Neck Node Squamous Cell Metastasis from Unknown Primary and Mutagen Sensitivity: A Case Series.

Most of the neck node metastases from cancer of unknown primary (CUP) are squamous cell carcinomas (SCCs). The majority of which are human papillomavirus (HPV)-related, frequently show cystic morphology referring to Waldeyer's ring origin. Here, we report four cases of neck node SCCs metastases from CUP. In our institute, 432 patients with head and neck (HN) SCC underwent pretreatment mutagen sensitivity (MS) assay between 1996 and 2006. Among them, 4 patients ≤50 years of age had metastatic cervical nodes from CUP. The primary treatment was cervical node dissection ± radiotherapy. All patients had elevated (>1.0 chromatid break/cell) MS. One male patient died of progressive neck metastasis within 3 years and the 3 female patients are still alive more than 15 years after initial treatment of HPV+ (two) or cystic (one) SCC. Two female patients developed second and third distant site metachronous primary cancers. HPV+ or cystic HNSCC from CUP with elevated MS indicates good outcome. Distant site metachronous cancers of different histologic origins cannot be explained by field cancerization. The clinical significance of elevated MS in neck node SCC metastasis from CUP requires further investigation.

Central Neck Lymph Node Size Measured by Ultrasound Significantly Predicts Central Neck Lymph Node Metastasis of Papillary Thyroid Carcinoma.

Objective: The aim of this study was to investigate whether Central lymph node (CLN) size as measured by an ultrasound can significantly predict CLN metastasis of papillary thyroid carcinoma (PTC). Materials and methods: This retrospective chart review of patients diagnosed with PTC who underwent ultrasound and central neck dissection (CND). We excluded patients who received previous thyroid surgery or radiation. We analyzed the correlation between CLN size and characteristics by ultrasound and histopathologic findings among positive CLN patients. Results: Of the 48 patients who underwent preoperative ultrasound and CND, 34 patients had positive CLN identified by ultrasound. The positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of ultrasound in this diagnostic setting was 88.0%, 21.0%, 73.2%, 42.9%, and 68.7%, respectively. The risk of CLN metastasis of PTC was 67.7% and 85.7% for lymph node size 3.1 to 4 mm and 4.1 to 5 mm, respectively. The risk increased to 100% when the lymph node size was >5 mm. Positive preoperative ultrasound of lateral neck lymph node was found to be a significant risk factor for CLN metastasis (P = .003). Conclusion: Ultrasound was found to be an effective preoperative evaluation in patients with PTC to determine the likelihood of CLN metastasis and whether CND is indicated, especially in the ultrasound-positive central lymph node. A high risk of metastasis was found in CLN size >3 mm by ultrasound, and the risk dramatically increased in CLN size >5 mm. We also found positive lateral neck node from preoperative ultrasound to be a significant risk factor for CLN metastasis.

Depth of Invasion, Lymphovascular Invasion, and Perineural Invasion as Predictors of Neck Node Metastasis in Early Oral Cavity Cancers.

Aims: The present study examines the role of demographic and pathological features of primary tumours in predicting neck metastasis in early oral cavity cancers, which has been a matter of debate. Methods: A single-centre, retrospective, institution review was conducted of all the patients presented to our centre from January 2014 to December 2021. Patient characteristics were compared between the two lymph node groups (lymph node positive and lymph node negative) and significant prognostic factors were determined. Results: A total of 462 oral squamous cell carcinoma (OSCC) patients were included, 407 male and 55 female. Tobacco chewing (59.2%) was a major habit with buccal mucosa (49.5%) and tongue (44.8%) as primary sites. The majority of the patient's histology was of SCC (96.8%) with grade II (moderately differentiated, 74.5%). Univariate logistic regression analysis to predict lymph node metastasis showed pT size (< 0.001), LVI (< 0.001), and PNI (< 0.001) as significant tumor characteristics. On multivariate, pT size (OR-1.58, P - 0.0001) and LVI (OR-19.70, P - 0.0001) were reported to be statistically significant to predict lymph node metastasis. Conclusion: Reporting and studying the clinico-pathological features of primary tumors can give vital information in predicting the neck node metastasis in OSCC patients.

