Neuroendocrine neoplasm (NEN)is a group of heterogeneous tumors originated from the peptidergic neurons and neuroendocrine cells. A revised system of classification, nomenclature and grading of NEN was proposed by the fourth edition of“World Health Organization classification of tumours of the digestive system”in 2010. It apparently contributes to unify the method of classification, put an end of the confusion in nomenclature, standardize the grading system and predict the outcomes more accurately. With the combination of the results by immunohistochemical studies, pathologists should be in accordance with the requirements to make a diagnosis of NEN with accurate classification, grading and the pathological parameters essential to staging. Recently, new advances in NEN study put forward a new view in the classification and grading system that will lead to the updates of the diagnostic system after further studies on a large scale of samples.

Purpose: To study the immunophenotype and the expression of cytotoxic granule proteins of nasal NK/T cell lymphoma and its significance. Methods: 44 cases of nasal NK/T cell lymphoma were studied by the two-step method of DAKO EnVisionTM using a series of antibodies including CD3, CD20, CD43, CD45, CEI45RO, CD56, CD57, CD79?, TIA-1, granzyme-B and perform. Results: All the cases of nasal NK/T cell lymphoma were CD45 positive. 43% of the cases expressed CD3 with positive signal located in the cytoplasm, which was different from peripheral T cell lymphoma. 45% and 52% of the cases were CD43 and CD45RO positive respectively. Cases that reacted to CD56 accounted for 52% of the cases, 43% of which were also positive to CD3. Concerning the reactions to both CD3 and CD56, 10 cases showed CD3 + CD56 + , 13 showed CD3-CD56 + , 9 were CD3 + CD56- and 12 were CD3-CD56-. None of the 44 cases showed positive reaction to CD20, CD79? and CD57. All cases were reactive to TIA-1. 93% and 95% of the cases showed the reactions to granzyme-B and perform. All the controls were negative to TIA-1, granzyme-B and perform. Conclusions: The immunophenotypes of nasal NK/T cell lymphoma showed less consistency. CD56 was not always positive in the cases of this tumor. The different locations of the positive signal to CD3 showed that the cell lineage of this tumor was different from T lymphocytes. The high frequency of the staining by cytotoxic granule proteins, TIA-1, granzyme-B and perform, showed that these cells may have originated from NK cells. The distinctive differences in immunohistochemical staining of cytotoxic granule proteins in nasal NK/T cell lymphoma make their detection very useful and important in diagnosis and differential diagnosis.

Objective To study the correlation between clinicopathological characteristics and lymph node metastasis and prognosis of rectal neuroendocrine tumors (NET),and try to explore the choice of surgical approach.Methods The clinicopathological data of 48 postoperative rectal NET patients were collected.The univariate and multivariate analysis of the correlation between clinicopathologic characteristics and lymph node metastasis were performed by chi-square test and Logistic regression.The prognosis single factor survival analysis was analyzed by Kaplan-Meier method.The survival rates were compared by Log-rank test.The prognosis multivariate survival analysis was performed by the use of Cox model.Results The results of univariate analysis indicated that clinicopathological characteristics related with lymph node metastasis were tumor distance from anal verge less than six cm,tumor diameter over two cm,muscularis invasion,distant metastasis and histological grade 3.The results of multivariate analysis showed that histological grade 3 was an independent risk factor of lymph node metastasis (OR=9.333,95 ％CI:1.054 to 82.635,P=0.045).The results of univariate survival analysis suggested that factors correlated with poor prognosis were tumor distance from anal verge less than six cm,tumor diameter over two cm,muscularis invasion,lymph node metastasis,distant metastasis and histological grade 3.The results of multivariate survival analysis indicated that tumor distance from anal verge less than six cm (HR=0.215,95 ％CI:0.047 to 0.980,P=0.047),distant metastasis (HR=8.788,95％CI:2.612 to 29.571,P＜0.01) and histological grade3 (HR=5.510,95％CI:1.692-17.944,P=0.005) were independent factors associated with poor prognosis.Conclusions For histological grade 1 and 2 rectal NET patients without distant metastasis,radical surgery is recommended when tumor diameter over two cm or muscularis invasion exists.For histological grade 3 rectal NET patients without distant metastasis,radical surgery is recommended.

