Clinicopathological and molecular analyses of uterine carcinosarcomas using next-generation sequencing: A single-center experience.

Background: Uterine carcinosarcomas (UCS) constitute 3-4% of all uterine malignancies and 16% of deaths caused due to uterine neoplasms. Aim: In this study, we aimed to perform DNA-based mutation analysis in 12 genes (KRAS, NRAS, EGFR, C-KIT, BRAF, PDGFRA, ALK, ERBB2, ERBB3, ESR1, RAF1, PIK3CA) to determine the molecular subtypes of UCS using next-generation sequencing (NGS) in patients with aggressive UCS and poor prognosis. We aimed to compare the results of our analysis with clinicopathological data to contribute to the development of targeted therapy approaches related to the molecular changes of UCS. Materials and Methods: In this study, we included 12 cases diagnosed with uterine carcinosarcomas and examined the changes in oncogenes that play a role in UCS pathogenesis. For the analysis of mutation, the clinicopathological data were compared with the variations in the DNA-based gene panel consisting of 12 genes and 1237 variants in the UCS using the NGS method. Results: EGFR mutation was found in 91.7% of the cases, mutation in 41.7%, PDGFRA mutation in 25%, KRAS and PIK3CA mutation in 16.7%, and C-KIT mutation in 8.3% of the cases. Although no statistical significance was found between the detected mutation and clinicopathological data, it was concluded that PDGFRA mutation might be associated with advanced-stage disease development. Conclusion: This study's findings regarding different molecular types of UCS and information on oncogenesis of UCS can provide inferences for targeted therapies in the future by identifying targetable mutations representing early oncogenic events and thereby contribute toward further studies on this subject.

Indomethacin-induced gastric damage in rats and the protective effect of donkey milk.

INTRODUCTION: Indomethacin is an anti-inflammatory drug with clearly known side effects on gastric mucosa. New treatment and side effect prevention methods are being studied. Donkey milk, as a nutritional support, has recently come into the spotlight with its anti-oxidant features, high antibody content and low allergenic properties. In this study, we investigated donkey milk's possible protective effect against acute gastric mucosal damage by indomethacin. MATERIAL AND METHODS: Four groups, each composed of 8 rats, were created. Rats in the first and third groups were fed with standard rat chow, while those in the second and fourth groups were additionally fed with 25 mg/kg of donkey milk per day via nasogastric gavage. On the 11th day gastric mucosal damage was induced by oral administration of 30 mg/kg of indomethacin to the rats in groups 3 and 4. Six h later all rats were sacrificed and their stomachs were removed for macroscopic and microscopic evaluation as well as biochemical examination of glutathione (GSH) and malondialdehyde (MDA) levels. Tumor necrosis factor-α (TNF-α) expression in the gastric mucosa was evaluated immunohistochemically. RESULTS: In the donkey milk-indomethacin group, total area of erosion and degree of linear ulceration were significantly lower than in the standard food-indomethacin group (p < 0.05). Also, GSH levels were increased and MDA levels were decreased significantly in this group. Tumor necrosis factor-α expression was more prevalent and stronger in the gastritis group, while lower expression was observed in the donkey milk group. CONCLUSIONS: Donkey milk was observed to have significant protective effects against gastric damage induced by indomethacin.

Survivin expression, HPV positivity and microvessel density in oropharyngeal carcinomas and relationship with survival time.

INTRODUCTION: Among head and neck cancers, those of the oral cavity and oropharynx are the second most prevalent following the larynx. This study aimed to research immunohistochemical expression of survivin, HPV positivity and microvessel density in tumors and their relationships with prognosis. MATERIAL AND METHODS: Pathological materials and demographic properties of 46 patients were retrospectively evaluated. Survivin, HPV and CD34 (for microvessel density evaluation) antibodies were applied tumoral tissues. Survival times, clinical stage and differentiation were evaluated. RESULTS: In univariate analysis, we observed that survivin, microvessel density and stage were significantly associated with survival time (p < 0.05). In multivariate analysis, only survivin and microvessel density were associated with survival time (p < 0.05). But we did not find significant correlation between neither tumor differentiation nor HPV positivity and survival (p > 0.05). CONCLUSIONS: Survivin levels and microvessel density were found to be effective prognostic factors and were related to survival in oral cavity and oropharyngeal cancers. Treatments targeting survivin expression and angiogenesis might be employed against these tumor groups.

