[Practical application of the Paris system for reporting urinary cytology].

Objective: To validate the diagnostic performance of the Paris system for reporting urinary cytology (TPS). Methods: A total of 7 046 urine cytology samples from 3 402 patients collected in the Department of Pathology, Beijing Hospital, China from January 2020 to January 2022 were analyzed. 488 patients had a biopsy or resection specimen during the follow-up period of 6 months. The sensitivity, specificity, risk of malignancy (ROM) and risk of high-grade malignancy (ROHM) of the TPS were evaluated using histological diagnosis as the golden standard. Results: Among the 7 046 samples, high-grade urothelial carcinoma (HGUC) accounted for 5.7% (399/7 046), suspicious for high-grade urothelial carcinoma (SHGUC) for 3.2% (227/7 046), atypical urothelial cells (AUC) for 8.4% (593/7 046), and negative for high-grade urothelial carcinoma (NHGUC) for 72.9% (5 139/7 046) including low-grade urothelial neoplasm (LGUN) for 0.8% (59/7 046) and insufficient samples for 9.8% (688/7 046). 488 patients had a bladder biopsy or resection in the follow-up of six months, including 314 males and 174 females, aged 27 to 92 years (average, 66 years). The ROHM of TPS was 94.7% in HGUC, 83.3% in SHGUC, 41.3% in AUC and 18.8% in NHGUC. The sensitivity and specificity of urine cytology were 70.1% (169/241) and 97.0% (162/167), respectively. The negative predictive value of NHGUC was 69.2% (162/234). Conclusions: The study has shown that TPS classification has high sensitivity and specificity, high ROHM for HGUC and SHGUC, and high negative predictive value for NHGUC. The application of TPS reporting system can better interpret the clinical significance of cytology samples, improve the accuracy of urine cytopathology and ensure continuous diagnostic consistency.

[Application and evaluation of artificial intelligence TPS-assisted cytologic screening system in urine exfoliative cytology].

Objective: To explore the application of manual screening collaborated with the Artificial Intelligence TPS-Assisted Cytologic Screening System in urinary exfoliative cytology and its clinical values. Methods: A total of 3 033 urine exfoliated cytology samples were collected at the Henan People's Hospital, Capital Medical University, Beijing, China. Liquid-based thin-layer cytology was prepared. The slides were manually read under the microscope and digitally presented using a scanner. The intelligent identification and analysis were carried out using an artificial intelligence TPS assisted screening system. The Paris Report Classification System of Urinary Exfoliated Cytology 2022 was used as the evaluation standard. Atypical urothelial cells and even higher grade lesions were considered as positive when evaluating the recognition sensitivity, specificity, and diagnostic accuracy of artificial intelligence-assisted screening systems and human-machine collaborative cytologic screening methods in urine exfoliative cytology. Among the collected cases, there were also 1 100 pathological tissue controls. Results: The accuracy, sensitivity and specificity of the AI-assisted cytologic screening system were 77.18%, 90.79% and 69.49%; those of human-machine coordination method were 92.89%, 99.63% and 89.09%, respectively. Compared with the histopathological results, the accuracy, sensitivity and specificity of manual reading were 79.82%, 74.20% and 95.80%, respectively, while those of AI-assisted cytologic screening system were 93.45%, 93.73% and 92.66%, respectively. The accuracy, sensitivity and specificity of human-machine coordination method were 95.36%, 95.21% and 95.80%, respectively. Both cytological and histological controls showed that human-machine coordination review method had higher diagnostic accuracy and sensitivity, and lower false negative rates. Conclusions: The artificial intelligence TPS assisted cytologic screening system has achieved acceptable accuracy in urine exfoliation cytologic screening. The combination of manual screening and artificial intelligence TPS assisted screening system can effectively improve the sensitivity and accuracy of cytologic screening and reduce the risk of misdiagnosis.

[Pathological study on the relationship between nucleic acid oxidative stress and heart failure with preserved ejection fraction in patients aged over 85 years].

Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.

[Diagnostic values of nuclear score combined with cyclin D1 immunocytochemistry in indeterminate thyroid follicular nodules in preoperative fine needle aspiration].

Objective: To assess the feasibility of nuclear score combined with cyclin D1 immunocytochemistry in classifying indeterminate thyroid nodules with fine-needle aspiration (FNA) cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 118 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and April 2022 at the Department of Pathology, Beijing Hospital, China. These cases were subjected to cytological evaluation and cyclin D1 immunocytochemistry. The optimal cut-off points of a simplified nuclear score and the percentage of cyclin D1-positive cells for the diagnosis of malignancy or low-risk neoplasm were determined using the receiver operating characteristic (ROC) curves and area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of nuclear score and cyclin D1 immunostaining were evaluated from the crosstabs based on cut-off points. The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining was estimated using ROC curve analysis. Results: Nuclear grooves, intra-nuclear inclusions and chromatin clearing were more commonly found in malignancy/low-risk neoplasms than benign lesions (P=0.001, P=0.012 and P=0.001 respectively). A cut-off point of≥2 for the simplified nuclear score was sensitive for defining malignancy/low-risk neoplasm, and its PPV, NPV, sensitivity and specificity were 93.6%, 87.5%, 99.0% and 50.0% respectively. A positive cut-off point of 10% positive thyroid cells in cyclin D1 immunostaining demonstrated sensitivity of 88.5%, specificity of 100%, PPV of 100% and NPV of 53.8% for correctly detecting thyroid malignancy or low-risk neoplasm. The sensitivity and PPV of simplified nuclear score combined with cyclin D1 immunostaining were 93.3% and 100%, respectively. Both specificity and NPV were maintained at high levels (100% and 66.7%, respectively). The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining in detecting thyroid malignancy/low-risk neoplasm was increased to 94.1% compared to using either of them alone. Conclusions: Combing simplified nuclear score and cyclin D1 immunostaining on FNA cytology specimens can increase the diagnostic accuracy in classifying thyroid nodules of indeterminate cytological categories. Thus, this supplementary approach provides a simple, accurate, and convenient diagnostic method for cytopathologists so that may reduce unnecessary thyroidectomies.

[Retrospective analysis of BI-RADS 4 and 5 lesions additionally detected by breast MRI].

Objectives: To establish a newly-designed scoring system for breast imaging-reporting and data system (BI-RADS) 4 and 5 breast lesions only visible on MRI, and to examine their clinical pathway of biopsy. Methods: The BI-RADS 4 and 5 breast lesions only visible on MRI but not suspected on mammograms or ultrasound between June 2007 and December 2021 at Beijing Hospital were evaluated retrospectively. A total of 209 lesions from 184 patients were finally included. All patients were female, aged (50±11) years (range: 27 to 76 years). All lesions were confirmed by pathology and divided into malignancy and non-malignancy. The lesions were divided into mass and non-mass type using BI-RADS. The receiver operator characteristic (ROC) curve was used to evaluate the diagnostic performance of the new scoring system. Four types of pathology-obtaining pathway were used: biopsy guided by second-look ultrasound, local excision guided by lesion position information on MRI, intraductal lesion excision guided by methylene blue stain and mastectomy. The data between mass and non-mass lesions were compared by Mann-Whitney U test, χ2 test or Fisher exact test,respectively. Results: There were 124 malignant and 85 non-malignant lesions, while 100 mass and 109 non-mass lessions. The sizes between mass and non-mass lesions showed significant difference(M(IQR)) (7.0 (3.0) mm vs. 25.0 (25.0) mm, U=568.000, P<0.01) and their BI-RADS diagnostic accuracy had no significant difference (53.0% (53/100) vs. 65.1% (71/109), χ2=3.184, P=0.074). The areas under ROC curve of the new scoring system for evaluating mass and non-mass were 0.841 and 0.802, respectively. When taking Score 3 as threshold, it can potentially avoid 14.0% (14/100) and 4.6% (5/109) of biopsies in mass and non-mass, respectively. As to pathway of obtaining pathology, second-look ultrasound succeeded more easily in mass than non-mass (41.0% (41/100) vs.26.6% (29/109), χ2=4.851, P=0.028). More MRI-guided local excisions were performed in non-mass than mass (52.3% (57/109) vs. 34.0% (34/100), χ2=7.100, P=0.008). Conclusions: For suspicious breast lesions detected by MRI but not suspected on X-ray or ultrasound, the new scoring system can further increase diagnostic accuracy. The second-look ultrasound plays an important role for obtaining pathology, especially for mass-type lesion.

