Neck Dissection Specimens Research Articles

Primary tumor lymphangiogenesis in oral squamous cell carcinoma with N0 neck is the key determinant of its therapeutics.

Vascular Endothelial Growth Factor-C (VEGF-C) plays a critical role in tumor growth and invasion through lymphangiogenesis and helps to identify the variability of lymphatic potential of oral squamous cell carcinoma (OSCC) cases with or without lymph node metastasis. A total of 65 cases of OSCC were included. The clinical details were obtained from patient records. The cases were grouped as N0 versus any N categories. All the cases were immunohistochemically evaluated for VEGF-C within the primary tumor using a standard protocol. An average of 5 lymph nodes were dissected from all neck dissection specimens and were evaluated histopathologically. The data obtained were statistically evaluated at 95% confidence interval and P ≤ 0.05. 100% cases in our study showed VEGF-C immunopositivity. The immunoreactivity increased linearly with advancing grades. A total of 31 out of 40 N0 OSCC revealed score 2 (26%-50%) of VEGF-C immunoreactivity. Eighteen cases were false negative clinically. Recognition of locoregional spread may empower clinicians for correct therapeutic decisions in N0 versus any N case.

FDG PET-CT for the Detection of Occult Nodal Metastases in Head and Neck Cancer: A Systematic Review and Meta-Analysis.

Because of an estimated 20-30% prevalence of occult lymph node (LN) metastases in patients with head and neck squamous cell carcinoma (HNSCC), neck dissection is often proposed, despite its potential morbidity. In this systematic review and meta-analysis, the diagnostic performance of FDG PET-CT in detecting occult LN metastases was evaluated in patients with clinically negative necks (cN0) and in whom histopathology of a neck dissection specimen served as gold standard. Overall, 16 studies out of 2062 screened on PubMed and EMBASE fulfilled the inclusion criteria (n = 1148 patients). Seven of these sixteen studies were split into two or three studies because they contained data that could be processed distinctly in our meta-analysis. For this reason, a total of 25 studies were identified and included in the analysis (n total = 1918 patients). The overall prevalence of metastatic nodes per patient was 22.67%. The pooled sensitivity, specificity, diagnostic odds ratios, and negative predictive value (NPV) were 0.71 (95%CI: 0.66-0.75), 0.90 (95%CI: 0.84-0.93), 20.03 (95%CI: 13.51-29.70), and 0.92 (95%CI: 0.89-0.95), respectively. The main causes of inter-study heterogeneity included different reference standards (evaluation per patient, per neck side, or per neck level). The current meta-analysis showed that FDG PET-CT has a high specificity and NPV for ruling out nodal involvement in cN0 necks, but a limited sensitivity.

Clinicopathological study on diameter of extranodal extension of cervical metastatic lymph nodes in the prognosis of oral cancer

ObjectivesTo investigate the relationship between the degree of destruction of the cervical lymph node capsule, extranodal invasion distance, and the prognosis of extranodal extension (ENE)-positive patients Study designWe retrospectively examined microscopic slides from neck dissection specimens of ENE-positive patients of our hospital. The ENE distance was measured by a pathologist who set up a virtual lymph node and measured the maximum extranodal invasion distance. The maximum distance was used for multiple ENEs. Forty patients with ENE were enrolled in this study. The Kaplan–Meier method was used to estimate survival. ResultsAmong the ENE-positive cases, the capsule was completely destroyed and partially destroyed in seven and 33 cases, respectively. Disease-specific survival (DSS) was 1251 days (range 156–3009 days). The median distance of extranodal invasion was 2500 µm (392–8500 µm) in the 33 ENE-positive cases in which the capsule was not completely destroyed. Receiver operating characteristic curve analysis of these 33 cases showed that the cutoff value of extranodal invasion distance for progression-free survival was 2241 µm. ConclusionsENE is a prognostic predictor of oral cancer; ENE was an independent prognostic factor; and ENE size cutoff of 2241 µm was a significant prognostic factor.

Elective Neck Dissection in Patients Undergoing Salvage Laryngectomy: Outcomes, Complications, and Considerations.

