Systemic Lymphadenopathy as the Initial Presentation of Malignant Mesothelioma: A Report of Three Cases

Systemic lymph node metastasis is a rare event in malignant mesothelioma. It is even more exceptional when systemic lymph node metastasis is the initial clinical presentation. Review of literature discloses only four cases in which metastatic lymphadenopathy was the only symptom of malignant mesothelioma. We, herewith, report three cases where the initial diagnosis of malignant mesothelioma was made by biopsy of enlarged lymph nodes, which were the only clinical presentation. Immunohistochemistry played a pivotal role in elucidating the mesothelial origin of their unusual systemic lymph node metastasis

Prognostic Significance of Serum Vascular Endothelial Growth Factor-C (Serum Vegf-C) and Lymph-Vascular Space Invasion in Early Stage Cervical Cancer

Background: Management of early stage cervical cancer is still challenging. Several clinical-pathological prognostic factors that are currently used in clinical practice include stage, bulky tumor, stromal deep invasion, differentiation, histology, lymph vascular space invasion and status of lymph-node. Serum Vascular Endothelial Growth Factor-C (VEGF-C) has an important role in metastasis as an angiogenic and lymphangiogenic factor. This study aimed to determine prognostic significance of serum VEGF-Cand lymph-vascular space invasionin early stage cervical cancer. Subjects and Method: This was a case-control study conducted at January to October 2007. A sample of47 early-stage cervical cancer patients including 14 patients with lymph node metastasis (case) and 33 patients without lymph node metastasis (control) was selected for this study. The dependent variable was lymph node metastasis. The independent variables were serum VEGF-C and lymph vascular space invasion. Serum VEGF-C levels were examined by ELISA method. The data were analyzed by logistic regression. Results: A cut-off point of serum VEGF-C level of 10.07 pg/ mLresulted in 78.57% sensitivity and 96.97% specificity. The risk of lymph node metastasis increased with serum VEGF-C level > 10.07 pg/ mL (OR= 80.0; 95% CI=7.99 to 800.71; p< 0.001) and lymph vascular space invasion (OR= 20.00; 95% CI=2.32 to 171.7; p= 0.006). Conclusion: Serum VEGF-C and lymph vascular space invasion can be used as independent prognostic factor on the risk of lymph-node metastasis in early stage cervical cancer. Keywords: cervical cancer, prognostic factor, serum VEGF-C, lymph node metastasis

The balance of VEGF-C and VEGFR-3 mRNA is a predictor of lymph node metastasis in non-small cell lung cancer

A positive association between vascular endothelial growth factor-C (VEGF-C) expression and lymph node metastasis has been reported in several cancers. However, the relationship of VEGF-C and lymph node metastasis in some cancers, including non-small cell lung cancer (NSCLC), is controversial. We evaluated the VEGF-C and vascular endothelial growth factor receptor-3 (VEGFR-3) expression in NSCLC samples from patients who had undergone surgery between 1998 and 2002 using real-time quantitative RT–PCR and immunohistochemical staining. We failed to find a positive association between VEGF-C and VEGFR-3 mRNA expression and lymph node metastasis in NSCLC. An immunohistological study demonstrated that VEGF-C was expressed not only in cancer cells, but also in macrophages in NSCLC, and that VEGFR-3 was expressed in cancer cells, macrophages, type II pneumocytes and lymph vessels. The VEGF-C/VEGFR-3 ratio of the node-positive group was significantly higher than that of the node-negative group. Immunohistochemical staining showed that VEGFR-3 was mainly expressed in cancer cells. The immunoreactivity of VEGF-C and VEGFR-3 was roughly correlated to the mRNA levels of VEGF-C and VEGFR-3 in real-time PCR. VEGF-C mRNA alone has no positive association with lymph node metastasis in NSCLC. The VEGF-C/VEGFR-3 ratio was positively associated with lymph node metastasis in NSCLC. This suggests that VEGF-C promotes lymph node metastasis while being influenced by the strength of the VEGF-C autocrine loop, and the VEGF-C/VEGFR-3 ratio can be a useful predictor of lymph node metastasis in NSCLC

SOD2 immunoexpression predicts lymph node metastasis in penile cancer

BACKGROUND: Superoxide dismutase-2 (SOD2) is considered one of the most important antioxidant enzymes that regulate cellular redox state in normal and tumorigenic cells. Overexpression of this enzyme in lung, gastric, colorectal, breast cancer and cervical cancer malignant tumors has been observed. Its relationship with inguinal lymph node metastasis in penile cancer is unknown. METHODS: SOD2 protein expression levels were determined by immunohistochemistry in 125 usual type squamous cell carcinomas of the penis from a Brazilian cancer center. The casuistic has been characterized by means of descriptive statistics. An exploratory logistic regression has been proposed to evaluate the independent predictive factors of lymph node metastasis. RESULTS: SOD2 expression in more than 50% of cells was observed in 44.8% of primary penile carcinomas of the usual type. This expression pattern was associated with lymph node metastasis both in the uni and multivariate analysis. CONCLUSIONS: Our results indicate that SOD2 expression predicts regional lymph node metastasis. The potential clinical implication of this observation warrants further studies.Dr. Lara Termini (FAPESP 2005/57274-9); Dr. Luisa Lina Villa (FAPESP 2008/57889-1 and CNPq 573799/2008-3)

