Detection Of Lymphovascular Invasion Research Articles

A New Method of Artificial-Intelligence-Based Automatic Identification of Lymphovascular Invasion in Urothelial Carcinomas.

The presence of lymphovascular invasion (LVI) in urothelial carcinoma (UC) is a poor prognostic finding. This is difficult to identify on routine hematoxylin-eosin (H&E)-stained slides, but considering the costs and time required for examination, immunohistochemical stains for the endothelium are not the recommended diagnostic protocol. We developed an AI-based automated method for LVI identification on H&E-stained slides. We selected two separate groups of UC patients with transurethral resection specimens. Group A had 105 patients (100 with UC; 5 with cystitis); group B had 55 patients (all with high-grade UC; D2-40 and CD34 immunohistochemical stains performed on each block). All the group A slides and 52 H&E cases from group B showing LVI using immunohistochemistry were scanned using an Aperio GT450 automatic scanner. We performed a pixel-per-pixel semantic segmentation of selected areas, and we trained InternImage to identify several classes. The DiceCoefficient and Intersection-over-Union scores for LVI detection using our method were 0.77 and 0.52, respectively. The pathologists' H&E-based evaluation in group B revealed 89.65% specificity, 42.30% sensitivity, 67.27% accuracy, and an F1 score of 0.55, which is much lower than the algorithm's DCC of 0.77. Our model outlines LVI on H&E-stained-slides more effectively than human examiners; thus, it proves a valuable tool for pathologists.

Ensemble Deep Learning Model to Predict Lymphovascular Invasion in Gastric Cancer.

Lymphovascular invasion (LVI) is one of the most important prognostic factors in gastric cancer as it indicates a higher likelihood of lymph node metastasis and poorer overall outcome for the patient. Despite its importance, the detection of LVI(+) in histopathology specimens of gastric cancer can be a challenging task for pathologists as invasion can be subtle and difficult to discern. Herein, we propose a deep learning-based LVI(+) detection method using H&E-stained whole-slide images. The ConViT model showed the best performance in terms of both AUROC and AURPC among the classification models (AUROC: 0.9796; AUPRC: 0.9648). The AUROC and AUPRC of YOLOX computed based on the augmented patch-level confidence score were slightly lower (AUROC: -0.0094; AUPRC: -0.0225) than those of the ConViT classification model. With weighted averaging of the patch-level confidence scores, the ensemble model exhibited the best AUROC, AUPRC, and F1 scores of 0.9880, 0.9769, and 0.9280, respectively. The proposed model is expected to contribute to precision medicine by potentially saving examination-related time and labor and reducing disagreements among pathologists.

Preoperative detection of lymphovascular invasion in rectal cancer using intravoxel incoherent motion imaging based on radiomics.

Lymphovascular invasion (LVI) status plays an important role in treatment decision-making in rectal cancer (RC). Intravoxel incoherent motion (IVIM) imaging has been shown to detect LVI; however, making better use of IVIM data remains an important issue that needs to be discussed. We proposed to explore the best way to use IVIM quantitative parameters and images to construct radiomics models for the noninvasive detection of LVI in RC. A total of 83 patients (LVI negative (LVI-): LVI positive (LVI+)=51:32) with postoperative pathology-confirmed LVI status in RC were divided into a training group (n=58) and a validation group (n=25). Images were acquired from a 3.0 Tesla machine, including oblique axial T2 weighted imaging (T2WI) and IVIM with 11 b values. The ADC, D, D* and f values were measured on IVIM maps. The ROIs of tumors were delineated on T2WI, DWI, ADCmap , and Dmap images, and three mapping methods were used: ROIs_mapping from DWI, ROIs_mapping from ADCmap , and ROIs_mapping from Dmap . Three-dimensional radiomics features were extracted from the delineated ROIs. Multivariate logistic regression was used for radiomics feature selection. Radiomics models based on different mapping methods were developed. Receiver operating characteristic (ROC) curves, calibration, and decision curve analyses (DCA) were used to evaluate the performance of the models. Model B, which was constructed with radiomics features from ADCmap , Dmap and fmap by "ROIs_mapping from DWI" and T2WI (AUC 0.894), performed better than other models based on single sequence (AUC 0.600-0.806) and even better than Model A, which was based on "ROIs_mapping from ADC" and T2WI (AUC 0.838). Furthermore, an integrated model was constructed with Model B and the IVIM parameter (f value) with an AUC of 0.920 (95% CI: 0.820-1.000), which was higher than that of Model B, in the validation group. The integrated model incorporating the radiomics features and IVIM parameters accurately detected LVI of RC. The "ROIs_mapping from DWI" method provided the best results.

