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.

Endoscopic removal of a suprasellar dermoid cyst in a pediatric patient: a case report and review of the literature.

INTRODUCTION: Dermoid cysts (DCs) are unusual benign congenital intracranial tumors that typicallyarise in the midline and form as a result of abnormal sequestration of ectodermal cells during neural tubeformation. In all age groups, endoscopic approaches are preferable for the removal of sellar lesions. A 6-year-old girl with recurrent meningitis underwent endoscopic endonasal surgery forsellar DC. CONCLUSION: To the best of our knowledge, we present the first case of a suprasellar DC in a pediatric patient that was removed endoscopically.

Gamma-glutamyltranspeptidase in predicting sustained virological response in individuals with chronic hepatitis C.

BACKGROUND/AIMS: Serum gamma-glutamyltranspeptidase (GGT) levels often increase in chronic hepatitis C. We aimed to identify whether GGT levels can predict sustained virological response (SVR) in patients with chronic hepatitis C and to investigate other potential predictive factors associated with SVR in patients with chronic hepatitis C treated with pegylated interferon and ribavirin at a single center. METHODOLOGY: We evaluated 112 consecutive patients with histologically proven chronic hepatitis C who were treated with pegylated interferon and ribavirin. As potential predictors of SVR to combination therapy, we analyzed age, gender, body mass index, pretreatment GGT and alanine transaminase levels, diabetes mellitus, receiving of anti-viral therapy before beginning combination therapy, viral load, and liver histology by use of a multivariate logistic regression model. RESULTS: SVR to combination therapy was seen in 57.2% of the patients. Variables associated with lower rates of sustained response were liver steatosis (p=0.026), diabetes mellitus (p=0.027), receiving anti-viral therapy before beginning combination therapy (p=0.016), higher GGT levels before therapy (>50IU/mL, p<0.001), and advanced fibrosis stage (p=0.017). On logistic regression analysis, the only independent predictor of SVR was the GGT level before therapy (p=0.003). CONCLUSIONS: Low serum levels of GGT before treatment are associated with higher rates of SVR in patients with chronic hepatitis C treated with pegylated interferon and ribavirin.

Pegylated interferon alfa-2B for chronic delta hepatitis: 12 versus 24 months.

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy of pegylated interferon (PEG-IFN) alfa-2b for short (one year) and long (two years) terms of treatment for chronic hepatitis D. METHODOLOGY: Eighteen patients with chronic hepatitis D were administered PEG-IFN alfa-2b 1.5µg/kg twice weekly for 1 month, after which they were randomly assigned (2:1) to receive PEG-IFN alfa-2b 1.5µg/kg/wk for an additional 23 months (n=11; group 1) or 11 months (n=7; group 2). All patients were followed-up for 6 months after completing therapy. RESULTS: In group 1, there was no significant difference between HDV-RNA and ALT levels at follow-up compared with baseline (p=0.219 and p=0.624, respectively). However, in group 2, HDVRNA levels, but not ALT levels, were significantly lower at the end of follow-up (EOF) than at baseline (p=0.016 and p=0.237, respectively). Three patients, all in group 2, had undetectable hepatitis B surface antigen (HBsAg) at the end of followup (EOF). However, there was no patient who had undetectable HBsAg in group I (p=0.043). There were statistical differences for all 18 patients in terms of baseline levels of HDV-RNA compared to end of treatment (EOT) (p=0.021) and EOF (p=0.003). CONCLUSIONS: Extending therapy from 12 to 24 months conferred no additional advantage in terms of HDV-RNA suppression and ALT normalisation.

Orbital schwannoma with fluid-fluid levels on MRI.

