gynecology and obstetrics
Endometrial Cancer
Pathology of Endometrial Cancer
Endometrial cancer is usually preceded by endometrial hyperplasia. Endometrial carcinoma is commonly classified into 2 types. Type I(non-aggressive) tumors are more common, are usuallyestrogen-responsive, and are usually diagnosed in women with obesity and at younger ages (perimenopause or early in menopause). They are preceded by endometrial hyperplasia. These tumors are usually low-grade; the prognosis is good. Endometrioid adenocarcinoma (grades 1 and 2) is the most common histology. These tumors may show microsatellite instability and have mutations inPTEN,PIK3CA,KRAS, andCTNNB1. mutations ( Pathology references ). Up to 10% of endometrial carcinomas are type II ( account for approximately 75 to 80% of endometrial cancers ( Pathology references ). of endometrioid endometrial carcinomas ( Pathology references ): POLE ultramutated (POLEmut): Characterized by pathogenic mutations in the exo nuclease domain of DNA polymerase-ε, resulting in an ultra-high tumor mutational burden and agood prognosis Mismatch repair-deficient (MMRd): Has loss of mismatch repair proteins, resulting in microsatellite instability and anintermediate prognosis No specific molecular profile (NSMP): Has no single identifying molecular feature and tumor stage- and grade-dependent outcomes and anintermediate prognosis p53-mutant: Has a low tumor mutational burden and high somatic copy-number alterations resulting in apoor prognosis Determining the molecular subtype, if feasible, adds valuable information to the standard clinicopathological risk factors to classify patients with endometrial cancer into risk groups, predict prognosis, and guide treatment recommendations. Uterine papillary serous carcinomas(10%),clear cell carcinomas(< 5%), andcarcinosarcomas(< 5%) are considered more aggressive, high-risk histologies and are associated with a higher incidence of extrauterine disease at presentation. Carcinosarcomas used to be categorized as sarcomas but are now considered and treated as high-grade epithelial tumors (carcinomas). Mucinous carcinomasare typically low-grade; the prognosis is good.KRASmutations are common in these tumors. Other histopathologic types of endometrial carcinoma are neuroendocrine, undifferentiated, and mixed carcinoma (composed of more than one type, with at least 10% of each component). Endometrial cancer may spread as follows: From the surface of the uterine cavity to the cervical canal Through the myometrium to the serosa and into the peritoneal cavity Via the lumen of the fallopian tube to the ovary, broad ligament, and peritoneal surfaces Via the bloodstream, leading to distant metastases Via the lymphatics The higher (more undifferentiated) the grade of the tumor, the greater the likelihood of deep myometrial invasion, pelvic or para-aortic lymph node metastases, or extrauterine spread. 1.Cancer Genome Atlas Research Network, Kandoth C, Schultz N, et al: Integrated genomic characterization of endometrial carcinoma [published correction appears inNature2013 Aug 8;500(7461):242].Nature497(7447):67-73, 2013. doi:10.1038/nature12113 2.Faber MT, Frederiksen K, Jensen A, et al: Time trends in the incidence of hysterectomy-corrected overall, type 1 and type 2 endometrial cancer in Denmark 1978-2014.Gynecol Oncol146(2):359-367, 2017. doi:10.1016/j.ygyno.2017.05.015 3.Lu KH, Broaddus RR: Endometrial cancer.N Engl J Med383(21):2053-2064, 2020. doi:10.1056/NEJMra1514010 4.WHO Classification of Tumours Editorial Board: 2020 WHO Classification of Tumours, 5th Edition, Volume 4: Female Genital Tumors. 