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High-risk human papillomavirus (hrHPV) and tumor-infiltrating lymphocytes (TILs) are known to have prognostic significance in oropharyngeal squamous cell carcinoma. However, their significance in ocular sebaceous carcinoma (OSC) remains unverified because of the rarity of the condition. This study aimed to investigate the association between clinicopathologic features, biomarkers, and hrHPV infection and their potential to predict prognosis in OSC patients. We analyzed the clinicopathologic features of 81 OSC patients from Asan Medical Center between 2000 and 2022. Seventeen biomarkers and hrHPV were examined using immunohistochemistry and DNA in situ hybridization on tissue microarray cores. hrHPV was identified in 31 cases (38.3%). Univariate analysis revealed that hrHPV infection was associated with comedonecrosis (P = .032), high Ki-67 labeling index (≥30%, P = .042), lower expression of E-cadherin (P = .033), and loss of expression of zinc finger protein 750 (P = .023). Multivariate analysis revealed that loss of expression of zinc finger protein 750 (P = .026) remained an independently associated factor for hrHPV. Progression-free survival analysis was performed on 28 patients who were continuously observed for more than 5 years. During a median follow-up duration of 86 months, recurrence or metastasis developed in 14 patients (50%) within the survival cohort, occurring at a median time of 48 months after excision. Univariate analysis indicated that recurrence or metastasis was associated with tumor size (P = .010), high TILs (≥10%; P = .025), lymphovascular invasion (P = 0.043), site of origin (P = .025), and high expression of bcl-2-associated athanogene 3 (P = .039). Multivariate analysis demonstrated that high TILs (P = .017) and site of origin (P = .025) were independent prognostic factors. The prognosis of OSC was hrHPV-independent, and a better prognosis was associated with the site of origin in the order of the gland of Zeis, meibomian gland, and multicentric site, as well as with high TILs., (Copyright © 2024. Published by Elsevier Inc.)

Tumors are composed of subpopulations of cancer cells with functionally distinct features. Intratumoral heterogeneity limits the therapeutic effectiveness of cancer drugs. To address this issue, it is important to understand the regulatory mechanisms driving a subclonal variety within a therapy-resistant tumor. We identified tumor subclones of HN9 head and neck cancer cells showing distinct responses to radiation with different levels of p62 expression. Genetically identical grounds but epigenetic heterogeneity of the p62 promoter regions revealed that radioresistant HN9-R clones displayed low p62 expression via the creation of repressive chromatin architecture, in which cooperation between DNMT1 (DNA methyltransferases 1) and HDAC1 (histone deacetylases 1) resulted in DNA methylation and repressive H3K9me3 and H3K27me3 marks in the p62 promoter. Combined inhibition of DNMT1 and HDAC1 by genetic depletion or inhibitors enhanced the suppressive effects on proliferative capacity and in vivo tumorigenesis following irradiation. Importantly, ectopically p62-overexpressed HN9-R clones increased the induction of senescence along with p62-dependent autophagy activation. These results demonstrate the heterogeneous expression of p62 as the key component of clonal variation within a tumor against irradiation. Understanding the epigenetic diversity of p62 heterogeneity among subclones allows for improved identification of the functional state of subclones and provides a novel treatment option to resolve resistance to current therapies.

Objectives: Soft tissue sarcomas of the head and neck (HNSTS) show various histological types and clinical behaviour. Recently, the 8th edition of the American Joint Committee on Cancer (AJCC) proposed a staging system for HNSTS independent of other body soft tissue sarcomas, which requires validation. Therefore, we evaluated the prognostic factors for the survival of HNSTS patients through a comparison between previous and current AJCC staging systems., Materials and Methods: This study involved 135 consecutive HNSTS patients who underwent primary surgery, chemoradiotherapy or chemotherapy. Patients were grouped into staged (S) and not staged (NS) cancer according to the AJCC 8th edition staging. Cox proportional-hazard regression analyses were used to identify factors associated with overall survival (OS), and progression-free survival (PFS) in all, S or NS patients., Results: Median follow-up period was 75 months and the 5-year OS and PFS rates of all patients were 67.8% and 53.4%, respectively, which was similar between S and NS groups. Age, tumour size and grade, overall stage (7th edition) and resection margin were the significant prognostic factors for OS and PFS in all patients and NS group (all P < 0.05), whereas positive resection margin was the only significant factor for OS and PFS in the S group (P < 0.001). While OS was poorly discriminated among different 8th edition T-categories, different 7th edition showed good discrimination among overall stages in all patients and the NS group., Conclusion: The revised staging system may not provide an improved risk stratification for survival of HNSTS patients., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Little is known about undifferentiated pleomorphic sarcoma (UPS) because of the low incidence and heterogeneous diagnosis of sarcoma. We investigated the oncologic outcomes of patients with UPS in a real-practice setting in association with adjuvant treatments and assessment of PD-L1 expression., Materials and Methods: We retrospectively reviewed consecutive patients who were diagnosed with UPS in Asan Medical Center between January 1995 and December 2016. PD-L1 staining was performed using formalin-fixed paraffin-embedded tumour tissue by immunohistochemistry, and positive PD-L1 expression was defined as staining in ≥1% of tumour cells. The PD-L1 H-score, which was calculated for statistical analysis as intensity (0-3) multiplied by proportion (0-100), ranged from 0 to 300., Results: Of 205 patients included in our analysis, 176 underwent a curative-intent operation for localised disease. The five-year disease-free survival (DFS) rate of resected UPS patients was 54.3%. Administration of adjuvant therapy did not overcome the poor prognostic factors such as primary tumour size (>5 cm) and locations, especially the abdomen and pelvis. The PD-L1 analysis was available for 114 patients, and 83 (72.8%) showed immunoreactivity for PD-L1 with weak (44/83), intermediate (29/83), and strong (10/83) staining intensities. The positive PD-L1 expression seemed to be associated with prolonged DFS, though no statistical significance was observed., Conclusion: Complete surgical resection was the most important UPS treatment strategy, and adjuvant radio- or chemotherapy was insufficient to improve survival. Our results raise the possibility that immunotherapy could be a breakthrough in the treatment of UPS patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: Adenoid cystic carcinoma (AdCC) is generally slow growing but has highly metastatic potential to distant organs. Several factors and biomarkers are associated with metastasis and treatment outcomes, although further definition is needed. Therefore, this study aimed to evaluate the risk factors for survival and distant metastasis in patients with head and neck AdCC., Methods: This study included 125 patients with previously untreated AdCC who underwent primary surgery with or without radiotherapy in our tertiary referral centre. Univariate and multivariate Cox proportional hazard regression analyses were used to identify risk factors associated with overall survival (OS), cause-specific survival (CSS), disease-free survival (DFS), and distant metastasis-free survival (DMFS). Factors associated with OS in patients with distant metastasis were separately analysed., Results: During a median follow-up of 9.8 years (range 3.0-22.6 years), 58 patients (46.4%) had distant metastasis and 29 (23.2%) died of disease. Multivariate analyses showed that lymphovascular invasion, lymph node metastasis, and distant metastasis were independent factors of OS and CSS outcomes (all P < 0.05). The T classification and extranodal extension were independent factors of DFS and DMFS outcomes (P < 0.05). After patients presented with distant metastasis, the median survival was 5.8 years. Multivariate analyses showed that extranodal extension and regional recurrence were independent factors of survival after occurrence of distant metastasis (P < 0.05)., Conclusion: Several clinicopathological factors can predict distant metastasis and survival of patients with AdCC treated with primary surgery. This may promote post-treatment surveillance in patients with AdCC.