Esophageal Cancer Initially Thought to be Accompanied by a Solitary Metastasis to an Intrathoracic Paraaortic Lymph Node

Esophageal cancers usually exhibit lymph-node metastases. Although a solitary lymph-node metastasis is occasionally found, the involvement of an intrathoracic paraaortic node is rare. We present here an intrathoracic mid-esophageal cancer case in which an accompanying solitary retroaortic mass was found within the posterior mediastinum by integrated positron emission tomography/computed tomography. For diagnosis, thoracoscopic resection of the mass was performed from a left thoracic approach, and histology revealed it to be a squamous cell carcinoma metastasized from the esophageal cancer. Upon radical esophagectomy after neoadjuvant therapy as a T3N1M0 Stage IIIa (AJCC/UICC) cancer, the esophageal cancer was found to have invaded unexpectedly deeply in the vicinity of the descending aorta. Another lymph node within the paraaortic region was also involved (T4N1M0 Stage IIIc). The present case and other cases we review here inform our understanding of metastasis to intrathoracic paraaortic nodes as follows:1) its existence may indicate extensive lymph-node metastasis or direct tumor invasion nearby, and 2) it may be accompanied by other lymph-node involvements in this region, even if it appears solitary upon preoperative investigation. Thus, for radical esophagectomy, sufficient lymph-node dissection is required, even at locations not reached by the usual right thoracic approach. Definitive chemoradiotherapy may be a better choice for preoperatively recognized T3 esophageal cancer when the cancer is accompanied by paraaortic lymph node metastasis

The significance of extended lymphadenectomy for colorectal cancer with isolated synchronous extraregional lymph node metastasis

SummaryBackground/ObjectiveThe significance of extended lymphadenectomy for colorectal cancer with extraregional lymph node metastasis, such as para-aortic lymph node metastasis, has not been established. The purpose of this study was to evaluate the significance of extended lymphadenectomy for colorectal cancer with synchronous isolated extraregional lymph node metastasis.MethodsBetween July 2004 and December 2013, 16 patients with synchronous extraregional lymph node metastasis without other organ metastases underwent curative resection and extended lymphadenectomy (R0 group). The clinical characteristics and survival outcomes of the R0 group were compared with those of 12 patients with extraregional lymph node metastasis who underwent palliative surgery (control group).ResultsIn the R0 group, the 5-year cancer-specific survival (CSS) rate was 70.3% and the 5-year relapse-free survival (RFS) rate was 60.5%. The 5-year CSS differed significantly between the R0 and control groups (70.3% vs. 12.5%; p = 0.0003). Univariate analyses revealed that the total numbers of metastatic lymph nodes and metastatic regional lymph nodes present were significantly associated with RFS (p = 0.019 for both).ConclusionFindings from our study suggest that extended lymphadenectomy for colorectal cancer with synchronous isolated extraregional lymph node metastasis might be effective in carefully selected patients

Intraoral ultrasonographic features of tongue cancer and the incidence of cervical lymph node metastasis

Purpose: The purpose of this study was to investigate the relationship between the visual characteristics of tongue lesion images obtained through intraoral ultrasonographic examination and the occurrence of late cervical lymph node metastasis in patients with tongue cancer. Patients and Methods: This study investigated patients with primary tongue cancer who were examined using intraoral ultrasonography at Hiroshima University Hospital between January 2014 and December 2017. The inclusion criteria were squamous cell carcinoma, curative treatment administration, lateral side of tongue, surgery or brachytherapy alone, no cervical lymph node or distant metastasis as primary treatment, and treatment in our hospital. The exclusion criteria were carcinoma in situ, palliative treatment, dorsum of tongue, and multiple primary cancers. The follow-up period was more than 1 year. The primary endpoint was the occurrence of late cervical lymph node metastasis, and the primary predictor variables were age, gender, longest diameter, thickness, margin or border shapes of the lesion, and treatment methods. The relationship between the occurrence of late cervical lymph node metastasis and the longest diameter, thickness, margin types, and border types as evaluated through intraoral ultrasonography were assessed. The data were collected through a retrospective chart review. Results: Fifty-four patients were included in this study. The analysis indicated that irregular lesion margins were significantly associated with the occurrence of late cervical lymph node metastasis (P < .0001). The cutoff value for late cervical lymph node metastasis was 21.2 mm for the longest diameter and 3.9 mm for the thickness. Conclusions: The results of this study indicates that the irregular lesion margin assessed using intraoral ultrasonography may serve as an effective predictor of late cervical lymph node metastasis in N0 cases. (C) 2020 American Association of Oral and Maxillofacial Surgeon

Correlation of c-erbB-2, EGF and EGFR expression with postoperative survival of patients with advanced carcinoma of the stomach.

