Hürthle cell tumors: applying molecular markers to define a new management algorithm.

OBJECTIVE To design a new management algorithm for all Hürthle cell tumors and variants based on histopathologic findings and the ret/PTC molecular marker. DESIGN A retrospective medical record review. SETTING A large tertiary care teaching center. PATIENTS Forty-five consecutive cases of Hürthle cell carcinoma were gathered from a database of 661 patients with well-differentiated epithelial thyroid cancers compiled over 22 years. Data collected included patient information, tumor information, and treatment factors. MAIN OUTCOME MEASURES Outcome parameters included tumor and treatment variables, which were analyzed statistically using the chi(2) and t tests. Disease-free survival and disease-specific survival analyses were performed using Kaplan-Meier analysis. RESULTS A female-male ratio of 3:1 was found, with a median patient age of 57 years. Twenty-three patients had American Joint Commission on Cancer stage II disease. Treatment factors had no significant effect on disease recurrence or survival. More than half of the patients had histologically proved regional metastases. Vascular invasion significantly diminished disease-specific survival and disease-free interval. CONCLUSIONS We found a high incidence of Hürthle cell carcinoma with cervical metastasis. On the basis of findings of this study and our previous clinical and molecular findings, we propose a treatment algorithm that combines histologic examination and molecular assays for the ret/PTC gene rearrangements specific to papillary thyroid carcinoma. After permanent section analysis demonstrating Hürthle cell metaplasia, the algorithm mandates completion thyroidectomy in patients with ret/PTC-positive Hürthle cell tumors and clinical observation for ret/PTC-negative Hürthle cell adenomas. We recommend more aggressive treatment of ret/PTC-positive Hürthle cell lesions (or Hürthle cell papillary thyroid cancer), because of the higher incidence of regional metastatic disease.