Receptor-Binding Cancer Antigen Expression in Thyroid Neoplasms: A Retrospective Study.

Background: Receptor-binding cancer antigen (RCAS1) is a membrane protein, regarded as a tumor-associated antigen. Cancer cells evade immune response with RCAS1 up-regulation, inducing apoptosis to tumor infiltrating lymphocytes. Thyroid cancer incidence is rising and its accurate diagnosis in early stage is targeted. The aim of this study is to access RCAS1 expression in benign and malignant thyroid pathology. Methods: This is a retrospective study of 110 patients, who had thyroidectomy in a single tertiary referral centre between January 2008 until December 2014. Immunohistochemistry study for RCAS1 expression was carried out and correlation with clinical and histopathological data is attempted. Results: RCAS1 immunostaining was found positive in 81 out of 110 cases. Notably it was deemed positive in all malignant thyroid tissue samples (p 0.001). In thyroid malignancy, tumor size, thyroid capsule invasion and positive lymph nodes status were positively correlated with moderate and strong expression of RCAS1. For papillary thyroid carcinoma, the vast majority (35/37 cases, 94.6%) were also classified as having moderate or strong RCAS1 expression. Conclusions: RCAS1 expression can aid in differential diagnosis between benign and malignant thyroid pathology, while its strong expression correlates with worse oncological features.

Survivin expression in hepatocellular carcinoma. Correlation with clinicopathological characteristics and overall survival.

PURPOSE: Survivin expression is a potential prognostic indicator in various carcinomas. The prognostic value of Survivin for survival in hepatocellular carcinoma, (HCC) however, remains controversial. The aim of the study is to examine the expression of the inhibitor of apoptosis Survivin in HCC and investigate the correlation with the clinic-pathologic characteristics and overall survival (OS) following surgical resection. METHODS: Specimens from patients with resected HCC were examined by Immunohistochemical staining for Survivin and BCL-2expression. Clinical and histopathological data were retrieved from medical and pathology records, while OS was determined by reviewing records from the department of Oncology and personal communication with survivors. Bivariate analysis was performed using the Chi-square and Mann-Whitney U tests, while survival was estimated by Kaplan Meier method and compared with log-rank test. RESULTS: Sixty patients were included in the study. Survivin was expressed in 26 patients (43.3%). Survivin expression was significantly correlated to OS (p=0.014). A statistically significant negative correlation between Survivin and BCL-2 was also noted (p<0.001). CONCLUSIONS: Survivin expression reflects aggressive histological and clinical behavior of HCC and correlates with poorer OS. Further studies are required to confirm if Survivin can be used as a predictive biomarker to evaluate prognosis and target treatments for HCC.

Contrast-Enhanced Color Doppler Ultrasonography for Preoperative Evaluation of Sentinel Lymph Node in Breast Cancer Patients.

BACKGROUND: Sentinel lymph node (SLN) biopsy is the standard of care for breast cancer patients with non-palpable axillary lymph nodes. We evaluated the usefulness of contrast-enhanced ultrasonography in preoperative detection of malignant SLNs. METHODS: 50 patients with breast cancer (median age: 60 years) underwent a color power Doppler ultrasonography with intravenous contrast (Sonovue®) preoperatively, and findings suggestive of metastatic disease to the SLN were documented. The final histopathological report and the radiological preoperative record were compared. Finally, the sensitivity, specificity and diagnostic accuracy of this evolving diagnostic modality were calculated. RESULTS: Contrast-enhanced ultrasound scan identified a negative SLN in the axilla of 27 patients and final histopathology was negative for 30 cases in total, so negative predictive value was calculated as 90% and positive predictive value was 75%. Overall sensitivity was 83.33% and specificity was 84.38%. Moreover, the ability of contrast-enhanced ultrasound to differentiate between SLN status was only statistically significantly correlated with the actual final histopathological report (p < 0.001), while successful ultrasound prediction was not correlated with any factor. CONCLUSIONS: SLN status can be evaluated preoperatively using contrast-enhanced color Doppler ultrasonography with high accuracy.

Sporadic versus inflammatory bowel disease-related colorectal adenocarcinoma: lessons learned from a single institution experience.

