Clinicopathological Correlates of PIT1 and SF1-Multilineage Pituitary Neuroendocrine Tumors and the Diagnostic Utility of NKX2.2 Immunohistochemistry in Pituitary Pathology.

CONTEXT.­: PIT1 and SF1-multilineage pituitary neuroendocrine tumors (PitNETs) have been defined since the classification of adenohypophysial tumors based on the PIT1, SF1, and TPIT transcription factors. OBJECTIVE.­: To describe the clinicopathologic features of PIT1 and SF1-multilineage PitNETs and to contribute to the pituitary pathology practice by questioning the expression of NKX2.2 in PitNETs. DESIGN.­: We reviewed 345 PitNETs and described the clinicopathologic features of 8 PIT1 and SF1-multilineage tumors. NKX2.2 positivity and staining pattern were compared to those of 45 PitNETs from the control group. RESULTS.­: PIT1 and SF1-multilineage PitNET patients had a mean age of 41.13 (range, 14-58 years) and a mean diameter of 14.0 mm (range, 8-20 mm). The most common clinical presentation was acromegaly (6 of 8), and postoperative remission was achieved in all patients. On histomorphologic examination, a pseudopapillary pattern was seen in 5 of the tumors, either focally or diffusely. In addition to PIT1 and SF1, there was a diffuse staining with growth hormone and a predominantly perinuclear staining with cytokeratin 18. With NKX2.2, all multilineage tumors were positive, of which 5 were diffuse and 3 were focal. In the control group, 8 tumors (8 of 45) were positive, of which only 1 was diffuse and 7 were focal. CONCLUSIONS.­: In conclusion, NKX2.2 is a transcription factor that can be used as an additional tool in pituitary pathology, and PIT1 and SF1-multilineage PitNETs are specific tumors that usually present with acromegaly, show signs of a nonaggressive clinical course, have a pseudopapillary histomorphology, and express NKX2.2.

The Impact of Metabolic 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Parameters on the Prognosis of Resectable Pancreatic Adenocarcinoma.

Objectives: 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) is a useful staging method in pancreatic cancer. The prognosis of pancreatic adenocarcinoma is affected by the tumor stage and resectable state. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary tumors are related to prognostic parameters in pancreatic cancer. This study compared 18F-FDG PET/CT findings with prognostic factors and overall survival of patients with pancreatic cancer. Methods: Patients with pancreatic adenocarcinoma, referred to our department between 2015 and 2022 for staging, were retrospectively evaluated. Head-to mid-thigh PET/CT images were obtained 1 h after 18F-FDG injection. Demographic data, survival, and clinical and pathological findings of 39 patients, who underwent surgery after PET/CT imaging, were collected. All primary tumor MTV, SUVmax, background SUVmax, and TLG data have were measured. Results: The images of 39 patients (24 women and 15 men) with a mean age of 66.62±9.60 years were evaluated. The mean SUVmax, MTV 40%, and TLG of the primary tumors in the pancreatic tissue were 6.28±2.33, 19.33±9.77, and 66.56±45.99, respectively. The average survival after disease diagnosis was 18.97±11.47 (2-55) months. MTV and TLG were significantly higher in patients who died during our study. SUVmax has a significant effect on mortality. Conclusion: 18F-FDG PET/CT metabolic parameters of SUVmax, MTV, and TLG could help predicting the prognosis of pancreatic cancer preoperatively and follow-up in patients with resectable tumors. Additionally, in our study group tumor grade and perineural invasion significantly affected overall survival.

Biallelic Novel USP53 Splicing Variant Disrupting the Gene Function that Causes Cholestasis Phenotype and Review of the Literature.

