Blood Markers Predicting Clinically Occult Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma.

INTRODUCTION: The presence of cervical lymph node metastases is an unfavorable prognostic factor in head and neck squamous cell carcinoma (HNSCC) and a potential cause of treatment failure. Occult lymph node metastasis occurs in approximately 15-20% of HNSCC patients with a clinically negative neck (cN0), greatly impacting on their prognosis. The present study aimed to investigate the role of pre-treatment peripheral blood markers in predicting clinically occult cervical lymph node metastasis. METHODS: This multicenter, retrospective study was performed in a cohort of 472 patients diagnosed with cN0 HNSCC who underwent up-front surgery. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated from available blood parameters. RESULTS: Oro-hypopharyngeal and oral cancers, locally advanced stage, moderately (G2), and poorly (G3) differentiated grade were associated with an increased risk of pathological lymph node involvement. NLR, LMR, PLR, SIM, and SII were significantly associated at multivariable analysis. NLR >2.12 was the most reliable at predicting occult lymph node metastasis (OR = 5.22; 95% CI: 2.14-12.75). We describe a predictive score integrating cancer site, local stage, and NLR which is effective at predicting positive lymph node pathological status. CONCLUSIONS: The present study provides evidence that pre-treatment peripheral blood markers, in particular NLR, represent reliable predictors of clinically occult cervical lymph node metastasis in cN0 HNSCC. Therefore, the present study provides a novel useful predictive score for directing the elective management of the neck in patients with cN0 HNSCC.

Malignant sublingual gland tumors: A single-center retrospective analysis of 79 patients.

OBJECTIVES: To analyze and summarize the clinicopathological features, risk factors for cervical nodal metastasis, and prognostic factors of malignant sublingual gland tumors (MSLGT). METHODS: Patients diagnosed with MSLGT were retrospectively reviewed from January 2005 to December 2017 at Shanghai Ninth Hospital. The clinicopathological features were summarized, and the correlations between clinicopathological parameters, cervical nodal metastasis, and local-regional recurrence were evaluated using the Chi-square test. Kaplan-Meier method and Cox regression analysis were performed to assess the survival and independent prognostic factors. RESULTS: Seventy-nine patients were included, and the 5-year overall survival and disease-free survival rates was 85.7% and 71.7%, respectively. Gender and clinical tumor stage were risk factors for cervical nodal metastasis. Tumor size and pathological lymph node (LN) stage were independent prognostic factors for adenoid cystic carcinoma (ACC) of the sublingual gland; while age, pathological LN stage, and distant metastasis were prognostic factors for patients with non-ACC of the sublingual gland. Patients with higher clinical stage were more likely to undergo tumor recurrence. CONCLUSIONS: Malignant sublingual gland tumors are rare, and neck dissection should be performed in male MSLGT patients with higher clinical stage. Among patients with both ACC and non-ACC MSLGT patients, pN+ indicate a poor prognosis.

Utility of UV Signature Mutations in the Diagnostic Assessment of Metastatic Head and Neck Carcinomas of Unknown Primary.

BACKGROUND: Metastatic carcinoma of unknown primary origin to the head and neck lymph nodes (HNCUP) engenders unique diagnostic considerations. In many cases, the detection of a high-risk human papillomavirus (HR-HPV) unearths an occult oropharyngeal squamous cell carcinoma (SCC). In metastatic HR-HPV-independent carcinomas, other primary sites should be considered, including cutaneous malignancies that can mimic HR-HPV-associated SCC. In this context, ultraviolet (UV) signature mutations, defined as ≥ 60% C→T substitutions with ≥ 5% CC→TT substitutions at dipyrimidine sites, identified in tumors arising on sun exposed areas, are an attractive and underused tool in the setting of metastatic HNCUP. METHODS: A retrospective review of institutional records focused on cases of HR-HPV negative HNCUP was conducted. All cases were subjected to next generation sequencing analysis to assess UV signature mutations. RESULTS: We identified 14 HR-HPV negative metastatic HNCUP to either the cervical or parotid gland lymph nodes, of which, 11 (11/14, 79%) had UV signature mutations, including 4 (4/10, 40%) p16 positive cases. All UV signature mutation positive cases had at least one significant TP53 mutation and greater than 20 unique gene mutations. CONCLUSION: The management of metastatic cutaneous carcinomas significantly differs from other HNCUP especially metastatic HR-HPV-associated SCC; therefore, the observation of a high percentage of C→T with CC →TT substitutions should be routinely incorporated in next generation sequencing reports of HNCUP. UV mutational signatures testing is a robust diagnostic tool that can be utilized in daily clinical practice.

Value of diffusion MRI versus [18F]FDG PET/CT in detection of cervical nodal metastases in differentiated thyroid cancer patients.

BACKGROUND: In differentiated thyroid cancer (DTC) patients, cervical nodal metastasis is a negative prognostic factor. Preoperative imaging plays an important role in treatment planning for nodal metastasis and recurrence. The aim of the study is to compare the diagnostic performance of the diffusion-weighted magnetic resonance imaging (DW-MRI) and the F-18 flurodeoxyglucose positron emission computed tomography ([18F]FDG PET/CT) in detection of cervical nodal deposits in DTC patients. MATERAL AND METHODS: The study was conducted on 30 patients, each performed both modalities just before the surgery. The gold standard was the pathological specimens with post-operative clinico-radiological follow-up, to assess the diagnostic performance of each modality. RESULTS: Based on pathological and post-operative clinico-radiological follow up data. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy were 84%, 80%, 50%, 95% and 83% for PET/CT compared to 84%, 60%, 42.8%, 91.3% and 80% for DW-MRI. On comparing the diagnostic performance of combined DW-MRI and PET/CT to each modality alone, the sensitivity and NPV were improved to 96% and 80% respectively. CONCLUSIONS: [18F]FDG PET/CT study is a valuable diagnostic modality for the assessment of cervical nodal deposits in DTC patients, surpassing DW-MRI. Combined PET/CT and DW-MRI techniques seemed to have synergistic performance, mainly in terms of sensitivity and NPV, for detection of nodal metastases.

