Demonstration of Epstein-Barr Virus by In Situ Hybridization in Papillary Thyroid Carcinomas Developing on Background of Hashimoto's Thyroiditis.

AIM: This study aimed to demonstrate the role of Epstein-Barr Virus (EBV) in papillary thyroid carcinomas (PTC) developing on the background of Hashimoto's thyroiditis (HT). METHODS: The presence of EBV in tumoral tissue, lymphocytes, and peritumoral normal thyroid tissue was investigated using the in situ hybridization method in paraffin blocks. The subtypes of PTC, tumor diameter, TNM stage, multifocality, invasion of thyroid capsule, perineural invasion, and muscular tissue invasion were identified and compared according to EBV involvement. RESULTS: Eighty-one patients with HT diagnosis, with 93.8% (n=76) female and 6.2% (n=5) male, were included in the study. Papillary microcarcinoma was the pathological diagnosis in 24.2% (n=15) of the cases. EBV was identified in 58.06% (n=36) of the tumor cells nuclei, 58.06% (n=36) in the tumor cell cytoplasm, 16.12% (n=10) in tumor infiltrative lymphocytes, and 53.2% (n=33) in normal parenchymal follicle epithelial cells (NPFEC). In the T2 stage, the rate of EBV nuclear positivity in patients was significantly higher (p=0.034). The classic variant of papillary carcinoma was accompanied by a significantly higher rate of EBV-negative NPFEC (67.6%, p=0.049). In multifocal tumors, EBV positivity was found to be significantly higher in lymphocytes in the surrounding tissues (58.3%, p=0.034). CONCLUSION: A significant increase in EBV positivity in the surrounding tissue lymphocytes was observed in multifocal PTC developing on a background of HT. This suggests a possible association between HT and EBV.

Real-life experience of patients with sarcomatoid renal cell carcinoma: a multicenter retrospective study.

Sarcomatoid renal cell carcinoma (sRCC) is a rare variant of renal cell carcinoma (RCC) and is associated with a poor prognosis. We reviewed the outcomes of patients from oncology centers in Turkey. Our aim is to share our real-life experience and to contribute to the literature. The demographic and clinical features, treatment, and survival outcomes of 148 patients with sRCC were analyzed. The median age at the time of diagnosis was 58 years (range: 19-83 years). Most patients (62.8%) had clear-cell histology. Most patients were in the intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk group (67.6%) and were stage 4 at the time of diagnosis (63.5%). The most common sites of metastasis were the lung (60.1%), lymph nodes (47.3%), and bone (35.8%). The patients received a median of two lines (range: 0-6) of treatment. The most common side effects were fatigue, hematological side effects, hypertension, and hypothyroidism. The median follow-up was 20.9 months (range: 1-162 months). The median overall survival (OS) was 30.8 months (95% confidence interval: 24.9-36.7 months). In multivariate analysis, high MSKCC scores, sarcomatoid differentiation rates >50%, having stage 4 disease, and having lung metastasis at the time of diagnosis were independent factors for poor prognosis affecting OS. No difference was observed between patients who received tyrosine kinase inhibitor (TKI) as the first or second-line treatments. Similarly, no difference between TKI and immunotherapy as the second-line treatment. In conclusion, sRCC is a rare variant of RCC with a poor prognosis and response to treatment. Larger-scale prospective studies are needed to define an optimal treatment approach for longer survival in this aggressive variant.

Pulmonary tuberculosis due to Mycobacterium bovis revealed by skin lesion in slaughterhouse worker.

A 46-year-old male patient who has worked as a butcher was admitted to the hospital with an unhealing wound on the dorsal side of his hand. Incisional biopsy was performed from the lesion and histopathological diagnosis revealed a granulomatous inflammatory process, compatible with tuberculosis. The patient was directed to the department of chest diseases for further investigation in terms of pulmonary Tuberculosis (TB) infection. On the chest X-ray and thoracic CT scan, a minimal infiltration was observed in the left upper lobe. In two respiratory samples obtained by fiberoptic bronchoscopy, Mycobacterium tuberculosis complex was isolated and identified as M. bovis in subspecies level. After overall clinical evaluation, anti-TB treatment was initialized and a radiologic/clinical regression was observed during the follow-up procedure. This case has been reported as a rare and noteworthy pulmonary TB disease due to M. bovis in a slaughterhouse worker with a cutaneous granulomatous inflammatory reaction.

Investigation of the Roles of Cyclooxygenase-2 and Galectin-3 Expression in the Pathogenesis of Premenopausal Endometrial Polyps.

