Genetic analysis of single disseminated tumor cells in the lymph nodes and bone marrow of patients with head and neck squamous cell carcinoma.

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.

Is the prediction of one or two ipsilateral positive lymph nodes by computerized tomography and ultrasound reliable enough to restrict therapeutic neck dissection in oral squamous cell carcinoma (OSCC) patients?

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).

Mandible handling in the surgical treatment of oral squamous cell carcinoma: lessons from clinical results after marginal and segmental mandibulectomy.

OBJECTIVE: The aim of this retrospective, single-center study was to analyze long-term results after marginal and segmental mandibulectomies in patients with oral squamous cell carcinoma (OSCC). STUDY DESIGN: The study included 259 patients treated for OSCC with mandibulectomy between 1996 and 2010. Data acquisition consisted of analysis of operation reports, re-evaluation of histologic bone specimens, and collection of clinical follow-up data. RESULTS: Of the included patients, 86.5% had received segmental and 13.5% marginal mandibulectomies. Patients who received segmental mandibulectomy generally displayed a higher TNM (tumor-node-metastasis) stage; 47% of patients who received segmental mandibulectomy and 14% of those receiving marginal mandibulectomy showed bone infiltration (pT4 a). Of all patients with bone infiltration, 49% showed an invasive histologic infiltration pattern, and 35% showed an erosive histologic infiltration pattern. We found healthy residual crestal bone height in 43% of all segmental mandibulectomies. Only 8% of all patients were prosthodontically rehabilitated. With regard to prognostic parameters, there was no significant difference between patients receiving marginal mandibulectomy and those receiving segmental mandibulectomy. CONCLUSIONS: Because healthy residual crestal bone height was found in 43% of all patients who had received segmental mandibulectomies, it is conceivable that a significant number of patients would profit from marginal mandibulectomy, at least in cases of absent or erosive bone infiltration pattern, because the residual crestal bone is functionally stable.