P16 may also be helpful in evaluation of cauterized cone biopsy margins and small tissue fragments in endocervical curettements. While the use of p16 immunostaining in the above settings has been strongly advocated and also has been shown to improve interobserver agreement, (5,7,12,13) several studies have reported positive p16 staining in normal epithelium and low-grade lesions as well: in a large meta-analysis of 34 studies on p16 expression in cervical tissue specimens, 2% of all benign cases (ranging between 0.4%-30% in individual studies) and 38% of low-grade intraepithelial lesions (range, 23%-53%) showed positivity (14) (Figure 2, A and B).
Adenocarcinoma: Endometrial Versus Endocervical Origin.--The origin, endometrial versus endocervical, of small tumor fragments in endometrial or endocervical biopsies and curettements may be difficult to identify by their morphologic features alone.
All 3 types of trophoblasts express low-molecular-weight cytokeratins (eg, CK18, CK8, CK AE1/AE3, CAM 5.2), (140,141) which are widely available and may be used to help in confirming intrauterine pregnancy/implantation site or identifying placental site nodule (PSN) in endometrial curettements. (142) Additional pan-trophoblastic markers also include hydroxyl-delta-5-steroid dehydrogenase (HSD3B1) and HLA-G, (143-145) although these are less commonly available in routine pathology laboratories.