P16 Immunohistochemistry Is Not Always Required for Accurate Diagnosis of Grade 2 Squamous Intraepithelial Lesions

Objectives Preinvasive squamous neoplasms of the lower genital tract are currently classified using a two-tier system (high-or low-grade squamous intraepithelial lesion) as directed by the Lower Anogenital Squamous Terminology (LAST) guidelines but may also be subclassified as intraepithelial neoplasia grade 1 (-IN1),-IN2, or-IN3. The LAST recommended that all diagnoses of-IN2 be supported by immunohistochemistry (IHC) for p16. We examined whether p16 and Ki-67 IHC are necessary to diagnose-IN2 when the lesion has obvious high-grade histology. Materials and Methods p16 and Ki-67 IHC were performed prospectively and retrospectively on vulvar, vaginal, and cervical specimens with an initial diagnosis of-IN2 based on hematoxylin and eosin morphology, and a final diagnosis was made after consensus review. Results Five of 46 prospective and four of 38 retrospective cases were p16 negative. The diagnosis of-IN2 was maintained in eight of these nine cases because of compelling high-grade squamous intraepithelial lesion histology. Overall, p16 and Ki-67 IHC altered the-IN2 diagnosis to a lower grade in only one of 84 cases (1.2%, <0.01%-7.1%). Moreover, p16 was positive in all cases where the preanalytic impression was of-IN2/3 (13/13). Conclusions p16 IHC lacks utility in cases of morphologically obvious-IN2, because the stain is positive in most cases. The LAST recommendation to use p16 IHC to support all diagnoses of-IN2 will result in performing the immunostain in many circumstances where it is not medically necessary. Among cases that are p16 negative, many have compelling high-grade morphology. The LAST perspective that the stain trumps histology may allow false-negative IHC results to prevail.