Endometrial cancer refers to several types of
malignancyCancer is a class of diseases in which a group of cells display uncontrolled growth , invasion , and sometimes metastasis...
which arise from the
endometrium-Function:The endometrium functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a thick, blood vessel-rich, glandular tissue...
, or lining of the
uterusThe uterus is a major female hormone-responsive reproductive sex organ of most mammals, including humans. It is within the uterus that the fetus develops during gestation. The term uterus is used consistently within the medical and related professions; the Germanic term, womb is more common in...
. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year in the U.S. The most common subtype,
endometrioid adenocarcinoma, typically occurs within a few decades of
menopauseMenopause is the time in a woman’s life when menstruation ends. It is part of a biological process that begins, for most women, in their mid-fifties. During this time, the ovaries gradually produce lower levels of natural sex hormones—estrogen and progesterone...
, is associated with excessive
estrogenEstrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone, their name comes from estrus/oistros + gen/gonos = to generate.Estrogens are used as part of some oral contraceptives, in estrogen replacement...
exposure, often develops in the setting of
endometrial hyperplasiaEndometrial 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...
, and presents most often with
vaginal bleedingVaginal bleeding refers to bleeding in females that is either a physiologic response during the non-conceptional menstrual cycle or caused by hormonal or organic problems of the reproductive system. Vaginal bleeding may occur at any age, but always needs investigation when encountered in female...
.
Endometrial cancer refers to several types of
malignancyCancer is a class of diseases in which a group of cells display uncontrolled growth , invasion , and sometimes metastasis...
which arise from the
endometrium-Function:The endometrium functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a thick, blood vessel-rich, glandular tissue...
, or lining of the
uterusThe uterus is a major female hormone-responsive reproductive sex organ of most mammals, including humans. It is within the uterus that the fetus develops during gestation. The term uterus is used consistently within the medical and related professions; the Germanic term, womb is more common in...
. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year in the U.S. The most common subtype,
endometrioid adenocarcinoma, typically occurs within a few decades of
menopauseMenopause is the time in a woman’s life when menstruation ends. It is part of a biological process that begins, for most women, in their mid-fifties. During this time, the ovaries gradually produce lower levels of natural sex hormones—estrogen and progesterone...
, is associated with excessive
estrogenEstrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone, their name comes from estrus/oistros + gen/gonos = to generate.Estrogens are used as part of some oral contraceptives, in estrogen replacement...
exposure, often develops in the setting of
endometrial hyperplasiaEndometrial 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...
, and presents most often with
vaginal bleedingVaginal bleeding refers to bleeding in females that is either a physiologic response during the non-conceptional menstrual cycle or caused by hormonal or organic problems of the reproductive system. Vaginal bleeding may occur at any age, but always needs investigation when encountered in female...
. Endometrial carcinoma is the third most common cause of gynecologic cancer death (behind
ovarianOvarian cancer is a cancerous growth arising from different parts of the ovary.The most common form of ovarian cancer arises from the outer lining of the ovary.. However, recent evidence shows cells that line the Fallopian tube also to be prone to develop into the same kind of cancer as seen in...
and
cervical cancerCervical cancer is malignant neoplasm of the cervix uteri or cervical area. It may present with vaginal bleeding but symptoms may be absent until the cancer is in its advanced stages...
). A total abdominal
hysterectomyA hysterectomy is the surgical removal of the uterus, usually performed by a gynecologist. Hysterectomy may be total or partial...
(surgical removal of the uterus) with bilateral salpingo-oophorectomy is the most common therapeutic approach.
Endometrial cancer may sometimes be referred to as
uterine cancerThe term uterine cancer may refer to any of several different types of cancer which occur in the uterus, namely:*Uterine sarcomas: sarcomas of the myometrium, or muscular layer of the uterus, are most commonly leiomyosarcomas.*Endometrial cancer:...
. However, different cancers may develop not only from the endometrium itself but also from other tissues of the uterus, including
cervical cancerCervical cancer is malignant neoplasm of the cervix uteri or cervical area. It may present with vaginal bleeding but symptoms may be absent until the cancer is in its advanced stages...
,
sarcomaA uterine sarcoma is a malignant tumor that arises from the smooth muscle or connective tissue of the uterus. If the lesion originates from the stroma of the uterine lining it is an endometrial stromal sarcoma, and if the uterine muscle cell is the originator the tumor is a uterine leiomyosarcoma...
of the
myometriumThe myometrium is the middle layer of the uterine wall consisting of smooth muscle cells and supporting stromal and vascular tissue.The inner layer of the uterine wall is the endometrium or uterine lining, and the outer layer the serosa or perimetrium...
