Objective:To investigate the clinicopathological, molecular pathological features, and family genetic pedigree of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT).Methods:A total of 16 cases of SCCOHT diagnosed in Obstetrics and Gynecology Hospital of Fudan University from January 2013 to January 2023 were collected. The clinicopathologic features, SMARCA4/2/B1 protein expression, outcomes and SMARCA4 gene detection were reported. A follow-up study was also carried out.Results:The average age at diagnosis was 28.7 years (range 17-38 years). The preoperative calcium level was evaluated in 3 of 6 patients. The tumor was unilateral in all 16 cases, ranged from 8 to 26 cm (average 15.8 cm) in the greatest dimension. Extraovarian spread was present in 7 cases. In 10 cases, the tumors were initially misinterpreted as other ovarian neoplasms. BRG1 and BRM expression by immunohistochemistry were all lost in detected cases, while INI1 exhibited retained nuclear expression. All BRM-negative SCCOHTs also lacked BRG1 protein,but retained INI1 expression. SCCOHTs were only focally positive for EMA, CKpan, Calretinin, SALL4, and diffusely positive for WT1. Two of nine cases exhibited mutation-type p53 immunoreactivity. Ki-67 index was 58% on an average. ER, PR, FOXL2, α-inhibin, chromogranin A and LCA were negative in all the cases. SMARCA4 sequencing was available in 8 cases of SCCOHT, which revealed a germline SMARCA4 mutation in one patient, and others carried somatic mutation. Furthermore, two daughters, mother and an aunt of a patient with germline mutation were reported to be SMARCA4 mutation carriers. Follow-up was available for 15 patients, and the 6-month, 1-year and 2-year survival rate was 65.8%, 45.1%, and 22.6%, respectively. For patients in FIGO stages Ⅱ+Ⅲ, 6-month, 1-year survival rate was 53.6% and 35.7% respectively, compared to 80% (6-month) and 60% (1-year) in patients of staged I ( P=0.358). Conclusions:With dismal prognosis of SCCOHT, accurate diagnosis is necessary. The typical age distribution, a panel of various staining results, especially concomitant loss of BRG1 and BRM may be of diagnostic aid and can be used to distinguish SCCOHT from its histological mimics. After the diagnosis of SCCOHT, genetic testing and genetic counseling are recommended.

