Female ; Humans ; Hydatidiform Mole ; diagnosis ; Pregnancy ; Uterine Neoplasms ; diagnosis

Objective: To investigate the clinicopathological characteristics and diagnosis of ovarian Brenner tumors. Methods: Forty-seven cases of ovarian Brenner tumors were enrolled from January 2012 to May 2018 at Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Clinical data, imaging examination, histopathological characteristics and immunohistochemical phenotype were analyzed. Results: The age of the patients ranged from 30-73 years and the mean age was 55 years. Thirty-nine patients (83.0%) were postmenopausal. Forty cases (85.1%) of the Brenner tumors were benign, five (10.6%) borderline and two (4.3%) malignant. Usual tumor markers of ovarian carcinoma, including CA199 and CA125 were normal or mild elevated in the 47 cases. Imaging before surgery was not specific to Brenner tumors. Microscopically, benign Brenner tumors were composed of nests of bland, transitional-type cells within a fibromatous stroma. In our 5 cases of borderline Brenner tumors, mildly atypical transitional-type cells were projected into the cyst lumens and lack of stromal invasion. In 2 cases of malignant Brenner tumors, different degrees of nuclear atypial transitional-type cells exhibited stromal invasion. Immunohistochemical stains for CK7, GATA3, p63 and CK5/6 were positive in all cases. Ki-67 was less than 5% in Brenner tumors, and up to 20%-30% in malignant Brenner tumors. Conclusion Brenner tumors are mostly seen in postmenopausal patients and are usually benign. Imaging examination and usual ovarian tumor markers do not provide diagnostic value. Diagnosis and classification of Brenner tumors depend on histopathological evaluation.

Objective: To investigate the value of short tandem repeat (STR) genotyping in the diagnostic workup of molar and non-molar gestations with correlation of histological characteristics. Methods: Six hundred and fifty-six cases were selected based on clinically suspected hydropic abortion and/or molar pregnancy from July 2015 to September 2017 at Beijing Obstetrics and Gynecology Hospital. DNA was extracted from dissected chorionic villi and paired maternal endometrial FFPE tissue samples by Simplex OUP™ FFPE DNA Tissue Kit. STR genotyping was performed by PowerPlex 16 HS system. Results: DNA genotyping was informative in 649 of 656 cases, leading to identification of 215 hydatidiform mole gestations and 434 non-molar gestations. Most of non-molar gestations (375 cases, 86.4%) were diploid hydropic abortion. Various trisomy syndromes were found (53 cases, 12.2%), including trisomy 2, 3, 4, 7, 8, 13, 16 and 21. Only 2(0.5%) digynic triploid gestations were detected. Moreover, 4 cases (0.9%) of uniparental disomies (homologous or heterologous) were found. There were 196 cases with histologic diagnostic suspicious of hydatidiform moles were accurate sub-classified. Among them, 59 cases hydatidiform moles were under-diagnosed as diploid hydropic abortions, and 28 cases diploid hydropic abortions were over-diagnosed as hydatidiform moles.Compared with partial moles(PHM), there were no specific histomorphological features between the various types of non-molar gestations and partial moles for definitive diagnostic separation. There was no significant difference in the expression of p57^kip2 among PHM, trisomy and diploid hydropic abortions group (P=0.247). Conclusions STR genotyping can distinguish non-molar gestations from early hydatidiform moles, and efficiently avoid misdiagnosis based only on histological evaluation. Therefore, using STR genotyping, not only can the overdiagnosis of non-molar pregnancy be avoided, but also individualized management can be offered to patients including monitoring of serum hCG.

Objective: To investigate the frequency of KRAS mutation in mucinous epithelial lesions of the endometrium, and analyze the correlation between KRAS mutation and the clinicopathologic features. Methods: The cohort included forty-three cases of mucinous epithelial lesions of the endometrium selected from July 2015 to October 2017 from Beijing Obstetrics and Gynecology Hospital, and 22 control cases. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for KRAS exons 2 and 3 was performed, followed by sequencing using capillary electrophoresis. The Fisher exact test was used to compare the prevalence of KRAS mutation among the different groups. Results: The patients′age ranged from 33 to 77 years [mean (55.12±9.34) years, median 55 years]. None of the eight cases of endometrial hyperplasia with mucinous differentiation without atypia showed KRAS mutation. The frequency of KRAS mutations was 1/10 in endometrial atypical hyperplasia, 1/12 in endometrioid carcinoma, 4/11 in endometrial atypical hyperplasia with mucinous differentiation (EAHMD), 6/15 in endometrioid carcinoma with mucinous differentiation (ECMD) and 8/9 in mucinous carcinoma (MC), respectively. The differences were statistically significant between MC versus EC (P<0.01) and MC versus ECMD (P<0.05). Conclusion The high frequency of KRAS mutation in EAHMD, ECMD and MC indicates that KRAS mutational activation is implicated in the pathogenesis of endometrial mucinous carcinoma.

