The Role of 18F-FDG PET/MRI in the Assessment of Primary Intrahepatic Neoplasms.

RATIONALE AND OBJECTIVES: To evaluate the results of 18F-FDG PET/MRI in relation to the histopathologic subtypes and histologic grades of mass-forming primary intrahepatic neoplasms. MATERIALS AND METHODS: We retrospectively evaluated 18F-FDG positron emission tomography/magnetic resonance imaging (PET/MRI) results for 39 patients with histopathologically confirmed primary hepatic neoplasms, 15 with mass-forming intrahepatic cholangiocarcinoma (ICC) and 24 with hepatocellular carcinoma (HCC). The apparent diffusion coefficient (ADC) and standardized uptake value (SUV) were analyzed in relation to the histopathologic diagnosis and histologic grade, including calculating the sensitivity and specificity of the imaging findings. RESULTS: The median SUV of ICC (6.0 [interquartile range, 5-10]) was significantly higher than that of HCC (4.0 [2.62-6.50]) (p = 0.002). An area under the curve (AUC) of 0.79 (95% confidence interval 0.649-0.932) had a sensitivity of 86.7% and a specificity of 67% at the best cut-off SUV of 4.41 to differentiate between ICC and HCC. ADC values did not differ significantly between HCCs and ICCs (p = 0.283). Both SUV and ADC values differed significantly between low-grade (well- and moderately differentiated) and high-grade (poorly differentiated) HCCs. Combining ADC and SUV further improved differentiation of low- from high-grade HCCs to a significant level (0.929). The SUV did not differ significantly between ICC histologic grades (p = 0.280), while the ADC differed significantly only between well and poorly differentiated ICCs (p = 0.004). CONCLUSION: Assessing primary hepatic neoplasms with 18F-Fluorodeoxyglucose PET/MRI may help to predict tumor grade and differentiate between types of intrahepatic neoplasms.

Value of Intravoxel Incoherent Motion for Hepatocellular Carcinoma Grading.

BACKGROUND: To evaluate the diagnostic accuracy of intravoxel incoherent motion (IVIM) parameters in estimation of hepatocellular carcinoma (HCC) grading. MATERIALS AND METHODS: Twenty-nine patients with histopathologically diagnosed as 42 HCC at explant were included in this retrospective study. All patients were examined by 1.5T magnetic resonance imaging with the use of 4-channel phased array body coil. In addition to routine pre- and postcontrast sequences, IVIM (16 different b factors varying from 0 to 1300 s/mm2) and conventional diffusion-weighted imaging (3 different b factors of 50, 400, 800 s/mm2) were obtained with single-shot echo planar spin echo sequence. Apparent diffusion coefficient (ADC) and IVIM parameters including mean D (true diffusion coefficient), D* (pseudo-diffusion coefficient associated with blood flow), and f (perfusion fraction) values were calculated. Histopathologically, HCC was classified as low (grade 1, 2) and high (grade 3, 4) grade in accordance with the Edmondson-Steiner score. Quantitatively, ADC, D, D*, and f values were compared between the low- and high-grade groups by Student t test. The relationship between the parameters and histologic grade was analyzed using the Spearman's correlation test. To evaluate the diagnostic performance of the parameters, receiver operating characteristic analysis was performed. RESULTS: High-grade HCCs had significantly lower ADC and D values than low grade groups (P = .005 and P = .026, retrospectively); ADC and D values were inversely correlated with tumor grade (r = -0.519, P = .011, r = -0.510, P = .026, respectively). High-grade HCCs had significantly higher f values when compared with the low-grade group (P = .005). The f values were positively correlated with tumor grade (r = 0.548, P = .007). The best discriminative parameter was f value. Cut-off value of 32% of f values showed sensitivity of 75.6% and a specificity of 73.5%. CONCLUSION: ADC values and IVIM parameters such as f values appear to reflect the grade of HCCs.

Body Mass Index and Unenhanced CT as a Predictor of Hepatic Steatosis in Potential Liver Donors.

