BACKGROUND:Malakoplakia is an uncommon granulomatous inflammatory disease which can mimic malignancy. Laryngopharyngeal malakoplakia associated with diabetes mellitus, hypertension, and uremia has not been previously described. There are numerous knowledge lacunae in our contemporary research on malakoplakia in patients with these comorbidities. METHODS AND RESULTS:A 49-year-old male complained of mechanical dysphagia for 30 days, and laryngoscopy revealed a huge mass at the base of tongue. Magnetic resonance imaging (MRI) demonstrated a lesion measured approximately 2.7 × 2.0 × 2.5 cm. After surgery, the patient was followed up for over 20 months without recurrence. IHC staining was positive for Vimentin and CD68, while SOX-10 and S-100 were negative. Histopathological examination revealed Michaelis-Gutmann bodies, confirming a diagnosis of malakoplakia. CONCLUSION:Malakoplakia should be considered in the differential diagnosis of a pharyngeal mass. Complete surgical excision could be an effective way to treat malakoplakia and patients need long-term follow-up.
BACKGROUND:This prospective study investigates trismus prevalence, quality of life (QOL), and trismus-related symptoms in HNC patients up to 10 years post-radiotherapy (RT). METHODS:A total of 211 patients with HNC receiving RT were followed pretreatment, 12, 60, and 120 months post-RT. Primary outcome was trismus defined as a maximum interincisal opening (MIO) ≤ 35 mm. Secondary outcomes included the European Organization for Treatment of Cancer Quality-of-Life Questionnaire Core-30 (EORTC QLQ-C30), Head and Neck-35 (EORTC QLQ-HN35) and Gothenburg Trismus Questionnaire (GTQ). RESULTS:At 10 years post-RT, 4/15 domains and items in EORTC QLQ-C30 showed a deterioration when compared to baseline. Corresponding figures for EORTC QLQ-HN35 and GTQ were 11/14 (six domains and five single items) and 4/7, respectively (domains only). The majority of scores remained unchanged between 5 and 10 years post-RT. Trismus was present in 35% of patients at 10 years post-RT. CONCLUSION:Trismus continues to be present in up to 35% of patients 10 years post-RT as well as a reduced QOL, with no significant changes occurring between 5 and 10 years post-RT.
BACKGROUND:Neoadjuvant immunotherapy is an emerging treatment for patients with head and neck cancer. Given the heterogeneity of response, novel methods of intraoperative tumor and margin assessment warrant investigation. METHODS:A 55-year-old male presented with a cT3N2c supraglottic squamous cell carcinoma with a combined positive score of 5. The patient received 2 cycles of neoadjuvant pembrolizumab prior to laryngectomy. The specimen underwent intraoperative micro-positron emission tomography/computed tomography (micro-PET/CT) imaging. RESULTS:Final pathology demonstrated a pathologic complete response (pCR). On pre-treatment whole body PET/CT, maximum standardized uptake value (SUVmax) was 21.8 in the tumor and 10.7 (~50%) at the tracheostomy site. Intraoperative micro-PET/CT showed residual uptake in the tumor region (SUVmax 16.1) and tracheostomy site (SUVmax 16.9). CONCLUSION:In this case report of pCR, intraoperative micro-PET/CT demonstrated similar avidity at the primary tumor site compared to the tracheostomy site, highlighting the potential utility of this novel imaging approach in patients receiving neoadjuvant immunotherapy.
BACKGROUND:Published survival rates for bone-anchored craniofacial implants exceed 85%, but derive largely from mixed populations. Whether these apply to head and neck oncologic surgery remains uncertain. METHODS:Retrospective survival analysis of implants placed for prosthetic rehabilitation following extirpative surgery at a UK center (2005-2024). RESULTS:Survival among 184 implants in 51 patients was 94%, 60% and 46% at 1, 3 and 5 years (median 4.1 years, 95% CI 3.0-6.3). 77% of patients received radiation therapy. Median dose to implant region was 57 Gy. On univariate analysis, radiation, diabetes and older age predicted implant loss. On multivariable analysis, diabetes, present in three patients, predicted implant loss (HR 4.0, 95% CI 1.5-10.7), while radiation therapy trended towards implant loss. Annual hazard rates demonstrated continual attrition without plateau. CONCLUSIONS:Five-year survival in this oncologic cohort was half the published rate. Ongoing attrition supports supernumerary implant placement and lifelong management.
