Department of Pathology and Laboratory Medicine, University of British Columbia (J.X.J., B.T.-C, B.G., D.G.H., L.N.H.) Department of Molecular Oncology, British Columbia Cancer Research Centre (D.R.C.) Genetic Pathology Evaluation Centre (S.L., A.S.C., C.C.) Department of Pathology, Vancouver General Hospital (B.G., L.N.H.), Vancouver, British Columbia, Canada.
Int J Gynecol Pathol. 2020 Jul;39(4):344-353. doi: 10.1097/PGP.0000000000000609.
The diagnosis of clear cell (CC) carcinoma of the endometrium can be challenging, especially when endometrioid (EC) and serous (SC) endometrial cancers exhibit nonspecific clear cell changes, in carcinomas with mixed histology and in the setting of Arias-Stella reaction (ASR). In this study, classic CC immunohistochemical markers (Napsin A, HNF-1β, and ER) and 2 recent novel markers, cystathionine gamma-lyase (CTH) and arginosuccinate synthase (ASS1), are assessed for their utility in distinguishing CC from its morphologic mimics. Tissue microarrays containing 64 CC, 128 EC, 5 EC with clear cell change, 16 SC, 5 mixed carcinomas, and 11 whole ASR sections were stained, with 12 additional examples of ASR stained subsequently. A cutoff of 70% and moderate intensity were used for HNF-1β, 80% of cells and strong intensity were used for CTH, and any staining was considered positive for the remaining markers. For differentiating CC from pure EC and SC, HNF-1β, Napsin A, and CTH all performed well. HNF-1β had higher specificity (99.3% vs. 95.1%) but lower sensitivity (55.8% vs. 73.1%) compared with Napsin A. CTH did not substantially outperform HNF- 1β or Napsin A (sensitivity 51.9%, specificity 99.3%). ASS1 and ER were not helpful (specificities of 60.1% and 22.6%). For differentiating CC from ASR, HNF-1β, Napsin A, and CTH stained a large proportion of ASR and were not useful. However, ER positivity and ASS1 negativity were helpful for identifying ASR (specificity 88.2% and 95.1%, respectively). EC with clear cell changes exhibited immunohistochemical patterns similar to pure EC (HNF-1β-, ER+, and CTH-). No markers were useful in confirming the CC components in mixed carcinomas.
子宫内膜透明细胞癌的诊断具有一定挑战性，特别是当子宫内膜样癌（EC）和浆液性癌（SC）表现出非特异性透明细胞改变、具有混合组织学的癌以及存在 Arias-Stella 反应（ASR）时。在这项研究中，评估了经典的透明细胞癌免疫组化标志物（Napsin A、HNF-1β 和 ER）和最近的两种新型标志物，半胱氨酸γ-裂解酶（CTH）和精氨琥珀酸合成酶（ASS1），以评估它们在区分透明细胞癌与其形态模拟物方面的效用。使用组织微阵列对 64 例透明细胞癌、128 例子宫内膜样癌、5 例具有透明细胞改变的子宫内膜样癌、16 例 SC、5 例混合癌和 11 例完整的 ASR 切片进行染色，随后对 12 例额外的 ASR 染色进行染色。使用 70%和中等强度作为 HNF-1β 的截断值，使用 80%的细胞和强强度作为 CTH 的截断值，任何染色均被认为是其余标志物的阳性。为了将 CC 与纯 EC 和 SC 区分开来，HNF-1β、Napsin A 和 CTH 的表现均良好。与 Napsin A 相比，HNF-1β 的特异性更高（99.3% vs. 95.1%），但敏感性更低（55.8% vs. 73.1%）。CTH 的敏感性为 51.9%，特异性为 99.3%，与 HNF-1β 的表现相当。ASS1 和 ER 没有帮助（特异性分别为 60.1%和 22.6%）。为了将 CC 与 ASR 区分开来，HNF-1β、Napsin A 和 CTH 染色了大量的 ASR，因此没有帮助。然而，ER 阳性和 ASS1 阴性有助于识别 ASR（特异性分别为 88.2%和 95.1%）。具有透明细胞改变的 EC 表现出与纯 EC 相似的免疫组化模式（HNF-1β-、ER+和 CTH-）。在混合癌中，没有任何标志物可用于确认 CC 成分。