Purpose: Cervical metastasis from unknown primary (CUP) is commonly classified as an advanced overall stage. P16 or human papillomavirus (HPV) positivity in metastatic lymph nodes (LN) might be associated with a favorable survival outcome of CUP. Therefore, we evaluated the prognostic values of p16 immuno-positivity in LN and other clinicopathological factors in patients with squamous cell carcinoma CUP (SCCUP)., Methods: This study involved 83 patients who underwent therapeutic neck dissection and panendoscopic examination and biopsy for suspected CUP. P16 immunostaining and HPV typing in LN were performed in 56 patients. Cox proportional hazard regression analyses were used to identify factors associated with overall survival (OS) and disease-free survival (DFS)., Results: Postoperatively, primary tumors (PT) were found in 32 (38.6%) patients, mainly (90.6%) in the oropharynx, and not found in 51 (61.4%) patients. The clinicopathological data (except for histological grade) and 5-year OS and DFS rates did not significantly differ between patients with and without PT identification (all P > 0.05). P16 positivity was associated with favorable OS and DFS outcomes in the patients with PT (P < 0.05) but not in those without PT (P > 0.1). Multivariate analyses showed that age (> 60 years) and LN ratio (≥ 0.1) were the independent predictors of OS and DFS outcomes (all P < 0.05). P16 positivity or other factors were not independent factors., Conclusion: Age and LN ratio are significant risk factors of survival and recurrence after primary surgery for SCCUP. Prognostic significance of LN p16 positivity should be further studied.

Ewing sarcoma family of tumor (ESFT) is a group of malignant neoplasms that affect children and young adults. Primary ESFT does not commonly arise from the head and neck region. This study aimed to elucidate the clinicopathologic characteristics of ESFT of the head and neck region except for central nervous system primitive neuroectodermal tumors. Among the 207 cases of ESFT of the bone and soft tissue, diagnosed at Asan Medical Center during a 20-year period, 25 (12.1%) involved the head and neck region. Of those, 21 were available for histologic, immunohistochemical, and molecular studies. EWSR1 rearrangement was detected in 19 cases by reverse transcriptase-polymerase chain reaction and/or fluorescence in situ hybridization. Primary sites included the cranial area (6 cases, 31.6%), sinonasal tract (6 cases, 31.6%), paraspinal space (4 cases, 21.0%), and other spaces (3 cases, 15.8%). The 5-year overall survival and disease-free survival rates for all cases were 69.7% and 33.6%, respectively. A large tumor size (>5 cm) correlated significantly with overall survival (P=0.009), but not with disease-free survival (P=0.210). Microscopically, 8 cases (42.1%) showed nested growth pattern. Clear and/or eosinophilic cytoplasm was observed in 68.4% cases. Immunopositivity for CD99, Friend leukaemia integration-1 (FLI-1), CD57, and caveloin-1 were detected in 100%, 88.9%, 83.3%, and 50% cases, respectively. ESFT in the head and neck region had a favorable prognosis and frequent atypical and epithelioid features. An awareness of these histologic and immunophenotypic characteristics will improve the diagnostic accuracy for head and neck round cell malignancies.

