Karunadhas Nesa S, Catherwood Mark, Stringfellow Helen, Arora Rupali, McCluggage W Glenn
Department of Pathology, Belfast Health and Social Care Trust.
Regional Molecular Diagnostics Service, Belfast Health and Social Care Trust, Belfast, Northern Ireland.
Am J Surg Pathol. 2025 May 6;49(9):901-908. doi: 10.1097/PAS.0000000000002415.
Clear cell carcinoma (CCC) is an uncommon malignancy accounting for ∼12% of ovarian carcinomas. Most cases arise from endometriosis, frequently an endometriotic cyst. We report a series of 6 cases where clear cell proliferations, morphologically, and immunophenotypically consistent with CCC, involve the epithelial lining of an endometriotic cyst without invasion into the surrounding stroma. The patients were aged 29 to 63 years (mean 45). In all cases, epithelial proliferations composed of cells with atypical nuclei, sometimes with a hobnail morphology, and clear or eosinophilic cytoplasm involved the epithelial lining of an ovarian endometriotic cyst. In areas, the proliferations comprised a monolayer, but in all cases, there was also significant epithelial stratification and multilayering, sometimes with a pseudopapillary architecture. There was no invasion of the atypical cells into the surrounding ovarian stroma. The proliferations were positive for Napsin A (6 of 6; 4 diffuse, 2 focal), racemase (5 of 5; 3 diffuse, 2 focal), hepatocyte nuclear factor 1-beta (5 of 5; all diffuse), oestrogen receptor (5 of 6; 2 diffuse, 3 focal), and PAX8 (3 of 3; all diffuse). p53 was wild-type in all 6 cases and WT1 and progesterone receptor were negative in the 4 and 6 cases tested, respectively. Mismatch repair immunohistochemistry was retained in the 3 cases tested. Next-generation sequencing was performed in 2 cases. In 1 case, a sole pathogenic MSH6 variant (p.Ser65fs) was identified. Follow-up (2 to 24 months) was available in 5 cases and there was no tumour recurrence. In reporting these "early" clear cell proliferations in endometriotic cysts, we provide recommendations for the reporting pathologist regarding the most appropriate terminology, which is important in patient management. We suggest that these proliferations be termed "CCC in situ" and that identification of such a lesion should prompt extensive sampling in order to exclude an invasive CCC component within the stroma outside the endometriotic cyst lining. We also stress the importance of close dialogue between the pathologist and the clinician and between the clinician and the patient in order to avoid overtreatment in such cases.
透明细胞癌（CCC）是一种罕见的恶性肿瘤，约占卵巢癌的12%。大多数病例起源于子宫内膜异位症，常见于子宫内膜异位囊肿。我们报告了一系列6例病例，其中透明细胞增生在形态学和免疫表型上与CCC一致，累及子宫内膜异位囊肿的上皮内衬，而未侵犯周围间质。患者年龄在29至63岁之间（平均45岁）。在所有病例中，由具有非典型核的细胞组成的上皮增生，有时呈鞋钉样形态，伴有透明或嗜酸性细胞质，累及卵巢子宫内膜异位囊肿的上皮内衬。在某些区域，增生为单层，但在所有病例中，也存在明显的上皮分层和多层化，有时呈假乳头结构。非典型细胞未侵犯周围卵巢间质。增生的细胞Napsin A呈阳性（6/6；4例弥漫性，2例局灶性）、消旋酶呈阳性（5/5；3例弥漫性，2例局灶性）、肝细胞核因子1-β呈阳性（5/5；均为弥漫性）、雌激素受体呈阳性（5/6；2例弥漫性，3例局灶性）、PAX8呈阳性（3/3；均为弥漫性）。6例病例中p53均为野生型，4例检测的WT1和6例检测的孕激素受体均为阴性。3例检测的病例错配修复免疫组化结果均保留。2例病例进行了二代测序。1例病例中，鉴定出一个单独的致病性MSH6变异（p.Ser65fs）。5例病例有随访（2至24个月），无肿瘤复发。在报告这些子宫内膜异位囊肿中的“早期”透明细胞增生时，我们为报告病理学家提供了关于最合适术语的建议，这对患者管理很重要。我们建议将这些增生称为“原位CCC”，识别出这样的病变应促使进行广泛取材，以排除子宫内膜异位囊肿内衬外间质内的浸润性CCC成分。我们还强调病理学家与临床医生之间以及临床医生与患者之间密切沟通的重要性，以避免在此类病例中过度治疗。
