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Increasing evidences have demonstrated the roles of epithelial-mesenchymal transition in tumor invasion and metastasis. In the invasive front of papillary thyroid carcinoma, the expressions of adhesion molecules are often lost. In anaplastic thyroid carcinoma, tumor cells showing cancer stem cell characteristics have been identified. Epithelial-mesenchymal transition may thus play a key role in the progression of thyroid cancer. Therefore, it provide new insight for the development of targeted drugs for anaplastic thyroid carcinoma.

Objective: To explore the value of detecting mutations on epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) tissue by TaqMan-amplification refractory mutation system (TaqMan-ARMS)., Methods: TaqMan-ARMS and DNA sequencing were used to detect the EGFR exon 19 and 21 mutations in tumor tissues and the samples collected from 199 patients at 4 different 3A hospitals in Beijing from January 2008 to March 2011., Results: The rate of mutations in EGFR exon 19 and 21 was 19.1% (38/199), according to their different pathological types. Based upon TaqMan-ARMS, the classification was as followed: adenocarcinoma (35.0% (36/103)), squamous carcinoma (2.2% (2/93)) and adenosquamous carcinoma (0). According to DNA sequencing, they were 19.6% (39/199), 35.9% (37/103), 2.2% (2/93) and 0 respectively. Thus, no statistically significant difference existed between two methods (McNemar Test, P = 1.000, κ = 0.984). The mutation rate of adenocarcinoma was higher than those of squamous and adenosquamous carcinoma., Conclusion: The detection of EGFR mutations is highly consistent in the NSCLC tissue by the methods of TaqMan-ARMS and DNA sequencing.

Objective: To explore the clinicopathological characteristics of primary thyroid-like follicular carcinoma of the kidney., Methods: A case of primary thyroid-like follicular carcinoma of the kidney was studied with histology and immunohistochemical staining, and its clinical and pathological findings were further analyzed with review of the literature., Results: The patient was a 26-year-old asymptomatic woman who had a kidney mass during her annual physical examination. The tumor was well-circumscribed. Pathologically, the tumor showed follicular structures with colloid-like material in the lumina. Immunohistochemically, the tumor cells showed intense staining for CK7 and vimentin and negative for thyoid transcripation factor-1, thyroglobulin, thyoid peroxidase and RCC., Conclusions: The diagnosis of primary thyroid-like follicular carcinoma of the kidney is based on the characteristic follicular architecture with colloid-like material, and the metastasis from a thyroid follicular carcinoma must be excluded clinically and pathologically before making the final diagnosis.

Objective: To explore the significance of succinate dehydrogenase B (SDHB) mutation and EPAS1 overexpression in Zuckerkandl paragangliomas (PGL) and examine their correlations with malignant infiltration and metastasis., Methods: From March 2008 to July 2011, the clinical profiles of 16 Zuckerkandl PGL patients were analyzed retrospectively. For increased diagnostic specificity, a complex immunohistochemical panel of tissue microarray was performed for SDHB, EPAS1 and MIB-1. Positive expression identified as a granular cytoplasmic staining. Greater than or equal to 50% as strongly positive (+++), 1% to 10% as weakly positive (+)., Results: Tissue microarray immunohistochemical staining showed SDHB immunoreactivity in the cytoplasm, whereas EPAS1 and MIB-1 in the nuclear of tumor cells. Positive expression of EPAS1 in which 13 cases of Zuckerkandl PGL. And high expression strongly associated with malignancy. SDHB mutation of 7 cases are all EPAS1 positive staining. Non-gene mutation 9 cases tumor specimens, 6 cases were EPAS1 positive expression (P < 0.05). CgA positive expression in 11 cases benign Zuckerkandl PGL, strongly positive in 4 malignant cases (4/4). MIB-1 below 1% in 12 cases of benign Zuckerkandl PGL. And in 4 malignant cases, MIB-1 was about 3%. Malignant neoplasms had significantly higher EPAS1, CgA and MIB-1 expression compared to benign counterparts (P < 0.05)., Conclusions: The SDHB mutation causes the EPAS1 over expression in PGL and correlation with higher positive expression of CgA and MIB-1. It may be one of the mechanisms of malignant invasiveness and metastasis in PGL.

Objective: To study the pathologic characteristics of eutopic endometrium in patients with endometriosis., Methods: Pathologic characteristics of eutopic endometrium were studied in 176 patients with endometriosis in Peking Union Medical College Hospital from January 2007 to December 2008 retrospectively., Results: About 72.2% (127/176) of eutopic endometrium were in proliferative phase, 19.9% (35/176) of were observed as endometrial polyp, including 32 cases with simple endometrial polyp and 3 cases with abnormal hyperplasia combined with endometrial polyp. And 4.0% (7/176) showed abnormal hyperplasia. The incidence of pathologic changes in eutopic endometrium was 22.2% (39/176). Among 53 endometriosis patients combined with infertility, the incidence of pathologic changes of eutopic endometrium was 35.9% (19/53), which was significantly higher than 16.3% in non-infertile patients (χ(2) = 8.24, P = 0.004). Among 65 cases with irregular menstruation, the incidence of endometrial polypus and endometrial hyperplasia were 20.0% (13/65) and 10.8% (7/65), which were significantly higher than 17.1% (19/111) and 0 in normal menstruation patients (χ(2) = 13.839, P = 0.003)., Conclusions: The eutopic endometrium of endometriosis were in proliferative phase state. The pathologic changes of eutopic endometrium were more in patients combined with infertility and irregular menstruation.

