Morphomolecular Correlation and Clinicopathologic Analysis in Endometrial Carcinoma.

Research groups have identified 4 groups [polymerase epsilon (POLE) mutant, mismatch repair-deficient, p53-abnormal, and no specific molecular profile)] reflecting the Tumor Cancer Genomic Atlas Research Network subgroups in endometrial carcinomas, improving the clinical applicability of molecular classification. We have analyzed the histopathologic and prognostic characteristics of our cases based on the ProMisE classification, supported by growing data on recommended treatment regimens. The study included 118 cases of endometrial carcinoma diagnosed between 2016 and 2020, which underwent mismatch repair and p53 immunohistochemistry. Next-generation sequencing was performed for POLE mutation analysis, dividing the cases into 4 subgroups. The histopathologic and clinical characteristics of these groups were then analyzed statistically. Four cases(3.4%) were classified as POLE mutant, 31 (26.3%) as mismatch repair-deficient, 22 (18.6%) as p53 mutant, and 61 (51.7%) as no specific molecular profile. We categorized 118 patients with endometrial carcinoma into low (n=43), intermediate (n=28), high-intermediate (n=21), high (n=22), and advanced metastatic (n=4) risk groups regardless of the molecular subtypes of their disease. When we reclassified all cases according to the molecular subtypes of endometrial carcinoma only the risk group of 3 (2.5%) cases changed. Using the new algorithm we designed, after narrowing down the number of patients, the microcystic, elongated, and fragmented pattern of invasion was revealed as an independent prognostic factor that reduces overall survival time (hazard ratio: 16.395, 95% CI: 2.140-125.606, P=0.007). In conclusion, using the new algorithm we have designed, and by identifying patients for whom molecular classification could alter risk groups, we observed that molecular tests can be utilized more efficiently in populations with limited economic resources and, in doing so, we discovered a new morphologic marker with prognostic significance.

The Contribution of Additional Sampling in Cholecystectomy Materials: A Multicenter Prospective Study.

OBJECTIVE: Cholecystectomy materials are frequently encountered in routine practice. The aim of this study was to determine the true frequency of gallbladder lesions, the diagnostic consistency, and standardization of reports after macroscopic sampling and microscopic evaluation based on previously defined criteria. MATERIAL AND METHOD: 14 institutions participated in the study within the Hepato-Pancreato-Biliary Pathology Study Group. Routinely examined cholecystectomies within the last year were included in the study in these institutions. Additional sampling was performed according to the indications and criteria. The number of blocks and samples taken in the first macroscopic examination and the number of blocks and samples taken in the additional sampling were determined and the rate of diagnostic contribution of the additional examination was determined. RESULTS: A total of 5,244 cholecystectomy materials from 14 institutions were included in the study. Additional sampling was found to be necessary in 576 cases (10.98%) from all institutions. In the first macroscopic sampling, the mean of the numbers of samples was approximately 4 and the number of blocks was 2. The mean of the numbers of additional samples and blocks was approximately 8 and 4, respectively. The diagnosis was changed in 144 of the 576 new sampled cases while the remaining 432 stayed unaltered. CONCLUSION: In this study, it was observed that new sampling after the first microscopic examination of cholecystectomy materials contributed to the diagnosis. It was also shown that the necessity of having standard criteria for macroscopic and microscopic examination plays an important role in making the correct diagnosis.

A grading dilemma; Gleason scoring system: Are we sufficiently compatible? A multi center study.

