Defining the Genomic Landscape of Diffuse Sclerosing Papillary Thyroid Carcinoma: Prognostic Implications of RET Fusions.

BACKGROUND: Diffuse sclerosing papillary thyroid carcinoma (DSPTC) is an aggressive histopathologic subtype of papillary thyroid carcinoma. Correlation between genotype and phenotype has not been comprehensively described. This study aimed to describe the genomic landscape of DSPTC comprehensively using next-generation sequencing (NGS), analyze the prognostic implications of different mutations, and identify potential molecular treatment targets. METHODS: Tumor tissue was available for 41 DSPTC patients treated at Memorial Sloan Kettering Cancer Center between 2004 and 2021. After DNA extraction, NGS was performed using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets platform, which sequences 505 critical cancer genes. Clinicopathologic characteristics were compared using the chi-square test. The Kaplan-Meier method and log-rank statistics were used to compare outcomes. RESULTS: The most common mutation was RET fusion, occurring in 32% (13/41) of the patients. Other oncologic drivers occurred in 68% (28/41) of the patients, including 8 BRAFV600E mutations (20%) and 4 USP8 mutations (10%), which have not been described in thyroid malignancy previously. Patients experienced RET fusion-positive tumors at a younger age than other drivers, with more aggressive histopathologic features and more advanced T stage (p = 0.019). Patients who were RET fusion-positive had a significantly poorer 5-year recurrence-free survival probability than those with other drivers (46% vs 84%; p = 0.003; median follow-up period, 45 months). In multivariable analysis, RET fusion was the only independent risk factor for recurrence (hazard ratio [HR], 7.69; p = 0.017). CONCLUSION: Gene-sequencing should be strongly considered for recurrent DSPTC due to significant prognostic and treatment implications of RET fusion identification. The novel finding of USP8 mutation in DSPTC requires further investigation into its potential as a driver mutation.

Epidemiology and management of oral cavity squamous cell carcinoma in Ireland.

INTRODUCTION: The epidemiology and management of oral cavity cancer have changed considerably in recent decades. This study examines epidemiological and management trends in oral cavity squamous cell carcinoma (OCSCC). METHODS: A retrospective cohort study of data from the National Cancer Registry of Ireland between 1994 and 2014. RESULTS: A total of 2725 patients were identified. The most common subsites were the tongue (34 %, n = 1025), lip (19 %, n = 575), floor of mouth (FOM) (18 %, n = 550), and retromolar trigone (RMT) (6 %, n = 189). The incidence of OCSCC remained largely unchanged (3.14 cases/100000/year) during the study period. 5-year disease-specific survival (DSS) was 58.6 % overall, varying between subsites (lip 85 %, RMT 62.9 %, tongue 54.7 %, and FOM 47.3 %). DSS improved over the study period (p = 0.03), in particular for tongue primaries (p = 0.007). Primary surgery significantly improved DSS versus radiotherapy (HR 0.28, p < 0.0001). Survival of T4 disease managed surgically was superior to that of T1 disease managed with radiotherapy. In node positive patients, chemotherapy improved overall survival (HR 0.8 p = 0.038) but not DSS (HR 0.87 p = 0.215). CONCLUSION: Primary surgery remains the standard of care in the management of OCSCC. Prognosis has improved in line with an increase in the use of primary surgery in the same time frame, though the incidence remains unchanged.

Diffuse Sclerosing Papillary Thyroid Carcinoma: Clinicopathological Characteristics and Prognostic Implications Compared with Classic and Tall Cell Papillary Thyroid Cancer.

BACKGROUND: The clinical behaviour and oncologic outcome of diffuse sclerosing papillary thyroid carcinoma (DS-PTC) is poorly understood. The objectives of this study were to compare the clinicopathological characteristics and oncological outcomes of DS-PTC to classic PTC (cPTC) and tall cell PTC (TC-PTC). METHODS: After institutional review board approval, 86 DS-PTC, 2,080 cPTC, and 701 TC-PTC patients treated at MSKCC between 1986 and 2021 were identified. Clinicopathological characteristics were compared by using chi-square test. Kaplan-Meier and log rank were used to compare recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). DS-PTC patients were propensity matched to cPTC and TC-PTC patients for further comparison. RESULTS: DS-PTC patients were younger with more advanced disease than cPTC and TC-PTC (p < 0.05). Lymphovascular invasion (LVI), extranodal extension, and positive margins were more common in DS-PTC (p < 0.02). Propensity matching confirmed more aggressive histopathological features in DS-PTC. The median number of metastatic lymph nodes was significantly greater and DS-PTC metastases were RAI avid. DS-PTC 5-year RFS was 50.4% compared with 92.4% in cPTC and 88.4% in TC-PTC (p < 0.001). Multivariate analysis confirmed DS-PTC as an independent prognostic factor of recurrence. Ten-year DSS for DS-PTC was 100% compared with 97.1% in cPTC and 91.1% in TC-PTC. Differentiated high-grade, thyroid carcinoma DS had more advanced T-stage and worse 5-year RFS than DS-PTC. CONCLUSIONS: DS-PTC presents with more advanced clinicopathological features than cPTC and TC-PTC. Large-volume nodal metastases and LVI are characteristic features. Almost half of patients develop recurrence despite aggressive initial management. Despite this, with successful salvage surgery DSS is excellent.

