Neck Metastasis Research Articles

Challenges and Considerations in Diagnosing and Managing p16+-Related Oropharyngeal Squamous Cell Carcinoma (OPSCC) with Neck Metastasis: Implications of p16 Positivity, Tobacco Exposure, and De-Escalation Strategies

Background: The incidence of patients showing neck metastasis and no obvious primary tumor at the initial diagnostic evaluation or neck cancer of unknown primary (NCUP) is rising. It is estimated that a relevant part of these tumors arises in the tonsillar crypts or base of the tongue and are p16+-related. However, today, the detection rate of the primary tumor is suboptimal. Identifying the primary tumor and its biomolecular characterization is essential since it influences the treatment administered, possibly reducing radiation fields and providing de-escalation to primary surgical management. However, p16 IHC (immunohistochemistry) might not be sufficient to diagnose HPV-related OPSCC. The other subset of patients discussed are the HPV-positive patients who have a history of tobacco exposure and/or p53 mutations. Possible factors that could negatively influence the outcomes of these patients are investigated and discussed below. So, this paper aims to analyze the diagnostic, bio-molecular, clinico-radiological, morphological, prognostic and therapeutical aspects of p16-positive OPSCC, highlighting the possible bias that can occur during the diagnostic and prognostic process. Methods: A narrative review was conducted to investigate the biases in the diagnostic and therapeutic process of two groups of patients: those who are p16-positive but HPV-negative patients, and those who are p16-positive and HPV-positive with exposure to traditional risk factors and/or p53 mutations. The keywords used for the literature research included the following: NCUP, OPSCC, p16IHC, HPV testing, p16 positive HPV negative OPSCC, p16 positive HPV positive OPSCC, tonsillectomy, tobacco exposure, p53 mutations, cystic neck metastasis, extranodal extension (ENE), radiotherapy, de-escalation and neck neck dissection. Results: HPV-positive OPSCC has specific clinico-radiological features. Bilateral tonsillectomy should be considered for the identification of the primary tumor. P16 IHC alone is not sufficient for diagnosing HPV-related OPSCC; additional detection methods are required. The role of tobacco exposure and p53 mutations should be investigated especially in cases of HPV-positive tumors. Extranodal extension (ENE) must be taken into consideration in the prognostic staging of HPV-positive tumors. Surgical primary treatment involving neck dissection (ND) and bilateral tonsillectomy followed by adjuvant radiation may represent the most appropriate approach for N3 cases. Diagnosis, prognosis and therapeutical implications must be addressed considering clinical, biomolecular and morphological aspects. At least today, the numerous biases that are still present influencing the diagnostic and prognostic process do not permit considering de-escalation protocols. Conclusions: A precise and accurate diagnosis is required in order to adequately stage and manage p16+ OPSCC, particularly with neck metastasis. The role of tobacco exposure and/or p53 mutations must be considered not only in p16+ OPSCC but especially in HPV-positive OPSCC. Until a more accurate diagnosis is possible, ENE should be considered even in p16+HPV+ OPSCC. Primary surgery with unilateral ND and bilateral tonsillectomy might be the treatment of choice given the numerous diagnostic and prognostic pitfalls. Therefore, it is inappropriate and risky to propose de-escalation protocols in routine clinical practice due to the risk of undertreatment.

Impact of contralateral occult neck metastasis in HPV-associated tonsil cancer: Is elective contralateral neck dissection required?

