AKT and mTOR expression in human pancreatic ductal adenocarcinoma. Relevance for tumor biology.

BACKGROUND AND STUDY AIMS: Several signaling pathways interfere with pancreatic ductal adenocarcinoma (PDAC) carcinogenesis processes, among which the AKT-pathway. The relevance of proteins in this pathway for the malignant phenotype or prognosis of PDAC is incompletely understood. We aimed to study AKT-pathway proteins in PDAC. METHODS: We examined immunohistochemical expression of two main AKT pathway proteins, AKT and mTOR, in 99 PDAC. Protein expression patterns were analysed with regard to tumor features, to MAPK and TGFbeta pathway protein expression and, to cell proliferation. RESULTS: Tumor AKT was more frequent in PDAC with an abundant stromal inflammatory infiltrate (p = 0.03). When considering intra-pancreatic PDACs, mTOR correlated to T2 as compared to T1-TNM stage tumors. When considering the entire series, mTOR correlated to intra-pancreatic tumors (T1- and T2-TNM stage) as compared to T3-TNM PDAC (Fisher p < 0.01 for both comparisons). mTOR expression was more frequent in PDAC with an abundant intratumor stromal component and tumors with a high Ki67-positive tumor cell component (Fisher p = 0.05 and p < 0.01, respectively). mTOR, related to SMAD4 (Fisher p < 0.01) as well as to nuclear ERK (Fisher p = 0.02). CONCLUSION: The results of this study indicate an intricated role, mainly for mTOR in PDAC cell proliferation and tumor components development. The relationships we have found between AKT and mTOR and, MAPK and SMAD-pathway proteins suggest interactions at several levels of the protein framework resulting in varied impact on cell proliferation and tumor behavior/development.

Lymph node angioma: Capsule or hilar angioma?

No abstract available.

Thyroid lymphoepithelial nodule.

Thyroid benign lymphoepithelial lesions are rare in adults, reported as associated with thyroiditis or adjacent to tumours. Here we report a unique case of a thyroid solid nodule with benign lymphoepithelial morphology. A 56-year-old woman presented with a thyroid nodule increasing in size. Thyroid function was normal. On the surgical resection specimen, in addition to a 2-cm follicular adenoma, there was, at distance, a 0.5-cm solid nodule with lymphoepithelial morphology, without Hassal's corpuscles or calcifications. On immunohistochemistry, the epithelial component was cytokeratin 5/6 positive and very focally cytokeratin 7 positive, the immunophenotype of the lymphoid tissue confirming the benign nature. The diagnosis of thyroid benign lymphoepithelial nodule was proposed. In conclusion, recognition of thyroid solid benign lymphoepithelial nodules is important since they can be misdiagnosed with other thyroid micronodule types including carcinoma, primary or metastatic.

Adult cervical thymus revealed by thyroid medullary carcinoma.

A 64-year-old man presented with elevated thyrocalcitonin, and a history of resected thyroid medullary carcinoma. Cervical thymus was detected incidentally in the neck dissection resection specimen for thyroid medullary carcinoma extension. This case was peculiar due to the presence of a thymic microcyst and the coexistence of parathyroid tissue along with the thymic lobules. Persistent hypocalcaemia, requiring calcium intake, occurred after resection. Although rare, the presence of such neck branchial arch abnormalities should be considered for a successful management of extensive malignant thyroid tumours.

Tumour epithelial vimentin expression and outcome of pancreatic ductal adenocarcinomas.

PURPOSE: Tumour epithelial vimentin expression is a marker of mesenchymal differentiation and may be a useful marker of carcinomas with more aggressive behaviour. The aim of this study was to determine the extent and prognostic significance of vimentin expression in pancreatic ductal adenocarcinomas. METHODS: Vimentin expression was detected by immunohistochemistry on tissue microarrays of surgically resected pancreatic ductal adenocarcinomas from 387 patients. The percentage of vimentin-immunolabelled neoplastic cells was correlated with outcome and with clinico-pathological factors using the Kaplan-Meier method and Cox multivariate survival models. RESULTS: In all, 45% of primary pancreatic adenocarcinomas contained neoplastic cells that expressed vimentin, and in 27.5% of the cancers >10% of cells expressed vimentin. Vimentin expression was correlated with poor histological differentiation. By both uni- and multivariate survival analysis, neoplastic vimentin expression (P<0.01, HR 1.52, 95% confidence interval 1.14-2.04) was an indicator of a shorter postsurgical survival independent of other clinico-pathological variables. CONCLUSION: The presence of vimentin-expressing tumour epithelial cells in surgically resected pancreatic adenocarcinomas independently predicted a shorter postsurgical survival.

Human pancreatic mucinous cystadenoma is characterized by distinct mucin, cytokeratin and CD10 expression compared with intraductal papillary-mucinous adenoma.

