Endometrial hyperplasia is a condition of excessive proliferation of the cells of the

endometrium The endometrium is the inner epithelium, epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The funct ...

, or inner lining of the

uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

. Most cases of endometrial hyperplasia result from high levels of

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

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

polycystic ovary syndrome Polycystic ovary syndrome, or polycystic ovarian syndrome, (PCOS) is the most common endocrine disorder in women of reproductive age. The name is a misnomer, as not all women with this condition develop cysts on their ovaries. The name origin ...

, 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 Endometrial cancer is a cancer that arises from the endometrium (the epithelium, lining of the uterus or womb). It is the result of the abnormal growth of cells (biology), cells that can invade or spread to other parts of the body. The first s ...

, so careful monitoring and treatment of women with this disorder is essential.

Classification

Histopathology of complex hyperplasia without atypia

Like other hyperplastic disorders, endometrial hyperplasia initially represents a

physiological Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...

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 Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

ous transformation. Several

histopathology Histopathology (compound of three Greek words: 'tissue', 'suffering', and '' -logia'' 'study of') is the microscopic examination of tissue in order to study the manifestations of disease. Specifically, in clinical medicine, histopatholog ...

subtypes of endometrial hyperplasia are recognisable to the

pathologist Pathology is the study of disease. 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 the context of modern medical treatme ...

, with different therapeutic and prognostic 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 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.

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, such as cyclic or continuous

progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a '' synthetic'' progestogen. ...

therapy, or

hysterectomy Hysterectomy is the surgical removal of the uterus and cervix. Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the ovaries (oophorectomy), fallopian tubes ( salpi ...

References

External links