Background: Contralateral elective neck dissection in human papillomavirus (HPV)- associated tonsil cancer is a matter of debate.Objectives: The aim of this study was to analyze rates of contralateral lymph node (LN) metastasis and their prognostic effects on HPV-associated tonsil cancer. We also assessed the necessity of elective contralateral neck dissection.Methods: To investigate the pathologic incidence of and risk factors for contralateral nodal disease in HPV-associated tonsil cancer treated with upfront primary surgery and bilateral neck dissection, the records of 68 patients were reviewed.Results: Six (8.8%) patients displayed pathologic contralateral nodal disease; four of the patients had LN metastasis confirmed in contralateral level II, one patient had LN metastasis in level III, and one patient had multi-level metastasis in contralateral levels II and III. Contralateral LN metastasis showed a significant association with greater depth of invasion (DOI) in primary tumor (p=0.032), count of positive LN (p=0.008), and positive LN ratio of the ipsilateral neck (p=0.01). Patients with contralateral LN metastasis showed a significantly worse five-year overall survival but no significant difference in disease-free survival.Conclusion: HPV-associated tonsil cancer has exceedingly low rates of occult contralateral LN metastasis. However, in cases of ipsilateral multiple node metastases and higher DOI, it may be worth considering elective contralateral neck dissection based on the risk of occult metastasis.

Nicotine-induced CHRNA5 activation modulates CES1 expression, impacting head and neck squamous cell carcinoma recurrence and metastasis via MEK/ERK pathway

The mucosal epithelium of the head and neck region (including the oral cavity, nasal cavity, pharynx, nasopharynx, and larynx) is the primary site exposed to tobacco smoke, and its presence of nicotinic acetylcholine receptors (nAChRs) has been observed in the mucosal epithelial cells of this area. It remains unclear whether HNSC cells can migrate and invade through nAChR signaling. A model of HNSC cells exposed to nicotine is established. Cell proliferation following nicotine exposure is assessed using the CCK-8 assay, while migration and invasion are evaluated through wound healing and Transwell assays. The effects of CHRNA5 knockdown and overexpression are also investigated. Immunofluorescence staining is used to analyze CHRNA5 expression and localization, and clonogenic assays are performed to measure colony proliferation after CHRNA5 knockdown and overexpression. The interaction between CHRNA5 and CES1 is examined using molecular docking, co-immunoprecipitation, and immunofluorescence. Differentially expressed genes are subjected to pathway enrichment analysis, and MEK/ERK protein expression and phosphorylation are validated via western blot. Tumor formation assays are performed in nude mice using sh-CHRNA5 Cal27 cells, followed by western blot and immunohistochemical staining. Additionally, laryngeal and hypopharyngeal cancer tissues are analyzed through immunohistochemistry. Nicotine significantly enhanced the proliferation, migration, and invasion capabilities of head and neck tumor cells, including Cal27, Fadu, HN6, and Tu686 cells, through the expression of CHRNA5. Knockdown of CHRNA5 can reduce cell migration, invasion, and proliferation, whereas nicotine exposure can reverse this trend. Additionally, the mRNA and protein expression of CES1 decreases with the knockdown of CHRNA5, indicating a regulatory relationship between the two. Transcriptomics revealed that the knockdown of CHRNA5 is associated with the MEK/ERK signaling pathway. Further cellular- and tissue-level evidence confirmed that the levels of p-MEK/MEK, p-ERK/ERK, and CES1 decreased following knockdown of CHRNA5, a trend that nicotine can reverse. Nicotine promotes the proliferation, migration, and invasion of HNSC by upregulating CHRNA5 expression. Knockdown of CHRNA5 reduces these effects, which can be reversed by nicotine. Nicotine exposure activates CHRNA5, regulating CES1 expression via the MEK/ERK pathway, contributing to the recurrence and metastasis of head and neck squamous carcinoma.

Predictive factors for lymph node metastasis in papillary thyroid cancer patients undergoing neck dissection: insights from a large cohort study

