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Squamous cell carcinoma (SCC) is one of the most common malignant neoplasms involving the anterior skull base, resulting from local invasion from an adjacent anatomical region. The primary sites of origin are most frequently the nasal cavity and paranasal sinuses, and less often the skin and orbit. Treatment strategies for these tumors have evolved, although management remains challenging due to the proximity to critical structures and their location at the intracranial-extracranial interface. The rarity of these tumors, and limited numbers at any one institution, has meant that most published series have grouped together different histologies in reporting outcomes. Data on SCC alone are thus limited. Treatment of SCC involving the anterior skull involves a multidisciplinary team approach. A number of potential treatment options exist, dependent on tumor, patient, and institutional factors. Current treatment strategies commonly involve multimodality therapy using a combination of surgery, radiotherapy, and chemotherapy. Primary surgery is considered the mainstay of initial treatment in those tumors which are deemed resectable, followed by adjuvant radiotherapy with or without chemotherapy. Preoperative assessment includes confirmation of the tissue diagnosis, and imaging to assess resectability, guide the surgical approach, and to plan the extent of surgery and method of reconstruction. Analysis of our institutional database for patients undergoing surgery with SCC involving the anterior skull base showed a 5-year disease-specific survival of 65% for sinonasal SCC and 71% for cutaneous SCC. The surgical margin status as well as dural and pterygopalatine fossa involvement were predictors of a poor prognosis.

A well 74 -year-old woman presented to routine ophthalmology clinic instituted following treatment of a frontoethmoidal sarcoma initially excised in 1989 and diagnosed then as a sinus mucosal melanoma. At review in ophthalmology clinic, a reduction in right visual fields was noted. CT scan showed recurrence of a mass now involving the frontoethmoidal region, frontal sinus and abutting the cribiform plate. Endoscopic biopsy confirmed the recurrence as a low-grade biphenotypic sarcoma. This was discussed at the sarcoma multidisciplinary meeting. Using a three-dimensional printed model of the patients skull for planning, primary surgery with craniofacial resection combining intracranial and transfacial approaches with reconstruction was decided on. The implications of no treatment would be tumour involvement of the dura and brain as well as the right only-seeing eye. Craniofacial surgery would involve otolaryngolical, neurosurgical and maxillofacial multispecialty involvement and close teamwork. The goal was en bloc excision with negative surgical margins.

Purpose: Tumor hypoxia is associated with a poor prognosis, hypoxia modification improves outcome, and hypoxic status predicts benefit from treatment. Yet, there is no universal measure of clinical hypoxia. The aim of this study was to investigate whether a 26-gene hypoxia signature predicted benefit from hypoxia-modifying treatment in both cancer types. Experimental Design: Samples were available from 157 T2–T4 laryngeal cancer and 185 T1–T4a bladder cancer patients enrolled on the accelerated radiotherapy with carbogen and nicotinamide (ARCON) and bladder carbogen nicotinamide (BCON) phase III randomized trials of radiotherapy alone or with carbogen and nicotinamide (CON) respectively. Customized TaqMan low density arrays (TLDA) were used to assess expression of the 26-gene signature using quantitative real-time PCR. The median expression of the 26 genes was used to derive a hypoxia score (HS). Patients were categorized as TLDA-HS low (≤median) or TLDA-HS high (>median). The primary outcome measures were regional control (RC; ARCON) and overall survival (BCON). Results: Laryngeal tumors categorized as TLDA-HS high showed greater benefit from ARCON than TLDA-HS low tumors. Five-year RC was 81% (radiotherapy alone) versus 100% (CON) for TLDA-HS high (P = 0.009). For TLDA-HS low, 5-year RC was 91% (radiotherapy alone) versus 90% (CON; P = 0.90). TLDA-HS did not predict benefit from CON in bladder cancer. Conclusion: The 26-gene hypoxia signature predicts benefit from hypoxia-modifying treatment in laryngeal cancer. These findings will be evaluated in a prospective clinical trial. Clin Cancer Res; 19(17); 4879–88. ©2013 AACR.

Computerized tomography (CT) scanning is a well recognised tool for the diagnosis of malignant external otitis. To investigate the degree of correlation between CT findings scan and the patients clinical status focusing on a subgroup of patients with cranial nerve palsies. Diagnosis of malignant external otitis was confirmed in 23 patients (average age 71 years, age range 39-87) based on criteria of severe pain, otitis externa refractory to conventional treatments and possibly diabetes mellitus and pseudomonas detection. CT was performed on 23 of these patients. Results from these scans were analysed and correlated with patient clinical status. Retrospective analysis of CT images and medical notes were used for data analysis.The CT scans of all 23 patients showed evidence of involvement of disease outside the external auditory canal, confirming the diagnosis. Sixteen out of 23 patients (70%) demonstrated evidence of bone erosion. Four of the 16 showed involvement of the petrous apex. From our subset of ten patients with cranial nerve involvement, eight demonstrated evidence of bone erosion and two showed mastoid and middle ear involvement without bone erosion. All four patients with petrous apical involvement presented with cranial nerve palsies (two lower cranial nerve palsies, one seventh nerve palsy and one combined lower and seventh nerve palsy). CT scanning was found to be a fast and economical tool in the initial assessment of patients with malignant external otitis. Petrous apex involvement was constantly associated with cranial nerve palsies, usually the lower cranial nerves. CT findings of temporal bone in itself however, were not closely correlated to the clinical outcome of the patients.