The Usefulness of Elastin Staining to Detect Vascular Invasion in Cancer.

Tumor prognosis hinges on accurate cancer staging, a pivotal process influenced by the identification of lymphovascular invasion (LVI), i.e., blood vessel and lymphatic vessel invasion. Protocols by the College of American Pathologists (CAP) and the World Health Organization (WHO) have been established to assess LVI in various tumor types, including, but not limited to, breast cancer, colorectal cancer (CRC), pancreatic exocrine tumors, and thyroid carcinomas. The CAP refers to blood vessel invasion as "angioinvasion" (vascular invasion) to differentiate it from lymphatic vessel invasion (lymphatic invasion). For clarity, the latter terms will be used throughout this review. The presence of lymphatic and/or vascular invasion has emerged as a pivotal prognostic factor; therefore, its accurate identification is crucial not only for staging but also for providing the patient with an honest understanding of his/her prognosis. Given the prognostic importance of the correct identification of LVI, specific staining techniques are employed to distinguish lymphatic vessel invasion from angioinvasion and to differentiate true LVI from artifact. These encompass hematoxylin and eosin (H&E) staining, elastic staining, Factor VIII staining, Ulex europaeus I agglutinin staining, CD31, CD34, D2-40, ERG, and D2-40 (podoplanin) immunohistochemical (IHC) stains among others. Based on a review of numerous publications regarding the efficacy of various methods for LVI detection, elastin staining demonstrated superior accuracy and prognostic value, allowing for more targeted treatment strategies. The clinical significance of accurately detecting LVI cannot be overstated, as it is strongly linked to higher cancer-related mortality and an increased risk of tumor recurrence. This review aims to examine the existing literature on the use of elastin stains in the detection of vascular invasion among different types of tumors and its prognostic value.

Abstract P5-01-08: Steps toward noninvasive lymph node staging (NILS) in clinically node negative patients: Artificial neural network model to preoperatively predict lymphovascular invasion

Abstract Background: Lymphovascular invasion (LVI) is one of the most important predictors for nodal status in breast cancer patients [1]. Multiple models have been published for prediction of preoperatively disease-free axillary using i.a. LVI [1-2]. However, LVI detection in preoperative core needle biopsy has been reported with a failure rate of 30% [3] and the analysis is not routinely performed in Sweden. Thus, a preoperative model of LVI status would be useful in prediction models for noninvasive lymph node staging (NILS). The purpose of this study was to develop an artificial neural network (ANN) model for LVI prediction using only clinicopathological variables that are routinely available in the preoperative setting. Methods: Data gathered prospectively during 2009-2012 in Lund, Sweden from 761 clinically node negative breast cancer patients were retrospectively extracted. Inclusion criteria were female sex, primary breast cancer and that each patient was scheduled for primary surgery. Patients with metastatic disease, bilateral cancer, tumor size greater than 50 mm, previous ipsilateral breast or axillary surgery, patients omitted of standard axillary staging procedure by SLNB or ALND, and those who had neoadjuvant treatment were excluded. LVI was assessed on surgical breast specimens and was defined as the presence of tumor cells within endothelium-lined vascular channels. Out of the 761 patients in the cohort, 613 patients were documented with LVI status. The LVI full case dataset was split 80/20 for training and validation. The remaining 148 patients were set aside for model testing. Since the test dataset did not contain information on LVI status, it was used to compare the predicted fraction of LVI positive patients to that of the development dataset. Only variables possible to obtain in the preoperative setting were included in the prediction models, comprising age, menopausal status, mode of detection (mammography screening or symptomatic representation), tumor size, multifocality (yes/no), histopathological type, histological grade, ki-67 percentage, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status. An ensemble approach was used, where each ensemble constituted 30 ANNs that were trained and validated using 5-fold cross validation. For every ensemble model, different model parameters, such as L2-regularization and the number of hidden nodes, were tested. Model selection was based on validation AUC. Results: The study cohort included female clinically node negative breast cancer patients scheduled for primary surgery. Data from 613 patients (lymph node stages N0: 67.4%, N1: 26.9%, N2+: 5.7%) were used to develop the model, and 148 patients (N0: 56.8%, N1: 35.8%, N2+: 7.4%) constituted the internal test cohort. Fifteen percentage of the patients in the development dataset were LVI positive. The selected ensemble model achieved a validation AUC of 0.80 (CI 0.75-0.85). This model predicted an LVI positive rate of 16.2% in the test dataset. Conclusion: LVI was predicted with high accuracy using an ANN model based on routine preoperative clinicopathological variables. The result of validation AUC 0.80 (CI 0.75-0.85) indicates a potential for preoperative prediction of LVI, and the model can putatively be useful when applying preoperative nodal prediction models in patients without known LVI status. To confirm these results, verification in an external dataset is needed. Validation of the LVI-model in an independent dataset from the National Breast Cancer Registry will be performed, as well as an evaluation of the usefulness of the LVI-model as an imputation in a nodal prediction model. [1] Dihge, L. et al. BMC Cancer (2019). PMID: 31226956 [2] Bevilacqua, J. L. et al. J Clin Oncol. (2007). PMID: 17664461 [3] Harris, G. C. et al. Am J Surg Pathol. (2003). PMID: 12502923 Citation Format: Malin Hjärtström, Looket Dihge, Pär-Ola Bendahl, Mattias Ohlsson, Lisa Rydén. Steps toward noninvasive lymph node staging (NILS) in clinically node negative patients: Artificial neural network model to preoperatively predict lymphovascular invasion [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-01-08.

