Jonathan Mark

Validation of American Thyroid Association Ultrasound Risk Assessment of Thyroid Nodules Selected for Ultrasound Fine-Needle Aspiration

OBJECTIVE The aim of this study was to validate the American Thyroid Association (ATA) sonographic risk assessment of thyroid nodules. METHODS The ATA sonographic risk assessment was prospectively applied to 206 thyroid nodules selected for ultrasound-guided fine-needle aspiration (US-FNA), and analyzed with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), as well as surgical pathology for the subset undergoing surgical excision. RESULTS The analysis included 206 thyroid nodules averaging 2.4 cm (range 1-7 cm; standard error of the mean 0.07). Using the ATA US pattern risk assessment, nodules were classified as high (4%), intermediate (31%), low (38%), and very low (26%) risk of malignancy. Nodule size was inversely correlated with sonographic risk assessment, as lower risk nodules were larger on average (p < 0.0001). Malignancy rates determined by cytology/surgical pathology were high 100%, intermediate 11%, low 8%, and very low 2%, which were closely aligned with ATA malignancy risk estimates (high 70-90%, intermediate 10-20%, low 5-10%, and very low 3%). ATA US pattern risk assessment also appropriately predicted the proportion of nodules classified as malignant or suspicious for malignancy through TBSRTC classification-high (77%), intermediate (6%), low (1%), and very low 0%-as well as benign TBSRTC classification-high (0%), intermediate (47%), low (61%), and very low (70%) (p < 0.0001). Malignancy rates of surgically excised, cytologically indeterminate nodules followed ATA sonographic risk stratification (high 100%, intermediate 21%, low 17%, and very low 12%; p = 0.003). CONCLUSION This prospective study supports the new ATA sonographic pattern risk assessment for selection of thyroid nodules for US-FNA based upon TBSRTC and surgical pathology results. In the setting of indeterminate cytopathology, nodules categorized as atypia of undetermined significance/follicular lesion of undetermined significance with ATA high-risk sonographic patterns have a high likelihood of being malignant.

Survival and Prognosis for Malignant Tumors of Odontogenic Origin.

Objective Determine survival and factors affecting survival for patients with malignant tumors of odontogenic origin. Study Design Retrospective analysis of the National Cancer Institute’s SEER database (Surveillance, Epidemiology, and End Results). Setting Tertiary medical center. Subjects and Methods All cases of malignant tumors of odontogenic origin were extracted from the SEER database for the period of 1973 to 2011. Demographic, tumor-specific, and survival data were tabulated and Kaplan-Meier survival analysis conducted according to histopathologic results. Cox regression analysis stratified for histopathology was conducted to determine factors that influenced survival. Results A total of 308 cases of malignant tumors with odontogenic origin were analyzed. Malignant ameloblastoma accounted for 59.7% of cases, followed by malignant odontogenic tumor (35.4%; including odontogenic carcinoma, odontogenic sarcoma, primary intraosseous carcinoma, and ameloblastic carcinoma) and ameloblastic fibrosarcoma (2.9%). The overall mean and median were 229 and 227 months, respectively, while the 5-year survival rate was 81% for the entire cohort. Malignant ameloblastoma exhibited the best mean survival (237 months), whereas malignant odontogenic tumor (139 months) and ameloblastic fibrosarcoma (42 months) had lower mean survival rates. Younger age, surgery with adjuvant radiation, and smaller tumor size were found to improve survival. Conclusions Significantly different survival can be expected depending on individual tumor histopathology, tumor size, age at diagnosis, and treatment modality.

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.

Thyroid Ultrasound-Guided Fine-Needle Aspiration Cytology Results: Observed Increase in Indeterminate Rate over the Past Decade

