Tumor Sprouting in Papillary Thyroid Carcinoma Is Correlated with Lymph Node Metastasis and Recurrence

BACKGROUND: Identification of poor prognostic factors in papillary thyroid carcinoma (PTC) patients is important for the patients' care and follow-up. We can sometimes see small tumor clusters without desmoplasia and no evidence of lymphatic emboli around the main tumor mass of PTC. We termed this form of tumor clustering, 'tumor sprouting,' and determined whether these tumors correlate with lymphovascular invasion, lymph node metastasis, and recurrence. METHODS: We analyzed a total of 204 cases of papillary thyroid macrocarcinoma. Number, size and distance from the main tumor of the tumor sprouting were observed and analyzed with clinicopathologic characteristics. RESULTS: Tumor sprouting was observed in 101 patients. Presence of tumor sprouting was significantly associated with positive resection margin (p=.002), lymphovascular invasion (p=.001), lymph node metastasis (p<.001), and recurrence (p=.004). Univariate analysis of recurrence-free survival revealed that tumor multiplicity (p=.037), positive resection margin (p=.007), lymphovascular invasion (p=.004), lymph node metastasis (p<.001), and tumor sprouting (p=.004) were poor prognostic factors. In multivariate analysis, positive resection margin was an independent poor prognostic factor of recurrence. CONCLUSIONS: In conclusion, tumor sprouting is significantly correlated with lymph node metastasis and recurrence. Evaluation of tumor sprouting in PTC patients could be helpful in predicting tumor recurrence or lymph node metastasis.

Clinicopathologic Characteristics in Node-negative Gastric Cancer Patients According to the Presence of Lymphatic Invasion

PURPOSE: We evaluated the clinicopathological charicterics and prognostic impacts of lymphatic vessel invasion in gastric cancer without lymph node involvement. MATERIALS AND METHODS: Among 1,795 patients who underwent gastric surgery with gastric cancer at the department of surgery, Hanyang university college of medicine from June 1992 to March 2009, we retrospectively evaluated 890 patients with lymph node negative gastric cancer. RESULTS: The lymphatic vessel invasion correlated significantly with tumor stage, age, tumor size, perineural invasion and operation method. The survival rates were only significantly different between the patients with and without lymphatic vessel invasion in patients with stage Ia (P=0.036). Univariate and multivariate analysis demonstrated that blood vessel invasion and preoperative serum CEA level were significant factor influencing the survival rate in lymph node negative gastric cancer patients with lymphatic invasion. CONCLUSIONS: In patients with lymph node negative gastric cancer, the survival rate is significantly lower in those with lymphatic vessel invasion than in those without. Especially, in patients with stage Ia gastric cancer, the survival rates is significantly different between those with and those without lymphatic vessel invasion. Blood vessel invasion and preoperative serum CEA level is an adverse prognostic indicator in patients with stage Ia gastric cancer with lymphatic invasion. Thus we should consider further adjuvant therapies in case of need and need to show more concern to identify gastric cancer patients early at risk for recurrence.

D2-40, a novel lymphatic endothelial marker: identification of lymphovascular invasion and relationship with axillary metastases in breast cancer

BACKGROUND: Studies of lymphatic vessels were limited by the lack of specific markers. Recently, they have become possible due to the release of new D2-40 antibody, a selective marker for lymphatic endothelium. The aim of our study was to compare neoplastic invasion in lymphatic and blood vessels detected in hematoxylin and eosin (H&E) and immunohistochemistry-stained sections. METHODOLOGY: A total of 123 cases of invasive mammary carcinomas were studied and sorted out into three subgroups according to axillary staging (macrometastasis, micrometastasis and lymph node negative). Lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) were initially evaluated in histological H&E and immunohistochemistry-stained sequential sections. Lymphatic and blood vessel invasions were assessed by immunohistochemistry, employing D2-40 and CD31 antibodies, respectively. LVI and BVI were related to size, type, histologic grade of primary tumors, and the presence of metastasis. RESULTS: LVI was detected through H&E staining procedure in 17/123 cases (13.8 percent), and through immunohistochemistry procedure in 35/123 cases (28.5 percent) (kappa = 0.433). BVI was detected through H&E in 5/123 cases (4.1 percent), and through immunohistochemistry in 19/123 cases (15.4 percent) (kappa = 0.198). LVI and BVI were positively related to higher histologic grade of primary tumors (p < 0.05). LVI was also positively related to the presence of macrometastasis. CONCLUSION: The detection of lymphatic and blood vessel invasions through immunohistochemistry employing D2-40 and CD31 was higher than the detection through H&E, and it was related to higher tumor grade and metastasis in axillary lymph nodes.