Does VEGF Expression Correlate with Lymphatic Metastasis in Breast Cancer?

IntroductionPrimary tumor characteristics are increasingly used for prognostication, predicting lymph node metastasis and planning adjuvant treatment in breast cancer. Vascular Endothelial Growth factor (VEGF) has been postulated to stimulate lymph vessels development and growth in tumors. Few studies on cell lines have documented how the new lymphatics develop or tumor cells invade these lymphatics. However, in human breast cancer the literature is sparse. Hence, this study is done to see the expression of VEGF and its correlation with lymphatic invasion in breast cancer patients.Materials & MethodsFormalin fixed paraffin embedded blocks of breast cancer specimens and controls were retrieved & 4u thick sections stained with H&E stains for morphological evaluation. Serial sections were cut on APES (3‐Triethoxysilylpropylamine) coated slides for performing immunohistochemistry using monoclonal antibodies against VEGF and DII40. The expression intensity of VEGF and its distribution in the tumor samples were observed and semi‐quantitatively analyzed. VEGF expression was interpreted as follows: negative (0): <5% staining; weak (+): 5–25% staining; positive (++): 26–50% staining; strongly positive (+++): >50% staining. Statistical analysis: samples with 0/+ staining were considered in low VEGF expression, while samples with ++/+++ expression were considered as high VEGF expression. For DII40 well demarcated vessels showing positivity in endothelial cells were counted per 10hpf after selecting hot spots at scanner view. For statistical analysis, 0 was considered as no expression and 1/10HPF was considered as high expression. Association between levels of VEGF and D II 40 was examined by the two‐way scatter plot and a linear regression analysis of DII 40 over VEGF. The association of positivity between the two markers was assessed using Chi Square test.ResultsHigh VEGF expression was seen 33 of the 43 evaluable patients (76.74%%; 95% CI 61.37%‐88.24%) and high DII 40 expression was seen in 30 of the 44 patients (68.18%; 95% CI 52.42%‐81.39%). Of the 33 patients with high VEGF expression, DII 40 was expressed in 26 of them (78.79%). There was a strong association between VEGF expression and DII 40 expression (p<0.01) (Figure 1). The variance explained by VEGF level in the variance of DII 40 as measured by the correlation (R2) was 0.1265 (p=0.02). When the expression of VEGF and D II 40 was compared with tumor characteristics, there was statistically significant correlation with lymphovascular invasion (LVI) but not with tumor size, type, grade, ER/PR status, Her2neu status or lymph node involvement.ConclusionVEGF expression is high in most tumors. There is significant association between LVI & lymph vessels detection as studied by D II 40 expression and VEGF expression. Further studies in clinical settings are essential before incorporating VEGF expression for prognostication and customized patient care.

Lymphovascular invasion in hormone-positive, human epidermal growth factor-negative, low-burden axillary disease in early breast cancer patients tested for oncotype DX recurrence score.