Introduction: Hereditary cholestasis is a heterogeneous group of liver diseases that mostly show autosomal recessive inheritance. The phenotype of cholestasis is highly variable. Molecular genetic testing offers an useful approach to differentiate different types of cholestasis because some symptoms and findings overlap. Biallelic variants in USP53 have recently been reported in cholestasis phenotype. Methods: In this study, we aimed to characterize clinical findings and biological insights on a novel USP53 splice variant causing cholestasis phenotype and provided a review of the literature. We performed whole-exome sequencing and then confirmed it with Sanger sequencing. In addition, as a result of in silico analyses and cDNA analysis, we showed that the USP53 protein in our patient was shortened. Results: We report a novel splice variant (NM_019050.2:c.238-1G>C) in the USP53 gene via whole-exome sequencing in a patient with cholestasis phenotype. This variant was confirmed by Sanger sequencing and was a result of family segregation analysis; it was found to be in a heterozygous state in the parents and the other healthy elder brother of our patient. According to in silico analyses, the change in the splice region resulted in an increase in the length of exon 2, whereas the stop codon after the additional 3 amino acids (VTF) caused the protein to terminate prematurely. Thus, the mature USP53 protein, consisting of 1,073 amino acids, has been reduced to a small protein of 82 amino acids. Conclusion: We propose a model for the tertiary structure of USP53 for the first time, and together with all these data, we support the association of biallelic variants of the USP53 gene with cholestasis phenotype. We also present a comparison of previously reported patients with USP53-associated cholestasis phenotype to contribute to the literature.

Comparison of Conventional Smear and Liquid-Based Cytology in Adequacy of Thyroid Fine-Needle Aspiration Biopsies without an Accompanying Cytopathologist.

Objectives: In this study, we aimed to compare the adequacy of conventional smear (CS) and liquid-based cytology (LBC) methods in thyroid fine-needle aspiration biopsy (FNAB) samples obtained without an accompanying cytopathologist during the procedure. Furthermore, we aimed to investigate the presence of a significant difference between the rates of nodules classified as Bethesda Category III and malignancy in both techniques and the features of the nodules affecting malignancy. Methods: A total of 625 nodules from 572 patients who were found suitable for biopsy were included in this retrospective study. FNABs were performed by interventional radiologists without an accompanying cytopathologist during the procedures. The specimens were either prepared using CS or LBC preparation methods. Cytopathological diagnostic adequacy and cytopathological results of the specimens were evaluated according to Bethesda category, and the relationship between the morphological findings was evaluated retrospectively. Results: Of all the biopsy preparations, 338 (54.1%) of them were transferred to pathology in liquid-based solution and 287 (45.9%) were transferred as CS. Malignancy rates of the biopsy samples were found similar in both LBC and CS methods. Considering the nodules classified as Bethesda Category II, III, IV, V, and VI, there was no statistical difference between the results of both methods. Non-diagnostic biopsy rate was higher in the specimens prepared by CS method (p<0.001). Conclusion: In this study, the adequacy rate of FNAB was found significantly higher in LBC method compared to the CS method. LBC was more practical and faster than the CS method. We think that LBC method may be preferred in FNAB of thyroid nodules.

Low Vitamin D Status is Not Associated with the Aggressive Pathological Features of Papillary Thyroid Cancer.

Objectives: In the present study, we investigated the effects of Vitamin D (vit D) deficiency on aggressiveness of papillary thyroid cancer (PTC). Methods: Patients with PTC confirmed with pathological examination, whom were operated by a single surgeon between 2012 and 2017, were included in the study. The data of the patients were analyzed retrospectively. Cancers other than PTC, patients with hyperthyroidism and/or using antithyroid drugs were excluded from the study. The patients were classified as four quartiles according to serum Vit D levels; category 1 (<7.1 ng/mL), category 2 (7.2-11.8 ng/mL), category 3 (11.9-23.4 ng/mL) and category 4 (>23.5 ng/mL). Results: A total of 133 patients (103 female, 30 male) with mean age of 46.4±13.6 (17-82) years were included in the study. There was no significant difference between the categories in terms of preoperative Vit D values according to the evaluated tumor aggressiveness characteristics. It was determined that the presence of tumor with a size above 1 cm and T3/4 tumor were not affected by Vit D level. There was no significant difference between Vit D categories regarding the characteristics of aggressiveness such as multicentricity, lymphovascular invasion, central, and lateral metastases. Conclusion: According to our results, serum Vit D levels are not associated with the aggressive tumor characteristics of PTC.

