Background.Althoughfine-needle aspiration (FNA) is 907 o sensitive in the detection of papillary carcinoma (PC) of the thyroid, its specz@city has been reported as low as 52 %.Consequently, patients who have an FNA suspicious for PC may undergo operation for a benign process.The ribonucleoprotein telomerase has been noted to be activated in a wide variety of carcinomas.We examined 30 PCs for telomerase activity to determine whether this would be a useful adjunct to FNA in the diaposis of lesions suspicious for PC.Methods.Standard telomere repeat amplajiication protocol assays were performed on fresh frozen tissue samples from 30 PCs, 3 benign nodules, and 10 normal thyroids.Results.Telomerase activity was documented in 20 of 30 (67%) of the PCs, 0 of 3 benign nodules, and 0 of 10 normal thyroids.In all, 11 of the 20 PCs had EVA cytology that was nondiagnostic of PC, and 2 of the benign nodules had FNA that was suspicious for PC.Conclusions.The telomerase assay appears useful in the distinction of benign from malignant thyroid lesions that have FNA suspicious for but not diagnostic of PC.On the basis of these findings, a prospective trial examining telomerase activity in FNAs suspicious for thyroid cancer has been initiated.
<div>Abstract<p>To inform novel personalized medicine approaches for race and socioeconomic disparities in head and neck cancer, we examined germline and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health in Black and non-Latino White (NLW) patients with head and neck cancer. Cox proportional hazards revealed that Black patients with squamous cell carcinoma of head and neck (HNSCC) with <i>PAX5</i> (<i>P</i> = 0.06) and <i>PAX1</i> (<i>P</i> = 0.017) promoter methylation had worse survival than NLW patients, after controlling for education, zipcode, and tumor–node–metastasis stage (<i>n</i> = 118). We also found that promoter methylation of <i>PAX1</i> and P<i>AX5</i> (<i>n</i> = 78), was correlated with neighborhood characteristics at the zip-code level (<i>P</i> < 0.05). Analyses also showed differences in the frequency of <i>TP53</i> mutations (<i>n</i> = 32) and tumor-infiltrating lymphocyte (TIL) counts (<i>n</i> = 24), and the presence of a specific C → A germline mutation in <i>JAK3</i>, chr19:17954215 (protein P132T), in Black patients with HNSCC (<i>n</i> = 73; <i>P</i> < 0.05), when compared with NLW (<i>n</i> = 37) patients. TIL counts are associated (<i>P</i> = 0.035) with long-term (>5 years), when compared with short-term survival (<2 years). We show bio-social determinants of health associated with survival in Black patients with HNSCC, which together with racial differences shown in germline mutations, somatic mutations, and TIL counts, suggests that contextual factors may significantly inform precision oncology services for diverse populations.</p></div>
Objective To determine if patients with human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) treated with chemoradiation have improved outcomes. Study Design A retrospective search was used to identify patients with OPSCC treated with concurrent chemoradiation. Pretreatment biopsy specimens were tested for HPV‐16 infection and p16 expression. Methods Forty‐four patients with OPSCC treated with concurrent chemotherapy and intensity‐modulated radiation therapy were identified. Eligibility criteria included a minimum two years of follow‐up, or biopsy‐proven recurrence. In situ hybridization was applied to archival tumor specimens, with HPV‐16‐positive status defined as positive staining of tumor cell nuclei. p16 expression was assessed by immunohistochemistry. Results Twenty‐seven tumors (61%) were positive for HPV‐16 and 29 tumors (66%) expressed p16. HPV‐16 infection was highly correlated with p16 expression ( P < 10 −7 ). Three‐year disease‐free and overall survival for all patients was 66 percent and 79 percent respectively. Patients with tumors infected with HPV‐16 had improved overall (OS) and disease‐free survival (DFS) after chemoradiation (OS: hazard ratio [HR] = 0.21, P = 0.01; DFS: HR = 0.30, P = 0.02). Conclusion Patients with OPSCC tumors that are infected with HPV‐16 have improved survival after treatment with concurrent chemoradiation.
The pulse granuloma (PG) is believed to represent a distinctive foreign body reaction to ingested particles of legumes. Its presentation in the neck is entirely unexpected.A woman presented with a mass of the lower neck that recurred following incision and drainage. The recurrent mass was found to be associated with an open sinus tract at the apex of the left pyriform sinus. The opening of the sinus tract was closed and the cyst was removed.Histologic examination of the neck mass showed vegetable material with an associated granulomatous reaction known as PG.The documentation of a PG arising in the neck would seemingly discredit the legume theory, but it only further supports it. Its association with a fourth branchial cleft cyst provides evidence for the existence of the complete fourth branchial cleft fistula with seeding of ingested material through sinus tract opening.
