MOLECULAR PROFILE AND CLINICAL OUTCOMES IN DIFFERENTIATED THYROID CANCER PATIENTS PRESENTING WITH BONE METASTASIS.

Objective: Differentiated thyroid cancer patients uncommonly present with bone metastasis as the initial manifestation. Their molecular profile is largely unknown. The aim of this study was to evaluate the histopathology, molecular profiles, and response to radioactive iodine therapy in these patients. Methods: Eight patients presented with symptomatic bone metastasis from an unknown primary tumor. We identified these patients by performing a retrospective chart review. Pathology slides were reviewed and the molecular analysis of 112 thyroid cancer-related genes was performed on bone metastasis specimens using targeted next-generation sequencing. Results: These patients presented with long bone fractures, spinal cord compression, or intractable bone pain. Histopathologic analysis of the bone and thyroid tumor specimens revealed follicular variant of papillary carcinoma in 7 patients and tall cell variant papillary carcinoma in 1 patient. Primary tumor size ranged from 0.4 to 7.5 cm. All patients received high dose radioiodine therapy following thyroidectomy. Molecular analysis revealed telomerase reverse transcriptase (TERT) mutations in 7 (88%) tumors, 4 (50%) contained co-occurring TERT and RAS GTPase gene (RAS) mutations, 2 had isolated TERT mutations, and 1 had TERT and proto-oncogene B-Raf (BRAF) V600E mutations, respectively. Tumors carrying RAS, TERT, or a combination of these mutations were radioiodine-avid, with predictable tumor response and reduction in serum thyroglobulin levels. One patient with radioiodine-refractory disease harbored BRAF and TERT mutations. Conclusion: These results demonstrate that differentiated thyroid cancers presenting with bone metastasis independent of the primary tumor size have a high prevalence of TERT mutations, frequently coexisting with RAS mutations. This molecular signature may predict a favorable response to radioiodine therapy. Abbreviations: BRAF = proto-oncogene B-Raf; DNA = deoxyribonucleic acid; DTC = differentiated thyroid cancer; FV = follicular variant; PTC = papillary thyroid carcinoma; RAI = radioactive iodine; RAS = Ras GTPase gene; TERT = telomerase reverse transcriptase; TG = thyroglobulin.

Elevated Troponin I in the Absence of Coronary Artery Disease: A Case Report With Review of Literature.

Cardiac troponins are the most sensitive and specific markers of myocardial injury. In fact, the Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction (MI) states that troponins are the preferred cardiac marker for detecting myocardial injury. For the aforementioned reasons, troponin levels are routinely ordered for patients presenting to the emergency department with chest pain, dyspnea, syncope, or any other possible presentations of MI. While troponin levels do reflect the extent of myocardial damage, they do not necessarily indicate myocardial ischemia in a subset of patients. Elevated troponin levels can be due to a wide array of mechanisms in the absence of myocardial ischemia and injury. Thus, relying solely on troponin levels, in the presence of a normal electrocardiogram (ECG), to diagnose myocardial ischemia can lead to unnecessary and expensive invasive testing. It is therefore important for the clinician to keep in mind the varying causes of troponin elevations in order to provide the highest value care to the patient. We present a case and review of literature regarding patients who present with elevated troponin levels in the absence of any coronary artery disease.