The Efficiency of Fractional Anisotropy, Apparent Diffusion Coefficient, and Contrast Enhancement Index in Liver Fibrosis Staging.

Objectives: Even though magnetic resonance imaging has been described as the most effective imaging method for the diagnosis of liver fibrosis, an accepted magnetic resonance imaging (MRI) technique is yet to be defined. The aim of this study is to determine the efficiency of MRI in the staging of liver fibrosis. Methods: Patients with chronic hepatitis B infection and had upper abdominal MRI with hepatocyte specific contrast agent were evaluated. Twenty-nine patients that had undergone liver biopsy were included in the study. ADC, FA, and signal intensity values of liver parenchyma were measured by two observers and contrast enhancement index (CEI) was calculated as well. Patients were grouped as early (A) and late fibrosis(B) according to Ishak grading system and then the correlations between the stage and MRI findings were analysed. The intraclass correlation coefficient was used to analyze the inter-rater agreements. ADC, FA, and CEI were compared with Student t-test between early and late fibrosis groups. Pearson's correlation was used to assess the correlation between ADC and FA values. Spearman correlation was used to evaluate the relationship between pathologic fibrosis grade and MRI parameters that were measured. Results: Twenty-two patients were staged as 1 and 2 (group A), seven patients were staged as 3 and above fibrosis(group B). Statistically, there was a strong, negative correlation between the FA values and the degree of fibrosis (r=-0.582, p=0.001). There was no correlation between the CEI and hepatocyte activity index (r=-0.88, p=0.655) and degree of fibrosis (r=0.0001, p=0.997). In terms of FA values, there was a statistically significant difference between two groups (group A=0.429 ± 0.06, group B=0.349 ± 0.06) (p=0.004). Conclusion: Correlation of FA values with fibrosis stage and significant difference in FA values between early-late stage fibrosis patients shows that diffusion tensor imaging can be a promising technique in the staging and follow-up of liver fibrosis.

Primary Hepatic Angiosarcoma: A Rare and Very Aggressive Liver Tumour.

Primary hepatic angiosarcoma (PHA) is a sporadic and aggressive tumour of the liver that originates from mesenchymal cells and represents less than 2% of all primary liver tumours. It is known to be associated with several environmental and industrial carcinogens; however, in 75% of cases, aetiology remains unclear. Patients generally present with nonspecific symptoms and laboratory findings. Imaging has a limited role in the diagnosis.  We herein present a case of a 52-year-old man with a history of hepatitis B-related cirrhosis who was referred to our hospital for liver transplantation assessment. Magnetic resonance imaging (MRI) revealed two small nodular lesions of 5 and 6 mm in segment IV of the liver, categorised as Liver Imaging Reporting and Data System (LI-RADS) category 3. The patient was discussed at a multidisciplinary tumour meeting, and an MRI follow-up in three months was planned. Three months later, MRI depicted a substantial increase in the lesion size measured 8.5 cm. An ultrasound-guided tru-cut biopsy was performed, and the diagnosis of PHA was confirmed by pathology. In this report, we aim to highlight PHA's MRI features and underline this rare entity's rapid and fatal progression.

Analysis of Clinical-Radiological-Pathological Factors in FN/SFN Bethesda Category Thyroid Nodules, Contribution of FNAB Repeat, Single Center Experience.