Context: - Interpretation of atypical squamous lesions of the head and neck has always been a nettlesome task for pathologists. Moreover, many different grading systems for squamous intraepithelial lesions have been proposed in past decades. The recent World Health Organization 2017 classification presents 2 types of 2-tier systems for laryngeal and oral precursor lesions., Objective: - To review the recent changes in classification and the clinical significance for squamous intraepithelial lesions of the head and neck., Data Sources: - Personal experience and data from the literature., Conclusions: - The 2-tier grading system for laryngeal dysplasia, presented by World Health Organization in 2017, is expected to improve diagnostic reproducibility and clinical implication. However, the diagnostic criteria for low-grade dysplasia do not distinguish it clearly from basal cell hyperplasia. The World Health Organization 2017 classification of oral epithelial dysplasia remains unclear, and complicated and variable grading systems still make head and neck intraepithelial lesions difficult to interpret.

Squamous cell carcinoma of unknown primary of the head and neck (SCCUP) is a heterogeneous disease entity that requires careful examination to locate the occult primary. We examined the diagnostic value of expression of biomarkers, such as human papillomavirus (HPV), p16 and Epstein-Barr virus (EBV), in metastatic lymph nodes vs. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT). We prospectively enrolled 54 consecutive SCCUP patients who received HPV, p16 and EBV analyses of lymph node fine-needle aspirates and 18 F-FDG PET/CT scans and subsequently underwent examinations and biopsies under general anesthesia to detect primary tumors. The diagnostic performance of the biomarkers and 18 F-FDG PET/CT were compared by using receiver operating characteristics (ROC) curve analyses with histopathological results for identification of primary tumors. Primary tumors were identified in 28 (51.9%) of 54 patients: the palatine tonsil in 24, base of the tongue in 1, nasopharynx in 2, and hypopharynx in 1. The sensitivity of p16 (85.7%) and accuracy of HPV (85.2%) were higher than those (42.9% and 68.5%) of 18 F-FDG PET/CT (p < 0.05). The area under the ROC curve of HPV was higher than that of 18 F-FDG PET/CT (0.857 vs. 0.666, p = 0.007). The disease-free survival rates were higher in the patients with primary tumor detection or p16 nodal immunopositivity than in the other patients (p < 0.05). The results showed that HPV and p16 detection in metastatic lymph nodes can help locate hidden primary tumors, guide definitive treatment and predict patient survival., (© 2016 UICC.)

Purpose: Head and neck soft tissue sarcoma (HNSTS) is a rare type of tumor with various histological presentations and clinical behaviors. 18 F-FDG PET/CT is being increasingly used for staging, grading, and predicting treatment outcomes in various types of human cancers, although this modality has been rarely studied in the survival prediction of HNSTS. Here we examined the prognostic value of tumor metabolic parameters measured using 18 F-FDG PET/CT in patients with HNSTS., Methods: This study included 36 consecutive patients with HNSTS who underwent 18 F-FDG PET/CT scanning prior to treatment at our institution. Tumor gross total volume (GTV) was measured from pretreatment contrast-enhanced CT scans, and maximum standardized uptake value (SUV max ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using pretreatment 18 F-FDG PET/CT scans. Univariate and multivariate Cox proportional hazard regression analyses were used to identify associations between imaging parameters and disease-specific survival (DSS) or overall survival (OS)., Results: Univariate analyses showed that SUV max , MTV, and TLG, but not GTV, were significantly associated with DSS and OS (all P < 0.05). After controlling for clinicopathological factors, SUV max , MTV, and TLG were significantly associated with DSS and OS (all P < 0.05). Patients with a tumor SUV max value of >7.0 experienced an approximately fivefold increase in mortality in terms of DSS and OS relative to those with a tumor SUV max <7.0., Conclusion: Quantitative metabolic measurements on pretreatment 18 F-FDG PET/CT can yield values that are significantly predictive of survival after treatment for HNSTS.

Background: Accurate assessment of the extent of cancer is essential for appropriate treatment planning and outcome prediction. This study prospectively evaluated whether adding (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) to the routine initial staging practice in head and neck squamous cell carcinoma (HNSCC) improved management and prognosis., Methods: All consecutive patients with newly diagnosed HNSCC who presented in October 2010 - December 2012 underwent conventional workups (CWU) followed by PET/CT. The clinical stage and management plans before and after PET/CT were compared. PET/CT was deemed to have no/low, moderate, and high impact on management planning depending on whether PET/CT changed the treatment modality or goal. The appropriateness of PET/CT staging and management impact was confirmed by histopathology and clinical follow-up, and its association with survival was analysed., Findings: Of the 248 patients, PET/CT changed the Tumour Node Metastasis (TNM) classification in 79 (31.9%). In the patients with discordant staging, PET/CT staging was significantly more sensitive and accurate than CWU staging (both P < 0.001). PET/CT had high or moderate impact on management in 39 (15.7%) patients. Patients with PET/CT upstaged disease had significantly worse progression-free survival (PFS) and overall survival (OS) than patients with no CWU-stage changes (3-year PFS = 56.8% versus 74.5%, P = 0.043; 3-year OS = 61.3% versus 85.3%, P = 0.006). Multivariate analyses revealed that PET/CT staging and second primary cancer were independent predictive factors for both PFS and OS (P < 0.05, each)., Interpretations: (18)F-FDG PET/CT added important staging information that improved management and prognostic stratification in HNSCC., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate whether contralateral neck metastasis (CNM) from previously untreated head and neck squamous cell carcinoma (HNSCC) can be accurately detected at combined computed tomography (CT)/magnetic resonance (MR) imaging and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT and assess the prognostic value of CNM., Materials and Methods: This prospective study was approved by the institutional review board, and written informed consent was obtained from all enrolled patients. In total, 160 patients with HNSCC were preoperatively evaluated with FDG PET/CT and CT/MR imaging. Histopathologic results of neck dissection samples served as the reference standard for all cases. McNemar test and logistic regression with generalized estimating equations were used to compare the diagnostic value of FDG PET/CT and CT/MR imaging, and Cox proportional hazard modeling was used to assess the prognostic value of CNM., Results: Of the 160 enrolled patients, 94 (58.8%) had a neck metastasis on 231 sides and with 974 levels, and 20 patients (21.3%) had a contralateral neck metastasis. FDG PET/CT was significantly more sensitive than CT/MR imaging according to per-patient (91.5% vs 73.4%; P < .001), per-side (91.1% vs 69.6%; P < .001), and per-level analyses (78.9% vs 53.0%; P < .001). On the per-side basis, FDG PET/CT was also significantly more sensitive and accurate than CT/MR imaging when evaluating the contralateral neck (85.0% vs 45.0%, P = .008, and 91.6% vs 80.3%, P = .008, respectively). However, at univariate analysis, CNM was significantly associated only with cancer-specific death (P = .001) and overall survival (P = .015)., Conclusion: CNM from HNSCC can be detected at FDG PET/CT with higher sensitivity and accuracy than at CT/MR imaging., ((©) RSNA, 2015 Online supplemental material is available for this article.)

