1.Atypical forms of microglandular hyperplasia of the cervix: a clinicopathological analysis of 29 cases
Jing ZHAO ; Rongkui LUO ; Lihong ZHANG ; Weiyong GU ; Yinping XIAO ; Xianrong ZHOU ; Xiang TAO ; Yan NING
Chinese Journal of Pathology 2025;54(12):1311-1316
Objective:To investigate the clinicopathological characteristics, immunophenotype and differential diagnosis of atypical forms of microglandular hyperplasia of the cervix (AMGH).Methods:A total of 29 cases of AMGH diagnosed at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China from January 2010 to December 2024 were analyzed. Relevant clinical and pathological data of the patients were collected using the electronic medical record system and medical records copied from the outside hospitals. The patients were followed up.Results:Among the 29 cases, 28 were consultation cases, 22 (79%) of the 28 cases were considered as glandular neoplastic lesions by the original institutions. The nature of the lesion was uncertain in 1 case, the diagnosis was suspicious for AMGH in another 1 case, and only 4 cases were clearly diagnosed as AMGH. The median age of the 29 patients was 44 (43, 48) years. Eighteen (62%) of the 29 cases presented as cervical polyp. Twelve of the 16 tested cases were negative for human papillomavirus. The pathological presentation was complex and diverse, including solid, trabecular, cribriform, and papillary patterns, forming pseudo-invasive structures. The glandular epithelium and proliferating reserve cells had diverse morphologies, which presented with abundant eosinophilic cytoplasm or clear cytoplasm. Signet-ring or hobnail cells were also seen. The nuclear atypia was mild, with 0-7 mitotic figures per 10 HPF. Immature squamous metaplasia was noted. The stroma showed edema, myxoid change and hyaline degeneration, accompanied by infiltration of acute and chronic inflammatory cells. Immunohistochemistry demonstrated that p16 was negative in 8/16 of the cases or patchy positive in the other 8/16, Ki-67 positive rate was less than 10% in all 16 cases, p53 was wild phenotype (9/9), and carcinoembryonic antigen was negative in 4/5 cases and focally positive in 1/5 cases, while p63 was positive in 6/9 of the tested cases.Conclusions:AMGH is a benign non-neoplastic lesion of the cervical glands. Half of the cases occur in perimenopausal or postmenopausal women, often presenting as polypoid hyperplasia or localized cervical thickening/elevation with a friable, fragile texture. Microscopically, it may show a pseudoinvasive pattern, making it prone to misdiagnosis as a malignant lesion. Thus, differentiation from cervical adenocarcinoma, clear cell carcinoma and microglandular endometrioid carcinoma is required. Integration of clinical history, immunohistochemistry and molecular testing may aid in the differential diagnosis.
2.Atypical forms of microglandular hyperplasia of the cervix: a clinicopathological analysis of 29 cases
Jing ZHAO ; Rongkui LUO ; Lihong ZHANG ; Weiyong GU ; Yinping XIAO ; Xianrong ZHOU ; Xiang TAO ; Yan NING
Chinese Journal of Pathology 2025;54(12):1311-1316
Objective:To investigate the clinicopathological characteristics, immunophenotype and differential diagnosis of atypical forms of microglandular hyperplasia of the cervix (AMGH).Methods:A total of 29 cases of AMGH diagnosed at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China from January 2010 to December 2024 were analyzed. Relevant clinical and pathological data of the patients were collected using the electronic medical record system and medical records copied from the outside hospitals. The patients were followed up.Results:Among the 29 cases, 28 were consultation cases, 22 (79%) of the 28 cases were considered as glandular neoplastic lesions by the original institutions. The nature of the lesion was uncertain in 1 case, the diagnosis was suspicious for AMGH in another 1 case, and only 4 cases were clearly diagnosed as AMGH. The median age of the 29 patients was 44 (43, 48) years. Eighteen (62%) of the 29 cases presented as cervical polyp. Twelve of the 16 tested cases were negative for human papillomavirus. The pathological presentation was complex and diverse, including solid, trabecular, cribriform, and papillary patterns, forming pseudo-invasive structures. The glandular epithelium and proliferating reserve cells had diverse morphologies, which presented with abundant eosinophilic cytoplasm or clear cytoplasm. Signet-ring or hobnail cells were also seen. The nuclear atypia was mild, with 0-7 mitotic figures per 10 HPF. Immature squamous metaplasia was noted. The stroma showed edema, myxoid change and hyaline degeneration, accompanied by infiltration of acute and chronic inflammatory cells. Immunohistochemistry demonstrated that p16 was negative in 8/16 of the cases or patchy positive in the other 8/16, Ki-67 positive rate was less than 10% in all 16 cases, p53 was wild phenotype (9/9), and carcinoembryonic antigen was negative in 4/5 cases and focally positive in 1/5 cases, while p63 was positive in 6/9 of the tested cases.Conclusions:AMGH is a benign non-neoplastic lesion of the cervical glands. Half of the cases occur in perimenopausal or postmenopausal women, often presenting as polypoid hyperplasia or localized cervical thickening/elevation with a friable, fragile texture. Microscopically, it may show a pseudoinvasive pattern, making it prone to misdiagnosis as a malignant lesion. Thus, differentiation from cervical adenocarcinoma, clear cell carcinoma and microglandular endometrioid carcinoma is required. Integration of clinical history, immunohistochemistry and molecular testing may aid in the differential diagnosis.