BackgroundThis study aimed to investigate the risk factors and metastatic patterns in papillary thyroid cancer (PTC) patients undergoing lymph node dissection, offering guidance for clinical practice.MethodsA total of 924 PTC patients who underwent thyroidectomy with central neck dissection (CND) or lateral neck dissection (LND) between January 2021 and November 2022 were included in the analysis. The study investigated the relationships between clinicopathological characteristics, lymph node metastasis, and various risk factor.ResultsAmong the 924 PTC patients, the cervical lymph node metastasis rate was 59.1% (546 patients). Of these patients, 381 had central neck metastasis (CNM, 41.2%), while the remaining 165 patients had lateral neck metastasis (LNM, 17.9%). Factors associated with increased risk of CNM and LNM included larger tumor diameter, presence of multiple tumors, and capsular invasion (p<0.05). Male sex, age <55 years, larger tumor diameter (>0.85 cm), multiple tumors, capsular invasion, and absence of Hashimoto’s disease were identified as independent risk factors for CNM (p<0.05), with an AUC value of 0.722. CNM, maximum diameter >1.15 cm, and multiple tumors were independent risk factors for LNM (p<0.05), with an AUC of 0.699.ConclusionThese findings suggest that tailored neck dissection based on individual risk factors is crucial, particularly in cases of suspected LNM with larger tumors, CNM, multiple tumors, and capsular invasion.

Utility of intraoperative Delphian lymph node sampling in pediatric thyroid surgery

ObjectivesThe Delphian lymph node (DLN) is the first lymph node receiving drainage from the thyroid. We aim to determine whether routine DLN sampling with frozen section analysis during pediatric thyroidectomy can alter intraoperative surgical decision making. Additionally, we aim to measure whether DLNs can predict a requirement for central neck dissection (CND) in the clinically node negative (CNN) pediatric population. MethodsRetrospective chart review for pediatric patients who underwent thyroidectomy between 2014 and 2022. Patients were included if they had prior FNA with a result of: benign nodule, atypia or follicular neoplasm of undetermined significance (AUS/FNUS), follicular neoplasm (FN), or papillary thyroid carcinoma (PTC). All patients had intraoperative DLN analysis via frozen section histopathology. Results27 patients were included, 9 males (33 %) and 18 females (67 %). On final pathology 19 patients (70.4 %) had PTC. The DLN was negative for carcinoma in all (n = 8, 100 %) patients with benign pathology. In 10 patients (100 %) with positive DLN on frozen section, postoperative pathology demonstrated central neck metastasis. Nine (90 %) of these patients were CNN and had alterations in the surgical plan based on the DLN. The tenth patient's surgical plan did not change given preoperative clinical disease. Three patients with negative DLNs had central neck metastasis. ConclusionThe DLN serves a role in guiding treatment for the pediatric population. Positive DLN altered surgical plans in 60 % of CNN PTC patients, allowing for CND to be performed and reducing need for additional surgical resection. The positive predictive value for DLN status was 100 % in this study, and the negative predictive value was 62.5 %. However, negative DLNs do not rule out central neck disease.

Utilization of traditional Chinese medicine in the management of cutaneous ulceration induced by cervical lymph node metastasis in tonsillar carcinoma: A case report

ObjectiveCutaneous ulcers induced by metastasis present a challenging clinical issue, often resistant to conventional dressing change interventions. In this case, we demonstrates the efficacy of Traditional Chinese Medicine in managing ruptured tumors. Case presentationWe present a case study of a 40-year-old Chinese male patient diagnosed with advanced tonsillar squamous cell carcinoma with cervical lymph node metastasis and cutaneous ulceration. Despite nearly six months of conventional dressing treatment yielding minimal improvement, significant healing of the ulcerated surface of the neck metastasis was observed after approximately two months of decoction therapy. The cancerous lesion exhibited a reduction of nearly 90 %, with concomitant alleviation of secondly symptoms such as cold intolerance, excessive sweating, anxiety and depression. ConclusionsIn this case, we introduces Traditional Chinese Medicine may be an effective alternative therapy for the treatment of cancer-related disease. And it may also be an optional therapeutic approach for healthcare practitioners with cutaneous carcinoma ulceration.

Prediction of lateral neck metastasis in patients with papillary thyroid cancer with suspicious lateral lymph ultrasonic imaging based on central lymph node metastasis features.