BACKGROUND: The pathogenesis and etiology of endometrial polyps has not been elucidated. In this study, we aimed to examine the pathogenic mechanisms of endometrial polyp development using immunohistochemistry. We evaluated the expression of galectin-3 and cyclooxgenase-2 (COX-2) during the menstrual cycle in premenopausal women with endometrial polyps or normal endometrium. METHODS: Thirty-one patients with endometrial polyps and 50 healthy control patients were included in this study. The levels of expression of COX-2 and galectin-3 were studied by immunohistochemistry. RESULTS: The percentage of COX-2-positive cells and the intensity of COX-2 staining in the endometrium did not vary during the menstrual cycle either in the control group or in patients with endometrial polyps. However, expression of galectin-3 was significantly lower in endometrial polyps and during the proliferative phase of the endometrium compared with the secretory phase. CONCLUSIONS: Our data suggests that the pathogenesis of endometrial polyps does not involve expression of COX-2 or galectin-3.

The Relation of Parafibromin Expression with Clinicopathological Factors in Invasive Breast Carcinomas.

OBJECTIVE: We aimed to find the relationship between parafibromin expression and clinicopathologic variables of breast carcinoma. MATERIAL AND METHOD: Ninety-seven cases of invasive breast carcinoma diagnosed at our department between the years 2010-2013 were included in the study. The parafibromin expression state was compared with the estrogen receptor, progesterone receptor, cerbB2, Ki67 results, and the clinicopathological variables. RESULTS: Among 97 breast carcinoma cases, 66 (68%) were invasive ductal carcinoma. The average age was 54.3 (min:25, max:100), and the average tumor size was 31.1 mm (min:7, max:120). Lymph node metastasis was detected in 58% of the cases. Eleven were diagnosed with metastasis amongst 77 cases whose distant metastasis data could be reached. Eleven cases were lost due to breast carcinoma. As the tumor grade increased, the possibility of distant metastasis and lymph node metastasis increased as well (p=0.04, p=0.05, respectively). The mean follow-up duration of the cases was 26.6 ± 9.8 (min. 6, max. 53) months, and there was no significant difference in survival between the other variables. Of the cases, 21.6% were negative, 9.3% were (+) positive, 11.3% were (++) positive and 57.7% were (+++) positive for parafibromin. It was found that there was an inverse correlation between the Ki67 proliferation index and lymph node metastasis and the parafibromin expression (p=0.018, p=0.029, respectively). CONCLUSION: We suggest that parafibromin may be a possible prognostic and predictive parameter for breast carcinomas. As the data on this matter in the literature is limited, it would be beneficial to investigate the matter and evaluate its relationship with survival in larger series.

[A Gossypiboma (Textiloma) Mimicking a Gastrointestinal Stromal Tumor: A Case Report]. / Gastrointestinal Stromal Tümörü Taklit Eden Gossypiboma (Tekstiloma): Olgu Sunumu.

Gossypiboma (textiloma) is a rare but preventable complication occurring due to oblivion of the surgical material during an operation that carries important diagnostic difficulties as well as high morbidity and mortality risks. The actual incidence is unknown because of its medicolegal aspects. Our case is a 36-years-old female patient, who had a caesarean section two years ago in another center. Clinical examination and radiological investigations gave the impression of "gastrointestinal stromal tumor" and the surgically taken out mass was sent to our pathology department. The case was reported as a "gossypiboma"' and presented here to emphasize the diagnostic difficulties in the preoperative period, the life-threatening nature of the condition and as well as the rarity of the reported cases.

The Role of Parafibromin, Galectin-3, HBME-1, and Ki-67 in the Differential Diagnosis of Parathyroid Tumors.

