Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the

uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...

. Most cases of endometrial hyperplasia result from high levels of

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

s, combined with insufficient levels of the progesterone-like hormones which ordinarily counteract estrogen's proliferative effects on this tissue. This may occur in a number of settings, including obesity,

polycystic ovary syndrome Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in women of reproductive age. The syndrome is named after the characteristic cysts which may form on the ovaries, though it is important to note that this is a sign and no ...

, estrogen producing tumours (e.g. granulosa cell tumour) and certain formulations of estrogen replacement therapy. Endometrial hyperplasia with atypia is a significant risk factor for the development or even co-existence of endometrial cancer, so careful monitoring and treatment of women with this disorder is essential.

Classification

Histopathology of complex hyperplasia without atypia

Like other

hyperplastic Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferatio ...

disorders, endometrial hyperplasia initially represents a physiological response of endometrial tissue to the growth-promoting actions of

. However, the gland-forming cells of a hyperplastic endometrium may also undergo changes over time which predispose them to

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

ous transformation. Several histopathology subtypes of endometrial hyperplasia are recognisable to the

pathologist Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in t ...

, with different therapeutic and

prognostic Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stable ...

implications. The most commonly used classification system for endometrial hyperplasia is the World Health Organization (WHO) system, which previously had four categories: simple hyperplasia without atypia, complex hyperplasia without atypia, simple atypical hyperplasia and complex atypical hyperplasia. In 2014, the WHO updated the classification system and removed the distinction between simple or complex hyperplasia, instead only on presence or absence of atypia. * Endometrial hyperplasia (simple or complex) - Irregularity and cystic expansion of glands (simple) or crowding and budding of glands (complex) without worrisome changes in the appearance of individual gland cells. In one study, 1.6% of patients diagnosed with these abnormalities eventually developed endometrial cancer. * Atypical endometrial hyperplasia (simple or complex) - Simple or complex architectural changes, with worrisome (''atypical'') changes in gland cells, including cell stratification, tufting, loss of nuclear polarity, enlarged nuclei, and an increase in mitotic activity. These changes are similar to those seen in true cancer cells, but atypical hyperplasia does not show invasion into the connective tissues, the defining characteristic of cancer. The previously mentioned study found that 22% of patients with atypical hyperplasia eventually developed cancer.

Diagnosis

Diagnosis of endometrial hyperplasia can be made by endometrial biopsy, which is done in the office setting or through

curettage Curettage ( or ), in medical procedures, is the use of a curette (French, meaning scoop Mosby's Medical, Nursing & Allied Health Dictionary, Fourth Edition, Mosby-Year Book 1994, p. 422) to remove tissue by scraping or scooping. Curettages are ...

of the uterine cavity to obtain endometrial tissue for histopathologic analysis. A workup for endometrial disease may be prompted by abnormal uterine bleeding, or the presence of atypical glandular cells on a

pap smear The Papanicolaou test (abbreviated as Pap test, also known as Pap smear (AE), cervical smear (BE), cervical screening (BE), or smear test (BE)) is a method of cervical screening used to detect potentially precancerous and cancerous processes in t ...

Prognosis

Many studies have shown that endometrial hyperplasia can progress to cancer, particularly when there are atypical cells. Nevertheless, such studies has typically dealt with atypical hyperplasia. A review of 65 articles on estimated risk of progression to cancer concludes that none of those studies reported estimates specifically for non-atypical hyperplasia patients. Further it states the need for population based studies including both non-atypical and atypical hyperplasia to accurately estimate the risk of progression to cancer. If untreated with hysterectomy, endometrial hyperplasia progresses to adenocarcinoma within 20 years in: * 28% of cases with atypia (95% CI, 8.6% to 42.5%), and * about 5% of cases without atypia. The rates are more favorable in cases with simple rather than complex hyperplasia, but as mentioned above this terminology was phased out of the WHO classification in 2014. In patients with samples showing atypia, carcinoma is already present in over 40% of cases. Given this, the aforementioned 28% atypia progression rate may be an underestimate, and the true number may closer to the 42.5% part of the study's remarkably wide confidence interval.

Treatment

Treatment of endometrial hyperplasia is individualized, and may include

hormonal therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are oncologic horm ...

, such as cyclic or continuous progestin therapy, or hysterectomy.

References

External links