, and trophoblastic disease.
Classification
Most endometrial cancers are
carcinomaA carcinoma is any malignant cancer that arises from epithelial cells. Carcinomas invade surrounding tissues and organs and may metastasize, or spread, to lymph nodes and other sites....
s (usually
adenocarcinomaAdenocarcinoma is a cancer originating in glandular tissue. This tissue is also part of a larger tissue category known as epithelial. Epithelial tissue includes skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium is derived embryologically from...
s), meaning that they originate from the single layer of
epithelialIn biology and medicine, an epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body. Many glands are also formed from epithelial tissue...
cells which line the endometrium and form the endometrial glands. There are many
microscopicHistopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
subtypes of
endometrial carcinoma, including the common
endometrioid type, in which the cancer cells grow in patterns reminiscent of normal endometrium, and the far more aggressive
papillary serous carcinomaIn gynecology, uterine serous carcinoma , also known as uterine papillary serous carcinoma and uterine serous adenocarcinoma, is an uncommon form of endometrial cancer that typically arises in postmenopausal women....
and
clear cell endometrial carcinomas. Some authorities have proposed that endometrial carcinomas be classified into two pathogenetic groups:
- Type I: These cancers occur most commonly in pre- and peri-menopausal
Menopause is the time in a woman’s life when menstruation ends. It is part of a biological process that begins, for most women, in their mid-fifties. During this time, the ovaries gradually produce lower levels of natural sex hormones—estrogen and progesterone...
women, often with a history of unopposed estrogenEstrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone, their name comes from estrus/oistros + gen/gonos = to generate.Estrogens are used as part of some oral contraceptives, in estrogen replacement...
exposure and/or endometrial hyperplasiaEndometrial 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...
. They are often minimally invasive into the underlying uterine wall, are of the low-gradeIn pathology, grading is a measure of the progress of tumors and other neoplasms. Some pathology grading systems apply only to malignant neoplasms ; others apply also to benign neoplasms....
endometrioid type, and carry a good prognosis.
- Type II: These cancers occur in older, post-menopausal women, are more common in African-Americans, are not associated with increased exposure to estrogen, and carry a poorer prognosis. They include:
- the high-grade
In pathology, grading is a measure of the progress of tumors and other neoplasms. Some pathology grading systems apply only to malignant neoplasms ; others apply also to benign neoplasms....
endometrioid cancer,
- the uterine papillary serous carcinoma
In gynecology, uterine serous carcinoma , also known as uterine papillary serous carcinoma and uterine serous adenocarcinoma, is an uncommon form of endometrial cancer that typically arises in postmenopausal women....
,
- the uterine clear cell carcinoma
Uterine clear cell carcinoma is a rare form of endometrial cancer with distinct morphological features on pathology; it is aggressive and has high recurrence rate. Like uterine papillary serous carcinoma CC does not develop from endometrial hyperplasia and is not hormone sensitive, rather it...
.
In contrast to
endometrial carcinomas, the uncommon
endometrial stromal sarcomas are cancers which originate in the non-glandular
connective tissueConnective tissue is a form of fibrous tissue.. It is one of the four types of tissue in traditional classifications ....
of the endometrium. Uterine
carcinosarcomaCarcinosarcoma is a malignant tumor that is a mixture of carcinoma and sarcoma .- External links :...
, formerly called
Malignant mixed müllerian tumorMalignant mixed Müllerian tumor is a rare uterine sarcoma or carcinosarcoma occurring in the female abdominal cavity. Because it is so rare, there is little research on MMMT...
, is a rare uterine cancer which contains cancerous cells of both glandular and
sarcomaA sarcoma is a cancer of the connective tissue resulting in mesoderm proliferation.This is in contrast to carcinomas, which are of epithelial origin...
tous appearance - in this case, the cell of origin is unknown.
Signs and symptoms
- Vaginal bleeding
Vaginal bleeding refers to bleeding in females that is either a physiologic response during the non-conceptional menstrual cycle or caused by hormonal or organic problems of the reproductive system. Vaginal bleeding may occur at any age, but always needs investigation when encountered in female...
and/or spotting in postmenopausal women
- Abnormal uterine bleeding, abnormal menstrual periods
- Bleeding between normal periods in premenopausal women in women older than 40: extremely long, heavy, or frequent episodes of bleeding (may indicate premalignant changes)
- Anemia
Anemia is a decrease in normal number of red blood cells or less than the normal quantity of hemoglobin in the blood...
