Evaluation Of Lymphovascular Invasion Research Articles

Evaluation of Lymphovascular Invasion by CD31 Expression in Gastric Adenocarcinoma.

Lymphovascular tumoral invasion is a typical histopathological feature of gastric carcinomas and supports the recognition of high-risk patients for the recurrence. We aimed to study CD31 expression in diverse subtypes of gastric carcinomas and to show its association with the histopathologic findings of the carcinoma to assess the prognosis. This cross-sectional study was conducted on 40 established patients with gastric adenocarcinoma from radical gastrectomy. The patients were classified according to the pathology assessments. Tumoral tissues were assessed by immunohistochemical staining for CD31 expression. Malignant behavior was estimated by histopathological evaluations. CD31 positivity was described in 23 (57.5%) of all evaluated patients. In assessment of CD31 expression and tumor features presented, no significant association between the CD31 expression and patients' age, sex, tumor site, size, grade and stage, subtypes of carcinoma, perineural invasion, and also lymphovascular invasion was found. (P>0.05). Lymphovascular invasion may make valuable additional evidence and may be useful to detect gastric carcinoma patients at high risk for recurrence, who could be candidates for more supplementary therapies. However, in our study, CD31 expression did not show any association with the aggressive histopathologic features of this tumor.

Prognostic Significance of Intramural and Extramural Lymphovascular Invasion in Colorectal Carcinoma

ABSTRACT Introduction: Evaluation of lymphovascular invasion (LVI) in Colorectal Carcinoma (CRC) may help to predict the metastatic potential and identify patients with aggressive tumor. Such patients may benefit from adjuvant therapy, hence improving their survival and disease-free outcome. Aims and Objectives: To identify LVI in cases of CRC and classify them as intramural and extramural and find its correlation with parameters such as tumor volume, location, growth pattern, histological type, grade, tumor budding, stage, and nodal metastasis. Materials and Methods: A prospective study was conducted from November 2018 to April 2020 at a tertiary care hospital, New Delhi, which included 27 cases of CRC. Demographic and perioperative data were collected. LVI identified on H and E, further differentiated into intramural and extramural and correlated with clinicopathological data. Observation and Results: About 70.3% of cases showed the presence of LVI. A statistically significant association between intramural and extramural LVI and nodal metastasis was identified. A statistically significant association was also noted between extramural LVI and staging. Conclusion: LVI is an independent predictor of recurrence and silent metastasis in many cancers, especially colorectal cancer. It is a cost-effective and simple method. The result of the present study adds on to the growing literature on the significance of LVI in CRC. However, more work needs to be done with a large sample size to fulfill the limitations.

An evaluation of lymphovascular invasion in relation to biology and prognosis according to subtypes in invasive breast cancer.

Lymphovascular invasion (LVI) is associated with a poor outcome in breast cancer. The purpose of the present study was to evaluate the clinical significance of LVI in primary breast cancer and to investigate disease-free survival as a prognostic marker according to the breast cancer subtypes. This study examined 4,652 consecutive cases of invasive breast cancer excluding the patients with non-invasive cancer, stage IV and those who underwent neo-adjuvant therapy from February 2002 to February 2021. The clinicopathological characteristics and prognosis of LVI-positive and -negative tumors were compared. LVI was evaluated in H&E staining specimens from surgically resected samples. The LVI expression rates were 29.2% (low, 19.7%; high, 9.5%) in all primary cases. The LVI-positive rate was significantly associated with specimens with the following characteristics: ER/PgR-negative, HER2-positive, p53 overexpression, higher Ki-67 index values, higher nuclear grade, positive nodes and larger tumors. Moreover, the subtypes were significantly associated with LVI positivity; 20% in Luminal A, 34.6% in Luminal B, 40.9% in Lumina/HER2, 38.1% in HER2-enriched and 29.8% in triple negative (TN). There were significant differences in disease-free survival between LVI status in Luminal A, Luminal B and TN subtypes, but there was no difference in the Luminal/HER2 and HER2-enriched subtypes. A multivariate analysis revealed that LVI was a significant factor in Luminal B and TN subtypes. Overall, LVI was significantly associated with the advanced and aggressive characteristics in breast cancer. Luminal A type had a lower LVI rate, and HER2 type had a higher LVI rate. Moreover, LVI was a significant prognostic factor in Luminal B and TN subtypes. These data suggested that the LVI status was useful in predicting the prognosis in HER2 negative breast cancer cases.

