Endometrial carcinoma: Histopathology and pathogenesis
- Margaret M Steinhoff, MD
Margaret M Steinhoff, MD
- Professor of Pathology and Laboratory Medicine
- The Warren Alpert Medical School of Brown University
- Section Editors
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Rochelle L Garcia, MD
Rochelle L Garcia, MD
- Section Editor — Obstetric and Gynecologic Pathology
- Professor of Pathology
- Adjunct Professor of Obstetrics & Gynecology
- University of Washington Medical Center
- Don S Dizon, MD, FACP
Don S Dizon, MD, FACP
- Section Editor – Gynecologic Oncology
- Clinical Co-Director, Gynecologic Oncology
- Founder and Director, The Oncology Sexual Health Clinic
- Massachusetts General Hospital Cancer Center
- Associate Professor of Medicine
- Harvard Medical School
Carcinoma of the endometrium (the lining of the uterus) is the most common gynecologic cancer in developed countries and the second most common in developing countries (cervical carcinoma is the most common in low-resource countries). (See "Endometrial carcinoma: Epidemiology and risk factors", section on 'Epidemiology'.)
There are several histologic types of endometrial carcinoma (EC). Endometrioid histology is the most common, and this typically presents at an early stage with abnormal uterine bleeding, and is most common in postmenopausal women. Other histologic types may have more aggressive clinical behavior.
The histopathology and pathogenesis of EC are reviewed here. Related topics are discussed in detail separately, including:
●Overview (see "Overview of endometrial carcinoma")
●Epidemiology and risk factors (see "Endometrial carcinoma: Epidemiology and risk factors")
- Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983; 15:10.
- Vargas R, Rauh-Hain JA, Clemmer J, et al. Tumor size, depth of invasion, and histologic grade as prognostic factors of lymph node involvement in endometrial cancer: a SEER analysis. Gynecol Oncol 2014; 133:216.
- Stephan JM, Hansen J, Samuelson M, et al. Intra-operative frozen section results reliably predict final pathology in endometrial cancer. Gynecol Oncol 2014; 133:499.
- Alcazar JL, Dominguez-Piriz J, Juez L, et al. Intraoperative Gross Examination and Intraoperative Frozen Section in Patients With Endometrial Cancer for Detecting Deep Myometrial Invasion: A Systematic Review and Meta-analysis. Int J Gynecol Cancer 2016; 26:407.
- WHO Classification of tumours of the female reproductive organs, 4, Kurman RJ, Carcangiu ML, Herrington CS, Young RH. (Eds), World Health Organization, 2014. p.126, 150.
- Conlon N, Leitao MM Jr, Abu-Rustum NR, Soslow RA. Grading uterine endometrioid carcinoma: a proposal that binary is best. Am J Surg Pathol 2014; 38:1583.
- Han G, Lim D, Leitao MM Jr, et al. Histological features associated with occult lymph node metastasis in FIGO clinical stage I, grade I endometrioid carcinoma. Histopathology 2014; 64:389.
- Hertel JD, Huettner PC, Pfeifer JD. Lymphovascular space invasion in microcystic elongated and fragmented (MELF)-pattern well-differentiated endometrioid adenocarcinoma is associated with a higher rate of lymph node metastasis. Int J Gynecol Pathol 2014; 33:127.
- Xiong J, He M, Jackson C, et al. Endometrial carcinomas with significant mucinous differentiation associated with higher frequency of k-ras mutations: a morphologic and molecular correlation study. Int J Gynecol Cancer 2013; 23:1231.
- Huang CY, Tang YH, Chiang YC, et al. Impact of management on the prognosis of pure uterine papillary serous cancer - a Taiwanese Gynecologic Oncology Group (TGOG) study. Gynecol Oncol 2014; 133:221.
- Quddus MR, Sung CJ, Zhang C, Lawrence WD. Minor serous and clear cell components adversely affect prognosis in ''mixed-type'' endometrial carcinomas: a clinicopathologic study of 36 stage-I cases. Reprod Sci 2010; 17:673.
- McCluggage WG. Malignant biphasic uterine tumours: carcinosarcomas or metaplastic carcinomas? J Clin Pathol 2002; 55:321.
- Lopez-Garcia MA, Palacios J. Pathologic and molecular features of uterine carcinosarcomas. Semin Diagn Pathol 2010; 27:274.
- Berton-Rigaud D, Devouassoux-Shisheboran M, Ledermann JA, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for uterine and ovarian carcinosarcoma. Int J Gynecol Cancer 2014; 24:S55.
- Broaddus RR, Lynch HT, Chen LM, et al. Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma. Cancer 2006; 106:87.
