Aneurysmal rib cyst.

Thoracic cage is the site of development of various primary or metastatic tumors. An aneurysmal rib cyst is a benign tumor arising from the chest wall. Aneurysmal rib cyst is considered a rare surgical entity and its presence must be followed by removal for histology examination. We present here the case of an aneurysmal rib cyst to a young 33-year-old female. The tumor was presented as an expanding left anterior second rib mass during a self-breast examination. Chest x-ray showed a shadow on the left upper lung area and CT scan revealed a large multicystic mass in the anterolateral left 2nd rib protruding underneath the thoracic major muscle. We discuss the clinicopathological characteristics of this tumor and its surgical management along with a short literature review.

Two foreign bodies embedded in the intraventricular septum: A case report.

A 23-year old male was presented at the outpatient clinic of our department reporting that he had been subjected to insertion of foreign bodies in his chest. Physical examination was unremarkable. Imaging studies revealed the presence of two bodies in the subcutaneous tissue of the anterior chest wall and two needle-shaped intramyocardial bodies that were impacted in the intraventricular septum. Due to late appearance, the position, and because of the absence of symptoms, it was decided that the patient should be managed conservatively. Today, five years after the incident, the patient remains asymptomatic and he is followed-up regularly.

Can the Ratio SUVmax of the Lesion/SUVmax of Mediastinal Tissues Guide the Choice of Surgical Access for the Resection of Thymic Epithelial Tumors?

Background: There are studies showing the utility of the 18-fluorodeoxyglucose positron emission tomography (18FDG PET) scan in the management of patients with thymic epithelial tumors. It seems to be a correlation between the standard uptake value (SUVmax) of thymic epithelial tumors and the histological type and the stage. This study aims to use the ratio of the SUVmax of the lesion to the SUVmax of the adjacent mediastinal tissues in order to guide the choice of the surgical access. Methods: All patients who presented an anterior mediastinal lesion with a high suspicion of being of thymic origin were included in a prospective database. A ratio inferior to 1 could predict a benign nature and less aggressive behavior, and a minimally invasive approach was performed. A ratio superior to 1 suggested a malignant and aggressive behavior, and a median sternotomy (or a thoracotomy) was performed. Results: There were 15 male (mean age 44.6 ± 16.26 years, range 25-73) and 15 female patients (mean age 50.1 ± 16.94 years, range 25-76). When the ratio is inferior to 1, it predicts benign disease in 80% of cases. When it is superior to 1, it predicts in half of cases advanced histological types (high risk thymomas and thymic carcinomas). On the contrary, it can quite accurately predict advanced Masaoka-Koga stages. Conclusions: The protocol of this study is in accordance with the current literature showing the utility of 18FDG PET scan in the treatment of thymic epithelial tumors. This study goes one step further since the choice of surgical access is based on the SUVmax values. The ratio SUVmax of the lesion/SUVmax of the mediastinal tissues could be a new marker, more pertinent than absolute SUVmax values.

Levels of cyclooxygenase-2 are increased in the oral mucosa of smokers: evidence for the role of epidermal growth factor receptor and its ligands.

Cyclooxygenase-2 (COX-2) is a promising pharmacologic target for preventing aerodigestive malignancies. In this study, we investigated the effects of tobacco smoke on the expression of COX-2 in oral mucosa. An approximately 4-fold increase in amount of COX-2 mRNA was observed in the oral mucosa of active smokers versus never smokers. Thus, a series of in vitro studies were carried out to elucidate the mechanism by which tobacco smoke induced COX-2. Treatment of a nontumorigenic oral epithelial cell line (MSK-Leuk1) with a saline extract of tobacco smoke (TS) stimulated COX-2 transcription, resulting in increased amounts of COX-2 mRNA, COX-2 protein, and prostaglandin E(2) (PGE(2)) synthesis. Exposure of cells to TS also caused an increase in epidermal growth factor receptor (EGFR) tyrosine kinase activity. Both an inhibitor of EGFR tyrosine kinase activity and a neutralizing anti-EGFR antibody blocked TS-mediated induction of COX-2. To define the mechanism by which TS activated EGFR, the release of amphiregulin and transforming growth factor alpha, two ligands of the EGFR, was measured. Exposure to TS caused a rapid increase in the release of both ligands. TS also markedly induced the expression of mRNAs for amphiregulin and transforming growth factor alpha. Importantly, increased expression of both ligands was also detected in the oral mucosa of active smokers. Taken together, these results suggest that activation of EGFR signaling contributes to the elevated levels of COX-2 found in the oral mucosa of smokers. Moreover, these findings strengthen the rationale for determining whether inhibitors of COX-2 or EGFR tyrosine kinase activity can reduce the risk of tobacco smoke-related malignancies of the aerodigestive tract.

Colonic wall thickening on computed tomography scan and clinical correlation. Does it suggest the presence of an underlying neoplasia?

The widespread use of computed tomography (CT) scanning technology frequently leads to the incidental discovery of thickened bowel wall. The clinical significance of such a CT scan finding is largely under-investigated. The purpose of our study was to determine the incidence of significant clinical pathology and, particularly, neoplasia in patients with abnormally thickened bowel on CT scan examination. This is a single institution retrospective analysis of patients that underwent CT scanning of their abdomen. The radiological picture was correlated with colonoscopic findings. A total of 40 consecutive patients with thickened bowel on CT scan that also underwent colonoscopy were identified and their records were reviewed. Thirty-five patients had no history of previous gastrointestinal disorder and form our study group. The median age of the patients was 69 years (range, 24-97 years). There were 26 female and 9 male patients. The incidental CT finding of bowel wall thickening was the only reason for the colonoscopy in 14 (35%) out of the 40 patients. Eight (23%) patients with thick bowel had colonic neoplasia based on pathology. Five (14%) patients had invasive adenocarcinoma of the colon. Four (11%) of the 5 patients with colon adenocarcinoma did not have any associated gastrointestinal symptoms or signs. One (3%) patient had lymphoma of the colon and two (6%) had benign polyps. Colonoscopy was unremarkable in 10 (28%) patients. The incidental finding of colonic thickening on CT imaging could be associated with underlying colonic malignancy and, more importantly, represent the initial disease presentation. Therefore, we propose that these patients should undergo colonoscopy.