Abstract P4-07-12: An evaluation of lymphovascular invasion in relation to biology and prognosis according to subtypes in invasive breast cancer

Abstract Background: Lymphovascular invasion (LVI) is associated with a poor outcome in breast cancer. The purpose of this study was to evaluate the clinical significance of LVI in primary breast cancer and to investigate disease-free survival (DFS) as a prognostic marker according to the breast cancer subtypes. The clinical significance of LVI was analyzed to investigate the biology and prognosis. Patients and Methods: This study examined 4,652 consecutive invasive breast cancer cases excluding the patients with non-invasive cancer, Stage IV and neo-adjuvant therapy from February 2002 to February 2021. Clinicopathological characteristics and prognosis of LVI positive and negative tumors were compared. LVI was evaluated in hematoxylin and eosin staining specimen from surgically resected samples. The ER, PgR, Ki-67, p53, HER2 status were evaluated using immunohistochemistry (IHC). Breast cancer subtypes were categorized based on the IHC data derived from ER/PgR, HER2 and Ki-67 (cutoff point: 20%) in invasive tumors. The median follow-up period was 95 months. Results: The LVI expression rates were 29.2%(low: 19.7% and high: 9.5%)in all primary cases. The LVI positive rate significantly correlated with ER/PgR negative, HER2 positive, p53 overexpression, higher Ki-67 index values, higher nuclear grade, positive nodes, and larger tumor. Moreover, the subtypes significantly correlated with LVI positivity; 20% in Luminal A, 34.6% in Luminal B, 40.9% in Lumina/HER2, 38.1% in HER2 enriched, and 29.8% in Triple Negative (TN). There were significant differences in DFS between LVI status in Luminal A, Luminal B, and TN subtypes, but there were no difference in the Luminal/HER2 and HER2 enriched subtypes. A multivariate analysis revealed that LVI was a significant factor in Luminal B and TN subtypes. Conclusion: LVI significantly correlated with the advanced and aggressive characteristics in breast cancer. Luminal A type had a lower LVI rate and HER2 type had a higher rate. Moreover, LVI was a significant prognostic factor in Luminal B and TN subtypes. These data suggest that the LVI status was useful in predicting the prognosis in HER2 negative breast cancer. Citation Format: Reiki Nishimura, Tomofumi Osako, Yasuhiro Okumura, Masahiro Nakano, Hiroko Otsuka, Mamiko Fujisue, Nobuyuki Arima. An evaluation of lymphovascular invasion in relation to biology and prognosis according to subtypes in invasive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-12.

Evaluation of lymphovascular invasion as a prognostic predictor of overall survival after radical prostatectomy

ObjectiveTo assess the prognostic ability of lymphovascular invasion (LVI) as a predictor of overall survival (OS). Materials and MethodsWe included 126,682 prostate cancer (CaP) cM0 patients who underwent radical prostatectomy with lymph node dissection between 2010 and 2015, within the National Cancer Database. Patients who received androgen deprivation therapy were included. Patients were divided into four sub-cohorts based on LVI and lymph node invasion (LNI) status: pL0N0, pL1N0, pL0N1, and pL1N1. Kaplan-Meier curves estimated OS and Cox-regression analysis tested the relationship between LVI and OS. ResultsMedian (IQR) age and PSA at diagnosis were 62 (57-66) years and 5.7 (4.5-8.9) ng/ml, respectively. Most patients had pT2 stage (68.5%), and pathological Gleason 3+4 (46.7%). 10.0% and 4.0% patients had LVI and LNI, respectively. Median follow-up was 42 months (27-58). At 5-years, OS was 96.5% in pL0N0 patients vs 93.1% pL1N0 patients vs 93.3% in pL0N1 patients vs 86.6% pL1N1 patients. LVI was an independent predictor of OS (hazard ratio [HR]:1.28). LVI showed interaction with LNI, as LVI was associated with a higher overall-mortality in patients with LNI (HR:1.66), than in patients without LNI (HR:1.22). (all P<0.0001) ConclusionsOur report highlights the detrimental impact of LVI on OS. Patients with LVI alone fared similarly to patients with LNI alone. Patients with both LVI and LNI had worse OS than those with only LVI or LNI, implying a synergetic detrimental interaction. Our findings demonstrate an important utility that LVI can provide in deciding patients’ prognoses.