Objective: To study the clinical and pathological features of pulmonary neuroendocrine cell hyperplasia and tumorlets with bronchiectasis., Methods: Both the clinicopathologic changes and immunohistochemical findings were examined with microscopy and EnVision method in 22 cases of pulmonary neuroendocrine cell hyperplasia and tumorlets., Results: The average age of the 22 patients was 53 years, with a male to female ratio of 9:13. On macroscopic examination the lungs showed bronchiectasis; one case was accompanied by gray-white, soft nodules (diameter < 5 mm). Microscopy of the HE sections showed the basic pathologic change was bronchiectasis, accompanied by neuroendocrine cell hyperplasia and tumorlet formation in the pulmonary parenchyma surrounding the bronchioles, presenting as single nodule (10 patients), or multifocal nodules (12 patients), with average size of 1.6 mm in diameter. No tumor cells were identified in the lymph nodes. Sixteen of 22 patients were disease-free after an average follow-up period of 58 months (17 - 117 months); one patient died suddenly after surgery; and five were loss of follow up. Immunohistologically, the tumor cells were positive for CgA (18/18), Syn (16/16), AE1/AE3 (16/16) , TTF-1 (14/15), and CD56 (14/14), and Ki-67 index was < 2% in 12 cases., Conclusions: Immunohistological staining for CgA, Syn, CD56, TTF-1 and AE1/AE3 can confirm the diagnosis. Early detection, pulmonary resection and follow-up help prevent the progression of these diseases.

Objective: To investigate the clinical and computed tomography (CT) appearances of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma., Methods: The CT findings and clinical data of 13 patients with pathologically proven pulmonary MALT lymphoma were retrospectively reviewed., Results: Among these 13 patients, seven presented no notable abnormalities, six manifested respiratory symptoms including cough, expectoration, and dyspnea; one of these six patients experienced fever. Chest CT showed solitary nodule in 2 patients and multiple nodules in 3 patients; meanwhile, it showed solitary consolidation in 3 patients and multiple consolidations in 5 patients. Other CT findings included air bronchogram (n = 13), airway dilatation (n = 4), ground glass opacities (n = 5), and interstitial changes (n = 5). One patient had mediastinal lymphoadenopathy and 2 had pleural effusion. Pathology showed massive lymphocyte infiltration; cells with notable nuclear atypia were also seen, which were generated from B cells., Conclusions: The main CT findings of pulmonary MALT lymphoma include nodules, mass or patchy consolidations with air brochogram; hilar and mediastinal lymphadenopathies are rare. Clinical diagnosis should also be based on pathological findings and immunohistochemical results.

Objective: To observe the clinical features and cardiac magnetic resonance imaging (CMR) characteristics of patients with endomyocardial biopsy (EMB)-proven cardiac amyloidosis (CA)., Methods: EMB proven CA patients underwent CMR examination from September 2006 to December 2010 were included. The findings of clinical manifestation, electrocardiogram, echocardiography and CMR were analyzed., Results: Among the 18 patients with EMB verified CA, 5 patients underwent CMR. All 5 patients had heart failure symptoms and electrocardiogram was abnormal. Echocardiogram showed concentric left ventricular hypertrophy, granular appearance of the myocardium, left atrial enlargement and moderate to severe left ventricular diastolic dysfunction. CMR revealed increased thickness of the left ventricular wall (especially at the inter-ventricular septum), enlarged bilateral auricle, restricted left ventricular filling with normal or mild to moderate reduced systolic function. Pleural and pericardial effusions were observed in 2 patients. Abnormal late gadolinium enhancement (LGE) was detected in all 5 patients. CMR revealed different patterns of LGE. Left ventricular global subendocardial delayed gadolinium enhancement or transmural delayed gadolinium enhancement were found, and patients also showed line-, granular- or patchy-like enhancement. The degree and range of LGE paralleled the disease course and were consistent with electrocardiogram changes., Conclusions: As a noninvasive diagnostic tool, CMR is valuable in the diagnosis of CA. For patients with clinical suspicion of CA, CMR could be a helpful diagnostic tool, especially in the hospitals where EMB is not available.

Objective: To establish an appropriate animal model of uterine leiomyoma and to understand the pathogenesis of this disease., Methods: Mature female rats were intramuscularly injected with estradiol benzoate at 200 μg or 300 μg twice a week. After injection for 8 or 10 weeks, the rats were sacrificed. We measured the serum levels of estrogen (E(2)) and progesterone (P), evaluated ER and PR expression, and calculated the leiomyoma forming rate and mortality of the rats. Histological changes were compared between rat uterine leiomyoma and human uterine leiomyoma with HE staining. The optimal dose and duration of E(2) for induction of uterine leiomyoma in rat were determined., Results: In the rats treated with estradiol benzoate 200 μg for 8 weeks ìn the serum E(2) level increased significantly (P<0.01). Uterine nodules were visible in some of the tested rats. Based on the pathohistological Results , the uterine leiomyoma developed in the treated rats demonstrated similar features as in human uterine leiomyoma. The expressions of ER and PR were increased in the leiomyoma tissues., Conclusion: The rat model of uterine leiomyoma can be established by intramuscular injection of estradiol benzoate at 200 μg twice per week for 8 weeks, with similar features as those of human uterine leiomyoma. The high concentrations of ER and PR in uterine tissue might be related with the development of uterine leiomyoma in animal.