PURPOSE: Inflammatory bowel disease (IBD) - related colorectal adenocarcinoma (CAC) is known to impose a less favorable prognosis than its sporadic counterpart. The determining factor in the prognosis of IBD patients is the early endoscopic detection of commonly occult pre-cancerous lesions. This retrospective study attempted to highlight the distinctive features of IBD-related CAC, as well as the importance of implementing an acceptable surveillance protocol in IBD patients. METHODS: The medical records and biopsies of all IBD patients undergoing surgery and of surgical patients with sporadic CAC, admitted in the 5-year period 2010-2014, were examined. Overall, 26 clinicopathological parameters were collected and compared between the two groups. RESULTS: A total of 370 patients with sporadic CAC and 103 patients with IBD were included in the study, of which 8.7% (9/103) proved to have CAC. Cancer in IBD patients appeared at a younger age, had a larger maximum diameter and was more likely to have multiple synchronous locations and a signet-ring cell differentiation (p<0.05). Only 25% of IBD patients with CAC had previously followed correct surveillance. CONCLUSIONS: The aggressive features of IBD-related CAC, as well as the rising incidence of poorly-surveilled IBD patients that eventually progress to cancer, reflect the necessity of establishing dedicated IBD centers for their optimal follow-up.

Classification of histological images of the endometrium using texture features.

OBJECTIVE: To present a texture analysis method in order to achieve texture classification for 240 histological images of the endometrium. STUDY DESIGN: A total of 128 patients with endometrial cancer and 112 subjects with no pathological condition were imaged. For each image 190 texture features were initially extracted, derived from the wavelets, the Gabor filters, and the Law's masks, which were reduced after feature selection in only 4 features. RESULTS: The images were classified into 2 categories using artificial neural networks, and the reported classification accuracy was 98.1%. CONCLUSION: The results showed that there was a strong discrimination between histological images of cancerous and normal tissue of the endometrium, based on the proposed set of texture features.

Neuroendocrine differentiation in embryonal type hepatoblastoma.

Hepatoblastoma, a malignant tumor which arises occasionally in older children but very rarely in adults, exhibits divergent differentiation with embryonal cells, fetal hepatocytes and immature elements. This report describes an embryonal type hepatoblastoma with neuroendocrine differentiation in a 16-year-old patient, which was diagnosed postoperatively. Clinical and radiologic work-up failed to reveal a primary gastrointestinal malignancy and no primary lesions were detected in any other organ. This feature of hepatoblastoma is considered to be a multidirectional differentiation of the small epithelial or stem cells of the liver. At 2-year follow up, the patient remains symptom-free, with normal laboratory and diagnostic imaging studies, and no recurrent or metastatic disease identified.

The expression of human leukocyte antigens class I and II in women with endometriosis or adenomyosis.

OBJECTIVES: The human leukocyte antigen (HLA) system has been implicated in the aetiology of endometriosis. We aimed to compare the HLA class I and II expression in endometrial specimens from women with endometriosis or adenomyosis. METHODS: We studied the HLA class I and II expression in endometrial specimens from 16 women with endometriosis and 15 with adenomyosis which were compared with 15 specimens from women without endometriosis or adenomyosis. Immunohistochemistry was performed using mouse antihuman IgG2a monoclonal antibody for HLA I and IgG1 for HLA II. RESULTS: Women with endometriosis had significantly higher HLA I and II expression in stroma (100% and 87.5% vs. 66.7% and 40%, p < 0.02 and p = 0.007, respectively) and glands (87.5% and 56.3% vs. 46.7% and 20%, p < 0.02 and p = 0.04, respectively) compared to controls, while in the adenomyosis group the expression of HLA I was comparable with controls and the HLA II expression was increased in stromal cells (73.3% vs. 40%, p = 0.03) and decreased in glands (6.6% vs. 20%, p = NS). CONCLUSION: Women with endometriosis had a significantly higher expression of HLA molecules whereas in adenomyosis there was a tendency of lower expression of these molecules. This could explain the suppression of cellular immunity in the peritoneal cavity.

Expression of c-kit in common benign and malignant breast lesions.

