OBJECTIVE: This study was presented to investigate the clinical-pathological characteristics of gestational trophoblastic neoplasia (GTN) following non-molar pregnancy and differentiated with ectopic pregnancy (EP).
METHODS: The clinical data of 83 patients who were admitted for suspected GTN after non-molar pregnancy at the Women\'s Hospital School of Medicine Zhejiang University from January 2015 to September 2022 were selected for analysis.
RESULTS: In total, 41 cases were confirmed non-molar GTN, including 31 choriocarcinoma, 9 PSTT (placental site trophoblastic tumor), and 1 ETT (epithelioid trophoblastic tumor), while 42 cases were confirmed EP. Compared with ectopic pregnancy, non-molar GTN patients had lower levels of serum progesterone compared with EP (3.81 nmol/L vs 17.70 nmol/L, P = 0.001). Based on the ultrasound, the thickness of the endometrium was thinner in patients with non-molar GTN compared with EP (0.565 cm vs 0.70 cm, P = 0.018). By histopathologic examination, the endothelium of non-molar GTN showed less decidual-like changes compared with EP (64.3% vs 14.6%, P = 0.001).
CONCLUSIONS: A combination of serum progesterone levels, endometrium thickness, and histopathologic features of the endometrium can help to differentiate non-molar GTN and EP. Surgeries including hysteroscopy with curettage and/or laparoscopy are needed.

Objective: To investigate the impact of lung metastases on the prognosis of patients with gestational trophoblastic neoplasia (GTN). Methods: Patients with International Federation of Gynaecology and Obstetrics (FIGO) stage Ⅰ-Ⅲ GTN receiving primary chemotherapy in Peking Union Medical College Hospital between July 2014 and December 2018 were retrospectively analyzed and divided into group 1 with lung metastasis and group 2 without lung metastasis. The baseline characteristics and treatment outcomes of the two groups were compared. The optimal cut-off values of the diameter of largest lung nodule associated with recurrence were identified by receiver operating characteristic (ROC) curves. Logistic regression analyses were performed to identify risk factors for prognosis. Survival analysis was performed by Kaplan-Meier method and Log rank test. Results: Of the 381 GTN patients enrolled (216 with lung metastases and 165 without lung metastases), the pretreatment β human chorionic gonadotrophin [median: 12 572 IU/L (1 832-51 594 IU/L) vs. 5 614 IU/L (559-26 140 IU/L), P=0.001] and FIGO score [median: 3 (1-6) vs. 2 (1-4), P=0.038] were significantly higher in patients with lung metastases than those without lung metastases. In patients with FIGO score≥5, the emergence of resistance (26.76% vs. 10.26%, P=0.036) and median number of chemotherapy courses to achieve complete remission [6 (6-8) vs. 5 (4-6), P<0.001] were significantly higher than patients with lung metastases. In patients with FIGO score 0-4, no significant difference was found in the treatment outcomes between the two groups(P=0.833). Among all patients with lung metastases, the ROC curve showed a sensitivity and specificity of 62.5% and 78.8%, respectively, for predicting recurrence when the length of the largest lung nodule was 1.6 cm, with an area under the curve (AUC) of 0.711 (95% CI: 0.550, 0.871, P=0.044). Multivariate logistic regression analysis suggested a significantly higher recurrence rate when the largest lung nodule was ≥1.6 cm (OR=7.394, 95% CI: 1.003, 54.520, P=0.049). The 1-year disease-free survival rate was significantly lower in patients with the largest lung nodule ≥1.6 cm than in patients with the nodule <1.6 cm (98.2% vs. 82.4%, P=0.001). Conclusions: Lung metastasis is associated with increased first-line chemotherapy resistance in patients with FIGO scores≥5. The diameter of the largest lung metastatic nodule ≥1.6 cm is an effective factor for predicting recurrence.
目的：探讨肺转移对妊娠滋养细胞肿瘤(GTN)患者预后的影响。 方法：选取2014年7月至2018年12月于北京协和医院初治的国际妇产科联盟Ⅰ~Ⅲ期GTN患者，根据有无肺转移分为肺转移组和无肺转移组，比较两组间的基线特征和治疗效果，采用受试者工作特征(ROC)曲线确定肺转移最大结节长径预测复发的最佳临界值，预后影响因素分析采用logistic回归分析，生存分析采用Kaplan－Meier法和Log rank检验。 结果： 381例GTN患者中，肺转移组216例，无肺转移组165例。肺转移组患者化疗前中位β人绒毛膜促性腺激素水平[12 572 IU/L(1 832~51 594 IU/L)]高于无肺转移患者[5 614 IU/L(559~26 140 IU/L)，P＝0.001]。肺转移组患者的中位预后评分分数[3分(1~6分)]高于无肺转移组[2分(1~4分)，P＝0.038]。在预后评分≥5分的患者中，肺转移组和无肺转移组患的治疗结局差异有统计学意义(P＝0.036)，肺转移组患者一线化疗达到完全缓解的中位疗程数[6个(6~8个)]高于无肺转移组[5个(4~6个)，P<0.001]。在预后评分0~4分的患者中，肺转移组和无肺转移组的治疗结局差异无统计学意义(P＝0.833)。ROC曲线显示，当肺转移最大结节长径为1.6 cm时，预测复发的灵敏度和特异度分别为62.5%和78.8%，曲线下面积为0.711(95% CI：0.550~0.871，P＝0.044)。多因素分析显示，肺转移最大结节长径≥1.6 cm为复发的独立危险因素(OR＝7.394，95% CI：1.003~54.520，P＝0.049)。肺转移最大结节长径≥1.6 cm患者的1年无病生存率(82.4%)低于肺转移最大结节长径<1.6 cm的患者(98.2%，P＝0.001)。 结论：单纯存在的肺转移是GTN预后评分≥5分患者一线化疗耐药的危险因素；存在肺转移时，肺转移最大结节长径≥1.6 cm是预测疾病复发的独立影响因素。.

