A presumed extragonadal germ cell tumor that turned out to be a gastric cancer-a case report.

A solely retroperitoneal mass in males in combination with elevated serum Alpha-Fetoprotein (AFP) and beta-human choriogonadotropin (ß-HCG) levels is highly indicative of a metastatic testicular cancer. Although testicular cancers are rare, they represent the most common diagnosed cancer in males between 14 and 40 years. However, in cases without evidence of a primary testicular tumor, the rare diagnosis of a retroperitoneal extragonadal germ cell tumor (EGCT) must be assumed. Here, we describe the first published case of a 66-year-old man presenting with this typical clinical picture and the diagnosis of an AFP and ß-HCG producing advanced gastric cancer with retroperitoneal lymph node metastases mimicking a primary retroperitoneal EGCT. The final diagnosis was only made by gastroscopy performed after a CT-guided retroperitoneal lymph node biopsy revealed an adenocarcinoma, suggesting an upper gastrointestinal tract primary origin. However, a specific initial anamnesis and also in the primary staging, including a full-body CT-scan there was no hint for another primary tumor. Only the slightly unusual extension of the retroperitoneal mass up to the ligamentum hepatoduodenale and the pylorus, as well as the atypical age made us question our initial diagnosis. This extraordinary case is of special clinical interest to all practising physicians and once again highlights the importance of keeping rare differential diagnosis such as AFP-producing gastrointestinal tumors in mind.

Immunohistochemical tracking of an immune response in mammary Paget's disease.

Dendritic cells (DC) are the most potent antigen-presenting cells of the organism. They are specialized to capture, process, and present antigen via the MHC class II as well as the MHC class I pathways to CD4+ and CD8+ T cells, respectively. This results in T cell-mediated immune responses that are likely to counteract the generation and propagation of tumors in vivo. Therefore, we studied the distribution of dendritic cells in mammary Paget's disease. Paraffin-embedded samples of Paget's disease of the breast (n=27) and of disease-free epidermis of the nipple (n=10) were investigated immunohistochemically for the presence of dendritic cells, in particular of Langerhans cells, using antibodies against S-100, CD1a, and HLA-DR, as well as novel reagents against Langerin/CD207, DC-LAMP/CD208 and p55 (Fascin), the latter two being specific for mature dendritic cells. Paget samples presented a decrease of CD1a+, S-100+, and Langerin+ intraepidermal Langerhans cells in almost all cases. This was paralleled by a concentration of immature dendritic cells in the tumor-infiltrated tissue itself. Similar to infiltrating breast carcinoma we observed a marked increase of DC-LAMP+ and p55+ mature dendritic cells in the corial tissue beneath the tumor. These cells were almost always found in ribbon-like or nodular lymphocytic infiltrates. Moreover, rare mature dendritic cells were also found in the Paget cell-infiltrated epidermis of the nipple, i.e. in the tumorous lesion itself. These findings may indicate an effective ongoing anti-tumor immune response in this part of spreading breast cancer.

STAT1 activation in squamous cell cancer of the oral cavity: a potential predictive marker of response to adjuvant chemotherapy.

BACKGROUND: For patients with squamous cell carcinoma of the oral cavity, both locoregional and distant recurrences are common, and an appropriate adjuvant treatment modality has yet to be defined. Thus, there is an urgent need to identify novel molecular markers with potential prognostic and/or predictive value to improve treatment outcome in these patients. This retrospective study was designed to investigate the predictive and/or prognostic value of STAT1 activation in squamous cell carcinoma of the oral cavity. METHODS: STAT1 expression and subcellular localization was examined immunohistochemically on a tissue microarray of paraffin-embedded tumor specimens from 89 patients who underwent surgical treatment in the period between 1980 and 1997. A nuclear staining score of greater than 35% was defined as high STAT1 activation. RESULTS: According to study criteria, 18% of analyzed tumor samples exhibited high STAT1 activation. High STAT1 activation was associated with negative lymph node status. Moreover, in the subgroup of patients who received chemotherapy, high nuclear STAT1 staining in the tumor was associated with good prognosis. CONCLUSIONS: This is the first report demonstrating the potential predictive value of STAT1 activation status in patients with squamous cell cancer of the oral cavity. If confirmed in large prospective trials, this molecular marker could help in guiding therapeutic decisions in these patients.

High EGFR expression predicts poor prognosis in patients with squamous cell carcinoma of the oral cavity and oropharynx: a TMA-based immunohistochemical analysis.

This retrospective study was designed to investigate the prognostic significance of EGFR overexpression in human oral squamous cell carcinoma on a long-term follow-up. EGFR expression was examined immunohistochemically on a tissue microarray (TMA) of paraffin embedded tissue specimens from 109 patients who underwent surgical treatment for squamous cell carcinoma of the oral cavity and oropharynx in the period between 1980 and 1997. High EGFR expression was found in 80 (73.42%) of the tumour samples. Kaplan-Meier curves showed that EGFR overexpression was significantly related to decreased overall survival (p=0.05). Multivariate analysis showed that EGFR overexpression is an independent prognostic marker in these patients (p=0.02, RR 3.6). These results confirm that EGFR overexpression is an independent prognostic marker in patients with squamous cell carcinoma of the oral cavity and oropharynx. The EGFR antigen represents an attractive target for targeted therapies with monoclonal antibodies or specific tyrosine-kinase inhibitors in these patients.