Objective: To summarize our experiences in the diagnosis and treatment of placenta accreta in the second trimester of pregnancy., Methods: We retrospectively analyzed the clinical data of 31 patients were admitted to Peking Union Medical College Hospital with placenta accreta in the second trimester of pregnancy from January 2002 to January 2010., Results: Among 31 cases, one case (3.2%) was suspected to be with placenta accreta by ultrasound examination and 30 cases (96.8%) were normal before delivery. Placenta accreta was identified during follow-up in 12 cases (38.7%) after delivery. Fourteen patients underwent curettage again after delivery,which was effective in 6 patients (42.9%) and failed in 8 patients,in whom uterine artery embolization (UAE) was further applied. Thirteen patients underwent UAE without curettage. In total,21 cases underwent UAE, which was effective in 19 patients (90.5%); one patient with abnormal β-human chorionic gonadotropin (β-HCG) 5 months after embolization underwent lesion resection and one case with slightly increased β-HCG were lost to follow-up. Hysteroscopy was effective in 3 patients,of whom two patients underwent lesion resection by hysteroscopy and one case who was suspected to be with trophoblastic disease by ultrasonography before surgery and confirmed to be placenta accreta during hysteroscopy examination underwent lesion resection. One case experienced hemorrhagic shock during vaginal delivery and underwent emergency laparotomy. Among all these 31 patients,massive hemorrhage occurred in 13 cases during delivery and hemorrhagic shock in 2 cases. Three cases had postpartum hemorrhage and stopped bleeding after UAE. None needed hysterectomy., Conclusions: Placenta accreta in the second trimester of pregnancy is usually diagnosed after childbirth,which may be delayed in some cases. Therefore,special attention should be paid to this disease during follow-up. Conservative treatment was the main therapy of placenta accreta in the second trimester of pregnancy. UAE is effective in stopping bleeding.

Objective: To investigate the diagnosis and treatment of cervical ectopic pregnancy., Methods: The clinical data of 27 patients with cervical ectopic pregnancy who were treated in Peking Union Medical College Hospital from January 1990 to November 2009 were retrospectively reviewed. The clinical effectiveness of three fertility-preserved treatment modes were compared., Results: Of these 27 patients,one underwent hysterectomy, while all the other 26 patients selected fertility-preserved treatment,which included curettage after uterine artery embolization (UAE) (n=14), curettage directly (n=8), and curettage after methotrexate (MTX) injection (n=4). The effectiveness rates of these three methods were 100%,75.0%,and 50.0%, respectively,which was significantly higher in curettage after UAE group than in curettage after MTX group (P=0.005). The duration of hospitalization was (17.0∓3.2) days in curettage after MTX group,which was significantly longer than that in curettage after UAE group (6.1∓2.9) d (P=0.004) and curettage directly group (4.9∓3.4) d (P=0.001). The mean hospitalization cost showed no significant difference among three groups (P=0.104)., Conclusion: Curettage after UAE is safe and effective for patients diagnosed or highly suspicious of cervical pregnancy.

Objective: To evaluate the value of ultrasonic monitoring in induced abortion during the first trimester., Methods: Totally 110 healthy women with a singleton pregnancy between 9 and 11 gestational weeks were enrolled. All the procedures of induced abortion were performed routinely. Ultrasonography was performed when the procedure of induced abortion was completed. Patients with normal ultrasonographic results were assigned in the control group, while patients with abnormal ultrasonographic findings were enrolled in the study group,in which these patients underwent further operations until the ultrasonography showed clear endomembrane line. All the recurretaged tissue in the study group were sent for pathological examinations., Results: Of these 110 patients, 28 (25.5%) entered study group and 82 (74.5%) entered control group. In the study group, trophoblastic cell or chorion was found in the recurretaged tissue in 11 patients (39.3%), in which 3 had trophoblastic cell embedded in smooth muscular tissue, 6 had pathologic deciduas, and 11 had pathologic secretory endometria. In this control group,1 patient (0.9%) had retained products of conception. The operation duration [(20.6∓2.1) min vs.(11.5∓3.5) min, P0.05]., Conclusions: Ultrasonic monitoring in induced abortion during the first trimester can decrease the incidence of retained products of conception and will not induce endometrial damage. It is especially useful for women whose fetuses were at older gestational ages.

Objective: restrictive cardiomyopathy (RCM) is characterized by impairment of ventricular filling during diastole with preserved systolic function. The clinical and histopathological profile on endomyocardial biopsy of 25 consecutive patients with RCM was analyzed in this study., Methods: twenty-five patients with diagnosis of RCM and underwent endomyocardial biopsy (EMB) were enrolled in the study. The clinical characteristics, electrocardiogram, serum chemistry, right heart catheter and cardiac pathology results were obtained., Results: heart failure symptom was present in all 25 patients and left ventricular size and function were normal or near normal while serum brain natriuretic peptide (577 pg/ml) was moderately elevated. Right atrial and ventricular end-diastolic as well as pulmonary capillary wedge pressures derived from right heart catheter examination were increased. Amyloid deposition were evidenced in 16 and eosinophilic myocarditis in 2 patients upon pathological examination of EMB. In the remaining 7 patients, 3 were diagnosed idiopathic RCM, 2 were diagnosed as amyloidosis by biopsy from non-cardiac tissue and etiology remained unknown in 2 patients. Thus, conclusive diagnosis was made on EMB samples in 84% (21/25) patients of RCM., Conclusion: RCM may result from various local and systemic disorders. EMB is helpful for identifying the underlying etiology.

Objective: To investigate the clinical and pathological features of eosinophilic diseases with cardiac involvement., Methods: We analyzed the clinical and cardiac pathological data of 7 patients with eosinophilic diseases with cardiac involvement under endomyocardial biopsy or autopsy., Results: Seven patients (5 male, average age 51 years) were enrolled. Four patients were diagnosed as idiopathic hypereosinophilic syndrome and three were Churg-Strauss syndrome. Peripheral blood eosinophilia count increased significantly in all patients. Cardiac involvement included angina pectoris, myocardial infarction, heart failure, presyncope and sudden death. Electrocardiogram showed cardiac ischemia, bundle branch block and third degree atrioventricular block. Echocardiography suggested ventricular and atrial enlargement, decreased ventricular systolic function, pulmonary hypertension, valvular prolapse and insufficiency and endocarditis. Pathology displayed infiltration of eosinophils, formation of granulomata, necrotizing vasculitis, myocardial necrosis and endomyocardial fibrosis in heart. Coronary artery could be also affected and led to myocardial infarction., Conclusions: Cardiovascular complications of eosinophilic diseases are a major source of morbidity and mortality in these disorders. The manifestations are multiple and early recognition and treatment with steroid and immunosuppressant can improve prognosis.