, caused by chronic loss of blood. (This may occur if the woman has ignored symptoms of prolonged or frequent abnormal menstrual bleeding.)
- Lower abdominal
In vertebrates such as mammals the abdomen constitutes the part of the body between the thorax and pelvis. The region enclosed by the abdomen is termed the abdominal cavity...
pain or pelvic cramping
- Thin white or clear vaginal discharge
Vaginal discharge is a form of Mucopurulent discharge from the vagina.It can be indicative of pelvic inflammatory disease, which is associated with Neisseria gonorrhoeae or Chlamydia. Along with discharge, the woman suffering from PID will also complain of lower abdominal tenderness, bilateral...
in postmenopausal women.
Risk factors
- high levels of estrogen
- endometrial hyperplasia
- obesity
- hypertension
- polycystic ovary syndrome
- nulliparity (never having carried a pregnancy)
- infertility (inability to become pregnant)
- early menarche (onset of menstruation)
- late menopause (cessation of menstruation)
- endometrial polyps or other benign growths of the uterine lining
- diabetes
- Tamoxifen
- high intake of animal fat
- pelvic radiation therapy
- breast cancer
- ovarian cancer
- heavy daily alcohol consumption (possibly a risk factor)
Clinical evaluation
Routine screening of asymptomatic women is not indicated, since the disease is highly curable in its early stages. Results from a
pelvic examinationA pelvic examination, also pelvic exam, is a physical examination of the female pelvic organs.Broadly, it can be divided into the external examination and internal examination.It is also called "Bimanual Exam" & "Manual Uterine Palpation"....
are frequently normal, especially in the early stages of disease. Changes in the size, shape or consistency of the uterus and/or its surrounding, supporting structures may exist when the disease is more advanced.
- A Pap smear
The Papanicolaou test is a screening test used in gynecology to detect premalignant and malignant processes in the ectocervix. Significant changes can be treated, thus preventing cervical cancer. The test was invented by and named after the prominent Greek doctor Georgios Papanikolaou...
may be either normal or show abnormal cellular changes.
- Endometrial curettage
Curettage, in surgery, is the use of a curette to remove tissue by scraping or scooping. It may be used to obtain a biopsy of a mass to determine if it is a granuloma, neoplasm, or some other tumor. It is often employed prior to definitive excisional surgery to more precisely delineate the extent...
is the traditional diagnostic method. Both endometrial and endocervical material should be sampled.
- If endometrial curettage does not yield sufficient diagnostic material, a dilation and curettage
Dilation and curettage literally refers to the dilation of the cervix and surgical removal of the contents of the uterus. It is a therapeutic gynecological procedure as well as a rarely used method of first trimester abortion. It is commonly referred to as a D&C.D&C normally refers to a...
(D&C) is necessary for diagnosing the cancer.
- Hysteroscopy
Hysteroscopy is the inspection of the uterine cavity by endoscopy. It allows for the diagnosis of intrauterine pathology and serves as a method for surgical intervention .-Method:...
allows the direct visualization of the uterine cavity and can be used to detect the presence of lesions or tumours. It also permits the doctor to obtain cell samples with minimal damage to the endometrial lining (unlike blind D&CD&C may stand for:* Doctrine and Covenants, part of the scripture of Mormonism* Dilation and curettage, a medical procedure involving the dilation of the cervix to remove uterine contents...
).
- Endometrial biopsy
A biopsy is a medical procedure used to remove a sample of tissue from the patient to be analyzed and diagnosed by a physician.An endometrial biopsy is the only procedure used to discover endometrial cancer. It is only given to high-risk patients...
or aspirationNeedle aspiration biopsy , also known as fine needle aspiration cytology , fine needle aspiration biopsy and fine needle aspiration , is a diagnostic procedure sometimes used to investigate superficial lumps or masses...
may assist the diagnosis.
- Transvaginal ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Although this limit varies from person to person, it is approximately 20 kilohertz in healthy, young adults and thus, 20 kHz serves as a useful lower limit in describing ultrasound...
to evaluate the endometrial thickness in women with postmenopausal bleeding is increasingly being used to evaluate for endometrial cancer.