BACKGROUND: In living-donor liver transplantation, donor hepatic steatosis is crucial for both the donor and the recipient. Body mass index (BMI) and the unenhanced computed tomography liver attenuation index (CT LAI) are noninvasive methods to predict hepatic steatosis in living-donor liver candidates. AIM: To analyze the diagnostic accuracy of CT LAI in conjunction with different BMI values for macrovesicular steatosis in living-donor liver candidates. METHODS: A total of 264 potential liver donors were included. The diagnostic accuracy of 2 CT LAI cut-offs and 3 BMI cut-off values for the assessment of hepatic steatosis ≥15% and ≤5% was determined. RESULTS: Using CT LAI, the area under the receiver operating characteristic curve was 0.97 (95% CI = 0.89-0.99) for hepatic steatosis ≥15% in donors with BMI <25 kg/m2. For detecting hepatic steatosis ≥15%, a CT LAI ≤0 had specificities of 100%, 76.2%, and 55.6% and positive predictive values of 100%, 95.5%, and 93.5% for patients with BMI values <25 kg/m2, 25 to 29.9 kg/m2, and ≥30 kg/m2, respectively. According to logistic regression analyses, only CT LAI ≤0 was found to be independently associated with hepatic steatosis ≥15%. CONCLUSIONS: In donors with BMI <30 kg/m2 and a CT LAI value >6, liver biopsy might be avoided. Biopsy may be reserved solely for donors with CT LAI value >0 and BMI ≥30 kg/m2 as the diagnostic accuracy of computed tomography for predicting hepatic steatosis decreases with increasing BMI.

Predictive and prognostic significance of p27, Akt, PTEN and PI3K expression in HER2-positive metastatic breast cancer.

BACKGROUND: The phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2- overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosis and resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast cancer (MBC), retrospectively. MATERIALS AND METHODS: Fifty-four HER2- positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group. All of the patient's breast tissue samples were examined for p27 and Akt expression. In addition, twenty-five patients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographic features, tumor characteristics, response to trastuzumab-based treatment and survival outcomes were analyzed. RESULTS: p27, Akt, PTEN and PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively. Nomne were significantly associated with response to trastuzumab and time to progression (TTP). A trend toward statistical significance for longer overall survival (OS) was found for PTEN-positive patients (p=0.058); there was no significant relationship between the other immunohistochemical variables and OS. When we analyzed groups regarding co-expression, the PTEN-negative/Akt-negative group had a significantly lower objective response rate (ORR) (20% vs 80%, p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negative groups had significantly lower median OS compared to other patients (26.4 months vs 76.1 months, p=0.005 and 25.6 months vs 52.0 months, p=0.007, respectively). CONCLUSIONS: p27, Akt, PTEN and PI3K expression is not statistically significantly associated with ORR, TTP and OS, individually. However, the combined evaluation of p27, Akt and PTEN could be helpful to predict the response to trastuzumab-based therapy and prognosis in HER2-positive MBC.

Emerin expression in well differentiated epithelial lesions of thyroid: implications in papillary thyroid carcinoma diagnosis and predicting malignant behavior.

Recently, it has been reported that identifying nuclear membrane irregularities with anti-emerin antibody is useful for papillary thyroid carcinoma diagnosis. However, literature regarding the significance of emerin immunohistochemistry in thyroid is limited. We evaluated the diagnostic accuracy of the well-established nuclear alterations, nuclear protrusions and recently described nuclear shapes (garlands and star-like shapes) with emerin immunohistochemistry and hematoxylin- eosin stain in thyroid lesions. We further evaluated the diagnostic accuracy measures of tissue microarrays evaluated with both stains, to detect whether emerin immunohistochemistry improves the diagnostic accuracy for papillary thyroid carcinoma. For papillary thyroid carcinoma, pseudo- inclusions were best performers with emerin (diagnostic accuracy: 0.91), whereas with hematoxylin- eosin diagnostic accuracy of grooves was the highest (0.92). For follicular variant of papillary thyroid carcinoma, with both stains, predominately oval nuclear shape had the best diagnostic performance (diagnostic accuracy: 0.95). Nuclear protrusions were poor identifiers for papillary thyroid carcinoma. However, with emerin immunohistochemistry, they could successfully identify malignancy in 83% of the cases. Using emerin immunohistochemistry, in addition to hematoxylin- eosin improved the diagnostic accuracy for papillary thyroid carcinoma when compared to hematoxylin- eosin evaluation only (sensitivity: 0.70 vs 0.86, negative predictive value: 0.81 vs. 0.94, diagnostic accuracy: 0.87 vs. 0.94). Consistent with the previous literature, our findings indicate that emerin immunohistochemistry may be used as an adjunct diagnostic method to identify papillary thyroid carcinoma. Additionally, we suggest that nuclear protrusions detected with emerin imunohistochemistry may be used as indicators of malignant behavior in small tissue samples of thyroid.

