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Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus.
Most cases of endometrial hyperplasia result from high levels of estrogens, 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, estrogen producing tumours (e.g. granulosa cell tumour) and certain formulations of estrogen replacement therapy. Endometrial hyperplasia 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.
Like other hyperplastic disorders, endometrial hyperplasia initially represents a physiological response of endometrial tissue to the growth-promoting actions of estrogen. However, the gland-forming cells of a hyperplastic endometrium may also undergo changes over time which predispose them to cancerous transformation. Several histopathology subtypes of endometrial hyperplasia are recognisable to the pathologist, with different therapeutic and prognostic implications. The most commonly used classification system for endometrial hyperplasia is the World Health Organization system, which has four categories: simple hyperplasia without atypia, complex hyperplasia without atypia, simple atypical hyperplasia and complex atypical hyperplasia.
- 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.
EIN lesions have been discovered by a combination of molecular, histologic, and clinical outcome studies beginning in the 1990s which provide a multifaceted characterization of this disease. They are a subset of a larger mixed group of lesions previously called "endometrial hyperplasia". The EIN diagnostic schema is intended to replace the previous "endometrial hyperplasia" classification as defined by the World Health Organization in 1994, which have been separated into benign (benign endometrial hyperplasia) and premalignant (EIN) classes in accordance with their behavior and clinical management.
EIN should not be confused with an unrelated entity, serous intraepithelial carcinoma ("serous EIC"), which is an early stage of a different tumor type known as papillary serous adenocarcinoma that also occurs in the same location within the uterus.
Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion of the uterine lining that predisposes to endometrioid endometrial adenocarcinoma. It is composed of a collection of abnormal endometrial cells, arising from the glands that line the uterus, which have a tendency over time to progress to the most common form of uterine cancer—endometrial adenocarcinoma, endometrioid type.
The changes in fibrocystic breast disease are characterised by the appearance of fibrous tissue and a lumpy, cobblestone texture in the breasts. These lumps are smooth with defined edges, and are usually free-moving in regard to adjacent structures. The bumps can sometimes be obscured by irregularities in the breast that are associated with the condition. The lumps are most often found in the upper, outer sections of the breast (nearest to the armpit), but can be found throughout the breast. Women with fibrocystic changes may experience a persistent or intermittent breast aching or breast tenderness related to periodic swelling. Breasts and nipples may be tender or itchy.
Symptoms follow a periodic trend tied closely to the menstrual cycle. Symptoms tend to peak in the days and, in severe cases, weeks before each period and decrease afterwards. At peak, breasts may feel full, heavy, swollen, and tender to the touch. No complications related to breastfeeding have been found.
Colposcopically, it presents itself similarly to columnar epithelium on the cervix, assisted with lugol's solution application for diagnosis. It can be discovered as nodules or cysts on the vaginal tube, with biopsy needed for further diagnosis. As seen cytologically, epithelial and stromal cells in vaginal adenosis show characteristic fusion through the basal lamina or with stromal fibroblasts. Adenosal cells can be distinguished as mucinous, tuboendometrial, and embryonic. Its mucinous cells resemble the normal cervical lining, while its tuboendometrial cells resemble the lining of normal fallopian tubes or endometrium.
It is sometimes considered a precancerous lesion, given clear-cell adenocarcinoma patients present these lesions in close proximity to atypical tuboendometrial glands, and microglandular hyperplasia has been seen to arise from these lesions.
Vaginal adenosis is a benign abnormality in the vagina, commonly thought to be caused by intrauterine and neonatal exposure of diethylstilbestrol and other progestagens and nonsteroidal estrogens, however it has also been observed in otherwise healthy women and has been considered at times idiopathic or congenital. Postpubertal lesions have also been observed to grow . It has a rather common incidence, of about 10% of adult women.
In ICD-10 the condition is called "diffuse cystic mastopathy", or, if there is epithelial proliferation, "fibrosclerosis of breast". Other names for this condition include "chronic cystic mastitis", "fibrocystic mastopathy" and "mammary dysplasia". The condition has also been named after several people (see eponyms below). Since it is a very common disorder, some authors have argued that it should not be termed a "disease", whereas others feel that it meets the criteria for a disease. It is not a classic form of mastitis (breast inflammation).