Objective In this study, we sought to identify the predictors for occult nodal disease (OND) and compare oncologic outcomes in patients undergoing elective neck dissection (END)at the time of salvage laryngectomy (SLE) versus the observation group. Methods A retrospective chart review was conducted involving all patients with clinically node-negative (cN0) necks who underwent SLE at atertiary academic center over 12 years. A total of 58 patients met the inclusion criteria and were divided into two groups: END (n=39) and observation (n=19). Primary endpoints were OND, regional recurrence-free survival (RRFS), and disease-specific survival (DSS). Univariate analysis was performed to establish the association between variables with Fisher's exact test and Mann-Whitney U test. Survival analysis was performed with the log-rank test. Results The cohort comprised 46 (79.3%) males and 12 (20.7%) females, with a mean age of 60 years. Pathological nodal disease was identified in five of 71 (7%) examined neck dissection specimens, with positive nodes found in levels II through IV. The only statistically significant predictor of OND was the rT3/rT4 stage (p=0.017). There were no differences in perioperative complications, RRFS (p=0.216), or DSS (p=0.298) between the END and observation groups. Conclusions In cN0 necks, the advanced recurrent T-stage (rT3-rT4) is a predictor for OND. As OND was found involving levels II, III, and IV in this study's specimens,formal lateral neck dissection should be the procedure of choice if END is to be performed alongside SLE. While END did not show a significantly higher morbidity profile versus conservative management in this cohort, the procedure did not improve loco-regional control or survival, even when stratifying by tumor stage.

Submandibular Gland-Sparing Technique Versus En-Bloc Level IB Dissection in Oral Cavity Cancers with N0 Neck Status: A Randomized Controlled Trial.

Metastases to the submandibular gland (SMG) from oral cavity primaries are very rare. Hence, a gland-preserving level IB dissection technique is a feasible option without compromising the lymph node yield (LNY). To assess the feasibility and noninferiority of the SMG-preserving dissection technique to the conventional en bloc removal of level IB in terms of LNY in patients with cN0 oral squamous cell carcinoma (OSCC) undergoing elective neck dissection. Parallel-design, single-center, open-label, randomized controlled trial. Tertiary care health care center-Department of Otorhinolaryngology-Head & Neck Surgery, AIIMS Rishikesh. Thirty-eight (n = 38) participants with 46 (n = 46) neck dissection specimens of OSCC were randomly allocated (1:1) into gland-preserving (n1 = 23) and en bloc (n2 = 23) dissection groups. Elective neck dissection comparing SMG-sparing level IB dissection technique versus en bloc level IB dissection. LNY, lymph node density, and level IB operative time in both groups were compared between groups (α < .05). Median LNY (P = .543) and lymph node density (P = 1.000) in level IB did not show significant differences between the groups. LNY in level IB by gland-preserving technique is also not inferior to the conventional en bloc dissection technique (mean difference = 0.217; 95% CI: [-0.597, 1.032]; P = .593). The mean level IB operative time is significantly longer in the gland-preserving group (P < .001). None of the examined SMGs were involved by the tumor. SMG-preserving technique is noninferior to the traditional technique of level IB clearance and can be used in elective neck dissections without compromising the LNY. Functional neck dissection has greatly evolved to decrease patient morbidity, and this method can be adopted in case-specific situations. The trial was registered in the Clinical Trials Registry-India (CTRI/2022/05/042344) on May 2, 2023, https://ctri.nic.in/.

Prognostic evaluation of tumour budding in oral squamous cell carcinoma: Evidenced by CD44 expression as a cancer stem cell marker

ObjectivesTumor budding is a sign of invasion and early step for metastasis of many cancers including oral squamous cell carcinoma (OSCC). Evidences suggest the presence of cancer stem cells in tumor buds. CD44 has been reported in tumor growth and metastasis as a cancer stem cell marker in OSCC. The study aims to highlight the prognostic significance of tumor budding in association with CD44 expression as a cancer stem cell marker in OSCC. MethodsA total of 60 radical neck dissection specimens of OSCC with and without lymph node metastasis were included in the study. The sections were evaluated for TB [Tumor Budding] in H&E and CD44 expression immunohistochemically. OSCC cases were then correlated with clinicopathologic and histomorphologic parameters such as age, gender, habit, site, staging, grading, recurrence, depth of invasion, pattern of invasion, and survival outcomes. Comparison of prognosis and CD44 expression were carried out by statistical methods. ResultsA high TB score was significantly correlated with grading (p = 0.037), POI [Pattern of invasion] (0.029), overall survival (p = 0.047). CD44 over expression showed strong correlations with POI (1HPF:p = 0.037;10HPF:p = 0.027), grading (p = 0.037), and overall survival (p = 0.047). Kaplan-Meier analysis revealed overall survival advantage for LTB [Low TB] (85 %) with OSCC compare to HTB [High TB] (75 %) for > 36 months. ConclusionAssessment of TB is effective in predicting prognosis of OSCC. Although CD44 expression has demonstrated strong prognostic influence, there were significant differences in its expression with the parameters.