Head and neck squamous cell carcinomas of unknown primary (HNSCCUP) accounts for up to 10% of presenting head and neck squamous cell carcinomas. Identification of the primary site allows for directed therapy. Where initial investigations have failed to locate the primary site, 18-fludeoxyglucose positron emission tomography-computed tomography (PET/CT) has emerged as a useful tool with improved sensitivity over positron emission tomography alone. Following PET/CT scan, the role of subsequent panendoscopy ± biopsy has not been fully assessed. We aim to evaluate and quantify the role of PET/CT and subsequent panendoscopy in HNSCCUP.Retrospective cohort study.Patients with HNSCCUP presenting between January 2005 and December 2010 at a regional oncology referral center were studied. All patients who presented with a metastatic neck node and unknown primary who had undergone PET/CT prior to panendoscopy were included. The accuracy of PET/CT was calculated and compared with panendoscopy and histopathological findings.Fifty-two patients were included. Twenty-seven PET/CT scans suggested a primary site. Calculated diagnostic parameters were 83% sensitivity, 87% specificity, positive predictive value 89%, and negative predictive value 80%. Three false-positive PET/CT scans were noted after panendoscopy and normal histology. Importantly, three confirmed tongue base tumors were found on panendoscopy, which were undetected on PET/CT.PET/CT is a valuable resource for locating tumors in HNSCCUP. It helps direct biopsy and aids in the detection of local and distant metastases along with synchronous primary tumors. Importantly, due to both false-positive and false-negative PET/CT rates, panendoscopy and biopsy remains an essential adjunct investigation irrespective of PET/CT results.4 Laryngoscope, 126:1354-1358, 2016.

Background:Surgery is currently the only curative treatment for medullary thyroid cancer. Unfortunately, the surgical strategy that will offer patients at each disease stage the best chance of a biochemical cure remains unclear. The American Thyroid Association and British Thyroid Association guidelines offer different strategies.Methods:A retrospective analysis of the surgical management of 47 patients with medullary thyroid cancer diagnosed between 1994 and 2013 was performed. Surgical management was compared with current American Thyroid Association and British Thyroid Association guidelines. Outcome was defined as the first post-operative calcitonin measurement.Results:All patients with stage I–III disease achieved a post-operative biochemical cure regardless of the guidelines followed. The overall biochemical cure rate for patients with stage IVa disease was significantly reduced to 10 per cent (p < 0.01), but the biochemical cure rate for stage IVa disease patients who underwent bilateral lateral lymph node dissection was 33.3 per cent.Conclusion:The conservative, surveillance-driven approach recommended by the American Thyroid Association is appropriate for stage I–III disease. However, the more aggressive approach advocated by the British Thyroid Association might provide stage IVa disease patients a greater chance of achieving a biochemical cure.

Anaplastic thyroid carcinoma (ATC) is an uncommon thyroid malignancy with a poor prognosis. American Thyroid Association (ATA) guidelines acknowledge the complexity of airway management in these patients. We studied our local experience with the aim of providing guidance in airway management in ATC.Patients with histologically confirmed ATC from January 2004 to December 2011 were identified from our institutional database. The data were retrospectively analyzed using hospital case notes.Twenty-six patients were identified with ATC, 25 of who died from the disease. Five of 26 patients (19%) had stridor at presentation. A further 6 of 26 patients (23%) developed stridor during or soon after radiotherapy. Nine patients (36%) died of airway obstruction.Tracheotomy can facilitate completion of palliative treatment in those patients with ATC and stridor. Given the short life expectancy of these patients, a balanced decision must be made regarding the role and timing of tracheotomy.