Understanding frozen section histopathology in Sinonasal and anterior skull base malignancy and proposed reporting guidelines.

BACKGROUND: Intraoperative frozen section histopathology (IFSH) in sinonasal and skull base surgery although widely used is not well studied. METHODS: We reviewed a database of sinonasal and anterior skull base tumors, between 1973 and 2019, and identified 312 suitable operative cases. Clinicopathologic data was collected and analyzed, in addition to descriptive data for histopathological reports classified as "ambiguous," or "limited/insufficient-quality/quantity." RESULTS: Overall, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for IFSH were 90.2%, 97.5%, 94.2%, 95.6%, and 95.2%, respectively. IFSH for adenocarcinoma, salivary carcinoma, and SCC all demonstrated a better clinical utility with a sensitivity of 90% or greater, while it was less than 90% for esthesioneuroblastoma, melanoma, and sarcoma. Other factors such as unclear reporting, poor quality specimens, or limited quality specimens were shown to lower diagnostic performance. Based on limitations identified, we proposed a novel IFSH reporting algorithm to improve IFSH in sinonasal and skull base surgery. CONCLUSIONS: IFSH is an accurate and clinically useful technique in sinonasal and skull base surgery patients; however, limitations exist.

High frequency and mortality of head and neck malignancy in organ transplant recipients in Ireland - A national cohort study.

BACKGROUND: Solid organ transplant recipients are recognized to carry a high burden of malignancy and frequently this cancer develops in the head and neck region. Furthermore, cancer of the head and neck post-transplant carries a significantly increased mortality. In this study, we aim to conduct a national retrospective cohort study to investigate the impact of head and neck cancer in terms of frequency and mortality in a large group of solid organ transplant recipients over a 20 year time span and compare the mortality in transplant patients to non-transplant patients with head and neck cancer. METHODS: Patients in the Republic of Ireland who underwent solid organ transplantation between 1994 and 2014 who developed post-transplant head and neck malignancy were identified from the records of two prospective, national databases (National Cancer Registry of Ireland (NCRI) and The Irish Transplant Cancer Group database) working in conjunction with each other. Incidence of head and neck malignancy post-transplant was compared with the general population by means of standardised incidence ratios (SIR). Cumulative incidence of all cause and cancer related mortality from head and neck keratinocytic was undertaken by a competing risks analysis. RESULTS: A total of 3346 solid organ transplant recipients were identified, 2382 (71.2 %) kidney, 562 (16.8 %) liver, 214 (6.4 %) cardiac and 188 (5.6 %) lung. During the period of follow up of 428 patients developed head and neck cancer, representing (12.8 %) of the population. 97 % of these patients developed keratinocytic cancers, specifically, of head and neck. The frequency of post-transplant head and neck cancer was related to the duration of immunosuppression with 14 % of patients developing cancer at 10 years and 20 % having developed at least one cancer by 15 years. 12 (3 %) patients developed non-cutaneous head and neck malignancy. 10 (0.3 %) patients died due to head and neck keratinocytic malignancy post-transplant. Competing risk analysis demonstrated that organ transplantation conferred a strong independent effect of death, compared to non-transplant patients with head and neck keratinocytes. This applied specifically for kidney (HR 4.4, 95 % CI 2.5-7.8) and heart transplants (HR 6.5, 95 % CI 2.1-19.9), and overall, across the four transplant categories (P < 0.001). The SIR of developing keratinocyte cancer varied based on primary tumor site, gender, and type of transplant organ. CONCLUSION: Transplant patients demonstrate a particularly high rate of head and neck keratinocyte cancer with a very high rate of associated mortality. Physicians should be cognizant of the increased rate of malignancy in this population and monitor for red flag signs/symptoms.

Surgical management of pediatric salivary malignant tumors-A single-center cohort study.