A 40-year-old man presented with a progressively growing left orbital mass producing proptosis. Orbital MRI revealed a large bilobed mass that was isointense with respect to the extraocular muscles on T1-weighted images and demonstrated heterogenous contrast enhancement. T2-weighted images revealed a markedly heterogenous internal appearance with fluid-fluid levels. The mass was completely excised in one piece. Histopathologically, the encapsulated tumor consisted mostly of spindle-shaped tumor cells with elongated nuclei forming bundles without obvious mitosis. Richly cellular areas were consistent with the Antoni A pattern, and more hypocellular edematous areas were consistent with the Antoni B pattern. Hemorrhagic and cystic areas were seen within the tumor. The tumor cells stained diffusely positive with S-100 protein. Findings were consistent with the diagnosis of orbital schwannoma. Fluid-fluid levels are usually seen in some vascular and bone tumors and soft tissue lesions. Fluid-fluid levels have previously been reported to occur in intracranial but not in orbital schwannomas. This case demonstrates that orbital schwannoma can also display fluid-fluid levels on MRI, which were thought to be due to intralesional hemorrhage in this case.

Ruptured Tentorium Originating Masson Tumor.

Intravascular papillary endothelial hyperplasia (IPEH) also known as Masson's tumor, is a benign, slow growing, vascular lesion which is seen very rarely and only a few cases have been reported intracranially in the literature. It has been reported at many sites, but the posterior fossa involvement is very rare. The preoperative diagnosis is very difficult, as there is no enough cases to achieve a clear understanding about the details of its radiological findings. Differential diagnosis have to be made especially from angiosarcoma and meningioma. It is curable by total surgical removal. In this article we presented the characteristic clinical, radiological, perioperative and pathological findings in a case of IPEH in an unusual location, origin and behavior. To best of our knowledge, we presented the first case of IPEH originating from tentorium.

ATA Index: A novel score for predicting fibrosis stage in chronic viral hepatitis.

Background and Aim: This study was designed to predict the fibrosis stage with a clinical scoring system that may reduce the need for liver biopsy. Materials and Methods: The study cohort included the treatment of 430 chronic hepatitis B (CHB) and 170 chronic hepatitis C (CHC) of naive patients. The patients were divided into two groups as mild to moderate and severe fibrosis. After an index obtained in the study cohort, the index was tested in a validation cohort and compared with the FIB-4 Index. Results: The AUC of CHC index was found of 0.89 the sensitivity of 0.91 the specificity of 0.74, the positive predictive value (PPV) of 0.54 and the negative predictive value (NPV) of 0.96. The FIB-4 Index was applied to the CHC study cohort and the ATA Index Hepatitis C was found to be superior in terms of AUC (0.89-0.82), sensitivity (0.91-0.76) and NPV (0.96-0.86). The AUC of CHB Index was determined of 0.92, the sensitivity of 0.90, the specificity of 0.84, the PPV of 0.53 and the NPV of 0.98. Compared to the FIB-4 Index in CHB study cohort, the ATA Index Hepatitis B was predominant in terms of AUC (0.92-0.88), sensitivity (0.90-0.75), NPV (0.98-0.94) and PPV (0.53-0.49). Conclusion: ATA Indexes can predict the non-existence of severe fibrosis with an accuracy similar to FIB-4 Index and may reduce the need for liver biopsy.

The characteristics and clinical outcome of drug-induced liver injury: a single-center experience.

BACKGROUND AND GOALS: The aim of this cohort study was to determine the characteristics and clinical outcome of 170 patients with drug-induced liver injury (DILI) in a single center. STUDY: Between January 2001 and June 2007, a total of 170 individuals who were diagnosed with DILI were retrospectively analyzed. The median follow-up period was 110.0 days. RESULTS: During the study period, a total of 5471 new patients were assessed for liver test abnormalities. Of those, 170 patients (3.1%) fulfilled the criteria of DILI. A total of 83 different drugs were considered to be related to the hepatotoxicity; a single drug was suspected in 57.6% of individuals. The median interval between the suspicious drug intake and DILI recognition was 15.0 days. Hepatocellular pattern was observed in 50.0% of patients with a mean alanine aminotransferase level of 952.2+/-907.0 U/L. The main causative group of drugs was antibiotics. Sixty-two patients required hospitalization; acute liver failure developed in 14 (8.2%), chronicity was observed in 19 (11.2%), and 7 died (4.1%). Overall, complete recovery occurred in 82% of patients. The presence of jaundice on admission and shorter interval period between drug intake and DILI recognition were identified as risk factors for the development of acute liver failure. CONCLUSIONS: DILI is an important cause of liver test abnormalities in outpatient clinics, and antibiotics represent the most common drug group. Overall, complete recovery after the withdrawal of the suspicious drug occurred in the majority of patients, but DILI may progress to acute liver failure, chronicity, and death.