BACKGROUND:Perineural invasion (PNI) is an established adverse prognostic factor in oral squamous cell carcinoma (OSCC), but the implications of its extent as well as its relationship with surgical margin status and the extent of microscopic tumor spread remain unclear. METHODS:We retrospectively analyzed 165 patients with OSCC treated surgically with curative intent between 2010 and 2019. PNI was assessed for presence, subtype, number of foci, location, and diameter of the largest involved nerve. Associations with margin status and survival outcomes were evaluated using univariate and multivariate analyses. RESULTS:PNI was present in 29 patients (17.6%) and was associated with advanced tumor stage, nodal metastasis, positive surgical margins (HR 3.4, 95% CI 1.1-10.2), and increased use of adjuvant radiotherapy. While PNI presence predicted poorer survival, the diameter of the largest invaded nerve provided superior prognostic discrimination. A cutoff of 200 μm independently predicted disease-specific survival (HR 5.7, 95% CI 1.7-19.0) and significantly improved multivariable model performance. CONCLUSIONS:PNI correlates with positive surgical margins. Quantifying PNI, particularly nerve diameter, enhances prognostic stratification and may inform individualized surgical margin planning in OSCC.
BACKGROUND:Tumor tissue-modified viral (TTMV) human papillomavirus (HPV) DNA testing has high diagnostic and surveillance performance in HPV-associated oropharyngeal squamous cell carcinoma, but its utility in HPV-associated non-oropharyngeal (non-OP) head and neck squamous cell carcinoma (HNSCC) is not well defined. METHODS:We performed a retrospective cohort study of patients with biopsy-confirmed HPV-positive non-OP HNSCC who underwent TTMV-HPV DNA testing at a single tertiary academic center from April 2020 to January 2025. Diagnostic performance was assessed for pretreatment testing, and surveillance performance was assessed per test and per patient. RESULTS:The diagnostic cohort included 19 patients and demonstrated 80% sensitivity and 100% specificity. The surveillance cohort included 15 patients who underwent 32 tests. Per-test surveillance sensitivity was 87%, specificity 100%, positive predictive value 100%, and negative predictive value 89%. Per-patient surveillance sensitivity was 86%, specificity 100%, positive predictive value 100%, and negative predictive value 89%. In two patients, positive surveillance tests preceded clinical or radiographic recurrence by 18 and 110 days. CONCLUSIONS:TTMV-HPV DNA testing demonstrated strong diagnostic and surveillance performance in HPV-associated non-OP HNSCC and may be a useful adjunct in posttreatment surveillance.
BACKGROUND:The incidence of human papillomavirus-associated (HPV) oropharyngeal squamous cell carcinoma (OPSCC) is rising, making accurate detection of synchronous primary tumors essential for staging and treatment planning. METHODS:This multi-institutional retrospective cohort study (2019-2026) included adult participants across three academic tertiary centers who underwent PET/CT and subsequent biopsy or surgical resection with histopathological confirmation of p16-positive disease. RESULTS:Among 306 patients meeting inclusion criteria, PET/CT identified 15 suspicious for synchronous primary tumors; seven (mean age 58.90 ± 11.48 years) were pathologically confirmed. PET/CT demonstrated 77.78% sensitivity, 97.31% specificity, 46.67% positive predictive value (PPV), and 99.31% negative predictive value (NPV). False positives were attributed to physiologic bilateral uptake, reactive lymphoid tissue, or inflammation. CONCLUSIONS AND RELEVANCE:PET/CT demonstrates excellent NPV for excluding synchronous primary tumors in HPV-positive OPSCC and moderate PPV for identifying them. In settings of multifocal fluorodeoxyglucose uptake, pathologic confirmation is warranted prior to definitive management.
