High-grade Dysplasia Carcinoma Research Articles

Imaging and Cytopathological Criteria Indicating Malignancy in Mucin-Producing Pancreatic Neoplasms: A Series of 68 Histopathologically Confirmed Cases.

This study aims to evaluate the performance of clinical, imaging, and cytopathological criteria in the identification of high-grade dysplasia/carcinoma (HGD/Ca) in pancreatic mucin-producing cystic neoplasms. Sixty-eight consecutive, histopathologically confirmed mucin-producing cystic neoplasms, evaluated by endoscopic ultrasound-guided fine-needle aspiration, were enrolled; specifically, 39 branch duct intraductal papillary mucinous neoplasms (BD-IPMNs), 21 main duct IPMNs, and 8 mucinous cystic neoplasms. The associations between HGD/Ca in histopathology and findings of endoscopic ultrasound and cytology, demographic, lifestyle, and clinical parameters were evaluated, separately in IPMNs and mucinous cystic neoplasms. Age 65 years or more was associated with HGD/Ca in IPMNs. In BD-IPMNs, cyst diameter 3 cm or greater (sensitivity, 68.8%; specificity, 65.2%), a mural nodule (sensitivity, 56.3%; specificity, 78.3%), main pancreatic duct diameter 5 to 9 mm (sensitivity, 50.0%; specificity, 87.0%), and suspicious cytology (sensitivity, 81.3%; specificity, 100%) signaled the presence of HGD/Ca. Similarly, in main duct IPMNs, suspicious cytology predicted HGD/Ca with high sensitivity (88.9%) and excellent specificity (100%). Regarding cytopathological criteria, in BD-IPMNs, HGD/Ca was associated with a high nuclear/cytoplasmic ratio, background necrosis, presence of papillary structures, hypochromatic nuclei, hyperchromatic nuclei, and major nuclear membrane irregularities (thickening and/or indentations). Clinical, imaging, and cytopathological criteria are useful in the identification of HGD/Ca in IPMNs.

P53 expression in low grade dysplasia in Barrett’s esophagus: correlation with interobserver agreement and disease progression

OBJECTIVES: The frequency of progression from low grade dysplasia (LGD) to high grade dysplasia/carcinoma (HGD/CA) in Barrett’s esophagus (BE) varies among studies. Current assessment is made more difficult because of pathologists’ interobserver variability in diagnosing LGD. We recently conducted an interobserver study on LGD and reported a positive correlation between the extent of agreement among GI pathologists and progression of LGD. In the current study, we analyzed the immunohistochemical staining for p53 in patients diagnosed with LGD with known clinical outcome and interobserver agreement data. METHODS: Fixed, paraffin-embedded endoscopic biopsy specimens from 16 patients diagnosed with LGD in BE were immunostained for p53 (DO-7, Dako, Carpinteria, CA). Hematoxylin and eosin-stained and immunostained sections were examined in tandem to determine whether the LGD areas in question stained for p53. The p53 immunoreactivity was correlated with clinical progression and with the interobserver agreement among three GI pathologists. RESULTS: The overall mean follow-up was 23 months (range 2–84 months). LGD areas in seven of eight patients (88%) who progressed to HGD/CA stained positively for p53 compared to only two of eight nonprogressors (25%). A correlation with clinical progression was seen for p53 positivity ( p = 0.017; log-rank test), and for either p53 positivity or complete agreement among three GI pathologists on LGD diagnosis ( p = 0.014; log-rank test). The p53 staining demonstrated 88% sensitivity and 75% specificity for progression of LGD to HGD/CA. Adding complete interobserver agreement on LGD among three experienced GI pathologists to p53 positivity resulted in improved sensitivity with no change in specificity (100% and 75%, respectively). CONCLUSIONS: In conjunction with histological evaluation by GI pathologists for a diagnosis of LGD, immunohistochemical staining for p53 can be used as an adjunctive test, as it correlated with progression to HGD/CA in this series.

Prevalence of activating K-ras mutations in the evolutionary stages of neoplasia in intraductal papillary mucinous tumors of the pancreas.

The purpose of the study was to determine the prevalence of activating K-ras mutations in the pancreas of patients with intraductal papillary mucinous tumors (IPMT) and to analyze their relation to the degree of site-specific histopathologic abnormality. Intraductal papillary mucinous tumors of the pancreas have a biologic behavior that is significantly different from pancreatic ductal adenocarcinoma. Activating K-ras mutations, which may be important events in a multistage process of carcinogenesis, have been reported in IPMT. Forty-six different histologic specimens (comprising normal pancreatic ducts, hyperplasia, low-grade dysplasia, high-grade dysplasia-carcinoma in situ, and carcinoma) from 16 patients with IPMT and 9 specimens from patients with pancreatic ductal adenocarcinomas were designated by a pathologist. Genomic DNA was extracted from paraffin-embedded tissue sections after microdissection. The K-ras gene was amplified by polymerase chain reaction and subjected to DNA sequencing. The K-ras mutations were detected in at least one specimen in 13 (81.2%) of 16 patients with IPMT. All mutations were found in codon 12. No codon 13 mutations were detected. The relative frequency of K-ras mutations in the different stages of IPMT was 16.7% in normal epithelium and papillary hyperplasia, 28.6% in low-grade dysplasia, and 57.1% in high-grade dysplasia-carcinoma in situ and invasive carcinoma. The K-ras mutations were detected in 6 (66%) of 9 pancreatic ductal adenocarcinomas. The K-ras codon 12 point mutations are as frequent in IPMT as in ductal adenocarcinoma. A stepwise increase in the frequency of codon 12 mutations correlated with the stage of neoplastic evolution to cancer. This finding is consistent with an important role of K-ras gene mutations in the transformation from normal epithelium to invasive carcinoma in the majority of patients with IPMT.