Anatomic Pathology / CK19 IMMUNOREACTIVITY IN PAPILLARY THYROID CARCINOMA

To evaluate the expression of cytokeratin (CK) 19, we stained sections obtained from formalin-fixed, paraffin tissue blocks of 35 thyroid tumors (follicular adenoma [FA], 20; papillary thyroid carcinoma [PTC], 10 follicular variant [FV] and 5 usual type) and scored the extent of staining as follows: 1+ (<5% positively stained cells), 2+ (5%-25% positively stained cells), 3+ (25%-75% positively stained cells), and 4+ (>75% positively stained cells). All 15 PTCs (including 10 FVPTCs) were CK19 positive: 14 were 4+ and 1 (FVPTC) was 2+. All 20 FAs also were CK19 positive: 15 were 1+, 1 was 2+, 4 were 3+, and none was 4+. In the FAs that were scored 1+, reactivity usually was confined to follicular cells lining cystically dilated atrophic follicles that lacked the typical nuclear features of PTC. The remaining FAs showed more diffuse reactivity, which was, however, less intense than that observed in the PTCs. Thus, immunoreactivity for CK19 is not specific for PTC, although we acknowledge that the extent and intensity of staining are considerably greater in this tumor than in FA. There were no significant differences in staining for CK19 between nonneoplastic follicles adjacent to PTCs and those adjacent to FAs. Papillary thyroid carcinoma (PTC) constitutes about 80% of all thyroid malignant neoplasms.1 Among the subtypes of papillary carcinoma, the follicular variant (FVPTC) is the most common.2-4 This lesion is characterized by an exclusive or almost exclusive follicular growth pattern and a set of nuclear features identical to those of the usual type of papillary carcinoma (UT-PTC). Some cases of FV-PTC are surrounded by a fibrous capsule, which may or may not be invaded by tumor. A common diagnostic dilemma arises when an encapsulated nodule with a follicular pattern of growth exhibits some but not all of the features of PTC, such as clear nuclei with grooves or darkly staining colloid. In such instances, distinguishing FA from encapsulated FV-PTC becomes difficult. Cytokeratin (CK) 19 has been proposed as an immunohistochemical marker to distinguish PTC (including FVPTC) from other benign and malignant follicular lesions.5-9 It also has been reported that, among nonneoplastic follicles, CK19 staining is limited to those adjacent to FV-PTC6 and those located within or near areas with chronic inflammation.10 The purpose of the present study was to compare the reactivity of CK19 in PTC (including the FV-PTC) with that observed in FA. We also sought to examine the pattern of CK19 reactivity in the nonneoplastic thyroid tissue adjacent to both tumor types. Materials and Methods We retrieved 20 cases of FA, 10 cases of FV-PTC, and 5 cases of UT-PTC from the files of the Department of Pathology, New York Presbyterian Hospital–Weill Cornell Anatomic Pathology / ORIGINAL ARTICLE Am J Clin Pathol 2001;116:696-702 697 © American Society of Clinical Pathologists Medical Center, New York, NY. The original slides were reviewed by all authors, and diagnostic consensus was achieved in all cases. The diagnosis of UT-PTC was made when the tumor had a predominant papillary pattern and the nuclei showed clearing, grooves, and pseudoinclusions, as described in the third series of the Armed Forces Institute of Pathology fascicle.4 The diagnosis of FV-PTC was made when the tumor had an exclusive follicular growth pattern and the nuclei showed the typical, aforementioned features of PTC. Follicular adenomas (FAs) were diagnosed when an encapsulated tumor had an exclusive follicular pattern of growth and lacked the nuclear features of PTC. Immunohistochemical staining was performed on 1 representative formalin-fixed, paraffin-embedded tissue section from each case using an automated immunostainer (Techmate 500, Ventana Medical Systems, Tucson, AZ). A monoclonal antibody to CK19 (BA17, DAKO, Carpinteria, CA) at a dilution of 1:200 was used for the study. Immunostaining was performed using the ChemMate ABC peroxidase secondary detection system (Ventana Medical Systems). Antigen retrieval was performed by heating the slides in a microwave for 20 minutes in a 10-mmol/L concentration of citrate buffer, pH 6.0. The peroxidase reaction was developed using diaminobenzidine substrate chromogen provided in the secondary detection system. Appropriate positive and negative controls were prepared. The following semiquantitative method was used to score the immunoreactivity of the tumor and nonneoplastic adjacent thyroid: 1+, fewer than 5% positively stained cells; 2+, 5% to 25% positively stained cells; 3+, 25% to 75% positively stained cells; and 4+, more than 75% positively stained cells. Results