Incidence of Micrometastasis and Isolated Tumour Cells in Clinicopathologically Node-Negative Head and Neck Squamous Cell Carcinoma.

INTRODUCTION: Occult neck node metastasis in head and neck squamous cell carcinoma (HNSCC) in the form of micrometastasis and isolated tumour cell (ITC) often goes unnoticed in the routine pathological examination. This limitation can be overcome by using serial sectioning and immunohistochemistry for detection of micrometastasis and ITC in clinically and pathologically node-negative neck. The primary objective was to determine the incidence of micrometastasis and ITC in the selective neck dissection specimen, whereas to determine the levels of lymph nodes involved, depending upon the site of primary tumour, was the secondary objective. MATERIALS AND METHODS: Lymph nodes from selective neck dissection specimen were subjected to serial sectioning and immunohistochemistry with pan-cytokeratin marker. Incidence of micrometastasis and ITC, site and stage of primary tumours and level of lymph nodes involved were determined. RESULTS: In total, 8.8% patients in the study got upstaged after serial sectioning and immunohistochemistry. Tongue and lower alveolar primaries showed the presence of micrometastasis and ITC in neck nodes. All the primary tumours were of pT1 stage. Level IB and II lymph nodes were primarily involved. CONCLUSION: Micrometastasis and isolated tumour cells are found in approximately 9% of cases of early-stage oral cavity squamous cell carcinoma. The predictive factors and clinical significance are still unknown. More prospective trials are required to solve this evolving aspect of HNSCC.

Prognostic value of nodal involvement in patients with oropharyngeal carcinoma according to the HPV status. / Valoración de la capacidad pronóstica de la afectación ganglionar de los pacientes con carcinoma de orofaringe en función del estatus HPV.

BACKGROUND AND OBJECTIVE: Different studies performed in populations with a high incidence of HPV infection have found no prognostic capacity of clinical nodal involvement (cN+) in patients with HPV-positive oropharyngeal carcinomas. The objective of this study was to assess the prognostic ability of nodal involvement in patients with oropharyngeal carcinomas according to HPV status in a cancer population with a low incidence of HPV infection. MATERIAL AND METHODS: Retrospective study of a cohort of 420 patients with oropharyngeal carcinomas treated during the period 1990-2016 for whom information on HPV status was available. RESULTS: 14.8% of the patients included in the study had HPV-positive tumours. In relation to patients without nodal involvement (cN0), nodal involvement at diagnosis (cN+) significantly decreased the specific survival of patients with HPV-negative oropharyngeal carcinomas. Conversely, no differences in survival were found for patients with HPV-positive tumours according to the presence of nodal involvement. A history of toxic consumption did not change the absence of prognostic significance of nodal involvement for patients with HPV-positive tumours. CONCLUSIONS: Regional involvement at the time of diagnosis is not a prognostic variable for patients with HPV-positive oropharyngeal carcinomas.

Extensive lymphatic spread of papillary thyroid microcarcinoma is associated with an increase in expression of genes involved in epithelial-mesenchymal transition and cancer stem cell-like properties.