Clinicopathological investigation of lymph node metastasis predictors in superficial esophageal squamous cell carcinoma with a focus on evaluation of lympho-vascular invasion

Objective. Reliable indicators of the risk of lymph node metastasis (LNM) in superficial esophageal squamous cell carcinoma (sESCC: intramucosal and submucosal invasive carcinoma) may contribute to assist optimal clinical decision-making for treating sESCC. In esophageal cancer, there is a possibility of metastasis, even in sESCC, and careful evaluation is needed when making a pathological diagnosis. In this study, we objectively evaluated predictive factors of LNM. Materials and methods. A total of 110 consecutive sESCC cases were obtained. We evaluated candidate predictive factors of LNM as follows: (1) maximum tumor diameter; (2) macroscopic type; (3) depth of tumor invasion; (4) histological differentiation; (5) infiltrative growth pattern; (6) tumor budding; (7) lymphatic invasion; (8) venous invasion and (9) lympho-vascular invasion (LVI). Both Elastica–Van Gieson staining (EVG) and immunohistochemistry (IHC: D2-40, CD31, CD34) were used to evaluate invasion into the lympho-vascular spaces. For statistical analyses, single and multiple logistic regression were performed. Results. LNM was observed in 37 cases (33.6%). LVI using EVG and IHC was the strongest independent predictor of LNM with an odds ratio of 12.01. Analysis of the relationship between LVI using EVG and IHC and LNM showed a negative predictive value of 94.6%. Conclusions. Evaluation of LVI using EVG and IHC may contribute to predict LNM in sESCC.

Accuracy and Completeness of Pathology Reporting — Impact on Partial Breast Irradiation Eligibility

AimsAccelerated partial breast irradiation (APBI) is an alternative to whole breast irradiation that is delivered over a shorter period of time with less toxicity. Appropriate patient selection is critical to its success and the American Society for Radiation Oncology (ASTRO) has published detailed selection criteria for ‘suitable’ patients. This study evaluated the effect of those selection criteria on APBI eligibility based on pathology reports. Materials and methodsFrom March 2004 to March 2007 all patients referred to a single cancer centre for breast radiotherapy were screened for participation in a phase I/II trial of permanent breast seed implant brachytherapy. Eligible patients underwent a computed tomography simulation and those referred from an outside institution had a secondary expert breast pathology assessment. Initial and expert pathology reports were compared regarding completeness and accuracy. ResultsIn total, 143 patients were eligible for the trial; 79 patients had surgery carried out outside our institution. In the initial pathology report, the most frequently missing critical information was the resection margin width (29.1%) and the presence of extensive in situ carcinoma (11.4%). Comparing initial and reviewed pathology, the agreement was higher than 90% for most features. The main source of disagreement was the width of the negative resection margin, with 34.4% disagreement (P=0.016), although it changed eligibility in only 3.6%. There was major disagreement in the evaluation of lymphovascular invasion. Overall, pathology review changed the eligibility for a patient from ‘suitable’ for APBI to ‘cautionary’ in 18.6% of the cases. ConclusionUsing stringent eligibility criteria has a direct effect on patient screening for APBI. The use of synoptic pathology reporting and a quality assurance programme with secondary expert assessments are recommended.

Lymphovascular Invasion in Colorectal Cancer

Lymphovascular invasion (LVI) in colorectal cancer (CRC) is considered a strong stage-independent prognostic factor and influences decisions regarding adjuvant chemotherapy in patients with stage II tumors. However, the degree of interobserver agreement among pathologists for LVI in CRC is largely unknown. This study was undertaken to examine such interobserver variability, and we hypothesized that the use of immunohistochemical markers for vascular and lymphatic channels could improve interobserver agreement. Fifty cases of American Joint Committee on Cancer stage II moderately differentiated CRC from 1990 to 2005 from the pathology archives were selected; mucinous, medullary, and other recognized special subtypes were excluded. Fifty hematoxylin and eosin (H&E) slides (1 from each case) were circulated to 6 gastrointestinal pathologists, who independently assessed small and large vessel invasion. No diagnostic guidelines were given to the participating pathologists; each was instructed to apply the criteria for LVI that he or she used in daily practice. Immunohistochemistry (IHC) for D2-40 and CD31 was performed on corresponding paraffin blocks. The IHC slides were randomized, recirculated, and rescored for LVI. Results were analyzed by kappa (kappa) statistics, which correct for agreement by chance, and for percentage agreement. The average kappa values were determined for the H&E slides (large and small vessel), CD31 (small vessel), and D2-40 (small vessel) (Fig. 1). Agreement was fair for H&E small vessel invasion [kappa=0.28; 95% confidence interval (CI): 0.22-0.34]. The least agreement was seen in interpretation of H&E large vessel invasion (kappa=0.18; 95%CI: 0.11-0.26). Agreement was not improved by use of immunohistochemical stains: CD31 (large vessel, kappa=0.42, 95%CI: 0.20-0.63, small vessel, kappa=0.26, 95%CI: 0.10-0.42) and D2-40 (kappa=0.32, 95%CI: 0.21-0.42). Interobserver variability in diagnosis of LVI was substantial on H&E slides and did not improve upon use of IHC. Agreement in evaluation of large vessel invasion was only slightly higher than would be seen by chance alone. This study highlights the need for criteria in evaluation of LVI, as this assessment may impact patient prognosis and thus change the course of clinical treatment.

