The accuracy of clinical neck staging for p16-positive and negative oropharyngeal cancer and its therapeutic implications.

PURPOSE: Oropharyngeal squamous cell carcinoma (OPSCC) may be treated with primary surgery or primary (chemo)radiation. While surgery with concurrent neck dissection provides definitive pathological staging of the neck, non-surgical treatment relies on clinical staging for treatment planning. To assess the accuracy of clinical neck staging, we compared clinical to surgical staging after primary surgery in patients with p16-negative and p16-positive OPSCC. METHODS: Retrospective analysis of clinical, pathological, and oncologic outcome data of patients with OPSCC treated with primary surgery and bilateral neck dissection. Clinical and pathological nodal status were compared for p16-negative and p16-positive patients. Patients with occult metastatic disease were analyzed in detail. RESULTS: 95 patients were included. 60.5% of p16-negative patients and 66.6% of p16-positive patients had pathologically confirmed metastatic neck disease. p16-positive patients had improved 24-month recurrence-free survival compared to p16-negative patients at 93.3% vs. 69.6%. Pathological N-status differed from clinical N-status in 36.8% of p16-negative patients vs. 31.6% of p16-positive patients. Occult metastatic disease was more common in p16-negative patients at 18.4% vs. 8.8% for p16-positive patients. Clinical detection sensitivity for extranodal extension was low overall; sensitivity was 27.3% and specificity was 91.6% for p16-negative patients vs. 61.5% and 80.0% for p16-positive patients, respectively. CONCLUSION: Our data show a considerable degree of inaccuracy of clinical neck staging results in all OPSCC patients which needs to be taken into consideration during therapy planning. For p16-positive patients, these findings warrant attention in the context of therapy deintensification to avoid undertreatment.

Peri-Implant Metastasis as First Manifestation of an Unknown Lung Cancer: Literature Review and Two New Cases.

Metastases around dental implants are extremely rare. They usually represent a secondary localization of a multiorgan metastatic neoplasm but also are, exceptionally, recognized as the first clinical manifestation of a still unknown cancer of whatever organ. Metastases usually manifest as rapidly growing lesions of hard and soft tissues and always represent a true diagnostic/therapeutic dilemma both for clinicians in choosing the more appropriate treatment and for pathologists in recognizing the primary tumor when still undiagnosed. We report 2 distinct cases of metastasis occurring around dental implants in the maxilla and mimicking peri-implantitis at the onset; more precisely, in one case, the lesion involved exclusively the alveolar bone, where an implant were previously inserted, while in the other case, a neoplasm caused bone destruction around the fixture with an impressive and rapid exophytic growth. In both cases, maxillary lesions were the first metastatic manifestation of an unknown adenocarcinoma of the lung.

Osteopontin Levels in Patients with Squamous Metastatic Head and Neck Cancer.

Background and Objectives: Increased osteopontin (OPN) concentrations in the plasma of patients with head and neck squamous cancer (HNSCC) have diagnostic significance, and it can indicate more aggressive biological behavior of cancer. The aim of this study was to determine OPN levels in patients with HNSCC of different primary locations and to assess its prognostic significance in metastasis development. Materials and Methods: This cohort study included 45 patients (41 male and 4 female patients) with HNSCC with different primary localization of head and neck. All patients underwent surgery-neck dissection. All patients were categorized according to the histological findings of the resected material and tumor-node-metastasis (TNM) classification system. After surgery, N categories were determined on the basis of histological features of resected material. Results: The histological findings of our patients showed: N0 in 11 patients, N1 in 8 patients, N2a in 4 patients, N2b in 14 patients and N2c in 8 patients. Plasma OPN values in all study participants ranged from 2.24 to 109.10 ng/mL. OPN levels in plasma of patients with negative nodes compared to the group of patients with positive nodes in the neck differed significantly (16.89 ng/mL to 34.08 ng/mL, respectively; p = 0.03). There were significantly lower OPN plasma levels in the group of subjects with histologically positive one lymph node in the neck (N1) compared to the group of patients with N2b histologically positive findings of resected neck material (10.4 ng/mL to 43.9 ng/mL, respectively; p = 0.02). Conclusions: The results have shown that growing N degrees of positive neck nodes classification were accompanied by growing values of plasma osteopontin. Osteopontin might be important for the development of neck metastases.