Acute seronegative autoimmune hepatitis.

A 52-year-old woman who had some atypical features of autoimmune hepatitis is described here. Acute presentation, negativity of all autoimmune markers and the features of multiple acinar confluent necrosis were interesting findings. She had a complete resolution under standart immunosuppressive therapy.

Therapy response and outcome of overlap syndromes: autoimmune hepatitis and primary biliary cirrhosis compared to autoimmune hepatitis and autoimmune cholangitis.

BACKGROUND/AIMS: We have assessed two different overlap syndrome groups in patients with AIH-PBC and AIH-AIC, with respect to therapy response and outcome. METHODOLOGY: In this retrospective, non-randomized study, a total of 22 overlap cases were collected, 12 of those had a simultaneous form of AIH-PBC and 10 of those with AIH-AIC. Two groups were compared in terms of clinical, biochemical, immunological, histological features and response to treatment. The mean follow-up time was 31.7 +/- 11.0 mo in AIH-PBC and 41.1 +/- 29.6 mo in AIH-AIC, respectively. RESULTS: The clinical and laboratory characteristics at presentation were not significantly different between the two groups, except a higher serum IgM level and lower AIH score in AIH-PBC group compared to AIH-AIC group (p < 0.05). First-line treatment was UDCA alone in 3 of AIH-PBC group and combination of UDCA and immunsuppressives in the remaining AIH-PBC (n = 9) and in all of the AIH-AIC (n = 10). During follow-up, only one of 10 patients in IIH-AIC group, but six of 12 patients in AIH-PBC group progressed to liver failure. So, complete remission was significantly higher in the AIH-AIC than in the AIH-PBC group ( % 90 vs % 50, p = 0.045). CONCLUSION: To our results, in cases of AIH-PBC/AIC overlap, patients with high AIH score and negative AMA should be treated with combined therapy of corticosteroids and UDCA. However, patients with low AIH score and positive AMA should use UDCA firstly, if no response, the addition of corticosteroids should be considered with close monitoring. In this cohort, the prognosis of AIH-PBC overlap was much worse than that of AIH-AIC.

Efficacy of combined interferon alpha and long-term lamivudine therapy in children with chronic hepatitis B.

The aim of this study was to evaluate the efficacy of interferon alpha (IFN-alpha) and long-term lamivudine therapy in children with chronic hepatitis B and to determine the optimal duration of lamivudine therapy. Thirty-eight HBeAg-positive children simultaneously received IFN-alpha2a 5 MU/m2 to 10 MU/m2 for six months and lamivudine (4 mg/kg/day). Lamivudine was administered until anti-HBe seroconversion and was continued for six months in responders. During the five-year study period, we evaluated the efficacy of treatment, occurrence of YMDD mutants and adverse effects. During the study period, alanine aminotransferase (ALT) normalization, clearance of hepatitis B virus (HBV) DNA, HBeAg/anti-HBeAb, HBsAg/anti-HBsAb seroconversion, and histological response were noted in 27 (71.1%), 14 (36.8%), 13 (34.2%), 2 (5.2%) and 10 (47.9%) patients, respectively. Complete response was determined in 34.2% (13/38), and in 69.2% of these responders, response was achieved within 18 months. Breakthrough and YMDD mutant rates were 65.8% and 55.2%, respectively. Breakthrough time was a median 24 months and was associated with low baseline ALT level (p < 0.01). In conclusion, although lamivudine was used for a longer period, the response rate was not higher than in previous reports. We suggest that 18 months' duration of lamivudine treatment is sufficient for combination therapy.

Optic nerve biopsy via a medial transconjunctival orbitotomy approach in the diagnosis of optic nerve and sheath tumors.