The Impact and Prognostic Significance of Extra-Nodal Extension in Clinically N0 Oral Cancer: A Prospective Clinical Study.

Oral cavity squamous cell carcinoma (OCSCC) demonstrates a high propensity to metastasize to regional lymph nodes. Despite technological and scientific advances, identification of pathological adverse features preoperatively remains elusive. This study intended to identify the true occurrence of extra-nodal extension (ENE) in clinically and radiologically N0 OCSCC patients and to investigate its impact and prognostic significance. A prospective, single-centre, non-randomized study was conducted at a tertiary cancer centre in South India to include all untreated operable patients of OCSCC without clinical, radiological, or cytological evidence of nodal metastasis (cN0). All the patients underwent tumor resection surgery with neck dissection and received adjuvant therapy when indicated. Patients were followed up and neck dissection specimens were histopathologically analyzed. The primary outcome was to assess the presence of ENE in cN0 OCSCC patients and its extent. The secondary outcomes were 2-year disease-free survival (DFS) and tumor characteristics. A total of 237 patients with operable OCSCC were evaluated. Out of these, 80 patients who were clinically and radiologically N0 were included in the study and they underwent tumor resection surgery and neck dissection. The final histopathological evaluation revealed that 21.25% of patients (n = 17) had metastatic neck disease and 7.5% of patients (n = 6) had ENE, and all were reported as microscopic ENE. Within the node-positive group, the 2-year DFS for patients with and without ENE were 50% and 90.9%, respectively (p = 0.0362). The results suggest that ENE remains a strong predictor of adverse outcomes, recurrence, and survival in oral cancer patients.

Association of Cervical Lymph Node Metastasis and Perineural Invasion in Patients with Oral Cavity Squamous Cell Carcinoma

Background: Cervical lymph node metastasis (CLNM) is one of the key prognostic factors in oral squamous cell carcinoma and positive perineural invasion (PNI) is a predictor of cervical lymph node metastasis, recurrence, and decline-free survival. This study determines perineural invasion association with cervical lymph node metastasis in oral cavity squamous cell carcinoma (OCSCC). Method: We analyzed the laboratory data collected from the surgical pathology files of a tertiary care hospital in Karachi. This retrospective study included all diagnosed cases of OCSCC that underwent cervical lymph node dissection during the 10-year period from June 2008 to March 2019. The cases were characterized according to age, gender, perineural invasion, and lymph node metastasis. The data was analyzed using SPSS and Chi-Square test was used to find the association between the cervical lymph node metastatic and PNI status. Results: A total of 527 diagnosed cases of OCSCC with cervical neck dissection were found. It is evident from our study that OCSCC with neck dissection specimens is frequently seen in males, mostly belonging to the middle adult age group followed by young adults. Of the 527 cases, 165 showed PNI (31.3%), and 20% of the PNI cases were positive for cervical lymph node metastasis, while 40% showed benign cervical lymph nodes with negative PNI. Conclusion: This study highlights the single parameter of PNI and its association with cervical lymph node metastasis and showed a significant relationship between perineural invasion and cervical lymph node metastatic status (p &lt; .001).

Histopathological Analysis of Nodal Disease After Chemoradiation Reveals Viable Tumor Cells as the most Important Prognostic Factor in Head and Neck Squamous Cell Carcinoma

