Lulu Sun1, Lingxin Zhang1, Hannah R Krigman1, Ian S Hagemann1,1. 1. Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
Abstract
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.
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.
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