Human papillomavirus type 16 (HPV-16) is a major causative factor in oropharyngeal squamous cell carcinoma (OPSCC). The detection of primary OPSCC is often delayed owing to the challenging anatomy of the oropharynx.To investigate the feasibility of HPV-16 DNA detection in pretreatment and posttreatment plasma and saliva and its potential role as a marker of prognosis.This is a retrospective analysis of a prospectively collected cohort. Among a cohort of patients with oropharyngeal and unknown primary squamous cell carcinoma with known HPV-16 tumor status from the Johns Hopkins Medical Institutions and Greater Baltimore Medical Center (from 1999 through 2010), 93 patients were identified with a complete set of pretreatment and posttreatment plasma or saliva samples, of which 81 patients had HPV-16-positive tumors and 12 patients had HPV-16-negative tumors. Real-time quantitative polymerase chain reaction was used to detect HPV-16 E6 and E7 DNA in saliva and plasma samples.Main outcomes included sensitivity, specificity, negative predictive value of combined saliva and plasma pretreatment HPV-16 DNA status for detecting tumor HPV-16 status, as well as the association of posttreatment HPV DNA status with clinical outcomes, including recurrence-free survival and overall survival.The median follow-up time was 49 months (range, 0.9-181.0 months). The sensitivity, specificity, negative predictive value, and positive predictive value of combined saliva and plasma pretreatment HPV-16 DNA status for detecting tumor HPV-16 status were 76%, 100%, 42%, and 100%, respectively. The sensitivities of pretreatment saliva or plasma alone were 52.8% and 67.3%, respectively. In a multivariable analysis, positive posttreatment saliva HPV status was associated with higher risk of recurrence (hazard ratio [HR], 10.7; 95% CI, 2.36-48.50) (P = .002). Overall survival was reduced among those with posttreatment HPV-positive status in saliva (HR, 25.9; 95% CI, 3.23-208.00) (P = .002) and those with HPV-positive status in either saliva or plasma but not among patients with HPV-positive status in plasma alone. The combined saliva and plasma posttreatment HPV-16 DNA status was 90.7% specific and 69.5% sensitive in predicting recurrence within 3 years.Using a combination of pretreatment plasma and saliva can increase the sensitivity of pretreatment HPV-16 status as a tool for screening patients with HPV-16-positive OPSCC. In addition, analysis of HPV-16 DNA in saliva and plasma after primary treatment may allow for early detection of recurrence in patients with HPV-16-positive OPSCC.
Abstract Alterations of the mitochondrial DNA (mtDNA) have been described in human tumors and in other tissues in association with smoking exposure. We did quantitative PCR of cytochrome c oxidase I (Cox I) and cytochrome c oxidase II (Cox II) genes on oral rinse samples obtained from 94 patients with primary head and neck squamous cell carcinoma (HNSC) and a control group of 656 subjects. Mitochondrial DNA/nuclear DNA in saliva from HNSC patients and controls in relationship to smoking exposure, ethanol intake, and tumor stage were examined. Mean levels of Cox I and Cox II in saliva samples were significantly higher in HNSC patients: Cox I, 0.076 [95% confidence interval (95% CI), 0.06-0.09] and Cox II, 0.055 (95% CI, 0.04-0.07) in comparison with controls Cox I, 0.054 (95% CI, 0.05-0.06), P < 0.0001 and Cox II, 0.046 (95% CI, 0.04-0.05), P = 0.003 (t test). MtDNA levels were elevated in primary tumors when compared with matched, pretreatment saliva and significant correlation was noted (Cox I, r = 0.30, P = 0.005 and Cox II r = 0.33, P = 0.002, respectively, Pearson's correlation). On univariate analysis, smoking, age, HNSC diagnosis, and advanced stage of HNSC were associated with higher level of mtDNA content in saliva. Multivariate analysis showed a significant and independent association of HNSC diagnosis, age, and smoking with increasing mtDNA/nuclear DNA for Cox I and Cox II. mtDNA content alteration is associated with HNSC independently of age and smoking exposure, can be detected in saliva, and may be due to elevation in mtDNA content in primary HNSC.
<p>This file contains Supplementary Table 2. Supplementary Table 2 shows that the proliferative capacity of PD-1 expressing CD8, CD4, and FoxP3+ TILs are decreased compared to non-PD-1 expressing TILs in OTSCC.</p>
