Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
J Low Genit Tract Dis. 2018 Apr;22(2):104-109. doi: 10.1097/LGT.0000000000000370.
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.
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.
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).
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.
目前，根据《下生殖道鳞状上皮肿瘤命名法（LAST）》指南，采用两级分类系统（高级别或低级别鳞状上皮内病变）对下生殖道的癌前鳞状肿瘤进行分类，但也可进一步细分为上皮内瘤变 1 级（-IN1）、-IN2 或 -IN3。LAST 建议所有 -IN2 的诊断均需通过 p16 免疫组化（IHC）来支持。我们研究了当病变具有明显的高级别组织学特征时，p16 和 Ki-67 IHC 是否有必要诊断 -IN2。
对初始诊断为基于苏木精和伊红形态学的 -IN2 的外阴、阴道和宫颈标本进行前瞻性和回顾性的 p16 和 Ki-67 IHC 检测，然后通过共识审查做出最终诊断。
46 例前瞻性和 38 例回顾性病例中有 5 例 p16 阴性。由于具有强烈的高级别鳞状上皮内病变组织学特征，这 9 例中有 8 例保留了 -IN2 的诊断。总体而言，仅在 84 例病例中的 1 例（1.2%，<0.01%-7.1%）中 p16 和 Ki-67 IHC 将 -IN2 诊断改变为较低级别。此外，在所有预分析印象为 -IN2/3 的病例中 p16 均为阳性（13/13）。
在形态学上明显为 -IN2 的病例中，p16 IHC 缺乏实用性，因为在大多数情况下染色呈阳性。LAST 建议使用 p16 IHC 来支持所有 -IN2 的诊断，这将导致在许多情况下进行免疫染色，而这些情况在医学上并非必要。在 p16 阴性的病例中，许多病例具有强烈的高级别形态。LAST 认为该染色优于组织学的观点可能导致假阴性 IHC 结果占主导地位。