Objective: To detect the infection of human papillomavirus (HPV) 16/18 in patients with head and neck squamous cell carcinoma and explore the relationship between HPV infection and expressions of Ki-67 and P53 proteins in tumor tissue., Method: The level of HPV 16/18 DNA was measured by real time polymerase chain reaction, and Ki-67 and P53 proteins were measured by immunohistochemistry in tissues from head and neck squamous cell carcinoma., Results: HPV 16/18 DNA was detected in 62.8% of our patients. In each cancer tissue sample, Ki-67 protein was expressed between 2% to 70%. P53 protein was expressed in 46.15% of our patients. No significant relation was found between HPV 16/18 DNA level and sex, smoking, drinking, and tumor clinical stages. However, level of HPV 16/18 DNA was found to have positive relation with tumor pathological grades and negative relation with P53 protein expression. No relation with Ki-67 protein expression was found., Conclusion: Head and neck squamous cell carcinoma may be initiated by HPV 16/18 infection and the mechanism in carcinogenesis involves abnormal expression in P53 protein.

Objective: To distinguish choriocarcinoma from gestational or non-gestational choriocarcinoma and also identify the causative pregnancy of gestational choriocarcinoma by the genetic origin through molecular genetic analysis., Methods: Twelve patients with choriocarcinoma, who had experienced surgery prior to chemotherapy were enrolled in this study. All 12 cases were diagnosed pathologically as choriocarcinoma. Peripheral venous blood samples and formalin-fixed paraffin-embedded blocks of choriocarcinoma tissue microdissected from haematoxylin and eosin-stained sections of tissue by microdissection method were available from the patient and (or) her husband. DNA was then prepared from the couples' blood samples and choriocarcinoma tissue by using standard techniques. PCR amplification and fluorescent microsatellite genotyping were performed by using DNA from the couples and captured choriocarcinoma tissues. The genetic contributions to the choriocarcinoma tissue were determined by comparing the fragments of genes from the choriocarcinoma tissue to those from blood samples of the couples., Results: The primary lesion was ovary in 7 cases, but only 4 of them had the maternal contribution, indicating a non-gestational origin; the other three were gestational choriocarcinoma. The primary lesion was uterus in 5 cases, which were all gestational choriocarcinoma confirmed by genetic analyses. The causative pregnancies of the 8 cases with gestational choriocarcinoma were identified as androgenetic complete hydatidiform mole (AnCHM) in six cases and normal pregnancies in two cases, respectively., Conclusion: Microsatellite polymorphism analysis is a molecular approach for distinguishing the non-gestational choriocarcinoma from the gestational one, and also be used to identify the causative pregnancy of gestational choriocarcinoma.

Objective: To study the impact of neoadjuvant therapy on lymph nodes retrieval in locally advanced mid-low rectal carcinoma., Methods: Data collected from 120 patients with locally advanced mid-low rectal cancer (T2-4 and/or N1-2M0) treated from January 2005 to June 2008 was investigated. The patients were divided into two groups: the study group (n=54) was treated with neoadjuvant therapy (preoperative radiation with a total dosage of 50 Gy and synchronous 5-Fu-based chemotherapy) followed by radical tumor resection 4-6 weeks after;the control group (n=66) underwent primary surgery without neoadjuvant therapy. The clinical stage was evaluated before and after neoadjuvant therapy. The total lymph nodes yields, as well as the tumor-positive lymph nodes of each resected specimen was compared between the two groups statistically., Results: Clinical downstage was achieved in 30 cases (56%) in study group after neoadjuvant therapy. The number of total lymph nodes and positive lymph nodes harvested from each resected specimen in the control group were 14+/-7 and 2.2+/-3.7, meanwhile those were 9+/-6 and 0.7+/-2.4 in study group, which were all significantly lower than those in control group (P<0.01)., Conclusions: Preoperative radiotherapy combined with chemotherapy can downstage the tumor and reduce the retrieval rate of total lymph nodes and positive lymph nodes in locally advanced rectal cancer. It is necessary to retrieve as many lymph nodes as possible for it has some prognostic significance for the patients.

Objective: To identify differentially expression of microRNAs associated with expression of estrogen receptor alpha (ERalpha) and progesterone receptor (PR) between type I and type II endometrial adenocarcinoma., Methods: Two kinds of endometrial adenocarcinoma cell lines, Ishikawa and KLE, was transplanted into nude mice and biopsied to identify the expression of ERalpha, PR and p53, and test their response to estrogen and progesterone. Cultured the two cell lines under the estrogen-free and progesterone-free circumstance, total RNA was isolated to identify the differentially expressed microRNAs by microarray for prediction the microRNAs which target ESR1 and PGR by software miRANDA and TargetScan, and then was validated by real-time PCR in two cell lines cultured both in vivo and in vitro and ten specimens from patients., Results: Ishikawa cell line was confirmed from type I endometrial adenocarcinoma, KLE cell line was confirmed from type II endometrial adenocarcinoma. One hundred and twenty-six differentially expressed microRNAs between the two cell lines were identified by microRNA microarray, among of which may target ESR1 included hsa-miR-100, 99a, and may target PGR included hsa-miR-378, 768-3p. The differential expression of hsa-miR-100, 99a, 378, 768-3p identified by microarray between Ishikawa and KLE in vivo and in vitro was equal to that by real-time PCR, while Hsa-miR-100 was significantly down expressed in type I group specimens compared to type II group (P < 0.01)., Conclusion: Hsa-miR-100 is significantly down-expressed in type I endometrial adenocarcinoma compared to type II, which may be a great potential to target ESR1.