BackgroundIn head and neck squamous cell carcinoma (HNSCC), salvage neck dissection (ND) is required after primary chemoradiation in case of residual nodal disease. Upon histopathological examination, viability of tumor cells is assessed but little is known about other prognostic histopathological features. In particular, the presence of swirled keratin debris and its prognostic value is controversial. The aim of this study is to examine histopathological parameters in ND specimens and correlate them with patient outcome to determine the relevant parameters for histopathological reporting.Materials and MethodsSalvage ND specimen from a cohort of n = 75 HNSCC (oropharynx, larynx, hypopharynx) patients with prior (chemo) radiation were evaluated on H&E stains for the following parameters: viable tumor cells, necrosis, swirled keratin debris, foamy histiocytes, bleeding residues, fibrosis, elastosis, pyknotic cells, calcification, cholesterol crystals, multinucleated giant cells, perineural, and vascular invasion. Histological features were correlated with survival outcomes.ResultsOnly the presence / amount (area) of viable tumor cells correlated with a worse clinical outcome (local and regional recurrence-free survival, (LRRFS), distant metastasis-free survival, disease-specific survival, and overall survival, p < 0.05) in both the univariable and multivariable analyses.ConclusionWe could confirm the presence of viable tumor cells as a relevant negative prognostic factor after (chemo) radiation. The amount (area) of viable tumor cells further substratified patients with worse LRRFS. None of the other parameters correlated with a distinctive worse outcome. Importantly, the presence of (swirled) keratin debris alone should not be considered viable tumor cells (ypN0).

Carotid Sheath Dissection and Histopathology During Neck Dissection in Head and Neck Carcinomas.

To investigate the carotid sheath in neck dissection (ND) specimens histopathologically in patients with head and neck carcinomas who had no evidence of previous neck surgery or direct involvement of the carotid sheath in their pre- or intra-operative evaluations. In this study, carotid sheath (CS) specimens of 40 patients with head and neck carcinomas (HNCA) who, depending on the condition of the primary tumor, required unilateral or bilateral elective or therapeutic selective neck dissection were histopathologically investigated by an expert head and neck pathologist to find any lymphoid or thyroid like tissue or tumor cells infiltration. A total of 50 carotid sheath (CS) specimens were investigated. None of the samples showed any evidence of tumor infiltration or accumulation of lymphatic tissue. We conclude that in patients with no histopathologic involvement of the carotid sheath in pre-operative or intra-operative tumor invasion, it is not necessary to remove CS in routine neck dissection.

Investigation of locoregional metastatic behavior in low-grade malignant tumors of the parotid gland

BackgroundThe aim of the study was to investigate primary locoregional metastatic behavior in a large sample of low-grade malignant tumors of the parotid gland following surgical treatment consisting of complete parotidectomy and neck dissection. MethodsThe records of all patients treated for low-grade malignant tumors of the parotid gland by complete parotidectomy and neck dissection between 2007 and 2022 were studied retrospectively. Results94 patients formed our study sample (50 females, 44 males, female to male ratio: 1.14). The mean age was 59 years (range 15–95 years). The mean number of lymph nodes in the specimen from complete parotidectomy was 3.33 (range: 0–12). The mean number of involved lymph nodes in the parotid gland was 0.05 (range: 0–1). The mean number of lymph nodes in the specimen from the ipsilateral neck dissection was 16.2 (range 4–42). The mean number of involved lymph nodes in the neck dissection specimen was 0.09 (range: 0–2). Comparison of T1-T2 vs. T3-T4 cases revealed no statistically significant difference concerning the tumorous involvement of the lymphatic network (x2 = 0.719, p = 0.396). ConclusionLow-grade primary malignant tumors of the parotid gland are characterized by an initially low metastatic potential, which justifies conservative forms of surgical treatment.

Rate of occult neck nodal metastasis in primary and salvage laryngectomy.

Rate of occult neck nodal metastasis in primary and salvage laryngectomy.

Analiza limfocitarnog infiltrata kao prediktivnog faktora pojave metastaza na vratu kod oralnog skvamocelularnog karcinoma

