1. Case 20 Thomas J. Giordano, M.D., Ph.D.

2. History A 54-year old man with a past medical history of goiter for approximately 4 years was followed by ultrasound and treated with thyroid hormone suppression. The goiter increased over the last 6 months and he presented to UMHS Endocrine Surgery for total thyroidectomy.

3. Primary Thyroid Tumor

8. History Subsequent to the diagnosis of papillary carcinoma, he was evaluated at the UMHS Multidisciplinary Thyroid Clinic, where he was felt to be at moderate risk of recurrence. Thus, he received 150 millicuries of radioactive iodine treatment 2 months after surgery. He did fine until January 2005 when he developed pain and swelling in his left lower leg. He underwent biopsy, which showed metastatic thyroid carcinoma.

9. Metastatic tumor

13. History The patient was referred for Oncologic evaluation. He underwent radiation treatment of the left lower leg. He was considered for a clinical trial at OSU and also evaluated by octreotide scan for possible treatment with Sandostatin. OctreoScan showed widespread metastatic disease, including brain metastases. Despite aggressive therapy, he developed malignant pleural effusions and expired 3.5 years after surgery.

14. Diagnosis Papillary thyroid carcinoma with progression to poorly differentiated carcinoma

15. New Frontiers Case illustrates that we still have much to learn about papillary thyroid carcinoma prognostication Current assessment tools failed to recognize this patient as being at high risk for histologic progression, recurrence, metastasis, and eventual poor outcome

16. Prognostication of PTC Conventional clinicopathologic evaluation -Patient age at time of diagnosis -Male gender -Tumor size -Extrathyroidal extension -Lymph node metastases -Distant metastases -Advanced tumor stage

17. Prognostication of PTC Histologic subtype (in order of aggressiveness) -Tall cell variant -Conventional -Follicular variant Histologic progression -Poorly differentiated carcinoma -Anaplastic carcinoma

18. Risk Stratification Determines the management of PTC -Extent of initial treatment -Completion thyroidectomy -Treatment with radioactive iodine -Degree of vigilance in follow-up -Frequency of testing

19. Risk Stratification The reliability of this clinicopathologic criteria-based approach, however, can be uncertain, particularly in patients with conventionally low clinicopathologic stages. Xing, M. Endocrine Reviews 28:742-762, 2007.

20. Can we do better? How?

21. BRAF Genotyping

22. Clinical Significance of BRAF V600E Xing, M. Endocrine Reviews 28:742-762, 2007. US, Caucasion Korean

23. Clinical Significance of BRAF V600E Numerous outcome studies -Consensus view: BRAF does provide some independent predictive information Soon to be standard of care Yet, too common (50-60% of PTC) to be very useful

24. Thyroid Cancer Biology

25. Need more sophisticated tools than simple genotyping to assess the underlying genetic and epigenetic complexity

26. Promise of Personalized Genomic Medicine Clinical Assessment Histologic Assessment Genotypic Assessment Genomic Molecular Assessment Improved Classification and Prognostication of Thyroid Tumors

27. Questions