[Diagnostic values of cyclin D1 immunocytochemistry and molecular testing in preoperative fine needle aspiration of undeterminate thyroid nodules].

Objective: To assess the value of cyclin D1 immunocytochemistry combined with a small panel molecular analysis in indeterminate cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 96 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and December 2021 in Department of Pathology, Beijing Hospital. The cases were evaluated by cyclin D1 immunocytochemistry and molecular testing of BRAFV600E or a small panel of markers (BRAF, N-RAS, H-RAS, K-RAS and TERT) in the FNA specimens. The identification of the optimal cut-off point of cyclin D1 for the diagnosis of malignancy was evaluated using the receiver operating characteristic (ROC) curves and the assessment of the area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of all these markers were evaluated with the crosstabs and significance was calculated. Results: Ninty-six patients with 96 thyroid nodules were enrolled, including 42 cases of TBSRTC-III, 10 cases of TBSRTC-IV and 44 cases of TBSRTC-V. There were 79 females and 17 males with a median age of 47 years (range, 25 to 75 years). A 7.5% cut-off value for positive cyclin D1 nuclear immunostaining in thyroid cells demonstrated 100% PPV, 57.1% NPV, 81.0% sensitivity and 100% specificity for thyroid malignancy diagnosis. The sensitivity of the BRAFV600E mutation test or combined with a small panel test alone for thyroid malignancy diagnosis were 65.5% and 69.0% respectively. The sensitivity for thyroid malignancy diagnosis increased to 94.0% and 95.2% respectively when combining the cyclin D1 immunocytochemistry with the molecular test, and the specificities remained 100% and 91.7% respectively.The accuracy of cyclin D1 immunocytochemistry combined with a small panel of molecular test in detecting thyroid malignancy increased to 94.8% compared to using these markers alone. Conclusions: The addition of cyclin D1 immunocytochemistry and a small panel of molecular testing to FNA cytology can increase the sensitivity and NPV of cytology in indeterminate categories, and this supplementary approach provides a simple, accurate and convenient diagnostic method for reducing unnecessary thyroidectomies.

[Treatment and prognosis of 826 infants with critical congenital heart disease: a single center retrospective study].