Follicular morphological characteristics may be associated with invasion in follicular thyroid neoplasms with papillary-like nuclear features.

The newly proposed nomenclature and diagnostic criteria for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could improve the consistency and accuracy of diagnosing this entity. Diagnosis of NIFTP requires evaluation of the complete tumor border or capsule. The presence of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear features has been recently discussed by many authors. In this study, we examined the predictive value and association of follicular morphological characteristics with the tumor invasion. In addition, we analyzed the association between tumor encapsulation and molecular profile in EFVPTC/NIFTP cases. A total of 106 cases of FVPTC were included in the study. The tumors were grouped based on the presence of tumor capsule and characteristics of tumor border, as 1) completely encapsulated tumors without invasion, 2) encapsulated tumors with invasion, 3) infiltrative tumors without a capsule. Clinicopathological features, histomorphological features [nuclear criteria, minor diagnostic features, follicles oriented perpendicular to tumor border/capsule (FOPBC)] and molecular alterations in BRAF, NRAS, and KRAS genes were evaluated. FOPBC were significantly more frequently seen in encapsulated tumors with invasion (p = 0.008). The nuclear features were not associated with the presence of encapsulation and characteristics of tumor border. BRAF mutation was more frequent in infiltrative tumors, while NRAS mutation was more frequent in encapsulated tumors, but the results were not statistically significant (p = 0.917). In conclusion, FOPBC histomorphological feature may be associated with tumor invasion in EFVPTC/NIFTP. Additionally, BRAF/KRAS/NRAS mutation analysis may prevent inadequate treatment in these patients.

TERT Expression in Pituitary Adenomas.

OBJECTIVE: Although pituitary adenomas have benign histomorphological features, some of them may present in an aggressive manner. To predict the behaviour of these tumours, telomerase reverse transcriptase (TERT) activity in pituitary adenomas has been the subject of a few studies with contradictory results. This study aims to investigate whether immunohistochemical expression of TERT differs in neoplastic and nonneoplastic pituitary tissues and aims to investigate whether TERT expression is related to clinicopathological features of pituitary adenomas. MATERIAL AND METHOD: The study included 48 patients who had been diagnosed with pituitary adenomas and had clinical follow-ups. Nonneoplastic pituitary tissues were obtained from autopsy specimens (n=20). Immunohistochemistry for TERT antibody was performed. Both the nuclear and cytoplasmic expression of TERT antibody was noted, and total combined TERT staining was evaluated according to nuclear and cytoplasmic stainings. RESULTS: TERT expression did not differ between neoplastic and nonneoplastic pituitary tissues. Neither total (combined nuclear and cytoplasmic) TERT nor nuclear TERT expression revealed any statistically significant relationship with any of the clinicopathological features. Higher cytoplasmic TERT expression was observed in adenomas with recurrence than adenomas without recurrence (p=0.035). CONCLUSION: This study introduces the notion that immunohistochemical expression of TERT does not differ in neoplastic and nonneoplastic pituitary tissues. Pituitary adenomas with cytoplasmic immunohistochemical expression of TERT have significantly higher rates of recurrence. Further studies, including combined methods of immunohistochemistry and molecular analyses in larger groups, may reveal applicable results for the clinical significance of TERT in pituitary adenomas.

Prognostic Value of Angiogenesis and Survivin Expression in Patients with Glioblastoma.