There is an increasing incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell cancers (OPSCC) mostly associated with favourable outcomes. p16 immunohistochemistry is a surrogate marker for HPV positivity in OPSCC. The prognostic strength of p16 over traditional prognostic factors is not fully characterised. In this study, we evaluated the clinical and demographic differences between p16-positive and -negative OPSCC and characterised its prognostic strength versus traditional prognostic factors.Formalin-fixed, paraffin-embedded blocks and clinical information from 217 OPSCC patients, treated with radiotherapy (alone or in combination with other therapies) between 2000 and 2010 were collected retrospectively. Immunohistochemistry for p16 protein was carried out; cancer-specific survival (CSS), recurrence-free survival (RFS) and locoregional control (LRC) were calculated for both univariate and multivariate analyses.Ninety-two per cent of the OPSCC originated from tonsil and tongue base sites, 61% were p16 positive. Patients with p16-positive OPSCC were younger (P0.0001), with lower alcohol (P = 0.0002) and tobacco (P = 0.0001) exposure. The tumours were less differentiated (P = 0.0069), had a lower T stage (P = 0.0027), higher nodal status (P = 0.014) and higher American Joint Committee on Cancer (AJCC) prognostic group (P = 0.0036). AJCC prognostic group was significant for RFS (P = 0.0096) and CSS (P = 0.018) in patients with p16-negative OPSCC, but not those with p16-positive tumours (P = 0.30 and 0.54). Other significant factors for CSS and RFS in univariate analysis were: pretreatment haemoglobin (P0.0001 and0.0001), chemoradiotherapy (P = 0.005 and 0.03) and P16 status (P0.0001 and 0.0001). In multivariate analysis, p16 positivity was the strongest independent prognostic variable for both CSS, RFS and LRC (P0.0001, hazard ratio 4.15; 95% confidence interval 2.43-7.08), (P0.0001, hazard ratio 6.15; 95% confidence interval 3.57-10.61) and (P = 0.001, hazard ratio 3.74; confidence interval 1.76-7.95).This study shows that p16 is the single most important prognostic variable in OPSCC, surpassing traditional prognostic factors for both CSS and RFS. Furthermore, disease stage has no prognostic significance in p16-positive patients, highlighting the need for routine p16 assessment in OPSCC.

Navin Mani and colleagues examine Occam’s razor, Hickam’s dictum, and Crabtree’s bludgeon Most clinicians will be familiar with Occam’s razor, a guiding principle that is interpreted as “the simplest explanation is to be preferred.” In relation to medical diagnosis this is taken to mean that when a patient has multiple symptoms and signs, a single diagnosis should be sought that accounts for all the clinical features rather than attributing a different diagnosis to each. To what extent should we rely on Occam’s wisdom? All clinicians can recall patients who have not conformed to this principle, and over reliance on it has the potential for misdiagnosis. Accurate diagnosis underpins good clinical practice; figures suggest that rates of diagnostic errors in the emergency department setting are as high as 10-15%1 and that misdiagnosis is responsible for around 10% of adverse events in hospitals.2 With this in mind, we present examples for and against the use of Occam’s razor from our area of interest: head and neck oncology, the management of which provides a good template to study these diagnostic dilemmas. Most patients undergo imaging of distant sites at diagnosis, and spread to the regional lymph nodes usually occurs in a predictable pattern before distant metastases. We also examine the views of other “wise men” who have proposed principles that caution against over reliance on Occam. A 60 year old female smoker presented with haemoptysis. Chest radiography showed an opacity in the middle lobe of her right lung. She underwent lobectomy. Histology showed adenocarcinoma with clear resection margins (stage T2 N0 M0). No adjuvant therapy was given. One year later she presented with a left tonsillar mass and left cervical lympadenopathy (fig 1⇓). Biopsy of the left tonsil was reported as adenocarcinoma (stage T2 N2b M0) with similar histological features …

Background: Malignant external otitis is an uncommon, potentially lethal infection of the temporal bone primarily affecting elderly diabetic patients. Objective: To determine whether cranial nerve involvement in malignant external otitis affects or predicts the clinical outcome in terms of morbidity and mortality. Methods: Diagnosis of malignant external otitis was established in 23 patients (average age, 71 yr; range, 39–87) based on inclusion criteria of severe pain, otitis externa refractory to conventional treatments, diabetes mellitus, and Pseudomonas aeruginosa detection. Computed tomography confirmed temporal bone involvement extending outside the external auditory canal. Data Analysis: Retrospective analysis of hospital records. Results: Ten of 23 (43.5%) patients showed cranial nerve involvement. The following cranial nerves were affected: facial nerve (6/10), lower cranial nerves (combination of IX, X, XI, XII) (3/10), and extended nerve palsy (VI, VII, IX, X, XI) (1/10). Thirteen of 23 (56.5%) patients displayed no cranial nerve involvement. All patients were treated with long-term, high-dose antibiotic treatment dependent on the microbiological findings. Conclusions: All patients with lower cranial nerve palsy recovered normal function; however, the facial nerve palsy was significantly less likely to improve by medical treatment. Cranial nerve involvement did not affect the patient survival rate under an optimized medical treatment in our series.