37岁男性,其表现为无痛的左侧颈部肿块和乳头,对轻触的敏感性增加。检查显示β-人绒毛膜促性腺激素显著升高,睾丸肿块,和无数的肺转移,提示转移性非精原细胞生殖细胞肿瘤。依托泊苷化疗开始后,异环磷酰胺,和顺铂(VIP),患者呼吸功能迅速下降,在开始治疗后六周,最终导致急性呼吸窘迫综合征和随后的呼吸衰竭死亡。该病例强调了早期发现和干预在管理非精原细胞生殖细胞肿瘤中的重要性,并强调了对绒毛膜癌综合征风险意识的迫切需要。生育保护的治疗延迟的挑战,并探索替代治疗策略以改善该高危患者人群的预后。
    Choriocarcinoma syndrome is a rare form of tumor lysis syndrome that predominantly occurs in patients with metastatic germ cell tumors, particularly those presenting with extensive lung metastases. We report a case of a previously healthy 37-year-old male who presented with a painless left-sided neck lump and nipples with an increased sensitivity to light touch. Workup revealed a significantly elevated beta-human chorionic gonadotropin, a testicular mass, and innumerable pulmonary metastases, suggesting metastatic non-seminomatous germ cell tumor. Following the initiation of chemotherapy with etoposide, ifosfamide, and cisplatin (VIP), the patient experienced a rapid decline in respiratory function, culminating in acute respiratory distress syndrome and subsequent death from respiratory failure six weeks after starting treatment. This case emphasizes the importance of early detection and intervention in managing non-seminomatous germ cell tumors and highlights the critical need for awareness of choriocarcinoma syndrome\'s risks, the challenges of treatment delays for fertility preservation, and the exploration of alternative therapeutic strategies to improve outcomes in this high-risk patient population.
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  • 文章类型: Journal Article
    生殖细胞肿瘤包括由生殖细胞谱系引起的广谱肿瘤,显示不同的组织学特征和临床表现。这些肿瘤包括一系列良性和恶性实体。虽然全球趋势提供了对其患病率的见解,特定的区域差异,比如印度西北部的那些,少探索。这项研究旨在通过检查三级癌症医院内生殖细胞肿瘤的患病率和特征来弥合这一知识鸿沟。在这个回顾性分析中,纳入了在指定三级癌症医院3年内诊断的所有生殖细胞肿瘤病例.排除记录不完整或病理资料不充分的病例。包括组织学亚型的数据,患者年龄分布,临床表现,收集并分析组织病理学特征。该研究包括145例生殖细胞肿瘤。畸胎瘤是最常见的亚型,成熟的畸胎瘤占大多数。最高的发病率发生在21-30岁年龄组,平均年龄为24.77岁。腹部肿块(56%)和腹痛(34%)是突出的临床表现。良性病例占多数85.5%。发现实体肿瘤(p<0.00001)和超过10厘米的肿瘤(p.029028)具有很高的恶性倾向,这被证明具有统计学意义。这项研究全面解释了生殖细胞肿瘤的患病率,临床特征,以及印度西北部一家三级癌症医院的组织病理学亚型。畸胎瘤占主导地位,特别是成熟的,与全球趋势保持一致。年龄分布和临床表现反映了共同的模式。不同的组织病理学表现强调了生殖细胞肿瘤的异质性。这项研究为临床管理和进一步的区域研究提供了有价值的见解。
    Germ cell tumors encompass a broad spectrum of neoplasms arising from germ cell lineage, demonstrating varying histological profiles and clinical presentations. These tumors encompass a range of benign and malignant entities. While global trends provide insights into their prevalence, specific regional variations, such as those within North-Western India, remain less explored. This study seeks to bridge this knowledge gap by examining the prevalence and characteristics of germ cell tumors within a tertiary cancer hospital. In this retrospective analysis, all cases of germ cell tumors diagnosed over a 3-year period in the specified tertiary cancer hospital were included. Cases with incomplete records or inadequate pathological data were excluded. Data encompassing histological subtypes, patient age distribution, clinical presentations, and histopathological features were collected and analyzed. The study comprised 145 cases of germ cell tumors. Teratomas were the most prevalent subtype, with mature teratomas accounting for the majority. The highest incidence occurred within the 21-30-year age group with a mean age of 24.77 years. Abdominal mass (56%) and abdominal pain (34%) were the prominent clinical presentations. Benign cases constituted the majority 85.5%. Solid tumors (p < 0.00001) and tumors more than 10 cm (p .029028) were found to have a high propensity to be malignant, which was proven to be statistically significant. This study comprehensively explains germ cell tumors\' prevalence, clinical features, and histopathological subtypes in a tertiary cancer hospital in North-Western India. The predominance of teratomas, particularly mature ones, aligns with global trends. The age distribution and clinical presentations reflect common patterns. The diverse histopathological appearances underscore the heterogeneous nature of germ cell tumors. This study offers valuable insights for clinical management and further regional research.
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