IntroductionThe oncotype DX recurrence score (ODX-RS) is a validated 21-gene assay that can quantify the recurrence risk and assess the likelihood of adjuvant chemotherapy benefit in breast cancer. The presence of lymphovascular invasion (LVI) in breast cancer patients is regarded as a predictor for worse prognosis. This study sought to explore the association of ODX-RS with LVI in oestrogen receptor-positive, human epidermal growth factor receptor–2-negative, low-burden nodal disease, early breast cancer.Material and methodsAfter clinical improvement unit approval, an institutional database was queried to identify the breast cancer cases diagnosed in the period between 2017–2021 that fulfilled the inclusion criteria. The total resected tumours comprised 107 in 102 patients (5 patients had bilateral disease). The data related to patients’ age and tumour grade, LVI detection, nodal status, and ODX-RS were analysed.ResultsLymphovascular invasion was identified in 32.6% of 107 tumours. In the age group > 50 years, 13 tumours had lymphovascular invasion (LVI +ve), 9 tumours had ODX-RS < 15 (69%), and only one tumour (8%) had ODX-RS ≤ 25, and this is associated with substantial chemotherapy benefit. In the age group ≤ 50 years, 21 tumours were LVI +ve, and 18 tumours had ODX-RS ≤ 25 (86%), which is associated with no chemotherapy benefit; only 3 tumours (14%) had ODX-RS > 25, and this indicated substantial chemotherapy benefit.ConclusionsThis study revealed that in the targeted patient population lympho-vascular invasion did not have a statistically significant impact on ODX-RS (p = 0.29).

Reevaluation of lymphovascular invasion in gastric cancer using endothelial markers D2-40 and EVG: Enhanced detection, better predictor of lymph node metastasis and biological aggressiveness.

The diagnosis of lymphovascular invasion (LVI) is often inaccurate with routine histology. This study aimed to evaluate the use of immunohistochemistry (IHC) in detecting LVI and reevaluate the clinical implications of LVI in gastric cancer. This prospective unrandomized cohort study analyzed the rates of LVI positivity and its relevance with other clinicopathologic features. Between November 2017 and April 2018, 558 patients undergoing curative gastrectomy were enrolled and assigned to the IHC group (n = 285) and hematoxylin-eosin group (n = 273). The use of IHC increased the rates of LVI positivity (60.8% vs. 43.3%, p < .001) and decreased the rates of undetermined LVI subtype (7.7% vs. 27.1%, p < .001). The LVI-negative patients identified by IHC had fewer lymph node metastases (16.8% vs. 34.6%, p = .002) and earlier pathological stage (p = .004) than those identified by routine histology. The LVI-positive patients identified by IHC had a higher percentage of perineural invasion (p = .019). The use of endothelial markers significantly enhanced the detection of LVI. The LVI detected by IHC could be a better predictor of lymph node metastasis and biological aggressiveness in gastric cancer.

Oncological and prognostic impact of lymphovascular invasion in Colorectal Cancer patients.

Objectives: Lymphovascular invasion (LVI) is correlated with unfavorable prognoses in several types of cancers. We aimed to identify the informative features associated with LVI and to determine its prognostic value in colorectal cancer (CRC) patients.Methods: We retrospectively analyzed 1,474 CRC patients admitted in Wuhan Union Hospital between 2013 and 2017 as the development cohort and 549 CRC patients from The Cancer Genome Atlas (TCGA) database as the validation cohort. Logistical and Cox regression analyses were conducted to determine the oncological and prognostic significance of LVI in CRC patients. A survival nomogram based on LVI status was established using the Wuhan Union cohort and validated using TCGA cohort.Results: The LVI detection rates were 21.64% in the Wuhan Union cohort and 35.15% in TCGA cohort. LVI was closely correlated with advanced T stage, N stage, and TNM stage. LVI positivity was an independent biomarker for unfavorable overall survival (hazard ratio [HR]=2.25, 95% confidence interval [CI]=1.70-2.96, P<0.0001) and worse disease-free survival (HR=2.34, 95% CI=1.76-3.12, P<0.0001) in CRC patients. The survival nomogram incorporating LVI exhibited good predictive performance and reliability in the Wuhan Union cohort and TCGA cohort.Conclusion: LVI is a significant indicator of advanced stage and is remarkably correlated with worse prognosis in CRC patients. The survival nomogram incorporating LVI may assist clinicians to better strategize the therapeutic options for patients with CRC.