SIN1, a critical component of the mTOR-Rictor complex, is overexpressed and associated with AKT activation in medullary and aggressive papillary thyroid carcinomas.

BACKGROUND: Mammalian target of rapamycin (mTOR) forms 2 active complexes in the cell: the rapamycin-sensitive mTOR-Raptor (mTORC1) and the rapamycin-insensitive mTOR-Rictor (mTORC2). The latter activates AKT kinase, which promotes tumor cell survival and proliferation by multiple downstream targets. Mammalian stress-activated protein kinase interacting protein 1 (SIN1), an essential subunit of the mTORC2 complex, maintains the integrity of the complex and substrate specificity and regulates Akt activation. The role of mTOR-Rictor complex activation in thyroid carcinogenesis remains unknown. Therefore, we investigated expression patterns of Sin1 in the cells lines of thyroid carcinoma and tumors and their association with AKT activation, histologic type, and tumor aggressiveness. METHODS: Tissue specimens from 42 patients with thyroid cancer, including follicular (5), papillary (18), medullary (16), and poorly differentiated (3) carcinomas were analyzed via immunohistochemistry for SIN1 expression and AKT phosphorylation at Ser473 residue (Ser473-p-AKT). Eight of 18 papillary carcinomas were aggressive histologic variants. In addition, expression of Sin1 and activation of AKT kinase were analyzed in fresh-frozen tissue samples (normal/tumor), primary cell cultures (papillary thyroid carcinoma [PTC]), and an established thyroid cancer cell line (medullary thyroid carcinoma) by Western blotting. RESULTS: With immunohistochemistry, we found that Sin1 was overexpressed in medullary thyroid carcinomas and aggressive variants of papillary thyroid carcinoma compared with conventional papillary and follicular carcinomas (P < .001). Sin1 expression correlated with AKT activation in the entire study group (P = .002). Using Western blot analysis, we found that Sin1 and p-AKT were detected at a greater level in cultured primary cells from aggressive PTC compared with conventional PTC as well as in cell lines of medullary and anaplastic thyroid carcinoma. High expression levels of SIN1 were detected in papillary thyroid carcinomas compared with benign nodules in immunoblots in which we used fresh-frozen patient samples. Two of the Sin1 protein isoforms, p76 and p55, were detected predominantly in PTC samples. CONCLUSION: Sin1, a critical factor of the mTORC2 complex is overexpressed in clinically aggressive thyroid cancer types and is associated strongly with activation of AKT kinase. Sin1-dependent AKT activation might represent a target for experimental therapy.

Activation of mTOR signaling in medullary and aggressive papillary thyroid carcinomas.

BACKGROUND: Because mammalian target of rapamycin (mTOR) may be involved in thyroid carcinogenesis, we investigated the expression and activation patterns of mTOR signaling proteins in thyroid carcinoma cells and tumors and their association with tumor histology and aggressiveness. METHODS: Tissue specimens from 50 patients with thyroid cancer were analyzed for eIF4E, a critical downstream target of the mTOR pathway, using immunohistochemistry. In addition, fresh-frozen samples from patients, and primary tumor cell cultures were analyzed for expression and activation of mTOR signaling proteins by Western blot. Moreover, pharmacologic studies with rapamycin were performed. RESULTS: High expression of eIF4E was observed in medullary thyroid carcinomas (MTC) and in aggressive variants of papillary thyroid carcinomas (PTC) as compared with conventional PTC and follicular thyroid carcinomas (P < .0001). The level of eIF4E expression also correlated with tumor stage (P = .002). Using Western blot analysis, p-rpS6, p-4EBP1, 4EBP1, and eIF4E were detected at higher levels in aggressive PTC and MTC cells. Treatment of MTC cells with increasing concentrations of rapamycin resulted in significant cell death and in decreased cell growth associated with deactivation of the mTOR pathway. CONCLUSION: mTOR signaling, which controls protein synthesis through regulation of translation initiation, is activated in aggressive PTC and MTC and represents a promising target for investigational therapies in these patients.

Clinical curiosity: cribriform-morular variant of papillary thyroid carcinoma.

BACKGROUND: There is an increasing awareness of the association of papillary thyroid carcinoma and familial adenomatous polyposis (FAP). Although the incidence is rare, most tend to occur in women. Several authors have described a distinctive histologic variant of papillary thyroid carcinoma, the cribriform-morular variant, which is associated with FAP but also may be encountered in patients with non-FAP. This diagnosis may precede the symptoms of colorectal polyposis. METHODS: A healthy 36-year-old woman was seen with a left thyroid nodule, and a 34-year-old woman with FAP was seen with a right thyroid nodule; both masses were suspicious for papillary thyroid carcinoma. Both patients underwent total thyroidectomy. RESULTS: Pathologic examination of both specimens revealed papillary thyroid carcinoma, cribriform-morular variant. The first patient subsequently underwent colonoscopy, which was negative for polyposis. CONCLUSIONS: Patients diagnosed with the cribriform-morular variant of papillary thyroid cancer should be screened for the presence of FAP.