OBJECTIVES: Follicular neoplasm/suspected follicular neoplasm (FN/FNS) Bethesda Category (BC)-4 group cases are known as the gray zone. Nodules diagnosed in cytology are excised. However, very few of these nodules are malignant. Our aim is to investigate the usability of clinical-radiological-pathological parameters to reduce unnecessary surgery. In addition, we questioned the benefit of repeating fine-needle aspiration biopsy (rFNAB) in these nodules, which is not recommended, but performed for clinical or patient-related reasons. METHODS: The files of all thyroid FNAB patients conducted in our institution between January 2014 and September 2020 were scanned in the database. In our study, 185 (5.1%) nodules with cytology results of which were classified as FN/FNS were identified among 3624 nodules that were applied FNAB during this period. Twenty-eight patients were excluded from the study group. 157 nodules belonging to 157 patients between the ages of 21 and 82 years who were operated and met the study criteria were identified from patients with these nodules. The files of all patients were scanned and the results of age, gender, ultrasonographic nodule characteristics, FNAB repeat, type of surgery, and postoperative pathology were recorded. All data were analyzed by comparing them with nodule features. SPSS 15.0 for Windows program was used for statistical analysis. RESULTS: A significant correlation was found between the incidence of malignancy and male gender and hypervascularization (p=0.017 and p=0.002, respectively). Malignancy was less in nodules larger than 2 cm (p=0.014). There was no relationship between other clinical and radiological features and malignancy. In 29 nodules with rFNAB, a significant correlation was found between malignancy and advanced age (52.9-years-old), presence of nodules smaller than 2 cm and hypervascularization (p=0.047, p=0.047, and p=0.030, respectively). CONCLUSION: We recommend careful review of patients with hypervascular, hypoechogenic, and microcalcific BC-4 nodules (male gender and older patients at greater risk). Because of the serious risk of malignancy, patients with these features should be prepared for patient management with total thyroidectomy after examination with frozen section applied to the nodule during the operation.

Evaluation of Thyroid Fine-Needle Aspiration Biopsies according to Cytological Methods and Comparison with Histopathological Diagnosis.

OBJECTIVES: In this study, we aim to compare the results of aspiration of thyroid nodules evaluated according to the Bethesda category (BC) with tissue diagnoses in the operation materials and to compare the sensitivity, specificity and accuracy rates according to cytology methods. METHODS: The previous fine-needle aspiration biopsy (FNAB) of thyroid nodules of 879 cases diagnosed histopathologically between 2010 and 2017 was examined. The FNAB results determined according to the Bethesda system were matched with tissue diagnoses, sensitivity, specificity, and accuracy rates were investigated according to cytology methods. RESULTS: Sensitivity, specificity, Positive predictive value (PPV), Negative predictive value (NPV) and accuracy rates were found in all FNAB results (in units of %; Sensitivity; 84.7, Specificity; 81.1, PPV; 74.1, NPV; 89.2, Accuracy; 82.5). All of the cytological evaluation methods of thyroid FNABs were found to be reliable and effective (Generally, the results are 80% and above). Specificity and accuracy rates were close to the general average (82.5%) in all methods. However, in cases evaluated with liquid base cytology (LBC) method and in addition to LBC or conventional smear (CS), the sensitivity rates in cases where cell block (CB) were evaluated together were higher than cases in which LBC and CS were used alone (92.6% and 91.0%). When examined statistically, there was no significant difference concerning sensitivity, specificity and accuracy rates of cytological methods (p>0.05, respectively, p=0.576, 0.065, 0.643). CONCLUSION: In cytopathology, when evaluating thyroid aspirations, it is seen that the LBC method is used instead of CS. In our study, we recommend the use of the LBC method, which seems to have the highest sensitivity (taking into account its technical advantages), instead of CS. However, we think that both CS and LBC methods should be evaluated by supporting them with cell block sections.

Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

AIMS: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. METHODS AND RESULTS: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, ß-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) ß-catenin-activated HCAs, three (6%) ß-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the ß-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the ß-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. CONCLUSION: In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that ß-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

Is Vitamin D Deficiency Associated with Chronic Lymphocytic Thyroiditis?