Neck lymphatic metastasis is a common occurrence with thyroid cancers, and pre operative lateral lymph node metastasis (LLNM) and postoperative lateral lymph node recurrence (LLNR) are two independent risk factors that are negatively associated with the prognosis of patients with thyroid cancer. The aim of the present study was to investigate the relationship between central lymph node metastasis (CLNM) and LLNM in patients with papillary thyroid carcinoma (PTC) with sonographically suspected LLNM, such as those without lymph node fine-needle aspiration (FNA) cytological results or negative FNA results at the time of diagnosis. The predictive ability of CLNM regarding LLNR was also investigated. The present study retrospectively reviewed the clinical data of 1,061 patients that were surgically treated for PTC and 128 patients with sonographically suspected lateral lymph nodes that received central lymph node dissection and lateral lymph node dissection at the Thyroid Department of The First Affiliated Hospital of Anhui Medical University (Hefei, China) from June 2019 to June 2021. In patients with suspicious ultrasonic images suggesting LLNM, a significant association between the central lymph node ratio (CLNR), the number of positive central lymph nodes and LLNM was demonstrated. Otherwise, there were no statistically significant differences between the CLNR in patients with PTC and patients with PTC without evidence of lateral cervical metastasis. However, the rate of LLNR increased significantly when the number of positive central lymph nodes was >3. In conclusion, the CLNR and the number of positive central lymph nodes could be used to predict LLNM in patients with PTC with sonographically suspect lateral lymph nodes, including those with no FNA cytological results or negative FNA results, which may potentially support physicians in making personalized clinical decisions.

Unilateral amelanotic conjunctival malignant melanoma: a case report

IntroductionCutaneous malignant melanomas rarely occur in the eye, usually in the eyelids or the conjunctiva. Conjunctival malignant melanomas are even rarer. Most melanomas are dark in color as they are pigmented. However, amelanotic conjunctival malignant melanomas, a scarce variant of the cancer, can be challenging to diagnose accurately.Case presentationWe present two cases of white Caucasian Swedish-born women who were diagnosed with unilateral amelanotic malignant melanoma in the conjunctiva of the eye. In the first case, the patient was an 81-year-old woman who was suffering from redness and foreign body sensation in the left eye. The initial diagnosis was blepharitis. Three biopsies were taken, which showed malignant melanoma in the eyelid and the conjunctiva. Unfortunately, the eye and the rest of the orbit could not be saved, and the patient had to undergo an orbital exenteration. In the second case, the patient was a 50-year-old woman, and the tumor was localized in the temporal conjunctiva of the left eye. The initial diagnosis was pinguecula, but at the time of surgery, the physician suspected conjunctival intraepithelial neoplasia. The tumor was not completely removed, so adjuvant brachytherapy and local chemotherapy were used. The eye was preserved. No neck and/or lung metastasis was detected in either case at the time of diagnosis.ConclusionsConjunctival amelanotic malignant melanomas should be suspected when tumors are present in the eye and/or the eyelids. By suspecting amelanotic malignant melanoma, the delay in treatment can be shortened. Treating them as soon as possible is essential to minimize the risk of metastasis.

Comparison of actual prognosis between unilateral and bilateral central neck dissection in modified radical neck dissection patients with no clinical central lymph node metastasis: a retrospective cohort study.

This study aimed to evaluate the long-term prognosis of contralateral central neck dissection (CND) in papillary thyroid cancer (PTC) patients with ipsilateral lateral neck metastasis. We compared the actual recurrence rate according to the extent of CND-ipsilateral and contralateral sides. A total of 708 PTC patients who underwent total thyroidectomy and concomitant ipsilateral or bilateral CND with ipsilateral lateral neck dissection between January 1997 and December 2022 at Samsung Medical Center were retrospectively analyzed. The median follow-up time was 118 months. Locoregional recurrence was observed in 26 patients (7.9%) and 30 patients (7.9%) in the ipsilateral and bilateral CND groups, respectively. There were 6 contralateral recurrence cases (1.8%) in the ipsilateral CND group and 6 cases (1.6%) in the bilateral CND group. There was only 1 contralateral central neck recurrence in the ipsilateral CND group. The incidence of hypocalcemia (P = 0.007) was higher in the bilateral CND group compared to the ipsilateral CND group. Surgeons may consider performing only unilateral CND-the side where tumor is for therapeutic purposes to reduce surgical complications.