OBJECTIVE: We aimed to compare weekly methotrexate (MTX) regimen and methotrexate-folinic acid (MTX-FA) 8-day regimen in the first line treatment of low-risk gestational trophoblastic neoplasia (GTN).
METHODS: The study included 73 patients with low-risk GTN according to FIGO risk score (FIGO risk score < 7). All patients received either weekly MTX (30-50 mg/m2 intramuscular weekly) or MTX-FA 8-day (MTX 1 mg/kg IV on day 1, 3, 5, and 7, FA 15 mg orally on day 2, 4, 6, and 8 given 24 h after each MTX dose, every 14 days) regimens in the first-line treatment of low-risk GTN. The baseline clinicopathological characteristics and treatment outcomes were analyzed retrospectively.
RESULTS: The median age of all patients was 29 (18-51) years, and the median FIGO risk score was 3 (1-6). Of the patients recruited, 53 received MTX-FA 8-day, and 20 had MTX weekly regimens. There was a significant difference between the two groups with respect to FIGO risk scores (3 [1-6] vs. 2 [1-5], p = 0.023, MTX-FA 8-day vs. MTX weekly, respectively). The complete response rate was significantly higher in MTX-FA 8-day group compared to MTX weekly group (83% [44/53] vs. 60% [12/20] p = 0.038). In univariate and multivariate regression analyses, only presence of lung metastasis was found to be an independent risk factor for treatment resistance (OR: 3.959, 95% CI 1.105-14.179, p = 0.035).
CONCLUSIONS: MTX-FA 8-day regimen is more effective than weekly MTX regimen in the first line treatment of low-risk GTN including patients even with higher FIGO risk scores. Treatment resistance may develop especially in patients with lung metastasis.

BACKGROUND: Invasive mole is a subtype of gestational trophoblastic neoplasms (GTNs) that usually develops from the malignant transformation of trophoblastic tissue after molar evacuation. Invasive moles mostly occur in women of reproductive age, while they are extremely rare in postmenopausal women.
METHODS: We present the case of a 55-year-old postmenopausal Syrian woman who was admitted to the emergency department at our hospital due to massive vaginal bleeding for 10 days accompanied by constant abdominal pain with diarrhea and vomiting. Following clinical, laboratory and radiological examination, total hysterectomy with bilateral salpingo-oophorectomy was performed. Histologic examination of the resected specimens revealed the diagnosis of an invasive mole with pulmonary metastases that were diagnosed by chest computed tomography (CT). Following surgical resection, the patient was scheduled for combination chemotherapy. However, 2 weeks later the patient was readmitted to the emergency department due to severe hemoptysis and dyspnea, and later that day the patient died in spite of resuscitation efforts.
CONCLUSIONS: Although invasive moles in postmenopausal women have been reported previously, we believe our case is the first reported from Syria. Our case highlights the difficulties in diagnosing invasive moles in the absence of significant history of gestational trophoblastic diseases. The present study further reviews the diagnostic methods, histological characteristics and treatment recommendations.