- Recently, a new method of testing has been introduced called the TruTest, offered through Gynecor. It uses the small flexible Tao Brush
The Tao Brush is a medical instrument used to perform an alternative method of endometrial biopsy.The traditional method of endometrial biopsies uses a specialized catheter to suction away a portion of the uterine lining. The Tao Brush method instead uses a small, flexible brush to gently brush...
to brush the entire lining of the uterus. This method is less painful than a pipelle biopsy and has a larger likelihood of procuring enough tissue for testing. Since it is simpler and less invasive, the TruTest can be performed as often, and at the same time as, a routine Pap smear, thus allowing for early detection and treatment.
- Ongoing research suggests that serum p53 antibody may hold value in identifying high-risk endometrial cancer.
Diagnostic test study of S-p53 Ab and agreement study for high-risk endometrial cancer
Kappa: 0.70 Sensitivity (%): 64 Specificity(%): 96 PPV: 78 NPV: 92
Pathology
The histopathology of endometrial cancers is highly diverse. The most common finding is a
well-differentiated endometrioid adenocarcinoma, which is composed of numerous, small, crowded glands with varying degrees of nuclear atypia, mitotic activity, and stratification. This often appears on a background of endometrial hyperplasia. Frank adenocarcinoma may be distinguished from atypical hyperplasia by the finding of clear stromal invasion, or "back-to-back" glands which represent nondestructive replacement of the endometrial stroma by the cancer. With progression of the disease, the myometrium is infiltrated. However, other subtypes of endometrial cancer exist and carry a less favorable diagnosis such as the
uterine papillary serous carcinomaIn gynecology, uterine serous carcinoma , also known as uterine papillary serous carcinoma and uterine serous adenocarcinoma, is an uncommon form of endometrial cancer that typically arises in postmenopausal women....
and the clear cell carcinoma.
Further evaluation
Patients with newly-diagnosed endometrial cancer do not routinely undergo imaging studies, such as CT scans to evaluate for extent of disease, since this is of low yield. Preoperative evaluation should include a complete medical history and physical examination, pelvic examination and rectal examination with
stool guaiac testA stool guaiac test detects the presence of fecal occult blood.It involves feces, a thick piece of paper attached to a thin film coated with guaiac , and hydrogen peroxide...
, chest X-ray, complete blood count, and blood chemistry tests, including liver function tests. Colonoscopy is recommended if the stool is guaiac positive or the woman has symptoms, due to the etiologic factors common to both endometrial cancer and colon cancer. The tumor marker
CA-125CA-125 also known as mucin 16 or MUC16 is a protein which in humans is encoded by the MUC16 gene. MUC16 is a member of the mucin family glycoproteins...
is sometimes checked, since this can predict advanced stage disease.
Staging
Endometrial carcinoma is surgically staged using the
FIGOThe International Federation of Gynecology and Obstetrics, usually just FIGO as the acronym of its French name Fédération Internationale de Gynécologie et d'Obstétrique, founded in 1954 is a worldwide NGO organisation representing obstetricians and gynecologists in over one hundred territories...
cancer stagingThe stage of a cancer is a descriptor of how much the cancer has spread. The stage often takes into account the size of a tumor, how deeply it has penetrated, whether it has invaded adjacent organs, how many lymph nodes it has metastasized to , and whether it has spread to distant organs...
system.
- Stage IA: tumor limited to the endometrium
- Stage IB: invasion of less than half the myometrium
The myometrium is the middle layer of the uterine wall consisting of smooth muscle cells and supporting stromal and vascular tissue.The inner layer of the uterine wall is the endometrium or uterine lining, and the outer layer the serosa or perimetrium...
- Stage IC: invasion of more than half the myometrium
- Stage IIA: endocervical glandular involvement only
- Stage IIB: cervical stromal invasion
- Stage IIIA: tumor invades serosa or adnexa, or malignant peritoneal cytology
- Stage IIIB: vaginal metastasis
- Stage IIIC: metastasis to pelvic or para-aortic lymph nodes
- Stage IVA: invasion of the bladder or bowel
- Stage IVB: distant metastasis, including intraabdominal or inguinal lymph nodes
Treatment
The primary treatment is surgical. Surgical treatment should consist of, at least, cytologic sampling of the peritoneal fluid, abdominal exploration, palpation and biopsy of suspicious lymph nodes, abdominal
hysterectomyA hysterectomy is the surgical removal of the uterus, usually performed by a gynecologist. Hysterectomy may be total or partial...
, and removal of both
ovariesThe ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in females are homologous to testes in males, in that they are both gonads and endocrine glands.-Human anatomy:...