Purpose: Distant metastasis (DM) of head and neck squamous cell carcinoma (HNSCC) is not common but remains a substantial problem. Here, we evaluated factors predictive of long-term survival in HNSCC patients presenting with DM after initial definitive treatment., Methods: The medical records of patients with HNSCC who underwent definitive treatment between 2006 and 2011 were reviewed. Univariate and multivariate analyses were performed to identify clinicopathological factors associated with long-term survival after DM., Results: Of 779 HNSCC patients, 98 (12.6 %) had DM after completion of definitive treatment, with a median time to DM of 15 months (range 1-87 months). Overall survival (OS) rates at 1 and 2 years after DM were 43.1 and 20.5 %, respectively. In multivariate analysis, hypoalbuminemia (P < 0.001, hazard ratio [HR] 3.45, 95 % confidence interval [CI] 2.01-5.92), prior or simultaneous locoregional failure events (P < 0.001, HR 2.36, 95 % CI 1.47-3.79), multisite DM (P = 0.001, HR 2.30, 95 % CI 1.42-3.72), and no salvage treatment for DM (P = 0.003, HR 2.19, 95 % CI 1.32-3.64) were independent predictors of OS after the development of DM. Seventeen (18 %) patients survived >2 years. Patients who did not have any of these risk factors had the most favorable outcomes, with a 2-year survival of 100 %., Conclusions: In the absence of risk factors, long-term survival can be achieved despite the development of DM after definitive treatment.

Background: Extranodal extension (ENE) is a poor prognostic indicator for patients with head and neck squamous cell carcinoma (HNSCC), but pretreatment detection assists with proper treatment planning. This study evaluated whether the ENE of HNSCC is accurately detected by computed tomography (CT) versus fluorine 18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT and whether it has any impact on patient prognosis., Methods: In this study, 186 HNSCC patients were preoperatively evaluated using contrast-enhanced CT and (18)F-FDG PET/CT. The histopathologic findings for the neck dissection samples served as a standard reference. McNemar's test and logistic regression using the generalized estimating equations were used to compare the diagnostic value of CT versus (18)F-FDG PET/CT, and Cox proportional hazard regression was used to assess the prognostic value of ENE., Results: Among the 186 study patients, 113 (60.8 %) had a neck metastasis, 44 (23.7 %) had pathologic ENE, and 37 (19.9 %) had macroscopic ENE. Radiologic ENE (rENE) on CT was documented for 48 patients (25.8 %) and 52 neck sides (19.8 %). Using 4.9 as the cutoff value for nodal maximum standardized uptake, (18)F-FDG PET/CT documented rENE for 44 patients (23.7 %) and 48 neck sides (18.3 %). Compared with (18)F-FDG PET/CT, CT detected ENE, with a specificity of 92.1 versus 74.4 % (p < 0.001) and an accuracy of 88.6 versus 75.3 % (p < 0.001). However, rENE was not a significant predictor of recurrence or survival (p > 0.05)., Conclusion: The findings showed that ENE of HNSCC is more accurately detected by using CT than by using (18)F-FDG PET/CT. The accurate pretreatment detection of ENE may help in the planning for HNSCC treatments.

Accurate tumor staging including involvement of laryngeal cartilage is important to treatment planning. Clinicians rely on imaging findings and determine initial laryngectomy for T4-stage cancer with functionless larynx or extralaryngeal spread (ELS). We examined the accuracy and prognostic value of preoperative CT findings for tumor staging in patients with locally advanced laryngeal and hypopharyngeal cancer. Ninety-four consecutive patients with clinically T3-T4-stage squamous cell carcinoma of the larynx or hypopharynx who underwent curative resection of primary tumor were reviewed. Preoperative CT findings were interpreted by a radiologist without pathologic information. Pathologic findings were used as the gold standard for correlating radiographic findings. CT imaging identified 23 (72%) of 32 cases of pathologically documented thyroid cartilage penetration and 24 (73%) of 33 cases of pathologically documented ELS. The positive predictive values for thyroid cartilage penetration and ELS were 70 and 80%, respectively. Pretreatment CT imaging up-staged 6 of 46 pT3 cases and all of 8 pT2 cases, while it down-staged 7 of 40 pT4 cases. The accuracy for clinical staging by CT imaging was 78%. Subglottic extension of the CT image was an independent variable for predicting thyroid cartilage penetration and ELS (P = 0.014). Thyroid cartilage penetration with or without ELS on CT scans is significantly associated with unfavorable DFS outcome of patients (P = 0.020). CT imaging is suboptimal in diagnosing TCP or ELS of advanced laryngeal cancer, but may be useful to predict patient survival by identifying clinically TCP.