Skip Metastases in Papillary Thyroid Carcinoma - Prevalence, Predictive and Clinicopathological Factors.

BACKGROUND: Cervical lymph node metastases are frequently found in papillary thyroid carcinoma (PTC) and occur in a stepwise fashion. Skip metastases that omit the central compartment and spread initially in lateral neck levels are present in a certain share of patients, and their significance is poorly understood. The aim of this prospective study was to identify their possible predictors and clinicopathological factors in a group of patients with PTC with lateral lymph node (LLN) metastases. METHODS: We enrolled 68 patients with PTC with preoperatively evaluated LLN metastases who underwent total thyroidectomy with lateral lymph node dissection between 2011 and 2018. We analysed the clinicopathological features and pattern of dissemination of continuous and skip metastases. RESULTS: The prevalence of skip metastases was 23.5%. Compared with the continuous metastases group, the patients were older, had primary tumors that were more often situated unilaterally, and had smaller primary tumor size. Level II was less often involved, and none of the patients with skip metastases had all LNN positive (p = 0.05). CONCLUSION: Skip metastases occur more frequently in older patients and display certain clinicopathological features like smaller size of the primary tumor and dissemination in less lateral neck levels. In the view of the fact that they are found rather frequently, lateral neck regions should be meticulously investigated in patients with PTC without central lymph node (CLL) metastases.

Current management of the neck in salivary gland carcinomas.

Salivary gland cancers include a diverse group of tumours with many histological subtypes which occur in both major and minor salivary glands. As a result of this heterogeneity and different sites of presentation, there have been no randomised controlled trials to evaluate the indications and efficacy of neck treatments by either surgery or radiotherapy for occult or apparent neck node metastases. Neck dissection is an important treatment strategy for neck metastases arising from major and minor salivary gland malignancy as well as being useful for disease staging. However, there is considerable controversy in how to manage the neck in these patients. In this review, we discuss the management of neck metastases relating to malignant salivary gland tumours.

Frequency of bilateral cervical metastases in hypopharyngeal squamous cell carcinoma: a retrospective analysis of 203 cases after bilateral neck dissection.

The decision whether to perform an elective neck dissection in patients with head and neck squamous cell carcinoma and clinically negative lymph nodes (cN0) is made based on the probability of micrometastases in the neck for the given subsite and size of the primary. A retrospective chart review was performed of 203 patients with hypopharyngeal SCC who received a bilateral neck dissection. The frequency of histologically unveiled bilateral neck metastases was determined. A high frequency of contralateral metastases above 20% was detected for all carcinomas affecting the midline and those involving the medial wall of the pyriform sinus except of T1-stages (13%) and a low frequency for laterally located primaries (3%). Ipsilateral nodal status predicted contralateral neck metastases. Bilateral neck dissection should be recommended for primaries affecting the midline and T2-4 tumors involving the medial wall of the pyriform sinus.

Intensity modulated perioperative HDR brachytherapy for recurrent and/or advanced head and neck metastases.

Recurrent neck metastases following surgery and full dose adjuvant radiotherapy of squamous cell head and neck cancer remain a clinical challenge. After revision neck dissection and chemotherapy re-irradiation dosage is often limited and survival prognosis deteriorates. Here, adjuvant high-dose rate intensity modulated perioperative brachytherapy (HDR IMBT) offers a second full radiation dose with a limited volume of normal tissue radiation in the neck. In this retrospective study patients were identified who underwent revision surgery and perioperative HDR IMBT for recurrent neck metastases. Survival rates were estimated and the scarce literature on interstitial brachytherapy of the neck was reviewed. From 2006 to 2014, nine patients were treated for recurrent or palliative neck metastases using salvage surgery and HDR IMBT. Eight patients received previous surgery and external beam radiotherapy with or without chemotherapy. Two and five year overall survival was calculated to be 78 and 67 %, respectively. HDR IMBT is a salvage treatment option for selected cases in the neck following surgical revision or last-line treatment strategies. In the literature and this small cohort radiation toxicity and the risk of "carotid blow-out" seemed to be low.