AIMS AND BACKGROUND: c-kit (CD117) is a transmembrane tyrosine kinase that acts as a type III receptor for mast cell growth factor. In recent years, the role of c-kit in the development of preinvasive and invasive breast carcinomas has been investigated. The aim of our study was to detect c-kit expression in the entire spectrum of common benign and malignant breast lesions in correlation with a well-studied myoepithelial or stem-cell like marker (p63). METHODS AND STUDY DESIGN: We evaluated 270 cases of benign and malignant breast lesions including fibrocystic disease, fibroadenoma, sclerosing adenosis, atypical ductal hyperplasia, ductal/lobular carcinoma in situ, and ductal/lobular/mixed type carcinoma. C-kit staining was evaluated in the cytoplasm/cell membrane in epithelial and myoepithelial cells and p63 in the nuclei of myoepithelial cells. RESULTS: c-kit was highly expressed (85.3%) in benign lesions (fibrocystic disease, sclerosing adenosis, fibroadenoma), and p63 expression was 95.5% in the aforementioned lesions. c-kit distribution in preinvasive and invasive lesions was as follows: ductal/lobular carcinoma in-situ, 43%/35%; ductal/lobular carcinoma, 36%/39%; and mixed type carcinoma, 20%. c-kit was highly expressed in myofibroblast/fibroblast cells only in grade III ductal/lobular carcinomas. c-kit was totally absent in stromal cells in benign lesions and in situ carcinomas whereas expression was weak in grade I and II carcinomas. CONCLUSIONS: Combined overexpression of c-kit and p63 is indicative of benign breast lesions. In contrast, there is reduced expression of c-kit in in situ and invasive breast carcinomas, with simultaneous overexpression in the stromal cells. This suggests that c-kit may play a role in breast cancer progression.

Unusual presentation of Mönckeberg's sclerosis in the thyroid vessels of three female patients.

Histopathological findings of Mönckeberg's sclerosis in the thyroid vessels of three female patients are described. Two of the patients presented with papillary carcinoma and the third presented with two cystic adenomatous nodules. Lesions of chronic lymphocytic thyroiditis were observed in two of the cases. The presence of Mönckeberg's sclerosis is an indication for further examination of patients' vascular systems because of the high risk for cardiovascular events.

Complete pelvic lymphadenectomy in patients with clinical early, grade I and II endometrioid corpus cancer.

AIM: To investigate the risk of pelvic lymph node metastasis in patients with a preoperative diagnosis of early endometrial cancer with favorable histological characteristics, assessed by complete pelvic lymphadenectomy. PATIENTS AND METHODS: A total of 108 patients with clinical early endometrioid grade I or II endometrial carcinoma underwent complete pelvic lymphadenectomy between 2001-2007. Only cases with at least 15 nodes histologically examined were included. All operations were performed by the same team. The preoperative tumor histology was compared with the final pathological findings. The incidence of pelvic nodal involvement was estimated in relation to the final grade and depth of myometrial invasion in halves. RESULTS: The median age of patients was 63 years. In the final histology, 10 tumors (9.3%) of non-endometrioid histology were found. The discordance between pre- and postoperative tumor grade was 32.4%, with 24.1% being upgraded. Nine patients (8.3%) had poorly differentiated tumors and 23 (21.3%) deep (>50%) myometrial invasion in the final pathology. A total of 11 patients (10.2%) had pelvic nodal metastasis. The rate of lymph node metastasis in relation to final grade I and II and myometrial invasion was as follows: grade I, 1.8% (inner half 0%, outer half 14.3%); grade II, 15.9% (inner half 12.1% outer half 27.3%). Overall 19.4% of patients were upstaged at surgery. CONCLUSION: A significant proportion of patients presenting with early endometrial cancer of optimal characteristics will have a more advanced disease at surgical staging. Complete pelvic lymphadenectomy may increase the possibility of detecting metastatic disease in the lymph nodes.

The sentinel node in cervical cancer patients: role of tumor size and invasion of lymphatic vascular space.

BACKGROUND: The sentinel lymph node (SLN) technique aims at predicting the absence of regional nodal metastasis and seems promising in the management of cervical cancer patients. PATIENTS AND METHODS: Forty patients undergoing surgery for early cervical cancer were submitted to the SLN procedure, using Blue Patente alone in 3, radiocolloid injection alone in 4 and both methods in 33 (82.5%). All patients underwent radical hysterectomy and pelvic lymphadenectomy. RESULTS: The detection rate was as follows: overall 85%, blue dye alone 66%, radiocolloid alone 75%, dual method 87%. Detection was successful in 34 patients, with one false-negative result. No micrometastases were demonstrated during ultrastaging of the sentinels. The detection rate was higher in tumors <2 cm (94.1%) than in larger tumors (78.2%, p>0.09). Significant negative correlation between lymphatic vascular space invasion (LVSI) and detection rate was found (p<0.001). CONCLUSION: SLN detection is feasible in early cervical cancer but presence of LVSI and a tumor size >2 cm negatively affect the detection rate and may increase the incidence of false negatives.