Multiple combinations of melanocytic and vascular endothelial markers enhance the detection rate of lymphovascular invasion in cutaneous melanoma.

Lymphovascular invasion (LVI) is believed to be the mechanism by which melanoma cells can disseminate to regional lymph nodes and distant sites and may be predictive of adverse outcome. Lymphovascular invasion often difficult to detect on hematoxylin-eosin (HE) stained sections, are readily identified with dual immunohistochemistry (IHC) for melanocytic and vascular markers. A total of 100 primary cutaneous malignant melanoma cases that had a Breslow thickness of 1-4 mm and lacked LVI by conventional HE assessment were included. We compared the LVI detection rates of double staining for CD31/S100 and CD34/S100, and D2-40/S100, and examined the association of LVI with clinical outcomes. The dual immunohistochemical positivity for CD31/S100, CD34/S100, and D2-40/S100 were 40(40%), 17(17%) and 35(35%), respectively. On multivariate analysis, LVI was an independent predictor of SLN status. Multivariate analysis revealed that LVI and male gender were independent risk factors for overall survival. The recognition of LVI is improved by dual IHC and predicts SLN metastasis. The detection of LVI using dual IHC, especially by a combination of CD31/S100 and D2-40/S100 is a useful step that inclusion should be recommended in basic evaluation parameters for cutaneous melanoma.

Importance of endothelial markers in detection of lymphovascular invasion in carcinoma breast and its correlation with axillary lymph node metastasis

Background: Lymphovascular invasion (LVI) is one of the important prognostic factors in carcinoma breast and its accurate diagnosis is important, particularly in node-negative cases for making the decision regarding aggressive adjuvant chemotherapy. Sometimes, it becomes very difficult to diagnose LVI on routine hematoxylin and eosin (H and E) stained tissue sections. Staining with endothelial immunomarkers makes the identification easy. Aim of the Study: This study aims to compare LVI detection on H and E and immunohistochemistry (IHC) stained sections and its correlation with axillary lymph node metastasis. Materials and Methods: A total of 45 cases of invasive breast carcinoma were studied. LVI was evaluated in routine H and E and IHC stained sections. The results were compared. The LVI status on IHC was correlated with axillary lymph node status. Results: The accuracy of H and E stained sections in detection of LVI was 75.6% with a false-positive and false-negative rate of 20% and 4.4%, respectively. There was no significant association between LVI on IHC and axillary lymph node status. Conclusions: The detection of LVI on routine H and E sections can be erroneous. IHC should be done in cases with confusing focus on routine H and E stained sections, particularly in node-negative cases.

Evaluation of Submucosal or Lymphovascular Invasion Detection Rates in Early Gastric Cancer Based on Pathology Section Interval.

PurposeThe guidelines for pathological evaluation of early gastric cancer (EGC) recommend wider section intervals for surgical specimens (5–7 mm) than those for endoscopically resected specimens (2–3 mm). Studies in surgically resected EGC specimens showed not negligible lymph node metastasis risks in EGCs meeting the expanded criteria for endoscopic submucosal dissection (ESD).Materials and MethodsThis retrospective study included 401 EGC lesions with an endoscopic size of ≤ 30 mm detected in 386 patients. Pathological specimens obtained by ESD or surgery were cut into 2-mm section intervals for reference. Submucosal or lymphovascular invasion (LVI) was evaluated arbitrarily in 4- or 6-mm section intervals. McNemar's tests compared the differences between submucosal and LVI.ResultsSubmucosal invasion was detected in 29.2% (117/401) and LVI in 9.5% (38/401) at 2-mm interval. The submucosal invasion detection rates in 4-mm intervals decreased to 88.0% or 90.6% (both P<0.001), while the LVI detection rates decreased to 86.8% or 57.9% (P=0.025 and P<0.001, respectively). In 6-mm intervals, the submucosal and LVI detection rates decreased further to 72.7–80.3% (P<0.001 for all three sets) and 55.3–63.2% (P<0.001 for all three sets), respectively. Among 150 out-of-indication cases at 2-mm interval, 4–10 (2.7%–6.7%) at 4-mm intervals, and 10–17 (6.7%–11.3%) at 6-mm intervals were misclassified as lesions meeting the curative resection criteria due to the underestimation of submucosal or LVI.ConclusionsAfter ESD, the 2-mm wide section interval was suitable for the pathological evaluation of focal submucosal or LVI. Thus, if an EGC lesion meets the expanded criteria for the ESD specimen pathological evaluation, it could be safely followed up.