Does Age Affect the Rate of Spinal Nerve Injury after Selective Neck Dissection? Age as a Prognostic Factor of Spinal Nerve Injury after Selective Neck Dissection.

OBJECTIVE: The objective of this study is to investigate whether age is a significant risk factor for spinal nerve injury following selective neck dissection (SND) in patients with head and neck cancer. METHODS: A retrospective cohort study was conducted on patients who had undergone SND for head and neck cancer at a tertiary hospital between 2020 and 2022. The primary outcome was the incidence of spinal nerve injury after SND. The secondary outcomes included the types and severity of spinal nerve injury and the impact of age on these outcomes. RESULTS: A total of 78 patients were included in the study and subdivided into two groups. Two shoulder-specific questionnaires (the Shoulder Pain and Disability Index (SPADI) and the Shoulder Disability Questionnaire (SDQ)) were administered to assess shoulder morbidity postoperatively. Twelve patients showed shoulder impairment following surgery. We divided the sample into two age-based groups; the older group showed a higher rate of SAN injury and the younger group showed a lower rate of improvement over time. CONCLUSION: This study suggests that age is a significant risk factor for spinal nerve injury following SND in patients with head and neck cancer. Older patients are more likely to experience spinal nerve injury after SND than younger patients. The findings of this study may help in the development of strategies to prevent spinal nerve injury in older patients undergoing SND for head and neck cancer.

Lymph Node Metastases from Non-Melanoma Skin Cancer of the Head and Neck.

Non-melanoma skin cancer (NMSC) represents the most common malignancy in the world, comprising exceedingly common lesions such as basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) and rare lesions such as Merkel cell carcinoma. Risk factors are widely recognized and include ultraviolet (UV) light exposure, radiation exposure, immunosuppression, and many others. As a whole, survival and functional outcomes are favorable, but each histopathological subtype of NMSC behaves differently. Treatment regimens for the primary site usually include wide surgical excision and neck dissection in cases of clinically involved metastatic lymph nodes. The elective management of draining nodal basins, however, is a contested topic. Nearly all subtypes, excluding BCC, have a significant risk of lymphatic metastases, and have been studied with regard to sentinel lymph node biopsy (SLNB) and elective neck dissection. To date, no studies have definitively established a true single standard of care, as exists for melanoma, for any of the NMSCs. As a result, the authors have sought to summarize the current literature and identify indications and management options for the management of the cervical lymphatics for each major subtype of NMSC. Further research remains critically necessary in order to develop complete treatment algorithms.

Efficacy of long-term ultrasonography in follow-up of patients with papillary thyroid carcinoma: a case of neck metastasis developed 19 years following primary treatment.

The cases of relapse in papillary thyroid cancer patients who were initially considered low-risk and for many years were without signs of the disease are extremely rare, but exist. This is supported by the clinical case of a patient who underwent a total thyroidectomy due to papillary thyroid cancer and 19 years later metastasis with extracapsular spreading in a presumed thyroid place was revealed. Due to such cases, the importance of long-term ultrasound monitoring is emphasized.

Advanced Nasopharyngeal Carcinoma with Generalized Lymphadenopathy Masquerade as Lymphoma.

Introduction: Nasopharyngeal carcinoma (NPC) is a nasopharyngeal epithelial neoplasm that has distinct aetiological, epidemiological and biological characteristics compared to other head and neck malignancies. Patients usually present late due to non-specific symptoms and deep location of the tumour in the nasopharynx. Case Report: We would like to highlight a case of advanced NPC presenting with generalised lymphadenopathy, without the presence of an obvious nasopharyngeal mass that masqueraded as lymphoma in the initial stage. Conclusions: NPC may share clinical features with other sinonasal pathologies or other malignant lymphoproliferative disorders that lead to a delay in diagnosis. NPC should be one of the differential diagnoses for any cases presenting with cervical lymphadenopathy, especially in adult male patients originating from East or Southeast Asia. Early diagnosis and treatment are crucial because early-stage NPC has an excellent chemoradiotherapy response and high survival rate.

