Extensive Local Invasion Research Articles

Life Expectancy Is Reduced in Differentiated Thyroid Cancer Patients ≥ 45 Years Old with Extensive Local Tumor Invasion, Lateral Lymph Node, or Distant Metastases at Diagnosis and Normal in All Other DTC Patients

Differentiated thyroid carcinoma (DTC) generally has a good prognosis. As yet, however, it is unclear whether life expectancy is reduced in these patients and, if so, to what extent. The aim of this study was to determine how the all-cause mortality rate in DTC patients compares to that of the general population. A prospective database study was conducted. The study included 2011 DTC patients treated in our hospital from 1980-2011. All patients received total thyroidectomy with subsequent (131)I ablation, except for those with an isolated papillary microcarcinoma. Survival data for the general German population were obtained from the German Federal Statistics Agency and matched to our DTC population for age and sex. Patients who were at least 45 yr old at diagnosis and had extensive perithyroidal invasion (UICC/AJCC TNM system, 7th edition, stages IVa and IVb), lateral cervical lymph node metastases (TNM stage IVa), or distant metastases (TNM stage IVc) showed a clearly reduced life expectancy [relative cumulative survival rate (observed:expected) for stage IVc after 20 yr, 0.295; 95% confidence interval, 0.033-0.556]. In patients over 60 yr of age at diagnosis, the loss of life expectancy was (much) greater than for those aged 45-59 yr in all groups. Life expectancy was not reduced in patients with TNM stages I, II, or III (86% of patients). Life expectancy is not significantly reduced in 86% of DTC patients; only patients at least 45 yr old with extensive local invasion, lateral lymph node metastases, and/or distant metastases (TNM stages IVa, IVb, and IVc) at diagnosis showed a clearly lower life expectancy.

Sinonasal non‐keratinizing squamous cell carcinoma with nasal skin extension as the initial presentation

Sinonasal non-keratinizing squamous cell carcinoma (SCC), previously designated as transitional cell carcinoma or cylindrical cell carcinoma, is an uncommon malignant neoplasm with distinct histopathological features, considered to be a low-grade malignancy that usually occurs in elderly patients. Extensive local invasion is uncommon. Here we report a case of 90-year-old woman whose original presentation was as erythematous nasal skin nodules, biopsy of which showed a dermal tumor with features of sinonasal non-keratinizing SCC. No epidermal dysplasia was present. A subsequent computed tomography scan confirmed the presence of an endophytic tumor on the nasal sidewall. The initial presentation of sinonasal non-keratinizing SCC as a skin lesion is previously unreported to our knowledge. Diagnosis in this context requires accurate evaluation of the histopathology as well as a comprehensive knowledge of pathology specific to this anatomic location.

The microRNA expression changes associated with malignancy and SDHB mutation in pheochromocytoma

Currently, the diagnosis of malignant pheochromocytoma can only be made when there is clinical evidence of metastasis or extensive local invasion. Thus, there is a need for new diagnostic marker(s) to identify tumors with malignant potential. The purpose of this study was to identify microRNAs (miRNAs) that are differentially expressed between benign and malignant pheochromocytomas and assess their diagnostic accuracy. Toward this aim, we analyzed miRNA expression in benign and malignant pheochromocytoma tumor samples using whole genome microarray profiling. Microarray analysis identified eight miRNAs that were significantly differentially expressed between benign and malignant pheochromocytomas. We measured a subset of these miRNAs directly by RT-PCR and found that miR-483-5p, miR-183, and miR-101 had significantly higher expression in malignant tumors as compared to their benign counterparts. Area under the receiver operating curve (AUC) analysis indicated that miR-483-5p, miR-101, and miR-183 could be useful diagnostic markers for distinguishing malignant from benign pheochromocytomas. In addition, these miRNAs could be detected in pheochromocytoma patient serum. Overall our data suggest that misexpression of miR-483-5p, miR-101, and miR-183 is associated with malignant pheochromocytoma.

DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/uPA

A major hallmark of pancreatic ductal adenocarcinoma (PDAC) is extensive local tumor invasion and early systemic dissemination. DJ-1 has been shown to prevent cell death via the Akt pathway, thereby playing an important role in cancer progression and Parkinson's disease development. Here, we investigated the role of DJ-1 in tumor invasion and metastasis of pancreatic cancer and showed that DJ-1 is upregulated in 68.5% of pancreatic cancer specimens, correlated with tumor stage and predictive of short overall survival. Knockdown of DJ-1 expression in two PDAC cell lines reduced cell migration and invasion potential in vitro and inhibited metastasis in vivo. Knockdown of DJ-1 led to cytoskeleton disruption and diminished urokinase plasminogen activator (uPA) activity and expression, without affecting plasminogen activator inhibitor-1 and uPA receptor (uPAR) expression. All these effects were reversed by restoration of DJ-1 expression. In determining the pathway through which DJ-1 regulated cell migration and invasion, DJ-1 was found not to regulate Akt phosphorylation. Rather, it promoted extracellular signal-regulated kinase (ERK) and SRC phosphorylation. Inhibition of the ERK pathway in PDAC mimicked the effects of DJ-1 on cell migration, invasion, actin cytoskeleton and uPA/uPAR system and abolished the effects on promoting PDAC cell invasion and migration. These data represent the first identification of an important function of DJ-1, which is to regulate the invasion and metastasis properties of PDAC through the ERK/uPA cascade.

Cancer Stem Cells and Pluripotency

Determining the functional roles of cancer stem cells (CSCs) and epithelial to mesenchymal transition (EMT) in carcinogenesis and tumorigenesis are pivotal topics in cancer biology research in general and pancreatic cancer in particular. Several publications, including ours, have demonstrated that CSCs and EMT function in tandem, ultimately leading to cancer progression and metastasis [1]. This has been demonstrated in breast, pancreas, and colorectal cancers and likely occurs in all types of cancers. A pressing issue in the field of CSC and EMT research is that of pancreatic adenocarcinoma (PDAC), as it has the worst prognosis of any major malignancy with a 3% 5-year survival rate [2]. Major obstacles in treating pancreatic cancer include delayed diagnosis, extensive local tumor invasion, and early metastasis. CSCs, or cancer initiating cells (CICs), represent approximately 1% to 5% of the tumor, and are capable of unlimited self-renewal, and are often resistant to chemotherapy and radiation therapy [3]. This may explain why these treatments do not cure or prevent recurrence of PDAC [4,5]. Improving survival for all types of cancer likely hinges on the identification and eradication of CSCs. The existence of CSCs was first demonstrated in acute myelogenous leukemia [6] and subsequently verified in breast [7], pancreatic [8], and brain tumors [9-11]. The CD133+ subpopulations from brain tumors can initiate clonally derived neurospheres in vitro showing self-renewal, differentiation, and proliferative characteristics similar to normal brain stem cells [9-11]. In a recent study, a subpopulation of CD44+ CD24+ ESA+ cells derived from primary human pancreatic adenocarcinoma CSCs [8] were implanted in immunocompromised mice and resulted in enhanced tumorigenic potential. We have recently demonstrated that doublecortin and CAM kinase-like-1 (DCAMKL-1) is a pancreatic stem cell marker that is upregulated in pancreatic cancer and may be a marker of CSCs [1,12].

Primary Giant Cell Tumor of Soft Tissue in the Mental Region

Giant cell tumors of soft tissue (GCT-ST) are considered to be the soft tissue analogue of giant cell tumors of bone. Although the majority of GCT-ST cases manifest histologically benign features, special consideration is required because GCT-ST can occasionally demonstrate extensive local invasion or distant metastases. Here, we present an extremely rare case of GCT-ST arising from subcutaneous mental soft tissue, rapidly growing over the mandibular gingiva and bone, and lacking overtly malignant features in clinical, radiological and cytological findings.

Role of staging laparoscopy in gastric malignancies - our institutional experience

To investigate the value of staging laparoscopy with laparoscopic ultrasound (LUS) and peritoneal lavage cytology in patients with newly-diagnosed gastric tumours in our department. Retrospective review of prospectively-collected data was conducted in all patients with newly-diagnosed gastric tumours on oesophagogastroduodenoscopy between December 2003 and July 2008. All the patients had a pre-treatment histological diagnosis and were discussed at the hospital multidisciplinary tumour board meeting for their definitive management. Computed tomography scan was performed in all patients as a part of standard preoperative staging work up. Staging laparoscopy was subsequently performed in selected patients and staging by both modalities was compared. Twenty seven patients were included. Majority of patients had cardio-oesophageal junction adenocarcinoma. Thirteen patients (48%) were upstaged following staging laparoscopy and one patient was downstaged (3.7%). None of the patients had procedure-related complications. None of the patients with metastasis detected at laparoscopy underwent laparotomy. Gastrectomy after staging laparoscopy was performed in 13 patients (9 R0 resections, 3 R1 resections and 1 R2 resection). Only one patient did not have gastrectomy at laparotomy because of extensive local invasion. Three patients were subjected to neoadjuvant therapy following laparoscopy but only one patient subsequently underwent gastrectomy. In this small series reflecting our institutional experience, staging laparoscopy appears to be safe and more accurate in detecting peritoneal and omental metastases as compared to conventional imaging. Peritoneal cytology provided additional prognostic information although there appeared to be a high false negative rate.

