Is Primary Poorly Differentiated Sarcomatoid Malignancy of the Parotid Gland Sarcomatoid Undifferentiated/Dedifferentiated Melanoma ? Report of three unusual cases diagnosed by fine needle aspiration combined with histological, immunohistochemical and molecular analyses.

INTRODUCTION: Poorly differentiated primary sarcomatoid parotid malignancies are extremely rare. These tumors have not been consistently studied by morphology, immunohistochemistry or molecular techniques. CASE PRESENTATION: We report three unusual cases of parotid gland poorly-differentiated sarcomatoid malignancy investigated by fine needle aspiration and studied histologically, by immunohistochemistry and molecular investigations. Aspirates showed poorly specific polymorphous sarcomatoid malignancy in all cases. Histologically, all cases were polymorphous high-grade malignancies, additionally one case showed epithelial structures and was finally classified as salivary carcinosarcoma. Immunohistochemistry showed classical melanocytic markers negativity but positivity for PRAME, CD10, WT1 in all three tumors and for CD56 in two tumors, which can potentially be supportive of melanocytic origin. Although not entirely specific, molecular characterization also suggested the melanocytic lineage of these tumors. CONCLUSION: Although rare, primary malignant melanoma of salivary gland was already described, but undifferentiated/dedifferentiated amelanotic forms are unknown in this localization up today. Further case reports of similar presentations are required to confirm the unequivocal primary origin of these obscure neoplasms in the parotid gland.

Upper Aerodigestive Tract Endoscopy Combining Rigid Laryngoscopy and Flexible Endoscopy.

Upper Aerodigestive Tract Endoscopy (UATE) is recommended for initial examination of head and neck squamous cell carcinomas. Reducing delay of initial examination must be a challenge to manage head and neck cancers. We hereby describe the technic combining UATE and flexible endoscopy in a unique general anesthesia with overview of hypopharyngeal, larygeal, tracheal, esophageal, nasopharyngeal sub sites in a unique procedure with system of magnificense and to perform percutaneous gastrostomy during the same time before initiation of therapy.

Curative high-dose reirradiation for patients with recurrent head and neck adenoid cystic carcinomas: outcomes and analysis of patterns of failure.

BACKGROUND: To investigate the outcomes of patients who underwent curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for unresectable recurrent or second primary head and neck adenoid cystic carcinoma (HNACC). METHODS: Ten patients, mostly KPS 90%, were reirradiated (3/10 with IMRT and 7/10 with PT) at a median maximum dose to the CTV of 64.2 Gy from July 2011 to November 2021. Locations at the time of reRT were mainly the sinus (4/10) and the salivary glands (including the parotid and submandibular gland, 3/10). CTCAEv5 was used to assess acute and late toxicities. Follow-up was the time between the end of reRT and the date of last news. RESULTS: The median time between the two irradiations was 53.5 months (IQR: 18-84). After a median follow-up of 26 months (range, 12.5-51.8 months), six patients had developed a locoregional recurrence (LR), of which four occurred within the previously irradiated volume. Two and three-year locoregional failure-free survival (LFFS) and overall survival (OS) were 55.6% [95%CI: 31-99.7%], and 41% [18.5-94%] and 66.7% [42-100%] and 44.4% [21.4-92.3%], respectively. LFFS and OS were significantly better in the subgroup of sinus tumors (p = .013) and the subgroup of patients re-irradiated more than two years after the first course of irradiation (p = .01). Seven patients had impairments before the start of reRT, including hearing impairment (3/10) and facial nerve impairment (3/10). The most severe late toxicities were brain necrosis (2/10), osteoradionecrosis (1/10) and vision decreased (1/10). CONCLUSION: Curative reRT for HNACC is possible for selected cases, but the LR rate in the irradiated field and the risk of severe toxicity remain high. Improved selection criteria and more carefully defined target volumes may improve outcome in these patients. A further study including larger cohort of patients would be useful to confirm these results.

Fine needle aspiration as a diagnostic modality for Warthin tumors identified as fluorodeoxyglucose positron emission tomography/computed tomography-positive.

