Background: The vast majority of thyroid cancer, in particular the non-anaplastic follicular cell-derived thyroid carcinomas (non-ANA FCDCs), are considered indolent tumors with very low mortality. Hence, it is crucial to analyze the subgroup of these patients who died of disease (DOD) in order to identify clinico-pathologic features predictive of disease specific mortality. Methods: All non-ANA FCDCs operated at a tertiary cancer center between 1985 and 2010 who were DOD were identified and submitted to a meticulous clinico-pathologic analysis. Results: Out of 3,750 non-ANA FCDCs, 58 (1.5%) DOD cases were identified. The DOD group was composed of 33 (57%) poorly differentiated carcinoma (PDTC), 14 (24%) papillary thyroid carcinomas (PTC) tall cell variant, 4 (7%) Hurthle cell carcinomas, 3 (5%) papillary microcarcinomas, 2 (3%) PTC classical variant, and 2 (3%) PTC follicular variant. Twenty-seven patients (47%) presented with distant metastases (DM), 28 (48%) developed DM during follow ups, while the remaining 3 (5%) had locally advanced non-resectable recurrence. Gross extension beyond thyroid (GET) was present in 36 (62%) and extensive vascular invasion (VI) in 21 (36%) of cases. All microcarcinomas had PDTC in their clinically apparent cervical lymph nodes at presentation. Encapsulated thyroid carcinomas were responsible for 17% of DOD cases and all had extensive VI and/or DM at presentation. All patients had at least one of these high risk features at diagnosis: DM at presentation, PDTC, GET, and/or extensive VI. The majority of patients died from DM (n=51, 88%), 3 (5%) of locoregional disease, 3 (5%) from both, and 1 (2%) from unknown cause. Conclusions: PDTC and tall cell variant PTC are responsible for the vast majority of death in differentiated thyroid carcinomas while the few fatal classical, follicular variant PTC and microcarcinomas all harbor PDTC component, DM or GET. Encapsulated differentiated thyroid carcinoma with focal capsular and/or VI without DM at presentation does not seem to cause death. Lack of DM at presentation, PDTC, GET and extensive VI identify thyroid carcinomas at almost no risk of DOD. The vast majority of patients die of DM rather than locoregional invasion, prompting the need for effective systemic treatment.

Objectives: Smoking is the commonest cause of oral cavity squamous cell carcinoma (OC-SCC), but the etiology of OC-SCC in nonsmokers is unknown. Our primary goal was to use metagenomic shotgun sequencing (MSS) to define the taxonomic composition and functional potential of oral metagenome in nonsmokers with OC-SCC. Methods: We conducted a case–control study with 42 OC-SCC case and 45 control nonsmokers. MSS was performed on DNA extracted from mouthwash samples. Taxonomic analysis and pathway analysis were done using MetaPhlAn2 and HUMAnN2, respectively. Statistical difference was determined using the Mann–Whitney test controlling false discovery rate. Results: There was no significant difference in age, sex, race, or alcohol consumption between OC-SCC and control patients. There was a significant difference in beta diversity between OC-SCC and controls. At the phylum level, Bacteroidetes and Synergistetes were overly represented in OC-SCC while Actinobacteria and Firmicutes were overly represented in controls. At the genus level, Fusobacterium was overly represented in OC-SCC compared with controls, while Corynebacterium, Streptococcus, Actinomyces, Cryptobacterium, and Selenomonas were overly represented in controls. Bacterial pathway analysis identified overrepresentation in OC-SCC of pathways related to metabolism of flavin, biotin, thiamin, heme, sugars, fatty acids, peptidoglycans, and tRNA and overrepresentation of nucleotides and essential amino acids in controls. Conclusions: The oral microbiome in nonsmoker patients with OC-SCC is significantly different from that of nonsmoker control patients in taxonomic compositions and functional potentials. Our study’s MSS findings matched with previous 16S-based methods in taxonomic differentiation but varied greatly in functional differentiation of microbiomes in OC-SCC and controls.

Background: Radiation exposure, especially in childhood, is known to increase the risk for the development of thyroid cancer. However, the prognosis of patients with thyroid cancer with a history of radiation treatment exposure remains unclear. Methods: One hundred and sixteen patients with a previous history of radiotherapy in the head and neck region were identified from an institutional database of 3664 patients with differentiated thyroid cancer treated between 1986 and 2010. Using the Kaplan–Meier method, disease-specific survival and recurrence-free survival were compared between patients with (RT; n = 116) and without (No RT; n = 3509) a prior history of radiation exposure. Results: The median ages of the RT and No RT cohorts were 52 and 47 years. The median follow-up for both groups was 54 months. Patients who had a prior history of radiation treatment exposure were more likely to be male (38.8% vs. 26.9%; p = 0.005) and older than 45 years of age (67.2% vs. 53.9%; p = 0.005). Other patient, tumor, and treatment characteristics were similar between the groups. There was no difference in the five-year disease-specific survival of the RT and No RT patients (97.4% vs. 98.7%; p = 0.798). The five-year recurrence-free survival was also similar between the RT and No RT patients (97.8% vs. 94.9%; p = 0.371). Conclusion: The findings suggest that differentiated thyroid cancer patients with a history of prior radiation treatment exposure have similar outcomes to those with no history of head and neck radiation exposure.