Objective: To analyze the current status of clinical treatment and factors influencing postoperative mortality in infants with critical congenital heart disease (CCHD) in China, optimize the perioperative management of CCHD, and provide a new scientific basis for clinical decision-making for the optimal management of these patients. Methods: This is a retrospective single-center study. Infants diagnosed with CCHD in Guangdong Provincial People's Hospital from January 2017 to December 2019 (aged 0-1 years at admission) were enrolled. General clinical information, inpatient treatment information, prognosis and complications were collected and analyzed. Multivariate logistic regression analysis was used to explore the independent risk factors of postoperative death in infants with CCHD. Results: A total of 826 infants with CCHD were included, including 556 males (67.3%) and the age at first admission was 51.0 (5.0,178.3) days. 264 (32.0%) cases were tetralogy of Fallot and 137 (16.6%) cases were total anomalous pulmonary venous return. 195 cases (23.6%) were diagnosed prenatally. 196 cases (23.7%) were treated with prostaglandin. The preoperative invasive ventilation time was 0 (0, 0) hour, and the postoperative invasive ventilation time was 95.0 (26.0, 151.8) hours. A total of 668 cases (80.9%) underwent surgical treatment. The age was 100.5 (20.0, 218.0) days during operation and the operation time was 190.0 (155.0, 240.0) hours. Sixty-two cases (7.5%) received medical treatment, and 96 cases (11.6%) gave up treatment. A total of 675 cases (81.7%) were discharged with improvement, 96 cases (11.6%) were discharged after giving up treatment, 55 cases (6.7%) died and 109 cases (13.2%) were readmitted within one year. Complications occurred in 565 (68.6%) cases, including pneumonia in 334 cases (40.4%) and cardiac arrhythmias in 182 cases (22.0%). Multifactorial analysis showed that delayed chest closure (OR=49.775, 95%CI 3.291-752.922, P=0.005), prolonged post-operative invasive ventilator ventilation (OR=1.003, 95%CI 1.000-1.005, P=0.038) and cardiac hypoplasia syndrome (OR=272.658, 95%CI 37.861-1 963.589, P<0.001) were the independent risk factors for mortality in CCHD infants post-operation. Conclusions: Tetralogy of Fallot and total anomalous pulmonary venous return account for the majority of infants with CCHD. The proportion of infants diagnosed prenatally was less than 1/4. The majority CCHD infants received surgical treatment. The main complications are pneumonia and arrhythmia. Delayed chest closure, prolonged postoperative invasive ventilator ventilation and low cardiac output syndrome are the independent risk factors for postoperative death in infants with CCHD.

Effect of congenital heart disease on the recurrence of cough variant asthma in children.

BACKGROUND: The research into the recurrence of cough variant asthma (CVA) in congenital heart disease (CHD) are few in number. The purpose of this study is to investigate the effect of CHD on the risk of the recurrence of CVA. METHODS: This study was a retrospective cohort study of 489 children with CVA aged between one and 14 years, of whom 67 had CHD complicated with CVA and 134 had CVA without CHD at a ratio of 1:2 according to age, sex and index year. The adjusted hazard ratio (aHR) of CVA recurrence in both the CHD cohort and the non-CHD cohort was determined by multivariate analysis using the Cox proportional hazard regression model. RESULTS: Adjusting for CHD classification, Mycoplasma pneumonia (MP) infection and immunoglobulin E (IgE) sensitization, the recurrence hazard of CVA in the complex congenital heart disease (CCHD) group (aHR = 3.281; 95% CI 1.648-6.530; P < 0.01) was significantly higher than that in the simple congenital heart disease group (aHR = 2.555; 95% CI 1.739-3.752; P < 0.01). Further, children with IgE sensitization (aHR = 2.172; 95% CI 1.482-3.184; P < 0.01) had a higher recurrence hazard of CVA than those without IgE sensitization, and children with MP infection (aHR = 1.777; 95% CI 1.188-2.657; P < 0.01) had a higher recurrence hazard of CVA than those without the MP infection. CONCLUSION: The hazard of recurrent CVA is higher in children with CHD, especially in the CCHD children. In addition, those children with IgE sensitization or a MP infection had an increased hazard of recurrent CVA.

[Effect of progesterone on expression of ER, PR, PCNA, bcl-2, c-myc, c-fos, and EGFR in normal breast tissue implanted into nude mice].