Intraoperative gross assessment of myometrial invasion and cervical involvement in endometrial cancer: Role of tumor grade and size.

OBJECTIVES: To evaluate the accuracy of visual examination of myometrial invasion and the involvement of the cervix in the hysterectomy specimen and to explore the role of tumor grade and size in the accuracy of gross estimation of myometrial invasion. METHODS: In 142 patients with apparent early endometrial cancer the uterus was opened after its removal and inspected. The size of the tumor (2 cm), the depth of myometrial invasion (less or greater than 50%) and the involvement of the cervix (as positive or negative) were visually estimated and recorded. All patients underwent surgical staging. The gross findings were compared with the final histological results. Estimations of myometrial invasiveness were analyzed according to the tumor grade and size. Accuracy, specificity, sensitivity, positive and negative predictive values were calculated. RESULTS: The overall accuracy rate for myometrial invasion was 81.7% (116/142). False positive and false negative results noted in 17/101 (17%) and 9/41 (21.9%) of patients. Sensitivity, specificity, positive and negative predictive values were 78%, 83.2%, 65.3% and 90.3% respectively. Gross estimation of invasion was more often successful in patients with smaller (

KIT-negative gastrointestinal stromal tumors with a long term follow-up: a new subgroup does exist.

AIM: To investigate the incidence of KIT immunohistochemical staining in (GI) stromal tumors (GISTs), and to analyze the clinical manifestations of the tumors and prognostic indicators. METHODS: We retrospectively analyzed 50 cases of previously diagnosed GISTs. Tissue samples were assessed with KIT (CD117 antigen), CD34, SMA, desmin, S-100, NSE, PCNA, Ki-67, and BCL-2 for immunohistochemical study and pathological characteristics were analyzed for prognostic factors. RESULTS: Fifteen tumors (30%) were negative in KIT staining. A significant association was observed between gender (male patients: 14/15) and KIT-negative staining (P = 0.003).The patients's mean age was 56.6 years. Tumors developed in stomach (n = 8), small intestine (n = 5), large intestine (n = 1) and oesophagus (n = 1). The mean tumor size was 5.72 cm. The mitotic count ranged from 0-29/50 HPF (mean: 3.4) and 73% of tumors showed no necrosis. The majority of the tumors (67%) had dual or epithelioid differentiation. Tumors were classified as very low or low risk (n = 7), intermediate risk (n = 5), and high risk (n = 3) groups. Twelve (80%) patients were alive without evidence of residual tumor for an average period of 40.25 mo (12-82 mo); three patients developed metastatic disease to the liver and eventually died within 2-12 mo (median survival: 8.6 mo). CONCLUSION: A small subgroup of GISTs fulfils the clinical and morphological criteria of these tumors, and lacks KIT expression. These tumors predominantly developed in the stomach, being dual or epithelioid in morphology, which are classified as low risk tumors and presented a better survival status than KIT-positive tumors. The ability to diagnose GISTs still depends on immunohistochemical staining but the research should extend in gene mutations.

"Solitary" necrotic nodule of the liver: an enigmatic entity mimicking malignancy.

AIM: The aim of the study is to further investigate the clinicopathological features of solitary necrotic nodules. MATERIAL AND METHODS: Twenty-three archived cases of solitary necrotic nodule of the liver, which were preoperatively misdiagnosed as liver metastases were studied. The pathological findings were correlated with the clinical data of the patients. RESULTS: The nodules were solitary in 20 cases and multiple (2) in three cases, and measured from 0.5-1.5 cm in diameter. Twenty-one cases were located in the right lobe of the liver (91.6%) and two in the left lobe (8.69%). Twenty nodules were found in the subcapsular region (86.95%), while three nodules were located within the hepatic parenchyma (13.04%). More then half of our cases (12) were accompanied by extended calcification. Granulomatous tissue resembling "burnt-out" parasitic granulomas was found in three cases. CONCLUSIONS: Solitary necrotic nodules of the liver often mimic malignancy in abdominal imaging. Thus, permanent histopathology of the operative specimen remains the only accurate method of diagnosis. Their pathogenesis is most likely variable, and most reported cases are linked either to a parasitic or a vascular origin. Despite the designation of these lesions as "solitary" they may occasionally be multiple. In addition to the standard histological criteria of solitary necrotic nodules, the relatively small size (15 mm or less) and the frequent presence of calcifications seem to further characterize this enigmatic entity. Solitary necrotic nodule should be included in the differential diagnosis of small liver lesions with extensive necrosis.