The early identification of patients who are being treated for low-risk gestational trophoblastic neoplasia (LRGTN) with single-agent chemotherapy, who are at high risk of developing chemoresistance, is of crucial importance. The aim of our research was to evaluate the pretreatment beta subunit of human chorionic gonadotropin (βhCG) concentration and its decrease after the administration of the first course of methotrexate (MTX) in predicting later chemo-resistance to single-agent chemotherapy.
A total of 46 patients diagnosed with LRGTN treated with a 5-day methotrexate (MTX) regimen were retrospectively studied. 24 of the patients were successfully cured with only MTX therapy (MTX group). The disease was considered resistant in the remaining 22 patients who, after MTX therapy, required further chemotherapy with an EMA/CO regimen (EMA/CO group). To compare changes in the βhCG concentrations between the two courses of treatment (and the two groups), we calculated the percentage of decline. We determined the specificity and sensitivity of the initial βhCG level and its percentage decline, as a potential predictor of the need for a future EMA/CO regimen. For diagnostic purposes, βhCG levels were measured before the first and second administrations of MTX with a commercial ELISA kit.
In the EMA/CO group, we found the initial βhCG level before the first MTX dose was higher (median = 6275 mIU/mL, range: 21.53-192.610.0 mIU/mL) than in the MTX group (median = 532 mIU/mL, range: 56.5 mIU/mL-360.397.0 mIU/mL) (p = 0.034, Mann-Whitney test). The percentage decreases in the βhCG values relative to the initial concentrations were higher in the MTX group (median decrease = 82.7%, range: from 13.3% to 99.9%) than in the EMA/CO group (median de- crease = 71.1%, range: from an increase of 56.1% to a decrease of 97.1%) (p = 0.0079, Mann-Whitney test). An analysis of the ROC curves implied optimal cutoff values for the initial βHCG (6054 IU, sensitivity = 55%, specificity = 86%) and the percentage change in βhCG levels (decrease by 76.5%, sensitivity = 72%, specificity = 71%).
Women with initially higher βhCG levels have a greater risk of developing MTX chemo resistance. It would be advantageous to consider administering an EMA/CO regimen in women with LRGTN when their initial βhCG levels are greater than 6000.

Gestational trophoblastic neoplasms (GTN) are highly curable tumors, with an overall patient survival of 90%, due to the individualized chemotherapy. However, chemotherapy regimens vary between different treatment centers and the comparable benefits and risks of these different regimens are unclear. Here, we reported a case of GTN with oculocutaneous albinism (OCA) is resistant to fluorouracil (5-FU), extremely sensitive to actinomycin D (Act-D) with severe hand-foot skin reaction (HFSR). We hypothesized that the known, or unknown, gene mutations might be correlated with drug resistance, supersensitivity and severe drug side effects in OCA patients. Thus, we considered that OCA related genes influence some drug sensitivity and that the absence of melanin likely contributes to some drug resistance. It is important to assess the OCA related gene mutations locus of drug sensitivity, and resistance in OCA patients in future research.