Purpose: We examined the effect of extranodal extension (ENE) and its thickness (ENET) of metastatic lymph node (LN) on the disease course of patients with head and neck squamous cell carcinoma., Methods: Data from 438 patients who were initially treated surgically at our center was retrospectively analyzed. ENE presence and ENET were examined in metastatic LN from each patient. Clinicopathologic characteristics, recurrence, and survival were then compared., Results: Of 438 patients, 219 (50%) showed positive nodal status, and ENE was identified in 84 (19.6%). Forty-five of 219 (20.5%) node-positive patients were classified with ENET ≥ 2 mm, which was associated with an increase in both the size and number of positive LN, bilateral cervical involvement, and a higher LN ratio. ENE-positive patients had a higher risk of recurrence and a lower overall survival rate; however, multivariate analysis failed to identify a significant difference in cancer-specific survival (CSS) between those with and those without ENE. On the contrary, ENET ≥ 2 mm was significantly associated with a poor CSS, even in multivariate analysis., Conclusion: ENET ≥ 2 mm might be a complementary prognostic marker in CSS estimation for ENE positivity., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Management of the neck in patients with salivary gland cancer is controversial. This study aimed to identify clinicopathologic characteristics associated with regional metastases and regional recurrence in patients with salivary gland carcinoma., Methods: Of 363 study patients, 51 underwent therapeutic neck dissection (TND) and 312 underwent either elective neck dissection (END, n = 110) or no neck dissection (NoND, n = 202). Univariate and multivariate analyses were performed to identify clinicopathologic characteristics associated with regional metastases and recurrence., Results: Pathologic neck metastases were identified in 17/110 (15.5%) END patients and neck recurrence was identified in 5/202 (2.5%) NoND patients. Histologic grade (P < 0.001), tumor site (P = 0.008), and lymphovascular invasion (P < 0.001) were independent risk factors for neck metastases. Nodal metastases were more common in high-grade tumors (P < 0.001), at levels I-III in END patients and levels I-V in TND patients. Multivariate analyses identified histologic grade (P = 0.020), clinical N2 classification (P = 0.007), and extranodal extension (P = 0.005) as independent factors for regional recurrence after treatment., Conclusions: Patients with high-grade cancers should receive END involving levels I-III, whereas patients with node-positive salivary cancers should receive comprehensive TND involving all levels (I-V)., (© 2015 Wiley Periodicals, Inc.)

Background: Head and neck soft tissue sarcomas (HNSTS) are rare tumors with various histological types displaying different clinical behavior. As a result, prognostic factors of this disease remain unclear. The aim of this study was to investigate the prognostic factors and oncological outcomes of HNSTS., Materials and Methods: This retrospective study included 122 patients with HNSTS who were treated at our institution between 1995 and 2012. Univariate and multivariate analyses using the Cox proportional hazards model were used to determine clinicopathologic characteristics associated with locoregional control (LRC), disease-specific survival (DSS), and overall survival (OS)., Results: Rhabdomyosarcoma was the most common tumor type (20 %), followed by dermatofibrosarcoma protuberance (13 %) and angiosarcoma (12 %). In a follow-up of 72 months, the 5-year LRC, DSS, and OS rates were 76, 77, and 75 %, respectively. Univariate analyses showed that age (>60 years), tumor size (>10 cm), nodal metastasis, and overall stage were significant prognostic factors for LRC, DSS, and OS (p < 0.05). Histological grade was also significantly associated with DSS (p = 0.012) and OS (p = 0.002). In multivariate analysis, tumor size and nodal metastasis were independent prognostic factors for LRC (p < 0.05), while age, histological grade, and nodal metastasis remained independent variables for both DSS and OS (p < 0.05)., Conclusions: Our data support that surgical excision of HNSTS contributes to acceptable survival rates. Several factors at diagnosis may be independently associated with recurrence and survival outcomes, and identification of these factors may help in selecting at-risk patients.

Objective: To evaluate the usefulness of measuring the apparent diffusion coefficient (ADC) in diffusion-weighted magnetic resonance imaging to distinguish benign from small, non-necrotic metastatic cervical lymph nodes in patients with head and neck cancers., Materials and Methods: Twenty-six consecutive patients with head and neck cancer underwent diffusion-weighted imaging (b value, 0 and 800 s/mm(2)) preoperatively between January 2009 and December 2010. Two readers independently measured the ADC values of each cervical lymph node with a minimum-axial diameter of ≥ 5 mm but < 11 mm using manually drawn regions of interest. Necrotic lymph nodes were excluded. Mean ADC values were compared between benign and metastatic lymph nodes after correlating the pathology., Results: A total of 116 lymph nodes (91 benign and 25 metastatic) from 25 patients were included. Metastatic lymph nodes (mean ± standard deviation [SD], 7.4 ± 1.6 mm) were larger than benign lymph nodes (mean ± SD, 6.6 ± 1.4 mm) (p = 0.018). Mean ADC values for reader 1 were 1.17 ± 0.31 × 10(-3) mm(2)/s for benign and 1.25 ± 0.76 × 10(-3) mm(2)/s for metastatic lymph nodes. Mean ADC values for reader 2 were 1.21 ± 0.46 × 10(-3) mm(2)/s for benign and 1.14 ± 0.34 × 10(-3) mm(2)/s for metastatic lymph nodes. Mean ADC values between benign and metastatic lymph nodes were not significantly different (p = 0.594 for reader 1, 0.463 for reader 2)., Conclusion: Measuring mean ADC does not allow differentiating benign from metastatic cervical lymph nodes in patients with head and neck cancer and non-necrotic, small lymph nodes.