OBJECTIVE: Gleason scoring is the grading system which strongly predicts the prognosis of prostate cancer. However, even being one of the most commonly used systems, the presence of different interobserver agreement rates push the uropathologists update the definitons of the Gleason patterns. In this study, we aimed to determine the interobserver agreement variability among 7 general pathologists, and one expert uropathologist from 6 different centers. METHODS: A set of 50 Hematoxylin & Eosin stained slides from 41 patients diagnosed as prostate cancer were revised by 8 different pathologists. The pathologists were also grouped according to having their residency at the same institute or working at the same center. All pathologists' and the subgroups' Gleason scores were then compared for interobserver variability by Fleiss' and Cohen's kappa tests using R v3.2.4. RESULTS: There were about 8 pathologists from 6 different centers revised all the slides. One of them was an expert uropathologist with experience of 18 years. Among 7 general pathologists 4 had surgical pathology experience for over 5 years whilst 3 had under 5 years. The Fleiss' kappa was found as 0.54 for primary Gleason pattern, and 0.44 for total Gleason score (moderate agreement). The Fleiss' kappa was 0.45 for grade grouping system. CONCLUSION: Assigning a Gleason score for a patient can be problematic because of different interobserver agreement rates among pathologists even though the patterns were accepted as well-defined.

Liver Transplant in Patients with Primary Sclerosing Cholangitis: Long-Term Experience of a Single Center.

OBJECTIVES: Primary sclerosing cholangitis is a chronic inflammatory disease of the intrahepatic and extrahepatic bile ducts. More than half of the patients will face end-stage liver disease and require liver transplant. Here, we describe the long-term outcomes of liver transplant in patients with primary sclerosing cholangitis at our center. MATERIALS AND METHODS: For this retrospective, observational study, we investigated all patients who underwent liver transplant for primary sclerosing cholangitis between January 2005 and June 2013 at the Dokuz Eylul University Hospital. Patient data were obtained from hospital records. Our inclusion criteria were patients over 18 years old and diagnosed with primary sclerosing cholangitis. RESULTS: Of 11 patients included the study, 6 (54.5%) were male and 5 (45.5%) were female. Mean age was 40.6 ± 11.0 years (range, 23-60 y). All patients had cirrhosis due to primary sclerosing cholangitis. With regard to Child-Turcot-Pugh classification, 2 patients (18.2%) were classified as having Child-Turcot-Pugh A cirrhosis, 7 patients (63.6%) were classified as having B cirrhosis, and 2 patients (18.2%) were classified as having C cirrhosis. Mean Modified End-Stage Liver Disease score was 17.5 ± 6.1 (range, 7-25). Cholangiocarcinoma was not detected in explant pathologic examinations. Primary sclerosing cholangitis recurrence developed in 2 patients (18.1%). Three patients (27.2%) died during the follow-up period. CONCLUSIONS: Liver transplant is a good therapeutic option for primary sclerosing cholangitis with satisfactory long-term outcomes. Liver transplant should be reserved for patients with end-stage liver disease and other conditions that significantly impair quality of life.

A Retrospective Evaluation of the Epithelial Changes/Lesions and Neoplasms of the Gallbladder in Turkey and a Review of the Existing Sampling Methods: A Multicentre Study.

OBJECTIVE: As there is continuing disagreement among the observers on the differential diagnosis between the epithelial changes/lesions and neoplasms of the gallbladder, this multicentre study was planned in order to assess the rate of the epithelial gallbladder lesions in Turkey and to propose microscopy and macroscopy protocols. MATERIAL AND METHOD: With the participation of 22 institutions around Turkey that were included in the Hepato-Pancreato-Biliary Study Group, 89,324 cholecystectomy specimens sampled from 2003 to 2016 were retrospectively evaluated. The numbers of adenocarcinomas, dysplasias, intracholecystic neoplasms/adenomas, intestinal metaplasias and reactive atypia were identified with the review of pathology reports and the regional and countrywide incidence rates were presented in percentages. RESULTS: Epithelial changes/lesions were reported in 6% of cholecystectomy materials. Of these epithelial lesions, 7% were reported as adenocarcinoma, 0.9% as high-grade dysplasia, 4% as low-grade dysplasia, 7.8% as reactive/regenerative atypia, 1.7% as neoplastic polyp, and 15.6% as intestinal metaplasia. The remaining lesions (63%) primarily included non-neoplastic polypoids/hyperplastic lesions and antral/pyloric metaplasia. There were also differences between pathology laboratories. CONCLUSION: The major causes of the difference in reporting these epithelial changes/lesions and neoplasms include the differences related to the institute's oncological surgery frequency, sampling protocols, geographical dissimilarities, and differences in the diagnoses/interpretations of the pathologists. It seems that the diagnosis may change if new sections are taken from the specimen when any epithelial abnormality is seen during microscopic examination of the cholecystectomy materials.