Limited evidence exists regarding the 2-deoxy-2-[fluorine-18]-fluoro-D-glucose (FDG) avidity of Warthin tumors, the second most common benign parotid gland tumor. This study aims to clarify this aspect by analyzing patients who underwent FDG positron emission tomography/computed tomography (PET/CT) and quantifying tumor standardized uptake values (SUV). Medical records of 29 patients with fine needle aspiration (FNA)-confirmed Warthin tumors who underwent FDG-PET/CT near the diagnosis of Warthin tumor were reviewed. Key parameters included cancer history, cytologic diagnosis of Warthin tumor, maximum SUV on FDG PET/CT, and tumor localization. Among the cohort, 18 males and 11 females (average age: 67.9 years) were included. Most patients had malignant neoplasms (lung, head and neck, breast, others). One patient had synchronous liver cancer. Three individuals had bilateral Warthin tumors, and three had bifocal tumors, resulting in 35 tumors for analysis. Tumors were located in the parotid gland (28) and vicinity (7). SUVmax for the Warthin tumors ranged from 3.6 to 26.8, with an average SUVmax of 10.1. Warthin tumors exhibit significant and variable FDG accumulation, exceeding expectations and mimicking high-grade malignancies. Awareness of this phenomenon is crucial for accurate staging and timely management. In cases of positive FDG PET/CT uptake in periparotid, perimandibular, and upper jugular areas, FNA is recommended to avoid misinterpretation or delays in management.

Safety and reliability of the internal jugular vein for venous anastomoses in head and neck oncological reconstruction: A retrospective study.

This study aimed to assess the efficacy of utilizing the internal jugular vein (IJV) as the primary recipient site for venous anastomoses in head and neck oncological reconstruction. Patients who underwent a free flap reconstruction of the head and neck were retrospectively included. Venous anastomoses were preferentially performed less than 1 cm from the IJV, either end-to-side (EtS) on the IJV, or end-to-end (EtE) on the origin of the thyrolingofacial venous (TLF) trunk. When the pedicle length was insufficient to reach the IJV, anastomoses were performed EtE to a size-matched cervical vein. Of the 246 venous anastomoses, 216 (87.8%) were performed less than 1 cm from the IJV, including 150 EtS on the IJV (61.0%), and 66 EtE on the TLF trunk (26.8%). Thirty veins (12.1%) were anastomosed EtE on other cervical veins more than 1 cm from the IJV. Two venous thromboses occurred (0.9%) and were successfully managed after revision surgery. There was no evidence of an increased thrombosis rate in high-risk or pre-irradiated patients. These findings suggest that the internal jugular vein is safe and reliable as a first-choice recipient vessel for free flap transfers in head and neck oncological reconstruction.

Head and neck INI1-deficient carcinoma without primary: a case report.

BACKGROUND: SMARCB1, also known as INI1, is a member of a large protein complex involved in chromatin remodeling and thus the regulation of gene expression. It is located on chromosome 22q11.2. SMARCB1 tumors have been found in various locations, including the sinonasal region, gastrointestinal tract, central nervous system (in atypical teratoid and rhabdoid tumors), and perirenal region (in malignant rhabdoid tumors) in both adults and children. CASE PRESENTATION: We describe here the first case in the literature of an INI1-deficient neck carcinoma without a primary tumor managed with surgical therapy and neck dissection in a young Caucasian woman of 29 years old, followed by chemotherapy before radiotherapy, with regional control after 18 months of follow-up. Histologic analysis showed an undifferentiated carcinoma without glandular or epidermoid differentiation. Biomolecular analysis of the tumor revealed a homozygous deletion of the SMARCB1 gene on RNA sequencing. CONCLUSION: Research of INI1 deletion should be performed for undifferentiated carcinoma of young patients because of possibilities of molecular therapies such as autophagy inhibitors or proteasome inhibitors could be used in clinical trials.

Predictors of toxicity after curative reirradiation with intensity modulated radiotherapy or proton therapy for recurrent head and neck carcinoma: new dose constraints for pharyngeal constrictors muscles and oral cavity.