Purpose: To assess the clinical usefulness of fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and CT/magnetic resonance (MR) imaging in detecting occult neck metastasis in patients with head and neck squamous cell carcinoma and negative neck palpation findings., Materials and Methods: This prospective study was approved by the institutional review board, and written informed consent was obtained from all enrolled patients. In total, 91 patients with head and neck squamous cell carcinoma and negative neck palpation findings were assessed prospectively with (18)F-FDG PET/CT and CT/MR imaging. Histopathologic analysis of neck dissection samples served as the standard of reference. Diagnostic values of (18)F-FDG PET/CT and CT/MR imaging were compared by using the McNemar test and logistic regression with generalized estimating equations., Results: Of 91 patients, 38 (42%) had metastasis in 43 neck sides and 70 levels of the neck. (18)F-FDG PET/CT demonstrated nodal metastasis more sensitively on a per-level basis than did CT/MR imaging (69% vs 39%, P < .001). CT/MR imaging demonstrated nodal metastasis with low sensitivity at all levels (0%-38%) except level II (55%), while (18)F-FDG PET/CT had generally high sensitivity at all levels (63%-100%) except level VI (0%). On a per-patient basis, the sensitivities of (18)F-FDG PET/CT and CT/MR imaging were 71% and 50%, respectively (P = .011). (18)F-FDG PET/CT accurately depicted CT/MR imaging false-negative findings in nine of 19 patients but yielded false-negative results in 11 patients. Use of (18)F-FDG PET/CT reduced the probability of occult neck metastasis to 12%., Conclusion: (18)F-FDG PET/CT is superior to CT/MR imaging in depicting occult cervical metastatic nodes in patients with negative neck palpation findings. The improved detection and nodal staging may promote appropriate therapeutic planning in these patients., (RSNA, 2013)

Objectives/hypothesis: This study was intended to evaluate prognostic factors and the role of postoperative radiotherapy (RT) in patients with adenoid cystic carcinoma (ACC) of the head and neck (ACCHN)., Study Design: Retrospective study., Methods: Eighty-eight patients with ACCHN who underwent curative intent surgery with or without RT between 1991 and 2009 at a single institute were retrospectively analyzed., Results: Patients with ACC of the sinonasal area (P=.005) and those with diabetes mellitus (DM; P=.027) showed a significantly higher risk of local recurrence. Age (<40 or >60 years, P=.028) and tumor stage III or IV (P=.022) were significant adverse factors predicting distant metastasis. High-grade histology (P=.014) and DM (P=.027) were independently associated with shorter disease-free survival (DFS). In addition, postoperative RT (≥59 Gy) significantly enhanced local control (P=.025) and DFS (P=.001) in both univariate and multivariate analyses., Conclusions: Age, DM, tumor site, histologic grade, and stage were independently significant prognostic factors for ACCHN. In addition, an adequate dose of postoperative radiotherapy can improve local control and DFS of patients with ACCHN., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Our aim was to compare the diagnostic performance of shear wave elastography (SWE) with that of gray-scale ultrasound (US) in differentiating metastatic from benign lymph nodes in patients with head and neck malignancies. Maximum shear elasticity modulus (maxSM) was measured on SWE. The reference standard was pathologic diagnosis after surgery. We examined 67 lymph nodes (34 metastatic, 33 benign) from 15 patients (8 men and 7 women; mean age, 54.2 years). The maxSM value was significantly higher for metastatic than benign lymph nodes (41.06 ± 36.34 kPa vs. 14.22 ± 4.19 kPa, p < 0.0001) at a cutoff level of 19.44 kPa. Accuracy, sensitivity and specificity were 94, 91 and 97%, respectively, for SWE, and 91, 88 and 94%, respectively, for gray-scale US. Multiple regression analysis showed that the maxSM value (r = 0.882) and gray-scale US criteria (r = 0.837) were independent variables. SWE may be a valuable quantitative reproducible method for characterizing cervical lymph nodes., (Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: The precise diagnosis of cervical lymph node metastasis (CLNM) of salivary gland cancer is important to determine the surgical extent and adjuvant therapy. This study assessed the clinical utility of (18)F-FDG PET in identifying CLNM in such patients., Methods: Fifty-four patients with intermediate or high-grade salivary gland cancer were preoperatively evaluated with (18)F-FDG PET/CT and CT/MRI. Histopathologic analysis of neck dissection tissues was used as the gold standard for assessing imaging techniques. Tumor and nodal maximum standardized uptake values (SUVmax) were measured for each patient. Univariate and multivariate analyses were used to identify CLNM predictive factors., Results: Of the 54 patients, 24 patients (44%) had CLNM. On a per-patient basis, the sensitivity and specificity of (18)F-FDG PET/CT and CT/MRI were not significantly different (92 vs. 83%, P = 0.625 and 93 vs. 97%, P = 1.000, respectively). On a per-level basis, (18)F-FDG PET/CT was significantly more sensitive and accurate than CT/MRI in the ipsilateral neck (96 vs. 54%, P < 0.001 and 92 vs. 83%, P < 0.001, respectively). The mean nodal SUVmax values of patients with and without nodal metastasis were 4.9 and 2.1, respectively (P = 0.008). Histologic grade was a significant predictor of CLNM (P = 0.014, odds ratio 14.46, 95% confidence interval 1.73-120.79)., Conclusions: (18)F-FDG PET/CT imaging and histologic grade are useful for detecting CLNM in patients with salivary gland carcinoma. This finding may guide preoperative planning for the necessity and extent of neck dissection in these patients.