The c-erbB-2 (HER-2/neu), EGF and EGFR (erbB-1) proteins, members of the epidermal growth factor receptor family, play a role in cell growth by binding to cell membrane receptors. The aim of the current study was to evaluate the expression of c-erbB-2, EGF and EGFR in advanced gastric carcinoma and to analyze its relationship with chosen anatomo-clinical parameters and prognosis. Standard avidin-biotin-peroxidase was used for c-erbB-2, EGF and EGFR immuno-histochemical staining (Novostain Super ABC Kit Universal); anti-human c-erbB-2 protein monoclonal antibody NCL-cerbB-2-316, anti-Epidermal Growth Factor monoclonal antibody (clone EGF-10) and EGFR goat polyclonal IgG (p-EGFR). A statistically significant correlation was found between c-erbB-2, EGF, EGRF expressions in the main mass of tumor and lymph node metastasis (p=0.000; p=0.000; p=0.00001, respectively). Also an association was observed between c-erbB-2 expression and Bormann's and Lauren's classifications (p=0.05; p=0.006, respectively). Similarly, the expression of EGFR in main mass of tumor was correlated with the depth of invasion (p=0.007) and histological differentiation (p=0.04). Moreover, the expression of c-erbB-2 in the main mass of tumor and lymph node metastasis was associated with the age of the patients (p=0.03; p=0.0002 respectively). Strong association was found between the expression of EGRF in lymph node metastasis and histological differentiation (p=0.04). Positive expression of c-erbB-2 in lymph node metastasis was correlated with lymph node involvement (p=0.04). Positive expression of c-erbB-2 in the main mass of tumor and in lymph node metastasis was strongly correlated with postoperative survival (p=0.00001; p=0.003 respectively). We also found a relationship between EGF expression in gastric tumor and survival time (p=0.003). No association was noted between the expression of EGFR in the main mass of tumor and in lymph node metastasis and between the expression of EGF in lymph node metastasis and survival time. Our results suggest that the expression of c-erbB-2 and EGF protein can help predict the postoperative survival time

Biological Ablation of Sentinel Lymph Node Metastasis in Submucosally Invaded Early Gastrointestinal Cancer

Currently, early gastrointestinal cancers are treated endoscopically, as long as there are no lymph node metastases. However, once a gastrointestinal cancer invades the submucosal layer, the lymph node metastatic rate rises to higher than 10%. Therefore, surgery is still the gold standard to remove regional lymph nodes containing possible metastases. Here, to avoid prophylactic surgery, we propose a less-invasive biological ablation of lymph node metastasis in submucosally invaded gastrointestinal cancer patients. We have established an orthotopic early rectal cancer xenograft model with spontaneous lymph node metastasis by implantation of green fluorescent protein (GFP)-labeled human colon cancer cells into the submucosal layer of the murine rectum. A solution containing telomerase-specific oncolytic adenovirus was injected into the peritumoral submucosal space, followed by excision of the primary rectal tumors mimicking the endoscopic submucosal dissection (ESD) technique. Seven days after treatment, GFP signals had completely disappeared indicating that sentinel lymph node metastasis was selectively eradicated. Moreover, biologically treated mice were confirmed to be relapse-free even 4 weeks after treatment. These results indicate that virus-mediated biological ablation selectively targets lymph node metastasis and provides a potential alternative to surgery for submucosal invasive gastrointestinal cancer patients

Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients

Gastric cancer is a leading cause of cancer-related mortality, and the presence of lymph node metastasis an important prognostic factor. Downregulation of RKIP has been associated with tumor progression and metastasis in several types of neoplasms, being currently categorized as a metastasis suppressor gene. Our aim was to determine the expression levels of RKIP in gastric tissues and to evaluate its impact in the clinical outcome of gastric carcinoma patients. RKIP expression levels were studied by immunohistochemistry in a series of gastric tissues. Overall, we analysed 222 non-neoplastic gastric tissues, 152 primary tumors and 42 lymph node metastasis samples. We observed that RKIP was highly expressed in ~83% of non-neoplastic tissues (including normal tissue and metaplasia), was lost in ~56% of primary tumors and in ~90% of lymph node metastasis samples. Loss of RKIP expression was significantly associated with several markers of poor clinical outcome, including the presence of lymph node metastasis. Furthermore, the absence of RKIP protein constitutes an independent prognostic marker for these patients. In conclusion, RKIP expression is significantly lost during gastric carcinoma progression being almost absent in lymph node metastasis samples. Of note, we showed that the absence of RKIP expression is associated with poor outcome features of gastric cancer patients, this being also an independent prognostic marker.Olga Martinho was recipient of a PhD fellowship (SFRH/BD/36463/2007) from Fundacao para a Ciencia e Tecnologia (FCT), Portugal