Solid-Pseudopapillary neoplasm of the pancreas: A clinicopathological review of 20 cases including rare examples.

AIMS: Solid-pseudopapillary neoplasm (SPN) is an uncommon malignant tumor of the pancreas with a favorable prognosis unlike other pancreatic neoplasms. We investigated the clinicopathological features of 20 patients with SPN in details. METHODS: The patients diagnosed as SPN in Dokuz Eylul University Hospital between January 2005 and March 2016 were reviewed in terms of clinical and histopathological data. RESULTS: Mean age of the patients was 33. Three of our cases were male and 4 were children. Some patients had synchronuous malignancies. Nine patients were diagnosed by fine needle aspiration cytology (FNAC). One of our tumors had 2×1mm of pancreas endocrine neoplasm in addition to SPN. One case had foci of atypical and multinucleated giant cells. All cases were positive for vimentin and CD10 antibodies and most were positive for PR and ß-catenin. The mean follow-up duration was 40 mo (range 2-110 mo). Only one case showed liver metastasis. CONCLUSION: Herein we present a series of 20 patients with 3 male and 4 pediatric cases, almost half of which were diagnosed with FNAC findings, and most of which are clinically being followed with one patient showing progression. Our series includes rare examples like collision tumor of SPN and pancreas endocrine neoplasm, SPN with multinucleated giant cells. Also cases with no surgical treatment and no progression, as well as cases with synchronous malignancies are presented. We believe that FNAC findings of any pancreatic mass should be investigated in detail for the designation of a therapy plan especially for the patients with high operation risks. The findings in our series also show that extensive necrosis, angioinvasion, perineurial invasion and larger tumor size might be predictive for worse prognosis and these patients should be more closely followed up.

CD40 expression in pancreatic cancer.

BACKGROUND: CD40, a tumor necrosis factor receptor family member, is expressed in a variety of cell types. This widespread expression suggests that CD40 may play an important role in normal physiology and disease pathogenesis. The objective of the current study was to investigate the expression of CD40, and its association with clinicopathological features and survival in patients with pancreatic ductal adenocarcinoma. METHODOLOGY: CD40 expression was assessed in 53 pancreatic ductal adenocarcinoma surgical specimens by immunohistochemistry, and expression was correlated with patient clinicopathological parameters and outcome. RESULTS: Among 53 pancreatic cancer specimens, CD40 expression was detected in 13 specimens (24.5%), and peritumoral lymphocytes were present in 45 specimens (84.9%). Patients with CD40-positive tumors exhibited prolonged median disease-free survival (DFS) compared with patients with CD40-negative tumors (15.60 +/- 3.87 versus 10.03 +/- 1.92); however, this was not significant (p = 0.845). Patients with peritumoral lymphocytic reaction exhibited prolonged median DFS compared with patients without peritumoral lymphocytes (10.96 +/- 1.40 vs. 7.60 +/- 0.47); however, this was not significant (p = 0.624). Patients with peritumoral lymphocytic reaction exhibited higher median overall survival compared with patients without peritumoral lymphocytes (15.20 +/- 1.78 vs. 10.13 +/- 1.39); however, again this was not significant (p = 0.100). CONCLUSIONS: These results suggest that CD40 expression on pancreatic cancer cells and peritumoral lymphocytic reaction may serve as prognostic markers.