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Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors.

初诊为卵巢子宫内膜样癌的肿瘤形态学和免疫组化再评估:重点为高级别肿瘤

Lim D,Murali R,Murray MP,Veras E,Park KJ,Soslow RA

Abstract

Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular, cribriform, solid, and transitional cell-like architecture) and were immunophenotypically indistinguishable from OSCs with papillary architecture. Sixty percent of OSC overexpressed p16, 50% overexpressed p53, and 82% expressed WT-1. At last follow-up, 52% had died of disease. Compared with OSC, OEC patients more frequently presented below 60 years of age (P=0.046), had low-stage tumors (P<0.001), were more frequently unilateral (P<0.001), more frequently had synchronous endometrial endometrioid carcinomas (P<0.001); and had no evidence of disease at last follow-up (P<0.001). Their tumors were of lower grade (P<0.001), had more CEFs (P<0.001), and less frequently overexpressed p16 and p53 (P=0.003 and P<0.001, respectively) and less frequently expressed WT-1 (P<0.001). This analysis emphasizes the diagnostic value of CEFs, the presence of a low-grade gland-forming endometrioid component, and WT-1 negativity, as valid, clinically relevant criteria for a diagnosis of OEC. Glandular and/or cribriform architecture alone may be seen in both OECs and OSCs and are therefore not informative of diagnosis. Further study is needed to elaborate the characteristics of the exceedingly rare high-grade OEC.

摘要

卵巢低级别子宫内膜样癌(OEC)具有典型形态学特征,但高级别肿瘤可类似高级别浆液性和未分化癌。我们复习了初诊为OEC的肿瘤,以明确病理学和免疫组化特征相结合是否能改善组织学亚分类。依据WHO标准评估初诊为OEC的肿瘤。我们也注意到出现相关确切的子宫内膜样特征(CEFs):(i)鳞状化生;(ii)子宫内膜异位症;(iii)腺纤维瘤样背景;和(iv)交界性子宫内膜样或混合性苗勒氏成份。选取27例有代表性的伴CEF的肿瘤和14例不伴CEF的肿瘤构建组织微阵列,进而切片行WT-1、P16和P53染色。109例初诊为OEC的肿瘤中,76(70%)例归为OEC,患者中位年龄55岁,75%患者年龄低于60岁。92%患者疾病限于盆腔,87%的肿瘤为单侧发生。中位肿瘤大小为11.8cm。仅3%的肿瘤为高级别(3级)。80%的病例至少出现1项CEF,59%至少出现2项CEFs。11%过表达P16,P53无过表达,3%表达WT-1。截止到最后随访时,仅10%患者死于该病。33例肿瘤、即30%最初分类为子宫内膜样癌的肿瘤被重新归为浆液性癌(OSC)。患者中位年龄54.5岁,59%的患者年龄低于60岁。仅27%的患者诊断时疾病限于盆腔,52%的肿瘤为单侧性,中位肿瘤大小8cm,所有病例均未见相关的鳞状分化、子宫内膜样腺纤维瘤和子宫内膜样或混合性苗勒氏交界性肿瘤(CEFs),但6%的患者合并子宫内膜异位症。大约一半重新分类为OSC的肿瘤显示SET样形态学(腺样、筛状、实性和移行细胞样结构混合),并且免疫表型与伴乳头状结构的OSCs无法区分。60%的OSC过表达P16,50%过表达P53,82%表达WT-1。到最后随访时,52%患者死于该病。与OSC比较,OEC更常见发生于60岁以下患者(p=0.046),呈早期肿瘤(p<0.001),更多为单侧发生(p<0.001),更常见同时性子宫内膜子宫内膜样癌(p<0.001);且到最后随访时多无疾病的证据(p<0.001)。她们的肿瘤是低级别的(p<0.001),CEFs多见(p<0.001),少见P16和P53过表达(分别为p=0.003和p<0.001),WT-1表达也低(p<0.001)。本分析强调了CEFs、出现低级别形成腺体的子宫内膜样成份、WT-1阴性的诊断价值,并强调了诊断OEC的临床相关标准。OECs和OSCs二者均可见腺性和/或筛状结构单独出现,因此不具有诊断性,仍需进一步研究极为罕见的高级别OEC所具有的特征。

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