Gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC): An immunohistochemistry study of 13 microsatellite stable cases.

BACKGROUND: Mixed adenoneuroendocrine carcinoma (MANEC) is currently included in the category of neuroendocrine carcinomas but the therapeutically management is not yet defined. AIMS: To present the immunohistochemical (IHC) features of the epithelial mesenchymal transition (EMT) of MANEC. MATERIALS AND METHODS: The clinicopathological features of 13 consecutive cases of MANEC (6 gastric and 7 colorectal) were correlated with the IHC expression of the biomarkers E-cadherin, ß-catenin, N-cadherin, vimentin, maspin, CD44 and S100. In all of the cases open surgery was performed. RESULTS: All of the cases showed microsatellite stable status, expressed E-cadherin and membrane ß-catenin in both components (neuroendocrine and adenocarcinoma) and were negative for N-cadherin, vimentin and S-100. The colorectal MANECs were negative for maspin. In gastric MANECs, maspin showed cytoplasm positivity in the neuroendocrine component and nuclear translocation in the adenocarcinoma cells. CD44 was positive in all of the cases, in both components. No tumor buddings were identified. Three of the 13 patients survived for at least 32 months, all of them showing lymphatic emboli but not lymph node metastases. Pure neuroendocrine lymph node metastases were seen in only four of the cases: one from stomach, two of the ascending colon and two cases of the upper rectum. CONCLUSIONS: Gastrointestinal MANEC is a microsatellite stable tumor with nodular growth, which components might originate from a CD44-positive stem-like precursor cell. Lymph node status remains the most reliable prognostic parameter and agressivity seems to not be influenced by tumor budding degree or EMT-related features. The histologic aspect of metastatic component (neuroendocrine versus adenocarcinoma) should be included in the histopathological reports and might be used for establishing the proper-targeted therapy of MANEC.

Immunohistochemical expression of Ki-67 and p53 along with their digitalized evaluation in the discriminatory analysis of reactive atypia and dysplastic lesions in gastrointestinal biopsies of the stomach.

The differential diagnosis between reactive atypia and non-invasive neoplasia (or dysplasia) can be challenging in the case of small conventional forceps biopsy specimens of the stomach. Despite the existence of several classifications for neoplastic epithelial lesions of the stomach, there are few auxiliary tools for aiding in this decision besides standard stains. We studied the utility of Ki-67 and p53 immunohistochemistry in this setting and their clinico-pathological correlations, based on a set of 99 cases with cytological or architectural atypia reviewed by three pathologists. We also tested a digitalized method based on the ImageJ software for the evaluation of Ki-67 expression to determine whether this could be of an additional help. CONCLUSIONS: Ki-67 and p53 expression correlates well with microscopic and morphological modifications in biopsies and can be a useful tool in confirming or dismissing an impression of dysplasia in routine pathological work-up. Digital processing is cumbersome and of limited value and it could only be of additional help if more automated methods are developed.

Histopathological evaluation and expression of the pluripotent mesenchymal stem cell-like markers CD105 and CD44 in the synovial membrane of patients with primary versus secondary hip osteoarthritis.

To present the morphological changes of classic primary versus rapidly progressive and secondary hip osteoarthritis (HO) and to examine the expression of two pluripotent mesenchymal stem cell-like markers in the synovial membrane. A prospective observational study was conducted in 57 consecutive cases of radiologically confirmed HO in which total hip arthroplasty was performed. Based on the radiological and clinicopathological features, the cases were divided into three categories: classic primary HO (group A; n=16), rapidly destructive HO (group B; n=24), and HO secondary to avascular osteonecrosis of the femoral head (group C; n=17). Immunostains were performed using the markers CD44 and CD105. The cases from group A were mainly characterized by a marked perivascular inflammatory infiltrate and simple synovial hyperplasia. In group B, the papillary type of synovial hyperplasia was found and presence of chondromatosis, ossification, and ectopic follicles with germinal centers in the subsynovial layer was characteristic, whereas marked calcification and/or ossification were seen in group C. Focal expression of the CD105 and CD44 was noted in the hyperplastic synovial cells and subsynovial layer in cases from group A, whereas synovial cells from group B were diffusely positive for both CD44 and CD105. In secondary HO, CD44 marked the inflammatory cells. Mobilization of the CD44/CD105 positive synovial cells seems to play a role in the genesis of HO. The number of the pluripotent mesenchymal stem cell-like cells derived from the hyperplastic synovial cells might be related to the severity of possible immune-mediated rapidly destructive HO.