AIM: Glioblastoma (GBM) is the most common and the most aggressive primary brain tumor with poor prognosis. We aimed to evaluate the association between immunohistochemical expression of survivin and angiogenic parameters (microvessel density and vascular pattern) in patients who underwent surgery for GBM. MATERIAL AND METHODS: The pathology reports and also clinical and follow-up data of patients with GBM were retrospectively evaluated. Control tissues were obtained from the archive for each antibody (Survivin, CD 34). Then, control staining of these antibodies was performed. Vessels were evaluated according to the standardized assessment of vascular pattern. RESULTS: Mean survival for classical vascular pattern was longer than bizarre vascular pattern (p < 0.001). The survival time of patients decreased with increasing score of survivin staining. There was a significant correlation between survivin and survival time (p < 0.001). There was no significant correlation between microvessel density and survival time (p > 0.05). CONCLUSION: With these findings, it is considered that high expression of survivin, bizarre vascular pattern and development of secondary GBM correlates with the low survival rates, however microvessel density has no correlation with the survival rates. Since only malignant cells express survivin, it might be a target protein for the development of novel therapies.

Pheochromocytoma presenting with rhabdomyolysis and acute renal failure: a case report.

Rhabdomyolysis ranges from an asymptomatic illness with elevated creatine kinase levels to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure, and disseminated intravascular coagulation. The most common causes are crush injury, overexertion, alcohol abuse, certain medicines, and toxic substances. A number of electrolyte abnormalities and endocrinopathies, including hypothyroidism, thyrotoxicosis, diabetic ketoacidosis, nonketotic hyperosmolar state, and hyperaldosteronism, cause rhabdomyolysis. Rhabdomyolysis and acute renal failure are unusual manifestations of pheochromocytoma. There are a few case reports with pheochromocytoma presenting rhabdomyolysis and acute renal failure. Herein, we report a case with pheochromocytoma crisis presenting with rhabdomyolysis and acute renal failure.

Turkish experience in rheumatoid arthritis patients with clinical apparent amyloid deposition.

OBJECTIVES: We evaluated the frequency of clinical apparent amyloid deposition, clinical features and outcome in our rheumatoid arthritis (RA) patients. METHODS: Medical records of 1415 RA patients were examined. During routine follow-up, RA patients with proteinuria on urinalysis, underwent rectal biopsy. RESULTS: Eleven patients (0.78%) were diagnosed with clinical apparent amyloid deposition. While the mean annual incidence of AA amyloidosis between 2001 and 2005 was 0.2%, it was 0.13% between 2006 and 2011. At initial presentation, three RA-related AA amyloidosis patients had nephrotic-range proteinuria and renal insufficiency, four had only nephrotic-range proteinuria, three had non-nephrotic-range proteinuria, and one had non-nephrotic-range proteinuria and renal insufficiency. The mean age in RA patients with AA amyloidosis was 60.8 years and disease duration was 12 years. Ten of 11 cases had positive rheumatoid factor. Two RA patients with AA amyloidosis who had been diagnosed in the pre-anti-TNF era died. Of the rest nine patients with AA amyloidosis, eight were administered anti-TNF therapy and one was given rituximab. In four patients, anti-TNF therapy led to disappearance of clinical features, decrement in proteinuria and resulted in improvement of or at least stabilization of renal functions. One patient using anti-TNF therapy died because of tuberculosis. One patient discontinued anti-TNF therapy and developed end-stage renal disease. Two patients have been started to be given anti-TNF therapy recently. In one patient who was given rituximab, there was regression of proteinuria and improvement in renal functions. CONCLUSIONS: We diagnosed a 0.78% frequency of AA amyloidosis in RA. It seems that - other than the risks of infection, tuberculosis - anti-TNF drugs seem to be effective on RA disease activity and also have renoprotective effects in RA patients with AA amyloidosis.

Effect of lidocaine on reducing injury in a rat electrical burn model.