PURPOSE: To evaluate the role of optic nerve biopsy in the diagnosis and management of optic nerve and sheath tumors. METHODS: Seven patients with progressive optic nerve and sheath tumors for whom treatment was deemed necessary were included in this study. Optic nerve biopsy via a medial transconjunctival orbitotomy approach was performed in all patients RESULTS: There were no complications related to the surgical procedure. Histopathological examination revealed that five patients had juvenile pilocytic astrocytoma (JPA) and two patients had optic nerve sheath meningioma (ONSM). All patients received external beam radiotherapy (EBRT). CONCLUSIONS: Many other benign and malignant optic nerve and sheath tumors have imaging features similar to those seen in JPA and ONSM. Therefore, it is important to establish histopathologic diagnosis before embarking on treatment. Furthermore, tissue diagnosis is required prior to EBRT in many institutions because of concerns about medicolegal liability. Optic nerve biopsy via a transconjunctival orbitotomy procedure in seven patients yielded histopathologic confirmation of the existing pathology and was not associated with any complications in this series.

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.

Effects of adipose derived stromal vascular fraction on diabetic neuropathy: an experimental study.

The stromal vascular fraction (SVF) obtained from inguinal adipose tissue was injected into the sciatic nerve region in diabetic rats. The effects of the SVF on the sciatic nerve and functional, electrophysiological and histopathological changes were examined in this study. Rats were divided into five groups; a non-diabetic control group, and four diabetic groups. In the first diabetic rat group, the SVF was obtained from inguinal adipose tissue. The remaining diabetic groups included a sham control group, a phosphate-buffered saline (PBS) injection group and an SVF injection group. Injections were made into the sciatic nerve region. Electromyography and walking track analyses were conducted on all groups at the beginning of the experiment. Diabetes was induced via a single dose of streptozotocin. Walking track analysis and electromyography measurements were repeated in week 8. SVF or PBS was injected into the right sciatic nerve region on week 8 of experiment group rats. Walking track analysis and electromyography were repeated in week 12 and all sciatic nerves were examined histopathologically. In the diabetic SVF group, the sciatic functional index calculated from walking track analysis in week 12 was better than week 8. Additionally, the myelin sheaths of the right sciatic nerve were thicker and more uniform and the nerve fibers were thicker than those of the left, untreated sciatic nerve. No statistical differences were detected in electromyographic measurements. The adipose-derived SVF may be beneficial for nerve regeneration in diabetic neuropathy.

The Prognostic Roles of the Ki-67 Proliferation Index, P53 Expression, Mitotic Index, and Radiological Tumor Invasion in Pituitary Adenomas.

The fourth edition of the World Health Organization (WHO) classification of pituitary tumors recommended evaluation of tumor proliferation and invasion to identify aggressiveness. We aimed to assess the prognostic roles of the Ki-67 proliferation index, mitotic index, P53 expression, and cavernous sinus invasion in pituitary adenomas (PAs). Among the 601 patients who underwent transnasal/transsphenoidal adenomectomy from 2001 to 2016, 101 patients (16.8%) who had tumors with a high (≥ 3%) Ki-67 index (group A) and a control group consisting of 43 patients with a low (< 3%) Ki 67 index who were matched for age, gender, and tumor type were included. Mitotic index and P53 expressions were evaluated. Patient characteristics, histopathology reports, pre/postoperative magnetic resonance imaging (MRI), and follow-up data were assessed retrospectively. The frequency of macroadenomas and mean tumor size were greater in group A when compared to group B (67.4 vs. 94.1%, p< 0.01 and 25 ± 10.6 vs. 18 ± 11 mm, p< 0.01, respectively). Invasion to cavernous sinus was found in 53 (36.8%) patients and was more frequent in group A (p<0.01). The mean number of surgery was higher in group A than group B (p< 0.05). The mean follow-up period was 46.6 ± 34 months. The postoperative MRIs and follow-up data for at least 24 months were available in 117 patients. Recurrence risk was higher in group A than group B (p = 0.03). Tumors with high Ki-67 proliferation index were grouped as 3-5, 6-10, 11-15, and > 15%. The risk of recurrence was not different between groups of high Ki-67 index. The optimal cutoff point of the Ki-67 proliferation index that predicted recurrence was 2.5% with 84.6% sensitivity and 47.4% specificity. The cavernous sinus invasion on MRI was associated with recurrence (p = 0.03). Tumor size and recurrence risk were not associated with P53 expression. High P53 expression was related with cavernous sinus invasion (p = 0.03). The mitotic index was not associated with recurrence risk and tumor invasion. Recurrence risk was higher in tumors with ≥ 2 histopathological atypia criteria (p = 0.01). High Ki-67 index with a 2.5% cutoff point and cavernous sinus invasion on MRI are reliable markers for predicting recurrence in PAs. Recurrence risk is also higher in tumors with two histopathological aggressiveness criteria. Strict follow-up and more aggressive treatment approaches may be necessary for invasive-proliferative PAs.