Detection of human papillomavirus DNA in breast cancer of patients with cervical cancer history.

BACKGROUND: Recent studies have revealed a possible role for the human papillomavirus (HPV) in the pathogenesis of breast cancer. In this study, patients having both a history of invasive cervical cancer and breast cancer as second primary cancer were selected for enrolment in a study of breast carcinomas for the presence of HPV. METHODS: Paraffin-embedded tissue from cervical cancer, pelvic lymph nodes, breast cancer and axillary lymph nodes of eleven patients were examined for the presence of HPV DNA using a polymerase chain reaction - enzyme immuno assay. DNA extraction was performed with the "QIAamp Tissue Kit" according to the manufacturer's instructions. Additionally, serum samples taken between diagnosis of cervical and breast cancer, were analyzed for the presence of HPV DNA to examine a possible haematogenous spread of oncogenic HPV DNA. RESULTS: All cervical carcinomas were HPV-positive. HPV DNA was detected in seven out of eleven cases in breast cancer and/or axillary lymph node tissue. Six patients had the same HPV type (HPV-16) in cervical cancer and in the corresponding breast cancer/lymph node tissue. In one case, the same HPV DNA type (HPV 16) was detected in cervical cancer, breast cancer and serum sample. CONCLUSION: These results suggest that HPV DNA might be transported from the original site of infection to the breast tissue by the bloodstream, and that it is possibly involved in the carcinogenesis of breast neoplasia in some patients.

Overexpression of epithelial cell adhesion molecule antigen in gallbladder carcinoma is an independent marker for poor survival.

PURPOSE: Gallbladder carcinoma is an aggressive type of cancer that is difficult to cure by conventional procedures. There thus is a need to identify novel molecular markers for the assessment of prognosis and as potential therapeutic targets. This retrospective study was designed to investigate the prognostic significance of epithelial cell adhesion molecule (Ep-CAM) overexpression in human gallbladder carcinoma. EXPERIMENTAL DESIGN: Ep-CAM expression was examined immunohistochemically on paraffin-embedded tissue specimens from 99 patients who underwent surgical treatment for gallbladder carcinoma in the period between August 1988 and May 1999. RESULTS: Ep-CAM overexpression was found in 63 (63.6%) of the tumor samples. Kaplan-Meier curves showed that Ep-CAM overexpression was significantly related to decreased overall survival (P < 0.01). Overall survival gradually worsened with increasing Ep-CAM scores. Notably, in the subgroup of pT1 tumors (n = 17), patients without Ep-CAM overexpression had a 5-year overall survival rate of 100% compared with 38% (P = 0.01) for patients with Ep-CAM-overexpressing tumors. By univariate analysis, no correlation was found with conventional clinicopathological parameters. Multivariate analysis, including Ep-CAM expression, pT stage, tumor grade, and resection margin involvement, showed that Ep-CAM overexpression was an independent prognostic marker in gallbladder carcinoma (P = 0.03; relative risk, 1.8). CONCLUSIONS: These results demonstrate for the first time that Ep-CAM overexpression is an independent prognostic marker in gallbladder carcinoma and that its prognostic impact should be validated prospectively. Furthermore, the Ep-CAM antigen represents an attractive target for specific therapies with monoclonal antibodies or specific vaccines in patients with Ep-CAM-overexpressing gallbladder carcinoma.

Phenotypic characterization and distribution of dendritic cells in parotid gland tumors.

Evidence on the relationship between the infiltration of dendritic cells (DCs) and prognosis in head and neck tumors exists. Interestingly, only limited information is available regarding the maturation state and distribution of DCs in parotid gland tumors. The purpose of our study was therefore to extend these observations and to investigate in more detail the density and distribution of mature DCs and Langerhans cells (LCs) in parotid gland tumors. We present immunohistochemical evidence of characterization and distribution of DCs and LCs in parotid gland tumors, enclosed pleomorphic adenomas and malignant parotid tumors. Two populations of mature DCs could be identified, P55(+)-DCs and DC-LAMP(+)-DCs, whereas LCs could be identified as Langerin(+)-LCs. The overall impression was that parotid gland tumors contained only few mature DCs and LCs. Considering the sparsity of mature DCs in the malignant tissues, anti-tumor response can be only limited. On the basis of our data, we imply that the application of DC vaccination in combination with other modalities for treatment of parotid gland carcinoma should be taken into account. In this regard, the utilization of DC immunotherapy for management of minimal residual disease after resection of primary tumor can be promising. Putative targets expressed in this type of tumors have to be defined.