Electrical injuries induce progressive tissue loss. We evaluated the effect of lidocaine on tissue necrosis after electrical burn injuries. Forty-two male Wistar albino rats (250-300 g) were divided into 3 groups [Group A (n=6), control group without an electrical burn injury; and Groups B (n=18) and C (n=18), electrical burn injury groups without and with lidocaine therapy, respectively]. Three separate analyses were performed at different time points on 6 of 18 rats from Groups B and C at each time point. Electrical burns were induced by applying 220 V AC between the left upper and right lower extremities for 10 seconds. Myeloperoxidase and malondialdehyde levels were measured in skin and muscle biopsy specimens after the first hour, fresh and dry weight differences in the amputated extremities were calculated after 24 hours, and live and necrotic tissue areas were measured at 7 days after burn injury. We found that lidocaine reduced edema, the number of neutrophils, and neutrophil damage in tissues. We conclude that lidocaine decreased the amount of necrotic tissue caused by electric injury.

Non-Hodgkin's lymphoma: A rare diagnosis on cervicovaginal cytology.

Cervicovaginal smear screening is well known to reduce morbidity and mortality rates of invasive cervical carcinoma. Herein, we report a case of 56-year-old woman whose cervicovaginal smear was found to consist of malignant cells characterized by high nuclear/cytoplasmic ratio, scant rim of cytoplasm, coarsely granular nuclear chromatin and irregular nuclear membrane that were all reminiscent of a malignant lymphoma. Histopathological examination of the hysterectomy and unilateral adnexectomy specimen confirmed the presence of a diffuse large B-cell non Hodgkin's lymphoma involving the cervix, endometrium, myometrium, serosa and the right ovary.

A metabolic syndrome case presenting with lymphocytic mastitis.

BACKGROUND: Lymphocytic mastitis is a disease of premenopausal women, and its association with type 1 diabetes mellitus is the basis for its alternative name 'diabetic mastopathy'. It is a benign condition but must be considered in the differential diagnosis of breast cancer, especially in diabetic patients. CASE REPORT: We present the case of an overweight 50-year-old dyslipidemic woman with metabolic syndrome presenting with lymphocytic mastitis. CONCLUSION: Although lymphocytic mastitis is usually regarded as an autoimmune disease seen mostly in diabetic patients, it may also be seen in nondiabetic patients with metabolic syndrome who do not have an autoimmune disease.

Fucoidin, a neutrophil rolling inhibitor, reduces damage in a rat electrical burn injury model.

BACKGROUND: Electrical injuries induce progressive tissue loss caused by free oxygen radicals released from neutrophil aggregates. Fucoidin, a potent inhibitor of L-selectin function, reduces the aggregation of neutrophils. The aim of this study was to evaluate the effect of fucoidin on tissue damage in rat electrical burn injury model. METHODS: Forty-two male Wistar albino rats (250-300 g) were divided into 3 groups (Group A (n=6), control group without electrical burn injury; Groups B (n=18) and C (n=18), electrical burn injury groups without and with fucoidin therapy, respectively). Three separate analyses were performed at different time points on 6 out of 18 mice from Group B and C at each time point. Biochemistry (myeloperoxidase and malondialdehyde levels) and histopathology (number of neutrophils) of the skin and muscle biopsies at 1st hour; tissue edema (ratio of wet weight/dry weight of extremities) at 24th hour; and necrotic areas at 7th day after electrical injury were evaluated. The electrical burn was induced by exposing rats to 220 V AC between their left upper extremity and right lower extremity for 10 s. Fucoidin was administered as 25 mg/kg intravenous bolus injection at 15 min after electrical burn injury. RESULTS: Myeloperoxidase and malondialdehyde levels, number of neutrophils, tissue edema, and necrotic area were significantly less in fucoidin-applied rats than the group without fucoidin therapy. CONCLUSIONS: Fucoidin inhibits tissue damage induced by electrical burn injury in rats by reducing necrotic area, edema and number of neutrophils.

Granulomatous hypophysitis: presentation and MRI appearance.

Granulomatous hypophysitis (GrHy) is a relatively rare inflammatory disease compared with lymphocytic hypophysitis. Only a few cases with magnetic resonance imaging (MRI) findings have been reported to date. We describe the MRI findings for two patients with GrHy with unusual histories and clinical outcomes.