Multiple pilomatrixomas affecting the eyelid and face.

A 3-year-old girl presented with a right upper eyelid mass. The lesion had a reddish appearance, was firm to palpation, and was fixed to underlying tissues. Fourteen months after the lesion was excised, a similar lesion was discovered on the left side of the nose and was also excised. Histopathologic examination of the excised tumors revealed variable basophilic hair matrix cells and sheets of nonviable eosinophilic shadow cells. Foci of dystrophic calcification were also seen in the necrotic tumor areas. The histopathologic findings were found to be consistent with pilomatrixoma. Results of limited clinical work-up of the child for Gardner's syndrome, sarcoidosis, and myotonic dystrophy were negative. Multiple periocular and facial pilomatrixomas can occur in children in the clinical absence of myotonic dystrophy, Gardner's syndrome, and sarcoidosis.

An unusual presentation of Wilson's disease in childhood: nodular fatty infiltration in liver.

Wilson's disease is a rare inherited disorder characterized by progressive accumulation of copper in the body tissues. Liver and brain are the most commonly involved organs and the disease is presented predominantly by hepatic manifestations in childhood. Histopathological findings of hepatic involvement may vary from steatosis to end stage cirrhosis. Although diffuse fatty infiltration is a typical finding of Wilson's disease, it can very rarely present in nodular pattern. We report the first case with Wilson's disease who presented with nodular fatty infiltration in the liver in childhood.

Do the Well Known Prognostic Parameters in Pancreatic Ductal Adenocarcinoma Really Reflect Survival?

OBJECTIVE: Pancreatic ductal adenocarcinoma is an aggressive tumor with short survival. In this study we aimed to investigate the effect of well-known prognostic parameters on survival in these tumors. MATERIAL AND METHOD: A total of 56 pancreatic ductal adenocarcinoma cases diagnosed between 2005 and 2014 were included in the study. Survival data were obtained and histopathological parameters were re-evaluated in each patient. RESULTS: Tumor size (p=0.029), mitotic count (p=0.030), lymph node metastasis (p=0.003), metastatic lymph node ratio (p < 0.001) and ampullary invasion (p=0.044) had a statistically significant relationship with survival. However, there was no relationship between survival and tumor grade, lymphovascular and perineural invasion, and peripancreatic soft tissue invasion. CONCLUSION: Our results showed that existent 2010 WHO pancreatic ductal adenocarcinoma grading parameters excluding mitotic count are subjective and not applicable. Considering that almost all of the tumors in our series were larger than 2 cm, we think that the 2 cm cut-off in tumor size is insufficient to make the tumor stage pT2. Peripancreatic soft tissue invasion, which is a common finding in pancreatic ductal adenocarcinoma, should also not be assessed like adjacent tissue invasion and make the tumor reach pT3 stage independent of tumor size. It is clear that the existent WHO tumor grading and pT staging parameters need to be revised and the mitotic count, which correlates with survival, should be presented in pathology reports.

Necrotic intraocular retinoblastoma associated with orbital cellulitis.

Orbital cellulitis associated with retinoblastoma is uncommon and is characterized by noninfectious inflammation of the periorbital structures. The underlying mechanism is thought to be necrosis of the intraocular tumor, leading to intraocular and periorbital inflammation. We report 2 retinoblastoma patients who presented with an orbital cellulitis-like picture and discuss clinical characteristics, histopathologic features, and treatment.