Abstract
Endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus, or corded and hyalinized endometrioid adenocarcinoma (CHEC), is a rare morphological variant of endometrioid carcinoma, for which there is limited literature and few cases reports. Most researchers tend to consider CHEC as a low-grade cancer with a favorable prognosis. Full-staging surgery is the primary choice for this disease, and no case of CHEC has been previously reported to be treated conservatively. Here, we present the following case to explore the possibility of fertility-preserving treatment for young women with CHEC. A 23-year-old nulliparous patient diagnosed with presumed stage IA CHEC received fertility-sparing treatment at the Obstetrics and Gynecology Hospital of Fudan University and got a complete response (CR) after 10 months of conservative treatment. The patient subsequently became pregnant spontaneously, successfully conceived, and gave birth to a healthy male neonate without any sign of recurrence during 37 months follow-up after CR. The patient’s postpartum follow-up is continuing. Presently, CHEC is not included in the fertility-sparing field of any available guidelines. This case indicates that fertility-sparing treatment may be an option for highly selected patients with CHEC. Continuous follow-up remains mandatory to observe long-term outcomes.
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Introduction
Corded and hyalinized and spindled endometrioid carcinomas of the uterine corpus (CHEC) are rare variants of endometrial endometrioid adenocarcinoma (EEC) that were first described in 2005 by Murray et al. [1] and are characterized by cords of low-grade epithelial cells within a hyalinized stroma or spindled epithelial cells in addition to the classical endometrioid adenocarcinoma components. CHEC has been considered a low-grade EEC, with most cases being classified as grade 1 or 2 [1,2,3,4,5]. The standard treatment is staging surgery, but for young nulliparous females, surgery constitutes a complete loss of fertility and may be unacceptable for them. Previous studies [ Here, we report the first CHEC case, in which the patient successfully conceived and delivered after receiving conservative treatment. Our report mainly highlights the feasibility of reproductive organ preservation for patients with CHEC. Uterine preservation may be feasible even in patients with CHEC under intensive monitoring. The CHEC is characterized by cords of epithelial cells with or without spindle cells embedded in a prominent hyalinized to myxoid stroma and exhibits “biphasic” morphology [1]. According to previous studies [1,2,3,4,5], most histological grades of the endometrioid adenocarcinoma components were grades 1–2 and associated with squamous epithelium. Sex cord structure accounted for 10–60%, which sometimes shows an epithelial-like morphology, similar to adenocarcinoma cells, while at other times demonstrating fusiform, similar to mesenchymal components. The chromatin of sex cord cells is relatively delicate, and the karyotypes can be classified into mild, moderate atypia, and severe atypia, with severe atypia being rare. Sex cord structures are often accompanied by hyalinization, and sex cord cells may appear as clusters or single cells embedded in hyalinization structures; moreover, some hyalurous mesenchyme may form small nodules (mimicking cartilage formation) or frequently show osseous metaplasia. Due to the “biphasic” morphology of CHEC, precise pathological diagnosis is vital, especially for conservative treatment cases. In previous studies [1,2,3,4,5], mismatch repair (MMR) protein expression was preserved in most CHEC tumors. A few cases had aberrant staining of p53. The glandular epithelium usually demonstrated moderate to strong staining of ER and PR, while the squamous and corded components displayed negative or weak expression of ER and PR. Nuclear staining of beta-catenin expression can be shown in the glandular, squamous, and corded components of the majority of cases. In molecular analysis, pathogenic CTNNB1 mutations involving exon 3 were identified in all 14 patients with CHEC [4, 5], and the majority of the 14 cases were considered as copy number low, except for two P53 mutation cases, according to the Cancer Genome Atlas (TCGA) molecular classification of endometrial cancer. Our study did not includemolecular analysis due to limitations at that time in our hospital. MMR protein expression was positive in our case. ER and PR staining was strongly positive in the epithelium and negative in the sex-cord area and P53 expression was wild type. Immunohistochemistry indexes were similar to those reported in previous cases. Molecular classification is an important factor for prognostic assessment and selection of adjuvant treatment options in patients undergoing radical surgery for endometrial cancer [12]. However, the clinical