The Interrelation Among Triad of Depth of Invasion, Perineural Invasion and Tumor Size in Squamous Cell Carcinoma of Tongue and Floor of the Mouth: An Analytical Appraisal.

Background: Head and neck cancer represents 5-10% of all malignancies. Squamous cell carcinoma (SCC) of the oral cavity represents about 2% of overall malignant neoplasms and 47% of the head and neck region. Squamous cell carcinoma of tongue has a peculiar behavior of occult and skips metastasis to regional lymph nodes. It occasionally occurs along with floor of the mouth. The purpose of this study is to evaluate the significance of correlation between, depth of invasion of the primary tumor, its proximity with the neurovascular bundle and subsequent perineural invasion and cervical lymph node metastasis in squamous cell carcinoma tongue and floor of the mouth and the sites involving both. Materials and Methods: A total of 108 patients with carcinoma tongue (59), floor of the mouth (20) and involving both together (29) who underwent treatment during January 2015 to June 2017 that were followed up until December 2019 were assessed. Out of 108 patients that were included in the study, 71 patients underwent primary surgery and 37 patients were inoperable (tongue-17, floor of the mouth-9 and involving both together-11). Results: Perineural invasion was seen in 15 cases of pT1-2 where depth of invasion was less than 1 cm and in 28 cases of pT3-4 where depth of invasion was more than 1cm (p-0.075). Skip metastasis was accounted for 61.9% overall. Conclusion: The triad of perineural invasion, depth of invasion and tumor size is interrelated and was responsible for cervical lymph node metastasis and prognosis of the disease. Obtaining clear deep margins of the tumor from the mucosal margin and removal of lympho-fatty tissue at the floor of the mouth is an important aspect which gives the indication about prognostic factors like depth of invasion, tumor size, cervical nodal metastasis and recurrence of the disease. High-grade tumors (T3-4), depth of invasion of tumor at 1 cm or > 1 cm, increase the propensity of perineural invasion highly.

Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: The Neck and Lymph Nodes, Metastasis, and Melanocytic Tumors.

The changes made in the fifth edition of the WHO Classification of Head and Neck Tumors demonstrate the recent diagnostic, histopathological, and molecular advances in the field, and this updated information will hopefully lead to improved and standardized tumor subtyping. This review summarizes the changes related tumors and tumor-like lesions of the neck and lymph nodes (Chapter 11), metastasis to the head and neck region (Chapter 15), and melanocytic tumors (Chapter 10).

Patterns and prognostic value of lymph node metastasis of nasopharyngeal carcinoma based on 2013 updated consensus guidelines of neck node levels / 中国癌症杂志

Background and purpose:In 2013, the ofifcial journal of European Society of Radiotherapy &Oncology (ESTRO) -Radiotherapy & Oncology published the updated version of Consensus Guidelines of Delineation of the neck node levels for head and neck tumors, which contributed to the standardization of description of neck nodal metastasis, as well as reduction of treatment variations from various institutions. This study applied this updated guidelines to analyze the patterns of lymph node metastasis of nasopharyngeal carcinoma and explore the prognostic value of the radiologic characteristics of nodes, in order to provide evidence for future revision of N staging system. Methods:A total of 656 patients from Jan. 2009 to Dec. 2010 were retrospectively recruited to analysis. All were pathologically diagnosed as non-metastatic nasopharyngeal carcinoma, treated with intensity-modulated radiotherapy. All patients received a pretreatment MRI scan. We retrospectively reviewed the MRI imaging of 656 patients and mapped the lymph node metastasis using the 2013 International Consensus Guidelines.Results:Median follow-up was 46.9 months. Four-year local recurrence-free survival, nodal recurrence-free survival, distant metastasis-free survival, disease-free survival and overall survival was 91.3%, 95.1%, 87.7%, 78.5% and 92.8%, respectively. The most common metastatic node levels were levelⅡ (76.2%) and levelⅦa (65.1%), followed by levelⅢ (50.4%),Ⅴa(17.5%) andⅣa (11.7%). There was a very low incidence of node skipping (1.0%). Cervical nodal necrosis was observed in 46.4%of patients with positive nodes and extracapsular spread was noted in 74.4% of them. Univariate analysis showed that bilateral nodal involvement, greatest dimension of positive nodes (≥6 cm), central nodal necrosis, T stage and N stage were prognostic factors for disease-free survival and distant metastasis-free survival (P<0.05). Extracapsular spread showed a trend to correlate with poor distant metastasis-free survival (P=0.060). The involvement of lower neck levels (below the caudal border of cricoid cartilage) did not have a signiifcant impact on disease-free survival and distant metastasis-free survival. In multivariate analysis, T stage and greatest dimension of nodes (≥6 cm) were independent prognostic factors for distant metastasis-free survival (P<0.05). T stage, greatest dimension of nodes (≥6 cm) and central nodal necrosis were independent prognostic factors of disease-free survival (P<0.05).Conclusion:This study demonstrates the patterns of lymph node metastasis of nasopharyngeal carcinoma based on 2013 International Consensus Guidelines. Bilateral nodal involvement, greatest dimension of positive nodes and central nodal necrosis had prognostic values on disease-free survival and distant metastasis-free survival. In our study, the involvement of lower neck levels was not proved to be a prognostic factor for disease-free survival and distant metastasis-free survival.