BACKGROUND: The purpose of this study was to report incidence, clinicopathologic behavior, management, and outcome of pediatric patients treated surgically for salivary gland (SG) malignancies. METHODS: Patients who underwent surgery for SG malignancies from 1985 to 2015 were identified. Clinical, pathological, treatment and outcomes data were collected. Disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS) were calculated using Kaplan-Meier method. RESULTS: Twenty-eight pediatric patients were included. The most common histopathological types were mucoepidermoid (n = 18, 64.3%), acinic cell (n = 7, 25.0%), adenoid cystic (n = 2, 7.1%), and adenocarcinoma (n = 1, 3.6%). Surgical approach varied and ranged from superficial parotidectomy (n = 11, 39.3%) to partial maxillectomy (n = 6, 21.4%). Nine patients (32%) required postoperative radiotherapy. DSS, OS, and RFS probability at 5 years were 96.4%, 96.4%, and 89.3%, respectively. CONCLUSION: Pediatric SG malignancies are rare and have favorable outcome at 5 years. Larger, multi-institutional studies are required to better understand the natural history of these rare tumors.

Therapeutic strategies: Surgery for human papillomavirus-associated oropharyngeal carcinoma.

Treatment of oropharyngeal cancer (OPC) has undergone considerable evolution since the discovery of human papillomavirus (HPV)-associated OPC. It is widely understood that HPV OPC affects a younger population and standard treatment offers improved oncologic outcomes compared with non-HPV OPC but can cause significant toxicities and long-term side effects. Surgery for treatment de-escalation is an active area of research. The purpose of this review is to explore surgery as it relates to the treatment of HPV OPC with a focus on the evolution of treatment, rationale for surgery, surgical techniques, outcomes, and the role of surgery in de-escalation of treatment.

Patient-reported outcomes in human papillomavirus-related oropharyngeal cancer.

This review explores how human papillomavirus-related oropharyngeal cancer affects health-related quality of life (HR-QoL) and the role patient-reported outcomes (PROs) can play in optimizing treatment. PRO measures (PROMs) are comprehensive, subjective assessments of patients' day-to-day HR-QoL. Developed through a scientifically robust, multistage process, PROMs offer insight into patients' symptoms, function, and satisfaction with care. The use of PROMs can increase symptom awareness, stimulate discussion, and enhance shared decision-making between patients and healthcare providers.

Predictors of surgical complications in patients with sinonasal malignancy.

OBJECTIVES: Sinonasal and skull base tumors are rare, making it difficult to identify trends in surgical outcome. This study examines complications in a large cohort of patients undergoing surgery for sinonasal malignancy. METHODS: Following IRB approval, an institutional database was reviewed to identify patients who underwent surgery for sinonasal or skull base malignancies from 1973 to 2016 at our institution. Charlson comorbidity index score and Clavien-Dindo grade were calculated. The main study endpoint was subgroup analysis of Clavien-Dindo Grade 0, Grades 1-2, and Grades 3-5 complications. An ordinal logistic regression model was constructed to assess the association between comorbidities, demographics, tumor characteristics, and surgical complications. RESULTS: In total, 448 patients met inclusion criteria. Perioperative mortality rate at 30 days was 1.6% (n = 7). The rate of severe complications (Clavien-Dindo 3 or higher) was 13.6% (n = 61). Multivariate analysis using an ordinal logistic regression model showed no association between Charlson comorbidity index score and Clavien-Dindo grade of postoperative complication. Advanced T-stage was significantly associated with complications (p = 0.0014; odds ratio: 3.442 [95% confidence interval: 1.615, 7.338]). CONCLUSION: Surgery for sinonasal and skull base tumors is safe with a low mortality rate. Advanced T-stage is associated with postoperative complications. These findings have implications for preoperative risk stratification. Key Points Surgery for sinonasal malignancy is safe with a 30 mortality of 1.6% and rate of severe complications of 12.8%. There is no association between patient comorbidity and post operative complication. On multivariate analysis, only advanced T stage was associated with increased rate of surgical complication.

Mortality risk in post-operative head and neck cancer patients during the SARS-Cov2 pandemic: early experiences.

PURPOSE: The objective of this report is to outline our early experience with head and neck cancer patients in a tertiary referral center, during the SARS-Cov2 pandemic, and to describe the poor outcomes of patients who acquired the infection. METHODS: In this case series from a single-center, national tertiary referral center for head and neck cancer we describe three consecutive head and neck cancer patients who contracted SARS-Cov2 during their inpatient stay. RESULTS: Of the three patients described in our case series that contracted SARS-Cov2, two patients died from SARS-Cov2 related illness. CONCLUSION: We have demonstrated the significant implications that SARS-Cov2 has on head and neck cancer patients, with 3 patients acquiring SARS-Cov2 in hospital, and 2 deaths in our that cohort. We propose a complete separation in the location of where these patients are being managed, and also dedicated non-SARS-Cov2 staff for their peri-operative management. LEVEL OF EVIDENCE: IV.