Randomized clinical trial of prophylactic central neck dissection in 2100 papillary thyroid carcinoma patients with clinically negative central neck metastasis: an interim analysis of a single institution

Randomized clinical trial of prophylactic central neck dissection in 2100 papillary thyroid carcinoma patients with clinically negative central neck metastasis: an interim analysis of a single institution

Metastatic malignancies in the parotid gland: A retrospective study

The aim of this study was to compare treatment modalities, pathological and clinical characteristics, and outcomes in patients with metastasis in a parotid gland.The medical records of 34 patients who received treatment for metastasis in the parotid gland over a twenty-year period were evaluated. Patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) metastasis were retrospectively reclassified using the P/N and N1S3 staging system.Patients with neck metastasis showed a significantly poorer prognosis (P = 0.025). Univariate analysis also revealed that extent of parotidectomy and type of neck dissection did not influence recurrence free survival (RFS) and overall survival (OS). When comparing the usefulness of the P/N and S1N3 staging systems, a positive correlation was observed between the P stage and the N1S3 stage in both RFS and OS.The extent of parotidectomy and concomitant neck dissection is still under discussion. Total parotidectomy and modified radical neck dissection did not improve RFS and OS. N1S3 is a less complex classification and possesses a higher predictive value when compared to the P/N staging system.

The Importance of the Time Interval Between Preoperative 18F-FDG PET/CT Imaging and Neck Dissection for the Detection of Nodal Metastases in Patients with Head and Neck Squamous Cell Carcinoma.

Detection of nodal metastasis is critical for the treatment and prognosis of head and neck cancer (HNC). Positron emission tomography/computed tomography (PET/CT) is increasingly being used to detect cervical lymph node involvement. The purposes of this study were to (1) investigate the diagnostic accuracy of PET/CT for the detection of neck metastasis in patients with HNC and (2) determine the effect of the time interval between surgery and PET/CT. Fifty patients with head and neck squamous cell carcinoma who underwent PET/CT before surgery were included in this study. Preoperative PET/CT images that determined lymph node metastasis were compared with the histopathological analysis of neck dissection samples. Neck dissections were divided into three groups according to the time interval between surgery and PET/CT (0-2 weeks, >2-4 weeks, and >4 weeks). The concordance between PET/CT and histopathology was measured using the neck sides at different time intervals. The specificity, sensitivity, accuracy, negative predictive value (NPV), and positive predictive value (PPV) of PET/CT in detecting metastatic lymph nodes in the neck were calculated. A total of 79 neck dissections were included in the study as 29 (58%) of the patients underwent bilateral neck dissection. The overall accuracy of PET/CT in detecting nodal metastasis was highest for the 0-2 weeks interval (95.6%). During this time interval, the sensitivity, specificity, NPV, and PPV of PET/CT were 100%, 90.9%, 100%, and 92.3%, respectively. Although PET/CT is an important and reliable diagnostic method for detecting nodal metastases in patients with HNC, its reliability decreases as the time between surgeries increases. The optimal interval was 2 weeks; however, up to 4 weeks was acceptable.

Treatment outcomes of elective neck dissection in intrathoracic esophageal carcinoma.

In the present study, the outcomes of elective neck dissection in patients with intrathoracic esophageal squamous cell carcinoma were investigated. From January 2016 to December 2022, 21 patients who underwent esophagectomy and elective neck dissection (both neck level IV) for intrathoracic esophageal squamous cell carcinoma were enrolled. Of these 21 patients, 19 patients were male and 2 were female. A total of 11 patients received concurrent chemoradiotherapy (CCRT) as preoperative treatment. As a result of elective neck dissection at both neck level IV, occult neck metastasis of esophageal squamous cell carcinoma was diagnosed in 3 cases, all of which involved left neck lymph nodes. The incidence of occult neck metastasis was statistically significant in patients with preoperative CCRT, high T stage and high N stage (P<0.05). In addition, 16 out of 21 patients had been under follow-up without disease recurrence after the completion of treatment. However, 3 out of 21 patients succumbed to esophageal squamous cell carcinoma and 2 out of 21 patients were alive with stable disease of esophageal carcinoma. The follow-up period was 19.2±18.4 months. In conclusion, three-field lymph node dissection for intrathoracic esophageal squamous cell carcinoma may be necessary in patients with certain phenotypes, such that collaboration between thoracic surgeons and otolaryngologists may help reduce surgical complications.

