Head-and-neck squamous cell carcinoma risk in smokers: no association detected between phenotype and AHR, CYP1A1, CYP1A2, or CYP1B1 genotype.

BACKGROUND: Head-and-neck squamous cell carcinoma (HNSCC) differs between smokers and nonsmokers in etiology and clinical presentation. Because of demonstrated unequivocal involvement in smoking-induced cancer in laboratory animals, four candidate genes--AHR, CYP1A1, CYP1A2, and CYP1B1--were selected for a clinical genotype-phenotype association study of HNSCC risk in smokers. Thirty-six single-nucleotide variants (mostly tag-SNPs) within and near these four genes [16 (AHR), 4 (CYP1A1), 4 (CYP1A2), and 12 (CYP1B1)] were chosen. METHODS: Extreme discordant phenotype (EDP) method of analysis was used to increase statistical power. HNSCC patients--having smoked 1-40 cigarette pack-years--represented the "highly-sensitive" (HS) population; heavy smokers having smoked ≥80 cigarette-pack-years without any type of cancer comprised the "highly-resistant" (HR) group. The vast majority of smokers were intermediate and discarded from consideration. Statistical tests were performed on N = 112 HS and N = 99 HR DNA samples from whole blood. CONCLUSIONS: Among the four genes and flanking regions--one haploblock, ACTTGATC in the 5' portion of CYP1B1, retained statistical significance after 100,000 permutations (P = 0.0042); among our study population, this haploblock was found in 36.4% of African-American, but only 1.49% of Caucasian, HNSCC chromosomes. Interestingly, in the 1000 Genomes Project database, frequency of this haplotype (in 1322 African and 1006 Caucasian chromosomes) is 0.356 and 0.003, respectively. This study represents an excellent example of "spurious association by population stratification". Considering the cohort size, we therefore conclude that the variant alleles chosen for these four genes, alone or in combinations, are not statistically significantly associated with risk of cigarette-smoking-induced HNSCC.

Ultra-small superparamagnetic iron oxide (USPIO) magnetic resonance imaging in benign mixed tumor of the parotid gland.

Historically USPIO has been used to help with nodal staging but not in primary tumors. The ability to concentrate USPIO may help to differentiate BMT from other types of parotid tumors.

Vacuum-assisted cell seeding in a microwell cell culture system.

We present a simple method to actively pattern individual cells and groups of cells in a polymer-based microdevice using vacuum-assisted cell seeding. Soft lithography is used to mold polymer microwells with various geometries on top of commercially available porous membranes. Cell suspensions are placed in a vacuum filtration setup to pull culture medium through the microdevice, trapping the cells in the microwells. The process is evaluated by determining the number of cells per microwell for a given cell seeding density and microwell geometry. This method is tested with adherent and nonadherent cells (NIH 3T3 fibroblasts, PANC-1 pancreatic ductal epithelial-like cells, and THP-1 monocytic leukemia cells). These devices could find applications in high-throughput cell screening, cell transport studies, guided formation of cell clusters, and tissue engineering.

Previously Unreported Complication of Coronary Artery Bypass Grafting: Suture Rupture Resulting in Patient's Death.

Traditionally, the manner of death in most hospital autopsy cases is natural, in which death is due to the natural course of disease or reasonably anticipated outcomes of medical interventions. Some cases fall into a potential gray zone between natural and accident, including rare or unanticipated outcomes of medical interventions. We present a case of a patient postcoronary artery bypass graft. Autopsy revealed the proximal anastomosis of the aorta-to-first-diagonal-coronary-artery-to-second-obtuse-marginal-artery graft was detached from the aorta. A broken suture was present at the disconnected anastomosis, with intact knots but was broken along its length. In-hospital mortality rates of CABG range from 1% to 3%, with several autopsy studies identifying surgical complications as the cause of death in one-third of perioperative deaths. No publications were found that described suture rupture as directly relating to the cause of death. This case report describes a previously unreported complication of coronary artery bypass grafting.

Tonsillar Small Cell Carcinoma: Potential Contribution of Human Papillomavirus.

BACKGROUND Extrapulmonary small cell carcinoma (SmCC) is a relatively rare clinical entity constituting only 2.5-5% of SmCCs. Recently, evidence has emerged that high-risk types of human papillomavirus (HPV) might play an etiologic role in oropharyngeal SmCC, similar to squamous cell carcinoma. CASE REPORT Here, we present a case of tonsillar SmCC that presented as combined SmCC-squamous cell carcinoma in a cervical lymph node, raising the possibility that the SmCC-component represents disease progression. CONCLUSIONS This case lends further support to the importance of HPV in the development of oropharyngeal SmCC and suggests a mechanism of disease progression.

Decreased plasma DEK Oncogene Levels Correlate with p16-Negative Disease and Advanced Tumor Stage in a Case-Control Study of Patients with Head and Neck Squamous Cell Carcinoma.

Head and neck cancer (HNC) remains the sixth most common malignancy worldwide and survival upon recurrence and/or metastasis remains poor. HNSCC has traditionally been associated with alcohol and nicotine use, but more recently the Human Papilloma Virus (HPV) has emerged as a favorable prognostic risk factor for oropharyngeal HNSCC. However, further stratification with additional biomarkers to predict patient outcome continues to be essential. One candidate biomarker is the DEK oncogenic protein, which was previously detected in the urine of patients with bladder cancer and is known to be secreted by immune cells such as macrophages. Here, we investigated if DEK could be detected in human plasma and if DEK levels correlated with clinical and pathological variables of HNSCC. Plasma was separated from the peripheral blood of newly diagnosed, untreated HNSCC patients or age-matched normal healthy controls and analyzed for DEK protein using ELISA. Plasma concentrations of DEK protein were lower in p16-negative tumors compared to both normal controls and patients with p16-positive tumors. Patients with lower plasma concentrations of DEK were also more likely to have late stage tumors and a lower white blood cell count. Contrary to previously published work demonstrating a poor prognosis with high intratumoral DEK levels, we show for the first time that decreased concentrations of DEK in patient plasma correlates with poor prognostic factors, including HPV-negative status as determined by negative p16 expression and advanced tumor stage.