Analysis of Treatment And Prognosis of 134 Thymic Carcinoma Patients

Analysis of Treatment And Prognosis of 134 Thymic Carcinoma Patients

Clinicopathologic and immunohistochemical characteristics of adult primary cardiac angiosarcomas: analysis of 10 cases

Primary cardiac angiosarcoma is a rare but the most common malignant neoplasm of the heart in adults. The objective of this study is to analyze the clinicopathologic characteristics of primary cardiac angiosarcoma. Ten cases of primary cardiac angiosarcoma treated in a single institution were analyzed for their clinical, pathologic, and immunohistochemical features. There were 6 men and 4 women, with a mean age of 40 years (range, 20-61 years). The patients commonly presented with dyspnea and distant metastasis. All tumors were located in the right atrium, with a mean tumor size of 6.8 cm. Tumors were hemorrhagic, with variegated tan-brown solid areas. Histologically, they exhibited high-grade morphology with mixed solid growth and anatomizing channels. Frequent mitoses and tumor necrosis were common. The tumors were strongly positive for CD31, CD34, FLI-1, and WT-1 but negative for AE1/3, D2-40, human herpesvirus 8, and epidermal growth factor receptor. The tumor cells were focally reactive to p53, with a high rate of Ki-67 expression. A complete tumor resection was not possible in any of the patients because of the size or extensive local invasion of the tumor. Overall survival ranged from 1 to 81 months (mean, 26.6 months) after initial histologic diagnosis. Primary cardiac angiosarcomas are rare tumors that commonly arise in the right atrium. The mean age is much younger than that of soft tissue angiosarcoma. Regional tumor extension and distant metastasis are extremely common at the time of diagnosis. Surgical resection with adjuvant chemotherapy is currently the preferred treatment, and survival time appears to be inversely correlated with the tumor size and degree of regional tumor extension at the time of surgery.

Mohs Micrographic Surgery in the Treatment of Microcystic Adnexal Carcinoma

Microcystic adnexal carcinoma is a rare neoplasm with a propensity for slow growth and extensive local invasion. Pathology is characterized by multiple islands of basaloid epithelial cells, ductal structures, and keratinizing cysts, located intradermally but often extending deep as thin strands of tumor cells intercalating between collagen bundles. Perineural and intramuscular invasion are common. Treatment with Mohs surgery allows for fewer procedures with increased likelihood of long-term cure and tissue conservation.

Expression of Galectin-3, nm-23, and Cyclooxygenase-2 Could Potentially Discriminate Between Benign and Malignant Pheochromocytoma

Currently, the only reliable indicator of malignancy in pheochromocytoma is the presence of distant metastasis or extensive local invasion; predicting behavior of pheochromocytoma remains challenging. We aimed to correlate the behavior of pheochromocytoma with its expression of nm-23, cyclooxygenase (COX)-2, and galectin-3 (genes used to predict the course of some neoplastic diseases), evaluated immunohistochemically in 55 paraffin blocks of formalin-fixed pheochromocytoma specimens with confirmed behavior. In 3 (7%) of 44 benign and 7 (64%) of 11 malignant pheochromocytomas, there was negative nm-23 expression (P = .000). COX-2 immunoreactivity was positive in 10 (23%) of benign and 9 (82%) of malignant tumors (P = .000). Galectin-3 was expressed in 5 (11%) of benign and 9 (82%) of malignant pheochromocytomas (P = .000). Negative nm-23, along with positive COX-2 or galectin-3, predicted malignancy with 100% specificity. Dual negativity for galectin-3 and COX-2, along with nm-23 positivity, indicated benign behavior with 100% sensitivity. In early pheochromocytoma, evaluation of nm-23, galectin-3, and COX-2 expression could predict the outcome. Larger studies seem necessary to confirm the potential practical value of our findings.