Multiparametric Ultrasound of Cervical Lymph Node Metastases in Head and Neck Cancer for Planning Non-Surgical Therapy.

BACKGROUND: We aimed to evaluate multiparametric ultrasound, to achieve a better understanding of the baseline characteristics of suspected cervical lymph node metastases in head and neck cancer before induction chemotherapy or chemoradiation. METHODS: From February 2020 to April 2021, our complete ultrasound examination protocol was carried out on clinically evident malignant lymph nodes of histologically proven HNSCC in the pre-therapeutic setting. RESULTS: A total of 13 patients were eligible for analysis. Using elastography, irregular clear hardening in areas in the center of the lymph node could be detected in all cases. Elastographic Q-analysis showed a significantly softer cortex compared to the center and surrounding tissue. The time-intensity curve analysis showed high values for the area under the curve and a short time-to-peak (fast wash-in) in all cases compared to the surrounding tissue. A parametric evaluation of contrast enhanced the ultrasound in the early arterial phase and showed an irregular enhancement from the margin in almost all investigated lymph nodes. These results show that the implementation of comprehensive, multiparametric ultrasound is suitable for classifying suspected lymph node metastasis more precisely than conventional ultrasound alone in the pre-therapeutic setting of HNSCC. Thus, these parameters may be used for improvements in the re-staging after chemoradiation or neoadjuvant therapy monitoring, respectively.

Pre-Treatment Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Predictors of Occult Cervical Metastasis in Clinically Negative Neck Supraglottic and Glottic Cancer.

Background. Among patients with diagnosis of Laryngeal Squamous Cell Carcinoma (LSCC), up to 37.5% of cases may have occult metastasis (OM), and this feature is linked to poor prognosis and high rate of local recurrence. The role of elective neck dissection (END) in clinically negative neck (cN0) LSCC remains controversial. It is of great value to search for low-cost and easily detectable indicators to predict the risk of OM in laryngeal cancer. Recent reports have shown that high values of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) represent a negative prognostic factor in head and neck cancers. The aim of our study has been to investigate the value of pre-treatment NLR and PLR with regard to predicting occult cervical metastasis in cN0 supraglottic and glottic LSCC. Materials and methods. Data of patients affected by LSCC, who had been surgically treated by means of laryngectomy (total, horizontal partial and supracricoid) and END between January 2006 and January 2021, were retrospectively reviewed, using information retrieved from a database dedicated to such procedures in a single tertiary care referral institute. Results. A total of 387 patients were treated for LSCC at our Institute from 2006 to 2021, but only 108 of them met the inclusion criteria. The median age at the time of diagnosis was 64 years (range, 39-89 years). All the tumors were treated with a laryngectomy and an END. A total of 27.7% of patients were found positive for neck node metastasis (the pN+ group), while 78/108 (72.3%) patients were found to be negative for the presence of neck metastasis (the pN0 group). High values of NLR, but not PLR, significantly correlated with the probability of OM, and according to the iterative algorithm of Newton-Raphson, an NLR value of 2.26 corresponds to a probability of OM of 20%. Conclusion. Our analysis revealed a statistical correlation between high NLR pre-treatment values and positive neck OM in patients with LSCC.

Prognostic value of elective neck dissection in adenoid cystic carcinoma of head and neck: a meta-analysis: A call for randomized trials and international consensus.

Adenoid cystic carcinoma of head and neck (AdCCHN) is an uncommon salivary gland cancer characterized for infrequent neck metastases, and high rate of local and distant recurrence. The aim of this meta-analysis was to analyse the significance of elective neck dissection (END) in terms of overall survival (OS) in patients with AdCCHN. A systematic literature search and meta-analysis was performed. Endpoint assessed by this meta-analysis included 5-year OS (death from any cause). Statistical heterogeneity was assessed using the Cochrane Q test and I2 statistic. A pooled odds ratio (OR) was reported with 95% confidence interval (CI). There were 1934 patients in the END arm and 3083 in the observation group. The pooled OR, calculated for END vs. observation, was 0.94. Patients receiving END had similar risk for death compared to observation cohort (P=0.76). No significant difference in final outcome after patient stratification based on T stage was identified (OR for T1/T2 1.27, P=0.39; OR for T3/T4 0.95, P=0.90). Observation for cN0 neck is a reasonable option in AdCCHN. These findings suggest the need for prospective trials on indications and extent of END in AdCCHN.