Objectives: Vitamin D deficiency is a very common global health problem. Evidence from recent studies focuses on the extraskeletal effects of vitamin D (Vit D) deficiency. Chronic lymphocytic thyroiditis (or Hashimoto's thyroiditis) is an autoimmune disease of the thyroid. Although there are many studies reporting that autoimmune thyroid diseases may be associated with Vitamin D deficiency, this is still a controversial issue that has not yet been proven. In this study, we aimed to appraise whether there is a relationship between lymphocytic thyroiditis diagnosed by histopathological evaluation and Vitamin D deficiency. Methods: Data of 256 patients whom were operated by a single surgeon in a single center between 2012 and 2017 and whose preoperative vitamin D tests and thyroid pathologies have been collected, were retrospectively evaluated. Due to the pathological examination, two groups were formed considering the presence of lymphocytic thyroiditis (Group 1), and the absence of lymphocytic thyroiditis (Group 2). Vitamin D deficiency was defined as the level <20 ng/mL (50 nmol/L) and Vitamin D insufficiency was defined as the level 21-29 ng/mL (525-725 nmol/L). Results: There were 108 (92F/16M) patients in Group 1, and 148 (116F/32M) patients in Group 2, and the mean age was lower in Group 1 (p=0.053). The mean vitamin D levels (16.6±15.2 vs. 14±10, p=0.409) and vitamin D deficiency rates (67.6% vs. 72.3%, p=0.416) were found similar between the Groups 1 and 2. No positive significant correlation was found between lymphocytic thyroiditis and vitamin D level or vitamin D deficiency rates. There was a positive correlation between lymphocytic thyroiditis and age, preoperative thyroid-stimulating hormone level, preoperative anti-thyroglobulin ,and anti-thyroid peroxidase levels, but no significant relationship was found with Vitamin D level. Conclusion: According to our results, lymphocytic thyroiditis was not associated with either Vitamin D deficiency or Vitamin D level.

Blind liver biopsy: a 17-year experience / Biopsia hepática a ciegas: experiencia de 17 años

ABSTRACT Objectives: Liver biopsy is the gold standard for assessing liver inflammation, necrosis and fibrosis. The aim of the study is to evaluate clinical indications and histopathological results of percutaneus liver biopsy. Materials and methods: A total of 516 children who underwent blind liver biopsy were evaluated retrospectively. Results: Blind liver biopsy was performed for chronic active hepatitis B in 50% of the cases (n=260), neonatal cholestasis in 14% (n=68), autoimmune hepatitis in 7.7% (n=40), Wilson disease in 7.3% (n=38), isolated elevation of the liver enzymes in 5% (n=26), chronic active hepatitis C in 4.2% (n=22), metabolic disease in 3.4% (n=17), malignancies in 2.2% (n=11) and the others in 3.4% (n=17). Major complications were observed in 0.19% of the cases (n=1) and minor complications such as pain at the biopsy site in 13.5% of the cases (n=70), hypotension and tachycardia in 1.9% (n=10). Conclusions: Blind liver biopsy is a safe method in diagnosing liver diseases in childhood.

RESUMEN Objetivos: La biopsia de hígado es el estándar de oro para evaluar la inflamación, necrosis y fibrosis del hígado. El objetivo del estudio es evaluar las indicaciones clínicas y los resultados histopatológicos de la biopsia hepática percutánea. Materiales y métodos: Se evaluó retrospectivamente a un total de 516 niños a los que se les realizó una biopsia hepática a ciegas. Resultados: Se realizó biopsia hepática a ciegas por hepatitis B crónica activa en el 50% de los casos (n = 260), colestasis neonatal en el 14% (n = 68), hepatitis autoinmune en el 7,7% (n = 40), enfermedad de Wilson en el 7,3%. % (n = 38), elevación aislada de las enzimas hepáticas en el 5% (n = 26), hepatitis C crónica activa en el 4,2% (n = 22), enfermedad metabólica en el 3,4% (n = 17), neoplasias en el 2,2% (n = 11) y los demás en un 3,4% (n = 17). Se observaron complicaciones mayores en el 0,19% de los casos (n = 1) y complicaciones menores como dolor en el sitio de la biopsia en el 13,5% de los casos (n = 70), hipotensión y taquicardia en el 1,9% (n = 10). Conclusiones: La biopsia hepática a ciegas es un método seguro en el diagnóstico de enfermedades hepáticas en la infancia.

Blind liver biopsy: a 17-year experience.