BACKGROUND: Our study aims to identify predictive factors of moderate to severe (grade ≥ 2) late toxicity after reirradiation (reRT) of recurrent head and neck carcinoma (HNC) and explore the correlations between dose organs at risk (OAR) and grade ≥ 2 toxicity. MATERIAL AND METHODS: Between 09/2007 and 09/2019, 55 patients were re-irradiated with IMRT or proton therapy with curative intent for advanced HNC. Our study included all patients for whom data from the first and second irradiations were available. Co-variables, including interval to reRT, size of re-irradiated PTV, and dose to OAR, were analyzed as potential predictors for developing moderate to severe long-term toxicity with death as a competing risk. Receiver-operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity. RESULTS: Twenty-three patients participated in our study. After a median follow-up of 41 months, 65% of the patients experienced grade ≥ 2 late toxicity. The average dose to pharyngeal constrictor muscles (PCM) at the time of reRT showed an association with the risk of grade ≥ 2 dysphagia: AUC = 0.78 (95% CI: 0.53-1), optimal cut-off value = 36.7 Gy (sensitivity 62%/specificity 100%). The average dose to the oral cavity at the time of reRT showed an association with the risk of grade ≥ 2 dysgeusia: AUC = 0.96 (0.89-1), optimal cut-off value = 20.5 Gy (sensitivity 100%/specificity 88%). CONCLUSION: Our analysis depicted an association between the dose to OAR and the risk of developing moderate to severe dysphagia and dysgeusia and proposed new dose constraints for PCM (36.7 Gy) and oral cavity (20.5 Gy).

Proton therapy and/or helical tomotherapy for locally advanced sinonasal skull base adenoid cystic carcinoma: Focus on experience of the Institut Curie and review of literature.

BACKGROUND: Sinonasal adenoid cystic carcinomas (SNACC) have high propensity for skull base (SB) infiltration. Unresectability or incomplete surgical resection in such cases make radiotherapy treatment paramount. Curative dose escalation is challenging because of adjacent organs at risk, especially in locally advanced cases. METHODS: Eighteen patients that had locally advanced SB SNACC with unresectable or incomplete surgical resection treated by proton therapy and/or helical tomotherapy at Institut Curie between 3/2010 and 8/2020 were retrospectively included. RESULTS: After median follow-up of 52 months, 5-year OS, LRRFS, DMFS, DFS rates were, respectively, 47% (95%CI: 26-83), 50% (95%CI: 36-88), 39% (95%CI: 26-81), 33% (95%CI: 22-73). One patient had grade 4 late optic nerve disorder. Eight patients had grade 3 late toxicity including mainly hearing impairments. CONCLUSION: Proton therapy and helical tomotherapy are effective and safe methods for curative dose escalation of locally advanced SB SNACC, which are a poor prognosis subgroup. Available literature suggests carbon-ion therapy could be an efficient alternative.

Curative high-dose reirradiation for patients with recurrent head and neck squamous cell carcinoma using IMRT or proton therapy: Outcomes and analysis of patterns of failure.

PURPOSE: To analyze outcomes of patients treated with curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS: Among the 55 patients reirradiated for head and neck cancer from 30/08/2012 to 08/04/2019, 23 had HNSCC and received IMRT (52.2%) or PT (47.8%) at a median maximum dose to the CTV of 66 Gy. RESULTS: After a median follow-up of 41.3 months, 18 patients developed a locoregional recurrence (LR), of which eight (44.4%) occurred within the previously reirradiated volume. Two-year locoregional failure-free survival and overall survival were 18.3%[95%CI:7.1%-47.1%] and 42.5%[95%CI:26.2%-69.1%], respectively. Disease-free survival was significantly longer in the PT group (p = 0.031). Main late grade ≥2 toxicities were dysphagia and trismus. CONCLUSION: Curative reRT in HNSCC is possible for selected cases, but the LR rate in the irradiated field and the risk of toxicity grade ≥2 remain high.

Equivalence Randomized Trial to Compare Treatment on the Basis of Sentinel Node Biopsy Versus Neck Node Dissection in Operable T1-T2N0 Oral and Oropharyngeal Cancer.