Introduction: Carcinoma of the stratified squamous epithelium of the oral cavity - oral squamous cell carcinoma (OSCC) is an invasive pathological lesion of the epithelium with varying degrees of squamous differentiation. It is characterized by early and extensive metastases, infiltration of adjacent anatomical structures, frequent recurrences, and a relatively low five-year survival rate of less than 50%. The aim of the study to determine the correlation between the analysis of the lymphocytic infiltrate of biopsy specimens with pathohistologically proven metastases of oral squamous cellular carcinoma on postoperative neck dissection specimens. Material and methods: The study included 42 patients with pathohistologically verified oral squamous cellular carcinoma who underwent surgery at the Department of Maxillofacial Surgery of the Clinic of Dental medicine in Niš in the period from 2018 to 2022. The histopathological analysis included the depth of tumor invasion, histopathological analysis of the lymph nodes of neck dissections, analysis of lymphocytic infiltration, and presence of lymphovascularand perineural invasion. Results: It was determined that the depth of invasion is statistically significantly different regarding the degree of lymphocytic infiltration (p=0.004). Invasion of over 4mm was present in 20% of patients with high infiltration, 44.4% of patients with medium infiltration, and 85.7% of patients with low infiltration. Conclusion: Given that the results of the study indicate that the analysis of the lymphocytic infiltrate can be a reliable predictive factor of the appearance of metastases in the lymph nodes of the neck, further research should be directed toward as sociating lymphocytic infiltration with certain biochemical and genetic parameters based on which a plan can be created for neck treatment in the N0 stage of oral squamous cellular carcinoma.

Prediction of extranodal extension in oropharyngeal cancer patients and carcinoma of unknown primary: value of metabolic tumor imaging with hybrid PET compared with MRI and CT.

The aim of this study was to investigate the value of metabolic tumor imaging using hybrid PET for the preoperative detection of extranodal extension (ENE) in lymph node metastases of oropharyngeal squamous cell carcinoma (OPSCC). We performed a retrospective analysis of a consecutive cohort of patients with OPSCC treated with primary surgery with or without adjuvant (chemo-) radiotherapy at the Kantonsspital Sankt-Gallen and the University Hospital Zurich, Switzerland, from 2010 until 2019. Hybrid PET was compared to conventional cross-sectional imaging with MRI and CT. Histopathological presence of ENE of neck dissection specimen served as gold standard. A total number of 234 patients were included in the study, 95 (40.6%) of which had pathological ENE (pENE). CT has a good specificity with 93.7%; meanwhile, MRI was the most sensitive diagnostic method (72.0%). The nodal metabolic tumor parameters (SUVmax, TLG, MTV) were significantly higher in patients with positive ENE (p < 0.001 for all three parameters) than in patients with negative ENE (p < 0.001, for all three parameters). CT achieved the best specificity, while MRI had the best sensitivity to detect ENE. Nodal metabolic tumor parameters differed significantly between ENE-positive/negative and p16-positive/negative patients. Hence, quantitative data obtained by metabolic imaging might predict presence of ENE and, therefore, could be helpful in customizing therapy management.

Specific Selective Neck Dissection for Isolated Regional Failure in Nasopharyngeal Carcinoma after Radiation.

To assess whether specific selective neck dissection (SND) with involved levels is a feasible treatment for isolated regional failure in nasopharyngeal carcinoma (NPC) after radiation. Between January 2011 and December 2019, a total of 46 patients were assigned to undergo SND in the Department of Head and Neck Surgery at our center. The dissection extent of specific SND usually only involved levels of lymph node sites for isolated regional failure; in addition, lesions of level II or III involved removing both level II and III lymph nodes. The patients' clinical, MRI and pathological characteristics, overall survival (OS), disease-free survival (DFS) and regional-free survival (RFS) were evaluated and analyzed. Level II was the most commonly involved cervical nodal region in 28 neck dissection specimens (54.9%), followed by level III with positive nodes in 11 specimens (21.6%). Eleven patients (34.8%) had post-SND locoregional recurrence without distant metastasis. Of the patients, 7 patients (30.4%) had regional recurrence, and only one patient (2.8%) had lymph node recurrence on the side of SND. In addition, 8 patients (17.4%) had post-SND distant metastasis. The OS, DFS, and RFS of the patients were 76.1%, 58.7%, and 69.6%, respectively, at 3 years. The OS, DFS, and RFS values of patients who underwent SND were similar to those of patients who underwent comprehensive neck dissection (CND) and/or SND in published articles. Specific SND was shown to be an effective and feasible treatment for isolated regional failure in NPC.

Node Count as a Quality Indicator in Surgically Treated Mucosal Head and Neck Squamous Cell Cancer.

