Mismatch repair deficiency and abnormal p53 expression has significant predictive value for progesterone resistance and endometrial tumorigenesis in patients with endometrial atypical hyperplasia receiving fertility-preserving treatment.

OBJECTIVE: This study aimed to evaluate the prognostic ability of mismatch repair deficiency (MMR-d) and abnormal p53 expression (p53abn) in patients with endometrial atypical hyperplasia (EAH) who underwent fertility-preserving treatment. METHODS: This retrospective study evaluated 51 patients with EAH who underwent fertility-sparing treatment. Endometrial biopsy specimens obtained before hormone therapy were collected and used for immunohistochemical staining for MMR and p53 proteins. Response, relapse, and progression rates were assessed based on age, body mass index, diabetes, polycystic ovary syndrome, reproductive history, MMR status, and p53 status. RESULTS: Overall, 11/51 (21.6%) patients had loss of MMR proteins and 6/51 (11.8%) had p53abn. Patients with MMR-d had lower complete response (CR) rates than those with normal staining patients at 12 months after initial treatment (p = 0.049). Patients with MMR-d had significantly higher relapse rates than those with MMR-p at the 1-year follow-ups after achieving CR (p = 0.035). Moreover, patients with MMR-d had a higher incidence of disease progression at 2, 3, and 4 years after fertility-sparing treatment (p = 0.001, p = 0.01 and p = 0.035, respectively). Patients with p53abn had higher relapse rates than those with p53wt at the 1- and 2-year follow-ups after achieving CR (p = 0.047 and p = 0.036, respectively). Moreover, patients with p53abn had a higher incidence of disease progression at 3 and 4 years after fertility-sparing treatment (p = 0.02 and p = 0.049, respectively). CONCLUSIONS: EAH patients with MMR-d and p53abn have a significantly higher risk of disease relapse and progression. Thus, MMR-d and p53abn may be used as predictive biomarkers of progestin resistance and endometrial tumorigenesis in EAH.

Extensive lesions and a positive cone margin are strong predictors of residual disease in subsequent hysterectomy following conization for squamous intraepithelial lesion grade 2 or 3 study design.

BACKGROUND: This study aimed to determine the predictive factors for post-conization of residual disease in subsequent hysterectomy for cervical intraepithelial neoplasia grade 2 or 3. METHODS: This retrospective study included 267 patients with histologically confirmed cervical intraepithelial neoplasia grade 2 or 3 who underwent hysterectomy within 7 months after conization. Clinical data (e.g., age, menopausal status, gravidity, parity, type of transformation zone, conization method) as well as pathological data pertaining to conization and hysterectomy were collected from medical records. A logistic regression model was used to analyze the relationship between the variables and risk of residual lesions in hysterectomy samples. RESULTS: Overall, 70 (26.2%) patients had residual lesions in their hysterectomy specimens. Univariate analyses revealed that age ≥ 50 years (p=0.019), endocervical gland involvement(p=0.013), positive margin(p < 0.001), and involvement of 3-4 quadrants(p < 0.001) were risk factors for residual lesions. Conversely, postmenopausal status, gravidity ≥ 3, parity ≥ 2, loop electrosurgical excision procedure, and type III transformation zone were not risk factors for residual lesions. A positive margin(p < 0.001) and multiple-quadrant involvement(p < 0.001) were identified as independent risk factors for residual lesions on multivariate analysis. CONCLUSIONS: Multiple-quadrant involvement and a positive cone margin were reliable predictive factors for residual disease. Total hysterectomy or repeated cervical conization should be considered for patients with these two risk factors. The identification of high-risk patients with extensive lesions by colposcopic examination before conization is indispensable, as it will enable surgeons to perform conization with consideration of risk factors and possibly improve the approach used for the excisional procedure. For high-risk patients, colposcope-guided cold-knife conization is preferred when resources permit.

Endometrial Cancer Following Levonorgestrel-Releasing Intrauterine System Insertion in Young Women with Atypical Hyperplasia: Two Case Reports and Literature Review.

Levonorgestrel-releasing intrauterine system (LNG-IUS) insertion is the first-line treatment for atypical hyperplasia (AH) in young women who wish to retain their fertility. However, the procedure is not always effective, and may allow AH to progress to endometrioid endometrial cancer (EEC). Two young women with AH who wished to preserve their fertility developed EEC following 52-mg LNG-IUS in insertion at our institution. One was a 34-year-old woman diagnosed with endometrial cancer 2 years after LNG-IUS insertion. The second was a 30-year-old woman diagnosed 17 months after LNG-IUS insertion. Proactive molecular risk classification for endometrial cancer (ProMisE) classification revealed that the first and second patients had p53-abnormal (p53abn) EEC and mismatch repair deficient (MMR-d) EEC, respectively. MMR-d and p 53abn were frequently observed in both AH and EEC specimens. Studies suggest that MMR-d and p53abn are predictors of the occurrence adverse effects after fertility-preserving treatment for EEC. AH is a precursor of EEC. Therefore, p53 and mismatch repair (MMR) mutation may be used to identify women with AH who will not likely benefit from progestin therapy. Molecular assays in women with AH will likely be useful for identifying novel predictive biomarkers of progestin resistance and to improve the safety of conservative treatment. Combined assessment of progesterone receptor (PR) with these predictive molecular markers may improve the predictive ability.

Uterine rhabdomyosarcoma complicated by cerebral venous thrombosis and uterine inversion in a young woman: case report and literature review.