Use of Immunomarkers D2-40 and CD31 in Detection of Lymphovascular Invasion in Breast Carcinoma

Use of Immunomarkers D2-40 and CD31 in Detection of Lymphovascular Invasion in Breast Carcinoma

Prognostic value of the detection of lympho-vascular invasion in hormone receptor positive early breast cancer in the era of molecular profiling.

e12539Background: Lympho-vascular invasion (LVI) is considered a negative prognostic factor in early breast cancer, but its value in clinical decisions regarding adjuvant chemotherapy is unclear in...

Intratumoral and peritumoral lymphovascular invasion detected by D2-40 immunohistochemistry correlates with metastasis in primary cutaneous Merkel cell carcinoma

Primary cutaneous Merkel cell carcinoma (MCC) is an aggressive neuroendocrine malignancy in which lymphovascular invasion (LVI) correlates with more aggressive phenotype. The prognostic significance of LVI detected by D2-40 immunohistochemistry (IHC) in MCC remains controversial. We aimed to determine how LVI detected by D2-40 IHC compares with LVI detected by hematoxylin and eosin (H&E) staining in predicting MCC metastasis. Clinical and histopathologic features of MCCs diagnosed and treated in 2002 to 2015 were assembled and included 58 MCC tumors from 58 patients. H&E-stained tissue sections and D2-40 IHC studies were reviewed. When LVI was present, the location (peritumoral or intratumoral) and the size of the largest invaded vessel were recorded. LVI findings by H&E staining and D2-40 IHC were compared with each other and with histologic features and clinical outcomes. H&E staining showed LVI in 37 of 58 cases; D2-40 IHC confirmed LVI in 30 of these cases but failed to confirm LVI in 7. D2-40 IHC also detected 14 cases of LVI not identified on H&E staining. Histologically, D2-40-detected LVI was associated with infiltrative growth pattern and nonbrisk lymphoid infiltrate (P = .005 and P = .055, respectively). There was a statistically significant difference between the frequency of detection of peritumoral LVI by H&E in comparison to D2-40 IHC (P = .0009). MCCs in which D2-40 IHC-detected both intratumoral and peritumoral LVI were typically larger than MCCs without (mean, 24.5 mm versus 17.3 mm; P = .03) and more frequently metastasized (87% versus 51%; P = .03). D2-40 IHC detection of both intratumoral and peritumoral LVI is associated with metastasis.

Accuracy and prognostic value of variant histology and lymphovascular invasion at transurethral resection of bladder.

To evaluate the concordance rate of lymphovascular invasion (LVI) and variant histology (VH) of transurethral resection (TUR) with radical cystectomy (RC) specimens. Furthermore, to evaluate the value of LVI and VH at TUR for predicting non-organ confined (NOC) disease, lymph node metastasis, and survival outcomes. Two hundred and sixty-eight patients who underwent TUR and subsequent RC were reviewed. Logistic regression analyses were performed to evaluate the association of LVI and VH with NOC and lymph node metastasis at RC. Cox regression analyses were used to estimate recurrence-free survival (RFS) and cancer-specific survival (CSS). LVI and VH were detected in 13.8 and 11.2% of TUR specimens, and in 30.2 and 25.4% of RC specimens, respectively. The concordance rate between LVI and VH at TUR and subsequent RC was 69.8 and 83.6%, respectively. They were both associated with adverse pathological features such as lymph node metastasis and advanced stage. TUR LVI and VH were both independently associated with lymph node metastasis and TUR VH was independently associated with NOC. On univariable Cox regression analyses, TUR LVI was associated with RFS and CSS while TUR VH was only associated with RFS. Only TUR LVI was independently associated with RFS. Detection of LVI is missed in a third of TUR specimens while VH seems more accurately identified. TUR LVI and VH are associated with more advanced disease and LVI predicts disease recurrence. Assessment and reporting of LVI and VH on TUR specimen are important for risk stratification and decision-making.

The relationship of lymphatic vessel density, lymphovascular invasion, and lymph node metastasis in breast cancer: a systematic review and meta-analysis.