Objective: To study the efficacy and adverse events of intravenous bisphosphonates in the treatment of patients of primary hyperparathyroidism (PHPT) complicated by hypercalcemia crisis., Methods: From October 2003 to December 2007, 14 patients admitted into our hospital were diagnosed as PHPT complicated by hypercalcemia crisis, which was defined as a serum calcium concentration greater than 3.50 mmol/L. Of them, 6 cases had parathyroid adenoma, 1 had hyperplasia and 7 had parathyroid carcinoma. One of the intravenous bisphosphonates including pamidronate, ibandronate and zoledronic acid was given for 29 times in all the 14 cases. Serum calcium, parathyroid hormone, hematology, and other biochemical markers were monitored. Adverse events were recorded., Results: After intravenous bisphosphonates, the serum total calcium (Ca) levels decreased from (3.85 +/- 0.50) mmol/L to (2.86 +/- 0.39) mmol/L in (1.4 +/- 0.6) days, and were kept below 3.50 mmol/L for (10.14 +/- 8.54) days. There was no significant difference of the magnitude of decrease in serum Ca levels among the patients using pamidronate, ibandronate or zoledronic acid. The change of serum Ca level was associated with the serum Ca level before treatment. The response to intravenous bisphosphonates evaluated by the decrease of serum total calcium levels was more significant in patients with parathyroid adenoma or hyperplasia than those with parathyroid carcinoma. The most common adverse event was pyrexia, which occurred 15 times (51.7%) and 75% of the pyrexia events occurred after the first infusion. Other manifestations included fatigue, flu-like symptom, myalgia, arthralgia and diarrhea with an incidence of 3.4% each (one event in the 29 times of treatment). There were 2 events (6.7%) with mild increase of serum creatinine concentration., Conclusion: Bisphosphonates can decrease serum total calcium levels in hypercalcemia crisis caused by PHPT effectively with mild adverse events.

Objective: To evaluate the prevalence of fetal anomalies in recent 10 years and explore the effective methods of early diagnosis and treatment., Methods: The clinical and pathological data of 116 pregnant women who underwent induced abortion in the second trimester due to fetal anomalies 1998 - 2007 were analyzed retrospectively., Results: The fetal anomaly rate in the period 2003 - 2997 was 8.7 per thousand, significantly higher than that in the period 1998 - 2002 (3.1 per thousand, P < 0.001). The diagnostic methods of fetal anomalies used during the period 2003 - 2007 did not show significant differences compared with those used during the period 1998 - 2002. The gestational week when the fetal anomalies were detected in 2002 - 2007 was 19.3 weeks, not significantly preceded compared with that during 1998 - 2002 (22.4 weeks, P > 0.05). The top 5 fetal anomalies with high incidence rates were Down' syndrome, anencephalus, lip/palate cleft, fatal cystic hygroma of the neck, and cardiac anomalies. There were 30 cases of advanced maternal age over 35 years, 60.0% of whose fetuses showed chromosome abnormality., Conclusion: The incidence of fetal anomalies increases in recent years. The risk of fetal anomalies is high in the pregnant women in elder age. Pregnancy in advanced maternal age show high risk to occur fetal anomaly. Better approaches to diagnose fetal anomaly earlier are still to be found.

Objective: To investigate the clinical, radiographic and pathological characteristics of intravascular lymphomatosis primarily manifested in the lung, without skin and central nervous system involvements., Methods: A case of T cell intravascular lymphomatosis presenting with fever and multiple pulmonary shadows on chest radiograph was described and 14 similar cases reported in the English literature were reviewed., Results: We described a case of T cell intravascular lymphomatosis, who was a 36 year old man, complained of fever and multiple pulmonary shadows on chest radiograph and admitted to Peking Union Medical College Hospital in march, 2008. Open lung biopsy showed features characteristic of intravascular lymphomatosis. He received CHOP chemotherapy, but died 20 days after diagnosis. Most cases of intravascular lymphomatosis primarily manifested in the lung occurred in older patients, ranging from 36 to 79 years of age (mean 59 years), with a male predominance (M : F = 11 : 4). The chief complaints were dyspnoea (10/15), cough (9/15), fever (5/15) and weight loss (5/15). Pulmonary function tests usually revealed some degree of decreased diffusing capacity. Eight cases had high serum lactate dehydrogenase levels. Chest CT scan showed multiple reticular or/and nodular density. Immunophenotypically, 10 cases were B cell lineage, 3 cases were T cell lineage. Six cases of B cell intravascular lymphomatosis were followed, of whom 4 and were alive, and 2 died of respiratory failure. Three cases of T cell intravascular lymphomatosis showed poor prognosis, both of whom died of respiratory failure., Conclusions: Intravascular lymphomatosis primarily manifested in the lung is a rare malignant disease. Its pulmonary symptoms were nonspecific, and pulmonary function tests and chest CT scan manifested as those of interstitial pneumonia or pulmonary infection. It can be pathologically diagnosed through transbronchial lung biopsy or surgical lung biopsy.

