Thyroid tumors of uncertain malignant potential: morphologic and imunohistochemical analysis of 29 cases

Thyroid tumors of uncertain malignant potential (TT-UMP) include follicular and well-differentiated tumors of UMP (FT-UMP/WDT-UMP), as it refers to the presence of questionable capsular/vascular invasion or incompletely developed papillary thyroid carcinoma (PTC)-type nuclear changes. However, these tumors are difficult to diagnose in most cases. We aimed to investigate whether immunohistochemistry (HBME-1, cytokeratin-19, galectin-3, CD56 and p63) provides additional information concerning such lesions.

We performed an immunohistochemical analysis on 29 TT-UMP cases (22 WDTs-UMP and 7 FTs-UMP) selected from the Rhone Alpes thyroid cancer registry and Departement of Pathology, Tîrgu-Mureş Emergency County Hospital database. The clinicopathological and follow-up data were obtained.

In the WDT-UMP group, HBME-1 was positive in 9/22 (40.9%) cases. CD56, a marker whose expression is reduced or absent in thyroid carcinoma, showed a "malignant" profile (no expression) in 13/22 (59.1%) cases. 7/22 (31.9%) cases were both HBME-1+ and CD56-. One case showed the co-expression of HBME-1, CD56, galectin-3 and cytokeratin-19. In the FT-UMP group, two cases were positive for HBME-1, other two for both galectin-3 and CK19 and only one case revealed a "malignant" CD56 profile. The follow-up data showed no distant metastases or persistent disease.

Our study demonstrated very heterogeneous immunohistochemical profiles for TTs-UMP, further supporting the borderline nature of these lesions. WDTs-UMP revealed a certain tendency toward a PTC profile, suggesting a possible pathogeneticlink between these two entities. However, immunohistochemistry is still to be regarded more as a supporting diagnostic tool, while morphological criteria should always prime in the diagnostic decision.