Objective:To investigate the application value of different metal stents place-ment position in endoscopic drainage of malignant hilar bile duct obstruction.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 300 patients with malignant hilar bile duct obstruction who were admitted to 3 medical centers, including 216 patients in the Third Affiliated Hospital of Naval Medical University, 48 patients in the Xijing Hospital of Air Force Medical University, 36 patients in the First People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, from January 2012 to January 2019 were collected. There were 164 males and 136 females, aged (67±12)years. All patients were determined to be unresectable by multidisciplinary consultation and underwent endoscopic retrograde cholangiopancreatography. Observation indicators: (1) clinicopathological features of patients; (2) follow-up; (3) analysis of influencing factors for patency time of metal biliary stents and overall survival time of patients. Follow-up was conducted using outpatient examination and telephone interview to detect patency of metal biliary stents and survival of patients up to July 2019 or death of patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the rank sum test. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-Rank test was used to conduct survival analysis. COX regression model was used for univariate and multivariate analyses. Factors with P<0.1 in univariate analysis were included in multivariate analysis. Results:(1) Clinicopathological features of patients. Of the 300 patients, 163 cases underwent endoscopic drainage with at least one metal biliary stent' distal portion crossing the duodenal main papilla (hereinafter referred to as crossing papilla), and 137 cases underwent endoscopic drainage with no metal biliary stent' distal portion crossing the duodenal main papilla (hereinafter referred to as no crossing papilla). Age, disease type (hilar cholangiocarcinoma, hepatocellular carcinoma, intrahepatic cholangio-carcinoma, gallbladder carcinoma, metastatic cholangiocarcinoma), metal biliary stents type (unilateral metal biliary stent, bilateral metal biliary stents) of patients with crossing papilla were (68±13)years, 95, 8, 11, 31, 18, 63, 100, respectively. The above indicators of patients with no crossing papilla were (64±12)years, 63, 22, 20, 23, 9, 126, 11, respectively. There were significant differences in the above indicators between patients with crossing papilla and patients with no crossing papilla ( t=2.70, χ2=17.69, 90.79, P<0.05). (2) Follow-up. All the 300 patients were followed up for 5.4(3.1,9.3)months. The patency time of metal biliary stents was 9.0(8.2,9.8)months and 6.4(4.8,8.0)months of patients with crossing papilla and patients with no crossing papilla, showing a significant difference between them ( χ2=8.23, P<0.05). The overall survival time was 5.5(4.2,6.8)months and 5.5(4.3,6.8)months of patients with crossing papilla and patients with no crossing papilla, showing no significant difference between them ( χ2=0.28, P>0.05). (3) Analysis of influencing factors for patency time of metal biliary stents and overall survival time of patients. Results of univariate analysis showed that type of metal biliary stents and the placement position of metal biliary stents were related factors affecting the patency time of metal biliary stents [ hazard ratio( HR)=0.44, 0.60, 95% confidence intervals as 0.30?0.64, 0.42?0.85, P<0.05]. Results of multi-variate analysis showed that bilateral metal biliary stents was an independent protective factor for the patency time of metal biliary stents ( HR=0.46, 95% confidence interval as 0.29?0.72, P<0.05). Results of univariate analysis showed that disease type (intrahepatic cholangiocarcinoma versus hilar cholangiocarcinoma), preoperative serum total bilirubin, type of metal biliary stents, anti-tumor therapy were related factors affecting the overall survival time of patients ( HR=1.05, 1.43, 0.72, 0.61, 95% confidence intervals as 0.70?1.57, 1.12?1.83, 0.55?0.92, 0.47?0.81, P<0.05). Results of multi-variate analysis showed that age >60 years, disease type as hepatocellular carcinoma, preoperative serum total bilirubin >200 μmol/L were independent risk factors for the overall survival time of patients ( HR=1.35, 1.98, 1.46, 95% confidence intervals as 1.02?1.79, 1.40?2.80, 1.13?1.89, P<0.05), and bilateral metal biliary stents, anti-tumor therapy were independent protective factors for the overall survival time of patients ( HR=0.68, 0.60, 95% confidence intervals as 0.53?0.89, 0.45?0.80, P<0.05). Conclusions:Endoscopic drainage with or without metal biliary stents' distal portion crossing the duodenal main papilla is safe and feasible for patients with malignant hilar bile duct obstruction. Bilateral metal biliary stents is an independent protective factor for the patency time of metal biliary stents. Age >60 years, disease type as hepatocellular carcinoma, preoperative serum total bilirubin >200 μmol/L are independent risk factors for the overall survival time of patients, and bilateral metal biliary stents, anti-tumor therapy are independent protective factors for the overall survival time of patients.

Gynecological pathology, formed in the late 19th century, has greatly prompted the development of gynecology with its continuous exploration since the early time. In the progress of over 130 years, gynecological pathology has formed a completed set of scientific system by absorbing the contemporary advanced technologies and cooperating with gynecologists. In China, the late-started gynecological pathology has been faced with the dilemma of imbalanced regional development and endowed with the dual tasks of dissemination and self-improvement. In future, gynecological pathology in China needs to solve the following problems: (1) improving diagnostic accuracy of squamous intraepithelial lesions of the female genital tract and cervical adenocarcinoma in situ; (2) giving special attention to the correct diagnosis of hormone-related diseases especially tumor-like lesions; (3) focusing our efforts on the difficulties in clinical practice as well as the growing demands of clinical treatments; (4) actively utilizing molecular biological techniques and exploring options in accord with domestic conditions; (5) standardizing diagnostic terminology and providing the essential prognostic parameters for clinical application.