INTRODUÇÃO: Estudos de vasos linfáticos eram limitados pela ausência de marcadores endoteliais linfáticos específicos. Recentemente, eles se tornaram possíveis após liberação comercial do novo anticorpo D2-40, marcador seletivo para endotélio linfático. O objetivo do nosso estudo foi comparar invasão neoplásica em vasos linfáticos e sanguíneos detectada em secções coradas pela hematoxilina e eosina (HE) e imuno-histoquímica (IIQ). MATERIAIS E MÉTODOS: Foram estudados 123 casos de carcinomas mamários invasores subdivididos em três subgrupos de acordo com o estadiamento axilar: macrometástases (Mac-Met), micrometástases (Mic-Met) e linfonodo negativo (LNN). Invasão de vasos linfáticos (IVL) e de vasos sangüíneos (IVS) foi inicialmente avaliada em secções histológicas coradas pela HE e através da IIQ realizada em cortes seqüenciais. A invasão de vasos linfáticos e sanguíneos foi avaliada pela imuno-histoquímica, empregando-se respectivamente os anticorpos D2-40, e CD31. IVL e IVS foram relacionadas com tamanho tumoral, tipo e grau histológico dos tumores primários e com a presença de metástases. RESULTADOS: IVL foi observada pela HE em 17/123 casos (13,8 por cento) e pela IIQ em 35/123 casos (28,5 por cento) (kappa = 0,433). IVS foi observada pela HE em 5/123 casos (4,1 por cento) e pela IIQ em 19/123 casos (15,4 por cento) (kappa = 0,198). IVL e IVS estavam positivamente relacionadas com maior grau histológico dos tumores primários (p < 0,05). IVL também estava positivamente relacionada com a presença de macrometástases. CONCLUSÃO: A detecção IIQ, respectivamente por D2-40 e CD31, de invasão de vasos linfáticos e sanguíneos foi maior que a detecção feita em cortes corados pela HE e relacionou-se com maior grau tumoral e metástases em linfonodos axilares.

Implication of Lymphatic or Blood Vessel Invasion in Early Gastric Cancer

PURPOSE: Various types of minimally invasive therapy have been attempted for early gastric cancer (EGC) patients. However, minimally invasive therapy can not fully evaluate the nodal status which has been suggested as an important prognostic factor for EGC patients. This study was conducted to evaluate the clinical implications and prognostic impact of lymphatic or blood vessel invasion (LBVI) in EGC patients in the era of minimally invasive therapy. METHODS: A total of 566 EGC patients who had undergone gastrectomy with D2 or more extended lymphadenectomy between July 1993 and December 1997 were retrospectively reviewed. The risk factors that determine LBVI and the clinicopathological features, recurrence rates, and prognoses according to LBVI were investigated by univariate and multivariate analyses. RESULTS: Lymphatic vessel invasion was noted in 59 patients (10.4%); blood vessel invasion in 13 patients (2.3%); LBVI in 61 patients (10.8%). LBVI was associated with submucosal invasion, larger tumor size, and elevated macroscopic type (P<0.05). LBVI and lymph node metastasis were found to be significantly correlated. LBVI was an independent risk factor for lymph node metastasis (relative risk 26.56, 95% confidence interval 12.77-55.23). Patients with LBVI had a recurrence rate of 15.3% while patients without LBVI had a 3.7% recurrence rate (P<0.01). The overall and disease-specific 5-year survival rates were 79.9 and 85.9% for patients with LBVI whereas they were 93.4 and 97.5% for patients without LBVI (P<0.01, respectively). On multivariate analysis, LBVI was an independent risk factor for poor prognosis (relative risk 2.38, 95% confidence interval 1.15-4.93). CONCLUSION: Lymphatic or blood vessel invasion is an adverse prognostic indicator for EGC patients. Considering the low rate of lymph node metastasis and recurrence in patients with LBVI negative EGC, minimally invasive therapy can be regarded as curative when LBVI is negative.