value of different molecular ty** for fertility preservation therapy in patients with EC/EAH remains unclear. Reports on whether MMR-d or NSMP molecular ty** affects patients’ with EC/EAH conservation outcomes are inconsistent. Our data [13] showed that the CR rate of patients with MMR-d and NSMP was close to 90%, and there was no statistical significance. However, patients with MMR-d had a higher risk of recurrence than patients with NSMP after CR [14]. Patients with p53mut type have a high risk of invasion and are thought to not be suitable for fertility preservation therapy. In addition, a small number of patients with POLE mutant may not be sensitive to progesterone, which is not consistent with other research. Molecular ty** helps to screen and assess whether these patients are suitable for fertility preservation therapy. Moreover, different gene expressions may play a role too. We suspect that in the future, integrated assessment, including liquid biopsy like tumor cells DNA and serum miRNA, and gene markers, together with molecular ty** and classical pathological diagnosis may be used to help make decisions in fertility-sparing management [15, 16]. More research is warranted. Due to limited cases, data on the long-term outcomes of CHEC is rare. As indicated in the research [1, 2], the prognosis of early-stage CHEC is similar to that of typical endometrioid carcinoma. Similarly, in another study [4], stage IA CHEC cases harbored favorable clinical outcomes, while IB to IIIA CHEC cases showed aggressive clinical courses and unfavorable outcomes. All of the above data is from patients with staging surgery. The prognosis of CHEC cases taking conservative treatment requires additional research. Tracking newborn outcomes following conservative treatment of endometrial cancer is also necessary. Our patient became pregnant naturally, and no signs of fetal chromosomal abnormalities or structural abnormalities were found during pregnancy and post-delivery. The growth curve of the fetus was within the normal range. The Extended Noninvasive Prenatal Screening (NIPT-Plus) test was completed at 17 weeks of pregnancy, indicating a low risk. We retrospectively reviewed this case and speculated that several factors may have attributed to the success. First, the sex cord structure was local and the lesion was local without any evidence of myometrium invasion. Second, the patient had no metabolic abnormalities or other infertility factors. Third, the patient was reliable and took regular inspections. We did not expect successful natural pregnancy given that the AMH value was considerably low. Furthermore, we applied typical conservative treatment of low-grade, presumed stage IA EEC for this CHEC case because no standards were available for reference. From this case, we believe that highly selected CHEC cases should not be rejected from conservative treatment; however, caution is warranted and further exploration is needed, including exploration of the best clinical practices, regimens, monitoring protocols, and maintenance treatment after CR. This study presents a case report. The follow-up time was not long, which may have limited our assessment of recurrence and long-term prognosis. We will continue to follow up. Additionally, molecular classification was not performed in this case due to technical limitations at that time. In conclusion, this is the first attempted case of fertility-sparing treatment for CHEC, and fortunately, it led to a spontaneous pregnancy and normal delivery. For highly selected, young, nulliparous patients with CHEC who have a strong desire for fertility, conservative treatment may be an option.Discussion
Limitations
Conclusion
Data availability
The datasets generated for this study are available upon request to the corresponding author.
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The authors thank the patient and the faculty, nurses, and staff who took part in this study.
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SWW and QJ oversaw data acquisition. SWW analyzed the data. SWW and QJ wrote the original draft. LXZ and CXJ reviewed and edited the manuscript. All authors contributed to the article and approved the submitted version of the manuscript.
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The authors have no ethical conflicts to disclose. The patient provided written informed consent and was counseled extensively on the advantages, disadvantages, and risks of surgery and conservative therapies.
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Gama, Q., Luo, S., Wu, P. et al. Endometrioid carcinomas with sex cord-like formations and hyalinization: spontaneous pregnancy after conservative treatment. BMC Pregnancy Childbirth 24, 30 (2024). https://doi.org/10.1186/s12884-023-06219-8
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DOI: https://doi.org/10.1186/s12884-023-06219-8