Recurrent malignant peripheral nerve sheath tumor presenting as an asymptomatic intravenous thrombus extending to the heart: a case report

Background Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma mainly treated via surgical resection. Herein, we report a case of MPNST wherein a massive tumor thrombus extended to the major veins and heart. Case presentation A 39-year-old female with a history of neurofibromatosis type 1 developed MPNST from the right radial nerve. In addition to adjuvant chemotherapy, she underwent wide tumor resection and concomitant radial nerve resection, followed by postoperative radiotherapy. Histological evaluation revealed marked venous invasion. The 2-year follow-up CT revealed an asymptomatic recurrent tumor thrombus extending from the right subclavian vein to the heart. An urgent life-saving operation was performed to ligate the base of the right subclavian vein and remove the entire intravenous thrombus that extended to the right ventricle. The remaining tumor in the right subclavian vein increased in size 3 months after thrombectomy. After confirming the absence of any metastatic lesions, the patient underwent extended forequarter amputation to achieve surgical remission. One year later, a new metastasis to the right diaphragm was safely resected. The patient remains alive without any evidence of disease 2 years after the extended forequarter amputation. Conclusions In cases of a previous history of microscopic venous invasion, recurrence can occur as a massive tumor thrombus that extends to the great vessels.

Combination of extramural venous invasion and lateral lymph node size detected with magnetic resonance imaging is a reliable biomarker for lateral lymph node metastasis in patients with rectal cancer

Purpose Pathological extramural venous invasion (EMVI) is defined as the active invasion of malignant cells into veins beyond the muscularis propria in colorectal cancer. It is associated with poor prognosis and increases the risk of disease recurrence. Specific findings on MRI (termed MRI-EMVI) are reportedly associated with pathological EMVI. In this study, we aimed to identify risk factors for lateral lymph node (LLN) metastasis related to rectal cancer and to evaluate whether MRI-EMVI could be a new and useful imaging biomarker to help LLN metastasis diagnosis besides LLN size. Methods We investigated 67 patients who underwent rectal resection and LLN dissection for rectal cancer. We evaluated MRI-EMVI grading score and examined the relationship between MRI-EMVI and LLN metastasis. Results Pathological LLN metastasis was detected in 18 cases (26.9%), and MRI-EMVI was observed in 32 cases (47.8%). Patients were divided into two cohorts, according to LLN metastasis. Multivariate analyses demonstrated that higher risk of LLN metastasis was significantly associated with MRI-EMVI (P = 0.0112) and a short lateral lymph node axis (≥ 5 mm) (P = 0.0002). The positive likelihood ratios of MRI-EMVI alone, LLN size alone, and the combination of both factors were 2.12, 4.84, and 16.33, respectively. Patients negative for both showed better 2-year relapse-free survival compared to other patients (84.4% vs. 62.1%, P = 0.0374). Conclusions MRI-EMVI was a useful imaging biomarker for identifying LLN metastasis in patients with rectal cancer. The combination of MRI-EMVI and LLN size can improve diagnostic accuracy.

Composite Scoring System and Optimal Tumor Budding Cut-Off Number for Estimating Lymph Node Metastasis in Submucosal Colorectal Cancer

Background Tumor budding is associated with lymph node (LN) metastasis in submucosal colorectal cancer (CRC). However, the rate of LN metastasis associated with the number of tumor buds is unknown. Here, we determined the optimal tumor budding cut-off number and developed a composite scoring system (CSS) for estimating LN metastasis of submucosal CRC. Methods In total, 395 patients with histologically confirmed T1N0–2M0 CRC were evaluated. The clinicopathological characteristics were subjected to univariate and multivariate analyses. The Akaike information criterion (AIC) values of the multivariate models were evaluated to identify the optimal cut-off number. A CSS for LN metastasis was developed using independent risk factors. Results The prevalence of LN metastasis was 13.2%. Histological differentiation, lymphatic or venous invasion, and tumor budding were associated with LN metastasis in univariate analyses. In multivariate models adjusted for histological differentiation and lymphatic or venous invasion, the AIC value was lowest for five tumor buds. Unfavorable differentiation (odds ratio [OR], 8.16; 95% confidence interval [CI], 1.80–36.89), lymphatic or venous invasion (OR, 5.91; 95% CI, 2.91–11.97), and five or more tumor buds (OR, 3.01; 95% CI, 1.21–7.69) were independent risk factors. In a CSS using these three risk factors, the rates of LN metastasis were 5.6%, 15.5%, 31.0%, and 52.4% for total composite scores of 0, 1, 2, and ≥ 3, respectively. Conclusions For the estimation of LN metastasis in submucosal CRC, the optimal tumor budding cut-off number was five. Our CSS can be utilized to estimate LN metastasis.

RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients

Background: Recently, markers related to molecular classification were suggested as promising therapeutic targets for treatment and prediction of prognosis in gastric cancer (GC), including c-MET, RhoA, and Claudin-18 (CLDN18). This study aimed to investigate their expression in GC and its correlation with clinicopathological characteristics and survival. Methods: We retrospectively evaluated GC patients who underwent curative gastrectomy. c-MET, RhoA, and CLDN18 were analyzed through immunohistochemistry (IHC), and groups for analysis were determined according to the median values obtained for each marker. Results: Among the 349 GC evaluated, 180 (51.6%), 59 (16.9%), and 61 (17.5%) patients were completely negative for c-MET, RhoA, and CLDN18, respectively. Total gastrectomy, D1 lymphadenectomy, poorly differentiated histology, and greater inflammatory infiltrate were more frequent in the c-MET-negative group. Diffuse type, greater inflammatory infiltrate, and advanced pT and pTNM stage were associated with low-RhoA GC. The venous invasion was more frequent in the low-CLDN18 group. Furthermore, c-MET was positively correlated with RhoA and negatively with CLDN18. HER2 expression was associated with c-MET-positive and high-CLDN18 GC; and loss of E-cadherin expression in c-MET-negative and low-RhoA GC. c-MET-negative and Low-RhoA were significantly associated with worse disease-free survival. Conclusions: c-MET, RhoA, and CLD18 expression occurred frequently in GC. RhoA GC had distinct clinicopathological characteristics related to prognosis. c-MET and RhoA were associated with survival but were not independent predictors of prognosis.

Risk Factors Associated with the Development of Metastases in Patients with Gastroenteropancreatic Neuroendocrine Tumors: A Retrospective Analysis

Neuroendocrine tumors develop from systemic endocrine and nerve cells, and their occurrence has increased recently. Since these tumors are heterogeneous, pathological classification has been based on the affected organ. In 2019, the World Health Organization introduced a change expected to influence neuroendocrine tumor research, as gastroenteropancreatic neuroendocrine tumors are now included within a unified classification. This retrospective study aimed to investigate the characteristics (e.g., lymph node metastases and all other metastases) of gastroenteropancreatic neuroendocrine tumors using this new classification in 50 cases. Tumor size, depth, MIB-1 index, lymphatic invasion, venous invasion, and neuroendocrine tumor grade were significantly correlated with lymph node metastasis and other metastases. The venous invasion was more strongly correlated with lymph node metastasis and all other types of metastases than with lymphatic invasion. Identification rates for lymphatic invasion were considered lower because of structural problems such as lymphatic vessels being much thinner than veins. However, venous invasion was considered effective in compensating for the low identification rate in cases of lymphatic invasion. In future research, a unified classification and standardized framework for assessment will be important when analyzing the characteristics of neuroendocrine tumors, and large-scale studies are required.