BACKGROUND: Uterine rhabdomyosarcoma is an extremely rare malignant tumor that usually affects young women and has a poor prognosis. CASE PRESENTATION: A 19-year-old nulliparous woman presented to the emergency department under sedation due to seizures. Imaging examination revealed cerebral venous thrombosis. During thrombolytic therapy, she developed vaginal bleeding followed by uterine inversion secondary to uterine rhabdomyosarcoma. The inverted uterus was mistaken for a cervical tumour and was removed vaginally. The patient's disease progressed despite chemotherapy with vincristine, actinomycin D and cyclophosphamide and she died within 6 months. To our knowledge, this is the first case of uterine rhabdomyosarcoma complicated with cerebral venous thrombosis. CONCLUSIONS: Malignancy is an important diagnostic in patients with cerebral venous thrombosis with no obvious cause. This case demonstrates the importance of considering uterine neoplasms in the differential diagnosis of adolescent girls with abnormal uterine bleeding. Further, careful anatomical evaluation of vaginal masses should be performed prior to surgical intervention.

Complete remission of choriocarcinoma with pulmonary vein thrombosis in the third trimester of pregnancy treated with systemic chemotherapy and anticoagulation: A case report.

RATIONALE: Choriocarcinoma is a highly aggressive tumor. It occurs infrequently during pregnancy. The management of choriocarcinoma during pregnancy poses several challenges. PATIENT CONCERNS: At 34 weeks of gestation, a 21-year-old primigravida was transferred to the emergency room for cephalgia, reduced fetal movements, and left intra-atrial intracavitary thrombus. DIAGNOSIS: Choriocarcinoma in the third trimester with lung and brain metastases, pulmonary vein thrombosis (PVT), and systemic thrombosis. INTERVENTION: An emergency cesarean section was performed. Subsequently, low-molecular-weight heparin anticoagulation combined with multiagent chemotherapy was administered. OUTCOME: A 1.59 kg live female was born. Multiagent chemotherapy combined with anticoagulation led to complete regression of the cerebral and pulmonary lesions and the dissolution of pulmonary vein thrombus. At the 11-month follow-up, the patient remained in complete remission without complications, and her child was disease-free. LESSONS: This is the first case of gestational choriocarcinoma with PVT. Our case suggests that conservative therapy can be the first choice for small, asymptomatic PVT secondary to choriocarcinoma.

Ovarian ependymoma presenting in pregnancy: a case report and literature review.

BACKGROUND: Ovarian ependymoma is a rare malignancy. Because of the extreme rarity, certain features of the neoplasm, including its clinical behaviour and optimal therapy, are incompletely characterized. CASE PRESENTATION: A 32-year-old pregnant woman at term presented with a left ovarian neoplasm that occurred in the early stage of pregnancy. She underwent left adnexectomy during the caesarean section, and the neoplasm was histologically and immunohistochemically identified to be ovarian ependymoma. Immunohistochemical staining with oestrogen receptors and progesterone receptors showed strong positive staining. According to reports in the literature, the pathological type of ovarian ependymoma in our patient was the extra-axial type. Interestingly, the foetus was also found to have bilateral ependymal cysts during pregnancy. The patient received no further surgical treatment or adjuvant therapy. She and her 14-month-old baby both have no evidence of disease at present. The follow-up of both mother and child is still continuing. CONCLUSIONS: The case presented here illustrates high levels of oestrogen during pregnancy may stimulate viable malignant ependymal cells to proliferate. Hence, young women with extra-axial-type ependymomas may not be suitable for fertility preservation. Moreover, hormone-based therapies can be a potentially effective treatment for women with extra-axial ependymomas.

Advanced endometrial cancer following the insertion of the levonorgestrel-releasing intrauterine system in a 34-year-old woman: A case report.

Advanced endometrial adenocarcinoma was diagnosed two years after a 34yo women had a 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) inserted for the treatment of atypical hyperplasia. The LNG-IUS can be an alternative treatment for women with atypical hyperplasia who desire to preserve their fertility. However, the risk of endometrial cancer should raise concern.

Successful management of nongestational ovarian choriocarcinoma complicated with choriocarcinoma syndrome: A case report and a literature review.

Nongestational ovarian choriocarcinoma (NGOC) accounts for <1% of ovarian germ cell tumors and may develop into the rare and fatal complication of choriocarcinoma syndrome. We reported a case of a 12-year-old girl with NGOC that metastasized to the lungs, retroperitoneal lymph nodes and brain. On day 2 of chemotherapy with actinomycin D and etoposide, choriocarcinoma syndrome developed due to a massive pulmonary hemorrhage, presenting as acute respiratory distress syndrome. The patient received mechanical ventilation and multimodal support and completed two cycles of an actinomycin D and etoposide regimen with intubation. After the patient's acute respiratory distress syndrome was under control, she received 9 cycles of more intensive chemotherapy regimens and achieved complete remission. An exploratory laparotomy with salpingo-oophorectomy confirmed ovarian choriocarcinoma. The patient remained disease-free at a 3-month follow-up visit. In conclusion, appropriate management consisting of multimodal support and timely, sequential and intensive chemotherapy is effective for NGOC complicated with choriocarcinoma syndrome. Stating with mild regimens would probably reduce the risk of choriocarcinoma syndrome, or at least lessen its severity. To our knowledge, we presented the first report of NGOC-related choriocarcinoma syndrome.