BACKGROUND: Active surveillance is an alternative management for patents with low-risk papillary thyroid microcarcinoma (PTMC); however, there is an absence of specific molecular markers that predict its progression. We compared gene expression patterns between PTMC with lateral neck-node metastasis (N1b) and PTMC-lacking nodal metastasis (N0). METHODS: We performed oligonucleotide microarray analysis in three PTMCs without cervical lymph-node metastases (N0), and five PTMCs with lateral neck-node metastasis (N1b) at initial diagnosis, using an Illumina HumanHT-12 v4.0 Expression BeadChip. Quantitative real-time PCR (qPCR) and western blot analysis confirmed microarray data. We performed immunohistochemistry (IHC) to confirm protein overexpression in samples from 20 N0 and 24 N1b PTMC patients who underwent thyroidectomy. RESULTS: Microarray analyses identified 52 probes corresponding to 45 genes. Expression of these genes differed significantly between the two PTMC groups. Forty genes were significantly upregulated and five genes were downregulated in N1b PTMC compared to N0. Four genes related to epithelial-to-mesenchymal transition (EMT) and stem cell markers, including ALDH1A3, TM4SF1, PROM1, and CAV1 were significantly upregulated in N1b PTMCs. Real-time qPCR confirmed this expression and western blot analysis confirmed higher expression of ALDH1A3, TM4SF1, PROM1, and CAV1 in N1b than in N0 PTMCs. IHC indicated overexpression of ALDH1A3 and CAV1 in N1b compared to N0 PTMCs. CONCLUSIONS: Genes related to EMT and thyroid cancer stem cell-like properties are upregulated in early extensive lymphatic spread of PTMC.

A nomogram for predicting the risk of neck node metastasis in pathologically node-negative oral cavity carcinoma.

OBJECTIVE: To generate a nomogram for predicting the risk of neck node metastasis in pathologically node-negative patients using a combination of variables comprising of protein expression, ultrastructural alterations and clinicopathological parameters. MATERIALS AND METHODS: Surgically removed oral tumours (n = 103) were analysed for the expression of desmosomal and hemidesmosomal assembly proteins by immunohistochemistry and ultrastructural alterations by transmission electron microscopy (TEM). Protein expression, ultrastructural alterations and clinicopathological variables were used to construct nomogram from the training set in 75 patients. Clinical utility of the nomogram was validated in a discrete set of 28 patients. RESULTS: Univariate and multivariate analyses were performed on the training set, and obtained significant variables comprising of integrin ß4 expression (p = .027), number of hemidesmosomes (p = .027)/desmosomes (p = .046), tumour differentiation grade (p = .033) and tumour thickness (p = .024) were used for construction of the nomogram. The area under the curve was calculated for both training 0.821 (95% CI 0.725-0.918) and validation sets 0.880 (95% CI 0.743-1.000). The nomogram demonstrated a predictive accuracy of 73.3% and 78.6% with the sensitivity of 81.4% and 83.3% in the training and validation sets, respectively. CONCLUSIONS: The nomogram constructed on postsurgical tumour samples will be a value addition to histopathology for the detection of neck node metastasis in pathologically node-negative patients.

Validation of the pathological classification of lymph node metastasis for head and neck tumors according to the 8th edition of the TNM Classification of Malignant Tumors.

OBJECTIVES: One of the main changes in the 8th edition of the TNM Classification for head and neck tumors is the inclusion of extracapsular spread (ECS) as a criterion for evaluating the regional extension, both clinical (cN) and pathological (pN). The objective of our study is to evaluate the prognostic capacity derived from the inclusion of the ECS in the pathological classification of head and neck squamous cell carcinoma (HNSCC) patients treated with a neck dissection, as established by the 8th edition TNM Classification. MATERIALS AND METHODS: Retrospective study of 1188 patients with HNSCC treated with a neck dissection between1990 and 2013. RESULTS: There were lymph node metastasis in 50.1% of the neck dissections. The pathological record revealed ECS in 50.5% of the positive neck dissections. The implementation of the changes of the 8th edition TNM classification produced the upstaging of 20.9% of the patients classified as pN1 with the 7th edition TNM classification to pN2a¸ and the upstaging of 58.4% of the patients classified as pN2 with the 7th edition TNM classification to pN3b. We conducted an objective comparison of the quality of both classifications. The 8th TNM classification edition achieved better results regarding both the discrimination in cause-specific survival between pN categories and in the distribution in the number of cases between categories than the 7th edition TNM classification. CONCLUSION: The inclusion of ECS in the pathological classification (pN) of the neck nodes improves the prognostic capacity of the 8th TNM Classification edition.