Unusual Presentation of Treated Colon Cancer with Extramural Venous Invasion: a Case Report

Introduction: Colon cancer is one of the leading malignancies globally and continues to be one of the most typical causes of cancer-related mortality. The clinical outcome of the disease depends on the primary tumor stage, regional nodal involvement, and distant disease dissemination. It often presents with hematogenous spread to the liver at the time of diagnosis. Another factor for increased mortality is the presence of extramural venous invasion (EMVI). This is exceedingly important as it has significant prognostic significance and helps predict survival. Case Description: A middle-aged female with a recent history of cesarean delivery presented with abdominal pain and occasional constipation, which led to a series of investigations. Initial Computed Tomography (CT) scan showed proximal to mid transverse colonic tumoral thickening with locoregional lymphadenopathy and solitary distant metastasis in the left hepatic lobe. This was followed by extended right hemicolectomy and hepatic metastasectomy. The patient remained on follow-up and later presented with thrombus formation in the splenoportal circulation. Initially, this was considered a bland thrombus, and the patient was advised a close follow-up. However, the patient was lost to follow and later presented with extensive thrombosis of the portal and splenic veins. Practical Implications: Confident differentiation of the bland versus malignant thrombosis is crucial to ascertain disease stage and appropriate management. Invasive tissue sampling gives a confident diagnosis of benign versus malignant thrombus. However, using a noninvasive imaging modality, we can still distinguish between the two with reasonable certainty.

Determination of Additional Surgery after Non-Curative Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer: A Practically Modified Application of the eCura System

Background: Additional surgery after non-curative endoscopic submucosal dissection (ESD) may be excessive as few patients have lymph node metastasis (LNM). It is necessary to develop a risk stratification system for LNM after non-curative ESD, such as the eCura system, which was introduced in the Japanese gastric cancer treatment guidelines. However, the eCura system requires venous and lymphatic invasion to be separately assessed, which is difficult to distinguish without special immunostaining. In this study, we practically modified the eCura system by classifying lymphatic and venous invasion as lymphovascular invasion (LVI). Method: We retrospectively reviewed 543 gastric cancer patients who underwent radical gastrectomy after non-curative ESD between 2006 and 2019. LNM was evaluated according to LVI as well as size >30 mm, submucosal invasion ≥500 µm, and vertical margin involvement, which were used in the eCura system. Results: LNM was present in 8.1% of patients; 3.6%, 2.3%, 7.4%, 18.3%, and 61.5% of patients with no, one, two, three, and four risk factors had LNM, respectively. The LNM rate in the patients with no risk factors (3.6%) was not significantly different from that in patients with one risk factor (2.3%, p = 0.523). Among patients with two risk factors, the LNM rate without LVI was significantly lower than with LVI (2.4% vs. 10.7%, p = 0.027). Among patients with three risk factors, the LNM rate without LVI was lower than with LVI (0% vs. 20.8%, p = 0.195), although not statistically significantly. Based on LNM rates according to risk factors, patients with LVI and other factors were assigned to the high-risk group (LNM, 17.4%) while other patients as a low-risk group (LNM, 2.4%). Conclusions: Modifying the eCura system by classifying lymphatic and venous invasion as LVI successfully stratified LNM risk after non-curative ESD. Moreover, the high-risk group can be simply identified based on LVI and the presence of other risk factors.

Risk Factors Associated with the Development of Metastases in Patients with Gastroenteropancreatic Neuroendocrine Tumors

Neuroendocrine tumors develop from systemic endocrine and nerve cells, and their occurrence has increased recently. Since these tumors are heterogeneous, pathological classification has been based on the affected organ. In 2019, the World Health Organization introduced a change that is expected to influence neuroendocrine tumor research, as gastroenteropancreatic neuroendocrine tumors are now included within a unified classification. In this retrospective study, we aimed to investigate the characteristics (e.g., lymph node metastases, all other metastases) of gastroenteropancreatic neuroendocrine tumors using this new classification in 50 cases. Tumor size, depth, MIB-1 index, lymphatic invasion, venous invasion, and neuroendocrine tumor grade were significantly correlated with lymph node metastasis and all other metastases. Venous invasion was more strongly correlated with lymph node metastasis and all other types of metastasis than with lymphatic invasion. Identification rates for lymphatic invasion were considered lower because of structural problems such as lymphatic vessels being much thinner than veins. However, venous invasion was considered effective in compensating for the low rate of identification in cases of lymphatic invasion. In future research, a unified classification and standardized framework for assessment will be important when analyzing the characteristics of neuroendocrine tumors, and large-scale studies are required.