Purpose:To assess the value and limitation of CT in staging colorectal carcinoma.Methods:CT was performed prior to surgery in 46 patients with 48 colorectal carcinomas for staging the tumor. The results were compared with those of surgical and pathological examinations in all cases in order to study the sensitivity of staging the tumor before operation.Results:(1) CT depicted 31 of 33 pathologically confirmed T4 lesions (beyond the serosa) in all 48 primary carcinomas,appearance of T4 lesion were defined as either strands of soft tissue or nodules into the peri-colorectal fat ,or hyperdensity of pericolorectal fat. (2)Pathologic examination of lymphatic metastases unfirmed 20 of 40 patients who underwent complete resections, and these lymph nodes were not larger than 1cm in 17 patients.The sensitivity is 70%(14/20)and the specificity 85%(17/20)respectively in detection of lymphatic metastases for CT. (3) The accuracy of CT staging was 81.25%,77.50% in T,N respectively in this group of patients,and CT showed all 4 cases of liver metastases and 6 of 7 peritoneal metastases. Conclusions:CT is accurate in detecting T4 stage of colorectal carcinoma. It is effective in depicting local extension and distant metastases. The value of CT for early T staging and N staging in colorectal carcinoma is limited.

Background and purpose: About 20 cases of BML have been reported in the literature,they occurred in females with history of uterus leiomyoma.BML appears as a histopathologic benign smooth muscle tumor located far from the uterus,often in the lungs.Firstly,it should be confirmed as originating from smooth muscle by immunohistochemistry,Secondly,its primary tumor should be confirmed as benign,with mucoid degenenation,it also should be distinguished from myxoid leiomyosacroma.Methods:We report a case of benign metastasizing leiomyoma,study its clinical,histopathologic and immunohistologic features,discuss the diagnosis and differential diagnosis and give a review of the related references.Results:The case occurred in a forty-two year old female who was found to have bilateral lung nodules after hysterectomy of her uterus leiomyoma six years ago.An open lung biopsy revealed the nodules to consist of proliferating smooth muscle cells with a histopathologic feature similar to her uterus leimyoma,consistent with the diagnosis of BML.Positive staining of estrogen and progesterone receptors was detected in both the uterus leiomyoma and the metastasizing lesions.No significant increase or enlargement of the lung nodules were found seven months after the operation with no therapy except taking Chinese traditional medicine.Conclusions:BML is a rare entity usually occurring in females with history of uterus leiomyoma.It appears as a histopathologic benign smooth muscle tumors distant from the uterus.It is hormone dependent and progresses slowly.

Background and purpose: Currently endoscopic ultrasonography is clinically accepted for preoperative staging of gastric cancers. Endoscopic raucosai resection (EMR) and endoscopic subraucosal dissection (ESD) have been widely applied in the treatment of early gastric cancer. We need to improve the accuracy of pre-operative staging of gastric cancers, especially of early gastric cancers. This paper was to investigate the clinical significance of high frequency endoscopic ultrasound mini probe (UMP) in the preoperative T-staging of gastric cancer. Methods: Both UMP and MSCT were performed in 63 patients with pathologically proven gastric cancer frora Oct. 2008 to Apr.2009, and the results of UMP and MSCT were compared with surgical pathologic findings. Results: The accuracy of UMP and MSCT in T staging was 82.26% (51/62) and 88.71% (55/62) respectively, and there was no statistical difference (P>0.05). The accuracy of UMP and MSCT for early gastric cancer was 100.00% and 88.89% respectively.The accuracy of UMP and MSCT for advanced gastric cancer was 79.25% and 88.68% respectively. Conclusion: UMP appears to have a substantial diagnostic value for early stage gastric cancer. It is the approach of choice for superficial lesions.

Objective To investigate the differentiation of neuroendocrine component (NEC) in colorectal adenocarcinoma in relation to its significance by comparing the outcome between patients with or without NEC.Methods The paraffin sections from patients with pathologically confirmed colorectal adenocarcinoma were retrospectively collected and screened for those with NEC by morphological examination and immunohistochemistry with neuroendocrine markers.Control patients (n=54) without NEC were selected from colorectal cancer database and 2: 1 matched on the basis of clinical features with NEC positive patients (n=27).Relative analysis was performed between two groups.Results With a median follow-up of 72 months,the 5-year disease free survival was 58.0% (16/27) in NEC positive group and 79.1% (43/54) in control group (P=0.036).Similarly,the 5-year cancer-specific overall survival was significantly lower in NEC positive group than in control group (58.3% versus 81.1%,P=0.037).Cox regression showed that the 5-year cumulative risks of disease recurrence and cancer-caused death in NEC positive patients were 2.38 and 2.41 times higher than those in control patients,respectively.Conclusions NEC appears to bear a poor prognosis in patients with colorectal adenocarcinoma.

