Hürthle cell tumors: using molecular techniques to define a novel classification system.

BACKGROUND Since ret/PTC gene rearrangements are specific to papillary thyroid carcinoma (PTC), the diagnosis of Hürthle cell PTC (HCPTC) has recently been expanded to include a subset of Hürthle cell tumors (HCTs) that may lack both papillary architecture and/or classic nuclear features but that harbor a ret/PTC gene rearrangement. We hypothesize that such HCPTCs behave in a fashion analogous to other papillary carcinomas, while Hürthle cell carcinomas (HCCs) behave similarly to follicular carcinomas. EDUCATIONAL OBJECTIVES At the conclusion of this article, participants should be able to discuss HCTs and to identify HCPTCS using molecular techniques. METHODS A retrospective chart review was carried out on 56 patients with HCTs. All pathological specimens were analyzed for ret/PTC gene rearrangements. Hürthle cell adenoma (HCA) was defined as an HCT that did not exhibit capsular and/or vascular invasion and that lacked a ret/PTC gene rearrangement when evaluated by immunohistochemical and reverse transcription polymerase chain reaction analysis. An HCC was defined as an HCT with capsular and/or vascular invasion that lacked a ret/PTC gene rearrangement, and an HCPTC was defined as any HCT that harbored a ret/PTC gene rearrangement. RESULTS The subclassification of the 56 HCTs was as follows: 21 HCAs, 15 HCCs, and 20 HCPTCs. No patients with HCA or HCC were ret/PTC positive. Five of the 6 patients with definite lymph node metastasis were in the HCPTC group, demonstrating that molecular analysis helps to explain biological behavior. CONCLUSIONS Hürthle cell neoplasms can now be classified using histopathological as well as molecular criteria. It appears that the new subclassification of malignant HCTs into follicular (HCC) and papillary (HCPTC) variants identifies 2 distinct biological groups.