Prognostic significance of extranodal extension in oral cavity squamous cell carcinoma with occult neck metastases

Mamic, M; Lucijanić, Marko; Manojlović, Luka; Müller, Danko; Suton, Petar; Lukšić, Ivica

doi:10.1016/j.ijom.2020.07.006

Cited by 22 publications

(8 citation statements)

References 26 publications

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“…We have pooled only articles comparing presence vs. absence of ENE, following the recommendation of the current TNM classification. However, few studies have attempted to determine clinically relevant qualitative and quantitative characteristics of ENE, including number of metastatic nodes with ENE, size of the metastatic focus and distance from the edge of the nodal capsule to the metastatic tumor edge (42)(43)(44). Although our study has not analyzed lymph node ratio (LNR), also called lymph node burden, recent systematic reviews have demonstrated its prognostic impact for OSCC (45,46).…”

Section: Discussionmentioning

confidence: 98%

The Impact of Histopathological Features on the Prognosis of Oral Squamous Cell Carcinoma: A Comprehensive Review and Meta-Analysis

et al. 2021

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ObjectiveOver many decades, studies on histopathological features have not only presented high-level evidence of contribution for treatment directions and prognosis of oral squamous cell carcinoma (OSCC) but also provided inconsistencies, making clinical application difficult. The 8th TNM staging system of OSCC has acknowledged the importance of some histopathological features, by incorporating depth of invasion (DOI) to T category and extranodal extension (ENE) to N category. The aim of this systematic review with meta-analysis is to determine the most clinically relevant histopathological features for risk assessment and treatment planning of OSCC and to elucidate gaps in the literature.MethodsA systematic review was conducted using PRISMA guidelines, and the eligibility criteria were based on population, exposure, comparison, outcome, and study type (PECOS). PubMed, Cochrane, Scopus, and Web of Science were searched for articles exploring the impact of histopathological features on OSCC outcomes with Cox multivariate analysis. Pooled data were subjected to an inverse variance method with random effects or fixed effect model, and the risk of bias was evaluated using quality in prognosis studies (QUIPS). Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.ResultsThe study included 172 articles published from 1999 to 2021. Meta-analyses confirmed the prognostic potential of DOI, ENE, perineural invasion, lymphovascular invasion, and involvement of the surgical margins and brought promising results for the association of bone invasion, tumor thickness, and pattern of invasion with increased risk for poor survival. Although with a small number of studies, the results also revealed a clinical significance of tumor budding and tumor-stroma ratio on predicted survival of patients with OSCC. Most of the studies were considered with low or moderate risk of bias, and the certainty in evidence varied from very low to high.ConclusionOur results confirm the potential prognostic usefulness of many histopathological features and highlight the promising results of others; however, further studies are advised to apply consistent designs, filling in the literature gaps to the pertinence of histopathological markers for OSCC prognosis.Systematic Review RegistrationInternational Prospective Register of Systematic Reviews (PROSPERO), identifier CRD42020219630.

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Section: Discussionmentioning

confidence: 98%

The Impact of Histopathological Features on the Prognosis of Oral Squamous Cell Carcinoma: A Comprehensive Review and Meta-Analysis

et al. 2021

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“…Since the publication of the eighth edition of the Union for International Cancer Control/American Joint Committee on Cancer staging manual, attempts to validate the 2-mm cutoff between major and microscopic ENE have been mixed. Mamic et al 40 found a similar cutoff of 1.9 mm by receiver operating characteristics curve analysis to be prognostic in multivariate analysis of oral cavity SCCs, although only patients with clinically occult nodal disease were included in the study. In contrast, a recent examination of ENE in oral cavity SCC 38 found that a 2-mm cutoff was not prognostic; instead, 5 mm imparted worse disease-free and overall survival but only in univariate analysis.…”

Section: Figure 1 Lymph Node Metastases Without Pathologic Extranodal Extensionmentioning

confidence: 93%

Assessment Criteria and Clinical Implications of Extranodal Extension in Head and Neck Cancer