OBJECTIVES: Liver biopsy is the gold standard for assessing liver inflammation, necrosis and fibrosis. The aim of the study is to evaluate clinical indications and histopathological results of percutaneus liver biopsy. MATERIALS AND METHODS: A total of 516 children who underwent blind liver biopsy were evaluated retrospectively. RESULTS: Blind liver biopsy was performed for chronic active hepatitis B in 50% of the cases (n=260), neonatal cholestasis in 14% (n=68), autoimmune hepatitis in 7.7% (n=40), Wilson disease in 7.3% (n=38), isolated elevation of the liver enzymes in 5% (n=26), chronic active hepatitis C in 4.2% (n=22), metabolic disease in 3.4% (n=17), malignancies in 2.2% (n=11) and the others in 3.4% (n=17). Major complications were observed in 0.19% of the cases (n=1) and minor complications such as pain at the biopsy site in 13.5% of the cases (n=70), hypotension and tachycardia in 1.9% (n=10). CONCLUSIONS: Blind liver biopsy is a safe method in diagnosing liver diseases in childhood.

Diagnostic accuracy of different noninvasive scores for detecting advanced fibrosis in chronic hepatitis B.

OBJECTIVES: The liver biopsy is the gold standard for determining the level of fibrosis in chronic hepatitis B infection (CHBI). Nonetheless, it is possible to predict liver fibrosis through some noninvasive methods such as noninvasive scoring (NIS) of some serum biomarkers obtained from routine blood tests. We aimed to evaluate the diagnostic accuracy of nine NIS for detecting advanced fibrosis in CHBI. PATIENTS AND METHODS: We reviewed the hospital records of CHBI cases with liver biopsy between January 2011 and December 2016 retrospectively. Using Ishak scoring method, we classified fibrosis stage 1-2 as mild and 3-6 as advanced fibrosis. We calculated the NIS by considering the age, platelet count, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, platelet, and international normalized ratio values at the time of the biopsy. RESULTS: The mean age of 202 patients was 37.69± 11.33 years. In cases with advanced fibrosis, the age, gammaglutamyltransferase, and international normalized ratio values were higher and platelet count was lower (P < 0.05). Mean platelet volume was not different between the two groups (P = 0.499). The median values of γ-glutamyl peptidase-platelet ratio (GPR), FibroQ, Goteborg University Cirrhosis Index, fibrosis-4 (FIB-4), aspartate aminotransferase-platelet ratio index, age-platelet index, and King scoring were significantly higher in the advanced fibrosis group. The highest area under the curve value was in GPR [AUC = 0.731 (0.639-0.788); P = 0.000] in the receiver operating characteristic curve analysis. Cirrhosis Discriminant Score and Aspartate aminotransferase-to-alanine aminotransferase ratio tests were not valuable in detecting advanced fibrosis. FIB-4 had the highest (0.678) diagnostic accuracy rate. CONCLUSION: We found that the calculation of NIS before liver biopsy, especially GPR and FIB-4, may be useful for predicting advanced fibrosis in cases with CHBI.

Comparison of Monitor-Image and Printout-Image Methods in Ki-67 Scoring of Gastroenteropancreatic Neuroendocrine Tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are classified according to tumor grade. Ki-67 and mitotic count are the two determinants of this classification. Therefore, Ki-67 scoring becomes very important in classifying the patients accurately. Eye-balling, counting of cells through the microscope, automated image analysis systems, and manual counting of printed image are the four major scoring methods in use. The aim of this study is to show the agreement between monitor-image method (MIM) and printout-image method (PIM) of Ki-67 scoring. In our study, 120 GEP-NETs from 85 patients diagnosed between January 2005 and July 2017 were evaluated. Thirty-seven cases with either polypectomy or resection material were selected. Seven different scoring methods using either a monitor-image or a printout-image were applied for Ki-67 scoring. They are as follows: whole-PIM, 1/9-PIM, whole-MIM, 1/4-MIM, 1/6-MIM, 1/9-MIM, and 1/12-MIM. In the comparison of Ki-67 scoring methods, intraclass correlation coefficients ranging from 0.951 to 0.999 were found. The Bland-Altman analysis showed near-perfect agreement between whole-MIM and whole-PIM as well as 1/9-MIM and 1/9-PIM. The level of agreements among the other methods were sufficient too, but there was a relative decrease in the level of agreement as the area of counting becomes smaller. The average application time decreased from 373.7 to 41.7 s gradually as the scoring area becomes smaller. Our study shows that there is a remarkable agreement between the MIM and PIM used in Ki-67 scoring.

