Age, operation time and surgical approach can be used to detect incidental gallbladder carcinoma in cholecystectomy specimens from low-incidence settings.

AIMS: Gallbladders resected for non-neoplastic diseases are systemically examined microscopically to rule out incidental dysplasia and carcinoma. The main aim of this study was to test whether a pre-grossing algorithm can detect incidental gallbladder carcinoma. The secondary aim was to test whether the algorithm can detect high-grade dysplasia. METHODS AND RESULTS: A retrospective study of clinical, pathological and radiological findings in cholecystectomy recipients was performed on a test set to develop a classification and regression tree algorithm. Cholecystectomy cases were included; exclusion criteria were age <18 years, missing pathology reports, preoperative suspicion of neoplastic disease, and cholecystectomy for non-gallbladder oncological disease. Five thousand nine hundred and eighty-two cholecystectomies from 2006 to 2018 were included in the study, with 18 cases of incidental gallbladder carcinoma and 11 cases of high-grade dysplasia. Three hundred and ninety controls were randomly selected for the testing set. Patient age, surgical approach, operation duration, dilatation of the biliary tract and gallbladder gross anomalies were statistically significant distinguishing factors in multivariate analysis (P < 0.00-0.026). Unsupervised testing with a conditional inference tree suggested that age, procedure type and operation duration can be used to identify incidental gallbladder carcinoma from controls, whereas high-grade dysplasia also requires grossing parameters to identify half of the cases (5/11). CONCLUSION: Readily available clinical parameters and postoperative data can be used to detect incidental gallbladder carcinoma. High-grade dysplasia mostly requires grossing and microscopic examination.

Gastric neuroendocrine tumours from long-term proton pump inhibitor users are indolent tumours with good prognosis.

AIMS: Proton pump inhibitors (PPIs) are among the most widely used medications in the United States. Most PPI users have persistent hypergastrinaemia during treatment. However, gastric neuroendocrine tumours diagnosed in long-term PPI users are rarely reported. Their clinicopathological features and prognosis are not characterised. It remains unclear whether or not they can be classified as Type III sporadic tumours. METHODS AND RESULTS: We retrospectively characterised 66 gastric neuroendocrine tumours from patients without atrophic gastritis and gastrinoma from two tertiary care medical centres, including 38 tumours in patients who had used PPIs for at least 1 year and 28 tumours from patients without long-term PPI use (control group, Type III tumours). Compared to controls, tumours from long-term PPI users tended to be in the pT1-2 category (98% versus 79%, P = 0.09) and less often invaded the serosa (3% versus 18%, P = 0.08) or lymphovascular spaces (11% versus 32%, P = 0.06). Using Kaplan-Meier analysis, long-term PPI users had significantly longer overall survival than controls (P = 0.035). While three control patients developed distant metastasis and seven died, long-term PPI users were without distant metastasis (P = 0.06) or death (P = 0.002) during follow-up. However, five long-term PPI users developed additional gastric neuroendocrine tumour(s), while none of the controls did (P = 0.07). CONCLUSIONS: Our results show that gastric neuroendocrine tumours of long-term PPI users are probably less aggressive compared to Type III sporadic tumours and have an indolent disease course. Our findings support the classification of gastric neuroendocrine tumours in long-term PPI users as a separate subtype.

Distinct Histologic, Immunohistochemical and Clinical Features Associated With Serous Endometrial Intraepithelial Carcinoma Involving Polyps.

The origin of serous endometrial intraepithelial carcinoma (SEIC) is debated, due to its premalignant and independently malignant nature. It often arises next to endometrial serous carcinoma (ESC), with a propensity for polypoid growth. We aimed to better characterize this discrepancy by analyzing the clinical, histologic, and immunohistochemical features of polypoid carcinoma associated with SEIC (P-SEIC), and compared them with usual endometrial serous carcinoma without SEIC (UESC). Consecutive patients with P-SEIC were recruited and compared with UESC controls from our institutional research center. Clinical, histologic, and immunohistochemical (IHC, ER, PR, P53, Napsin-A, WT1, P16) were analyzed. BRCA testing results and familial history were also extracted from clinical databases. Welch T test, Pearson χ, and Fisher exact test were performed in SPSS version 23. A total of 37 P-SEIC and 25 UESC were the basis of a case-control study. P-SEIC was associated with more bilateral ovarian involvement (P=0.026), yet showed lower rates of myometrial invasion (P=0.002). P-SEIC showed a statistically different IHC profile: p53+, p16+, ER+, PR+, and WT-1+, and high rates of Napsin-A, while UESC was p53+, p16+, WT-1-, Napsin-A-, with lower rates of ER and PR. We also identified 2 patients who received prophylactic salpingo-oophorectomy for BRCA mutations and who subsequently developed P-SEIC with its unique IHC pattern. Our results suggest different underlying expression profiles and possibly diverging molecular signatures between both P-SEIC and UESC. If confirmed in further molecular studies, it could lead to a distinct molecular subclass.