SUMMARY Objectives The epidermal growth factor receptor (EGFR) is a validated target in head and neck squamous cell carcinoma (HNSCC). In recurrent and/or metastatic (R/M) HNSCC, resistance to anti-EGFR therapy inevitably occurs. Downstream activation of the PI3K/Akt/mTOR pathway is an established resistance mechanism. Concurrent mTOR blockade may improve efficacy of anti-EGFR therapy. Materials and methods Erlotinib 150 mg daily and temsirolimus 15 mg weekly were administered to patients with platinum-refractory R/M HNSCC and ECOG performance status 0–2. The primary endpoint was progression-free survival (PFS). Correlative studies determined PIK3CA and HRAS mutation status; p16, EGFR, pS6K, pAkt and PTEN expression; and pre- and post-treatment plasma levels of 20 immunomodulatory cytokines. Results Twelve patients enrolled; six withdrew within 6 weeks due to toxicity or death, prompting early closure of the trial. Grade ≥3 toxicities included fatigue, diarrhea, gastrostomy tube infection, peritonitis, pneumonia, dyspnea, and HN edema. Median PFS was 1.9 months. Median overall survival was 4.0 months. Six/12 tumors were p16(+), 9/11 lacked measurable PTEN expression, and 1/12 harbored a PIK3CA mutation. On exploratory analysis, high baseline plasma VEGF and interferon-gamma levels marginally associated with tumor progression. Conclusions The combination of erlotinib and temsirolimus was poorly tolerated. Low prevalence of PTEN expression and 8% incidence of PIK3CA mutations indicate biological relevance of this pathway in R/M disease. Investigation of more tolerable combinations of EGFR and PI3K/Akt/mTOR pathway inhibitors in selected HNSCC patients is warranted.

We present the second reported mammary analog secretory carcinoma (MASC) apparently arising in the thyroid and propose a potential close relationship to ETV6-NTRK3 fusion papillary thyroid carcinoma. The patient, a 36 year old woman, presented with a neck mass of 1 year's duration. Imaging studies showed a tumor involving most of the thyroid with enlarged regional lymph nodes. FNA biopsy yielded a diagnosis of ''papillary thyroid carcinoma''. Resection revealed a 4.5 cm infiltrative tumor. Final diagnosis was ''papillary thyroid carcinoma (PTC) consistent with diffuse sclerosing variant'' with positive lymph nodes (2?/4) and margins. Histologic features included mixed microcystic, solid, follicular and papillary architecture, prominent nucleoli, abundant nuclear grooves and rare nuclear pseudo-inclusions. Despite radioactive iodine, radiotherapy and multiagent chemotherapy, the patient progressed over 6 years with local recurrence and additional lymph node involvement finally developing widespread distant metastases. Prompted by the breast carcinoma-like histopathology of a metastasis, immunohistochemical staining was performed and revealed strong expression of GATA3 and mammaglobin with no reactivity for thyroglobulin or TTF-1. The original tumor was then tested and showed the same immunoprofile. RT-PCR confirmed the presence of an ETV6-NTRK3 fusion consistent with a diagnosis of MASC. Our patient's clinical, imaging and morphologic features remarkably mimicked papillary thyroid carcinoma. At the molecular level, the ETV6-NTRK3 fusion in this patient involved exons reported in the rare ''papillary thyroid carcinoma'' with this translocation. Given the immunophenotype of this case, it is possible that at least some ETV6-NTRK3 fusion positive PTC are actually MASC masquerading as papillary thyroid carcinoma.

The paradigm of image-guided FESS surgery, which integrates CAS into FESS, will serve to increase surgical effectiveness and decrease surgical morbidity.

The introduction of computed tomography (CT) in 1972 revolutionized the radiographic evaluation of patients who have experienced trauma. However, panoramic tomography (PT) continued to be superior in sensitivity to CT in the identification of mandible fractures and has been considered the gold standard for the past 3 decades. In 1989, a faster, higher-resolution spiral or helical CT (HCT) became widely available, and its efficacy in multiplanar evaluation and diagnosis of fractures of the upper two thirds of the face has been well established. The sensitivity of this new-generation HCT in comparison to PT in the detection of mandible fractures has not been determined. The purpose of this study was to compare the sensitivity, physician interpretation error, and interphysician agreement of HCT and PT in the identification of mandible fractures. The number and anatomical location of mandible fractures identified by HCT and PT was not significantly different. However, the number and location of 96% of fractures identified by HCT was agreed on by neuroradiologists compared with only 91% of fractures identified by PT. Furthermore, the interphysician agreement when no fracture was identified was 96% by HCT versus only 81% by PT. In conclusion, HCT has enhanced imaging quality, equivalent sensitivity in identification of fractures, decreased interpretation error, and greater interphysician agreement in the identification of mandible fractures. HCT has surpassed PT as the current gold standard for the radiographic evaluation and diagnosis of mandible fractures.

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