Expression of Bcl-2 and Ki-67 in tamoxifen-associated endometrial polyps: comparison with postmenopausal polyps.

BACKGROUND: The aim of this study was to evaluate the expression of Bcl-2 and Ki-67 in tamoxifen (TAM)-associated endometrial polyps and postmenopausal polyps. MATERIAL AND METHODS: For this purpose, a retrospective analysis of paraffin-embedded specimens was carried out. Polyps of 20 postmenopausal and 14 TAM-treated patients, 11 simple endometrial hyperplasia, 10 atypical complex endometrial hyperplasia and 8 endometrial adenocarcinoma specimens were included in the study. Hematoxylin/eosin-stained sections were evaluated. Immunohistochemical staining was performed to investigate the expression of Bcl-2 protein and the Ki-67 proliferation index. RESULTS: There was no statistically significant difference between the 5 groups with regard to Bcl- 2 staining (p > 0.05). However, Bcl-2 expression in TAM-associated polyps was higher (86%) than in the postmenopausal control group (80%). Positive Ki-67 was highest in the endometrial adenocarcinoma specimens, followed by the atypical complex endometrial hyperplasia group (p < 0.0001). Compared to these 2 groups, Ki- 67 expression was lower in TAM-associated polyps, but Ki-67 indexes were significantly higher in the TAM-associated group than in the control group (p < 0.0001). CONCLUSION: Since TAM-associated polyps tend to have higher proliferation indexes and Ki-67 ratios than control groups, we suggest that they are likely to have a higher malignant potential.

Multifocal mesenchymal hamartoma of the chest wall.

Chest wall hamartomas are extremely rare. Frequently mesenchymal hamartomas are presented as a single mass and contain some primitive mesenchymal elements such as chondroid and trabecular bone structures. A 60-year-old man presented to hospital with chest pain. Thirteen years earlier, his CXR and thoracic CT showed three masses on the right and two masses on the left, but he had not received any treatment thereafter. His CT showed the same masses present 13 years earlier, but they were bigger and right thoracotomy was undertaken. At thoracotomy, two sections of the mass in the right posterior mediastinum and one section of the mass in the right apex were excised. They had an occasional bloody appearance and contained small cystic areas, and some areas were extremely hard. Microscopic examination showed that the lesions consisted of mature adipose tissue, a large number of veins of different diameters and collagen tissue. Besides, primitive mesenchymal elements, lymphoid cell accumulations and trabecular bone structures were seen focally. Bilateral chest wall hamartomas are extremely rare and may be confused with malignancy.

Regenerative hyperplasia of follicular epithelium in chronic lymphocytic thyroiditis.

The thyroid gland is an endocrine organ composed of stable cells. It is well known that regenerative capacity of the thyroid tissue is minimal. Various degrees of morphologic alterations do occur in chronic lymphocytic thyroiditis (CLT), including Hashimoto's thyroiditis. Eighty-five CLT cases were analyzed for these morphologic alterations. Small, irregular, atrophic or hyperplastic thyroid follicles were seen adjacent to the lymphocytic infiltration. There was nuclear enlargement, loss of nuclear polarity in thyrocytes and intrafollicular thyrocyte proliferation in these follicles. We thought that the morphologic alterations in involved follicles could be due to regenerative hyperplasia with increased proliferative activity and basement membrane abnormalities. To examine this hypothesis we investigated Ki-67 and laminin immunoreactivity in the involved follicles adjacent to lymphocytic infiltration areas. The uninvolved follicles were used as controls. Immunopositivity of Ki-67 in involved follicles was significantly higher than that in uninvolved follicles (2.97% +/- 2.16 versus 0.83% +/- 1.63, P < 0.001). Laminin immunostaining indicated the destruction or irregular distribution of basement membrane in involved follicles. We conclude that the increased cell proliferation activity and basement membrane abnormalities in the follicles with morphologic changes adjacent to CLT occur in conjunction with regenerative hyperplasia.