Objective:Placental pathology reflects the health condition of both mother and fetus during pregnancy, providing information about pathogenesis especially in adverse pregnancies, and may provide guidance on subsequent pregnancies. Description on the placental changes after long-term use of rivanol is lacking, and this evaluated the placental changes, with emphasis on the differential diagnosis from other primary placental lesions.Methods:A total of 85 placentas from rivanol induced abortion submitted to the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University from Januaury 2017 to October 2019 were reviewed; and 81 gestational-age-matched cases of spontaneous abortion or preterm delivery during the same period were also included as the control group. Diagnoses were based on the consensus statement of 2016 Amsterdam Placental Workshop Group. Statistical differences were analyzed by individual diagnostic terms.Results:The maternal age in rivanol group was (30.5±4.1) (range 22-41) years, compared with (30.9±4.3) (range 22-44) years in the control group. Gestational age was (23.2±3.5) (range 17-35) weeks and (23.3±2.8) (range 17-33) weeks in the rivanol and control groups. The incidence of chorioamnionitis in rivanol group was 91.8%, significantly higher than the control (63.0%, P<0.05); and there were more stage 1 (subchorionic) maternal response in rivanol than in the control (61.0% vs.28.6%, P<0.05) groups. In addition, acute deciduitis was also more common in rivanol group (27.1% vs. 13.6%, P<0.05). No significant difference was observed in fetal inflammatory responses (vasculitis of vessels in chorion plate and umbilical cord); maternal malperfusion (narrowing of intervillous space, increased intervillous fibrin deposition, decidual arteriopathy, villous infarction and retroplacental hematoma); and fetal malperfusion (villous stromal hemorrhage and avascular villi). Conclusions:The chemical chorioamnionitis caused by rivanol is characterized by maternal inflammatory response of low stage and high grade. The use of rivanol has no obvious impact on the fetal inflammatory response, maternal malperfusion and fetal malperfusion. Such morphologic changes may reflect the original placental lesions.

Objective To analyze clinical outcome of high grade squamous intraepithelial lesion (HSIL) within 24 months after loop electrosurgical excision procedure (LEEP),and to explore risk factors of recurrent cervical HSIL,the risk of progress into cervical cancer and methods of follow-up.Methods This retrospective study was carried out on 1 005 patients who underwent LEEP,diagnosing with HSIL after LEEP from January 2011 to December 2013 at Obstetrics and Gynecology Hospital Affiliated to Fudan University to confer the difference between non-recurrent group and recurrent group 24 months after the LEEP conization.Patients were followed with ThinPrep cytologic test (TCT),high risk HPV (HR-HPV) test,colposcopy guided biopsy.Results A total of 1 005 cases were enrolled in this study with HSIL in the LEEP specimen,no residual HSIL in the 6-month follow up,and have follow up records in 24 months after LEEP.HSIL recurred in 5 cases,microinvasive carcinoma in 1 case,low grade squamous intraepithelial lesion (LSIL) in 17 cases at 12 months follow-up.HSIL recurred in 8 cases,LSIL in 11 cases,adenocarcinoma in situ in 1 case,and invasive cervical carcinoma in 1 case in Ⅰ b1 stage at 24 months after LEEP.The recurrence rate was 1.3％ (13/1 005),and the progression rate was 0.3％ (3/1 005).There was no significant difference in age,length,circumference and width of LEEP between recurrent and non-recurrent patients (P ＞ 0.05).The recurrence rate was highest in the endocervical positive margin group with 3/16,which was higher than ectocervical positive margin and negative margin (P＜0.01,P=0.040,respectively).The recurrence rate of endocervical positive margin group and fibrous interstitial positive margin group showed no significant difference (P=0.320).There was no significant difference between ectocervical positive margin and negative margin [2.8％ (2/72) vs 0.7％ (6/882),P=0.117].Postoperative cytological examination combined with HR-HPV detection has a high sensitive and high negative predictor value of HSIL recurrence with both 100.0％.Multivariate logistic regression analysis showed that positive endocervical positive margin,abnormal follow-up cytological examination and positive HR-HPV after LEEP were independent factors affecting recurrence of HSIL patients after LEEP (P＜0.05).Conclusions Age,length,circumference and width of LEEP have no effect on recurrence within 24 months after HSIL.The high risk factors for HSIL recurrence within 24 months after LEEP in HSIL patients include:positive HPV,abnormal cytology,and positive endocervical positive margin.Colposcopy biopsy and endocervical curettage have important role in diagnosing HSIL recurrence and progression.