OBJECTIVES: Parathyroid carcinoma (PC) is a rare parathyroid tumor compared to parathyroid adenoma (PA) and atypical parathyroid adenoma (APA). Recent studies have suggested parafibromin has a role in the differential diagnosis of parathyroid tumors. We sought to determine the role of parafibromin as well as galectin-3, Ki-67, and HBME-1 as diagnostic markers in the differential diagnosis of parathyroid tumors. METHODS: A total of 92 cases diagnosed with PA, APA, or PC at Sifa University and Private Ege Pathology Laboratory between 2006-2012 were included in the study. Parafibromin (microarray), galectin-3, Ki-67, and HBME-1 were evaluated using immunohistochemistry in all parathyroid tumors. RESULTS: Eighty-four cases were diagnosed with PA, six with APA, and two with PC. The study group consisted of 82 females and 10 males. Their mean age was 50.9 years, and the mean tumor diameter was 1.97 cm. Parafibromin was negative in the two PC cases but positive in all APA and PA cases. Positivity was observed with galectin-3 in 17 adenoma cases, three atypical adenomas, and two carcinoma cases. Positivity with HBME-1 was found in 26 PA cases and one PC case. Parafibromin and galectin-3 expression was significant between the three tumor groups but not for HBME-1 expression. Parafibromin expression increased in PA whereas galectin-3 expression decreased. A statistical significance was found between the three tumor groups according to the Ki-67 score (p=0.010). Additionally, the Ki-67 proliferation index was under 1% in PAs. CONCLUSION: The number of PCs in our series was small so our data mostly reflects the immunohistochemical characteristics of PAs. Parafibromin expression, galectin-3 negativity, and a Ki-67 proliferation index under 1% were estimated as beneficial in the differential diagnosis of difficult parathyroid tumors.

Does St. John's Wort cause regression in gastrointestinal system adenocarcinomas?

St. John's Wort (SJW) is an old herb which has long been consumed widely for its anti-inflammatory, antiviral, and anti-depressive properties. Here we present a detailed clinical evaluation of three cases (two colon and one duodenal adenocarcinoma) with remarkable and intensive lymphoplasmocytic host reaction, at the basal part of tumor, intensive fibrosis, giant cells, plasma cell increase in lymph nodes and few giant cells in germinal centers in resection specimens. The observation of similar host reaction in those tumors having otherwise usual appearance was interesting. None of the cases received neoadjuvant chemoradiotherapy or additional treatment before surgery but only SJW. These cases are presented to increase the awareness about such cases. Further research is needed to reveal the possible effect of SJW, which has long been consumed for different treatment purposes, on human tumors.

Parafibromin Staining Characteristics in Urothelial Carcinomas and Relationship with Prognostic Parameters.

BACKGROUND: Parafibromin is a recently defined tumor suppressor gene. The aim of our study was to determine the relationships of parafibromin expression in urothelial carcinomas (UCs) with prognostic parameters and to evaluate the use of parafibromin as a potential marker of UC. METHODS: Parafibromin expression was assessed in 49 UC specimens using immunohistochemistry. The correlations between parafibromin expression and clinical and pathologic parameters were investigated. RESULTS: Of the patients, 42 (85.7%) were male, and the mean age was 69.6 ± 8.2 years (range, 54 to 88 years). Morphologically, the UCs were divided into two groups: papillary (n = 27) and non-papillary (n = 22). There were seven low-grade (14.3%) and 42 high-grade (85.7%) tumors. Parafibromin was negative in 13 tumors (26.5%), partially positive in 19 tumors (38.8%), and positive in 17 tumors (34.7%). Parafibromin expression was more negative in UCs from upper urinary locations (n=17) and with muscularis propria invasion (n=28), which was statistically significant (p = .009 and p = .007, respectively). There was no statistically significant relationship between parafibromin expression and gender, age, tumor grade, survival, or disease-free survival. CONCLUSIONS: We found that UC cases with parafibromin positivity had less of a tendency to show muscularis propria invasion and were more commonly located in the lower urinary system. These results need to be confirmed with studies based on larger case series.

Evaluation of the role of Epstein-Barr virus in cases of nodal or extranodal T- and NK-cell lymphoma using eber in situ hybridization.

Various racial and geographic differences have been observed in studies questioning the role of Epstein-Barr virus (EBV) infection in the etiology of T- and NK-cell lymphomas. The aim of this study was to evaluate the relationship of EBV with nodal or extranodal (skin excluded) T- and NK-cell lymphoma subtypes encountered in our geographic area. Sixty-two cases of peripheral T-cell lymphoma were included in the study. EBV-encoded early RNA (EBER) was detected by in situ hybridization. The distributions of T- and NK-cell lymphoma subtypes were as follows: 32 peripheral T-cell lymphomas, unspecified (PTCL, NOS), 13 anaplastic large-cell lymphomas (ALCL), 8 angioimmunoblastic T-cell lymphomas (AITCL), 4 extranodal NK/T-cell lymphomas, nasal type (NKTCL), 3 enteropathy-type T-cell lymphomas (ETTCL), 1 hepatosplenic T-cell lymphoma (HSTCL), and 1 subcutaneous panniculitis-like T-cell lymphoma (SPTCL). Using a cut-off value of >25% of EBER-positive neoplastic lymphoid cells, EBV was positive in 22.6% of all cases. According to subtype, the neoplastic cells of 31.3% of PTCL, NOS and 100% of extranodal NKTCL, nasal type were EBER positive, whereas some cases of ALCL, AITCL, and ETTCL presented EBER-positive non­neoplastic cells, and all cells of HSTCL and SPTCL were EBV negative. Extranodal NKTCL, nasal type, presented the strongest association with EBV, followed by PTCL, NOS.