Congenital infantile fibrosarcoma of the forearm

Congenital infantile fibrosarcoma is a rare soft tissue neoplasm in the infant of which only a few cases are reported as congenital. This tumor has a rapid growth and extensive local invasion, but metastasis rarely occurs. Distal extremities involvement is more common and metastasis are rare. We report a case of a congenital infantile fibrosarcoma of the forearm, which was initially confused with a hemangioma, treated successfully by surgical resection.

Synovial Sarcoma of the Thyroid Gland

Primary synovial sarcoma of the thyroid is an extremely rare condition which has only been reported twice in the literature. We herein report a case of highly aggressive and rapidly lethal primary synovial sarcoma of the thyroid. A 72-year-old woman presented with extensive local invasion, rapid progression, and early distant metastasis secondary to primary thyroid synovial sarcoma. The tumor exhibited an atypical histologic and immunohistochemical staining pattern. Detection of SYT/SSX fusion transcript confirmed the diagnosis of synovial sarcoma. Due to the aggressive nature of primary synovial sarcoma of the thyroid gland, early diagnosis and comprehensive treatment including wide resection and postoperative chemoradiation is required.

Primary major airway tumors; management and results

Primary major airway tumors are rare. A retrospective analysis of referral centers experience could be helpful for their management. Fifty-one patients, including 44 (86%) malignant and seven (14%) benign with primary tumors of subglottis, trachea, carina, and main stem bronchi, were managed in a 14-year period. Based on computed tomography (CT) scan and rigid bronchoscopy findings, those who evaluated as resectable underwent airway resection and reconstruction. The others were managed by one or a combination of these methods: core out, laser, chemotherapy, radiotherapy, and tracheostomy. Follow-up was completed in 88.2%, mean (35.2 ± 33.2 months). Extraluminal extension of the tumor found in CT scan was significantly associated with unresectability (p = 0.006). Thirty-two patients underwent resection with three complications (9%) and one mortality (3%). Nineteen were managed by non-resectional methods; of these, 15 were found unresectable, because of tumor length, extensive local invasion or diffuse distant metastases, and four due to risk-benefit ratio or patient preference. Among 18 patients with adenoid cystic carcinoma 13 (72%) were resected (seven with negative margins). Overall 1-, 2-, 5-, and 8-year survival was 90.9%, 90.9%, 77.9%, and 19.5%, respectively. In unresectable tumors with adenoid cystic carcinoma, overall 1- and 2-year survival was 60% and 40%, respectively. Data analysis found significant association of long-term survival with resection (p = 0.005) but not with negative margins in adenoid cystic carcinoma. Among 15 patients with carcinoid tumors, all were alive at the end of follow-up, except one who died after surgery. Airway resection, if feasible, may extend survival and may even be curative, with low morbidity and mortality, in most patients with major airway tumors.

Two Cases of Small Cell Carcinoma of the Gallbladder

Small cell carcinoma of the gallbladder is a rare disease process with approximately 40 cases reported in the literature. It is most often found in elderly female population and is associated with cholelithiasis and cigarette smoking. A multidisciplinary approach to treatment with wide surgical resection and adjuvant chemotherapy is the current standard of care. Notwithstanding prompt medical intervention, it is a disease with a poor prognosis. The pathology is characterized by early metastases and extensive local invasion. Herein, we report two cases of small cell carcinoma addressed at our institution. In both cases, a radical resection was performed with subsequent referral to oncology for additional therapy.

Invasive neuroendocrine tumor of the kidney: a case report

Neuroendocrine tumors (NETs) involve the genitourinary system in less than 1% of cases, with primary renal carcinoids comprising only 19% of reported genitourinary NETs (56 cases worldwide). We report a case of a renal NET presenting as a large renal mass with extensive local invasion, requiring definitive radical en bloc resection via a thoracoabdominal approach.

UP-3.017: Cytoplasmic MislocalizatIon of the Orphan Nuclear Receptor is a Prognostic Factor in Bladder Cancer

One of the reasons for poor prognosis is that bladder cancer, being highly invasive, is frequently associated with extensive local invasion or regional lymph node metastasis, even at initial diagnosis. Therefore, identification of novel targets associated with progression of bladder cancer is sorely needed. In recent years several new specific biomarkers for predicting prognosis of bladder cancer patients have been identified. Nurr1 belongs to the orphan nuclear receptor NR4A family which consists of Nur77 (NGIF-B/NR4A1), Nurr1 (NOT/NR4A2), and NOR-1 (MINOR/NR4A3).