Lymph node status is one of the key parameters used for determining the stage of breast cancer progression. The relationship of lymphatic vessel density (LVD), lymphovascular invasion (LVI), and lymph node metastasis (LNM) has not been clearly demonstrated yet. Databases of PubMed, Embase, and Web of Science were searched from inception up to 25 May 2016. Spearman correlation coefficient (r) and 95% confidence interval (CI) were used to determine the relationship within each group. Based on pre-established inclusion criteria, 28 studies involving 2920 breast cancer patients were included in this study. The r values of LVD-LVI, LVD-LNM, and LVI-LNM were 0.45 (95% CI: 0.31 to 0.57), 0.32 (95% CI: 0.23 to 0.40), and 0.24 (95% CI: 0.19 to 0.28), respectively. Compared with intratumoral LVD, peritumoral LVD showed more robust correlation with LVI (r = 0.53, 95% CI: 0.27 to 0.72) and LNM (r = 0.33, 95% CI: 0.18 to 0.46). The patients in LNM positive group presented with higher LVI detection rate of 45.85%, while in LNM negative group with detection rate of 23.85%. The results describe a triangle relationship between LVD, LVI, and LNM in breast cancer. Both LVD and LVI are indicated to be valuable predictors of LNM occurrence. Compared with intratumoral lymphatic vessels, peritumoral lymphatics might be the main disseminate route for breast tumor cells.

Enhanced detection of lymphovascular invasion in small rectal neuroendocrine tumors using D2-40 and Elastica van Gieson immunohistochemical analysis.

Rectal neuroendocrine tumor (RNET) lymphovascular invasion (LVI) is regarded as an important predictor of nodal metastasis after endoscopic resection (ER). However, little is known about the frequency of immunohistochemical detection of LVI in RNETs. This study was performed to establish the actual detection of LVI rate in RNETs ≤10 mm and to evaluate associated clinical outcomes. We retrospectively reviewed the records for 98 consecutive patients treated by ER with a total of 102 RNETs ≤10 mm. Tissue sections were labeled with hematoxylin–eosin (HE) stain, the D2‐40 monoclonal antibody to evaluate lymphatic invasion, and Elastica van Gieson (EVG) stain to detect venous invasion. LVI detection rate by HE versus immunohistochemical analysis was compared. Follow‐up findings and clinical outcomes were also evaluated for 91 patients who were followed for ≥12 months. Lymphatic and venous invasion were detected using HE staining alone in 6.9% and 3.9% of patients, respectively, whereas they were detected using D2‐40 and EVG staining in 20.6% and 47.1% of the patients, respectively. Thus, the LVI detection frequency using D2‐40 and EVG staining (56.9%) was significantly higher than with HE (8.8%). Two out of seven patients who required additional surgery had regional lymph node metastases. However, among the 84 patients who were followed up without surgery, no distant metastases or recurrences were detected. Compared with HE staining, immunohistochemical analysis significantly increased the frequency of LVI detection in RNETs ≤10 mm. However, the clinical impact of LVIs detected using immunohistochemical analysis remains unclear. Clarification of the actual role of LVI using immunohistochemical analysis requires a patient long‐term follow‐up and outcomes.

Lymphovascular invasion in more than one-quarter of small rectal neuroendocrine tumors.

AIMTo identify the frequency, clinicopathological risk factors, and prognostic significance of lymphovascular invasion (LVI) in endoscopically resected small rectal neuroendocrine tumors (NETs).METHODSBetween June 2005 and December 2015, 104 cases of endoscopically resected small (≤ 1 cm) rectal NET specimens at Hallym University Sacred Heart Hospital in Korea were retrospectively evaluated. We compared the detected rate of LVI in small rectal NET specimens by two methods: hematoxylin and eosin (H&E) and ancillary immunohistochemical staining (D2-40 and Elastica van Gieson); in addition, LVI detection rate difference between endoscopic procedures were also evaluated. Patient characteristics, prognosis and endoscopic resection results were reviewed by medical charts.RESULTSWe observed LVI rates of 25.0% and 27.9% through H&E and ancillary immunohistochemical staining. The concordance rate between H&E and ancillary studies was 81.7% for detection of LVI, which showed statistically strong agreement between two methods (κ = 0.531, P < 0.001). Two endoscopic methods were studied, including endoscopic submucosal resection with a ligation device and endoscopic submucosal dissection, and no statistically significant difference in the LVI detection rate was detected between the two (26.3% and 26.8%, P = 0.955). LVI was associated with large tumor size (> 5 mm, P = 0.007), tumor grade 2 (P = 0.006). Among those factors, tumor grade 2 was the only independent predictive factor for the presence of LVI (HR = 4.195, 95%CI: 1.321-12.692, P = 0.015). No recurrence was observed over 28.8 mo regardless of the presence of LVI.CONCLUSIONLVI may be present in a high percentage of small rectal NETs, which may not be associated with short-term prognosis.