OBJECTIVETo investigate the clinical utility of short tandem repeats(STR) genotyping technique for diagnosis of partial hydatidiform moles (PHM).

METHODSTen cases with the original diagnosis of PHM and six cases diagnosed as "favour PHM" or "abnormal villous, PHM not excluded" were selected for the study. The clinical information and follow-up data were reviewed. Histopathologic features were evaluated along with p57 immunohistochemistry. After DNA extraction from each sample, genotyping was performed by AmpFlSTR(®) Identifiler™ PCR kit to amplify 15 STR polymorphism loci plus the amelogenin gender-determining in a single robust PCR.

RESULTSThe age of patients ranged from 18 to 49 years (mean=29 years, median=29 years). Two villous populations (7/16), irregular villous contour (13/16), at least moderate trophoblastic hyperplasia (2/16), cistern formation (8/16), syncytiotrophoblastic knuckles (14/16), trophoblastic pseudoinclusions (6/16) and nucleated fetal red blood cells (8/16) were presented in these cases. Of the cases in the study, STR genotyping identified 4 monospermic complete hydatidiform moles (MCM), 3 dispermic partial hydatidiform moles (DPM) and 9 hydropic abortions (HA). The misdiagnosis rate was 13/16 only relied on morphology evaluation. Immunostaining of p57 showed 3/4 of MCM were focally positive (<5%-20%+), 1/4 of MCM were diffusely positive (70%+), 3/3 of DPM were diffusely positive (≥50%+), 7/9 of HA were diffusely positive (≥50%+), and 2/9 of HA were focally positive (10%+).

CONCLUSIONSCombination of histomorphologic evaluation and p57 immunostaining is insufficient for a definitive diagnosis of PHM. STR genotyping offers an accurate diagnosis of PHM.

Abortion, Spontaneous ; Adolescent ; Adult ; Cyclin-Dependent Kinase Inhibitor p57 ; metabolism ; Female ; Genotype ; Genotyping Techniques ; Humans ; Hydatidiform Mole ; diagnosis ; genetics ; Immunohistochemistry ; Microsatellite Repeats ; Middle Aged ; Polymerase Chain Reaction ; Pregnancy ; Trophoblasts ; pathology ; Uterine Neoplasms ; diagnosis ; genetics ; Young Adult

OBJECTIVETo evaluate the sensitivity and specificity of immunohistochemical (IHC) staining of DNA mismatch repair (MMR) protein for the screening of microsatellite instability (MSI) colorectal cancer (CRC).

METHODSA total of 255 CRC cases were studied, including 140 cases of routine paraffin-embedded tissue samples and 115 cases constructed on tissue microarray. Expressions of 4 MMR proteins including MHL1, MSH2, MSH6 and PMS2 were investigated by IHC. Negative protein expression was defined as complete absence of nuclear staining within tumor cells in the presence of positively labeled internal non-neoplastic cells. Focal staining was defined as the presence of staining in < 5% of the tumor cells. CRCs showing negative staining for any MMR proteins were interpreted as MMR deficient tumors. PCR-genescan MSI analysis was performed in each case by a five marker panel including Bat26, Bat25, NR-21, NR-24 and MONO-27.

RESULTSAmong the 140 CRCs with routine formalin-fixed paraffin embedded tissue sections, concordance rate between IHC and PCR-genescan was 98.6% (138/140), the sensitivity and specificity of IHC in detecting MSI tumors were 94.9% (37/39) and 100.0% (101/101), respectively. The 2 disconcordant cases showed focal staining in at least one of the MMR proteins but were confirmed to be MSI-H CRCs by PCR-genescan assay. On tissue microarray, 91.3% (105/115) of the cases had informative results. The concordance rate between IHC and PCR-genescan was 100.0% (105/105). Both the specificity and sensitivity of IHC in detecting MSI tumors on available tissue microarray samples were 100.0%. Ten cases were inclusive due to the presence of negative stains of MMR proteins in both the tumor and internal control cells.

CONCLUSIONSDetection of 4 MMR proteins expression by IHC is reliable for identifying MSI CRCs and is recommended for routine practice. Tumors with focal MMR protein staining are highly suspected for the presence of MSI-H and PCR-genescan based MSI analysis should be performed to confirm.

Colorectal Neoplasms ; genetics ; DNA Mismatch Repair ; DNA-Binding Proteins ; deficiency ; genetics ; Humans ; Immunohistochemistry ; Microsatellite Instability ; Polymerase Chain Reaction ; Sensitivity and Specificity