Purpose: Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the clinical outcomes of LASCCHN patients who showed response to ICT are heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of LASCCHN patients who achieved partial response (PR) after ICT to predict clinical outcomes after concurrent chemoradiotherapy (CCRT)., Methods and Materials: Twenty-one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In Solid Tumors before definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2-4 weeks after ICT to assess the extent of disease at baseline and the metabolic response to ICT, respectively. We examined the correlation of the metabolic response by the percentage decrease of maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes including complete response (CR) rate to CCRT, progression-free survival (PFS), and overall survival (OS)., Results: A SUVmax of 4.8 on interim FDG-PET could predict clinical CR after CCRT (100% vs. 20%, p=0.001), PFS (median, not reached vs. 8.5 mo, p<0.001), and OS (median, not reached vs. 12.0 months, p=0.001) with a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax after ICT from baseline also could predict clinical CR after CCRT (100% vs. 33.3%, p=0.003), PFS (median, not reached vs. 8.9 months, p<0.001) and OS (median, not reached vs. 24.4 months, p=0.001) of the patients., Conclusion: These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcomes in patients with LASCCHN receiving sequential ICT followed by CCRT., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: (18)F-fludeoxyglucose (FDG) positron emission tomography (PET) is a sensitive and specific method for detecting active residual disease after chemoradiotherapy or radiotherapy, but few studies have accurately evaluated its diagnostic accuracy with histopathologic correlation. We therefore investigated the clinical utility of (18)F-FDG PET/computed tomography (CT) in patients undergoing salvage surgery for residual head and neck squamous cell carcinoma (HNSCC) after primary nonsurgical treatments., Methods: Thirty-nine patients who initially received chemotherapy (n = 23), radiotherapy (n = 3), or chemoradiotherapy (n = 13) were evaluated 8-28 weeks later by (18)F-FDG PET/CT and CT/magnetic resonance imaging (MRI) prior to salvage surgery to clear residual disease. These results were compared with those of histopathologic analysis of the primary tumor and neck dissection tissue samples., Results: Of these 39 patients, 22 (56%) had residual primary tumor. The sensitivity, specificity and accuracy of (18)F-FDG PET/CT for detecting primary tumors were 91, 65, and 79%, respectively. Of 56 dissected heminecks, 37 (66%) had residual metastatic lymph nodes. (18)F-FDG PET/CT and CT/MRI had accuracies for positive heminecks of 91 and 75%, respectively (P = 0.004). On a cervical level-by-level-based analysis, (18)F-FDG PET/CT and CT/MRI had accuracies of 89 and 78%, respectively (P < 0.001); (18)F-FDG PET/CT had a specificity of 93% and a negative-predictive value of 92% for detection of positive levels., Conclusions: (18)F-FDG PET/CT is superior to CT/MRI in detecting residual nodal disease in head and neck squamous cell carcinoma patients undergoing salvage surgery. Accurate preoperative diagnosis using (18)F-FDG PET/CT may help to determine the extent of salvage surgery.

We evaluated the clinical utility of combined [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT), as well as CT and magnetic resonance imaging (MRI) in identifying nodal metastases in the contralateral neck in patients with head and neck squamous cell carcinoma (HNSCC). A total of 114 patients were preoperatively evaluated with PET/CT and CT/MRI. Histopathologic analysis from bilateral neck dissection tissues was used as the gold standard in assessing these imaging techniques. Of the 114 patients, 63 (55%) had neck metastases and 26 (23%) had contralateral neck metastases. On a per-level basis, FDG PET/CT was significantly more sensitive and accurate than CT/MRI in the ipsilateral (88% vs. 70%, P<0.01 and 93% vs. 89%, P<0.01, respectively) and contralateral (52% vs. 36%, P<0.01 and 91% vs. 90%, P=0.039, respectively) neck. PET/CT and CT/MRI were less sensitive in detecting contralateral than ipsilateral neck metastases due to the lower incidence of metastases and smaller nodes on the contralateral side. Combined PET/CT is superior to CT/MRI in detecting metastatic neck nodes in HNSCC patients. However, PET/CT may not abrogate the need for contralateral neck surgery or radiotherapy in these patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

(18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) has been reported to identify primary tumors in patients with cervical metastases from cancer of unknown primary (CUP). However, few reports have assessed the use of combined FDG-PET/computed tomography (CT) in this setting. We therefore examined the utility of combined FDG-PET/CT in the detection of primary tumors and unrecognized metastases in these patients. Patients with previously untreated CUPs underwent head and neck CT and whole-body FDG-PET/CT before panendoscopy and guided biopsy. The diagnostic accuracy of CT and FDG-PET/CT in detecting primary tumors and cervical metastases was compared with that of histopathology. The ability of FDG-PET/CT to detect distant metastases was also tested. Of the 44 eligible patients, 16 had occult primary tumors in the head and neck. FDG-PET/CT was significantly more sensitive than CT for detecting primary tumors (87.5% vs. 43.7%, P=.016), but their specificity did not differ (82.1% vs. 89.3%, P=.500). Thirty-four of 44 patients underwent neck dissection; 67 of 182 dissected cervical levels had metastatic nodal diseases. On a level-by-level basis, FDG-PET/CT was significantly more sensitive than CT (94.0% vs. 71.6%, P<.001), but the two methods were equally specific (94.8% vs. 96.5%). FDG-PET/CT correctly detected distant metastases in 6 of 6 patients. Combined FDG-PET/CT is a useful screening method for primary tumor detection, accurate nodal staging, and distant metastases in patients with CUPs.