Objective: To investigate the effect of progesterone on estrogen receptor(ER), progesterone receptor(PR), proliferating cell nuclear antigen (PCNA) , bcl-2 , c-myc, c-fos, and epidermal growth factor receptor(EGFR) expression in normal human breast tissues implanted into nude mice. Methods: A xenograft-model, pieces of normal human breast tissue implanted subcutaneously into 9-10-week-old athymic nude mice, was established.The tissue of each case was divided into 4 parts, and were transplanted into 4 nude mice.These mice were randomly divided into 4 groups, namely control group: normal saline 0.1 ml; estrogen group: estradiol benzoate 20 µg (0.1 ml, 1 mg/kg); progesterone group: 60 µg (0.1 ml, 3 mg/kg); estrogen plus progestin group: estradiol benzoate 20 µg (0.1 ml, 1 mg/kg) and progesterone (0.1 ml, 3 mg/kg) 60 µg.Treatment was given every other day, and human breast tissues were removed for experiments after treatment for 4 weeks.The implanted breast tissue were fixed and sliced.The expression of ER, PR PCNA and bcl-2 were assayed by immunohistochemical, c-myc, c-fos, and EGFR mRNAs were determined by in situ hybridization. Results: In estrogen group, and estrogen plus progestin group, the positive expression of ER was lower and PR was higher than those of the control group (P<0.05); the expression of ER and PR in progesterone group had no differences compared with the control group (P>0.05); the expression of PCNA and bcl-2 in estrogen group were higher than that of the control group (P<0.01, P<0.05), while they showed no significant difference in the other two drug groups compared with the control group (P>0.05). The expression of c-myc, c-fos and EGFR in estrogen group and estrogen plus progestin group were higher than those in control group (P<0.01). The expression of c-myc in the progesterone group was higher than that in the control group (P<0.01), and the expression of c-fos and EGFR in the estrogen and progesterone groups were not significantly different compared with those in the control group (P>0.05). Conclusions: Progesterone did not affect the proliferation and apoptosis of human normal breast tissue, but may have anti-proliferative and pro-apoptosis effects when coupled with estrogen.And it can up-regulate the expression of c-myc.

[Myocardial amyloid deposition in patients aged over 85 years with heart failure and preserved ejection fraction].

Objective: To determine the frequency and extent of left ventricular amyloid deposition in patients aged over 85 years with heart failure and preserved ejection fraction (HFpEF). Methods: A total of 43 patients aged 85 to 100 years old were enrolled in this study based on the autopsy database of Beijing Hospital from February 1, 2003 to October 31, 2016. The frequency and extent of left ventricular amyloid deposition and myocardial fibrosis were determined in left ventricular specimens from patients with antemortem diagnosis of HFpEF without clinically apparent amyloid (n=28) and from control subjects (n=15) post Congo red staining and Masson's trichrome staining. Kappa test was used to evaluate the consistency of the myocardial amyloidosis and fibrosis. Results: The heart weight of the patients in HFpEF group and in control group were similar((452.7±107.7)g vs. (415.0±70.8)g, t=-1.218, P=0.23)). Positive Congo-red staining was found in 24 examples (24/28) in HFpEF group and 5 examples (5/15) in the control group; severe amyloid deposition was found in 7 examples (7/28) in HFpEF group, but not in the control group. Amyloid deposition was more severe in HFpEF group than in control group (χ(2)=12.205, P<0.01). Masson's trichrome staining evidenced moderate to severe fibrosis in 19 cases (19/28) in HFpEF group and 8 cases (8/15) in control group (χ(2)=1.019, P=0.35). A consistent evaluation of the degree of myocardial fibrosis and the degree of myocardial amyloid deposition in all selected participants was performed and results showed that these two parameters were not consistent (Kappa value=0.2, P=0.820). Conclusion: Amyloid deposition is common in the elderly patients with heart failure and preserved ejection fraction, suggesting that myocardial amyloidosis may be related to the development of HFpEF. There is no significant correlation between myocardial amyloidosis and myocardial fibrosis in this cohort.

[Comparison of prognosis between invasive micropapillary carcinoma and invasive ductal carcinoma of breast: a single center, retrospective case-control study].