PURPOSE: Sentinel node (SN) biopsy is accurate in operable oral and oropharyngeal cT1-T2N0 cancer (OC), but, to our knowledge, the oncologic equivalence of SN biopsy and neck lymph node dissection (ND; standard treatment) has never been evaluated. METHODS: In this phase III multicenter trial, 307 patients with OC were randomly assigned to (1) the ND arm or (2) the SN arm (experimental arm: biopsy alone if negative, or followed by ND if positive, during primary tumor surgery). The primary outcome was neck node recurrence-free survival (RFS) at 2 years. Secondary outcomes were 5-year neck node RFS, 2- and 5-year disease-specific survival (DSS), and overall survival (OS). Other outcomes were hospital stay length, neck and shoulder morbidity, and number of physiotherapy prescriptions during the 2 years after surgery. RESULTS: Data on 279 patients (139 ND and 140 SN) could be analyzed. Neck node RFS was 89.6% (95% CI, 0.83% to 0.94%) at 2 years in the ND arm and 90.7% (95% CI, 0.84% to 0.95%) in the SN arm, confirming the equivalence with P < .01. The 5-year RFS and the 2- and 5-year DSS and OS were not significantly different between arms. The median hospital stay length was 8 days in the ND arm and 7 days in the SN arm (P < .01). The functional outcomes were significantly worse in the ND arm until 6 months after surgery. CONCLUSION: This study demonstrated the oncologic equivalence of the SN and ND approaches, with lower morbidity in the SN arm during the first 6 months after surgery, thus establishing SN as the standard of care in OC.

MMP2 as an independent prognostic stratifier in oral cavity cancers.

Background: Around 25% of oral cavity squamous cell carcinoma (OCSCC) are not controlled by the standard of care, but there is currently no validated biomarker to identify those patients. Our objective was to determine a robust biomarker for severe OCSCC, using a biology-driven strategy. Patients and methods: Tumor and juxtatumor secretome were analyzed in a prospective discovery cohort of 37 OCSCC treated by primary surgery. Independent biomarker validation was performed by RTqPCR in a retrospective cohort of 145 patients with similar clinical features. An 18-gene signature (18 G) predictive of the response to PD-1 blockade was evaluated in the same cohort. Results: Among 29 deregulated molecules identified in a secretome analysis, including chemokines, cytokines, growth factors, and molecules related to tumor growth and tissue remodeling, only soluble MMP2 was a prognostic biomarker. In our validation cohort, high levels of MMP2 and CD276, and low levels of CXCL10 and STAT1 mRNA were associated with poor prognosis in univariate analysis (Kaplan-Meier). MMP2 (p = .001) and extra-nodal extension (ENE) (p = .006) were independent biomarkers of disease-specific survival (DSS) in multivariate analysis and defined prognostic groups with 5-year DSS ranging from 36% (MMP2highENE+) to 88% (MMP2lowENE-). The expression of 18 G was similar in the different prognostic groups, suggesting comparable responsiveness to anti-PD-1. Conclusion: High levels of MMP2 were an independent and validated prognostic biomarker, surpassing other molecules of a large panel of the tumor and immune-related processes, which may be used to select poor prognosis patients for intensified neoadjuvant or adjuvant regimens.

Immune gene expression in head and neck squamous cell carcinoma patients.

BACKGROUND: Nivolumab and pembrolizumab targeting programmed cell death protein 1 (PD-1) have recently been approved among patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) who failed platinum therapy. We aimed to evaluate the prognostic value of selected immune gene expression in HNSCC. PATIENTS AND METHODS: We retrospectively assessed the expression of 46 immune-related genes and immune-cell subpopulation genes including immune checkpoints by real-time polymerase chain reaction among 96 patients with HNSCC who underwent primary surgery at Institut Curie between 1990 and 2006. Univariate and multivariate analyses were performed to assess the prognostic value of dysregulated genes. RESULTS: The Median age of the population was 56 years [range: 35-78]. Primary tumour location was oral cavity (45%), oropharynx (21%), larynx (18%) and hypopharynx (17%). Twelve patients (13%) had an oropharyngeal human papillomavirus-positive tumour. Most significantly overexpressed immune-related genes were TNFRSF9/4-1BB (77%), IDO1 (75%), TNFSF4/OX40L (74%) and TNFRSF18/GITR (74%), and immune-cell subpopulation gene was FOXP3 (62%). Eighty-five percent of tumours analysed overexpressed actionable immunity genes, including PD-1/PD-L1, TIGIT, OX40/OX40L and/or CTLA4. Among the immune-related genes, high OX40L mRNA level (p = 0.0009) and low PD-1 mRNA level (p = 0.004) were associated with the highest risk of recurrence. Among the immune-cell subpopulation genes, patients with high PDGFRB mRNA level (p < 0.0001) and low CD3E (p = 0.0009) or CD8A mRNA levels (p = 0.004) were also at the highest risk of recurrence. CONCLUSIONS: OX40L and PDGFRB overexpression was associated with poor outcomes, whereas PD-1 overexpression was associated with good prognosis in patients with HNSCC treated with primary surgery, suggesting their relevance as potential prognostic biomarkers and major therapeutic targets.