Patients with epithelial cell abnormality in PAP smears: correlation of results with follow-up smears and cervical biopsies.

OBJECTIVE: Cervical carcinoma has been included in the preventable diseases category ever since the use of cervical cytology in routine practice. The Pap test is an efficient screening test. We aimed to compare the cervical cytology diagnosis with biopsy and smear follow up results in our institution. MATERIAL AND METHOD: We aimed to compare the diagnosis of cytology material examined in our institution during the 2009-2012 period with their biopsy and smear follow ups. The diagnoses were compared with the follow up smears and/or cervical biopsies. RESULTS: 13610 Pap tests were examined during September 2009-July 2012. Among these cases, there were 370 atypical squamous cells of undetermined significance (ASCUS), 29 atypical squamous cells-high grade intraepithelial lesions cannot be excluded (ASC-H), 155 low grade squamous intraepithelial lesion (LSIL), 33 high grade squamous intraepithelial lesion (HSIL), and 5 atypical glandular cell (AGC) diagnoses. The ratio of atypical squamous cell (ASCUS and ASC-H) to squamous intraepithelial lesions was 2.12. Squamous intraepithelial lesion was verified in 47 of 91 ASCUS cases. Among patients who had a cervical biopsy, 52 of 64 LSIL cases and all of the 21 HSIL cases had biopsy-proven SIL. CONCLUSION: Atypical squamous cell (ASC) is the most common diagnosis in abnormal cervical cytology. As it is indefinite, ASC is used as a quality assurance parameter and the aim is to decrease its use. As the ratio of epithelial cell abnormality is variable in different populations, the ASC/SIL is a more definite variable to be used for quality assurance. The efficiency in clinical use of the cervical cytology screening test is determined by biopsy verification. Our epithelial cell abnormality, ASC/SIL ratio and cytology-histology correlation values were parallel to the literature, proving that the methods are used reliably at our institution.

Serrated polyps of the colon: how reproducible is their classification?

For several years, the lack of consensus on definition, nomenclature, natural history, and biology of serrated polyps (SPs) of the colon has created considerable confusion among pathologists. According to the latest WHO classification, the family of SPs comprises hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The term SSA/P with dysplasia has replaced the category of mixed hyperplastic/adenomatous polyps (MPs). The present study aimed to evaluate the reproducibility of the diagnosis of SPs based on currently available diagnostic criteria and interactive consensus development. In an initial round, H&E slides of 70 cases of SPs were circulated among participating pathologists across Europe. This round was followed by a consensus discussion on diagnostic criteria. A second round was performed on the same 70 cases using the revised criteria and definitions according to the recent WHO classification. Data were evaluated for inter-observer agreement using Kappa statistics. In the initial round, for the total of 70 cases, a fair overall kappa value of 0.318 was reached, while in the second round overall kappa value improved to moderate (kappa = 0.557; p < 0.001). Overall kappa values for each diagnostic category also significantly improved in the final round, reaching 0.977 for HP, 0.912 for SSA/P, and 0.845 for TSA (p < 0.001). The diagnostic reproducibility of SPs improves when strictly defined, standardized diagnostic criteria adopted by consensus are applied.

AFP level and histologic differentiation predict the survival of patients with liver transplantation for hepatocellular carcinoma.

BACKGROUND: In liver transplantation or resection for hepatocellular carcinoma (HCC), patient selection depends on morphological features. In patients with HCC, we performed a clinicopathological analysis of risk factors that affected survival after liver transplantation. METHODS: In 389 liver transplantations performed from 2004 to 2010, 102 were for HCC patients. Data were collected retrospectively from the Organ Transplantation Center Database. Variables were as follows: age, gender, preoperative alpha-fetoprotein (AFP) levels, Child-Pugh and MELD scores, prognostic staging criteria (Milan and UCSF), etiology, number of tumors, the largest tumor size, total tumor size, multifocality, intrahepatic portal vein tumor thrombosis, bilobarity, and histological differentiation. RESULTS: One hundred and two patients were evaluated. The 5-year overall survival rate was 56.5%. According to the UCSF criteria, 63% of the patients were within and 37% were beyond UCSF (P=0.03). Ten patients were excluded (one with fibrolamellary HCC and 9 because of early postoperative death without HCC recurrence), and 92 patients were assessed. The mean age of the patients was 56.5+/-6.9 years. Sixty-two patients underwent living donor liver transplantations. The mean follow-up time was 29.4+/-22.6 months. Fifteen patients (16.3%) died in the follow-up period due to HCC recurrence. Univariate analysis showed that AFP level, intrahepatic portal vein tumor thrombosis, histologic differentiation and UCSF criteria were significant factors related to survival and tumor recurrence.The 5-year estimated overall survival rate was 62.2% in all patients. According to the UCSF criteria, and the 5-year overall survival rate was 66.7% within and 52.7% beyond the criteria (P=0.04). Multivariate analysis showed that AFP level and poor differentiation were independent factors. CONCLUSIONS: For proper patient selection in liver transplantation for HCC, prognostic criteria related to tumor biology (especially AFP level and histological differentiation) should be considered. Poor differentiation and higher AFP levels are indicators of poor prognosis after liver transplantation.