Transaxillary robotic modified radical neck dissection: a 5-year assessment of operative and oncologic outcomes.

BACKGROUND: Robotic modified radical neck dissection (MRND) using a gasless transaxillary approach has been reported to be a safe and meticulous technique in patients with papillary thyroid carcinoma (PTC) and lateral neck node metastasis (N1b). Few studies, however, have attempted to assess the long-term oncologic outcomes of robotic MRND in these patients. This study aimed to compare perioperative and 5-year oncologic outcomes of robotic MRND with conventional open procedures in patients with N1b PTC. METHODS: Between September 2007 and February 2010, 193 patients with N1b PTC underwent total thyroidectomy and MRND by a single surgeon. Of these, 42 (21.8 %) underwent robotic procedures and 151 (78.2 %) underwent conventional open procedures. All patients received 3.7- to 5.5-GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBSs), and diagnostic WBS (DxWBSs) during follow-up. An exact 1:3 matching for age and stage was performed to minimize selection bias, and perioperative and 5-year oncologic outcomes were compared in the matched groups. RESULTS: The mean follow-up period was 66.0 months (range 60-90 months). Number of retrieved cervical lymph nodes (LNs) (p = .102) and postoperative ablation success rates (p = .864) were similar between the two groups. TSH-suppressed serum Tg concentrations after 5 years (0.7 ± 1.5 vs. 2.4 ± 14.1 ng/ml; p = .471) and recurrence rates in the robotic and open groups (1/41 [2.4 %] vs. 3/102 [2.9 %]; p = .864) were similar for the 5-year follow-up period. Four patients experienced recurrence: Three exhibited regional lymph node metastasis, and one showed bilateral lung metastases. CONCLUSION: The perioperative and 5-year oncologic outcomes were similar after robotic and conventional open MRND. Large, prospective randomized controlled trials with long-term follow-up data are needed to validate these results.

A scoring system for prediction of lateral neck node metastasis from papillary thyroid cancer.

Lateral neck node metastasis is an important prognostic factor in thyroid carcinoma. We developed a scoring system for use in prediction of lateral neck node metastasis from papillary thyroid cancer. In this study, 161 consecutive patients were included in the training data set. This scoring system, named the Yonsei Estimated Value (YEV) for lymph node metastasis in papillary thyroid cancer, was developed on the basis of results from multivariate logistic regression analysis of preoperative clinical and radiologic data. Sixty eight consecutive patients were included for testing of the validity of the scoring system. The equation for prediction of lateral neck node metastasis was follows:YEV (Yonsei Estimated Value) = 1/(1+X)X = Exp (5.333-[0.902 × sex]+[0.036 × age]-[1.020 × tumor size]-[0.177 × lymph node size]-[0.032 × lymph node density])When the YEV was 0.3 or more, the probability of lateral neck node metastasis was 79.0%, with sensitivity of 76.3%, specificity of 69.8%, positive predictive value of 56.7%, and negative predictive value of 85.1% in the training set. When fine needle aspiration biopsy for suspicious lateral neck nodes is not possible, or the results are inadequate, our scoring system for prediction of lateral neck node metastasis can be helpful in optimization of the surgical extent for each patient.

Pattern of Lateral Neck Metastasis and Predictors of Level V Metastasis in Papillary Thyroid Carcinoma / 대한내분비외과학회지

PURPOSE: Cervical lymphadenectomy is frequently performed in patients with lateral cervical lymph node metastasis to improve regional control of disease. However, there is controversy regarding appropriate levels of the neck that need to be dissected. In particular, the routine dissection of level V remains an annoying and time consuming procedure due to the injury of the spinal accessory nerve. METHODS: To identify clinical and pathological predictors of cervical node metastases to level V in papillary thyroid carcinoma, we analyzed 42 patients who underwent modified radical neck dissection (MRND), which were separately performed by each strict anatomical level. Five patients underwent both MRND, 29 patients received total thyroidectomy with central neck node dissection and MRND at the time of initial operation. Thirteen patients underwent MRND later when lateral neck metastases were found at the follow-up after total thyroidectomy with central neck node dissection. RESULTS: In our series, 11.9% of neck specimens harbored metastatic thyroid carcinoma at level V. The metastatic rate of level II, III, and IV was 54.7%, 85.7%, and 64.2%, respectively. The presence of level V metastases was not significantly associated with level II, III metastases, age, sex, and histopathologic findings. But, it seemed to be associated with level IV metastases if the proportion of metastasis of level IV exceeded 50%. CONCLUSION: Cervical node metastasis seems to be associated with level IV metastases if the proportion of metastasis of level IV exceeds 50%.