3.Small cell carcinoma of the ovary of hypercalcaemic type: a clinicopathological analysis of sixteen cases
Jing ZHAO ; Rongkui LUO ; Tingting CHEN ; Jing LIN ; Jie ZHANG ; Shilei ZHANG ; Xianrong ZHOU ; Xiang TAO ; Yan NING
Chinese Journal of Pathology 2024;53(12):1210-1216
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.
4.Prenatal diagnosis and genetic analysis of a 46,XN,del(11)(q14q22) fetus.
Liping ZHAO ; Huayu LUO ; Guixiang LUO ; Xianrong QIU ; Yanjie LIAO
Chinese Journal of Medical Genetics 2020;37(8):879-882
OBJECTIVE:
To diagnose a 46,XN,del(11)(q14q22) fetus by non-invasive prenatal testing (NIPT), karyotype analysis and whole genome sequencing (WGS).
METHODS:
Peripheral blood sample of the gravida was taken for NIPT screening. Blood samples of the gravida, her husband, and umbilical cord blood were also taken for chromosome karyotyping and whole genome sequencing (WGS).
RESULTS:
NIPT screening indicated the fetus has carried partial deletion of chromosome 11, while no chromosomal abnormality was found with the cord blood sample due to the low resolution of G-banding analysis. WGS analysis of the cord blood indicated 46,XN,del(11q14.3q22.1). seq[GRCh37/hg19] (90 623 404-97 469 319)×1, 6.85 Mb. The karyotype of the fetus was eventually determined as 46,XN,del(11)(q14q22). Karyotyping analysis suggested that the gravida and her husband were 46,XX,del(11)(q14q22)[8]/46,XX[92] and 46,XY, respectively. However, neither of them was found to harbor the del(11)(q14q22) by WGS.
CONCLUSION
The abnormal karyotype of the fetus has derived from its mother's low percentage mosaicism. Combined NIPT, karyotyping analysis and WGS can detect chromosomal disorders with accuracy.
5.Coagulation dysfunction in a newborn infant caused by maternal exposure to clozapine during pregnancy
Yemin HU ; Liang HUANG ; Xianrong WEN ; Hao LUO
Adverse Drug Reactions Journal 2020;22(11):644-645
A 31-year-old female patient with schizophrenia got pregnant naturally during the treatment with clozapine (50 mg/d) and had been taking the drug during the pregnancy. Prenatal fetal ultrasound and chromosome examination showed no obvious abnormalities. The mother received subcutaneous injections of insulin aspart injection and insulin detemir injection and oral iron polysaccharide complex capsules for gestational diabetes mellitus and mild anemia successively during pregnancy. One live male infant was delivered by cesarean section at 39 +2 weeks of gestation, with a birth weight of 3 280 g. The infant′s Apgar score was 10. Physical examination of the newborn showed scattered ecchymosis on limbs skin, pinpoint-like petechiae on whole-body skin, and arrhythmia by heart auscultation. Laboratory tests showed prothrombin time 14.4 s, activated partial thromboplastin time 69.4 s, thrombin time 22.9 s, fibrinogen 1.27 g/L, and platelet count 366×10 9/L. Neonatal coagulation dysfunction was diagnosed, which was considered to be possibly related to clozapine. Intravenous infusions of vitamin K 1 injection and human fibrinogen were given. Four days later, ecchymosis and petechiae on his whole body were less than before, prothrombin time was 11.4 s, activated partial thromboplastin time was 45.0 s, thrombin time was 20.6 s, and fibrinogen was 2.22 g/L. Eight days later, his ecchymosis and petechiae basically disappeared.