Objective: To study the proteomics of papillary thyroid carcinoma (PTC), and to detect the differential expression of proteins compared to normal thyroid (NT) tissue., Methods: Protein extracts of papillary thyroid carcinoma and normal thyroid tissues from 10 patients were separated by proteomics technique and identified using Image Master software. The selected differential proteins were sent to Proteomics Research Center of Chinese Academy of Medical Sciences for mass-spectrometry identification., Results: The basic 2-dimensional electrophoresis (2-DE) images of PTC and NT were obtained, and four potential differential expression spots were selected for mass-spectrometry identification. Among them, annexin I, peroxiredoxin I, mitochondrial aconitase were up-regulated while carbonic anhydrase I was down-regulated., Conclusion: Proteomics may provide a new direction to study PTC, by identifying some tumor-specific markers, leading to elucidation of the mechanism of tumorigenesis and identification of therapeutic targets.

Objective: To analyze the clinical characters and prognosis of postpartum choriocarcinoma., Methods: Retrospective analysis of 103 patients diagnosed with postpartum choriocarcinoma in Peking Union Medical College Hospital between 1985 and 2005 was performed., Results: In a total of 103 cases of postpartum choriocarcinoma treated with multiagent cytotoxic chemotherapy and combined modality therapy, 92 patients (89.3%) achieved a complete remission while 2 patients had a partial remission, and 9 patients died. Regarding 25 cases with chemorefractory choriocarcinoma and 4 relapsed cases, 18 and 3 cases achieved a complete remission respectively. According to the new International Federation of Gynecology and Obstetrics (FIGO) 2000 staging and risk factor scoring system, 17 cases were at FIGO stage I, 8 cases at stage II, 56 cases at stage III, and 22 cases at stage IV. Complete remission was achieved in 100%, 8/8, 95% and 64% respectively. Thirty-five cases in low risk group had FIGO scores < or = 6, and all achieved a complete remission. Of 68 cases in high risk group with FIGO scores > or = 7, 57 (84%) of them obtained a complete remission. There were significant differences in the two groups (P < 0.05)., Conclusion: Postpartum choriocarcinoma could have an increasing probability of cure with early diagnosis and the use of modern multiagent cytotoxic chemotherapy and combined modality therapy.

Objective: To determine the parental origin of the genome in the molar pregnancies of two familes with familial recurrent hydatidiform mole (FRHM) and to investigate whether the gene responsible for FRHM is likely to be located within the 19q13.4 region in these familes., Methods: The features of complete hydatidiform mole (CHM) were confirmed by pathological examination. DNA of CHM was prepared from sections of formalin-fixed paraffin-embedded blocks of molar tissue following laser capture microdissection. The polymerace chain reaction was used to amplify microsatellite polymorphisms in DNA from the patients, their husbands and the captured molar tissue. Parental contributions to the molar tissue were determined using ABI 310 GeneScan software. Genotyping and haplotype analysis of the candidate region on 19q13.4 was performed for members of both families using 25 microsatellite markers., Results: One CHM from each family was identified as a biparental complete hydatidiform mole. All patients were heterozygous for most of the markers in the chromosome region of interest. In addition the two affected sisters in one of the families had different genotypes for the 19q13.4 region, suggesting that mutations in a different locus might be responsible for the disorder in this family., Conclusion: The location of the gene responsible for FRHM is unlikely to be located in the 19q13.4 chromosomal region in these two families suggesting that FRHM shows genetic heterogeneity.

Primary thyroid lymphomas (PTLs) are closely correlated with the autoimmune reaction of thyroid. However, the molecular mechanisms of PTLs are still unclear. It is really necessary to improve the ability to differentiate between benign and malignant PTLs along with the introduction of some new molecular biology methods. The diagnosis and prognosis of PTLs depend on their histological features, pathological classification, and clinical stages. Customized therapy of PTLs becomes possible with the further advances in lymphoma's pathological classification, clinical stages, and international prognosis index standard.

Objective: To study the immunoglobulin gene rearrangement patterns in Hashimoto's thyroiditis (HT) and primary thyroid lymphoma (PTL), and to analyze the relationship between the two diseases., Methods: Formalin-fixed and paraffin-embedded tissues of 11 cases of PTL and 38 cases of HT as well as their clinical data, were retrieved. The latter group was further subcategorized into classic HT and suspicious PTL. Gene rearrangement studies for immunoglobulin heavy chains and light chains were carried out by polymerase chain reaction (PCR) using VH, FR3A and FR3kappa primers., Results: There was an increasing trend in immunoglobulin gene rearrangement rate for classic HT (10.7%), suspicious PTL (40.0%) and PTL (72.7%) groups. In general, a female predilection was observed. This sex predilection however was less obvious in the PTL group. There was no relationship between serum antibody (both thyroglobulin and thyroid peroxidase) titers and gene rearrangement patterns., Conclusions: HT and PTL show morphologic overlaps and may not be clearly distinguished on the basis of light microscopy alone. PCR-based immunoglobulin gene rearrangement study may be helpful in the detection of cases with early lymphomatous transformation of HT.

Objective: To determine the characteristics of anatomical distribution of pelvic endometriosis and the correlation between visual and histologic findings of endometriosis at laparoscopy., Methods: A prospective study of 62 patients undergoing laparoscopy for the pelvic pain, infertility and/or pelvic masses was carried out. All lesions with the diagnosis of endometriosis laparoscopically were excised and examined pathologically. Normal-appearing peritoneal biopsies were obtained randomly. All lesions were identified by anatomical site and color of the foci. The positive predictive value (PPV), sensitivity, negative predictive value (NPV), and specificity were determined for visually identified endometriosis versus the histologic findings., Results: Totally, 219 peritoneal endometriotic lesions, 54 normal peritoneal biopsies, and 71 ovarian endometriotic cysts were obtained. Peritoneal lesions tended to locate in posterior part of the pelvis (80.8%, 177/219) and in left (58.0%, 127/219) with most in black (39.2%). The PPV was 67.6%; sensitivity, 93.7%; NPV, 81.4%; and specificity, 38.3% for visual versus histologic diagnosis of peritoneal endometriosis. Lesions in black or from sacral ligaments were confirmed histologically in 94.2% and 84.7% respectively, and 80.3% (57/71) of ovarian endometriotic cysts diagnosed by laparoscopy were confirmed histologically with 43.6% in the left, 27.3% in the right; and 29.1% (16/55) in both sides of the ovary. In addition, 18.5% (10/54) of normal-appearing peritoneal biopsy were identified as endometriosis by pathological examination. Laparoscopy was confirmed to be in 100% diagnostic accordance with pathology for patients with endometriosis., Conclusions: Our study showed asymmetrical distribution of pelvic endometriosis. Peritoneal lesions in black or from sacral ligament are more likely to be histologically confirmed, and microscopic lesions are not a rare phenomenon of endometriosis.