BACKGROUND:The AJCC 8th edition distinguishes p16-positive oropharyngeal head and neck carcinoma of unknown primary (HNCUP) due to its superior prognosis. However, standardized radiation volume guidelines are lacking. This study evaluates the safety of p16-guided mucosal volume reduction. METHODS:A retrospective review of 126 HNCUP patients (2009-2023) was conducted. p16-negative patients received comprehensive mucosal and laryngeal irradiation; p16-positive patients received risk-adapted, reduced-volume radiation limited to the ipsilateral naso- and oropharyngeal mucosa and elective nodal regions. Acute and late toxicities were reviewed. RESULTS:The cohort included 97 p16-positive and 29 p16-negative patients (median follow-up 38 months). Five-year overall survival was 90.0% versus 69.2% for p16-positive and p16-negative patients. All mucosal emergences and neck recurrences occurred within the radiation fields. Acute grade 3 toxicities were comparable between groups. CONCLUSIONS:p16-guided mucosal volume reduction in HNCUP appears oncologically safe, without compromising disease control or survival, supporting radiotherapy volume de-intensification for p16-positive disease.
INTRODUCTION:A Phase II trial demonstrated that neoadjuvant cemiplimab was associated with pathologic complete response (pCR) in 51% of patients with locoregionally advanced cutaneous squamous cell carcinoma (cuSCC). We evaluated real-world radiographic and pathologic responses to neoadjuvant cemiplimab and assessed radiologic-pathologic concordance. METHODS:Retrospective single-institution cohort study including 18 patients with locoregionally advanced head and neck cuSCC treated with neoadjuvant cemiplimab before curative-intent surgery between 2019 and 2024. Pathologic and radiographic responses were assessed using pathology review and RECIST 1.1/iRECIST. RESULTS:pCR occurred in 11 patients (61%) and major pathologic response (MPR) in 2 (11%), yielding a 72% combined pathologic response rate. Among 16 patients with evaluable imaging, only 33% demonstrated radiographic partial response (PR), and none achieved radiographic complete response. Radiologic response frequently underestimated tumor clearance. CONCLUSIONS:Neoadjuvant cemiplimab produced high pathologic response rates in real-world practice, while RECIST-based imaging underestimated true tumor response, highlighting limitations of anatomic imaging in immunotherapy-treated cuSCC.
IMPORTANCE:Significant international variations exist for prevention methods, diagnostic, and management criteria for pharyngocutaneous fistula. OBJECTIVE:To formulate best practice management guidelines for pharyngocutaneous fistula after total laryngectomy. DESIGN:Modified Delphi consensus study conducted between January 2024 and November 2025 using two rounds of a structured survey. Levels of consensus were evaluated through a 9-point Likert scale and predefined cutoffs: strong consensus (≥ 80% in 7-9 range, median ≥ 9), consensus (≥ 80% in 7-9 range, median 8-9), near-consensus (≥ 70% in 7-9 range), or no-consensus (< 70% agreement). SETTING:International multicenter study. Participation of experts from 18 countries of America, Europe, Asia, South America, and Oceania, under the guidance of the International Federation of Oto-rhino-laryngological Societies (IFOS). PARTICIPANTS:A multidisciplinary international panel of 36 experts in head and neck surgery, otolaryngology, radiation oncology, radiology, and plastic surgery. The panelists were chosen for their clinical expertise in the area of total laryngectomy and pharyngocutaneous fistula management; published work in the form of peer-reviewed publications, as well as geographical representation. MAIN OUTCOMES AND MEASURES:The level of consensus in 59 statements regarding fistula definition and classification, preoperative risk factors, prevention strategies, diagnostic modalities, conservative management protocols, surgical intervention criteria, nutritional support, and patient outcomes. RESULTS:A consensus or strong consensus was reached on 30 of 59 statements (50.8%). Strong consensus levels were reached for preoperative nutrition optimization (median 9.0), postoperative enteral feeding support (median 9.0), standardized surveillance protocols (median 9.0), and revision surgery for persisting fistulae (median 9.0). Consensus was also achieved for the use of vascularized tissue reinforcement in selected high-risk settings, although the preferred reconstructive strategy varied according to flap type and clinical scenario. Of the 29 statements, 5 (8.5%) were excluded at Round 1 as a result of conceptual repetition as highlighted by panel feedback, and 24 (40.7%) did not reach consensus after both rounds, including fistula classification systems, prophylactic salivary bypass tubes, time to resume oral feeding postoperatively and negative pressure wound therapy. CONCLUSIONS AND RELEVANCE:This Delphi study from an international panel provides areas of agreement and ongoing equipoise across the prevention, diagnosis, and management of PCF, while demonstrating significant practice variability in terms of their classification, the use of prophylactic interventions, and conservative therapies.
