3.1.7: Endometrial Carcinoma (EC)
- Page ID
- 94916
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Primary malignant tumor of the endometrial glandular component (i.e., endometrial epithelial cells), not stromal cells.16
3.1.7.2 Pathogenesis
Similar to endometrial hyperplasia, estrogen excess increases the risk of developing endometrial carcinoma (particularly the endometroid type, also known as type I ECs) in perimenopausal women. Non-endometroid (serous is the most common subtype) endometrial carcinoma (Type II ECs) occurs in postmenopausal women and arises from atrophic endometrium. In contrast, serous cancers originate in the setting of endometrial atrophy in older postmenopausal women.
As previously mentioned, EIN is the precursor lesion of endometroid endometrial carcinoma, representing most of endometrial carcinoma (80%). Several genetic mutations, including mutations of the mismatch repair genes and the tumor suppressor genes (e.g., PTEN), have been identified as early events in the stepwise carcinogenesis of endometrioid carcinoma. Most of these mutations are acquired somatic mutations; however, other germ-line mutations have also been identified, such as Cowden Syndrome (PTEN mutations) and Lynch Syndrome (DNA mismatch repair genes mutations).
The more aggressive non-endometroid endometrial carcinoma represents around (10%- 20%) of endometrial carcinoma cases. Contrary to the endometroid type, it is not associated with increased estrogen levels or endometrial hyperplasia. This type of tumor exhibits genetic mutations of the TP53 tumor suppressor gene. Serous Endometrial Intraepithelial Neoplasia (SEIC) is believed to be the precursor lesion because of the TP53 mutations.
3.1.7.3 Histopathology
Endometrioid endometrial carcinomas exhibit morphological features of normal endometrium glands. The irregular glands are lined by columnar epithelium with low cytological atypia. ECs can exhibit other architectural patterns (Figure 3.1.20). Invasion of the myometrium by malignant glands could be seen. To differentiate EIN from low-grade endometroid adenocarcinoma, the glands in EIN are crowded but not confluent, and endometrial stroma is preserved around the glands. (Figure 3.1.21, A and B).
Figure 3.1.20 Architectural patterns that meet qualitative criteria for classifying an endometrial proliferation as grade 1 endometrioid carcinoma: confluent glandular growth (A); cribriform growth (B); confluent papillary growth (C); complex labyrinthine growth (D). There is no evidence-based consensus on the minimum size of these patterns needed to classify as endometrioid carcinoma. The absence of endometrial stroma between the glands is required for classification as endometrioid carcinoma (E); however, there may be other cell types in between the glands, such as lymphocytes, neutrophils, plasma cells, histiocytes, and/or endothelium of blood vessels (F).
Image Source: Rabban, Joseph T., C. Blake Gilks, Anais Malpica, Xavier Matias-Guiu, Khush Mittal, George L. Mutter, Esther Oliva, et al. “Issues in the Differential Diagnosis of Uterine Low-Grade Endometrioid Carcinoma, Including Mixed Endometrial Carcinomas: Recommendations from the International Society of Gynecological Pathologists.” International Journal of Gynecological Pathology 38 (January 2019):S25-S39. This work is distributed under a CC BY 4.0 license. doi.org/10.1097/PGP.0000000000000512
Figure 3.1.21
Image Source: Rabban, Joseph T., C. Blake Gilks, Anais Malpica, Xavier Matias-Guiu, Khush Mittal, George L. Mutter, Esther Oliva, et al. “Issues in the Differential Diagnosis of Uterine Low-Grade Endometrioid Carcinoma, Including Mixed Endometrial Carcinomas: Recommendations from the International Society of Gynecological Pathologists.” International Journal of Gynecological Pathology 38 (January 2019):S25-S39. This work is distributed under a CC BY 4.0 license. doi.org/10.1097/PGP.0000000000000512
Serous endometrial carcinomas exhibit papillary growth and cellular atypia. Glandular arrangements can also be detected with more cellular atypia than endometroid carcinomas. Strong immunohistochemistry staining for p53 is characteristic (Figures 3.1.22 and 3.1.23).
Figure 3.1.22
Image Source: Rabban, Joseph T., C. Blake Gilks, Anais Malpica, Xavier Matias-Guiu, Khush Mittal, George L. Mutter, Esther Oliva, et al. “Issues in the Differential Diagnosis of Uterine Low-Grade Endometrioid Carcinoma, Including Mixed Endometrial Carcinomas: Recommendations from the International Society of Gynecological Pathologists.” International Journal of Gynecological Pathology 38 (January 2019):S25-S39. This work is distributed under a CC BY 4.0 license. doi.org/10.1097/PGP.0000000000000512
Figure 3.1.23 Mutation-type p53 immunoexpression in endometrial serous carcinoma is defined as either diffuse strong nuclear staining in >80% of tumor cells (A) or complete absence of any staining in tumor cells (B). In the latter setting, weak patchy p53 staining of lymphocytes, stroma, and normal endometrial glands serves as a positive internal control. p53 staining in grade 1 endometrioid carcinoma is weak and patchy (wild-type immunoreactivity) (C). p16 staining in serous carcinoma is typically diffuse and strong (D) and is typically patchy in grade 1 endometrioid carcinoma (E).