A yield of ≥18 nodes from neck dissection has been shown to be associated with improved locoregional recurrence rates and survival. We sought to determine factors associated with lymph node yields below this threshold. A retrospective review of patients who underwent neck dissection as part of definitive surgical treatment for mucosal head and neck squamous cell carcinoma (SCC) between January 2015 and December 2018 at an academic tertiary referral center was performed. Patients with a history of prior radiation or neck dissection were excluded. There were 412 neck dissections performed in 323 patients. Specimens containing <18 nodes decreased from 16.2% in 2015-2016 to 7.4% of neck dissections in 2017-2018. The proportion of neck dissections removing <3 levels decreased from 9.1% of neck dissections in 2015-2016 to 4.0% in 2017-2018. Multivariable regression analysis demonstrated that dissection of ≥3 levels (OR=0.2 [0.1-0.4]) and neck dissection in 2017-2018 compared to 2015-2016 (OR=0.4 [0.2-0.8]) were significantly associated with a lower odds of <18 nodes. Stage, site, race, sex, human papillomavirus status, positive nodes, surgeon volume, and pathologist volume were not associated with neck dissection specimens with <18 nodes, after controlling for all other variables. Increased recognition of the importance of node count as a quality indicator, and the extent of neck dissection is associated with increased nodal yield from neck dissection. These data suggest that node count can be used as a quality measure of neck dissection for mucosal SCC. 4 Laryngoscope, 133:2160-2165, 2023.

High-Accuracy Nodal Staging of Head and Neck Cancer With USPIO-Enhanced MRI: A New Reading Algorithm Based on Node-to-Node Matched Histopathology.

Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) is a potential diagnostic tool for lymph node assessment in patients with head and neck cancer. Validation by radiologic-pathologic correlation is essential before the method is evaluated in clinical studies. In this study, MRI signal intensity patterns of lymph nodes are correlated to their histopathology to develop a new USPIO-enhanced MRI reading algorithm that can be used for nodal assessment in head and neck cancer patients. Ten head and neck cancer patients underwent in vivo USPIO-enhanced MRI before neck dissection. An ex vivo MRI of the neck dissection specimen was performed for precise coregistration of in vivo MRI with histopathology. Normal clinical histopathological workup was extended with meticulous matching of all lymph nodes regarded as potentially metastatic based on their in vivo MRI signal intensity pattern. On the basis of histopathology of resected nodes, in vivo MRI signal characteristics were defined separating benign from malignant lymph nodes. Fifteen of 34 node-to-node correlated lymph nodes with remaining signal intensity on T2*-weighted MRI were histopathologically metastatic and 19 were benign. Radiological analysis revealed that metastatic lymph nodes showed equal or higher MRI signal intensity when compared with lipid tissue on T2*-weighted MGRE sequence (15/16 lymph nodes; 94%), whereas healthy lymph nodes showed lower (17/19 lymph nodes; 89%) or complete attenuation of signal intensity (273/279; 98%) when compared with lipid tissue on T2*-weighted MGRE. Histopathology of all resected specimens identified 392 lymph nodes. Six lymph nodes with (micro)metastases were missed with in vivo MRI. Whether these 6 lymph nodes were correlated to a nonmalignant lymph node on in vivo MRI or could not be detected at all is unclear. We developed a new reading algorithm to differentiate benign from malignant lymph nodes in head and neck cancer patients on the basis of their appearance on high-resolution T2*-weighted USPIO-enhanced MRI. Next steps involve validation of our reading algorithm to further improve the accuracy of neck lymph node staging with USPIO-enhanced MRI in prospective clinical studies with larger number of patients.

Frequency and Consequences of Cervical Lymph Node Overstaging in Head and Neck Carcinoma.

Clinical lymph node staging in head and neck carcinoma (HNC) is fraught with uncertainties. Established clinical algorithms are available for the problem of occult cervical metastases. Much less is known about clinical lymph node overstaging. We identified HNC patients clinically classified as lymph node positive (cN+), in whom surgical neck dissection (ND) specimens were histopathologically negative (pN0) and in addition the subgroup, in whom an originally planned postoperative radiotherapy (PORT) was omitted. We compared these patients with surgically treated patients with clinically and histopathologically negative neck (cN0/pN0), who had received selective ND. Using a fuzzy matching algorithm, we identified patients with closely similar patient and disease characteristics, who had received primary definitive radiotherapy (RT) with or without systemic therapy (RT ± ST). Of the 980 patients with HNC, 292 received a ND as part of primary treatment. In 128/292 patients with cN0 neck, ND was elective, and in 164 patients with clinically positive neck (cN+), ND was therapeutic. In 43/164 cN+ patients, ND was histopathologically negative (cN+/pN−). In 24 of these, initially planned PORT was omitted. Overall, survival did not differ from the cN0/pN0 and primary RT ± ST control groups. However, more RT ± ST patients had functional problems with nutrition (p = 0.002). Based on these data, it can be estimated that lymph node overstaging is 26% (95% CI: 20% to 34%). In 15% (95% CI: 10% to 21%) of surgically treated cN+ HNC patients, treatment can be de-escalated without the affection of survival.

