Thyroid Uptake on FDG PET/CT: What the Radiologist Needs to Know Puneet Belani MD, Mansi Shah, and Jeffrey Kempf MD FACR Rutgers - Robert Wood Johnson University Hospital New Brunswick, NJ

PURPOSE AND METHODS With the increasing use of FDG PET in oncology, unexpected thyroid uptake is not uncommonly encountered The purpose of this educational exhibit is to review the most commonly encountered uptake patterns of FDG PET in the thyroid gland and their clinical significance, with review of the literature Selected instructional cases from an academic university based practice that reflect the most common incidentally encountered patterns of thyroid uptake on FDG PET/CT are presented The two most common patterns for incidental FDG thyroid uptake are focal as well as diffuse Rarely, a diffuse and focal pattern may be also be encountered

Patient 1. Coronal and fused axial FDG Pet images in a patient with metastatic melanoma and incidental intense focal thyroid uptake Case 1 Normal thyroid gland does not take up significant FDG due to its main energy substrate of free fatty acids Thyroid incidentaloma defined as thyroid uptake incidentally detected; management can be confusing “PAIN”- PET associated incidental neoplasm Many papers in literature with wide reported incidence of thyroid incidentalomas on PET in up to 8.9% of scans. Overall pooled incidence of thyroid incidentalomas from meta-analysis of 27 studies in literature reported to be 2.46% (Bertagna et al. 2012)

Focal Incidental Thyroid Uptake Malignancy rate: Generally reported between approximately 25% to 50% Overall malignancy ratio from recent literature meta-analysis: 34.6% Does SUV help predict Malignancy? -Many conflicting study results in literature with overlap of benign and malignant thyroid nodules -Trend towards increasing Suv max and malignancy but no safe SUV max cutoff -Some benign nodules such as Hurthle cell adenomas and follicular adenomas may be very hypermetabolic on PET -Dual time point imaging not shown to be generally helpful in differentiating benign from malignant thyroid nodules Thyroid Cancer Pathologic Types of Incidentalomas Papillary Thyroid Cancer most common subtype-approximately 85%, up to 100% in some studies; may be more aggressive Follicular, Hurthle cell, poorly differentiated, anaplastic, medullary, and metastases all reported Benign Causes Follicular pathology/ adenoma Toxic adenoma Hurthle cell adenoma Hemorrhagic cyst Benign colloid pattern Hashimoto’s thyroiditis Multinodular hyperplasia

Focal Incidental Thyroid Uptake Since there is considerable malignancy risk in FDG avid incidentally discovered thyroid nodules, and these nodules may be more aggressive, they should be further evaluated when patient’s clinical condition permits NCCN guidelines: include FDG avid thyroid nodules as a high risk clinical feature (along with radiation exposure as child or adolescent, first degree relative with thyroid cancer or MEN2, personal history of thyroid cancer-associated conditions) ATA guidelines: FDG avid thyroid nodules “require prompt investigation” -perform thyroid ultrasound; FDG avid thyroid nodules considered high risk category - If nodule can be biopsied and patient co-morbidities would not preclude thyroid surgery, further histological correlation usually attempted

Patient 2: 58 y. o. female with breast cancer and brain metastases Patient 2: 58 y.o. female with breast cancer and brain metastases. Transaxial and coronal PET, trans-axial PET/CT fusion, and transaxial CT images demonstrate incidental diffuse symmetric FDG uptake in the thyroid with SUV max of 7.4 Case 2

Case 2: Diffuse Uptake Diagnosis: Hashimoto’s thyroiditis Diffuse uptake is most commonly due to Hashimoto’s thyroiditis Other less frequent diagnoses include Graves disease, hormone replacement therapy for hypothyroidism, thyroid lymphoma, benign goiter, as well as normal variants SUV does not have a predictive value of final diagnosis

Diffuse Incidental Thyroid Uptake Hashimoto’s Thyroiditis Most common etiology of incidental diffuse thyroid uptake on FDG PET; SUV can be variable AKA Chronic lymphocytic thyroiditis; autoimmune disorder; may be familial Most common cause of hypothyroidism in the US; may result in hyperthyroidism Common middle age females, but may occur at any age. Female/Male-8:1; up to 5% adults May be asymptomatic for years; goiter Dx: TFT’s, elevated antithyroid peroxidase and thyroglobulin antibodies Complications: hypothyroidism, hyperthyroidism, rarely thyroid cancer Fine needle aspirations often inaccurate-limits usefulness in this population Focal versus Diffuse Focal incidental >>diffuse incidental thyroid uptake, approximately 70% focal/30% diffuse Recommendations for diffuse uptake Physical exam and thyroid laboratory data (TSH, T4, T3, anti-TPO, and thyroglobulin antibody) correlation Diffuse plus focal Rare.  Can be associated with thyroid malignancy including thyroidal primary or secondary carcinoma, as well as thyroid lymphoma possibly superimposed on a background of thyroiditis.

