A 3-D study of capsular invasion in follicular thyroid tumors : a novel approach to an old dilemma

Objective. The diagnosis of follicular tumors of the thyroid mainly rests on the examination of peri-lesional capsule. Lesions with an intact shell are labeled as adenoma, those with capsular invasion are considered carcinoma and those with doubtful aspects are regarded as tumors of uncertain malignant potential. Aim. To better understand the biology of capsular invasion and its practical implication by applying a peculiar three dimension (3-D) reconstruction. Method. Two follicular carcinoma (FC) and one follicular tumour of uncertain malignant potential (FT-UMP) were considered. Areas of true/doubtful capsular invasion were labeled using Tissue Micro Array technology and the corresponding paraffin blocks underwent serial sectioning. H&E slides (range 30-100, mean 70) were captured as pictures, aligned using automated method based on the maximization of mutual information and imported into a 3-D image processing software (AMIRA). Results. The 3-D reconstruction revealed that capsular openings were oval shaped and sized ≅100-200 μm. In one FC the hole was entirely engaged by a tumor mass. In the remaining cases (1 FC and 1 FT-UMP) the 3-D reconstruction showed a small feeding vessel (μ 50 μm) passing through the capsule together with the bulge of the lesion [see 3-D reconstruction at http://www.ibfm. cnr.it/ricerca/inv-cap.php]. Conclusions. Our approach allows a better spatial reconstruction of the exact point of capsular interruption; the results obtained suggest that capsular invasion can be due either by abruptly interruption of the shell or by a protrusion along the path of a small feeding vessel.