Post-transplant malignancy in solid organ transplant recipients in Ireland, The Irish Transplant Cancer Group.

OBJECTIVE: Solid organ transplant recipients are at increased risk of cancer compared to the general population. To date, this risk in Ireland has not been investigated. We conducted a national registry study of cancer incidence following solid organ transplantation. METHODS: National centers for solid organ transplantation supplied their respective registry databases to cross-reference with episodes of malignancy from the National Cancer Registry Ireland (NCRI) between 1994 and 2014. Standardized incidence of cancer post-transplant was compared to the general population by means of standardized incidence ratios (SIRs), and between solid organ transplant types by incidence rate ratios. RESULTS: A total of 3346 solid organ transplant recipients were included in this study. Kidney transplant recipients constituted the majority of participants (71.2%), followed by liver (16.8%), heart (6.4%), and lung (5.6%) transplants. The most common cancers within the composite of all transplant recipients included the following (SIR [95% CI]): squamous and basal cell carcinoma (20.05 [17.97, 22.31] and 7.16 [6.43, 7.96], respectively), non-Hodgkin lymphoma (6.23 [4.26, 8.59]), and renal cell carcinoma (3.36 [1.96, 5.38]). CONCLUSIONS: This study reports the incidence of cancer following solid organ transplantation in Ireland. These results have significant national policy implications for surveillance, and early diagnosis in this patient group.

Significant laryngeal destruction in a northern European cohort of Behçet's disease patients.

OBJECTIVES: Behçet's disease (BD) is a multisystem autoimmune disease of unknown origin typically affecting the triad of oral and genital mucosa and the eye. Limited data are available in the literature regarding the otolaryngology-related manifestations of BD, particularly in northern Europeans. This is a novel study detailing surprising and significant laryngeal structural changes in a northern European cohort of BD. METHODS: Patients meeting the International Study Group for Behçet's Disease (ISGBD) and the International Criteria for Behçet's Disease (ICBD) criteria for diagnosis were identified from an institutional database. Patients underwent examination with an otolaryngologist, including flexible laryngoscopy. Intra-oral, pharyngeal and laryngeal manifestations of BD were documented and characterised. Patients underwent hearing assessment with pure-tone audiometry. RESULTS: Fifteen patients with BD were identified (4 male, 11 female; median age 36 years). 60% (n=9) showed evidence of disease on examination and flexible laryngoscopy. 33% (n=5) showed laryngeal changes related to BD. 13% (n=2) demonstrated bilateral sensorineural hearing loss. The 5 cases demonstrating laryngeal manifestations of disease are described in detail with photographic records. CONCLUSIONS: Limited data has been published regarding the laryngeal manifestations of BD, particularly in a northern European population. Our cohort of BD patients demonstrate significant laryngeal structural changes. It would appear that these clinically relevant changes may be more common than was previously thought. Raised awareness of the risk of laryngeal pathology in BD patients, often in the absence of overt clinical symptomatology, may result in earlier diagnosis and treatment. Rheumatologists and otolaryngologists should consider closer multi-disciplinary co-operation in the management and follow up of patients with BD.

VEXAS syndrome as a cause for multifocal, relapsing head and neck inflammation.

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a novel autoinflammatory syndrome. We describe a case of VEXAS syndrome with upper airway and oral cavity involvement which are not well described in the literature.

HPV overtakes smoking as the leading cause of oropharyngeal cancer in Ireland: experience of a head and neck surgery tertiary referral centre.

BACKGROUND: Worldwide, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by human papillomavirus (HPV), a sexually transmitted virus, is increasing. This increase has yet to be demonstrated in an Irish cohort. AIMS: To evaluate the number of OPSCC presentations locally, to stratify cases by HPV status and to estimate if any changes in the patient population had occurred over a 10-year period. METHODS: A STROBE-compliant, retrospective evaluation of patients with OPSCC at St James's Hospital between 2012 and 2022 was performed. Patients with non-SCC histology, undocumented HPV status and residual or recurrent tumours were excluded. RESULTS: We included 294 patients with a mean age of 60.4 years (95% CI 59.2-61.5 years) and 175 (59.5%) patients had HPV+ OPSCC. The number of new OPSCC diagnoses increased from 115 patients (39.1%) between 2012 and 2016 to 179 patients (60.9%) between 2017 and 2021. This was associated with an increased proportion of HPV-linked OPSCC (50.4% 2012-2016 vs. 65.4% 2017-2021, p = 0.011). Over time, more patients had a functionally limiting comorbidity (p = 0.011). The mean age of HPV+ OPSCC cases increased by 3.6 years (p = 0.019). Patients with HPV+ OPSCC had greater 2-year OS (83.9% vs. 54.9%; p < 0.001) and 2-year DFS (73.5% vs. 45.6%; p < 0.001). The 2-year OS and DFS did not change over time for HPV+ or HPV- patients. CONCLUSIONS: In our institution, the number of patients with OPSCC is increasing due to an escalation in cases associated with HPV. Population-level interventions such as vaccination programs may alter the current increase in the incidence of these tumours.