They often cause no symptoms. Where they occur, symptoms include irregular menstrual bleeding, bleeding between menstrual periods, excessively heavy menstrual bleeding (menorrhagia), and vaginal bleeding after menopause. Bleeding from the blood vessels of the polyp contributes to an increase of blood loss during menstruation and blood "spotting" between menstrual periods, or after menopause. If the polyp protrudes through the cervix into the vagina, pain (dysmenorrhea) may result.
APAs are characterized by glands with abnormal shapes that: (1) often have squamous metaplasia, and (2) are surrounded by benign smooth muscle. Nuclear atypia, if present, is mild.
The microscopic differential diagnosis includes endometrial carcinoma and endocervical adenocarcinoma.
In breast pathology, pseudoangiomatous stromal hyperplasia, commonly abbreviated PASH, is an overgrowth of myofibroblastic cells and has an appearance similar to fibroadenomatoid changes.
The diagnostic significance is currently uncertain, but it appears to be benign. There have been cases of PASH diagnosed where the tumors co-exist with breast cancer. Other cases have made screening for breast cancer difficult and in some cases impossible due to the number and density of the existing PASH tumors. These cases have resulted in the necessity of a mastectomy and double mastectomy.
An endometrial polyp or uterine polyp is a mass in the inner lining of the uterus. They may have a large flat base (sessile) or be attached to the uterus by an elongated (pedunculated). Pedunculated polyps are more common than sessile ones. They range in size from a few millimeters to several centimeters. If pedunculated, they can protrude through the cervix into the vagina. Small blood vessels may be present, particularly in large polyps.
The diagnosis of PASH is by biopsy.
The important differential diagnosis is angiosarcoma, from which it was first differentiated in 1986.
It is important to correctly identify, as it can be confused with atypical ductal hyperplasia, cribriform ductal carcinoma in situ (DCIS), and adenoid cystic carcinoma.
Some of the more commonly known clinical forms of hyperplasia, or conditions leading to hyperplasia, are:
- Benign prostatic hyperplasia, also known as prostate enlargement.
- Cushing's disease – Physiopathology of hyperplasia of adrenal cortex due to increased circulating level of ACTH (adrenocorticotropic hormone).
- Congenital adrenal hyperplasia – Inherited disorder of gland (adrenal).
- Endometrial hyperplasia – Hyperproliferation of the endometrium, usually in response to unopposed estrogen stimulation in the setting of polycystic ovary syndrome or exogenous administration of hormones. Atypical endometrial hyperplasia may represent an early neoplastic process which can lead to endometrial adenocarcinoma. The development of endometrial adenocarcinoma from endometrial hyperplasia is a typical example of how the effects of pathologic hyperplasia can lead to neoplasia, and females who exhibit hyperplasia of the endometrium are indeed more likely to develop cancer of these cells.
- Hemihyperplasia when only half (or one side) of the body is affected, sometimes generating limbs of different lengths.
- Hyperplasia of the breast – "Hyperplastic" lesions of the breast include "usual ductal hyperplasia", a focal expansion of the number of cells in a terminal breast duct, and "atypical ductal hyperplasia", in which a more abnormal pattern of growth is seen, and which is associated with an increased risk of developing breast cancer.
- Intimal hyperplasia – The thickening of the tunica intima of a blood vessel as a complication of a reconstruction procedure or endarterectomy. Intimal hyperplasia is the universal response of a vessel to injury and is an important reason of late bypass graft failure, particularly in vein and synthetic vascular grafts.
- Focal epithelial hyperplasia (also known as Heck's disease) – This is a wart-like growth in the mucous tissues of the mouth or, rarely, throat that is caused by certain sub-types of the human papillomavirus (HPV). Heck's disease has not been known to cause cancer.
- Sebaceous hyperplasia – In this condition, small yellowish growths develop on the skin, usually on the face. This condition is neither contagious nor dangerous.
- Compensatory liver hyperplasia – The liver undergoes cellular division after acute injury, resulting in new cells that restore liver function back to baseline. Approximately 75% of the liver can be acutely damaged or resected with seemingly full regeneration through hepatocyte division, i.e., hyperplasia. This is what makes living-donor liver transplants possible.