6.Coagulation dysfunction in a newborn infant caused by maternal exposure to clozapine during pregnancy
Yemin HU ; Liang HUANG ; Xianrong WEN ; Hao LUO
Adverse Drug Reactions Journal 2020;22(11):644-645
A 31-year-old female patient with schizophrenia got pregnant naturally during the treatment with clozapine (50 mg/d) and had been taking the drug during the pregnancy. Prenatal fetal ultrasound and chromosome examination showed no obvious abnormalities. The mother received subcutaneous injections of insulin aspart injection and insulin detemir injection and oral iron polysaccharide complex capsules for gestational diabetes mellitus and mild anemia successively during pregnancy. One live male infant was delivered by cesarean section at 39 +2 weeks of gestation, with a birth weight of 3 280 g. The infant′s Apgar score was 10. Physical examination of the newborn showed scattered ecchymosis on limbs skin, pinpoint-like petechiae on whole-body skin, and arrhythmia by heart auscultation. Laboratory tests showed prothrombin time 14.4 s, activated partial thromboplastin time 69.4 s, thrombin time 22.9 s, fibrinogen 1.27 g/L, and platelet count 366×10 9/L. Neonatal coagulation dysfunction was diagnosed, which was considered to be possibly related to clozapine. Intravenous infusions of vitamin K 1 injection and human fibrinogen were given. Four days later, ecchymosis and petechiae on his whole body were less than before, prothrombin time was 11.4 s, activated partial thromboplastin time was 45.0 s, thrombin time was 20.6 s, and fibrinogen was 2.22 g/L. Eight days later, his ecchymosis and petechiae basically disappeared.
7.Effects of Cimetidine on L ow Dose Rate Irradiation-induced Liver Cell Apoptosis in Beagle Dogs and Its Mechanism
Qingrong WANG ; Ying HE ; Yining ZHAO ; Xianrong SHEN ; Yuming LIU ; Kexian LI ; Qun LUO ; Wei CHEN ; Dengyong HOU
China Pharmacy 2019;30(12):1623-1628
OBJECTIVE: To study the effects of cimetidine on low dose rate irradiation-induced liver cell apoptosis in Beagle dogs. METHODS: Healthy male Beagle dogs were randomly divided into normal control group, model control group, positive drug group (lentinan, 21.33 mg/kg) and cimetidine low-dose, medium-dose and high-dose groups (5.33, 10.67, 21.33 mg/kg), with 4 Beagle dogs each. Except for normal control group, other groups were given 60Co-γ accumulative irradiation (dosage rate: 0.040 8 mGy/min) for 23 d; the medication groups were given relevant medicine orally before irradiation, once a day. Twenty-four hours after stopping irradiation, TUNEL method was used to detect the apoptosis of liver cells in Beagle dogs. The percentage of apoptotic cells was calculated. The expression level of apoptosis-related proteins (Bax, Bcl-2, Caspase-3, p53) in liver tissue was detected by immunohistochemistry. RESULTS: Compared with normal control group, apoptotic cells and Bax, Caspase-3, p53 positive cells were increased significantly in liver tissue of Beagle dogs in model control group; the percentage of apoptotic cells, protein expression levels of Bax, Caspase-3 and p53 were increased significantly; Bcl-2 positive cells were decreased significantly, and its protein expression level was decreased significantly (P<0.05 or P<0.01). Compared with model control group, above positive cells of liver tissue in Beagle dogs were changed to different extents in medication groups; the percentage of apoptotic cells and protein expression levels of p53 in medication groups, protein expression levels of Bax in positive drug group, cimetidine low-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were decreased significantly; protein expression levels of Bcl-2 were increased significantly in cimetidine groups. The percentage of apoptotic cells in cimetidine medium-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were all lower than positive control group. Protein expression level of p53 in cimetidine low-dose group was significantly higher than positive drug group (P<0.05 or P<0.01). CONCLUSIONS: Cimetidine can inhibit the low dose rate irradiation-induced apoptosis of liver cells in Beagle dogs, and certainly protect liver cells against irradiation. The mechanism of it may be associated with up-regulating the protein expression of Bcl-2 and down-regulating the protein expression of Bax, Caspase-3 and p53 in liver cells.
