Wang H, Liu J, Cheng Y, Wang S N, Zhong F F, Gu W Y
Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China.
Department of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai 264001, China.
Zhonghua Fu Chan Ke Za Zhi. 2025 Jun 25;60(6):469-476. doi: 10.3760/cma.j.cn112141-20241217-00675.
To investigate the clinical and pathological characteristics, treatment and prognosis of endometriosis (EM)-associated ovarian mesonephric-like adenocarcinoma (MLA). Clinical and pathological data were collected from nine patients diagnosed with EM-associated ovarian MLA at the Obstetrics and Gynecology Hospital of Fudan University between January 2022 and December 2024. Histological slides were re-reviewed, immunohistochemical examination and molecular testing were performed, and patient follow-up was conducted. (1) Clinical characteristics: the median age of the nine patients was 54 years (range: 38-69 years). All patients presented with a pelvic mass; five cases also reported abdominal pain. Tumor location included five cases in the right ovary, two in the left ovary, and two involving both ovaries. International Federation of Gynecology and Obstetrics (FIGO) staging showed 3 cases at stage Ⅰ, 4 at stage Ⅱ, and 2 at stage Ⅲ. (2) Pathological features: gross examination revealed mixed solid-cystic masses with solid areas appearing gray-white or yellow-brown; the median maximum tumor diameter was 9.0 cm (range: 2.6-13.0 cm). Microscopically, tumors exhibited various architectural patterns, including tubular, glandular, papillary, slit-like, sex cord-like, glomeruloid, and solid structures, with tubular and glandular patterns being most common. Tumor cells demonstrated mild to moderate nuclear atypia. Of the 11 tumor foci in the 9 cases, 8 showed coexistence of MLA with other tumor components, such as endometrioid carcinoma, borderline endometrioid or borderline seromucinous tumors. In 1 case of MLA mixed with a borderline endometrioid tumor, both components exhibited squamous metaplasia. Immunohistochemistry showed variable expression of GATA-binding protein 3, thyroid transcription factor-1, CD, and calretinin, with positive rates of 9/11, 8/11, 5/11, and 3/6, respectively. Two tumor foci (2/11) exhibited focal expression of estrogen receptor and progesterone receptor. All cases displayed wild-type p53 expression. Molecular testing via next-generation sequencing in five patients revealed pathogenic mutations in the KRAS gene (5/5), with 3 cases (3/5) harboring additional pathogenic mutations in other genes. (3) Treatment and prognosis: all patients underwent surgery, supplemented by chemotherapy and (or) targeted therapy. Five patients underwent comprehensive staging surgery, four received cytoreductive surgery, and one patient received targeted therapy. The median follow-up duration was 7 months (range: 2-27 months). Three patients (3/9) experienced recurrence, and no deaths were reported during the follow-up period. EM-associated ovarian MLA demonstrates diverse morphological patterns and frequently coexists with other tumor types. Accurate diagnosis relies on an integrated evaluation of histomorphology, immunohistochemistry, and molecular testing. The primary treatment for EM-associated ovarian MLA is surgery, followed by adjuvant chemotherapy. Patients harboring pathogenic KRAS p.G12C mutations may benefit from targeted therapies. Ovarian MLA is an aggressive tumor, prone to recurrence in the short term, and has a poor prognosis.
探讨子宫内膜异位症(EM)相关的卵巢中肾样腺癌(MLA)的临床病理特征、治疗及预后。收集2022年1月至2024年12月在复旦大学附属妇产科医院确诊为EM相关卵巢MLA的9例患者的临床和病理资料。重新复查组织学切片,进行免疫组化检查和分子检测,并对患者进行随访。(1)临床特征:9例患者的中位年龄为54岁(范围:38 - 69岁)。所有患者均表现为盆腔肿块;5例还伴有腹痛。肿瘤位置包括右卵巢5例,左卵巢2例,双侧卵巢2例。国际妇产科联盟(FIGO)分期显示,Ⅰ期3例,Ⅱ期4例,Ⅲ期2例。(2)病理特征:大体检查显示为实性 - 囊性混合肿块,实性区域呈灰白色或黄棕色;肿瘤最大直径中位数为9.0 cm(范围:2.6 - 13.0 cm)。显微镜下,肿瘤呈现多种结构模式,包括管状、腺管状、乳头状、裂隙状、性索样、肾小球样和实性结构,其中管状和腺管状模式最为常见。肿瘤细胞表现为轻度至中度核异型性。9例患者的11个肿瘤病灶中,8个显示MLA与其他肿瘤成分共存,如子宫内膜样癌、交界性子宫内膜样或交界性浆液性肿瘤。在1例MLA与交界性子宫内膜样肿瘤混合的病例中,两种成分均表现为鳞状化生。免疫组化显示GATA结合蛋白3、甲状腺转录因子 - 1、CD和钙视网膜蛋白表达各异,阳性率分别为9/11、8/11、5/11和3/6。两个肿瘤病灶(2/11)表现为雌激素受体和孕激素受体的局灶性表达。所有病例均显示野生型p53表达。5例患者通过二代测序进行分子检测,发现KRAS基因存在致病性突变(5/5),其中3例(3/5)在其他基因中还存在额外的致病性突变。(3)治疗及预后:所有患者均接受了手术治疗,并辅以化疗和(或)靶向治疗。5例患者接受了全面分期手术,4例接受了减瘤手术,1例患者接受了靶向治疗。中位随访时间为7个月(范围:2 - 27个月)。3例患者(3/9)出现复发,随访期间无死亡病例报告。EM相关的卵巢MLA表现出多样的形态学模式,且常与其他肿瘤类型共存。准确诊断依赖于组织形态学、免疫组化和分子检测的综合评估。EM相关卵巢MLA的主要治疗方法是手术,其次是辅助化疗。携带致病性KRAS p.G12C突变的患者可能从靶向治疗中获益。卵巢MLA是一种侵袭性肿瘤,短期内易复发,预后较差。