A Scoring System for Prediction of Lateral Neck Node Metastasis from Papillary Thyroid Cancer

Lateral neck node metastasis is an important prognostic factor in thyroid carcinoma. We developed a scoring system for use in prediction of lateral neck node metastasis from papillary thyroid cancer. In this study, 161 consecutive patients were included in the training data set. This scoring system, named the Yonsei Estimated Value (YEV) for lymph node metastasis in papillary thyroid cancer, was developed on the basis of results from multivariate logistic regression analysis of preoperative clinical and radiologic data. Sixty eight consecutive patients were included for testing of the validity of the scoring system. The equation for prediction of lateral neck node metastasis was follows: YEV (Yonsei Estimated Value) = 1/(1+X) X = Exp (5.333-[0.902 x sex]+[0.036 x age]-[1.020 x tumor size]-[0.177 x lymph node size]-[0.032 x lymph node density]) When the YEV was 0.3 or more, the probability of lateral neck node metastasis was 79.0%, with sensitivity of 76.3%, specificity of 69.8%, positive predictive value of 56.7%, and negative predictive value of 85.1% in the training set. When fine needle aspiration biopsy for suspicious lateral neck nodes is not possible, or the results are inadequate, our scoring system for prediction of lateral neck node metastasis can be helpful in optimization of the surgical extent for each patient.

Radiotherapy of Neck Node Metastases from an Unknown Primary Cancer / 대한방사선종양학회지

PURPOSE: The aim of this retrospective analysis was to analyze the results of radiotherapy administered to patients with neck node metastases from an unknown primary cancer, with or without neck dissection. MATERIALS AND METHODS: From January 1986 to December 2005, 88 patients with neck node metastases from an unknown primary cancer were treated with curative intent. The age of the patients ranged from 35 to 74 years (median age, 59 years). There were 74 male and 14 female patients. Distribution of patients by N status was as follows: N1, 4 patients; N2a, 10 patients; N2b, 48 patients; N2c, 8 patients; N3, 18 patients. Fifty-one patients underwent neck dissection and 37 patients had only a biopsy (31 patients had fine-needle aspiration and 6 patients had an excisional biopsy). All patients received radiotherapy. The follow-up time ranged from 1 to 154 months, with a median time of 32 months. RESULTS: The overall survival (OS) and disease-free survival (DFS) rate at 5 years were 43.9% and 41.7%, respectively. The factors associated with the OS rate were neck dissection, and a subsequent primary tumor. Factors associated with the DFS rate were N stage, neck dissection, and a subsequent primary tumor. Neck failure was noted in 15 patients, distant metastases in 18 patients, and a subsequent primary tumor in 8 patients. CONCLUSION: With comprehensive radiotherapy given to the bilateral neck and the potential mucosal sites, good survival rates can be obtained in patients with neck node metastases from an unknown primary cancer. However, considering the side effects, a randomized trial is required to determine the optimal radiotherapy volume.