Cystic jejunal duplication with Heinrich's type I ectopic pancreas, incidentally discovered in a patient with pancreatic tail neoplasm.

The aim of this study was to present a case of enteric duplication cyst and criteria for a proper differential diagnosis. A 51-year-old male was hospitalized for pancreatic tail neoplasm and distal pancreatectomy with splenectomy was performed. During surgery, a jejunal cystic lesion was incidentally detected and jejunectomy was performed. Microscopically, the cyst was observed to be covered by Keratin 7/Keratin 20 positive intestinal type epithelium and the muscularis layer was shared by the cyst and adjacent jejunum, without a cleavage plane between the cyst wall and jejunal muscularis propria. In the deep muscularis propria, a Heinrich's type I ectopic pancreas was also noted. In the pancreatic tail, a low grade intraepithelial lesion (panIN-1a) was diagnosed. This case highlights the necessity for a correct differential diagnosis of such rare lesions. Roughly 30 cases of jejunal duplication cysts have been reported to date in the PubMed database.

Tuberculosis terminal ileitis: A forgotten entity mimicking Crohn's disease.

Intestinal tuberculosis (TB) is an uncommon lesion for which differential diagnosis can be difficult. We present a case of a 53-year-old male and a systematic review of the literature, from clinical symptoms to differential diagnosis, unusual complications and therapy. The patient was admitted to the hospital with signs of acute abdomen as a result of a perforated terminal ileitis. Based on the skip lesions of the terminal ileum and cecum, Crohn's disease (CD) was clinically suspected. An emergency laparotomy and right colectomy with terminal ileum resection was performed and systematic antibiotherapy was prescribed. The patient's status deteriorated and he died 4 d after the surgical intervention. At the autopsy, TB ileotyphlitis was discovered. The clinical criteria of the differential diagnosis between intestinal TB and CD are not very well established. Despite the large amount of published articles on this subject, only 50 papers present new data regarding intestinal TB. Based on these studies and our experience, we present an update focused on the differential diagnosis and therapy of intestinal TB. We highlight the importance of considering intestinal TB as a differential diagnosis for inflammatory bowel disease. Despite the modern techniques of diagnosis and therapy, the fulminant evolution of TB can still lead to a patient's death.

Systematic review of the old and new concepts in the epithelial-mesenchymal transition of colorectal cancer.

Epithelial-to-mesenchymal transition (EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and the gain of mesenchymal markers positivity. In the field of colorectal cancer (CRC), first data about EMT was published in 1995 and more than 400 papers had been written up to March 2016. Most of them are focused on the molecular pathways and experimentally-proved chemoresistance. In the present article, an update in the field of EMT in CRC based on the review of the literature and personal experience of the authors is presented. The information about the molecular and immunohistochemical (IHC) particularities of these processes and their possible role in the prognosis of CRC were also up-dated. This article focuses on the IHC quantification of the EMT, the immunoprofile of tumor buds and on the relation between EMT, angiogenesis, and stem cells activation. The EMT-induced chemoresistance vs chemotherapy- or radiotherapy-induced EMT and cellular senescence was also synthesized for both conventional and targeted therapy. As a future perspective, the EMT-angiogenesis-stemness link could be used as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management of patients with CRC. Association of dexamethasone and angiotensin converting enzyme inhibitors combined with conventional chemotherapies could have clinical benefits in patients with CRC. The main conclusion is that, although many studies have been published, the EMT features are still incompletely elucidated and newly discovered EMT markers provide confusing data in understanding this complicated process, which might have significant clinical impact.