Huang

Chernock

Fakhry

2021

American Society of Clinical Oncology Educational Book

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Tumor breaching the capsule of a lymph node is termed extranodal extension (ENE). It reflects aggressiveness of a tumor, creates anatomic challenges for disease clearance, and increases the risk of distant metastasis. Extranodal extension can be assessed on a pathology specimen, by radiology studies, and by clinical examination. Presence of ENE in a pathology specimen has long been considered a high-risk feature of disease progression and would ordinarily benefit from the addition of chemotherapy to adjuvant radiotherapy. Although the eighth edition of the Union for International Cancer Control/American Joint Committee on Cancer stage classification dichotomizes pathologic ENE according to its presence or absence, emerging evidence suggests that the extent of a pathologic ENE may provide additional value for risk stratification to guide adjuvant therapy. Recent data suggest that the prognostic importance of pathologic ENE is also applicable for HPV-associated head and neck squamous cell carcinoma. In addition, compelling data demonstrate that indisputable radiologic ENE is a powerful risk stratification tool to identify patients at high risk for treatment failure, especially distant metastasis, applicable for both HPV-positive and HPV-negative head and neck squamous cell carcinoma. However, the definition and taxonomy of radiologic ENE requires standardization. The goal of this review is to clarify the contemporary understanding of the prognostic implications of ENE in head and neck squamous cell carcinoma, present the nuances of what is presently known and unknown, and elucidate how to classify ENE pathologically and radiologically with an understanding of the strengths and weaknesses of each approach. Finally, with the development of several risk stratification methods, the relative role of ENE and other prognostic schema will be explored.

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“…Although several studies have investigated the risk factors of ECS occurrence in HNC, findings have been inconsistent results among studies. The number and size of metastatic nodes and the depth and pattern of invasion were reported to be independent predictors for the ECS of LNM in HNC [17,27,[29][30][31][32][33]35,45]. However, another study found that tumor size, location, histologic grade, and DOI were not risk factors for the ECS of LNM in oral cavity cancer [40].…”

Section: Discussionmentioning

confidence: 99%

Extra-Capsular Spread of Lymph Node Metastasis in Oral, Oropharyngeal and Hypopharyngeal Cancer: A Comparative Subsite Analysis

Kang,

Park,

Park

et al. 2024

Cancers

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Background: The extra-capsular spread (ECS) of lymph node metastasis (LNM) is a hallmark of aggressive primary tumor phenotype in head and neck cancer (HNC); however, the factors influencing ECS are poorly understood. Patients and Methods: This was a retrospective study, including 190 cases of oral tongue cancer (OTC), 148 cases of oropharyngeal cancer (OPC) (118 HPV-positive and 30 HPV-negative), and 100 cases of hypopharyngeal cancer (HPC). Tumor dimension, tumor biological variables (lymphovascular/perineural invasion and histologic grade), and LNM variables (LNM number and size) were analyzed according to the presence of ECS using multivariable logistic regression and receiver operating characteristic (ROC) curve analyses. Results: LNM variables were significant factors for ECS in all subsites of HNC (p < 0.05), except HPV-positive OPC. In OTC, tumor dimensional variables were significantly related to ECS (p < 0.01). Meanwhile, in OPC and HPC, neither the primary tumor dimension nor the T status were significant factors for ECS occurrence. The predictability of ECS by ROC curve using multiple variables was 0.819 [95% confidence interval: 0.759–0.878] in OTC, 0.687 [0.559–0.815] in HPV-positive OPC, 0.823 [0.642–1.000] in HPV-negative OPC, and 0.907 [0.841–0.973] in HPC. Conclusion: LNM variables were correlated with ECS occurrence for most HNC subsites, and site-dependent primary tumor characteristics might contribute differentially to the ECS development of LNM in HNC.

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Prognostic significance of extranodal extension in oral cavity squamous cell carcinoma with occult neck metastases

Cited by 22 publications

References 26 publications

The Impact of Histopathological Features on the Prognosis of Oral Squamous Cell Carcinoma: A Comprehensive Review and Meta-Analysis

The Impact of Histopathological Features on the Prognosis of Oral Squamous Cell Carcinoma: A Comprehensive Review and Meta-Analysis

Assessment Criteria and Clinical Implications of Extranodal Extension in Head and Neck Cancer

Extra-Capsular Spread of Lymph Node Metastasis in Oral, Oropharyngeal and Hypopharyngeal Cancer: A Comparative Subsite Analysis

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