Objectives To evaluate changes in distribution of reported thyroid nodule fine-needle aspiration (FNA) cytopathology results since implementation of the Bethesda classification and revised 2015 American Thyroid Association (ATA) guidelines for selecting nodules for biopsy. Study Design Retrospective review. Setting Tertiary academic medical center. Subjects and Methods Evaluation of ultrasound (US)–guided thyroid FNA by a single surgeon using 2015 ATA nodule selection criteria and Bethesda reporting on 211 thyroid nodules in a 1-year period (2015). Comparison is made to an earlier sample wherein any nodule >1 cm underwent US FNA with cytology reported prior to Bethesda consensus (2006). Results The current cohort involved mostly women (79%); nodules ranged from 1 to 7 cm (mean ± SEM, 2.4 ± 0.07 cm). Mean ± SEM age was 53.5 ± 1.1 years. Bethesda reporting yielded 6% nondiagnostic, 57% benign, 3% malignant, and 34% indeterminate (27% atypia of undetermined significance [AUS]/follicular lesion of undetermined significance [FLUS], 4% follicular neoplasm [FN]/Hürthle neoplasm [HN], and 2% suspicious for malignancy [SFM]). The malignancy rate in indeterminate nodules was 26% (18% AUS/FLUS, 33% FN/HN, and 80% SFM). Age, sex, or nodule size did not correlate with indeterminate cytology. The comparator sample of 447 nodules had significantly different distribution, with 7% nondiagnostic, 80% benign, 5% malignant, and 8% indeterminate (P < .00001). Conclusion We observed a significantly increased proportion of indeterminate cytology and corresponding decrease in benign nodules compared with an earlier sample, predominately from an increase in AUS/FLUS. Multiple factors are likely involved, including selection of sonographically suspicious nodules for biopsy based upon 2015 ATA guidelines coupled with cytopathological interpretation by a new generation of cytopathologists trained in the era of Bethesda reporting; further study is required to make a definitive conclusion.

Re-operative Parathyroid Surgery

Re-operative parathyroid surgery can result from prior parathyroid surgery or proximate neck surgeries. When a patient remains hypercalcemic and hyperparathyroid within 6 months following initial parathyroid surgery, he or she is considered to have persistent primary hyperparathyroidism. Recurrent primary hyperparathyroidism may occur after initial successful parathyroidectomy and postoperative period of normocalcemia. Over time, less invasive surgical techniques coupled with preoperative localization studies have shifted many initial operations away from initial four-gland exploration. Prior to embarking on re-operative parathyroid surgery, the surgeon should (1) review the prior and current biochemical workup to confirm the diagnosis, and (2) review the prior operative, pathology, imaging, and intraoperative PTH results in attempt to understand the extent of original surgery and potential cause for failure. Parathyroid embryology and anatomy, intraoperative PTH monitoring, preoperative imaging, radiopharmaceutical guidance, jugular venous sampling, and RLN monitoring are all important considerations and adjuncts which may be helpful in re-operative parathyroid surgery. Re-operative parathyroid surgery requires a systematic approach as the chance of cure in re-operative surgery is reduced and the chance of complication is increased in comparison to primary surgery. It is incumbent on the surgeon to optimize chances of success utilizing available localization techniques, and by exercising careful, calculated clinical judgement.

Validation of ATA Ultrasound Risk Assessment of Thyroid Nodules Selected for Ultrasound Fine Needle Aspiration

OBJECTIVE The aim of this study was to validate the American Thyroid Association (ATA) sonographic risk assessment of thyroid nodules. METHODS The ATA sonographic risk assessment was prospectively applied to 206 thyroid nodules selected for ultrasound-guided fine-needle aspiration (US-FNA), and analyzed with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), as well as surgical pathology for the subset undergoing surgical excision. RESULTS The analysis included 206 thyroid nodules averaging 2.4 cm (range 1-7 cm; standard error of the mean 0.07). Using the ATA US pattern risk assessment, nodules were classified as high (4%), intermediate (31%), low (38%), and very low (26%) risk of malignancy. Nodule size was inversely correlated with sonographic risk assessment, as lower risk nodules were larger on average (p < 0.0001). Malignancy rates determined by cytology/surgical pathology were high 100%, intermediate 11%, low 8%, and very low 2%, which were closely aligned with ATA malignancy risk estimates (high 70-90%, intermediate 10-20%, low 5-10%, and very low 3%). ATA US pattern risk assessment also appropriately predicted the proportion of nodules classified as malignant or suspicious for malignancy through TBSRTC classification-high (77%), intermediate (6%), low (1%), and very low 0%-as well as benign TBSRTC classification-high (0%), intermediate (47%), low (61%), and very low (70%) (p < 0.0001). Malignancy rates of surgically excised, cytologically indeterminate nodules followed ATA sonographic risk stratification (high 100%, intermediate 21%, low 17%, and very low 12%; p = 0.003). CONCLUSION This prospective study supports the new ATA sonographic pattern risk assessment for selection of thyroid nodules for US-FNA based upon TBSRTC and surgical pathology results. In the setting of indeterminate cytopathology, nodules categorized as atypia of undetermined significance/follicular lesion of undetermined significance with ATA high-risk sonographic patterns have a high likelihood of being malignant.