PD41-06 CLINICAL VALUE OF IMMUNOHISTOCHEMICALLY DETECTED LYMPHOVASCULAR INVASION IN TRANSURETHRAL BLADDER TUMOR RESECTION SPECIMEN FOR BLADDER CANCER STAGING BEFORE RADICAL CYSTECTOMY

You have accessJournal of UrologyBladder Cancer: Staging1 Apr 2015PD41-06 CLINICAL VALUE OF IMMUNOHISTOCHEMICALLY DETECTED LYMPHOVASCULAR INVASION IN TRANSURETHRAL BLADDER TUMOR RESECTION SPECIMEN FOR BLADDER CANCER STAGING BEFORE RADICAL CYSTECTOMY Tatsuo Gondo, Jun Nakashima, Rie Inoue, Takeshi Hashimoto, Yoshio Ohno, Makoto Ohori, Toshitaka Nagao, and Masaaki Tachibana Tatsuo GondoTatsuo Gondo More articles by this author , Jun NakashimaJun Nakashima More articles by this author , Rie InoueRie Inoue More articles by this author , Takeshi HashimotoTakeshi Hashimoto More articles by this author , Yoshio OhnoYoshio Ohno More articles by this author , Makoto OhoriMakoto Ohori More articles by this author , Toshitaka NagaoToshitaka Nagao More articles by this author , and Masaaki TachibanaMasaaki Tachibana More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2414AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It is one of our major concerns to investigate the clinical implication of lymphovascular invasion (LVI) in transurethral resection of bladder tumor (TURBT) specimens (TUR-LVI) in clinical decision making in patients with bladder cancer. Immunohistochemistry (IHC) may improve LVI detection in small TUR specimens. We aimed to investigate the clinical significance of TUR-LVI for bladder cancer staging and compare the clinical values of IHC-detected LVI (IHC-LVI) with HE-detected LVI (HE-LVI). METHODS This study included 157 non-metastatic bladder cancer patients treated with radical cystectomy (RC) at our institution. A single pathologist with expertise in genitourinary malignancies evaluated all TURBT specimens and assessed the venous, lymphatic and lymphovascular invasions in HE and IHC stained specimens. Two IHC markers for lymphatic channels (D2-40) and endothelial cells (CD31) were used to clarify lymphatic (ly) and venous (v) invasions in IHC studies. The univariate and multivariate logistic regression analyses were used to identify preoperative factors correlated with extra-vesical disease (≥pT3) at RC.□ RESULTS Sixty-nine patients (44%) were diagnosed with ≥pT3 disease on RC specimens. HE-LVI was detected in 38 (24%) patients while IHC-LVI in 57 (36%). Twenty-six (46%) of the 57 patients with positive IHC-LVI was determined negative for HE-LVI, while 7 (18%) of the 38 patients with positive HE-LVI was determined negative by IHC. In univariate analyses, clinical T (cT) stage, tumor multifocality, hydronephrosis, and HE-LVI were significantly associated with ≥pT3 disease, but v and ly by both HE and IHC staining and IHC-LVI were not. In multivariate analyses, cT stage (p<0.001), hydronephrosis (p=0.002), and HE-LVI (p=0.025) were significant factors for the prediction of ≥pT3 disease. We developed a nomogram using these variables (Figure) and the area under the curve was 0.79. CONCLUSIONS cT stage, hydronephrosis, and HE-LVI were significant preoperative predictors for ≥pT3 disease at RC. Although IHC could detect more LVI in TURBT samples, it failed to be an independent factor in this setting. Additionally, detailed distinction between v and ly invasion status added no clinical value. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e842 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tatsuo Gondo More articles by this author Jun Nakashima More articles by this author Rie Inoue More articles by this author Takeshi Hashimoto More articles by this author Yoshio Ohno More articles by this author Makoto Ohori More articles by this author Toshitaka Nagao More articles by this author Masaaki Tachibana More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...