3.1.6: Endometrial Hyperplasia
- Page ID
- 94915
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Endometrial hyperplasia (EH) is an irregular proliferation of the endometrial glands leading to an increase in the gland-to-stroma ratio in contrast to proliferative endometrium.15
3.1.6.2 Etiology and Pathogenesis
- A marked and prolonged increase of estrogen levels more than progesterone induces endometrial hyperplasia. Underlying causes include:
- Obesity: Steroid precursors are converted into estrogens in adipose tissue. Excess adipose tissue promotes a chronic proinflammatory status, which stimulates the release of cytokines that are also involved in developing EH and EC
- Polycystic ovarian syndrome: Chronic anovulation results in hyperandrogenic status with prolonged estrogen production that is not balanced by progesterone.
- Estrogen-secreting ovarian tumors (granulosa and theca cell tumors)
- Exogenous/iatrogenic: Prolonged estrogenic therapy with increasing doses not opposed by an adequate intake of progestins, especially in post-menopausal women. Tamoxifen is the most widely used among selective estrogen receptor modulators (SERMs) against breast cancer in both pre-and post-menopausal women.
- Genetic diseases such as Lynch Syndrome, also known as hereditary non-polyposis colonic cancer (HNPCC), caused by a mutation in one of the genes involved in the DNA repair system (MLH1, MSH2, MSH6, PMS2, and EP-CAM) are associated with increased risk of endometrial hyperplasia and carcinoma. Similar to endometrial carcinoma, endometrial hyperplasia with atypia has acquired mutations affecting the tumor suppressor gene PTEN.
3.1.6.3 Histopathology
- Endometrial Hyperplasia without atypia (Benign Hyperplasia): An increased endometrial gland-to-stroma ratio without nuclear atypia (Figure 3.1.18).
- Endometrial hyperplasia with atypia/Endometrial Intraepithelial Neoplasia (EIN): There is an increased endometrial gland-to-stroma ratio with complex proliferating glands with nuclear atypia (Figure 3.1.19). It is a premalignant lesion with an approximately 30% risk of progression to endometrial carcinoma. Because of the shared genetic mutations of PTEN with endometrial carcinoma, EIN is considered a precursor of endometrial carcinoma.
3.1.6.4 Treatment
Surgical removal of the uterus (total hysterectomy) is the treatment of choice for EIN in patients who no longer consider conception. In younger patients, the condition is treated by the administration of high-dose progestins.
Figure 3.1.18 Histopathology of complex hyperplasia without atypia: Cystically dilated endometrial glands lined by a single layer of columnar epithelium (Hematoxylin and eosin stain, ×20)
Image Source: Rao, Shalinee, Sandhya Sundaram, and Raghavan Narasimhan. "Biological behavior of preneoplastic conditions of the endometrium: A retrospective 16-year study in south India". Indian Journal of Medical and Paediatric Oncology 30 (4): 131 (2009). doi.10.4103/0971-5851.65335. Distributed under the terms of the CC BY 2.0 license. Available from Wikipedia Commons.
Figure 3.1.19 Endometrial Hyperplasia with Atypia: Atypia (mainly seen as signs of endometrial intraepithelial neoplasia (EIN), which has the following criteria: Architectural gland crowding - Altered cytology relative to background glands (rounded vesicular nuclei with prominent nucleoli) - Minimum size of 1 mm - Exclusion of adenocarcinoma.
Image Source: Haggstrom, Mikael. "Endometrial Intraepithelial Neoplasia". Image from Archives of Pathology & Laboratory Medicine 138, No. 4 (2014): 484–491. Distributed under the terms of the CCO license. doi.10.5858/arpa.2012-0709-RA
Glossary Terms
- Adipose tissue
- specialized areolar tissue rich in stored fat
- Anovulation
- suspension or cessation of OVULATION in animals or humans with follicle-containing ovaries (OVARIAN FOLLICLE). Depending on the etiology, OVULATION may be induced with appropriate therapy
- Atypia
- abnormality in cells in tissue
- 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
- Cytokines
- class of protein signaling molecules; in the cardiovascular system, they stimulate the proliferation of progenitor cells and help to stimulate both nonspecific and specific resistance to disease
- Exogenous
- describes substance made outside of the human body
- Hyperandrogenic
- when you have an excess amount of androgens (a group of sex hormones) in your body
- Hyperplasia
- abnormal growth due to the production of cells
- Iatrogenic
- adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment
- Introepithelial 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
- Progestins
- compounds that interact with PROGESTERONE RECEPTORS in target tissues to bring about the effects similar to those of PROGESTERONE
- Proinflammatory
- promoting inflammation : capable of causing inflammation
- Proliferative
- phase of the menstrual cycle in which the endometrium proliferates
Footnotes
- Giannella, Luca, Camilla Grelloni, Marco Bernardi, Camilla Cicoli, Federica Lavezzo, Gianmarco Sartini, Leonardo Natalini, et al. “Atypical Endometrial Hyperplasia and Concurrent Cancer: A Comprehensive Overview on a Challenging Clinical Condition.” Cancers 16, no. 5 (2024): 914. Distributed under the terms of the CC
BY 4.0 doi.org/10.3390/cancers16050914
Image Acknolwedgements
- Haggstrom, Mikael. "Endometrial Intraepithelial Neoplasia". Image from Archives of Pathology & Laboratory Medicine 138, No. 4 (2014): 484–491. Distributed under the terms of the CCO license. doi.10.5858/arpa.2012-0709-RA
- Rao, Shalinee, Sandhya Sundaram, and Raghavan Narasimhan. "Biological behavior of preneoplastic conditions of the endometrium: A retrospective 16-year study in south India". Indian Journal of Medical and Paediatric Oncology 30 (4): 131 (2009). doi.10.4103/0971-5851.65335. Distributed under the terms of the CC BY 2.0 license. Available from Wikipedia Commons.