Objective: To investigate the clinical and pathological characteristics, treatment measures and prognosis of pseudomyxoma peritonei (PMP)., Methods: The clinical records and follow-up data of the patients with PMP were retrospectively analyzed. Survival analysis (Kaplan-Meier method and Cox regression) was used to investigate the prognosis., Results: Thirty-three patients (twenty-two women, eleven men) have a median interval between onset and definite diagnosis of 12 months with an average age of 50. The main clinical presentation includes bloating, abdominal mass and abdominal distention. A delay in diagnosis is common and many patients are labeled as other diseases (84.8%). Positive results were often found in the assistant examinations such as erythrocyte sedimentation rate, gastrointestinal tumor markers (carcinoembryonic antigen, carcinomatous antigen 19-9 and so on), imaging (B ultrasound and computer tomography) and abdominal paracentesis which was usually unsuccessful. The most frequently practiced approach is debulking surgery with the main assistant means of chemotherapy which was lack of the uniform rationale. Benign type of pathological samples accounts for 66.7% of all, while mid-type 21.2% and malignant 12.1%. The general median survival time is 70 months with a follow-up rate of 79%. The pathological type and chemotherapy are main factors which influence the cumulative survival rate (P < 0.05). Up to the end of 2004, sixteen patients died of various complications, multiple organ failure and severe infection, while ten patients survival and seven patients lost., Conclusions: PMP is a rare condition of borderline malignancy with its unique clinical and pathological characteristics. Gastrointestinal tumor markers, imaging and abdominal paracentesis are very important to the diagnosis. The existing treatment measures need to be improved further. The pathological type and chemotherapy are main factors which influence the prognosis.

Objective: To study the clinicopathologic features of osteomalacia or rickets-associated mesenchymal tumors., Methods: The clinical and pathologic findings of 10 cases of osteomalacia or rickets-associated mesenchymal tumors were evaluated. Hematoxylin and eosin stain, immunohistochemistry and histochemistry were performed on the archival paraffin sections., Results: Amongst the 10 patients studied, 6 were males and 4 were females. Their age at the time of operation ranged from 28 to 69 years ( mean = 45.6 years). A history of long-standing bone pain, arthralgia, limitation in movement, hypophosphatemia and hyperphosphaturia was present in all cases. The duration of symptoms ranged from 2 to 27 years (mean = 9.6 years). The tumor size ranged from 1 to 7 cm (mean size = 3.52 cm). Microscopically, the tumors were composed of various mesenchymal cells, including spindled fibroblast-like cells, adipocytes, chondroid cells and mucinous cells. The background was rich in blood vessels. In 8 of the 10 cases, there was also dystrophic calcification in an unusual flocculent or "grungy" pattern. Peripheral woven bone shell formation was noted in 2 cases and non-urate crystal deposition in 2 cases. Mitotic figures were rare in 9 cases. In 1 of the 10 cases however, mitotic figures and bizarre cells were commonly encountered. On immunohistochemical study, the tumor cells were all positive for vimentin. There was focal positivity for smooth muscle actin and CD34 in 5 and 3 cases respectively. The staining for desmin, S-100 and AE1/AE3 was negative. Ki-67 proliferation index was less than 4% in 8 cases and 30% in 1 case. Alcian blue-positive mucinous matrix and mucinous degeneration around vessels were noted in 8 cases., Conclusions: Most of the osteomalacia or rickets-associated tumors are either benign or low-grade malignant mesenchymal tumors. They can be mistaken as other neoplasms due to the morphologic heterogeneity present. Thorough understanding of the associated clinical features and laboratory investigation results is helpful in arriving at the correct diagnosis.

Objective: To investigate surgical treatment results and clinical pathological specifics in the treatment of non-functional islet cell tumor., Methods: To perform retrospective analysis of 78 cases of non-functional islet cell tumor treated at Peking Union Medical College Hospital from July 1968 through January 2005, and summarize clinical symptoms and signs, primary diagnosis before surgery, surgical treatment, pathologic specifics and immuno-histological analysis., Results: Of 78 cases, 27 cases (34.6%) was found in physical examinations, the most common symptoms was upper abdominal pain and upper abdominal discomfort, 30.7% (24 cases) and 26.9% (21 cases) respectively; the most common sign being abdominal masses 35.9% (28 cases). B-us and CT are most commonly used forms of preoperative examination, with positive rates being 98.6% (71/72), 100% (53/53) respectively. Operative mortality was 1.28%, Radical surgery of malignant cases with 5 year survival rate 75% (9/12). Immuno-histological examinations showed that tumors with multi peptide linked hormones 78.6% (55/70), a larger number of positive examinations of neuron specific enolase and chromaffin, 91.4% (32/35) and 79.4% (27/34) respectively. Insulin, glucagon, pancreatic polypeptide, somatostatin, vasoactive intestinal peptide and gastrin positive rates are 64.6% (42/65), 47.5% (22/53), 45.8% (22/48), 37.5% (21/56), 23.9% (11/46) and 22.6% (7/31)., Conclusions: Non-functional islet cell tumor lack specificity, Bus and CT are primary examination methods, immuno-histological analysis indicates various different hormones, but lacks the presence of related clinical symptoms. Surgery is an effective form of treatment in the treatment of non-functional islet cell tumor, even with distal metastasis, immediate surgical removal and treatment, extend prognosis.