Spindle cell lipoma of the soft palate.

Intraoral spindle cell lipomas (SCL) are very rare and comprise ranging between 1.4%-9.8% of all intraoral lipomas. To our knowledge, no case of a SCL located on the soft palate has been reported in the English-language literature. A 31-year-old female was admitted with a swelling in her soft palate. On examination, a 3 cm sessile, nontender swelling was observed on her soft palate. After surgical excision, it was diagnosed as a SCL.

Diagnosis, PET/CT imaging, and treatment of extranodal non-Hodgkin lymphoma in keratinized gingiva: a case report.

A 58-year-old patient who smoked and had uncontrolled type 2 diabetes mellitus was referred to our clinic. The patient had a suspicious asymptomatic lesion that was diagnosed as B-cell non-Hodgkin lymphoma (NHL). Immunohistochemistry revealed intense and diffuse expression of CD20, CD10, BCL-6, and Ki-67. A positron emission tomography/computed tomography (PET/CT) scan showed focal pathological uptake of F-18-fluorodeoxyglucose only in the subcutaneous tissue anterior to the left maxillary sinus. After lesion excision and five courses of chemotherapy, PET/CT scans demonstrated complete resolution of the lesion. Smoking, uncontrolled diabetes mellitus, and periodontal disease might be predisposing factors for oral NHL.

The role of cytokines in first trimester pregnancy losses with fetal chromosomal anomaly.

OBJECTIVES: The contribution of local inflammation to the pathophysiology of abnormal choromosomally miscarriages remains unclear The objective of this study was to investigate the inflammatory response at the maternofetal interface of women presenting with first trimester miscarriage with abnormal choromosomally MATERIAL AND METHODS: Level of TNF-α , IL-6 ve IL-17 were asseyed using immunohistochemistry technique at decidual and placental bed biopsy samples from 23 women with elective termination of pregnancy 21 euploid and 18 aneuploid missed miscarriages. Immunostainig for TNF-α, IL-6 ve IL-17 has been evaluated semi-quantitatively by 'quickscore' method. RESULTS: We found that the intensity of TNF-α staining was high in the miscarriage group, and this has been found in previous studies. Unlike some previous studies, the intensity of IL-6 staining was higher in the miscarriage groups only in decidual glandular epithelium. The intensity of IL-6 staining was found to be higher in the miscarriage group with chromosome anomaly than in the miscarriage group without chromosome anomaly. There was no significant difference in IL-17 levels between any of the groups. CONCLUSIONS: Cytokines are considered to play an important role in the maintenance of pregnancy but the exact mechanism between them and the mutual regulation relationship were not been fully understood, which need our further study.

The relationship of melanocytic differentiation with prognostic markers in medullary thyroid carcinomas.

INTRODUCTION: Medullary thyroid carcinoma (MTC) makes up 5-10% of thyroid malignancies. Small cell, squamous, giant cell or melanocytic differentiation can rarely be seen in MTCs. It is important to determine those with the potential to act aggressively such as cases with melanocytic differentiation at the time of diagnosis. MATERIALS AND METHOD: A total of 46 MTC cases diagnosed at four different centers between 2002 and 2013 were included in the study. Immunohistochemical (IHC) staining with Melan-A and HMB-45 was performed in all cases. RESULTS: Six of the 46 MTC cases were medullary microcarcinomas and three were multicentric medullary carcinomas. There were 34 females and 12 males with a mean age at onset of 51.4 years and mean tumor diameter of 23.2mm. Lymph node metastasis (LNM) was found in 13 of the 38 cases that had data regarding the lymph nodes. Immunohistochemically, Melan A staining was seen in four cases. HMB45 staining was seen in four cases. A statistically significant relationship was found between LNM and diameter, Melan A expression (p=0.02, p=0.03 respectively) but there was no significant relationship with HMB45 expression (p=0.07). General survival data were present for 35 of the 46 cases. All cases without lymph node metastasis survived (21/21) while 8 of 11 cases with lymph node metastasis survived among cases with survival data; one case that was diffuse-strong positive for both HMB45 and Melan A was lost due to distant organ metastasis six months after the diagnosis. DISCUSSION: Should the possibility of melanocytic differentiation be evaluated in cases where melanocytic differentiation is not reflected in the morphology (lack of pigment) in MTCs? We did not come across a study on the subject in the English literature. The effect of melanocytic differentiation on the prognosis in MTCs should be investigated in larger series.