Objective: To describe the clinicopathological features of synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT). Methods: The sample consisted of 7 cases of SMMN-FGT recorded from November 2014 to September 2017 at Obstetrics and Gynecology Hospital, Fudan University.PAP method was used in immunohistochemistry.Clinical histories were retrieved and pathological slides were reviewed. Results: The patients were 37 to 70 years old(mean 54 years old). All patients showed endometrial mucinous lesions associated with cervical lesions. Three cases were an admixture of minimal deviation adenocarcinoma(MDA) and gastrictype adenocarcinoma(GAS). Three cases were an admixture of lobular endocervical glandular hyperplasia (LEGH), atypical LEGH and focal gastrictype adenocarcinoma in situ, one of which had early invasive gastrictype adenocarcinoma.Endometrium showed a structure of LEGH in one patient with focal simple gastric mucinous metaplasia in her cervix. Gastric mucinous differentiation was found in unilateral fallopian tube in 6 patients. Ovarian mucinous lesions were found in 3 patients. p16 was negative staining in 6 cases and positive in 1 case. CK7 was diffusely positive in all lesions. CK20 and CDX2 were negative or only focally positive.The expression of MUC6 was strongly positive staining or focal staining. p53 in GAS and GAS in situ had mutant expression, but wild expression in MDA region. Patients were followed up for 2 to 34 months and no recurrence was found. Conclusions SMMN-FGT is a series of rare mucinous lesions involving multiple areas of the female genital tract, including benign or malignant lesions with gastric differentiation. It is not related to infection with high-risk human papilloma virus. When cervical gastrictype lesions are found, SMMN-FGT should be considered and should be differentiated from metastatic mucinous adenocarcinoma.

Objective: To identify underlying reasons for discrepant cases of positive cytology but negative histology. Methods: Cases with positive cytology and negative histology from 2008 to 2016 were retrieved from Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University. Low grade squamous intraepithelial lesion or higher grade lesions were considered as positive cytology test in the study. Consecutive follow-up biopsies and as well as sites of biopsy were documented for analysis. Results: Overall positive rate of biopsy followed positive cytology was 74.3%(8 990/12 097). Of the negative biopsies, 675 cases were followed-up with multiple biopsy. Two-hundred and eighty-seven cases (42.5%, 287/675) were confirmed to have lesions. Comparing with those with initial positive biopsiews, patients of the latter group were significantly older and had other specimen types including vaginal biopsy, cone biopsy and hysterectomy. The final histological diagnoses were well correlated with cytological results (Kappa=0.505, P<0.01). Conclusions Qualified cervical cytology is complimentary to histological diagnosis. Clinicians should not ignore the positive cytological result prior to a normal histological diagnosis. In contradictory cases, repeated colposcopy and biopsy at extended anatomic sites may reveal additional lesions.

