Characterization of "Dysplastic" Foci in Chronic Lymphocytic Thyroiditis.
M Herman Chui, Ozgur Mete, Clarissa Cassol, Sylvia L Asa. University Health Network, Toronto, ON, Canada
Background: Epidemiological studies have shown an increased risk of papillary thyroid carcinoma (PTC) in patients with chronic lymphocytic thyroiditis (CLT). The follicular epithelium in CLT is often atypical, with nuclear features resembling PTC. There is considerable debate as to whether these cells are pre-malignant, and previous studies have been equivocal. In this study, we examined the expression of immunomarkers in reactive, hyperplastic, and malignant lesions in CLT and compared them with lesions classified as "dysplastic" based on pre-defined morphologic criteria.
Design: A tissue microarray was constructed from 70 cases diagnosed as PTC with background CLT. For each case, representative cores were taken in triplicate, where applicable, from areas of normal epithelium with bland nuclei (N), reactive atypia in follicular cells maintaining normal architecture (RA), reactive epithelium surrounding lymphoid aggregates (RA-L), nodular hyperplasia/adenoma with bland (NH-n) or atypical (NH-atyp) nuclei, microcarcinoma (PMC), PTC and dysplasia (Dys). The term dysplasia was reserved for foci of atypical cells <0.1 cm with complex architecture distinct from the surrounding parenchyma. Immunostains for HBME-1 and Galectin-3 (Gal3) were analyzed using automated image analysis software (ScanScope and Spectrum Plus, Aperio, Membrane and Color Deconvolution algorithms respectively).
Results: Staining patterns were clearly distinct between normal and carcinomas with no normal tissue showing immunoreactivity for either marker. CLT lesions had different immunohistochemical profiles as shown in the table below. While atypical cells were present in all cases, lesions qualifying as dysplastic were found in 25/70 cases.
|Lesions||HBME-1 Positivity||Mean Score of HBME-1+ cases (0-3)||Gal3 Positivity||Mean Score of Gal3+ cases (0-300)|
|N||0% (0/60)||-||0% (0/60)||-|
|RA||4.5% (3/66)||1.0**||3.0% (2/67)||36*|
|RA-L||89% (62/70)||1.1**||36% (25/70)||41*|
|NH-n||0% (0/32)||-||0% (0/32)||-|
|NH-atyp||28% (9/32)||1.4**||3.1% (1/32)||52|
|PMC||91% (21/23)||2.6||74% (17/23)||120**|
|PTC||73% (51/70)||2.5||53% (37/70)||97**|
|Dys||92% (23/25)||2.4||72% (18/25)||60|