Objective: To elucidate the clinicopathological characters and prognostic factors of invasive micropapillary carcinoma of the breast (IMPC) by compared with invasive ductal carcinoma, not otherwise specified of the breast (IDC). Methods: The retrospective study was performed with female patients who had undergone curative resection for breast cancer without neoadjuvant chemotherapy from June 2008 to April 2016 in Breast Center of Beijing Hospital. Forty-seven mixed or pure IMPC patients and 93 pure IDC patients(admitted in the same center from October 2008 to January 2016 ) were matched for tumor stage, nodal status and age. Follow-up was done every 3 to 6 months postoperatively. The deadline was July 31, 2016. The curves of disease free survival and overall survival were drawn by the Kaplan-Meier method, and survival rates were compared by means of the Log-rank test. Potential prognostic variables that were identified on univariate analysis were analyzed with Cox's proportional hazards regression model for multivariate analysis. The χ(2) test or Fisher's exact test was used to compare distributions across 2 groups and the Mann-Whitney U test or t test was used to analyze the medians or means of 2 groups. Results: With exact matches, the rates of lymphovascular invasion (LVI) (29.8% vs. 12.9%, χ(2)=5.885, P=0.015)and histological grade 3 (40.4% vs. 21.5%, χ(2)=-2.690, P=0.007) were both significantly higher in patients with IMPC than that in IDC group, but the survival between the two pathological types were not significantly different (all P>0.05). The percent of IMPC component didn't influence the clinicopathologic characters (all P >0.05), but a significantly longer median disease free survival (χ(2)=11.731, P=0.001) when the patients had more than 50% of IMPC component was found. Conclusions: Higher rates of LVI and histological grade 3 were found in IMPC than that in IDC, but the survival was comparable between the two groups. A longer DFS occurred in patients with IMPC component more than 50%.

[The comparison of characters between invasive micropapillary carcinoma and invasive ductal carcinoma not otherwise specified of the breast].

Objective: To analyze the differences of clinicopathological characters and prognostic factors between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC) not otherwise specified of the breast. Methods: Patients who were treated from June 2008 to April 2016 in Breast Center of Beijing Hospital were retrospectively analyzed to evaluate the differences between IMPC (n=59) and IDC (n=1 080). Follow-up was done every 3 to 6 months postoperatively with a deadline of July 31, 2016. The curves of disease free survival (DFS) and overall survival (OS) were drawn by Kaplan-Meier method, and survival rates were compared by means of the Log-rank test. Potential prognostic variables which were identified on univariate analysis were analyzed with Cox's proportional hazards regression model for multivariate analysis. Results: More lymph nodes were involved in IMPC group (χ(2)=12.168, P=0.007) which led to more later stage in this group (χ(2)=8.950, P=0.011). IMPC group displayed a significantly increased rate of lymphovascular invasion (LVI) compared to IDC group (χ(2)=13.511, P = 0.001). The expression rate of estrogen receptor (ER) and progesterone receptor (PR) was higher in IMPC group than that in IDC group (89.8% vs. 76.3% and 88.1% vs. 70.7%, respectively, χ(2)=5.786, 8.332, all P<0.05). In multivariate analysis performed with the variables found significant in univariate analysis, the only variable found significantly affecting DFS of IMPC group was the T stage (T1-2 and T3-4, OR=5.217, 95%CI: 1.401 to 19.430, P=0.014), while in IDC group, pathological stage (stage Ⅰ to Ⅱ and stage Ⅲ to Ⅳ, OR=1.870, 95% CI: 1.262 to 2.771, P=0.002), lymph node positive ratio (LNR) (OR=2.222, 95%CI: 1.561 to 3.162, P=0.000), PR (OR=1.856, 95%CI: 1.118 to 3.082, P=0.017), and age (<50 years old and ≥50 years old, OR=0.695, 95%CI: 0.488 to 0.989, P=0.043) were prognostic factors. There were two variables found significantly affecting OS of IMPC group, which were T stage (OR=3.713, 95%CI: 1.539 to 8.959, P=0.004) and LNR (OR=2.850, 95%CI: 1.033 to 7.862, P=0.043). While in IDC group, LNR was the only variable found significantly affecting OS (OR=2.129, 95%CI: 1.324 to 3.425, P=0.002). Compared with IDC, the patients with IMPC were more likely to have local or regional recurrence (P=0.006). Although the median DFS interval was longer in IDC group (χ(2)=9.739, P=0.002), the median OS interval was comparable between the two groups (χ(2)=0.787, P=0.375). Conclusion: Although IMPC has lymphotropic feature, tendency of LVI and local or regional recurrence, it has an OS which is comparable with IDC.