Unexpected Urine Drug Testing Results in a Hospice Patient on High-Dose Morphine Therapy

A 41-year-old African-American woman was admitted to an inpatient hospice facility with advanced, inoperable cervical cancer. The patient was experiencing severe pain secondary to extensive local tumor invasion, osseous pelvic metastases, and sacral decubitus ulcers. Her pain was treated with an escalating-dose schedule of morphine sulfate until satisfactory analgesia was achieved with stable doses of a combination of controlled-release morphine sulfate (MSContin®, Purdue Pharma LP) 400 mg orally every 8 h, and immediate-release morphine sulfate (MSIR®, Purdue Pharma LP), 180 mg orally every 4 h, as needed for breakthrough pain (average 2 to 3 doses per day). The patient experienced several episodes of life-threatening vaginal bleeding for which she was hospitalized for red blood cell transfusions and bilateral hypogastric artery embolizations. She spent the final 12 weeks of her life exclusively on the inpatient hospice unit. Approximately 3 weeks before her death, the patient underwent urine specimen collection and analysis of morphine and metabolites. GC-MS analysis revealed the presence of morphine as well as small quantities of hydromorphone. During the past 2 decades, chronic opioid analgesic therapy (COAT) for chronic nonmalignant pain has gained increasing clinical acceptance. An unintended consequence of more liberal opioid prescription practices has been a dramatic increase in the abuse and diversion of these drugs. According the most recent National Survey on Drug Abuse and Health (1), the number of new, past-year abusers of prescription opioids was 2 147 000—more than the number of new abusers of any other single class …

Effects of small interfering RNAs targeting Fascin on gene expression in oral cancer cells

Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. The prognosis of OSCC is usually poor because of extensive local invasion at initial diagnosis. In the literature, Fascin has been reported responsible for cell motility and over-expression of Fascin contributes to an unfavorable clinical course. Nevertheless, the roles of Fascin protein playing in aggressiveness of OSCC and their potential mechanisms need to be elucidated. Two cell lines of OSCC (OECM-1 and SCC-25) via the vector-based small interfering RNA (siRNA) to suppress the expression of the Fascin gene were used. Subsequent analyses and observation regarding the expression of Fascin protein and cyto-morphological alterations were detected by Western blot and immunofluorescent microscopy. Boyden chamber invasion assay, cell migration assay and adhesion assay were also applied to investigate the functional changes of OSCC. There were statistically significant differences (P < 0.05) of Fascin expression before and after silencing. Down-regulation of Fascin protein directly led to changes of cell surface protrusions under immunofluorescent microscopy and resulted in suppression of migration, invasion and increase of adhesion in both cell lines (P < 0.05). Furthermore, down-regulation of Fascin expression also resulted in alterations of E-cadherin, beta-catenin and TWIST at certain level, implicative of an association with epithelial-mesenchymal transition (EMT). Our results suggest that expression of Fascin protein may play an essential role in regulation of progression of OSCC and contributes to the event of EMT in the early aggressiveness of OSCC.

Stathmin as a Marker for Malignancy in Pheochromocytomas

Pheochromocytomas of the adrenal medulla may be life-threatening catecholamine-producing tumors which are malignant in about 10% of cases. Differential diagnosis between malignant and benign tumors is dependent on the development of metastasis or extensive local invasion. A number of genetic aberrations have been described in pheochromocytomas, but no marker associated to malignancy has been reported. We applied an expression microarray containing 7770 cDNA clones and analysed the expression profiles in eleven tumors compared to normal adrenal medulla. Stathmin (STMN1, Op18) was most conspiciously overexpressed among the differentially expressed genes. RT-PCR analysis further confirmed mRNA overexpression, 6 to 8-fold for benign and malignant tumors, and 16-fold for metastases. Stathmin protein overexpression was observed by immunohistochemistry, and distinct differential protein expression between benign and malignant/metastasis specimens was confirmed by Western blot analysis. The results introduce stathmin as a possible diagnostic marker for malignant pheochromocytomas, and further evaluations are warranted.