CK17: An Adjunctive Marker of Invasion in Squamous Neoplastic Lesions of the Anus
Andrea Primiani, Rosalynn M Nazarian, Katy Linskey, Leona A Doyle, Lyn M Duncan, Robert Odze, Lawrence R Zukerberg. Massachusetts General Hospital, Boston, MA; Brigham and Woman's Hospital, Boston, MA
Background: Anal squamous cell carcinoma (SCC) is a rare malignancy often preceded by anal intraepithelial neoplasia (AIN). Establishing a diagnosis of anal SCC may be challenging in small biopsy specimens, particularly if poorly oriented. In addition, anal gland involvement by AIN can simulate invasion. Cytokeratin 17 (CK17) is a basal/myoepithelial cell keratin induced in activated keratinocytes and associated with disease progression in SCCs of the uterine cervix, esophagus, and oral cavity. The aim of this study was to investigate the utility of CK17 in diagnosing invasion in anal squamous neoplastic lesions.
Design: Immunohistochemical staining for CK17 was evaluated in anal squamous neoplastic lesions [11 AIN, 11 invasive SCC, 8 invasive SCC with basaloid features (BSCC), and 2 invasive pure basaloid carcinoma] from 25 patients. In 6 patients, concurrent AIN and invasive lesions were evaluated. We defined BSCC as a SCC with keratinization and basaloid features (i.e. peripheral palisading, small cells without distinct intercellular bridges, and retraction artifact). Pure basaloid carcinoma was defined as a tumor with basaloid features but without typical features of SCC and keratinization, thereby resembling cutaneous basal cell carcinomas. The pattern of CK17 staining was scored as superficial/central (staining of the superficial 2/3 of epithelial cells), peripheral/rim (staining of the basal 1/3 of epithelial cells), diffuse, or absent.
Results: All cases (100%) of invasive SCC and BSCC stained positive for CK17 by immunohistochemistry. Eleven of 11 (100%) SCC cases showed diffuse staining. Of the BSCC cases, 6 of 8 (75%) showed diffuse staining and 2 of 8 (25%) showed peripheral staining. Both pure basaloid carcinomas stained negatively for CK17. Finally, 3 of 11 (27%) AIN (all grade 3) showed superficial CK17 staining; all other AIN lesions were negative. Of the 6 patients with concurrent AIN and invasive carcinoma, only 1 showed superficial CK17 staining in AIN, but all SCCs showed diffuse staining. Sixteen patients tested for HPV (by a variety of methods) were positive.
Conclusions: Peripheral and diffuse staining for CK17 is a useful marker of invasion in anal squamous neoplastic lesions, especially in difficult cases with early/superficial or blunt-type invasion. However, a potential pitfall in the utility of CK17 is that the pure basaloid variant of anal carcinoma is negative for CK17. This finding may suggest a different pathogenesis of pure basaloid anal carcinoma compared to the other SCC variants.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 102, Wednesday Morning