Objective To investigate the association of promoter hypermethylation of secreted frizzled-related proteins (SFRPs) in patients with colorectal cancer. Methods The promoter hypermethylation of SFRPs in 20 sporadic colorectal cancer tissues and adjacent mucosa were detected by methylation-specific PCR. The amplified DNA was subcloned into the T-A cloning vector and sequenced. Two colorectal cancer cell lines (HCT116 and SW480) were treated with 5-aza-2' deoxycytidine for demethylation. The promoter hypermethylation and protein expression of SFRPs in colorectal cancer cell lines were detected by methylation-specific PCR and Western blotting. Results It was demonstrated that the hypermethylation of SFRP 1, 2, 4 or 5 was 19/20,17/20,3/20 or 13/20in cancer tissues, respectively, whereas it was 12/20, 8/12, 1/20 or 7/20 in adjacent mucosa,respectively. SFRP 1, 2 or 5 methylation was more frequently found in cancer tissue than in adjacent mucosa (P～0.05). Methylation of SFRP 1, 2, 4 and 5 were found in HCT116 cell line, but only SFRP1 and SFRP2 were found in SW480 cell line. There was a negative correlation between protein expression and methylation of SFRPs. The Western blotting revealed that SFRP protein re-expressedafter it treated with 5-aza-2' deoxyeytidine. Conclusion Methylation of SFRP 1, 2 or 5 gene is associated with the evolution of eolorectal cancer, and is closely related to silencing expression.

Background and purpose:Tumor budding is a poor prognostic factor in colorectal cancer. In this study, we studied the tumor budding by counting the actual number in 10 high power fields and evaluated itsclinical application in predicting lymph node metastasis of T1 colorectal cancer.Methods:Tissue specimens from 307 patients with histologically conifrmed T1 colorectal cancer were enrolled. The clinicopathological characteristics including tumor budding were evaluated for their predictive value in lymph node metastasis. A formula was created to calculate the risk score for prediction of lymph node metastasis which was validated by 14 new cases.Results:In the multivariate analysis, it showed that tumor grade, lymphovascular invasion and the number of tumor budding were signiifcantly associated with lymph node metastasis. The probability of lymph node metastasis was calculated using the following equations:Z=1.571×(lymphovascular state: invasion, 1; no invasion, 0)+2.661×(tumor grade: high grade, 1; low grade, 0)+0.024×(budding counts)-3.885; Probability=1/1+e-Z. The high scores were correlated with the lymph node metastasis in the validations.Conclusion:We can accurately assess the risk of lymph node metastasis by counting the number of tumor budding in 10 high power fields. Therefore tumor budding could potentially assist treatment decision making in T1 colorectal cancer patients with high-risk lymph node metastasis.

Background and purpose:Metastatic colorectal cancer (mCRC) patients with K-ras mutation won’t benefit in the anti-epidermal growth factor receptor (EGFR) treatments. Thus K-ras mutation analysis is mandatory before this treatment. There is controversy that K-ras mutation analysis should be performed on primaries or related metastases. The aim of our study was to evaluate the concordance of K-ras status between primary and related metastases tumors, thus investigate the validity and rigorousness of clinical K-ras testing. Methods:Seventy-six patients with confirmed mCRC treated in Fudan University Shanghai Cancer Center were enrolled. After DNA extraction and PCR amplification, tumor specimens with paired primary tumors and related metastatic sites were put into sequencing analysis. And the K-ras mutation status in exon 2 was assessed. Results: K-ras mutation was detected in 31 out of 76 primary tumours (40.8%) and also 40.8%of the metastatic sites. But discordance was found between primary tumor and metastasis in 15 cases (19.7%):8 primary tumors had a K-ras mutation with a wild-type metastasis, meanwhile 7 primary tumors were wild type with a K-ras-mutated metastasis. Conclusion:Our study indicated that quite a few mCRC cases have different K-ras status between primary tumors and related metastatic sites, and it’s not very rigorous to choose the anti-EGFR treatments merely according to the primary tumor-K-ras mutation.Further study and consultation are needed on this problem.