Distribution of Neck Metastases and Survival in Patients with Breast Carcinoma.

PURPOSE: Neck metastases in breast carcinoma are relatively rare and patients show poor survival rates. A controversy exists over whether neck metastases can be treated as distant or loco-regional metastases. The literature concerning the distribution of metastases in the neck is lacking, as well as data about whether metastases in the higher neck regions cause poorer survival than those in the supraclavicular fossa. METHODS: Ultrasound investigation with fine-needle biopsy was performed on 41 breast cancer and confirmed neck metastases patients in a 6-year period. We analysed the distribution of neck metastases and patient survival rates using Kaplan-Meier survival curves and Cox regression. RESULTS: The median survival time from the diagnosis of primary disease to that of neck metastases was 21 months. The presence of metastases in sites other than the neck significantly worsened survival, but multiple metastatic sites did not make it significantly worse. The number of nodes and presence of conglomerates did not considerably affect survival. CONCLUSION: Neck metastases in breast carcinoma can be found not only in the supraclavicular fossa, but elsewhere in the neck as well. Survival of patients with metastases in higher neck regions was shorter, but not very much so. Survival of patients with metastases limited just to the neck was substantially better, therefore early detection and aggressive treatment that could include neck dissection should be considered.

Prognostic significance of bone morphogenetic protein 6 (BMP6) expression, clinical and pathological factors in clinically node-negative oral squamous cell carcinoma (OSCC).

Bone morphogenetic protein 6 (BMP6) has unique properties regarding structure and function in supporting bone formation during development and adult life. Despite its known role in various malignant tumors, the prognostic significance of BMP6 expression in oral squamous cell carcinoma (OSCC) remains unknown. The aim of the study was to investigate immunohistochemical expression of BMP6 in OSCC in correlation with clinical and pathological parameters, disease recurrence and survival. In addition, we investigated other parameters in order to identify prognosticators of neck metastases and final outcome. The study included 120 patients with clinically T1-3N0 OSCC who were primarily surgically treated between 2003 and 2008. There were 99 (82.5%) male and 21 (17.5%) female patients. The five-year disease-specific survival for the whole cohort was 79.7%. Tumors smaller than 2 cm in diameter showed higher incidence of strong BMP6 expression. No statistical correlation was observed between other clinico-pathological factors and BMP6 expression. Expression of BMP6 was not associated with disease recurrence and survival. BMP6 may not serve as prognosticator of final outcome or recurrence in clinically node-negative OSCC subjects. In multivariate analysis predictors of poorer survival were positive surgical margin, moderate tumor cell differentiation and pathological involvement of levels IV and/or V.

Significance and management of incidentally diagnosed metastatic papillary thyroid carcinoma in cervical lymph nodes in neck dissection specimens.

BACKGROUND: The management of patients with incidentally discovered metastatic thyroid cancer in cervical lymph nodes in neck dissection specimens for other pathologies is unclear. METHODS: Retrospective review of neck dissection specimens for nonthyroid malignancy during a 30-year period was undertaken to identify incidental metastatic papillary thyroid cancer (PTC). RESULTS: Twenty-six patients had an incidental finding of PTC in lymph node(s) in neck dissection specimens. Subsequent ultrasound of the thyroid showed nodules in 20 patients. Eleven (42%) underwent total thyroidectomy, 1 (4%) had a lobectomy, and 14 (54%) were kept under active surveillance only. At a median follow-up of 48 months (range 10-189 months), all patients who had undergone surgery and those under surveillance were free of PTC recurrence. CONCLUSION: Evaluation for detection of a primary thyroid tumor is essential in all patients with incidentally discovered metastatic PTC. Decision regarding surgery or surveillance is dependent on clinical and radiological tumor features and patient factors.