Nonneoplastic Lesions of the Pancreas: A Retrospective Analysis of 20 Cases.

OBJECTIVES: In the pancreatic lesion cases, surgery is often planned based only on imaging results and without a preoperative histological diagnosis, due to the high risk of malignancy in combination with the difficulty of invasive interventions and limited cytopathological evaluation. In this study, the records of 20 patients who had undergone a pancreatectomy procedure and who were diagnosed with nonneoplastic pancreatic lesions were retrospectively evaluated according to the clinical and histopathological findings. METHODS: A total of 122 cases of patients who underwent a pancreatectomy with suspicious lesions between 2004 and 2016 were retrospectively assessed in detail using the clinical and histopathological findings. RESULTS: Nonneoplastic lesions were observed in 20 (16%) of 122 patients who underwent a pancreatectomy. Histopathological examination revealed 11 cases of chronic pancreatitis, 1 hematoma, 1 instance of hemorrhagic necrosis secondary to trauma, 1 pseudocyst, 1 granulation tissue, 1 retention cyst, 1 bile duct cyst, 1 patient with Castleman disease, and 1 instance of fat necrosis were seen. In 1 patient, no evidence of disease was found. In addition, among the patients with chronic pancreatitis, autoimmune pancreatitis was observed in 1, adenomyoma of the ampulla of Vater was present in 1, and a pseudocyst was found in 1 patient. CONCLUSION: A clinical and histopathological analysis of nonneoplastic lesions found in pancreatectomy patients was performed.

Sarcoidosis with Hepatic Involvement: A Case Report.

Sarcoidosis is a systemic, noncaseating granulomatous disease with an unknown etiology. The liver is one of the most frequently affected organs. This case is presented to emphasize that hepatic granulomatous foci can lead to a determination of etiology in a diagnosis of sarcoidosis. A 53-year-old-female patient with complaints of fatigue and abdominal pain was admitted to the clinic of gastroenterology. The blood levels of alanine transaminase, aspartate transaminase, alkaline phosphatase and gamma-glutamyl transferase were markedly increased. The autoimmune parameters were negative. A Tru-Cut biopsy (Becton, Dickinson and Co., Franklin Lakes, NJ, USA) of the liver was performed based on the initial diagnoses of tuberculosis, lymphoma, and sarcoidosis. Histopathological evaluation revealed noncaseating granulomatous inflammation with Grade 3 macrovesicular steatosis. An investigation for hepatic sarcoidosis was recommended. The angiotensin-converting enzyme levels were 5 times higher than normal. Based on this result, the diagnosis was sarcoidosis with hepatic involvement. The treatment and follow-up of the patient continues.

Is only Thyroid Peroxidase Antibody Sufficient for Diagnosing Chronic Lymphocytic Thyroiditis?

OBJECTIVES: Recently, only anti-thyroid peroxidase (anti-TPO) has been suggested as an autoantibody in the diagnosis of chronic lymphocytic thyroiditis (CLT). In contrast, anti-thyroglobulin (anti-Tg) positivity has also been reported to be important. To evaluate this relationship more clearly, we planned to retrospectively investigate the autoantibody levels of the patients who underwent thyroid surgery for various reasons and those with CLT in postoperative pathology. METHODS: We evaluated 670 patients who underwent thyroid surgery (total/subtotal thyroidectomy) for various reasons at our hospital between January 2015 and March 2017. Patients with indications of Graves' disease, toxic multinodular goiter, and all malignancies except for thyroid papillary carcinoma (TPC) were excluded. Eighty-nine patients whose pathology findings were compatible with CLT and preoperative thyroid autoantibodies were identified enrolled in to the study. Patients with absence and presence of thyroid antibodies were included in the seronegative CLT group and seropositive CLT group, respectively. In addition, patients were divided into thyroid papillary carcinoma (TPC) and benign groups. RESULTS: According to the study criteria, 89 (83 females, six males) (mean age, 46.08±11.19 years) patients who had preoperatively identified autoantibodies were detected. Anti-TPO positivity was found in 47 (52.8%) cases, whereas anti-Tg positivity was found in 49 (55.1%). Only anti-TPO positivity was found in 18 (20.2%) cases, whereas only anti-Tg positivity was detected in 20 (22.5%). Twenty-two (24.7%) of the patients were seronegative. On comparing the seronegative and seropositive groups, seronegativity was more frequent in male patients (p=0.03). Thyroid-stimulating hormone was found to be significantly higher in the seropositive group (p=0.01). TPC was detected in 36 (40.4%) of all cases. No difference regarding age, thyroid function tests, and antibody levels was found between the benign and TPC groups. CONCLUSION: Although all of our cases were histopathologically diagnosed with CLT, serologically, 75.3% of thyroid autoimmunities could be shown when both antibodies were evaluated together. When only anti-TPO was considered, this rate decreased to 52.8%. Therefore, anti-Tg appears to be still important in showing autoimmunity. Prospective studies are needed to evaluate this relationship more clearly.

