It is not the time to abandon intraoperative frozen section in endometrioid adenocarcinoma: A large-scale, multi-center, and retrospective study

Xiaohang Yang; Jingjing Yin; Yu Fu; Yuanming Shen; Chuyao Zhang; Shuzhong Yao; Congjian Xu; Min Xia; Ge Lou; Jihong Liu; Bei Lin; Jianliu Wang; Weidong Zhao; Jieqing Zhang; Wenjun Cheng; Hongyan Guo; Ruixia Guo; Fengxia Xue; Xipeng Wang; Lili Han; Xiaomao Li; Ping Zhang; Jianguo Zhao; Wenting Li; Yingyu Dou; Zizhuo Wang; Jingbo Liu; Kezhen Li; Gang Chen; Chaoyang Sun; Beibei Wang; Xingsheng Yang

doi:10.1002/cam4.5643

It is not the time to abandon intraoperative frozen section in endometrioid adenocarcinoma: A large-scale, multi-center, and retrospective study

Cancer Med. 2023 Apr;12(7):8897-8910. doi: 10.1002/cam4.5643. Epub 2023 Jan 31.

Authors

Xiaohang Yang^{1

2}, Jingjing Yin^{1

2}, Yu Fu^{1

2}, Yuanming Shen³, Chuyao Zhang⁴, Shuzhong Yao⁵, Congjian Xu⁶, Min Xia⁷, Ge Lou⁸, Jihong Liu⁴, Bei Lin⁹, Jianliu Wang¹⁰, Weidong Zhao¹¹, Jieqing Zhang¹², Wenjun Cheng¹³, Hongyan Guo¹⁴, Ruixia Guo¹⁵, Fengxia Xue¹⁶, Xipeng Wang¹⁷, Lili Han¹⁸, Xiaomao Li¹⁹, Ping Zhang²⁰, Jianguo Zhao²¹, Wenting Li^{1

2}, Yingyu Dou^{1

2}, Zizhuo Wang^{1

2}, Jingbo Liu^{1

2}, Kezhen Li^{1

2}, Gang Chen^{1

2}, Chaoyang Sun^{1

2}, Beibei Wang^{1

2}, Xingsheng Yang²²

Affiliations

¹ Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
² Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
³ Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
⁴ Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
⁵ Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
⁶ Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
⁷ Department of Gynecology and Obstetrics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
⁸ Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
⁹ Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning, China.
¹⁰ Peking University People's Hospital, Beijing, China.
¹¹ Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.
¹² Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China.
¹³ The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
¹⁴ The Third Hospital of Peking University, Beijing, China.
¹⁵ Department of Gynecology and Obstetrics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
¹⁶ Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.
¹⁷ Department of Gynecology and Obstetrics, XinHua Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
¹⁸ Department of Gynecology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
¹⁹ Department of Gynecology and Obstetrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
²⁰ Department of Gynecology, The Second Hospital of Shandong University, Jinan, Shandong, China.
²¹ Department of Gynecologic Oncology, Tianjin Central Hospital of Gynecology and Obstetrics, Affiliated Hospital of Nankai University; Tianjin Clinical Research Center For Gynecology and Obstetrics; Branch of National Clinical Research Center For Gynecology and Obstetrics, Tianjin, China.
²² Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Abstract

Introduction: Stage IB (deep myometrial invasion) high-grade endometrioid adenocarcinoma (EA), regardless of LVSI status, is classified into high-intermediate risk groups, requiring surgical lymph node staging. Intraoperative frozen section (IFS) is commonly used, but its adequacy and reliability vary between reports. Hence, we determined the utility of IFS in identification of high-risk factors, including deep myometrial invasion and high-grade.

Method: We retrospectively analyzed 9,985 cases operated with hysterectomy and diagnosed with FIGO stage I/II EA in postoperative paraffin section (PS) results at 30 Chinese hospitals from 2000 to 2019. We determined diagnostic performance of IFS and investigated whether the addition of IFS to preoperative biopsy and imaging could improve identification of high-risk factors.

Results: IFS and postoperative PS presented the highest concordance in assessing deep myometrial invasion (Kappa: 0.834), followed by intraoperative gross examination (IGE Kappa: 0.643), MRI (Kappa: 0.395), and CT (Kappa: 0.207). IFS and postoperative PS presented the highest concordance for high-grade EA (Kappa: 0.585) compared to diagnostic curettage (D&C 0.226) and hysteroscope (Hys 0.180). Sensitivity and specificity for detecting deep myometrial invasion were 86.21 and 97.20% for IFS versus 51.72 and 88.81% for MRI, 68.97 and 94.41% for IGE. These figures for detecting high-grade EA were 58.21 and 96.50% for IFS versus 16.42 and 98.83% for D&C, 13.43 and 98.64% for Hys. Parallel strategies, including MRI-IFS (Kappa: 0.626), D&C-IFS (Kappa: 0.595), and Hys-IFS (Kappa: 0.578) improved the diagnostic efficiencies of individual preoperative examinations. Based on the high sensitivity of IFS, parallel strategies improved the sensitivities of preoperative examinations to 89.66% (MRI), 64.18% (D&C), 62.69% (Hys), respectively, and these differences were statistically significant (p = 0.000).

Conclusion: IFS presented reasonable agreement rates predicting postoperative PS results, including deep myometrial invasion and high-grade. IFS helps identify high-intermediate risk patients in preoperative biopsy and MRI and guides intraoperative lymphadenectomy decisions in EA.

Keywords: endometrioid adenocarcinoma; high-grade; intraoperative frozen section; myometrial invasion; retrospective studies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Endometrioid* / diagnosis
Carcinoma, Endometrioid* / pathology
Carcinoma, Endometrioid* / surgery
Endometrial Neoplasms* / diagnosis
Endometrial Neoplasms* / pathology
Endometrial Neoplasms* / surgery
Female
Frozen Sections
Humans
Immunoglobulin E
Neoplasm Invasiveness / pathology
Neoplasm Staging
Reproducibility of Results
Retrospective Studies

Substances

Immunoglobulin E