AIMS: To examine cytokeratin, epithelial glycoprotein (mucin) and glycoprotein CD10 expression in benign mucinous cystdenomas (MCAs) in comparison with intraductal papillary mucinous adenomas (IPMAs). METHODS AND RESULTS: Thirty MCAs of the pancreas were analysed for immunohistochemical expression of cytokeratin (CK) 7, CK20, MUC1, MUC2, MUC5AC and CD10 and were compared with 16 IPMAs. CK7 was expressed in all neoplasms. CK20 was significantly more frequent in MCAs compared with IPMAs (56.66% versus 18.75%, P = 0.027). MUC1 was more frequent in MCAs (40% versus 12.5%, P = 0.0915), whereas MUC5AC was significantly less frequent in MCAs (33.33% versus 100%). MUC2 was expressed in goblet cells of seven MCAs. In MCAs, CD10 was observed both in epithelial cells and in the ovarian-type stromal cells (24/30). Epithelial expression of CD10 was significantly lower in IPMAs (66.66% versus 6.25%, p = 0.0001). CONCLUSIONS: MCA is characterized by a significantly greater frequency of expression of CK20 and CD10 when compared with IPMA, which preferentially expresses MUC5AC.

Familial multiple gastrointestinal stromal tumours with associated abnormalities of the myenteric plexus layer and skeinoid fibres.

AIMS: Multiple familial gastrointestinal stromal tumours are rare. We report the third family with two cases of multiple gastrointestinal stromal tumours showing skeinoid fibres. Associated abnormalities of the myenteric plexus layer are described and new hypotheses for the histogenesis of gastrointestinal stromal tumours are formulated. METHODS AND RESULTS: Multiple gastrointestinal stromal tumours developed in the duodenum and proximal jejunum were removed from mother and son. No history of a specific syndrome or of mastocytosis was known. Light microscopy revealed typical gastrointestinal stromal tumours with skeinoid fibres. An unusual abnormality of the myenteric plexus layer, showing a diffuse spindle cell hyperplasia, was noted in the macroscopically normal digestive wall. No abnormalities of the ganglion cells were associated. Tumours and the spindle cell hyperplasia showed similar morphological and immunohistochemical features with expression of CD34 and CD117 antigens. Follow-up revealed recurrences in the mother. CONCLUSION: The morphological characteristics of these two cases of familial gastrointestinal stromal tumours and of the associated abnormalities of the myenteric plexus layer, help to better explain the histogenesis of multiple familial gastrointestinal stromal tumours. The hyperplasia of the myenteric plexus could be considered a risk factor for recurrent tumours.

[Immunohistochemical and ultrastructural heterogeneity of gastrointestinal stromal tumors]. / Hétérogénéité immunohistochimique et ultrastructurale des tumeurs stromales digestives.

AIMS AND METHODS: Digestive stromal tumors are the most frequent undifferentiated mesenchymal tumors. The prognosis of these tumors is difficult to predict and the histogenesis is still subject to controversy. However, the frequent and specific expression of CD117 (c-kit) by these tumors could suggest an origin from interstitial cells of Cajal. The aim of this study was to analyse the histological and immunohistochemical characteristics of 46 digestive stromal tumors surgically resected, with comparaison of CD34 and CD117 expression in these tumors. Sixteen tumors were analyzed on electron microscopy. RESULTS: Sixty three and 74% of the stromal tumors were positive for CD117 and CD34 respectively. While CD117 expression was similar in all locations, on the contrary, there was a decreasing gradient of CD34 expression between gastric (87%) and jejunal (33%) tumors. All tumors with skeinoid fibers expressed CD117. Focal expression of smooth muscle actin was noted in 43% of the cases. The ultrastructural study showed no correlation with the immunohistochemical results. CONCLUSION: Digestive stromal tumors show an immunophenotypic and ultrastructural heterogeneity. CD117 expression is frequent, but not constant.

Spindle cell squamous carcinoma of the oesophagus: an analysis of 17 cases, with new immunohistochemical evidence for a clonal origin.

AIMS: To study the morphological and immunohistochemical characteristics of spindle cell squamous carcinoma of the oesophagus, in order better to understand the histogenesis of this tumour. METHODS AND RESULTS: In this study we analysed the morphological and immunohistochemical characteristics of 17 cases of spindle cell squamous carcinoma of the oesophagus. Most tumours were polypoid, but tumours with an ulcerated and infiltrative pattern were also observed. Histologically, most tumours were of superficial type, with a characteristic morphological aspect consisting of two types of tumour cells, i.e. differentiated squamous cells, and spindle cells with transition zones between the two components. On immunohistochemistry, the squamous cells were positive for cytokeratin and the spindle cells showed variable expression of cytokeratin, vimentin and smooth muscle actin. p53 protein was over-expressed in 10 cases, both tumour cell types showing strong nuclear positivity. In most tumours, E-cadherin was expressed in the squamous cells and absent in the spindle cells. CONCLUSIONS: The similar pattern of p53 protein expression in the two tumour cell types of spindle cell squamous carcinoma of the oesophagus suggests their common origin. The change in adhesion molecule expression with loss of E-cadherin expression may be associated with the acquisition of spindle cell morphology by the squamous tumour cells.

[Adenomatoid tumor of the pleura. Case report]. / Tumeur adénomatoïde pleurale. A propos d'un cas.

We report a case of an adenomatoid tumor of particular location within the pleura, incidentally discovered on a pulmonary lobectomy specimen after surgical resection of a pulmonary squamous cell carcinoma. This adenomatoid tumor appeared as a unique pleural mass located away from the primary carcinoma and consisted of a cellular proliferation organised in tubes and sheets. Adenomatoid tumors are considered as benign tumors of mesothelial nature. Their morphological and immunohistochemical features in association with their location to the pleura, warrant a precise analysis to eliminate malignant tumours such as malignant mesothelioma or metastatic adenocarcinoma.