Squamous cell cancer of the temporal bone: a review of the literature.

BACKGROUND AND AIMS: Squamous cell carcinoma (SCC) of the temporal bone is a rare malignancy accounting for only 0.2% of head and neck cancers. There is currently no clear consensus on staging or common approach to management. It is the aim of this work to provide the readers with a review of the current literature on this malignancy. METHODS: A literature review was performed identifying 16 case series with patient numbers ranging from 12 to 124. A total of 708 patients were included in this review, 67% presented with advanced disease. 578 cases were managed operatively with lateral temporal bone resection, some underwent local resection alone in early stage disease. In all studies radiation therapy was used as an adjunct to some degree. RESULTS: More than half of studies reported 100% either 2-, 3- or 5-year survival for T1 and T2 disease with no nodal involvement. Survival correlated with disease stage and in five studies SCC differentiation was found to be a significant prognostic factor. Post-operative radiotherapy was found to improve survival in only one study. CONCLUSIONS: Temporal bone SCC is a readily treatable malignancy in early stage disease, however late stage disease has a poor prognosis. Differentiation of the SCC and stage of disease at presentation appear to have the greatest influence on 5-year survival rates. Further work is required in both the identification of early stage disease and in the treatment of later T3 and T4 lesions.

International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System.

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p = 0.036). Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

Follow-up in head and neck cancer: patients' perspective.

PURPOSE: The purpose of this paper is to determine head and neck cancer patients' perspective of their follow-up regime and to suggest ways in which these perspectives can be incorporated into current practice. DESIGN/METHODOLOGY/APPROACH: This is a prospective survey-based study. A total of 263 patients consecutively attending a head and neck cancer clinic completed a survey about their experience of the follow-up process in the post-treatment period between January 2009 and October 2009. FINDINGS: The paper finds that, of the patients, 67 per cent (n = 176) felt that the clinic met the goals they hoped would be achieved during their visit; 84 per cent (n = 221) felt that their follow-up visits were too frequent. In total 60 per cent (n = 159) were booked to see both an allied health professional and the attending clinician. Of these, 84 per cent (n = 134/159) felt that issues addressed at follow-up with the clinician duplicated those addressed by the allied healthcare professionals. When asked about their opinion of a less intensive follow-up system based on patients reporting problems and requesting appointments, 73 per cent (n = 192) favoured it. When asked who they would like to contact first in such a system, most patients (n = 118, 45 per cent) stated a clinical nurse specialist. PRACTICAL IMPLICATIONS: Current follow-up regimes may be too prescriptive in their approach without taking patient perspective into consideration. Patients felt that being seen intensively for the first year, then having visits tapered off over the next two years and finally being seen according to symptoms thereafter to be appropriate and felt that this represented an overall better system. ORIGINALITY/VALUE: These data suggest the need for a more patient-focused, individualised approach to follow-up in head and neck cancer.

Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma.

INTRODUCTION: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy. METHODS: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763). RESULTS: Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD). CONCLUSIONS: This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

The Eagle Has Landed: an unusual case of Eagle's syndrome.

Eagle's syndrome refers to a group of characteristic symptoms affecting the oropharynx and neck that are caused by regional compression of structures due to a calcified stylohyoid ligament or an elongated styloid process. Of its two types, the former type is more common than the latter, but carotid artery dissection as a result of an elongated styloid is exceptionally rare. Following an extensive literature review, we present a case of carotid artery dissection causing multiple strokes secondary to direct compression from an elongated styloid process. Managed surgically through excision of the elongated styloid and post-operative rehabilitation, the patient recovered well and was discharged on anti-thrombotic medication, preventing further potentially detrimental attacks.

Frequent HPV-independent p16/INK4A overexpression in head and neck cancer.