Objective: To determine the expression status of survivin gene in pancreatic carcinoma., Methods: Expression of survivin gene was evaluated by immunohistochemistry, Western Blot and RT-PCR in 59 cases of pancreatic carcinoma along with their corresponding adjacent benign tissues, 11 cases of chronic pancreatitis, and 7 pancreatic carcinoma cell lines., Results: The positive expression rate of survivin in pancreatic carcinoma was 72.8% (43/59). There was no relationship between the expression of survivin and tumor stage and differentiation. No expression of survivin was detected in benign tissue adjacent to the tumors as well as in samples of chronic pancreatitis. All 7 pancreatic carcinoma cell lines showed a positive expression of survivin mRNA and protein., Conclusions: The expression of survivin appears to be tumor specific to some extent in our pancreatic carcinoma samples. Survivin may be an ideal target for therapy against pancreatic carcinoma.

A large number of data derived from molecular analyses support the hypothesis that human cancer is a genetic disease and a distinct subset of genes have been found to be genetically changed in most tumors. Molecular alterations in pancreatic cancer include: (1) oncogenes such as K-ras, c-myc, c-fos, and c-erbB-2; (2) tumor suppressor genes such as p53, p16, DPC4/SMAD4, and DCC; and (3) growth factors such as EGF, FGF, HGF, PDGF, VEGF, TGF-beta. Genetic alterations of K-ras and p53 are common in human pancreatic cancer, but the occurrence of pancreatic cancer is a multi-step phenomenon in which the accumulation of genetic changes is extremely important.

Objective: To analyze the clinical characteristics and treatment of hematogenous disseminated tuberculosis., Methods: Twenty-seven cases of hematogenous disseminated tuberculosis diagnosed by autopsy from 1961 to 2000 were retrospectively analyzed., Results: Among these patients the disease was acute in 22 cases (including 3 non-reactive) and chronic in 5. Twenty cases (74%) were misdiagnosed before death, most of which were due to concomitant with or misdiagnosed as connective tissue disease, hematological disease or tumor. 63% of the cases had long-term use of corticosteroids or repeated chemotherapy. Most cases showed atypical clinical manifestations and chest X-ray lesions. The positive rate of tuberculin skin test and sputum for smear were low. Autopsy showed that all cases had active lung tuberculosis and the major extra-pulmonary organs involved were liver, spleen and lymph nodes., Conclusion: Unaware of the risk for tuberculosis among immune compromised patients was the main reason for misdiagnosis and corticosteroid abuse was common. Physician should be alert to the occurrence of hematogenous disseminated tuberculosis, especially in immune compromised patients with long-term fever and systemic injury. Direct smear and cultural examination as well as newer diagnostic approaches with sputum and tissue may be useful for a rapid and correct diagnosis.

Objective: To further understanding of lymphoma of salivary gland through clinicopathologic analysis., Methods: Clinical findings, pathologic features, clinical staging, therapy and prognosis of 4 cases were reviewed and clinically analysed., Results: Different treatment were received by the 4 patients, one had stage IIIA disease and three had stage IE disease. All patients got their illness completely remitted., Conclusion: Mucosa-associated lymphoid tissue lymphoma of the salivary glands is an indolent disease. Different treatments can all result in prolonged remission, and it has better outcome than other NHL.

Objective: To demonstrate the alterations of DPC4/SMAD4/MADH4 gene in paraffin-embedded tissues of pancreatic carcinomas., Methods: Forty-six cases of resected specimens containing carcinomatous tissue and normal pancreatic tissue were analysed for possible DPC4 gene mutations by polymerase chain reaction (PCR)and single-strand conformation polymorphism (SSCP). The DNA sequencing technique was applied to determine the patterns of gene mutation in the PCR-SSCP positive cases. Fifty-six cases of pancreatic carcinoma along with the specimens corresponding normal pancreatic tissues were studied by in situ hybridization (ISH) and immunohistochemistry (IHC) techniques for gene expression in mRNA and protein level., Results: The homozygous deletion rate of exon 1, 2, 3, 4, 8, 11 of DPC4 gene in pancreatic carcinoma was 28.26%, while the mutation rate of DPC4 gene was 21.74%. In these tumors, there were 3 cases of nonsense mutation, 5 cases of missense mutation, 1 case of deletion and missense mutation, 1 case of insertion mutation. Positive rates of SMAD4 in carcinomatous tissues detected by the ISH and IHC were 53.57% and 58.93% respectively, whereas they were 91.07% and 89.29% in the matched normal tissue respectively. There were significant difference between cancer and normal tissue (P < 0.05). Thrity-two cases were positive of DPC4/SMAD4 with all methods mentioned above, the coincident rate was 87.50% (28/32). The coincidence between gene detection and ISH of SMAD4 was 87.50%, and it was 96.88% between gene detection and IHC of SMAD4. Of all 56 cases, the coincidence of the positive rates of SMAD4 detected by ISH and IHC was 91.07%. No significant difference among the positive rates of DPC4/SMAD4 as detected by the three different techniques (P > 0.05)., Conclusions: The main mechanisms of inactivation of DPC4 gene in pancreatic carcinoma are homozygous deletion and mutation. The product of DPC4 expression is significantly decreased in cancer group compared with the normal tissues. As a tumor suppressor gene, DPC4 alteration is an important molecular event in pancreatic carcinoma, and probably plays a crucial role in cancer development and progression.