Novel pathological predictive factors for extranodal extension in oral squamous cell carcinoma: a retrospective cohort study based on tumor budding, desmoplastic reaction, tumor-infiltrating lymphocytes, and depth of invasion

BackgroundExtranodal extension (ENE) is a poor prognostic factor for oral squamous cell carcinoma (OSCC). Identifying ENE by clinical and/or radiological examination is difficult, thereby leading to unnecessary neck dissections. Currently, no definitive predictors are available for ENE. Thus, we aimed to determine the histological predictors of ENE by routine histopathological examination using biopsy and surgically resected specimens.MethodsThis retrospective study included 186 surgically resected OSCC and 83 matched biopsy specimens. Clinical features associated with the tumor microenvironment, including desmoplastic reaction (DR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs), were evaluated using hematoxylin and eosin-stained primary OSCC and neck dissection specimens. These histological features were divided into two groups: DR-immature (DR-I) and DR-mature (DR-M); TB-high (TB-H) and TB-low (TB-L); and TILs-low (TILs-L) and TILs-high (TILs-H). Clinical depth of invasion (cDOI) and pathological DOI (pDOI) were adapted for biopsies and resections, respectively; DOI was evaluated as DOI > 10 mm and DOI ≤ 10 mm. The clinicopathological relationships between these histopathological features and ENE and the independent risk factors for ENE were analyzed. The histological predictors of ENE were evaluated.ResultsThe histological status of DR, TILs, and TB present in biopsy and resection specimens showed high accuracy with that of ENE. DR-I, TILs-L, and TB-H were significantly associated with lymph node metastasis, cDOI, and pDOI. Bivariate and multivariate analyses revealed that TB-H and pDOI > 10 mm in resections were independent factors for the presence of ENE (ENE +). The combination of TB-H/pDOI > 10 mm in resection specimens showed high specificity (91%) and accuracy (83%) regarding ENE + . Although there proved to be no independent factors in biopsies, DR-I and TILs-L were significantly associated with ENE + (p < 0.001). The combination of DR-I/TILs-L/cDOI > 10 mm in biopsies exhibited high sensitivity and specificity with ENE + (70% and 77%, respectively, p < 0.001). These histological predictors could detect even minor ENE (< 2 mm).ConclusionsThe tumor microenvironment status in primary OSCC was significantly associated with that of ENE, and TB-H was an independent risk factor for ENE. The histological status of DR-I/TILs-L/cDOI > 10 mm in biopsy specimens and TB-H/pDOI > 10 mm in resection specimens is a useful predictor of ENE.

Management of malignant submandibular gland tumors: A 30-year experience from a single center

Owing to histologic heterogeneity, biological behavior, and rarity, recommendations for the treatment of malignant submandibular gland tumors (MSGT) are inconsistent. The aim of this study was to present a single-center experience in the treatment of MSGT with an emphasis on surgical treatment, including indication on elective neck dissection (END). Twenty-four MSGT were primary surgically treated (gland excision with neck dissection). Their records were retrospectively collected and analyzed. The most frequent histology was adenoid cystic carcinoma (41.6%), followed by mucoepidermoid carcinoma (25%) and carcinoma ex pleomorphic adenoma (16.7%). There were 18 elective and 6 therapeutic neck dissections. Histopathologic examination confirmed 29% (7/24) of positive neck dissection specimens. The Kaplan-Meier analysis presented rates of disease-specific survival, disease-free survival, and overall survival (OS) of 81%, 78%, and 52% at 5 years, respectively. Patients undergoing postoperative radiotherapy had significantly higher OS rates compared with patients treated with surgery alone (P=.0209). Results of this study suggest that END has questionable benefit in early stage MSGT. Elective selective neck dissection levels I-III is recommended in high-grade and advanced stage MSGT without evidence of multilevel lymphadenopathy.