Risk Factors for Lymph-ode Metastasis in Early Gastric Carcinomas

BACKGROUND: Although regional lymph-ode metastasis from early gastric cancer (EGC) is rare, it is well known that EGC patients with lymph-ode metastasis constitute a high-isk group for recurrence. Thus, it is important to clarify the characteristics of patients having lymph-ode metastasis in order to ascertain the optimal therapy. METHODS: We analyzed the clinical aspects of 34 cases of node-ositive EGC and compared them to 197 cases of node-egative EGC. All patients were operated on from June 1994 to December 1997 at Ajou University Hospital. Also, by using immunohistochemical staining, we examined the expression of cathepsin D in the tumors to identify its significance in EGC. RESULTS: Lymph-ode involvement correlated significantly with deeper tumor invasion, severity of lymphatic invasion, and larger tumor size. Age, sex, histologic type, location, gross appearance, and serum carcinoembryonic antigen (CEA) level were unrelated to lymph-ode involvement. Positive cytoplasmic staining for cathepsin D was detected in 100% of the tumors, and strongly positive staining was found in 33.3%. Also, strong positivity was found more frequently in tumors with lymph-ode involvement. CONCLUSION: Prophylactic lymph-ode dissection may be necessary for patients with EGC with submucosal invasion, lymphatic invasion, and larger tumor size. Also, cathepsin D can be a useful tool for understanding the pathophysiology of early gastric cancer.

Early Prognostic Significance of Lymphatic Vessel Invasion in Gastric Cancer

In gastric cancer, the significance of lymphatic invasion as a prognostic factor is controversial. This study was performed to investigate the significance of lymphatic invasion as a prognostic factor in early results of gastric cancer after gastrectomy. We had been prospectively analyzed 362 consecutive patients resected from June 1994 to June 1996 in the Department of Surgery, Ajou University Hospital. Grading of the lymphatic invasion was determined by pathologists according to the JRSGC classification. The difference in the survival rate between the ly0 group and the ly1 group was statistically insignificant, so we only used ly2 and ly3 as the risk group. The prognostic values of lymphatic invasion as a single parameter for survival and early recurrence were determined by using univariate and multivariate analyses. Lymphatic invasion was observed in 90 (24.9%) of the 362 gastric cancer cases, and ly2 or ly3 were 66 (18.3%)cases. The incidence of ly> or =2 steadily increased with advancing TNM stage : stageI, 9/124 (7.3%); stageII, 5/50 (10.0%); stageIII, 24/111 (21.6%); stageIV, 28/78 (35.9%). The incidence of ly> or =2 was significantly correlated with other prognostic factors such as lymph node metastasis, the depth of the primary tumor, and the stage (p or =2 and 90.9% in patients with ly or =2 group (p or =2) as an independent prognostic factor (p=0.0008, Exp(B)=3.55). The cummulative recurrence free rate determined by the Kaplan-Meirer method was 78.7% in the ly> or =2 group and 90.54% in the ly or =2 group (p=0.0055). Therefore lymphatic invasion with ly2 or ly3 grade is an independent prognostic factor that is associated with poor prognosis for early results after gastrectomy. In grading of lymphatic invasion by gastric cancer, simple differentiation of whether lymphatic invasion is present or not was insignificant in the results of our study. In the future, the grade of lymphatic invasion in gastric cancer should be carefully classified by pathologists.