Identifying factors related to delayed neck metastasis after surgical treatment in patients with oral squamous cell carcinoma

BackgroundGeneral treatment of oral squamous cell carcinoma (OSCC) is surgical treatment with or without neck dissection. Although the incidence of delayed neck metastasis is rare, it may occur after the surgery and is known to be the most important factor in the prognosis. The purpose of is study is to evaluate the clinical and histopathological factors associated with delayed neck metastasis case among patients.MethodsA total of 195 patients who underwent surgical treatment for OSCC from 2016 to 2022 were investigated. Among them, delayed neck metastasis (DNM) was analyzed. The criterion for delayed neck metastasis was a newly developed neck lesion after the primary operation without neck dissection in cN0 necks. To identify the correlation between prognostic factors and the incidence of delayed neck metastasis, χ2 analysis with phi correlation and Cramer’s V test was performed. Cumulative survival rates (CRS) were compared between the groups with the incidence of DNM and without DNM. Also, the log rank test for CSR and Cox proportional hazard model was analyzed to estimate the significance of the CSR and confirm the correlations between prognostic factors and DNM.ResultAmong 195 patients, 14 were discovered to have DNM. The primary tumor locations were the tongue (n = 5), floor of the mouth (n = 2), mandibular gingiva (n = 1), maxillary gingiva (n = 4), retromolartrigone (n = 1), and buccal mucosa (n = 2) each. The cases consisted of TNM stage I (n = 1), stage II (n = 3), stage III (n = 3), and stage IV (n = 8), respectively. The result of the χ2 analysis identified a correlation between positive neck (p = 0.01), depth of invasion (p = 0.09), radiation therapy (p = 0.003), and DNM. Groups without DNM showed better prognosis compared to groups with DNM. Regarding positive neck, depth of invasion, and radiation therapy, only depth of invasion showed significance in CSR analysis.ConclusionDNM after surgical treatment of OSCC is a rare event, and few were found in a review of the literature. Also, many prognostic factors have been suggested but controversial. However, in our study, some prognostic factors have been identified to have a significant correlation with the incidence of DNM, and analysis of such factors provides important information predicting neck metastasis and the prognosis.

The machine learning-based model for lateral lymph node metastasis of thyroid medullary carcinoma improved the prediction ability of occult metastasis.

For medullary thyroid carcinoma (MTC) with no positive findings in the lateral neck before surgery, whether prophylactic lateral neck dissection (LND) is needed remains controversial. A better way to predict occult metastasis in the lateral neck is needed. From January 2010 to January 2022, patients who were diagnosed with MTC and underwent primary surgery at our hospital were retrospectively reviewed. We collected the patients' baseline characteristics, surgical procedure, and rescored the ultrasound images of the primary lesions using American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS). Regularized logistic regression, 5-fold cross-validation and decision curve analysis was applied for lateral lymph node metastasis (LLNM) model's development and validation. Then, we tested the predictive ability of the LLNM model for occult LLNM in cN0-1a patients. A total of 218 patients were enrolled. Five baseline characteristics and two TI-RADS features were identified as high-risk factors for LLNM: gender, baseline calcitonin (Ctn), tumor size, multifocality, and central lymph node (CLN) status, as well as TI-RADS margin and level. A LLNM model was developed and showed a good discrimination with 5-fold cross-validation mean area under curve (AUC) = 0.92 ± 0.03 in the test dataset. Among cN0-1a patients, our LLNM model achieved an AUC of 0.91 (95% CI, 0.88-0.94) for predicting occult LLNM, which was significantly higher than the AUCs of baseline Ctn (0.83) and CLN status (0.64). We developed a LLNM prediction model for MTC using machine learning based on clinical baseline characteristics and TI-RADS. Our model can predict occult LLNM for cN0-1a patients more accurately, then benefit the decision of prophylactic LND.