Acellular fish skin matrix on thin-skin graft donor sites: a preliminary study.

OBJECTIVE: Surgery for head and neck cancer often requires free flap reconstructions, whose harvesting site often requires a thin-skin graft. Wounds from the thin-skin donor site are comparable to an intermediate or deep second-degree burn. This is uncomfortable and can lead to complications such as a long healing time, local infections and pain. Since they are reproducible, these wounds may serve as a model for an objective assessment of new healing medical devices. The acellular fish skin matrix is a new medical device designed to improve healing quality and time. METHODS: We compared the outcomes between standard procedure and the use of this matrix placed on the split-thickness skin graft (STSG) donor site, in patients operated on in our centre for radial forearm free flap reconstruction for head and neck wounds. RESULTS: There were 21 patients included. The healing time was halved when using the acellular fish skin matrix, from 68 to 32 days on average. Acellular fish skin matrix reduced pain levels and local infection. The visual analogue pain scale (VAS) was ≥3 at five days (p=0.0034) and infection rate reduced from 60% to 0% (p=0.0039). CONCLUSION: These results are extremely encouraging. However, it is important to take into account the relatively high cost of this matrix for its future indications. A larger study including an overall cost estimation and an assessment on different wound types would be interesting, to better target the indications of the acellular fish skin matrix.

Fine-needle aspiration features of ossifying fibromyxoid tumor in the breast: A case report and literature review.

Ossifying fibromyxoid tumor (OFT) is a very rare soft tissue tumor which is characterized by incomplete peripheral mature bone shell. To date, cytological features of OFT have been poorly studied with only seven case reports. In this study, an additional case of OFT investigated by fine-needle aspiration is presented. A 75-year-old man with advanced nasopharyngeal carcinoma presented with peripherally calcified right breast mass. Smears were hypercellular and stroma-rich. Tumor cells were mainly dispersed, with epithelioid morphology and eccentrically located nuclei. In the background, there was abundant eosinophilic myxoid secretion. No necrosis, atypia, or mitotic activity was found. The tumor showed diffuse S-100, CD10, STAT6 expression and focal desmin, estrogen receptor (ER), and progesteron receptor (PgR) expression. Fluorescence in situ hybridization study revealed PHF1 rearrangement in 9% of cells. Cytological characteristic of OFT is quite distinctive and precise diagnosis can be made, especially when it is coupled with compatible radiological findings.

Transoral robotic resection of benign tumors of the upper aerodigestive tract: Experience of the French group of GETTEC.

BACKGROUND: The purpose of this study was to assess the current use of transoral robotic surgery (TORS) in benign tumors of the upper aerodigestive tract through a case series and a literature review. METHODS: This multicentric retrospective study was conducted in 6 French centers between November 2009 and July 2017. RESULTS: Twenty-one patients had a TORS resection of a tumor at varied locations with differing histopathologic characteristics. The mean postoperative hospital stay was 6.1 days. Eight patients had nasogastric tubes, which were removed after a mean of 5.6 days. Two patients had a prophylactic tracheostomy for an average of 5.5 days. A third tracheostomy was performed secondarily for postoperative bleeding. No recurrences were observed during the 2-year follow-up. CONCLUSION: This technique caused few complications and resulted in short hospitalization, with satisfactory functional and recurrence outcomes. However, the risk of bleeding and edema must be considered, and the need for a tracheostomy must be approached wisely.

Multicenter assessment of exclusive endoscopic endonasal approach for the treatment of 53 olfactory neuroblastomas.