Fatal cerebritis and ventriculitis secondary to tracheoesophageal prosthesis.

Tracheoesophageal puncture and voice prosthesis placement is the preferred method of voice restoration following total laryngectomy. Although this is a safe and effective means of optimizing voice, severe complications can occur. We present the case of a patient who developed cerebritis and ventriculitis secondary to a tracheoesophageal prosthesis eroding his cervical vertebrae 20 years following pharyngo-laryngo-esophagectomy. Despite optimal antimicrobial therapy, he deteriorated and succumbed to his disease. Although tracheoesophageal prostheses are a safe and effective means of voice restoration, life-threatening complications can occur. This case report highlights a rare but severe case of cervical osteomyelitis, epidural abscess, and cerebritis and ventriculitis secondary to tracheoesophageal prosthesis. Clinicians must be aware of this severe complication in postlaryngectomy patients with tracheoesophageal prostheses.

Outcomes of SMARCB1-deficient sinonasal carcinoma: Largest single-center cross-sectional study.

BACKGROUND: We evaluate outcomes of SMARCB1-deficient sinonasal carcinomas in the largest single-institution study. METHODS: Retrospective cross-sectional study of patients with SMARCB1-deficient sinonasal carcinoma between 1998 and 2024. Disease-specific survival (DSS) and recurrence-free probability (RFP) at 1 and 5 years were measured by Kaplan-Meier method. RESULTS: There were 47 patients with a median age of 53. Initial pathological diagnosis was altered in 33%. Twelve (34%) patients received neoadjuvant chemotherapy, with one partial response. Curative surgical approach was undertaken in 73%. Definitive chemoradiation was administered in 20%. DSS at 1 and 5 years was 93% and 45%, respectively. RFP at 1 and 5 years was 73% and 33%, respectively. On multivariate analysis, cranial nerve involvement (p = 0.01 for DSS) remained significantly worse for DSS and overall survival. CONCLUSIONS: SMARCB1-deficient tumors had limited response to neoadjuvant chemotherapy. Cranial nerve involvement was associated with worse prognosis. Optimal treatment is unclear. Surgery should be offered to patients with resectable disease.

Airway decision making in major head and neck surgery: Irish multicenter, multidisciplinary recommendations.

Major head and neck surgery poses a threat to perioperative airway patency. Adverse airway events are associated with significant morbidity, potentially leading to hypoxic brain injury and even death. Following a review of the literature, recommendations regarding airway management in head and neck surgery were developed with multicenter, multidisciplinary agreement among all Irish head and neck units. Immediate extubation is appropriate in many cases where there is a low risk of adverse airway events. Where a prolonged definitive airway is required, elective tracheostomy provides increased airway security postoperatively while delayed extubation may be appropriate in select cases to reduce postoperative morbidity. Local institutional protocols should be developed to care for a tracheostomy once inserted. We provide guidance on decision making surrounding airway management at time of head and neck surgery. All decisions should be agreed between the operating, anesthetic, and critical care teams.

Virtual Surgical Planning and Three-Dimensional Models for Precision Sinonasal and Skull Base Surgery.

Sinonasal and skull base malignancies represent a rare, heterogenous group of pathologies with an incidence of 0.556 per 100,000 persons in the population. Given the numerous critical anatomic structures located adjacent to the sinonasal cavity and skull base, surgery for tumors in this region requires careful pre-operative planning with the assistance of radiological imaging and intraoperative image guidance technologies to reduce the risk of complications. Virtual surgical planning (VSP) and three-dimensional models (3DMs) are adjunctive technologies which assist clinicians to better visualize patient anatomy using enhanced digital radiological images and physical stereolithographic models based on patients' personal imaging. This review summarizes our institutional experience with VSP and 3DMs in sinonasal and skull base surgical oncology. A clinical case series is used to thematically illustrate the application of VSP and 3DMs in surgical ablation, reconstruction, patient communication, medical education, and interdisciplinary teamwork in sinonasal and skull base surgery.