Case 3 Patient 3. 51 y.o. female with history of lung nodules. Axial and coronal PET and axial CT images demonstrate incidental diffuse intense FDG uptake in the thyroid gland, with enlargement of the right lobe. SUV max 16.5.

Case 3: Thyroid Lymphoma Diagnosis: B-Cell Lymphoma Primary thyroid lymphomas are practically always non-Hodgkin lymphomas (NHLs) Only 2% of extra nodal lymphomas arise in the thyroid gland and only up to 2% of thyroid malignancies are thyroid lymphomas Primary thyroid Hodgkin disease is extremely rare NHLs can be divided into aggressive and indolent cell types The most common cell type is diffuse large-cell lymphoma, either associated or unassociated with mucosa-associated lymphoid tissue (MALT) lymphoma (MALToma) They most frequently arise from lymph nodes, but an extranodal site can be the primary source in approximately 30% of cases, and the thyroid gland is among the most common of these extranodal sites Thyroid NHL has a high rate of cure without the need for extensive surgery

Conclusions Thyroid incidentalomas on FDG PET/CT are not infrequent with a combined incidence of 2.5% Incidental focal thyroid uptake is a more common pattern compared to incidental diffuse thyroid uptake Diffuse thyroid uptake most commonly caused by benign disease-most commonly Hashimoto’s thyroiditis About one third to one half of incidental focal thyroid uptake are malignant, most commonly secondary to papillary thyroid carcinoma; may be more aggressive sub-types but reports are conflicting All thyroid incidentalomas need further investigation and clinical evaluation SUV cutoff values do not play a role in ruling in or ruling out malignancies in this scenario It is therefore important for the radiologist to become knowledgeable of the importance of the different types of thyroid uptake patterns on FDG PET scans and to be able to convey to the ordering physician the most likely diagnostic possibilities as well as further recommendations for additional thyroidal workup, if needed

References Are C, Hsu JF, Schoder H, et al. FDG-PET detected thyroid incidentalomas: Need for further investigation? Ann Surg Oncol 2007; 14:239–247. Bertagna F, Treglia G, Piccardo A, and Giubbini R. Diagnostic and clinical significance of F-18-FDG-PET/CT thyroid incidentalomas. JCEM 2012; 97(11): 3866-3875. Cooper D, et al. Revised American thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. November 2009. The American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. http://thyroidguidelines.net/revised/taskforce. Accessed March 2014. Kwak JY, Kim EK, Yun M, et al. Thyroid incidentalomas identified by 18FFDG PET: sonographic correlation. AJR Am J Roentgenol 2008; 191: 598–603. Lowe VJ, Mullan BP, Hay ID, et al. 18 FDG PET of patients with Hürthle cell carcinoma. J Nucl Med 2003; 44:1402–1406. Mehdi G, Siddiqui F, and Ali Rizvi SA. Hurthle cell adenoma as an incidental finding in Hashimoto’s thyroiditis - case report and short review of literature. The Internet Journal of Pathology 2008; 8:1. Pampaloni MH, Win AZ . Prevalence and characteristics of incidentalomas discovered by whole body FDG PET CT. Int J Mol Imaging 2012; article ID 476763. Shie P, Cardarelli R, Sprawls K, et al. Systematic review: prevalence of malignant incidental thyroid nodules identified on fluorine18 fluorodeoxyglucose positron emission tomography. Nucl Med Commun. 2009; 30:742–748. Watanabe N, Noh JY, Narimatsu H, et al. Clinicopathological features of 171 cases of primary thyroid lymphoma: a long-term study involving 24,553 patients with Hashimoto's disease. Br J Haematol 2011; Apr;153(2):236-43.