Enhancing the management of locally advanced head and neck malignancies and cases with local/neck recurrence and metastasis through the integration of anlotinib with concurrent radiochemotherapy.

The aim of this study is to assess the effectiveness and safety of anlotinib in conjunction with concurrent radiochemotherapy for the treatment of locally advanced head and neck malignant tumors, including cases exhibiting local or neck recurrence and metastasis. Between June 2020 and June 2023, 42 patients diagnosed with locally advanced head and neck malignant tumors or presenting with local or neck recurrence and metastasis were recruited. These individuals received treatment that combined anlotinib with concurrent radiochemotherapy, followed by a minimum of two cycles of oral anlotinib upon completion of the initial treatment regimen. Among the 19 patients diagnosed with nasopharyngeal carcinoma, 14 patients attained a complete response, while four patients achieved partial response, resulting in an overall response rate of 94.74% (18/19). Conversely, among the 23 patients with non-nasopharyngeal carcinoma, two patients achieved complete response and 16 attained partial response, yielding a response rate of 78.26% (18/23). The 6-month progression-free survival rate was 95.24%. After treatment, serum vascular endothelial growth factor receptor levels exhibited a significant decrease compared with pretreatment levels. Notably, no instances of treatment-related serious adverse reactions were recorded. The combination of anlotinib with concurrent radiochemotherapy demonstrates favorable efficacy in managing locally advanced head and neck malignant tumors, including instances of local or neck recurrence and metastasis. Furthermore, the treatment regimen is characterized by an acceptable safety profile and tolerability.

Tissue expression of miR-449a as risk factor for occult neck metastasis in patients with cT3-T4 N0 laryngeal cancer. A pilot study.

To explore the potential role of miR-449a as biomarker for laryngeal squamous cell carcinoma (LSCC), especially in the decision strategy of neck dissection (ND). Each patient underwent total laryngectomy and bilateral ND (levels II-IV); during surgery, tissue samples of around 1 × 0.5cm were extracted from both healthy tissue adjacent to the tumor and the visibly affected tumor tissue. The extraction of total RNA, encompassing miRNA, was performed using a mirVana PARIS kit. To detect miR449a, cDNA was synthesized from 200ng of RNA using a TaqMan miRNA reverse transcription kit. The study group was formed of 66 patients (62 males, and 4 females) with LSCC, aged between 39 and 77years (mean 60 + 14.56yr). MiR-449a was up-regulated in twenty-eight tumors (42%), while it was down-regulated in 38 samples (58%). In the present study, there was a statistical relevance for miR-449a tissue expression for pN staging (p = 0.017), and PNI (p = 0.005). Eight tumors (12%) cN0 became pN + showing occult cervical lymph node metastases at the final histopathological examination, and all of these patients showed miR-449a downregulation. Super-selective ND (sparing the sub evels IIb and IV) might be the approach to cT3-T4 N0 LSCCs with upregulation of miR-449a; on the other hand, to ensure and effective control of occult neck metastases it would be appropriate to reserve elective ND (including sublevels IIb and IV) for cT3-T4 N0 LSCCs with miR-449a downregulation. Although promising, due to the small size of the cohort, the results of this work can be considered preliminary and need to be confirmed by prospective and larger studies.

Laryngeal Paraganglioma with Neck Metastasis.

Paragangliomas are neoplasms of neural crest cells. They represent less than 1% of head and neck tumors. Laryngeal paragangliomas constitute a smaller fraction of head and neck paragangliomas. Malignant laryngeal paragangliomas with metastasis are extremely rare tumors. Definitive treatment includes complete surgical excision with maximum preservation of laryngeal function. Here, we report a rare case of a 55year old woman who was diagnosed with recurrent laryngeal paraganglioma along with neck metastasis. A complete excision of mass with a lateral pharyngotomy approach along with neck dissection followed by chemotherapy was done.