Objective: To elucidate the clinicopathologic characteristics of atypical epithelioid trophoblastic lesions with cyst and fistula formation after cesarean section. Methods: The clinical and pathological data of 4 cases of post-cesarean atypical epithelioid trophoblastic lesions with cyst and fistula formation diagnosed at Women\'s Hospital, School of Medicine, Zhejiang University during April 2007 to June 2018 were evaluated by hematoxylin and eosin stain and EnVision two-step immunohistochemical staining technique. Results: The age of the 4 patients ranged from 32 to 41 years, with a mean age of 36.5 years. Three patients recieved cystectomy and one underwent subtotal hysterectomy. Histologically, the lesions were well circumscribed and consisted of uniform cells of medium size, irregularly enlarged with hyperchromatic nuclei and 1 to 2 inconspicuous nucleoli embedded in abundant hyalinized matrix with fibrinoid material in the center. The cells exhibited immunohistochemical feature of chorionic-type intermediate trophoblastic cells (CK18+, p63+ and CD146-). All patients were alive without recurrence during follow-up of 1 to 40 months (mean=22 months). Conclusion: Atypical epithelioid trophoblastic lesion with cyst and fistula formation after cesarean section has unique histological features, and its biological behavior and prognosis are still unclear, which need further exploration.
目的： 探讨剖宫产术后不典型上皮样滋养细胞病变伴囊肿或瘘管形成的临床病理学特征，以进一步认识此类病变。 方法： 收集2007年4月至2018年6月浙江大学医学院附属妇产科医院4例子宫下段瘢痕处的剖宫产术后不典型上皮样滋养细胞病变伴囊肿或瘘管形成的患者临床病理学资料，免疫组织化学染色采用EnVision二步法，观察病变的组织学特征并总结临床病理学特点。 结果： 4例患者均为女性，发病年龄为32~41岁（平均36.5岁）。4例患者中，3例为包块切除标本，另1例为子宫次切标本。4例病变边界清楚，囊肿壁内衬4~10层单核滋养细胞，细胞膜清楚，核染色质略增粗，可见1~2个不明显的核仁，具有丰富的透明或嗜酸性细胞质，细胞周围可见纤维素样或透明变性物质沉积。免疫组织化学证实其具有典型的绒毛膜型中间型滋养细胞特点（CK18+，p63+，CD146-）。4例患者均有随访资料，随访时间1~40个月（平均22个月），均无复发。 结论： 剖宫产术后不典型上皮样滋养细胞病变伴囊肿或瘘管形成具有独特的组织学特征，其生物学行为及预后尚不明确，有待进一步探索。.

The immune checkpoint proteins, programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1), are crucial for maintaining fetomaternal immune tolerance and immune escape in cancers. In this study, we performed a comprehensive immunohistochemical study of PD-L1 expression in a large cohort of trophoblastic tissues and tumors. We found that normal villi and hydatidiform moles showed a heterogeneous PD-L1 staining among trophoblast (strong in syncytiotrophoblast, moderate in intermediate trophoblast, and weak/negative in cytotrophoblast). Eleven exaggerated placental sites (100%) showed variable PD-L1 staining, whereas 7 (36.8%) of 19 placental site nodules/plaques were weakly positive for PD-L1 (P < .001). All gestational choriocarcinomas (CCs; n = 63), epithelioid trophoblastic tumors (n = 12), and placental site trophoblastic tumors (n = 41) were PD-L1 positive, with most showing strong staining. However, PD-L1 expression was lower in epithelioid trophoblastic tumors compared with placental site trophoblastic tumors and CCs (P = .004). Three presumably germ cell-derived pure CCs, the CC elements in 13 mixed germ cell tumors, and 4 gastric/rectal CCs were also positive for PD-L1, with widespread staining. The background nontrophoblastic tissues, such as endometrial glands, squamous cells, and adenocarcinomas, were PD-L1 negative. Western blot analysis showed that PD-L1 was expressed in all 3 trophoblastic cell lines. We conclude that PD-L1 is a sensitive but nonspecific marker for trophoblast and related tumors. The frequent strong PD-L1 expression suggests that immune checkpoint blockade could be a promising approach in treating trophoblastic tumors that merits further investigation.

BACKGROUND: Gestational trophoblastic neoplasms (GTNs) encompass a wide spectrum of diseases, of which choriocarcinoma is one of the most common. Choriocarcinoma occurs mainly in relation to pregnancy and rarely after the menopause. It has the potential to metastasize to organs other than the uterus.
METHODS: We describe a 62-year-old woman who presented with postmenopausal bleeding 11 years after the menopause. Pelvic ultrasound and abdominal/pelvic computerized tomography showed an intrauterine mass. Choriocarcinoma was diagnosed by Pipelle endometrial biopsy with positive staining for beta-human chorionic gonadotropin (hCG) and KI 67 along with an elevated serum beta-hCG level. The tumor was managed with multiple cycles of multidrug chemotherapy and follow-up based on serum beta-hCG levels according to the guidelines of the International Federation of Gynecology and Obstetrics (FIGO).
CONCLUSIONS: This case report highlights that choriocarcinoma, a tumor normally associated with pregnancy, can present after the menopause.