[Accurate grading of pancreatic neuroendocrine tumors with Ki-67 index in fine-needle aspiration specimens: a comparative cytologic and histologic study].

Objective: To study the cytomorphologic features and determine whether pancreatic neuroendocrine tumors (PanNET) sampled by fine-needle aspiration (FNA) can be accurately graded based on the Ki-67 index when compared to surgical samples. Methods: Corresponding intraoperative (19 cases) or endoscopic ultrasound-guided (3 cases) FNA cytology and surgical tissue specimens were obtained from 22 tumors, which were reviewed and stained for Ki-67 proliferation marker. The cytological samples included more than 200 tumor cells. Samples were graded by scoring the Ki-67 positive index in accordance with the 2010 WHO criteria. The grading scores assigned to the FNA cytology samples were compared with the scores assigned to the corresponding histological samples. Concordance was achieved by using 5% (instead of 2%) as a cut-off value for defining G2 tumors. One cytological sample included less than 500 tumor cells was excluded in the concordance calculation. Results: The cytological smears consisted of uniform, monotonous and isolated cells, loose cellular aggregates and rosette-like formations. Some tumor cells clustered around segments of capillaries. The cells demonstrated distinct cytoplasmic and nuclear features. Mitoses and necrosis were rarely seen. When traditional 2% Ki-67 index cut-off value were used to classify G2 tumors, the majority (86.4%, κ=0.812, P<0.01) of FNA cytology samples and corresponding surgical tissue specimens demonstrated concordance. When a 5% cut-off value was adopted, the concordance rate was 95.5% (21/22, κ=1.000, P<0.01). Similar concordance rates between the cytological and histological grades were achieved with threshold value of cytological assessment material set at more than 500 or 200 cells. Conclusions: The cytological Ki-67 index in adequate material (>200 tumor cells) is useful in grading pancreatic neuroendocrine tumors, and a cut-off value of 5% showed better predictive value compared with that of 2%. Accurate grading of PanNET is critical for predicting tumor biology, patient prognosis, and making informed decisions regarding patient management and treatment.

Cloacogenic adenocarcinoma of the vulva: one new case and literature review.

Primary adenocarcinoma of the vulva is uncommon, and cloacogenic adenocarcinoma of the vulva is extremely rare. Here the authors report a vulvar neoplasm, arising in continuity with the epidermis, characterized by villoglandular architecture, and mucinous-type ep- ithelium with intestinal differentiation (goblet cells). Histochemistry, immunohistochemistry, and gene mutation analysis revealed a colon-like pattern, except for CK7 expression. Extensive workup failed to reveal other primary cancers. In order to provide a much bet- ter experience for diagnosis, the authors compared the previously published cases with the present case regarding clinical presentation and histopathologic aspect. They believe that the notion of the tumor arising from cloacal remnants is a more acceptable viewpoint, and its behavior is mostly indolent. In the present case, a wide local excision was sufficient for radical cure.

[Clinical and anatomic study of preserving parathyroid specific adipose attachments in total thyroidectomy].