BACKGROUND:Head and neck tumors with skull base involvement may require drilling of tumor infiltrated bone. We hypothesize that bone dust generated during this process contains viable tumor cells that may seed the surgical field. METHODS:Tumors with gross bone invasion were drilled, and dust was collected for H&E, cell viability analysis, and single-cell sequencing (scRNAseq). An ultrasonic bone aspirator (UBA) and synthetic barrier were evaluated as methods to decrease dust dispersion. RESULTS:H&E confirmed the presence of viable tumor cells in bone dust, while scRNAseq demonstrated keratinocyte and epithelial cells expressing tumor-associated gene sets. UBA decreased viable tumor cell count compared to a drill both on H&E and cell count viability analysis. The synthetic barrier prevented bone dust accumulation on the surrounding field after drilling. CONCLUSIONS:Viable cancer cells and supporting TME elements can be isolated from bone dust. An UBA or synthetic barrier may reduce dust dispersion and accumulation on the surrounding tissue.
BACKGROUND:Multi-flap reconstruction is often required for extensive head and neck defects, especially in recurrent disease, prior reconstruction, or vessel-depleted necks. While traditional donor sites remain foundational, the reliability of alternative soft tissue free flaps is less defined. METHODS:This retrospective cohort study compared traditional and alternative soft tissue free flaps in multi-flap head and neck reconstruction. Outcomes were analyzed in unmatched and propensity score-matched cohorts. Primary endpoints included overall recipient site complications, flap loss, thrombosis, reoperation, and length of stay. RESULTS:The unmatched cohort included 171 patients and 347 flaps: 297 traditional (86%) and 50 alternative (14%). After matching, outcomes were comparable between groups. No statistically significant differences were seen in recipient site complications, reoperation, thrombosis, flap loss, or hospital stay. CONCLUSIONS:Alternative soft tissue free flaps appear safe and reliable when traditional workhorse flaps are unavailable.
BACKGROUND:Radiation-associated dysphagia is common after radiotherapy for head and neck cancer and may occur early or years later. The effect of preventive exercises might be undermined by poor adherence. AIM:To evaluate the effect of a simple preventive exercise protocol on swallowing function up to 12 months after radiotherapy. METHODS:Patients were randomized to an active group (n = 45) or control group (n = 44). The active group performed preventive exercises including the tongue hold exercise. Assessments were conducted before radiotherapy and at 1, 6, and 12 months post-treatment using the Penetration-Aspiration Scale, DIGEST-FEES, and the M. D. Anderson dysphagia inventory. RESULTS:No significant differences were found between groups. However, participants with ≥ 75% adherence in the active group showed significantly less deterioration at 12 months on the penetration-aspiration scale. CONCLUSIONS:Overall, no significant effect on swallowing function was demonstrated. However, results indicate that high adherence reduces deterioration.
BACKGROUND:Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with limited population-based data. METHODS:Incidence trends and survival outcomes were analyzed using the Surveillance, Epidemiology, and End Results database. RESULTS:A total of 955 cases were identified. The age-adjusted incidence rate increased from 0.158 in 2000 to 1.18 in 2022 (average annual percent change, 10.38%; p < 0.001), accelerating after 2012. Increases were more pronounced among females, older patients, regional-stage disease, and tumors > 2 cm. The 5-year disease-specific survival (DSS) and overall survival were 60.6% and 51.2%, respectively. Advanced age, non-parotid site, larger tumor size, lymph node metastasis, advanced stage, and non-surgical management were independent predictors of worse DSS. Patients diagnosed in 2013-2022 showed better DSS compared with those in 2004-2012 (64.7% vs. 52.0%, p = 0.048). CONCLUSION:SDC incidence has increased rapidly, possibly reflecting improved diagnostic recognition and reclassification, with only modest survival improvement over the past decade.