Synchronous Solid Pseudopapillary Tumor and Insulinoma in an Adolescent MEN1 Patient Presenting with Diagnostic Dilemmas.

Multiple endocrine neoplasia (MEN1) is a rare autosomal dominant disorder characterized by primary hyperparathyroidism, enteropancreatic neuroendocrine tumors, and anterior pituitary adenomas. A 16-year-old male presented to the emergency outpatient clinic with tonic convulsions. Physical examination in the postconvulsive period was unremarkable and revealed a muscular, postpubertal adolescent. Biochemical tests at admission were consistent with hyperinsulinemic hypoglycemia and remarkable for elevated levels of liver transaminases and creatine kinase. Work-up for a potential inborn error of metabolism and Doppler ultrasound for congenital portal-hepatic shunt were negative. When the patient was questioned, he reported using the anabolic steroid stanozolol to strengthen his muscles. His enzyme levels normalized after cessation of stanozolol. Hypoglycemia did not recur on diazoxide therapy. Magnetic resonance imaging showed two discrete lesions in the pancreas. Distal pancreatectomy revealed two masses 1.1 and 1.4 cm in diameter: a solid pseudopapillary tumor and an insulinoma. The patient also had asymptomatic primary hyperparathyroidism. DNA sequence analysis of the MEN1 gene in the index patient and his father and brother revealed a previously reported "pW183S" heterozygous mutation. This case further adds to the "pancreatic tumor" phenotype of MEN1 with the presence of a solid pseudopapillary tumor. This case report also confirms the need to meticulously question drug abuse in adolescents presenting to clinics with diagnostic challenges.

Helicobacter pylori is undetectable in intraductal papillary mucinous neoplasm.

BACKGROUND: About half of the world population is infected with Helicobacter pylori (H. pylori), a bacterium associated with gastric cancer and considered to be a risk factor for pancreatic ductal adenocarcinoma. Whether the bacterium is associated with intraductal papillary mucinous neoplasm, believed to be a precursor of pancreatic ductal adenocarcinoma, is unknown. The aim of this study was to investigate the presence of H. pylori DNA in tissue sections of intraductal papillary mucinous neoplasm. METHODS: The presence of H. pylori DNA was tested in a retrospective controlled study of formalin-fixed, paraffin-embedded pancreatic tissues from 24 patients who underwent surgery for intraductal papillary mucinous neoplasm. Histologically normal tissues surrounding neoplasms were used as control. H. pylori DNA was evaluated after deparaffinization, DNA extraction, and purification, and results were evaluated statistically. RESULTS: Samples were collected from 13 males and 11 females with mean age 59 years (range 44-77), and consisted of 19 cases of main-duct and three cases of branched-duct intraductal papillary mucinous neoplasm. Two patients were diagnosed with pancreatic cancer and main-duct intraductal papillary mucinous neoplasm. H. pylori DNA was not detected either in intraductal papillary mucinous neoplasm tissue, or in surrounding normal tissue. CONCLUSIONS: Although H. pylori has been implicated in pancreatic ductal adenocarcinoma, it may not play a key role in the development of intraductal papillary mucinous neoplasm.