Treatment Results and Patterns of Failure after Surgery for the Squamous Cell Carcinoma of Hypopharynx / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Radical surgery with radiotherapy is regarded as a standard treatment modality of hypopharyngeal squamous cell carcinoma. However, reports on results of treatment and patterns of failure after surgery for hypopharyngeal cancer are lacking. PATIENTS AND METHODS: From July 1992 to December 1998, 39 previously untreated hypopharyngeal carcinoma patients were treated with surgery with or without postoperative radiotherapy at Severance Hospital. Ten were treated with surgery alone, RESULTS: The overall 5-year survival rate was 58.1%, of which 47.2% accounted for the group who received surgery only and 64.6% for the group who received surgery plus postoperative radiotherapy. Survival was best for posterior pharyngeal wall cancer (64.6%) and worst for pyriform sinus cancer (56.1%). Recurrence was noted in 31% (12/39) of the cases. The most common Failure site was the neck, Among the neck failures, three unusual retropharyngeal and paratracheal nodal failures were noted. CONCLUSION: Treatment with radical surgery may improve survival of patients with this notorious cancer. The extent of neck dissection for hypopharyngeal carcinoma may need to be evaluated with future trials. (Korean J Otolaryngol 2000; 43: 528-34)

Angiogenesis, Cellular Proliferation Index and Expression of nm23, p53 according to Lymph Node Metastasis in Supraglottic Cancer / 대한이비인후과학회지

BACKGROUND: Squamous cell carcinoma of the supraglottic larynx have a propensity to metastasize earlier to the regional lymph nodes compared to their glottic counterpart owing to their unique embryological origin and abundant lymphatic tissues. However, reliable biological markers for predicting lymph node metastasis with its associated poor outcome is lacking. OBJECTIVES: As a search for biologic markers related to nodal metastasis in supraglottic cancer, the authors have performed immunohistochemical staining of various gene products and tissue factors. The results were analysed to see if these markers influenced the metastatic capability of supraglottic cancers. MATERIALS AND METHODS: Twenty-nine cases of supraglottic cancers were subdivided into node negative group(group I, N=13) and node positive group(group II, N=16). Tumor angiogenesis was assessed by counting the peritumoral microvessels in which the endothelial cells are selectively stained by von Willebrand factor. PCNA-proliferation index(PI) was obtained, and the positivity of nm23 protein, a metastasis suppressor gene product and p53 protein, a tumor suppressor gene product were assessed. RESULTS: The mean vessel counts per high power fields(X 200) were 16.6 and 27.3 for node negative and node positive groups respectively(p=0.001). The mean PCNA-PI was 8.1 in node negative group and 18.4 in the node positive group(p=0.001). The expression of nm23 was 30.8% in the node negative group and 50.0% in the node positive group. p53 expression rate was higher in the node positive group; 50.0% compared to the node negative group; 38.5%, however there was no statistical significance. CONCLUSION: We conclude that the number of new vessels and PCNA-proliferation index, but not the nm23 and p53 expression rate, may be related to the lymph node metastasis in squamous cell carcinoma of the supraglottic larynx.

Metastatic Carcinoma of the Neck Node from an Unknown Primary Site / 대한치료방사선과학회지

From 1980 to 1986, 26 patients with metastatic carcinoma of the neck node from an unknown primary site were seen in the Department of Therapeutic Radiology of Seoul National University Hospital. Among these, three patients were excluded from further analysis due to incomplete treatment. So a retrospective analysis was undertaken on 23 patients who had complete treatment with radiation therapy alone or in combination with surgical treatment and chemotherapy. The overall three year actuarial survival rate was 32%. According to the staging system of the American Joint Committee on Cancer, the three year survival rates with N2 and N3 patients were 43% and 13%, respectively. In 16 patients with squamous cell carcinoma and seven with non-squamous cell carcinoma, the three year survival rates were 34% and 29%, respectively. Analysis according to site of nodal involvement was also done. Patients with cervical node and supraclavicular node involvement recorded 44% and 17% of three year survival rate, respectively. In the study, six patients eventually manifested the primary sites (three in the lung, one in the esophagus, one in the stomach, one in the nasopharynx). Presence of the primary site seemed to influence the prognosis (17% vs 38%). In analyzing the prognostic factors, the nodal stage and site of nodal involvement were important prognostic factors, and the presence of a primary site seemed to influence the patients' survival, but histology did not.