BACKGROUND:Head and neck cancer patients often experience polypharmacy due to complex treatments and comorbidities. The Beers Criteria is a list of potentially inappropriate medications (PIMs) for patients above age 65 developed by the American Geriatrics Society. We hypothesize that increased use of PIMs will be associated with inferior health and quality of life outcomes in elderly patients with head and neck cancer. METHODS:We retrospectively examined patients aged ≥ 65 years with head and neck cancer diagnosed between 2011 and 2015 using SEER-Medicare data, analyzing associations between Beers Criteria Medications (BCMs) and survival as a primary outcome. Emergency department (ED) utilization served as a secondary outcome. RESULTS:Among 5213 patients (mean age 72.6 years), 44% received no BCMs within 1 year of diagnosis, while 41.3% received 1 BCM, 9.3% received 2 BCMs, and 5.4% received ≥ 3 BCMs. The most common medications prescribed were Lorazepam (12.3%), Zolpidem (7.9%), and Alprazolam (7.5%). Two-year survival decreased with BCM use in a dose-dependent fashion: 88.2% (0 BCM), 86.8% (1 BCM), 86.7% (2 BCMs), and 81.4% (≥ 3 BCMs; p < 0.001). BCM users had higher ED utilization in the year after diagnosis (mean 1.21 vs. 0.95 claims, p = 0.004). CONCLUSIONS:BCMs in elderly head and neck cancer patients were associated with inferior survival and increased healthcare utilization. These findings highlight the need for medication reconciliation and systematic reviews by multidisciplinary care teams to optimize outcomes in this vulnerable population.
OBJECTIVE:To evaluate the diagnostic performance of shear wave elastography (SWE) and strain elastography (SE) as complementary techniques to conventional B-mode ultrasound for differentiating benign, indeterminate, and malignant thyroid nodules. METHODS:This prospective cross-sectional study included 208 thyroid nodules evaluated using B-mode ultrasound, Color Doppler, SWE, and SE. Nodules were classified according to the ACR TI-RADS and Bethesda systems, and histopathological diagnosis was obtained when surgery was performed. Receiver operating characteristic (ROC) analysis determined the optimal SWE cutoff value and generalized estimating equations (GEE)-based multivariable logistic regression models were used to identify independent predictors of malignancy. RESULTS:SWE demonstrated excellent diagnostic performance for distinguishing Bethesda V/VI from Bethesda II nodules (AUC, 87.6%), with an optimal cutoff value of ≥ 26 kPa (80.0% sensitivity and 81.0% specificity). After multivariable adjustment, hard strain elastography, SWE ≥ 26 kPa, male sex, irregular margins, and predominantly central vascularization independently predicted malignant cytology (Bethesda V/VI vs. Bethesda II). In the comparison with indeterminate cytology (Bethesda III/IV), SWE remained an independent predictor together with male sex, macrocalcifications, microcalcifications, and predominantly central vascularization. Hard strain elastography was the only independent predictor of malignant histopathological diagnosis. CONCLUSION:SWE and SE provide complementary diagnostic information beyond conventional B-mode ultrasound. SWE demonstrated excellent performance for cytological risk stratification, whereas hard strain elastography was the only independent predictor of malignant histopathological diagnosis. These findings support the complementary use of elastography alongside conventional ultrasound in thyroid nodule risk stratification.