- Shapiro S, Kelly JP, Rosenberg L, et al. Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens. N Engl J Med 1985; 313:969.
- Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371:569.
- Soliman PT, Wu D, Tortolero-Luna G, et al. Association between adiponectin, insulin resistance, and endometrial cancer. Cancer 2006; 106:2376.
- Murali R, Soslow RA, Weigelt B. Classification of endometrial carcinoma: more than two types. Lancet Oncol 2014; 15:e268.
- Mutter GL, Lin MC, Fitzgerald JT, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000; 92:924.
- Djordjevic B, Broaddus RR. Role of the clinical pathology laboratory in the evaluation of endometrial carcinomas for Lynch syndrome. Semin Diagn Pathol 2014; 31:195.
- Cancer Genome Atlas Research Network, Kandoth C, Schultz N, et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013; 497:67.
- Brinton LA, Felix AS, McMeekin DS, et al. Etiologic heterogeneity in endometrial cancer: evidence from a Gynecologic Oncology Group trial. Gynecol Oncol 2013; 129:277.
- Ambros RA, Sherman ME, Zahn CM, et al. Endometrial intraepithelial carcinoma: a distinctive lesion specifically associated with tumors displaying serous differentiation. Hum Pathol 1995; 26:1260.
- Fadare O, Liang SX, Ulukus EC, et al. Precursors of endometrial clear cell carcinoma. Am J Surg Pathol 2006; 30:1519.
- Fadare O, Zheng W, Crispens MA, et al. Morphologic and other clinicopathologic features of endometrial clear cell carcinoma: a comprehensive analysis of 50 rigorously classified cases. Am J Cancer Res 2013; 3:70.
- Hoang LN, McConechy MK, Meng B, et al. Targeted mutation analysis of endometrial clear cell carcinoma. Histopathology 2015; 66:664.
- Zorn KK, Bonome T, Gangi L, et al. Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer. Clin Cancer Res 2005; 11:6422.
- Pothuri B, Ramondetta L, Eifel P, et al. Radiation-associated endometrial cancers are prognostically unfavorable tumors: a clinicopathologic comparison with 527 sporadic endometrial cancers. Gynecol Oncol 2006; 103:948.
- Taylor NP, Zighelboim I, Huettner PC, et al. DNA mismatch repair and TP53 defects are early events in uterine carcinosarcoma tumorigenesis. Mod Pathol 2006; 19:1333.
- McConechy MK, Ding J, Cheang MC, et al. Use of mutation profiles to refine the classification of endometrial carcinomas. J Pathol 2012; 228:20.
- Le Gallo M, Bell DW. The emerging genomic landscape of endometrial cancer. Clin Chem 2014; 60:98.
- Billingsley CC, Cohn DE, Mutch DG, et al. Polymerase ɛ (POLE) mutations in endometrial cancer: clinical outcomes and implications for Lynch syndrome testing. Cancer 2015; 121:386.
- Diaz-Padilla I, Romero N, Amir E, et al. Mismatch repair status and clinical outcome in endometrial cancer: a systematic review and meta-analysis. Crit Rev Oncol Hematol 2013; 88:154.
- Alkushi A, Köbel M, Kalloger SE, Gilks CB. High-grade endometrial carcinoma: serous and grade 3 endometrioid carcinomas have different immunophenotypes and outcomes. Int J Gynecol Pathol 2010; 29:343.
- Voss MA, Ganesan R, Ludeman L, et al. Should grade 3 endometrioid endometrial carcinoma be considered a type 2 cancer-a clinical and pathological evaluation. Gynecol Oncol 2012; 124:15.
- Alvarez T, Miller E, Duska L, Oliva E. Molecular profile of grade 3 endometrioid endometrial carcinoma: is it a type I or type II endometrial carcinoma? Am J Surg Pathol 2012; 36:753.
- Lancaster JM, Powell CB, Kauff ND, et al. Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol 2007; 107:159.
- Committee opinion no. 634: Hereditary cancer syndromes and risk assessment. Obstet Gynecol 2015; 125:1538.
- Garg K, Leitao MM Jr, Kauff ND, et al. Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumor morphology enhances detection of mismatch repair abnormalities. Am J Surg Pathol 2009; 33:925.
- GROSS PATHOLOGY
- Endometrioid carcinoma
- Mucinous carcinoma
- Serous carcinoma
- Clear cell carcinoma
- Mixed cell tumors
- Carcinosarcoma (malignant mixed müllerian tumor)
- Rare subtypes
- PATHOGENESIS AND GENETICS
- Endometrioid carcinomas (type 1)
- Nonendometrioid carcinomas (type 2)
- Genomic subtypes
- Hereditary cancer syndromes
- - Lynch syndrome
- - Cowden syndrome