Atypical ductal hyperplasia, abbreviated ADH, is the term used for a benign lesion of the breast that indicates an increased risk of breast cancer.
The name of the entity is descriptive of the lesion; ADH is characterized by cellular proliferation (hyperplasia) within one or two breast ducts and (histomorphologic) architectural abnormalities, i.e. the cells are arranged in an abnormal or atypical way.
In the context of a core (needle) biopsy, ADH is considered an indication for a breast lumpectomy, also known as a surgical (excisional) biopsy, to exclude the presence of breast cancer.
Uterine serous carcinoma (USC), also known as uterine papillary serous carcinoma (UPSC) and uterine serous adenocarcinoma, is an uncommon form of endometrial cancer that typically arises in postmenopausal women.
It is typically diagnosed on endometrial biopsy, prompted by post-menopausal bleeding.
Unlike the more common low-grade "endometrioid endometrial adenocarcinoma", USC does not develop from endometrial hyperplasia and is not hormone-sensitive. It arises in the setting of endometrial atrophy and is classified as a type II endometrial cancer.
In the case of endometrial hyperplasia usually a Pap smear is done, also a biopsy during the pelvic examination, may be done of the individuals endometrial tissue. You may want to consult your doctor for further examination.
In regards to Cushing's disease, the diagnosis of salivary cortisol in an elevated level around "late-night" is a way to detect it in many patients.
Atypical polypoid adenomyoma, abbreviated APA, is a rare uncommon benign tumour of the uterus.
Atypical hyperplasia is a high-risk premalignant lesion of the breast. It is believed that atypical ductal hyperplasia (ADH) is a direct precursor for low-grade mammary ductal carcinoma, whereas atypical lobular hyperplasia (ALH) serves as a risk indicator.
Vaginal bleeding or spotting in women after menopause occurs in 90% of endometrial cancer. Bleeding is especially common with adenocarcinoma, occurring in two-thirds of all cases. Abnormal menstrual cycles or extremely long, heavy, or frequent episodes of bleeding in women before menopause may also be a sign of endometrial cancer.
Symptoms other than bleeding are not common. Other symptoms include thin white or clear vaginal discharge in postmenopausal women. More advanced disease shows more obvious symptoms or signs that can be detected on a physical examination. The uterus may become enlarged or the cancer may spread, causing lower abdominal pain or pelvic cramping. Painful sexual intercourse or painful or difficult urination are less common signs of endometrial cancer. The uterus may also fill with pus (pyometrea). Of women with these less common symptoms (vaginal discharge, pelvic pain, and pus), 10–15% have cancer.
ADH, generally, is asymptomatic. It usually comes to medical attention on a screening mammogram, as a non-specific suspicious abnormality that requires a biopsy.
The lesion is found in patients who present typically with abnormal or postmenopausal bleeding. Such bleeding is followed by further evaluation leading to a tissue diagnosis, usually done by a dilatation and curettage (D&C). A work-up to follow would look for metastasis using imaging technology including sonography and MRI. The median age at diagnosis in a study of 138 women was 67 years, of these 54 had stage I, 20 stage II, 41 stage III, and 23 stage IV disease.
Histopathologically, uterine serous carcinomas is typically characterized by (1) nipple-shaped structures (papillae) with fibrovascular cores (2) marked nuclear atypia (irregularies in the nuclear membrane, enlarged nuclear size), (3) psammoma bodies and (4) cilia.
Mesothelial hyperplasia is a hyperplasia of mesothelial cells in serous membranes (pleura, pericardium, peritoneum).
Mesothelial hyperplasia is usually an incidental finding during peritoneal examination during laparotomy or laparoscopy. Grossly, mesothelial hyperplasia is characterized by the presence of small white nodules or flat plaques on the serous surface.
Lobular carcinoma "in situ" (LCIS) is a condition caused by unusual cells in the lobules of the breast.
Many do not consider it cancer, but it can indicate an increased risk of future cancer. The national database registrars, however, consider it a malignancy.
Unlike ductal carcinoma "in situ" (DCIS), LCIS is not associated with calcification, and is typically an incidental finding in a biopsy performed for another reason. LCIS only accounts for about 15% of the "in situ" (ductal or lobular) breast cancers.