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Purpose: We evaluated the current performance of diagnostic ultrasound (US) for detecting cervical lymph node (LN) metastases based on objective measures and subjective findings in comparison to the gold standard, histopathological evaluation., Patients and Methods: From 2007 to 2016, we prospectively included patients with head and neck cancer who were scheduled for surgical therapy including neck dissection. LNs were examined by multimodal US by a level III head and neck sonologist and individually assigned to a map containing six AAO-HNS neck LN levels preoperatively. During the operation, LNs were dissected and then assessed by routine histopathology, with 86% of them examined individually and the remaining LNs (14%) per AAO-HNS neck LN level. The optimal cutoff points (OCPs) of four defined LN diameters and 2D and 3D roundness indices per AAO-HNS neck LN level were determined., Results: In total, 235 patients were included, and 4539 LNs were analyzed by US, 7237 by histopathology and 2684 by both methods. Of these, 259 (9.65%) were classified as suspicious for metastasis by US, whereas 299 (11.14%) were found to be positive by histopathology. Subjective US sensitivity and specificity were 0.79 and 0.99, respectively. The OCPs of the individual LN diameters and the 2D and 3D roundness index were determined individually for all AAO-HNS neck LN levels. Across all levels, the OCP for the 2D index was 1.79 and the 3D index was 14.97. The predictive performance of all distances, indices, and subjective findings improved with increasing metastasis size. Anticipation of pN stage was best achieved with subjective US findings and the smallest diameter (Cohen's κ = 0.713 and 0.438, respectively)., Conclusion: Our LN mapping and meticulous 1:1 node-by-node comparison reveals the usefulness of US for detecting metastatic involvement of neck LNs in head and neck carcinomas as compared to histopathology. The predictive ability for small tumor deposits less than 8 mm in size remains weak and urgently needs improvement., (© 2023. The Author(s).)

Considering the limited information on the biology and molecular characteristics of disseminated tumor cells (DTCs) in head and neck squamous cell carcinoma (HNSCC), we examined the genomic alterations in DTCs from HNSCCs and their potential clinical relevance. To analyze both the lymphatic and hematogenous routes of tumor cell dissemination, we investigated samples from lymph nodes (LNs) and bone marrow (BM) of 49 patients using immunofluorescence double staining for epithelial cells expressing cytokeratin 18 (KRT18) and/or epithelial cell adhesion molecules (EpCAM, CD326). The identified marker-positive cells were isolated by micromanipulation followed by single-cell whole-genome amplification and metaphase-based comparative genomic hybridization (mCGH) to determine genome-wide copy number alterations. The findings were correlated with clinical parameters and follow-up data. We detected chromosomal aberrations in KRT18- and EpCAM-positive cells from both compartments; BM-derived cells showed a significantly higher percentage of aberrant genome (PAG) per cell than cells detected in LNs. No significant association was found between DTC data and clinical follow-up. Genomic profiling of BM-DTCs revealed genomic alterations typical for HNSCC, suggesting hematogenous dissemination of subclones around the time of surgery. In contrast, DTC data in LNs revealed that several marker-positive cells were not of malignant origin, indicating the presence of epithelial glandular inclusions in parts of the processed neck LN samples. Therefore, DTC detection of LNs in the neck based only on epithelial markers is not advisable and requires detection of chromosomal instability (CIN), gene mutations, or additional markers, which have yet to be identified. Nevertheless, our investigation paves the way for larger studies to focus on HNSCC BM-DTCs with high-resolution methods to gain deeper insights into the biology of hematogenous metastasis in this cancer., (© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Introduction: Proper management of the clinically involved neck in OSCC patients continues to be a matter of debate. Our aim was to analyze the accuracy of computerized tomography (CT) and ultrasound (US) in anticipating the exact location of lymph node (LN) metastases of OSCC patients across the AAO-HNS (American Academy of Otolaryngology-Head and Neck Surgery) levels ipsi- and contralaterally. Furthermore, we wanted to assess the suitability of therapeutic selective neck dissection (SND) in patients with one or two ipsilateral positive nodes upon clinical staging (cN1/cN2a and cN2b(2/x) patients)., Methods: We prospectively analyzed the LN status of patients with primary OSCC using CT and US from 2007 to 2013. LNs were individually assigned to a map containing the AAO-HNS levels; patients bearing a single or just two ipsilateral positive nodes (designated cN1/cN2a or cN2b(2/x) patients either by CT (CT group) or US alone (US group) or in a group combining findings of CT and US (CTUS group)) received an ipsi-ND (I-V) and a contra-ND (I-IV). 78% of the LNs were sent individually for routine histopathological examination; the remaining were dissected and analyzed per neck level., Results: Upon the analysis of 1.670 LNs of 57 patients, the exact location of pathology proven LN metastases in cN1 patients was more precisely predicted by US compared to CT with confirmed findings only in levels IA, IB und IIA. Clearly decreasing the number of missed lesions, the findings in the CTUS group nearly kept the spatial reliability of the US group. The same analysis for patients with exactly two supposed ipsilateral lesions (cN2b(2/x)) yielded confirmed metastases from levels I to V for both methods individually and in combination and, therefore, render SND insufficient for these cases., Conclusion: Our findings stress the importance of conducting both, CT and US, in patients with primary OSCC. Only the combination of their findings warrants the application of therapeutic SND in patients with a single ipsilateral LN metastasis (cN1/cN2a patients) but not in patients with more than one lesion upon clinical staging (≥ cN2b).