OBJECTIVE:To establish a method for simultaneous determination of gallic acid,magnoflorine,ellagic acid,jatrorrhizine hydrochloride,palmatine hydrochloride,berberine hydrochloride and curcumin in Siwei jianghuang decoction powder.METHODS:HPLC method was adopted.The determination was performed on Capcell Pak C18-MG Ⅱ column with mobile phase consisted of acetonitrile-0.1％ phosphoric acid (gradient elution) at the flow rate of 0.8 mL/min.The detection wavelengths were 270 nm (0-60 min,gallic acid,magnoflorine,ellagic acid,jatrorrhizine hydrochloride,palmatine hydrochloride,berberine hydrochloride) and 428 nm (60-70 min,curcumin).The column temperature was set at 30 ℃,and sample size was 10 μL.RESULTS:The linear ranges of gallic acid,magnoflorine,ellagic acid,jatrorrhizine hydrochloride,palmatine hydrochloride,berberine hydrochloride and curcumin were 0.249 6-1.497 6,0.284 0-1.704 0,0.075 6-0.453 6,0.015 9-0.095 9,0.023 6-0.141 6,0.098 2-0.589 0 and 0.060 4-0.362 4 μtg (r≥0.999 8).The limits of detection were 6.24,4.73,7.56,2.36,3.20,6.54,6.04 ng,and the limits of quantitation were 17.47,16.08,20.86,7.31,10.24,19.62,19.32 ng,respectively.RSDs of precision,stability (12 h),reproducibility tests were lower than 2.0％ (n=6).The recoveries were 95.45％-103.47％ (RSD=0.86％-1.98％,n=9).CONCLUSIONS:Established method is simple,accurate,reliable and suitable for simultaneous determination of 7 components such as gallic acid in Siwei jianghuang decoction powder.

OBJECTIVE:To optimize extraction technology of cortex of Berberis dictyophylla by ethanol. METHODS:Using the contents of magnoflorine,jatrorrhizine hydrochloride,palmatine hydrochloride and berberine hydrochloride,the amount of extract as evaluation indexes,the effects of ethanol amount,volume fraction of ethanol and extraction time on extraction technology were investigated by uniform design method-comprehensive scoring method. The extraction methods of first time, second time and third time were investigated by 3 times of uniform design test. The optimal schemes of 3 times of extraction test were determined and validation test was conducted,and the transfer rates were calculated. RESULTS:The optimal technology was as follows as coarse powder of cortex of B. dictyophylla,15-fold 75% ethanol,extracting for 2 times,120 min each time. In validation test,the contents of magnoflorine,jatrorrhizine hydrochloride,palmatine hydrochloride and berberine hydrochloride were 58.96,4.82,3.07,23.29 mg/g after B. dictyophylla was extracted by optimization technology for 2 times. The transfer rates were 93.85%,95.02%,96.28%,94.88%,respectively(RSD=3.87%,2.64%,4.00%,3.91%,n=3). CONCLUSIONS:The optimal ethanol reflux extraction technology of cortex of B.dictyophylla is reasonable and feasible with good stability.

Objective: To investigate the clinicopathologic features of microcystic, elongated and fragmented (MELF) pattern invasion of endometrial adenocarcinoma. Methods: HE and immunohistochemistry staining method were used to analysis morphologic features and immunophenotype of 72 patients of endometrial adenocarcinoma with MELF pattern invasion, and chi-square test was used to analysis the clinicopathologic features. Results: The mean age of 72 patients was 54 years (40 to 70 years). Thirty-two patients were pre-menopausal and 40 were post-menopausal. According to the FIGO staging system (2014), 32 cases(44.4%)were at stage Ⅰ, 22 cases(30.6%)at stage Ⅱ, 17 cases(23.6%)at stage Ⅲ and 1 case(1.4%) at stage Ⅳ. Microscopically, MELF invasion showed microcystic, elongated slit-like or fragmented glands in myometrium and their lining cells usually were cube or flat, as well as the single or clusters of eosinophilic tumor cells mimicking histocytes. In addition, a fibromyxoid or inflammatory stromal response was often present.Immunohistochemical staining showed that MELF invasion was positive for p16, CA125 and CA19-9, but negative for ER, PR and p53.Compared with non-MELF pattern invasion, significant differences were noted in menopause pausimenia, FIGO stages, deep invasion into myometrium, lymph metastasis, lymphovascular space invasion (LVSL), serum CA125 and CA19-9 in patients with MELF pattern invasion (all P<0.05). Conclusions MELF pattern invasion of endometrial adenocarcinoma is characterized by advanced FIGO stage, deep myoinvasion, high metastasis rate to lymph node and LVSL. Pathologists should recognize the MELF invasion and evaluate the depth of myometrium of infiltration and LVSL with special attention to the presence of MELF invasion with necessary immunohistochemistry for more accurate pathological diagnosis.