Fibroblasts from HPV-negative oropharynx squamous cell carcinomas stimulate the release of osteopontin from cancer cells via the release of IL-6.

HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) shows distinct biological and clinical behaviour when compared to HPV-negative OPSCC. The overall role of the tumour microenvironment (TME) in head and neck cancer progression and metastasis has been studied intensively, but differences in HPV-negative and HPV-positive OPSCCs are less understood. To investigate the role of cancer-associated fibroblasts (CAFs) and the functional interactions of normal tonsil fibroblasts (NTFs) and OP CAFs with HPV+ and HPV- OPSCC cells and explore novel candidates in tumour-fibroblast crosstalk. A retrospective cohort of 143 primary OPSCCs was characterised using HPV16/18 RNAScope assay, p16 IHC and ɑ-SMA. Four OPSCC, three NTF and 2 new OPSCC CAF cultures were used to assess the cytokine-based interactions using cytokine arrays on conditioned media (CM), followed by co-culture approaches to identify the role of individual cell types and the role of OPN (SPP1) and IL-6 in SCC/fibroblast communication. HPV status was associated with better overall survival. Although ɑ-SMA expression was observed in both OPSCC subtypes, it provided survival stratification only in the HPV-positive group (Log-Rank p = 0.02). Three normal tonsillar fibroblast cultures (NTFs) were characterised by induction of myofibroblastic and senescent phenotypes with similar reactivity to our published NOF phenotype. The OPSCC-derived CAF cultures were characterised and their baseline myofibroblastic and senescence phenotypes varied. Cytokine array analysis of CM to identify novel candidates in the crosstalk between OPSCC tumour cells and NTFs/CAFs identified differences in the cytokine profiles on comparison of HPV+ and HPV- OPSCC cells. Osteopontin (OPN/SPP1) was identified, particularly in HPV-negative OPSCC cell analyses. We have demonstrated that OPN was produced by the OPSCC cells and revealed an associated upregulation of IL-6 in fibroblasts. Treatment of NTFs with rOPN showed alteration in phenotype, including increased contraction and IL-6 production. Antibody-mediated inhibition of CD44v6 attenuated the production of IL-6 by OPN in NTFs. This investigation with OPSCC fibroblasts provides novel insights into the role of CAFs in OPSCC mediated by IL-6 stimulated release of OPN from HPV negative OPSCC cells. The details of HPV-positive SCC cell/fibroblast cytokine crosstalk remain elusive.

The Depth of Invasion and Level IV Cervical Node Metastasis in Patients with Clinically N0 Tongue Cancer.

The accurate indication for level IV dissection is crucial for preventing complications such as phrenic nerve damage and chylous fistulas in clinically N0 tongue cancer. Although the depth of invasion is an established independent risk factor for occult lymph node metastasis in tongue cancer, its relationship with level IV metastasis has not been evaluated. This study investigated the relationship between the depth of invasion and level IV nodal metastasis in clinically N0 tongue cancer. We retrospectively investigated clinical N0 patients who underwent glossectomy and level I-IV neck dissection. We examined lymph node metastasis, risk factors, and the relationship between depth of invasion and metastasis. Our study included 58 patients, and no patient had isolated level IV metastasis. Additionally, there was no level IV metastasis in well-differentiated tumors. Tumor size, depth of invasion, differentiation, and perineural invasion were significantly associated with level IV neck metastasis. We found a critical tumor size of 2.5cm and depth of invasion of 8mm for level IV neck metastasis. Based on our findings, we recommend that level IV dissection should be considered for poorly differentiated tumors, tumors greater than 2.5cm in size, and those deeper than 8mm. This study highlights the importance of depth of invasion as a prognostic factor for predicting level IV metastasis and suggests that our findings can be used to prevent unnecessary level IV dissections that may lead to complications in tongue cancer surgery.