Goellner, John R.

Abstract The PAX8/PPARγ (PPFP) fusion-oncogene is moderately specific for follicular thyroid carcinomas (FTC). It remains unknown whether this can be translated into improved diagnosis, classification, or outcome prediction. We studied a cohort of well-characterized follicular adenomas (FA), FTC, and Hürthle cell carcinomas (HCC) from patients with complete clinical follow-up, to determine whether PPARγ immunohistochemistry (as a surrogate of PAX8/PPARγ expression) helps to distinguish FA from FTC and to assess its diagnostic accuracy as an adjunct to frozen section. We also correlated PPARγ staining with clinical outcomes to assess its role as a prognostic marker. PPARγ staining was more common in FTC (31 of 54; 57%) than in HCC (one of 23; 4%) or FA (four of 31; 13%) (P < 0.000001). Adjunctive use of PPARγ immunohistochemistry improved diagnostic sensitivity of intraoperative frozen section from 84% to 96% (P < 0.05) but reduced specificity from 100% to 90% (P < 0.05). PPARγ staining was associated with favorable prognostic indicators (female gender, better tumor differentiation, and lesser risk of metastases). PPARγ staining may be helpful in the differential diagnosis of FA, FTC, and HCC, particularly when diagnostic sensitivity of histomorphology is reduced (e.g. during intraoperative frozen section). PPARγ staining also shows an association with favorable prognosis and may have a role in risk stratification.

It is uncertain whether more extensive primary surgery and increasing use of radioiodine remnant ablation (RRA) for papillary thyroid carcinoma (PTC) have resulted in improved rates of cause‐specific mortality (CSM) and tumor recurrence (TR). Details of the initial presentation, therapy, and outcome of 2444 PTC patients consecutively treated during 1940–1999 were recorded in a computerized database. Patients were followed for more than 43,000 patient‐years. The 25‐year rates for CSM and TR were 5% and 14%, respectively. Temporal trends were analyzed for six decades. During the six decades, the proportion with initial MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) scores <6 were 77%, 82%, 84%, 86%, 85%, and 82%, respectively (p = 0.06). Lobectomy accounted for 70% of initial procedures during 1940–1949 and 22% during 1950–1959; during 1960–1999 bilateral lobar resection (BLR) accounted for 91% of surgeries (p <0.001). RRA after BLR was performed during 1950–1969 in 3% but increased to 18%, 57%, and 46% in successive decades (p <0.001). The 40‐year rates for CSM and TR during 1940–1949 were significantly higher (p = 0.002) than during 1950–1999. During the last 50 years the 10‐year CSM and TR rates for the 2286 cases did not significantly change with successive decades. Moreover, the 10‐year rates for CSM and TR were not significantly improved during the last five decades of the study, either for the 1917 MACIS <6 patients or the 369 MACIS ? 6 patients. Increasing use of RRA has not apparently improved the already excellent outcome, achieved before 1970, in low risk (MACIS <6) PTC patients managed by near‐total thyroidectomy and conservative nodal excision.

AbstractThe association between thyroid cancer and familial adenomatous polyposis (FAP), albeit rare, is well known. It has been suggested that the thyroid tumors have unique histologic characteristics and may be follicular in origin. Because of their rarity, treatment and long‐term prognosis are uncertain. Twelve such patients (prevalence 399/100,000) seen during 1949–1995 were retrospectively reviewed. Histology was independently re‐reviewed by two pathologists. There were 11 female patients (two sisters) and 1 male patient, with a mean age of 28 years (range 15–61 years). Eight patients (66%) had multicentric tumors and five (42%) bilateral disease. Average tumor diameter was 1.8 cm (range 0.2–5.0 cm). Regional nodal metastases were present in two patients. All 12 thyroid cancers in this series were papillary. The one male patient demonstrated “typical” histology with variable papillary and follicular architecture, whereas the 11 female patients had tumors with unusual histology as described by Harach. Five patients (41%) were treated by total thyroidectomy, five with near‐total thyroidectomy, and two with lobectomy alone. Mean follow‐up was 142 months (range 7 months to 30 years). Regional recurrent disease occurred in two patients, one of whom died of the disease. The 5‐ and 20‐year survivals were 90% and 77%, respectively. The results indicated that all tumors in this study were papillary, although atypical histology was encountered in 91%. The mean age (28 years) is younger than that of patients with sporadic disease. Multicentricity and bilateral disease are common. In view of this finding, total thyroidectomy should be strongly considered. Long‐term prognosis is excellent. The finding of unusual histology in a young patient with papillary thyroid carcinoma should arouse the suspicion of FAP.