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Yolk sac tumors (YSTs), also known as endodermal sinus tumors, are malignant germ cell neoplasms that primarily arise in the ovaries and testes. However, the occurrence of YSTs in extragonadal sites, particularly the endometrium, is exceedingly rare, representing a diagnostic and therapeutic challenge, especially in post-menopausal women. Despite their rarity, YSTs of the endometrium demand attention due to their aggressive nature and potential for adverse outcomes. In this review, we explore the clinical characteristics, diagnostic approaches, treatment options, and prognostic factors associated with YSTs of the endometrium in post-menopausal women, drawing insights from the available literature [2].

Clinical Presentation

YSTs of the endometrium often present with nonspecific symptoms, including abnormal uterine bleeding, pelvic pain, and vaginal discharge. In post-menopausal women, the presentation may be subtle, leading to delays in diagnosis and treatment initiation. Differential diagnoses may include endometrial hyperplasia, endometrial carcinoma, and other benign or malignant uterine lesions [3,4]. The rarity of YSTs in this demographic underscores the importance of considering this diagnosis in the evaluation of post-menopausal women with uterine pathology.

Diagnostic Modalities

Diagnostic evaluation of YSTs of the endometrium typically involves imaging studies such as transvaginal ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT) scans. Histopathological examination of endometrial biopsy specimens remains the cornerstone for definitive diagnosis, with characteristic histological features including Schiller-Duval bodies, clear cells, and glandular papillary structures. Immunohistochemical analysis, including markers such as alpha-fetoprotein (AFP) and glypican-3, may aid in confirming the diagnosis of YSTs and differentiating them from other uterine malignancies.

Discussion

Yolk sac tumors (YSTs) occurring in post-menopausal women, particularly as primary endometrial YSTs, are infrequent occurrences believed to originate from pre-existing somatic epithelial neoplasms [5]. Several proposed mechanisms elucidate the histogenesis of extra-gonadal YSTs, including:

(1) misplacement or arrested migration of germ cells during embryogenesis

(2) retrograde migration of germ cells

(3) abnormal or retro-differentiation of somatic tumor cells towards more primitive forms

(4) specialized differentiation from a somatic carcinoma

(5) emergence from residual fetal tissue following incomplete abortion

(6) metastasis from a concealed primary germ cell tumor within the gonad (Euscher, 2019). Specifically addressing patients with uterine YSTs, mechanisms involving somatic carcinoma originating from a pluripotent somatic stem cell, retro-differentiation of mature cells into embryonal cells, and hindered migration of pluripotent germ cells have garnered attention, particularly in peri-menopausal or postmenopausal cohorts.

Treatment Strategies

The optimal management of YSTs of the endometrium in postmenopausal women remains unclear due to the limited evidence base and heterogeneous clinical presentations. Surgical resection, including total hysterectomy with bilateral salpingo-oophorectomy, is often recommended as the primary treatment modality. Adjuvant therapy, including chemotherapy and radiation therapy, may be considered in cases of advanced disease or metastatic spread. The role of targeted therapy and immunotherapy in the management of YSTs of the endometrium warrants further investigation.

Prognostic Factors

Prognosis in YSTs of the endometrium depends on various factors, including tumor stage, histological grade, depth of myometrial invasion, and presence of metastasis [6-8]. Early-stage tumors confined to the endometrium generally carry a more favorable prognosis compared to advanced-stage disease with lymph vascular invasion or distant metastasis. Long-term follow-up and surveillance are essential for monitoring disease recurrence and evaluating treatment response in affected patients.

Conclusion

Yolk sac tumors of the endometrium in post-menopausal women represent a rare and clinically challenging entity. Despite their rarity, prompt recognition, accurate diagnosis, and multidisciplinary management are essential for optimizing patient outcomes. Further research efforts are needed to elucidate the molecular mechanisms underlying the pathogenesis of YSTs and to explore novel therapeutic strategies aimed at improving prognosis in affected individuals. Through collaborative efforts among clinicians, pathologists, and researchers, we can advance our understanding of YSTs of the endometrium and enhance the quality of care for patients affected by this rare gynecological malignancy. In the end, insights into primary endometrial yolk sac tumors (YSTs) in post-menopausal women primarily stem from case reports, including our own. While cytoreductive surgery combined with adjuvant therapy using BEP and active surveillance with AFP monitoring seem promising for treatment, ongoing vigilant follow-up is essential due to the rarity of this condition, making it challenging to conduct larger-scale studies to predict its behavior. Delving into the specific genetic mutations linked to endometrial YSTs could offer deeper understanding into the disease's origins.

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