Stereology, flow cytometry, and immunohistochemistry of follicular neoplasms of the thyroid gland

Abstract

A retrospective analysis of surgically resected thyroid cold solitary nodules was performed by stereology, DNA flow cytometry, and immunohistochemistry in 15 follicular adenomas and 15 well-differentiated follicular carcinomas to determine if a differential diagnosis of both follicular neoplasms can be done exclusively from cytologic criteria. Between 150 and 200 tumor cell nuclei (TCN) were studied per case for their TCN profile area, perimeter, and density, as well as for stereologic estimates, including the new parameter, volume-weighted mean particle volume ( V v). Flow-cytometric analyses included measurement of the DNA index and the percentage of cells in S phase and G 2M phase. The same tumors were examined for the expression of thyroglobulin and the intermediate filaments vimentin and keratin. Follicular adenomas and follicular carcinomas did not show any significant differences in stereologic estimates related to TCN size. Both groups included similar proportions of diploid and aneuploid neoplasms. Aneuploid follicular neoplasms showed a significantly greater area, perimeter, and volume of TCN as compared with diploid tumors, regardless of their histologic diagnosis. Follicular adenomas and follicular carcinomas expressed a similar staining pattern for the tested immunoreagents, with a few cases coexpressing vimentin and keratin. From our results, a differential diagnosis of follicular neoplasms cannot be performed on the basis of cytologic aspirates exclusively. Infiltration of capsula or vessels remains the only safe indicator of malignancy in the absence of metastases. The lack of cytologic differences suggests that some follicular adenomas are preinvasive carcinomas, not yet showing infiltrative growth at the time of resection.