8.Application of subjective visual otolith function test on the medical evaluation of pilots
Lihong ZHAI ; Jinye LUO ; Xianrong XU ; Yuhua LIU
Chinese Journal of Aerospace Medicine 2019;30(1):25-29
Objective To provide the references on otolith function evaluation by investigating subj ective visual vertical (SVV)and subj ective visual horizontal (SVH),as well as the tilt range of SVV and SVH when pilot,s head tilted 45°to the left or right side for the selection and the medical evaluation of pilots . Methods XZ-2008 Otolith function test instrument was chosen for the tests.①One hundred active fighter pilots were chosen as the subj ects and the angle range of their head upright SVV was recorded.②Twenty-four active fighter pilots were chosen as the subjects.The angle range of their head upright SVV and the angle ranges of head 45°right or left tilt SVH and SVV were recorded.Normal value range was caculated according to Mean±1 .96 SD Results ①The angle range of head upright SVV of 100 pilots was -1 .61°-1 .73°.②The angle range of head upright SVH of 24 pilots was -2.34°-3.18°,the angle range of head 45°left tilt SVV was -7.12°-6.12°,and the range of -6.76°-4.84°for their head 45°right tilt.The angle range of 45°left tilt and 45°right tilt SVH was respectively -9 .84°-6.74°,and -6 .70°-6 .20°. Conclusions The study has established the test method and the normal angle range of SVV and SVH in military pilots,which is crucial for the assessment of the otolith function in medical selection and medical evaluation of military pilots.When head tilts to left or right by 45°the angles of SVV and SVH will change.We will further study its clinical signification and provide more evidence for the vestibular function medical evaluation of military flying personnel.
9.Application of subjective visual otolith function test on the medical evaluation of pilots
Lihong ZHAI ; Jinye LUO ; Xianrong XU ; Yuhua LIU
Chinese Journal of Aerospace Medicine 2019;30(1):25-29
Objective To provide the references on otolith function evaluation by investigating subj ective visual vertical (SVV)and subj ective visual horizontal (SVH),as well as the tilt range of SVV and SVH when pilot,s head tilted 45°to the left or right side for the selection and the medical evaluation of pilots . Methods XZ-2008 Otolith function test instrument was chosen for the tests.①One hundred active fighter pilots were chosen as the subj ects and the angle range of their head upright SVV was recorded.②Twenty-four active fighter pilots were chosen as the subjects.The angle range of their head upright SVV and the angle ranges of head 45°right or left tilt SVH and SVV were recorded.Normal value range was caculated according to Mean±1 .96 SD Results ①The angle range of head upright SVV of 100 pilots was -1 .61°-1 .73°.②The angle range of head upright SVH of 24 pilots was -2.34°-3.18°,the angle range of head 45°left tilt SVV was -7.12°-6.12°,and the range of -6.76°-4.84°for their head 45°right tilt.The angle range of 45°left tilt and 45°right tilt SVH was respectively -9 .84°-6.74°,and -6 .70°-6 .20°. Conclusions The study has established the test method and the normal angle range of SVV and SVH in military pilots,which is crucial for the assessment of the otolith function in medical selection and medical evaluation of military pilots.When head tilts to left or right by 45°the angles of SVV and SVH will change.We will further study its clinical signification and provide more evidence for the vestibular function medical evaluation of military flying personnel.
10.Optimization of the liquid fermentation medium of the marine petroleum-degrading bacteria Acinetobacter sp.Y9
Xue TANG ; Dengyong HOU ; Xianrong SHEN ; Ying HE ; Qun LUO ; Qingrong WANG
Chinese journal of nautical medicine and hyperbaric medicine 2018;25(1):27-31
Objective To investigate the impact of the types and concentrations of major medium components on the growth of the marine oil-degrading bacterial strain Acinetobacter sp.Y9.Methods Carbon,nitrogen and phosphorus sources in the medium of Y9 fermentation were screened and optimized by using single factor and orthogonal experiments,and the optimized medium was applied for initial fermentation of Acinetobacter sp.Y9 in the 10 L fermentor.Results After optimization,the optimal fermentation medium of Y9 included 1% glucose,2% peptone,0.1 mol/L phosphate buffer solution(Na2HPO4 · 12H2O + KH2PO4),0.05% NaCl2,0.001% CaCl2 and 0.019 % MgCl2.The value of OD~ of Y9 reached 8.24 after cultivation in the optimized medium in the 10 L fermentor for 12 hours.Conclusions The optimized medium could be used in the pilot fermentation production of Y9 strain,which might lay a solid foundation for large scale fermentation production of Y9.

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