Therapeutic lateral neck dissection in well-differentiated thyroid cancer: Analysis on factors predicting distribution of positive nodes and prognosis.

BACKGROUND: Neck dissection is considered the treatment of choice in patients with lateral neck metastases from well-differentiated thyroid cancer. METHODS: A multicenter, retrospective review of patients who underwent therapeutic lateral neck dissection for well-differentiated thyroid carcinoma was carried out. RESULTS: The study included a total of 405 lateral neck dissections performed in 352 patients; 197 women (56%) and 155 men (44%). When considering ipsilateral neck metastases, levels IIa, IIb, III, IV, Va, Vb, and V (not otherwise specified) were involved in 42%, 6%, 73%, 67%, 11%, 31%, and 35% of cases, respectively. Five-year and 10-year overall survival (OS) were 93% and 81%, respectively. Age >55 years, pathologic T (pT)4 category, tumor diameter >4 cm, aggressive variants of well-differentiated thyroid carcinoma, endovascular invasion, and number of positive nodes >5 turned out to be the most important prognostic factors. CONCLUSION: Neck dissection is a valid treatment option in the presence of neck metastasis from well-differentiated thyroid carcinoma. Levels IIa, III, IV, and Vb should always be removed.

Dural Invasion Predicts the Laterality and Development of Neck Metastases in Esthesioneuroblastoma.

Objectives Neck metastases in patients with esthesioneuroblastoma (ENB) constitute the most significant predictor of poor long-term survival. Recently, researchers discovered the existence of dural lymphatic channels that drain to the cervical lymph nodes. From this physiologic basis, we hypothesized that patients with ENB who develop dural invasion (DI) would exhibit a proclivity for neck metastases. Design Retrospective review. Setting Tertiary referral center. Participants All patients treated for ENB from January 1, 1994 to December 31, 2015. Main Outcome Measures Incidence, laterality, and recurrence rate of neck metastases by DI status. Results Sixty-one patients were identified (38% female; median age 49, range, 10-80), 34 (56%) of whom had DI and 27 (44%) did not. Of patients with DI, 50% presented with or developed neck disease following treatment compared with just 22% of those without DI ( p = 0.026). Bilateral neck disease was more common in patients with DI (11/34, 32%) compared with those without (2/27, 7%) ( p = 0.018). Five-year regional recurrence-free survival rates were 88% for those without and 64% for those with DI ( p = 0.022). Kadish C patients with DI were more likely to develop regional recurrence when compared with Kadish C without DI and Kadish A/B ( p = 0.083). Further, Kadish C patients with DI displayed worse overall survival than Kadish C without DI and Kadish A/B. Kadish D patients displayed the worst overall survival. The difference in overall survival among these four groups was significant ( p < 0.001). Conclusion DI by ENB is associated with increased incidence of cervical nodal metastases, bilateral neck disease, worse regional recurrence-free survival, and poorer overall survival. These data support the division of Kadish C by DI status.

Lymph Nodes of the Perimandibular Area and the Hazard of the Hayes Martin Maneuver in Neck Dissection.

Objective To provide an anatomic description of submandibular nodes at risk of being left undissected during neck dissection (ND) and to assess whether the Hayes Martin maneuver is a safe procedure in oncologic surgery of level IB nodes. Study Design Prospective study. Setting Academic medical center. Subjects and Methods We recruited 62 patients who were candidates for level IB ND. Perifacial nodes (PFNs) were identified and their characteristics noted. The Hayes Martin maneuver was simulated, and its oncologic safety was tested. Results The study included 63 NDs. PFNs were identified in 84% of cases: their number ranged from 0 to 5, and their mean greatest diameter was 12.45 mm. Anterior PFNs were found to be in direct contact with the marginal mandibular nerve. In 59% of NDs, the Hayes Martin maneuver would have failed to remove all PFNs. Conclusions The PFNs were identified in 84% of cases and ranged in number from 0 to 5. In some cases, the distinction between retro- and preglandular nodes and PFNs is not useful. The Hayes Martin maneuver may not be oncologically sound for complete treatment of level IB nodes.