Aaron P. Hoschar

Background: Tumor human papillomavirus (HPV) status has emerged as one of the most powerful prognostic factors for disease control and survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). We reviewed our experience in patients with OPSCC and known tumor HPV status treated with definitive chemoradiotherapy (CRT). Methods: Patients with stage III-IVb OPSCC and known tumor HPV status treated with CRT between 2006 and 2011 were identified from an IRB approved registry for this retrospective review. Outcomes were estimated using the Kaplan-Meier method and compared between HPV-positive and negative patients using the log-rank test. Results: Of the 121 pts (89% male, 93% Caucasian) included in this study, median age was 57 (range: 40–73) and median follow-up was 21 months (range: 6–63). Ninety-seven (80%) patients were HPV-positive and 24 (20%) were HPV-negative. Primary site was base of tongue (55%), tonsil (44%), and oropharyngeal wall (2%). Two year rates of locoregional recurrence (3% vs. 26%; p = 0.002), disease free survival (93% vs. 64%; p = 0.001) and overall survival (94% vs 73%; p = 0.002) were superior in HPV-positive patients, while rates of distant recurrence were similar (3% vs. 5%; p = 0.98). While acute toxicities were similar between both groups, patients with HPV-positive disease were more likely to resume a normal diet (90% vs. 65%; p = 0.017) at last follow up. Also, no HPV-positive patient required a feeding tube beyond 6 months after treatment, compared with 24% of HPV-negative patients. Conclusions: Definitive CRT produces excellent rates of disease control with minimal late toxicity for patients with HPV-positive OPSCC. Studies of OPSCC should account for tumor HPV status when identifying factors prognostic for outcome.

Middle ear adenomas (MEAs) are benign neoplasms along a spectrum with neuroendocrine neoplasms (carcinoid tumors). Immunohistochemical (IHC) staining for myoepithelial markers has not been reported in these tumors. The archives of the Cleveland Clinic, University of Virginia and Armed Forces Institute of Pathology were retrospectively searched for tumors arising within the middle ear with material available for IHC staining. Twelve cases of MEAs, four cases of jugulotympanic paragangliomas (JPGs), 10 cases of ceruminous adenomas (CAs) and four cases of ceruminous adenocarcinomas (CACs) were obtained. IHC staining was performed for smooth muscle actin (SMA), p63, S-100 protein, cytokeratin 5/6 (CK5/6), and cytokeratin 7 (CK7). The MEAs were positive for: CK7 (92 %, luminal), CK5/6 (92 %, abluminal), p63 (83 %, abluminal), and negative for SMA and S-100 protein. The JPGs were negative for CK7, CK5/6, p63 and SMA; S-100 protein highlighted sustentacular cells. The CAs were positive for: CK7 (100 %, luminal), CK5/6 (100 %, abluminal), S-100 protein (80 %, abluminal), p63 (100 %, abluminal), and SMA (90 %, abluminal). CACs demonstrated two patterns, (1) adenoid cystic carcinoma-type: positive for CK7 (100 %, luminal), CK5/6, S-100 protein, p63, and SMA (all 100 %, abluminal); and (2) conventional-type: CK7 (50 % luminal), and no CK5/6, SMA, S-100 protein, or p63 expression. The IHC profile of MEAs suggests that these tumors harbor at least two cell populations, including luminal and basal cells. However, unlike ceruminous adenomas, MEAs lack true myoepithelial differentiation given the absence of S-100 protein and SMA staining in all cases.