Surgical Management of Low-Risk Papillary Thyroid Cancer

Current medical literature clearly defines a group of low-risk papillary thyroid carcinomas that may be treated effectively with thyroid lobectomy alone. Considerations regarding overall survival, local control, and perioperative morbidity in addition to patient monitoring, disease features, and patient preference, guide the treatment team in the extent of surgical intervention. The effectiveness of thyroid lobectomy for papillary thyroid carcinoma is dependent upon accurate preoperative and intraoperative exclusion of bilateral disease, extrathyroidal extension, or nodal metastasis. The advantages over total thyroidectomy are reduced perioperative morbidity and less dependence upon thyroid hormone replacement. The disadvantages are more dependence upon ultrasound surveillance, inability to use radioiodine, and potential need for completion thyroidectomy.

Abstract 50: Plasma concentrations of the DEK oncogene correlate with pathological variables in a case-control study of patients with HNSCC

Background: Head and neck squamous cell carcinoma (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 chromatin remodeling DEK protein, which is both an auto-antigen in autoimmune diseases and an oncogene in epithelial tissues. DEK is secreted by stimulated macrophages and neutrophils and was previously detected in the urine of patients with bladder cancer. Previously, we have reported that DEK mRNA and protein is upregulated in HNC tumor tissue and higher DEK levels are associated with poor prognoses in many types of solid tumors. We hypothesized that DEK could be detected in the plasma of HNC patients, either due to secretion from the tumor or as part of the antitumor immune response, and therefore may be a biomarker for disease status. Methods: We recruited 38 newly diagnosed HNSCC patients and 37 age-matched normal healthy controls into the study. Plasma isolated from peripheral blood was subjected to DEK specific ELISA and DEK concentration levels were compared to levels found in normal controls, and to clinical and pathological variables. Results: We show for the first time that DEK can be detected in human plasma. We did not find an association between DEK plasma concentrations and variables including sex, age, race, or drinking/smoking status. However, we detected decreased concentrations of DEK in HNC patients with p16-negative disease and in patients with larger tumor sizes, indicating an association between DEK levels and known prognostic markers. In addition, HNC patients with lower DEK concentrations had a decreased white blood cell count, largely due to differences in lymphocyte and eosinophil counts. This direct association between plasma DEK levels and white blood cell count was independent of p16 status. Conclusions: Together, the data suggest that lower levels of DEK in HNC patient plasma may be predictive of poor outcome. This is in direct contrast to what is observed with intratumoral levels of DEK protein, in which higher levels of DEK expression are an independent factor predicting poor prognosis. Future studies will investigate the role that secreted DEK, such as that found in the plasma, may have in the antitumor immune response. Citation Format: Trisha Wise-Draper, Arun Sendilnathan, Sarah Palackdharry, Nicholas Pease, Julianne Qualtieri, Randy Butler, Nooshin Hashemi Sadraei, John C. Morris, Yash Patil, Keith Wilson, Jonathan Mark, Keith Casper, Vinita Takiar, Adam Lane, Lisa M. Privette Vinnedge. Plasma concentrations of the DEK oncogene correlate with pathological variables in a case-control study of patients with HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 50.

Primary laryngotracheal melanoma.

Head and neck mucosal melanomas represent 0.7% to 3.8% of all melanomas. Among this group, primary melanoma of the larynx and trachea are very rare. There are 8 reports of primary tracheal melanoma and about 60 reported cases of primary laryngeal melanoma in the literature. We present an unusual case of primary laryngotracheal melanoma. This article was submitted for review by our institutional review board and deemed not subject to review.