Conclusion: Surgical treatment of carotid invasion may give an improved 2-year survival in selected patients without significant morbidity., Objective: To evaluate survival outcomes in patients with head and neck squamous cell carcinomas invading the carotid artery., Patients and Methods: At the time of carotid invasion, 23 patients underwent surgery (n=11), chemoradiotherapy (n=6), or palliation (n=6). Surgical methods included carotid resection and ligation (n=5), carotid resection and reconstruction with saphenous vein (n=4), and peeling (n=2). Survival outcomes among different treatments were compared., Results: None of the 11 surgical patients experienced perioperative mortality or major neurologic complications. Three of these patients survived, but two had recurrent disease at last follow-up; their 2-year overall survival and disease-free survival rates were 24.5% and 18.2%, respectively. In contrast, all patients treated with chemoradiation or palliation died within 15 months. Median survival time was 16.5 months in the surgery group, 11.5 months in the chemoradiation group, and 3 months in the palliation group (p=0.025).

The combination of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) has been reported to be more accurate than CT or PET alone in a preoperative setting. We compared the diagnostic utility of preoperative PET/CT, PET and CT/MRI in 167 patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), of whom 104 underwent FDG PET and 63 underwent combined PET/CT with all receiving CT/MRI. These preoperative PET, PET/CT, and CT/MRI results were reviewed and their accuracies were compared in patients in whom diagnosis was confirmed histopathologically. Age, sex, primary sites and stage, and nodal involvement were comparable between two groups. The accuracy of PET and PET/CT for detecting primary tumors and cervical metastases was comparable, but significantly higher than that of CT/MRI (98%-97% vs. 86-88% for primary; 92%-93% vs. 85%-86% for neck on a level-by-level basis; P<.05). PET and PET/CT gave false negative results: in 2 (2%) and 2 (3%) patients for primary tumors; in 6 (6%) and 3 (5%) patients for neck metastases, respectively. PET and PET/CT also gave false-positive results for cervical metastases in 5 (5%) and 4 (6%) patients, respectively. Compared with PET alone, preoperative FDG PET/CT may not yield significantly improved diagnostic accuracy in patients with HNSCC. Moreover, despite their high accuracy, PET and PET/CT may not abrogate the need for conventional imaging and pathologic staging based on primary resection and neck dissection.

Objective: Solitary fibrous tumor (SFT) is a very rare tumor. The purpose of this study is to determine the MR imaging features of SFT in the intracranial and extracranial head and neck regions., Materials and Methods: We retrospectively reviewed six MR images and two CT images of six histologically proven cases of SFT that occurred in four men and two women, and their ages ranged from 46 to 59 years. These imaging findings were correlated with the microscopic findings of their surgical specimens., Results: Six SFTs arose in the meninges (the petrous ridge and the pituitary fossa), the parotid gland, the parapharyngeal space, the buccal space and the maxillary sinus. On the MR images, SFTs in the intracranial and extracranial head and neck regions were mostly isointense to the muscle on the T1-weighted images, they were hyperintense on the T2-weighted images and they all had intense enhancement. On the T1- and T2-weighted images, hypointense lines were observed within in five SFTs. On the CT images, the SFTs were hypodense to the muscle on the unenhanced images and they were heterogeneously enhanced on the contrast-enhanced images. An exceptional case of pituitary SFT was hypointense on the T2-weighted images and it was hyperdense on the unenhanced CT images, which correlated with the increased collagenous component and the cellular compactness., Conclusion: The imaging features of SFT are nonspecific; however, SFT should be included in the differential diagnosis of masses involving the intracranial and extracranial head and neck regions.

Cancers of the upper aerodigestive tract (UADT) constitute 3.5-4% of all malignancies. Since the majority of cases are squamous cell carcinomas which are related with epidemiologic factors, a different pattern of UADT cancer might be present between the Western and Asian populations. We performed a pathology based statistical study on UADT cancers in Korean patients. Cases from Korea Cancer Center Hospital, from January 1, 1988 through December 31, 1998, were subjected to the study. Among 2,842 cases, epithelial malignancies accounted for 87.8%, with squamous cell carcinoma as the major type (76.5%). The larynx was the most commonly affected site (26%), followed by the oral cavity (25.1%), oropharynx (13%), nasopharynx (9%), hypopharynx (8.4%), paranasal sinuses (6.4%), nasal cavity (6%) and salivary glands (6.1%). The percentage of squamous cell carcinoma was highest (98.7%) at the hypopharynx, and lowest at the nasal cavity (42.3%), which showed the most diverse tumor entities. Korean patients with UADT cancers presented with a higher incidence of non-epidermoid malignancy including sarcoma (1.5%) and malignant melanoma (1.4%), and a higher frequency of involvement of the sinonasal tract, compared with the Western patients.