BACKGROUND: Given the particularities of olfactory neuroblastoma (ONB) and the lack of studies on the subject, a multicenter collaborative study was conducted to assess treatment strategy. METHODS: Fifty-three patients with ONB were included from the French Rare Head and Neck Cancer Expert Network (REFCOR) database: 16T1, 8T2, 19T3, and 10T4. All cases were treated endoscopically with skull base removal and repair in 26 cases (49%) and without external craniotomy. RESULTS: The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 87% and 71%, respectively, with mean follow-up of 45.4 ± 26.5 months. The complication rate was 18.8% with 4 cases of meningitis. Pathological analysis showed positive margins in 26.8%, notably on the dura-mater and periorbita, without impairment of OS or DFS. Forty-eight patients received adjuvant radiotherapy on T ± N. Ten patients had a recurrence (18.9%). Six patients died of their disease. Prophylactic neck irradiation seemed to reduce the recurrence rate. CONCLUSION: Exclusively endoscopic treatment proved efficient and reliable in a large controlled series.

Prognostic value of the seventh AJCC/UICC TNM classification of intestinal-type ethmoid adenocarcinoma: Systematic review and risk prediction model.

BACKGROUND: The purpose of this study was to propose a prognostic classification of intestinal-type adenocarcinoma (ITAC) based on literature search and prognostic modeling of cohort data. METHODS: We first conducted a literature search to assess the homogeneity of the reported estimates of 5-year survival and to identify the influence of T classification. We then pooled prospective data from 3 large French and Italian series to predict time to all-cause mortality. The sample was randomly split to derive and then to validate the proposed prognostic model. RESULTS: Literature analysis confirmed the heterogeneity in 5-year survival rates, partly explained in subsets of homogeneous T-values. The sample included 223 patients, randomly separated into a derivation (n = 141) and a validation set (n = 82). Invasion of the sphenoid lateral and/or posterior walls and dura/cerebral invasion were systematically associated with a poor survival. CONCLUSION: The incorporation of the invasion of the sphenoid lateral or posterior walls should be considered for ITAC management and prognostication. © 2017 Wiley Periodicals, Inc. Head Neck 39: 668-678, 2017.

Intensive nutritional care for patients treated with radiotherapy in head and neck cancer: a randomized study and meta-analysis.

Nutritional care improves quality of life (QOL) in head and neck cancer patients treated with radiotherapy. The aim of our study was to determine whether intensive nutritional care (INC) would further improve QOL. In addition to a control group based on European and American guidelines, patients included in the INC group received six meetings with a dietitian. QOL was measured after radiotherapy using the EORTC QLQ-C30. We performed a meta-analysis to determine the best nutritional care. In the 87 patients, the QOL scores, weight, energy, and protein intakes were similar between the INC group (n = 43) and the control group (n = 44). The meta-analysis revealed no heterogeneity and significant differences in QOL (three studies) (p = 0.46) or weight changes after radiotherapy (four studies) (p = 0.06). The nutritional care specified in the European and American guidelines is composed of well-defined recommendations, and appears sufficient to maintain QOL without further intervention.

Endoscopic nasal versus open approach for the management of sinonasal adenocarcinoma: A pooled-analysis of 1826 patients.

BACKGROUND: Surgical resection represents the gold standard for the treatment of sinonasal malignancies. This study reviewed the published outcomes on endoscopic surgery or endoscopic-assisted surgery versus open approach for the management of sinonasal adenocarcinomas. METHODS: PubMed, EMBASE, the Cochrane Library, and CENTRAL electronic databases were searched for English language articles on endoscopic surgery, endoscopic-assisted surgery, and open approach for sinonasal adenocarcinomas. Each article was examined for patient data and outcomes for analysis. RESULTS: Thirty-nine articles including 1826 patients were used for the analysis. The endoscopic surgery and endoscopic-assisted surgery showed low rates of major complications (6.6% and 25.9%, respectively) compared to open approaches (36.4%; p < .01). The incidence of local failure was lower in the endoscopic surgery group as compared with open approach patients (17.8% vs 38.5%; p < .01, respectively). The multivariate Cox regression model showed a worst overall survival related to advanced T classification and open approach. CONCLUSION: From the existing body of data, there is growing evidence that endoscopic nasal resection is a safe surgical option in the management of sinonasal adenocarcinomas. © 2015 Wiley Periodicals, Head Neck 38: E2267-E2274, 2016.