Objective: To discuss the anatomical characteristic and important role of specific adipose attachments in preserving parathyroid function in total thyroidectomy. Methods: Parathyroid glands of 91 cases underwent total thyroidectomy in Department of General Surgery, Beijing Hospital from January to November 2015 were observed prospectively. There were 19 male and 72 female patients, aging from 25 to 74 years with an average age of (52±12) years. Preoperative ultrasound examination, analysis of intraoperative high definition images, and postoperative pathological examination were used to detect the origins of the parathyroid micro vascular structures and the characteristics of parathyroid specific adipose attachments. Parathyroid specific adipose attachments preserving technique was used in all procedures. The results of parathyroid hormone (PTH), serum calcium and phosphorus were compared pre- and 1-month post-operatively. Paired t test was statistically used to analyze data. Results: Parathyroid micro vascular vessels were closely attached to parathyroid, and they were mainly originated from inside and (or) outside thyroid. Twenty patients received intraoperative high definition images analysis, 62 parathyroids were detected, in which 48 parathyroids (77.4%) had its specific adipose attachments. Lymphatic tissues could be distinguished from adipose tissue using carbon nanoparticles lymphatic tracer technique, which resulted in better preservation of parathyroid specific adipose attachments. There was no significant difference in PTH ((39±17) ng/L vs. (30±16) ng/L), serum calcium ((2.23±0.10) mmol/L vs. (2.20±0.14) mmol/L) and phosphorus ((1.27±0.20) mmol/L vs.(1.26±0.25) mmol/L) pre- and 1-month post-operatively (P>0.05). Conclusions: Preservation of parathyroid specific adipose attachments in total thyroidectomy could result in better protection of parathyroid micro vascular structure and function. It could be benefit to preservation of parathyroid in situ and its function recovery, thus may reduce the incidence of permanent postoperative hypoparathyroidism.

[Cytology of basaloid squamous cell carcinoma and small cell carcinoma of lung: a comparative study].

OBJECTIVE: To evaluate the roles of cytomorphology and immunohistochemistry in distinguishing between basaloid squamous cell carcinoma (BSC) and small cell carcinoma (SCC) of lung. METHODS: The direct smears and/or liquid-based cytology preparation (ThinPrep) of bronchial brushing/washing and fine-needle aspiration (FNA) specimens from 17 cases of biopsy-proven BSC of lung were retrospectively reviewed and compared with those from 17 cases of SCC. The cytomorphologic parameters analyzed included proportion of cohesive cell clusters, cell palisades/rosettes, adenoid cystic features, crushing artifact, nuclear maximum diameter, nuclear molding, scantiness of cytoplasm,"salt-and-pepper"nuclei, distinct nucleoli, spindly configuration, individual cell keratinization, necrosis, hyaline material, apoptosis and mitotic activity. Immunocytochemical/immunohistochemical study of 25 cases was performed. Ten FNA samples of basaloid squamous cell carcinoma were also analyzed for epidermal growth factor receptor mutations in exons 18, 19, 20 and 21 using amplification refractory mutation system. RESULTS: Most of the 17 BSC cases (15/17) showed a predominance of tightly cohesive tumor cell clusters. The proportion of isolated tumor cells was high in SCC (more than 60% in 14 cases). The nuclear maximum diameter of BSC was slightly larger than that of SCC (9 to 11 µm in BSC versus 7 to 9 µm in SCC)."Salt-in-pepper"nuclei, nuclear molding and crushing artifact were detected in all SCC cases (15/17, 17/17 and 14/17, respectively). These features were only occasionally found in BSC group. Nucleoli were present in BSC and rarely (2/17) in SCC. Only 9 of 17 BSC cases showed individual cell keratinization. The differences in the above-mentioned cytomorphologic features were statistically significance (P<0.05). The results of immunohistochemistry performed on the cell block sections and immunocytochemistry performed on the ThinPrep slides were identical to that performed on the corresponding biopsy specimens. The tumor cells in BSC were consistently positive for CK5, p40 and p63. TTF1, chromogranin A, synaptophysin and CD56 were positive in most of SCC. One of SCC cases showed focal PAX5 expression. No EGFR mutations were detected in the 10 BSC cases studied. CONCLUSIONS: Selected cytomorphologic features, including presence of cohesive cell clusters, larger nuclear size, distinct nucleoli, lack of crushing artifact, absence of nuclear molding and presence of individual cell keratinization, are helpful in diagnosing BSC on cytology specimens. Immunohistochemistry using a panel of TTF1, CK5, p40/p63 and chromogranin A/synaptophysin/CD56 provides further clues in differential diagnosis between BSC and SCC. EGFR mutation study is often negative in lung BSC.