Living-donor liver transplant in 3 patients with Budd-Chiari syndrome: case report.

Budd-Chiari syndrome is a rare but life-threatening disorder characterized by obstruction of the hepatic venous outflow. Treatment depends on the underlying cause, the location, and extent of the obstruction, and the functional capacity of the liver. A stepwise therapeutic approach is commonly accepted. When all other therapy options are unsuccessful, or in case of end-stage liver disease, transplant should be considered. We present case reports of 3 patients with Budd-Chiari syndrome who underwent living-donor liver transplant. Characteristic features of Budd-Chiari syndrome, diagnostic and therapeutic interventions, complications, and overall outcomes are discussed. We believe that when a deceased donor graft is unavailable, a living-donor liver transplant can be a safe option for patients with end-stage liver disease associated with Budd-Chiari syndrome.

Xanthogranulomatous sialadenitis clinically mimicking a malignancy: case report and review of the literature.

BACKGROUND: Xanthogranulomatous tissue reaction is a well-documented process that is most common in kidney. There are other uncommon sites being documented as case reports in the literature. We would like to describe the clinicopathologic findings in a case of xanthogranulomatous sialadenitis that involved the parotid gland, which was clinically thought to be a tumoral mass, and compare it with the 4 previously reported cases. CASE REPORT: A 52-year-old man presented with a left parotid mass. Fine needle aspiration biopsy was consistent with Warthin's tumor. The mass lesion was excised. DISCUSSION: The lesion measured 2.5 × 1.5 × 1.5 cm. Microscopic examination revealed sheets of foamy macrophages centrally admixed with neutrophils, eosinophils, lymphocytes, plasma cells and scattered giant cells indicating a xanthogranulomatous reaction. As a conclusion xanthogranulomatous tissue reaction can mimic neoplasms.

General evaluation of hepatectomy and hepatocellular carcinoma cases.

OBJECTIVE: Although the clinical and histopathological findings of hepatocellular carcinoma are well described, there are few national studies. In this study, we aimed to investigate the relationship between these findings in total or partial hepatectomy specimens in our series. MATERIAL AND METHOD: We first collected 190 cases of total or partial hepatectomies performed because of hepatocellular carcinoma, cirrhosis or other disorders from the archives of Pathology. After re-examining the histopathological and clinical features such as age, gender and etiology, the relationship between them and serology results were statistically analyzed using the chi square and Multiple Comparison Tests. RESULTS: Among 190 cases, there were 168 (88.5%) total and 18 (9.5%) partial hepatectomies and 4 (2%) tumorectomy or metastasectomy cases. After gross and microscopic examination, 170 (89.5%) cases had a diagnosis of cirrhosis, 85 (44.7%) hepatocellular carcinoma, 3 parasitic cyst, 7 metastasis, 1 hepatoblastoma, 1 hepatocellular adenoma, 2 cholangiocarcinoma, 2 Budd Chiari Syndrome, 1 focal nodular hyperplasia, 1 cavernous hemangioma, and 2 acute fulminant hepatitis. Among the hepatocellular carcinoma cases, 53 had Hepatitis B virus, 15 Hepatitis C virus , 3 Hepatitis B virus and Hepatitis C virus, and 3 Hepatitis B virus and Hepatitis delta virus etiology, while 6 were alcoholic and 4 were due to other causes. Among cirrhosis patients, 84 (49.4%) had hepatocellular carcinoma. The male to female ratio of hepatocellular carcinoma cases was 74/11. The mean age was 55 and the median age 56.7. CONCLUSION: The results of this study demonstrated that the most common hepatic disorder was cirrhosis due to Hepatitis B virus in the hepatectomy specimens of our series that mostly consisted of total hepatectomies performed for transplantation where 50% had hepatocellular carcinoma.