Hürthle Cells on Fine-Needle Aspiration Cytology Are Important for Risk Assessment of Focally PET/CT FDG Avid Thyroid Nodules.

This study assesses the role of [18F] FDG PET/CT, fine needle aspiration (FNA) cytology and ultrasound in the 1-2% of patients with focally positive thyroid nodules on FDG PET/CT. All FDG PET/CT scans with focally increased thyroid FDG PET/CT uptake performed over 37 months in one institution were matched to patients undergoing thyroid FNA. Diffuse FDG PET/CT uptake patients were excluded. A total of 47 patients showed focally increased thyroid uptake. Consistent with previous studies, 18 (38.2%) patients had malignancy-12 primary thyroid carcinoma, 1 parathyroid carcinoma, 3 metastatic carcinoma to the thyroid and 2 lymphoma. A total of 15 (31.9%) lesions categorized as non-malignant contained Hürthle cells/oncocytes. A total of 14 lesions (29.8%) had focally increased FDG PET/CT uptake with no specific cytological or histopathological cause identified. No focally PET avid Hürthle cell/oncocytic lesions were found to be malignant. Exclusion of oncocytic lesions increased the calculated risk of malignancy (ROM) of focally PET avid nodules from 38% to 68%. It may be useful to exclude focally FDG PET/CT avid Hürthle cell/oncocytic lesions, typically reported as follicular neoplasm or suspicious for a follicular neoplasm, Hürthle cell type (Oncocytic) type, RCPath Thy 3F: Bethesda IV or sometimes Thy 3a: Bethesda III FNAs) from ROM calculations. Oncocytic focally PET/CT FDG avid lesions appear of comparatively lower risk of malignancy and require investigation or operation but these lesions should be readily identified by FNA cytology on diagnostic work up of focally PET avid thyroid nodules.

Author Correction: Pan-cancer deconvolution of tumour composition using DNA methylation.

The original version of this Article contained an error in Figure 4. In panel a, the colour code for hot and cold clusters was inadvertently inverted. In the correct version of panel a, the hot clusters are blue and the cold clusters are yellow. This error has now been corrected in both the PDF and HTML versions of the Article.

Pan-cancer deconvolution of tumour composition using DNA methylation.

The nature and extent of immune cell infiltration into solid tumours are key determinants of therapeutic response. Here, using a DNA methylation-based approach to tumour cell fraction deconvolution, we report the integrated analysis of tumour composition and genomics across a wide spectrum of solid cancers. Initially studying head and neck squamous cell carcinoma, we identify two distinct tumour subgroups: 'immune hot' and 'immune cold', which display differing prognosis, mutation burden, cytokine signalling, cytolytic activity and oncogenic driver events. We demonstrate the existence of such tumour subgroups pan-cancer, link clonal-neoantigen burden to cytotoxic T-lymphocyte infiltration, and show that transcriptional signatures of hot tumours are selectively engaged in immunotherapy responders. We also find that treatment-naive hot tumours are markedly enriched for known immune-resistance genomic alterations, potentially explaining the heterogeneity of immunotherapy response and prognosis seen within this group. Finally, we define a catalogue of mediators of active antitumour immunity, deriving candidate biomarkers and potential targets for precision immunotherapy.

Staging and treatment of oropharyngeal cancer in the human papillomavirus era.

BACKGROUND: Oropharyngeal squamous cell carcinoma (SCC) is staged using the TNM system. Human papillomavirus (HPV)-positive tumors have improved prognosis, despite presenting at advanced stage. Optimal treatment and stratification of HPV-positive patients are not clearly defined. METHODS: We retrospectively analyzed 266 patients with oropharyngeal SCC for mortality and feeding tube dependency related to TNM stage, HPV status, and treatment. RESULTS: TNM staging was prognostic in HPV-negative patients (stage III/IV hazard ratio [HR], 2.00; p = .05; N(+) HR, 2.19; p = .02). Only T classification was prognostic in HPV-positive tumors (T3/T4 HR 3.31; p = .006). HPV-positive tumors showed improved survival regardless of treatment. Patients receiving chemotherapy had a significantly increased risk of feeding tube dependency (odds ratio [OR], 1.72; p = .03). CONCLUSION: These data suggest that the current TNM system has little prognostic value in HPV-positive oropharyngeal SCC. Patients with HPV-positive tumors show improved survival independent of treatment. The addition of chemotherapy increases the risk of feeding tube dependency and could potentially be avoided in T1/T2 HPV-positive tumors without compromising survival.

Ophthalmoplegia secondary to raised intracranial pressure after unilateral neck dissection with internal jugular vein sacrifice.

BACKGROUND: Neck dissection is commonly performed in the management of head and neck malignancy and may involve internal jugular vein (IJV) sacrifice. Potential complications include intracranial hypertension. This is well documented after bilateral neck dissection, although only scattered reports exist after unilateral IJV sacrifice. METHODS: A 54-year-old man underwent unilateral left modified radical neck dissection for T1N2b squamous cell carcinoma of the tongue base. He presented 13 days postoperatively with symptoms of headache and diplopia. RESULTS: Investigations revealed intracranial hypertension and bilateral abducens nerve palsies. He was treated with serial lumbar puncture, and his symptoms improved over the course of 2 weeks. CONCLUSIONS: Intracranial hypertension sufficient to cause visual disturbance is a serious complication of unilateral neck dissection. Head and neck surgeons must be aware of this and have a low threshold for investigation of the signs and symptoms of intracranial hypertension in the postoperative period. © 2010 Wiley Periodicals, Inc. Head Neck, 2011.

Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability.

OBJECTIVE: To examine n-3 polyunsaturated fatty acid (PUFA) incorporation into atherosclerotic plaques and the association with plaque inflammation and stability. METHODS AND RESULTS: Patients awaiting carotid endarterectomy (n=121) were randomised to consume control capsules or n-3 PUFA ethyl ester capsules until surgery (median 21 days). The fatty acid compositions of plasma and carotid plaque phospholipids, plaque features, and expression of inflammatory genes were determined. The proportion of eicosapentaenoic acid (EPA) was higher (P<0.0001) in carotid plaque phospholipids in patients in the n-3 PUFA group. Plaques from patients in the n-3 PUFA group had fewer foam cells (P=0.0390). There were no other differences between plaques in the two groups with regard to histological characteristics or morphology. Plaque stability was not different between the two groups. However, the EPA content of plaque phospholipids was inversely associated with plaque instability (P=0.0209), plaque inflammation (P=0.0108), the number of T cells in the plaque (P=0.0097) and a summary score considering a range of plaque features (P=0.0425). Plaques from patients who received n-3 PUFAs had significantly lower levels of mRNA for matrix metalloproteinases (MMP)-7 (P=0.0055), -9 (P=0.0048) and -12 (P=0.0044) and for interleukin-6 (P=0.0395) and intercellular adhesion molecule 1 (P=0.0142). CONCLUSIONS: Atherosclerotic plaques readily incorporate EPA. A higher plaque EPA content is associated with a reduced number of foam cells and T cells, less inflammation and increased stability.