Endometriosis localized to urinary bladder wall mimicking urinary bladder carcinoma.

Although endometriosis is a common disease in women of reproductive age, urinary system endometriosis is an exceedingly rare disease that may cause important clinical problems. In this paper we discussed a 42-year-old woman who had urinary bladder endometriosis misdiagnosed as urinary bladder tumor in imaging modalities. The diagnosis of endometriosis was made by histopathological examination of the operative material after partial resection of the urinary bladder. Urinary bladder endometriosis causes nonspecific signs and symptoms in many patients. In female patients presenting with unexplained urinary symptoms the differential diagnosis should include urinary bladder endometriosis that may mimic urinary bladder cancer and lead to difficulties in making definitive preoperative diagnosis.

Mucinous tubular and spindle cell carcinoma of kidney and problems in diagnosis.

OBJECTIVE: Mucinous tubular and spindle cell carcinomas (MTSCC's) are recently described rare type of renal cell carcinoma (RCC). MTSCC's are characterized by small, elongated tubules lined by cuboidal cells and/or cords of spindled cells separated by pale mucinous stroma. They have morphological similarities to papillary RCC (papRCC). We evaluated the importance of the immunohistochemical features in the differential diagnosis of MTSCC and papRCC. MATERIAL AND METHOD: We re-evaluated 9 cases of MTSCC diagnosed between 2004 and 2010 and compared 10 cases of papRCC. All tumors were stained with alpha-methylacyl-CoA racemase (AMACR), cytokeratin 7 (CK7), CK19, renal cell carcinoma marker (RCC Ma), CD10 and kidney specific cadherin (KspCad). RESULTS: A total of 6/9 cases were considered classical. Two of 9 MTSCC's were classified as "mucin-poor". Foamy macrophages were identified in 4 cases. The immunoreactivity in MTSCC was AMACR 100%, CK7 100%, CK19 100%, RCC Ma 50%, CD10 11%, and KspCad 38% while the values for papRCC were AMACR 100%, CK7 90%, CK19 100%, RCC Ma 100%, CD10 80%, and KspCad 0%. CONCLUSION: MTSCCs may include little mucin and show a marked predominance of either of its principal morphological components. They may mimic other forms of RCC. Pathologists should be aware of the histological spectrum of MTSCCs to ensure an accurate diagnosis. Careful attention to the presence of a spindle cell population may be helpful in the differential diagnosis in tumors with predominant compact tubular growth. Immunohistochemical stains for papRCC are also expressed in MTSCC, but strong CD10 expression may not favor MTSCC.

Expression of Epstein-Barr-virus-encoded small nuclear RNA in nasopharyngeal carcinomas of Aegean Turkish patients.

Nasopharyngeal carcinomas (NPC) are epithelial neoplasms which show a distinct geographical distribution and have a characteristic histology. These tumors have multifactorial etiology, including virological, environmental, and genetic components. The aim of the present study is to assess the relation between Epstein-Barr-virus (EBV) and subtypes of NPC in Aegean Turkish patients. In the present study, nasopharyngeal biopsies of 84 cases diagnosed as nasopharyngeal carcinoma, between 1998 and 2004, were reevaluated. In situ hybridization with the fluorescein-conjugated EBV-encoded small nuclear RNA (EBER) oligonucleotide probe was performed on paraffin-embedded tissue sections using an automated slide stainer system. Of 84 patients, 55 were men and 29 were women with ages ranging between 7 and 77 years (median 50, mean 46.73). Seventy-three of 84 cases were EBER positive. All of 62 cases (100.0%) with undifferentiated carcinoma, 8 of 16 (50.0%) with differentiated nonkeratinizing carcinoma, and three of six (50.0%) with keratinizing squamous cell carcinoma were EBV positive. EBER positivity was statistically significantly higher in undifferentiated carcinomas, compared to the other morphological subtypes (p = 0.000). Our results showed that all morphological subtypes of NPC are highly associated with EBV latent infection in our region, and a higher prevalence was found for the undifferentiated subtype.