BACKGROUND:The role of radiation therapy (RT) in improving survival outcomes for patients with high-risk cutaneous squamous cell carcinoma (cSCC) and perineural invasion (PNI) remains incompletely defined. We evaluated overall survival (OS) in surgically treated patients with head and neck cSCC with or without PNI, stratified by receipt of RT. METHODS:This retrospective cohort study queried the National Cancer Database (NCDB) for adults with head and neck cSCC diagnosed between 2018 and 2021, identified by cutaneous head-and-neck primary-site codes (C44.0-C44.4) together with squamous-cell histology coding (ICD-O-3 8050-8084). Only patients who underwent definitive surgery were included; biopsy-only patients were excluded. Patients with missing data on race/ethnicity, age, sex, or PNI status were excluded. OS was evaluated using Kaplan-Meier curves and compared with the log-rank test. Multivariable Cox proportional-hazards regression, adjusted for the available demographic covariates, assessed associations between clinicopathologic variables and OS, with an interaction term used to test whether the association of RT with OS differed by PNI status. Results are reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Statistical significance was defined as p < 0.05. RESULTS:Among 929 patients included in the final analysis (276 PNI-positive, 653 PNI-negative), PNI-positive patients were more likely to be White (92.0% vs. 85.8%, p = 0.018) and to have received RT (49.6% vs. 11.3%, p < 0.001). OS did not differ significantly between PNI-positive and PNI-negative patients on univariate or multivariable analysis (log-rank p = 0.120; adjusted HR = 1.38, 95% CI: 0.98-1.96, p = 0.066). A statistically significant PNI-RT interaction was identified on both univariate (HR = 0.60, 95% CI: 0.34-1.06, p = 0.042) and multivariable analysis (HR = 0.65, 95% CI: 0.37-1.15, p = 0.016), indicating that the apparent survival association of RT was concentrated among PNI-positive patients. CONCLUSIONS:In this NCDB cohort, PNI-positive patients who did not receive RT had worse survival than PNI-negative patients not receiving RT, whereas PNI-positive patients who received RT had outcomes comparable to the PNI-negative reference group. These hypothesis-generating findings are consistent with the possibility that RT may attenuate the adverse prognostic association of PNI in head and neck cSCC; however, the analysis is susceptible to confounding by indication and to the limitations of administrative data, and prospective studies are warranted to validate these results.
OBJECTIVE:To evaluate the diagnostic value of arterial enhancement fraction (AEF) derived from dual-layer detector spectral CT (DLCT) in preoperative assessment of cervical lymph node metastasis in patients with papillary thyroid carcinoma (PTC), and to compare its performance with other spectral CT quantitative parameters and conventional CT features. METHODS:This retrospective study included 42 PTC patients, with a total of 94 lymph node lesions. The conventional CT morphological features of PTC primary lesions and lymph nodes were assessed. Quantitative spectral CT parameters evaluated in primary PTC lesions comprised arterial phase iodine density (AP-ID), venous phase iodine density (VP-ID), and the AEF was calculated accordingly. For lymph nodes, parameters evaluated in both arterial and venous phases comprised conventional images (CIs), virtual monoenergetic images (VMI), iodine density (ID), effective atomic number (Zeff), electron density (ED), spectral curve slope (λHU), and AEF. Receiver operating characteristic (ROC) curve analysis was employed to evaluate diagnostic performance. RESULTS:The diameter, cystic change, and contrast enhancement pattern were significantly different between metastatic and nonmetastatic lymph nodes (p < 0.05). No statistically significant differences were observed between metastatic and nonmetastatic lymph nodes in terms of anatomical level, density, boundary, outline, and calcification (p > 0.05). Metastatic lymph nodes demonstrated significantly higher values in AP-CI, AP-VMI 40 keV, AP-VMI 100 keV, AP-ID, AP-Zeff, AP-λHU, and AEF compared to nonmetastatic nodes (p < 0.05). Among the evaluated spectral CT parameters, AEF showed the highest individual diagnostic performance, with an AUC of 0.775 (95% CI: 0.675-0.875). The combined model achieved an AUC of 0.809 (95% CI: 0.716-0.901), and the difference in AUC between AEF and the combined model was not statistically significant (p = 0.155). CONCLUSIONS:AEF demonstrated significant differences between metastatic and nonmetastatic cervical lymph nodes and showed the highest individual diagnostic performance among the evaluated spectral CT parameters. AEF may serve as a quantitative imaging biomarker to assist the preoperative assessment of cervical lymph node metastasis in patients with PTC. CRITICAL RELEVANCE STATEMENT:Quantitative parameters derived from DLCT, particularly the AEF, provided additional quantitative information for the preoperative assessment of cervical lymph node metastasis in patients with PTC. AEF showed promising diagnostic performance and may complement conventional CT evaluation for lymph node characterization.