Value of endoscopic ultrasound staging in conjunction with the evaluation of lymphovascular invasion in identifying low‐risk esophageal carcinoma

With increasing emphasis on endoscopic therapy (ET) for T1 esophageal carcinoma, the identification of low-risk patients is critical. It was hypothesized that endoscopic ultrasonography (EUS) in concert with detailed histopathologic evaluation would identify low-risk cancers for an appropriate but organ-preserving strategy. All patients who had pretreatment EUS and underwent esophagectomy as primary therapy for esophageal cancer between 1999 and 2006 were analyzed retrospectively. The accuracy of EUS in predicting the correct pathologic stage was assessed along with a histopathologic reevaluation including lymphovascular invasion (LVI). Pathologic stage and various features were incorporated into a multivariate logistic regression model. A total of consecutive 87 esophageal cancer patients (81 with adenocarcinoma) were evaluable for this analysis. EUS correctly diagnosed 59 T1 cancers and 20 T2-4 cancers but understaged cancers in 2 patients and overstaged cancers in 6 patients. EUS correctly identified 8 patients with lymph node metastases but not 13 other patients. The accuracy, sensitivity, and specificity of EUS for T1 cancers were 91%, 91%, and 91%, respectively; for T1a (intramucosal) cancers, the accuracy, sensitivity, and specificity were: 82%, 67%, and 93%, respectively, and for lymph node involvement these same values were 81%, 38%, and 94%, respectively. LVI was found to be an independent predictor of lymph node metastases on the multivariate analysis (P = .02). Data from the current study demonstrate that EUS has excellent accuracy, sensitivity, and specificity (91% each) for identifying T1 esophageal cancers and LVI is an independent predictor of lymph node metastases. A strategy for preservation of the esophagus may be possible in patients who have EUS-designated T1 cancer without LVI after successful ET.

Issues Relating to Lymphovascular Invasion in Breast Carcinoma

Lymphovascular invasion (LVI) by tumor cells is histologically evident in approximately 15% of invasive mammary duct carcinomas and is present in approximately 10% of cases with pathologically negative lymph nodes. LVI is indicative of unfavorable prognosis in the breast cancer-as manifested by increased local failure and reduced overall survival. It is for this reason that LVI is routinely included in the evaluation and reporting of all breast cancers. There are a variety of interpretative difficulties in the histopathologic assessment of LVI, and the clinical implications of any misinterpretation can be profound. This brief review seeks to highlight the difficulties in the evaluation of LVI in breast cancer.

Problems in Pathologic Staging of Lung Cancer

Tumor stage is the most important prognostic and predictive factor for patients with lung cancer, the most lethal neoplasm in the United States. It is used by thoracic surgeons, radiation therapists, and oncologists to determine whether patients with these neoplasms will be treated surgically with curative intent or with palliative radiation therapy and/or chemotherapy. To review the variety of practical problems that can arise during the assessment of the pathologic stage and other prognostic/predictive factors included in the College of American Pathologist checklist for evaluation of resected lung neoplasms. Potential practical difficulties that can arise during the pathologic staging of lung cancer patients include the distinction between pT1, pT2, and pT3 lesions based on their location and the presence of visceral pleura and/or parietal pleura invasion; the differential diagnosis between multiple synchronous or metachronous primary lung neoplasms (pT1m) and intrapulmonary metastasis of non-small cell carcinoma of the lung (pT4 or pM1 according to their location); and the role of the recent American Joint Committee on Cancer terminology for the classification of lymph nodes (isolated tumor cells, micrometastases, and metastases). The variety of practical problems that can arise during the assessment of important prognostic and predictive features such as resection margin status and evaluation of lymphovascular invasion are reviewed. A brief discussion of the assessment of the effects of neoadjuvant therapy on resected lung neoplasms is also included.