Image Source: Rabban, Joseph T., C. Blake Gilks, Anais Malpica, Xavier Matias-Guiu, Khush Mittal, George L. Mutter, Esther Oliva, et al. “Issues in the Differential Diagnosis of Uterine Low-Grade Endometrioid Carcinoma, Including Mixed Endometrial Carcinomas: Recommendations from the International Society of Gynecological Pathologists.” International Journal of Gynecological Pathology 38 (January 2019):S25-S39. This work is distributed under a CC BY 4.0 license. doi.org/10.1097/PGP.0000000000000512
3.1.7.4 Clinical Features
Carcinoma of the endometrium in women less than 40 years of age is associated with non-invasive cancers, less lymph-vascular space invasion, and a higher body mass index. However, more aggressive, higher grade, late-stage, non-endometrioid endometrial cancers are more prevalent in women >65 years of age. Endometrial carcinomas characteristically present with irregular or postmenopausal bleeding. Serous carcinoma is more prevalent in older (65 to 70 years of age) women with relatively lower body mass index. Generally, the prognosis of serous carcinoma is poor due to the tumor's aggressive behavior and higher-stage
Glossary Terms
- Atrophy
- loss of mass and function
- Atypia
- abnormality in cells in tissue
- Carcinogenesis
- the production of cancer
- Carcinoma
- condition in which abnormal cells that look like cancer cells under a microscope are found only in the place where they first formed and haven’t spread to nearby tissue
- Columnar
- having a tall or long, narrow shape, like a column, as in columnar cells
- Confluent
- two things, such as areas of skin or cells that join or come together without any space between them, or flow together in the same direction
- Cytological
- elated to structure, function, or pathology of cells
- Endometrium
- inner lining of the uterus, part of which builds up during the secretory phase of the menstrual cycle and then sheds with menses
- Epithelium
- sheets of cells that cover the exterior surfaces of the body, line internal cavities and passageways, and form certain glands; also known as epithelial tissue
- Germ-line mutation
- detectable and heritable alteration in the lineage of germ cells
- Hyperplasia
- abnormal growth due to the production of cells
- Immunochemistry
- field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies
- Intraepithelial neoplasia
- term used to describe the presence of abnormal cells on the surface of or in the tissue that lines an organ, such as the cervix, breast, prostate, anus, vagina, vulva, penis, and mouth
- Lesion
- area of abnormal tissue
- Lymph-vascular
- of, relating to, or containing lymphatic vessels
- Morphology
- form and structure of an organism or any of its parts
- Myometrium
- smooth muscle layer of uterus that allows for uterine contractions during labor and expulsion of menstrual blood
- Papillary
- of, relating to, being, or resembling a papilla or nipple-shaped projection, mass or structure; marked by the presence of papillae
- Serous
- having to do with serum, the clear liquid part of blood
- Somatic
- having to do with the body
- Stromal cells
- connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere
Footnotes
- Zheng, Wenxin. “Molecular Classification of Endometrial Cancer and the 2023 FIGO Staging: Exploring the Challenges and Opportunities for Pathologists.” Cancers 15, no. 16 (2023): 4101. Work is Distributed under the terms of the CC BY 4.0 license. doi.org/10.3390/cancers15164101; Baiden-Amissah, Regina Esi Mensimah, Daniela Annibali, Sandra Tuyaerts, and Frederic Amant. “Endometrial Cancer Molecular Characterization: The Key to Identifying High-Risk Patients and Defining Guidelines for Clinical Decision-Making?” Cancers 13, no. 16 (2021): 3988. The work is distributed under the terms of the CC BY 4.0 license. doi.org/10.3390/cancers13163988
- Njoku, Kelechi, Chloe E. Barr, and Emma J. Crosbie. “Current and Emerging Prognostic Biomarkers in Endometrial Cancer.” Frontiers in Oncology, 12 (2022). This work is distributed under the terms of the CC BY 4.0 license. doi.org/10.3389/fonc.2022.890908
Image Acknolwedgements
Rabban, Joseph T., C. Blake Gilks, Anais Malpica, Xavier Matias-Guiu, Khush Mittal, George L. Mutter, Esther Oliva, et al. “Issues in the Differential Diagnosis of Uterine Low-Grade Endometrioid Carcinoma, Including Mixed Endometrial Carcinomas: Recommendations from the International Society of Gynecological Pathologists.” International Journal of Gynecological Pathology 38 (January 2019):S25-S39. This work is distributed under a CC BY 4.0 license. doi.org/10.1097/PGP.0000000000000512