A Case of Hodgkin Lymphoma Mimicking Lymphomatoid Granulomatosis Diagnosed at Autopsy.

Hodgkin lymphoma and lymphomatoid granulomatosis (LYG) are entities that contain a small number of large, variably Epstein-Barr virus (EBV)-positive neoplastic cells scattered within background non-neoplastic mixed inflammatory infiltrate. The 2 entities can typically be distinguished histologically by the angiocentric and angiodestructive pattern of lymphomatoid granulomatosis (LYG); also, they differ in overall prognosis. Herein, we report a case of Hodgkin lymphoma in a 64-year-old Caucasian woman, diagnosed at autopsy with unusual histologic features and aggressive clinical course that mimicked LYG.

Mucoepidermoid carcinoma post-radioactive iodine treatment of papillary thyroid carcinoma: unique presentation and putative etiologic association.

We report the development of mucoepidermoid carcinomas of the parotid gland in 2 adult patients after a relatively short duration of radioactive iodine (RAI) treatment of papillary thyroid carcinoma. Both instances, together with those previously reported, underscore the selective nature of the mucoepidermoid carcinoma phenotype development in patients with papillary thyroid carcinoma as a consequence of RAI treatment. Efforts to alleviate salivary pathophysiologic damage by RAI in these patients are warranted.

Head and Neck Schwannomas: 20-Year Experience of a Single Institution Excluding Cutaneous and Acoustic Sites.

While head and neck sites comprise the most common location of schwannomas, clinicopathologic data regarding those tumors occurring in non-acoustic and non-cutaneous locations are relatively sparse. In this study, therefore, we sought to examine retrospectively the clinical and pathologic features of head and neck schwannomas excised at our institution over a 20-year period. During this period, we identified a total cohort of 85 patients, which included 36 males (42.4 %) and 49 females with average age of 41.3 years, the majority of which presented asymptomatically with a mass. Localized symptoms were, however, associated with all of the schwannomas that arose in the oral cavity and larynx, while tumors within or adjacent to bone were often associated with neurologic complaints (7 of 15 such tumors [46.7 %]). Clinical follow-up data was available in 86.4 % of all cases and demonstrated no recurrences or mortality. Pathologically, the microscopic features were characteristic of those well-described for schwannomas in other sites, including alternating Antoni A and B areas and the presence of degenerative changes. Tumor encapsulation, however, was variable and was completely absent in schwannomas of the nasal cavity, paranasal sinuses, and larynx. Additionally, a significant minority of the tumors (28.2 %) exhibited foci that resembled neurofibroma. Non-acoustic, non-cutaneous schwannomas of the head and neck appear to have clinicopathologic features similar to their soft tissue counterparts with some subsite variation in presentation and/or microscopic features.

Evaluation of PAX2 and PAX8 expression in salivary gland neoplasms.

PAX2 and PAX8 are transcription factors involved in embryogenesis that have been utilized as immunohistochemical indicators of tumor origin. Specifically, PAX2 is a marker of neoplasms of renal and müllerian origin, while PAX8 is expressed by renal, müllerian, and thyroid tumors. While studies examining these transcription factors in a variety of tumors have been published, data regarding their expression in salivary gland neoplasms are limited. The goal of this study was to assess expression of PAX2 and PAX8 in a large cohort of salivary gland tumors. Utilizing tissue microarrays, samples of normal salivary glands (n = 68) and benign and malignant salivary gland neoplasms (n = 442) were evaluated for nuclear immunoreactivity with PAX2 and PAX8. No expression was observed with either marker in the normal salivary glands, and PAX8 was negative in all neoplasms. Focal expression of PAX2 was observed in one example each of oncocytoma and acinic cell carcinoma. These results indicate that evaluation of PAX2 and/or PAX8 expression would be valuable in differentiating primary salivary gland tumors from metastases known to express PAX2 and/or PAX8.

An immunohistochemical panel for reliable differentiation of salivary duct carcinoma and mucoepidermoid carcinoma.

Salivary duct carcinoma is a highly aggressive salivary gland malignancy that may be misdiagnosed as high-grade mucoepidermoid carcinoma. We utilized tissue microarrays with 78 examples of mucoepidermoid carcinoma and 47 salivary duct carcinomas to evaluate the utility of an immunohistochemical panel consisting of androgen receptor, Her2/neu, p63, and cytokeratin 5/6 in distinguishing these entities. Among all cases in the cohorts, androgen receptor was highly specific for salivary duct carcinoma, while cytokeratin 5/6 and p63 were specific for mucoepidermoid carcinoma. While the rate of unequivocal Her2/neu overexpression among the salivary duct carcinomas was low (8.9 %), discrimination of salivary duct carcinoma was enhanced when this marker was used in combination with androgen receptor due to profound sensitivity. The immunohistochemical panel was particularly efficacious at distinguishing the problematic subset of high-grade mucoepidermoid carcinomas from salivary duct carcinoma. Utilization of this set of immunohistochemical markers allows reliable differentiation of salivary duct and mucoepidermoid carcinoma, a distinction with important prognostic and therapeutic implications.