OBJECTIVES: p16INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven. MATERIALS AND METHODS: We integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project. Samples were queried for alterations in CDKN2A, and other pathway genes to investigate possible drivers of p16 expression. RESULTS: While p16 levels as measured by RPPA were significantly different by HPV status, there were multiple HPV (-) samples with similar expression levels of p16 to HPV (+) samples, particularly at non-oropharyngeal subsites. In many cases, p16 overexpression in HPV (-) tumors could not be explained by mutation or amplification of CDKN2A or by RB1 mutation. Instead, we observed enrichment for inactivating mutations in the histone H3 lysine 36 methyltransferase, NSD1 in HPV (-)/p16-high tumors. CONCLUSIONS: RPPA data suggest high p16 protein expression in many HPV (-) non-oropharyngeal HNSCCs, limiting its potential utility as an HPV biomarker outside of the oropharynx. HPV-independent overexpression of wild-type p16 in non-oropharyngeal HNSCC may be linked to global deregulation of chromatin state by inactivating mutations in NSD1.

Follicular dendritic cell sarcoma arising from the hypopharynx.

Follicular dendritic cell (FDC) tumours have been described recently as malignant tumours arising from accessory cells of the lymph nodes. They are rare tumours with fewer than 70 cases occurring worldwide. They usually present in cervical or abdominal lymph nodes, with very few occurring extranodally. We present the first case of an FDC tumour to occur in the hypopharynx with simultaneous cervical node metastases. The pathology is discussed and the literature reviewed.

Use of the Venner™ A.P. Advance™ video laryngoscope for biopsy examination of the base of the tongue.

Biopsy specimens taken from the base of the tongue can be non-diagnostic, because of errors in sampling and tissue samples that are too small or superficial. The Venner™ A.P. Advance™ video laryngoscope (Intavent Direct, Maidenhead, UK) is an anaesthetic laryngoscope designed for use in patients with a difficult airway. We present a pilot study that compares video laryngoscope-assisted biopsy examination of the base of the tongue with the standard technique using a surgical laryngoscope. The video laryngoscope gives a wide view of the base of the tongue and the ability to use sinus biopsy forceps, which can take larger and deeper specimens.

Identification and functional validation of HPV-mediated hypermethylation in head and neck squamous cell carcinoma.

BACKGROUND: Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) represents a distinct clinical and epidemiological condition compared with HPV-negative (HPV-) HNSCC. To test the possible involvement of epigenetic modulation by HPV in HNSCC, we conducted a genome-wide DNA-methylation analysis. METHODS: Using laser-capture microdissection of 42 formalin-fixed paraffin wax-embedded (FFPE) HNSCCs, we generated DNA-methylation profiles of 18 HPV+ and 14 HPV- samples, using Infinium 450 k BeadArray technology. Methylation data were validated in two sets of independent HPV+/HPV- HNSCC samples (fresh-frozen samples and cell lines) using two independent methods (Infinium 450 k and whole-genome methylated DNA immunoprecipitation sequencing (MeDIP-seq)). For the functional analysis, an HPV- HNSCC cell line was transduced with lentiviral constructs containing the two HPV oncogenes (E6 and E7), and effects on methylation were assayed using the Infinium 450 k technology. RESULTS AND DISCUSSION: Unsupervised clustering over the methylation variable positions (MVPs) with greatest variation showed that samples segregated in accordance with HPV status, but also that HPV+ tumors are heterogeneous. MVPs were significantly enriched at transcriptional start sites, leading to the identification of a candidate CpG island methylator phenotype in a sub-group of the HPV+ tumors. Supervised analysis identified a strong preponderance (87%) of MVPs towards hypermethylation in HPV+ HNSCC. Meta-analysis of our HNSCC and publicly available methylation data in cervical and lung cancers confirmed the observed DNA-methylation signature to be HPV-specific and tissue-independent. Grouping of MVPs into functionally more significant differentially methylated regions identified 43 hypermethylated promoter DMRs, including for three cadherins of the Polycomb group target genes. Integration with independent expression data showed strong negative correlation, especially for the cadherin gene-family members. Combinatorial ectopic expression of the two HPV oncogenes (E6 and E7) in an HPV- HNSCC cell line partially phenocopied the hypermethylation signature seen in HPV+ HNSCC tumors, and established E6 as the main viral effector gene. CONCLUSIONS: Our data establish that archival FFPE tissue is very suitable for this type of methylome analysis, and suggest that HPV modulates the HNSCC epigenome through hypermethylation of Polycomb repressive complex 2 target genes such as cadherins, which are implicated in tumor progression and metastasis.

Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors.

BACKGROUND: Human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) is an emerging disease, representing a distinct clinical and epidemiological entity. Understanding the genetic basis of this specific subtype of cancer could allow therapeutic targeting of affected pathways for a stratified medicine approach. METHODS: Twenty HPV+ and 20 HPV- laser-capture microdissected oropharyngeal carcinomas were used for paired-end sequencing of hybrid-captured DNA, targeting 3,230 exons in 182 genes often mutated in cancer. Copy number alteration (CNA) profiling, Sequenom MassArray sequencing and immunohistochemistry were used to further validate findings. RESULTS: HPV+ and HPV- oropharyngeal carcinomas cluster into two distinct subgroups. TP53 mutations are detected in 100% of HPV negative cases and abrogation of the G1/S checkpoint by CDKN2A/B deletion and/or CCND1 amplification occurs in the majority of HPV- tumors. CONCLUSION: These findings strongly support a causal role for HPV, acting via p53 and RB pathway inhibition, in the pathogenesis of a subset of oropharyngeal cancers and suggest that studies of CDK inhibitors in HPV- disease may be warranted. Mutation and copy number alteration of PI3 kinase (PI3K) pathway components appears particularly prevalent in HPV+ tumors and assessment of these alterations may aid in the interpretation of current clinical trials of PI3K, AKT, and mTOR inhibitors in HNSCC.

Sequential improvements in organ procurement increase the organ donation rate.

PURPOSE: Organ demand exceeds availability of transplantable organs. Organ procurement continues to suffer from failures to identify potential donors, inability to obtain consent for donation, as well as failures to retrieve certain organs as donor demographics change. The purpose of this article is to propose how sequentially introduced measures can increase organ donation rates as well as improve organ procurement. METHODS: We analysed the effect of stepwise improvements in the organ procurement process patients in a university-based surgical intensive care unit over a 20-year period. We related newly introduced measures in the organ retrieval process with changes in donation rates. We specifically targeted these three main steps in the donation process: donor identification, conversion of potential donors to actual donors, and organ protection during the procurement process. Finally, we assessed the effect of the same measures on organ procurement after introduction in other hospitals of the same organ procurement region. RESULTS: Introduction of quality improvement steps increased all of the observed parameters. The number of organ donors was stabilised due to a better identification of potential donors, a major increase in conversion from potential to actual donors, and an increase in extended criteria donor. Improvements in organ protection led to higher rates of organs transplanted per donor and increased recovery of lungs and hearts despite increasing donor age. The same measures were introduced successfully in other hospitals in our organ procurement region. CONCLUSION: Sequential improvements in organ procurement can increase the yield of retrieved organs. The same measures can be applied to other hospitals and lead to comparable improvements in organ donation.

Endoscopic management of an internal laryngopyocele presenting with acute airway obstruction.

Statement of Problem. Laryngocele is a rare laryngeal disease, where there is an abnormal dilatation of the saccule of the laryngeal ventricle. It can either be internal or external, and a laryngopyocele is a rare complication of this anomaly. Internal laryngopyoceles can prove difficult to manage, as they often present with airway compromise. Method of Study. Case Report. Results. We present a case of a laryngopyocele that was successfully managed with suspension laryngoscopy and endoscopic marsupialisation and resection. To our knowledge, this is the first such case described in the literature. Conclusions. Surgical drainage of a laryngopyocele via the external approach is well documented in the literature. We feel that endoscopic resection of laryngopyoceles in an emergency situation is a viable alternative and also prevents the associated surgical morbidity.