(bilateral salpingo-oophorectomy). Lymphadenectomy, or removal of pelvic and para-aortic lymph nodes, is sometimes performed for tumors that have high risk features, such as pathologic grade 3 serous or clear-cell tumors, invasion of more than 1/2 the myometrium, or extension to the cervix or adnexa. Sometimes, removal of the
omentumOmentum can refer to two different components of the peritoneum:* greater omentum* lesser omentum...
is also performed.
Abdominal hysterectomyA hysterectomy is the surgical removal of the uterus, usually performed by a gynecologist. Hysterectomy may be total or partial...
is recommended over
vaginal hysterectomyA hysterectomy is the surgical removal of the uterus, usually performed by a gynecologist. Hysterectomy may be total or partial...
because it affords the opportunity to examine and obtain washings of the abdominal cavity to detect any further evidence of cancer.
Women with stage 1 disease who are at increased risk for recurrence and those with stage 2 disease are often offered surgery in combination with
radiation therapyRadiation therapy is the medical use of ionizing radiation as part of cancer treatment to control malignant cells . Radiotherapy may be used for curative or adjuvant cancer treatment...
.
ChemotherapyChemotherapy, in its most general sense, is the treatment of disease by chemicals especially by killing micro-organisms or cancerous cells. In popular usage, it refers to antineoplastic drugs used to treat cancer or the combination of these drugs into a cytotoxic standardized treatment regimen...
may be considered in some cases, especially for those with stage 3 and 4 disease.
hormonal therapyHormonal therapy is one of the major modalities of medical treatment for cancer, others being cytotoxic chemotherapy and targeted therapy . It involves the manipulation of the endocrine system through exogenous administration of specific hormones, particularly steroid hormones, or drugs which...
with progestins and antiestrogens has been used for the treatment of endometrial stromal sarcomas.
The antibody Herceptin, which is used to treat breast cancers that overexpress the
HER2/neuHER2/neu stands for "Human Epidermal growth factor Receptor 2" and is a protein giving higher aggressiveness in breast cancers. It is a member of the ErbB protein family, more commonly known as the epidermal growth factor receptor family...
protein, has been tried with some success in a phase II trial in women with
uterine papillary serous carcinomaIn gynecology, uterine serous carcinoma , also known as uterine papillary serous carcinoma and uterine serous adenocarcinoma, is an uncommon form of endometrial cancer that typically arises in postmenopausal women....
s that overexpress HER2/neu.
Complications of treatment
- A perforation (hole) of the uterus may occur during a D&C or an endometrial biopsy.
- Asherman's syndrome
Asherman's syndrome , also called "uterine synechiae" or intrauterine adhesions , presents a condition characterized by the presence of adhesions and/or fibrosis within the uterine cavity due to scars...
(intrauterine adhesions) may occur from D&CD&C may stand for:* Doctrine and Covenants, part of the scripture of Mormonism* Dilation and curettage, a medical procedure involving the dilation of the cervix to remove uterine contents...
, resulting in infertility and an increased risk of future obstetric complications.
Prognosis
Because endometrial cancer is usually diagnosed in the early stages (70 % to 75 % of cases are in stage 1 at diagnosis; 10 % to 15 % of cases are in stage 2; 10 % to 15 % of cases are in stage 3 or 4), there is a better probable outcome associated with it than with other types of
gynecological cancersGynecologic oncology is a specialized field of medicine that focuses on cancers of the female reproductive system, including ovarian cancer, uterine cancer, endometrial cancer, cervical cancer, and vulvar cancer...
such as
cervicalCervical cancer is malignant neoplasm of the cervix uteri or cervical area. It may present with vaginal bleeding but symptoms may be absent until the cancer is in its advanced stages...
or
ovarian cancerOvarian cancer is a cancerous growth arising from different parts of the ovary.The most common form of ovarian cancer arises from the outer lining of the ovary.. However, recent evidence shows cells that line the Fallopian tube also to be prone to develop into the same kind of cancer as seen in...
. While endometrial cancers are 40% more common in Caucasian women, an African American woman who is diagnosed with uterine cancer is twice as likely to die, possibly due to the higher frequency of aggressive subtypes in that population.
Survival rates
The 5-year survival rate for endometrial cancer following appropriate treatment is:
- 75% to 95% for stage 1
- 50% for stage 2
- 30% for stage 3
- less than 5% for stage 4
Epidemiology
It's the most frequent cancer ocurring in the female genital tract in the United States and many other Western countries. However, it has been dramatically reduced in the incidence due to early detection of
CINCin, CIn or CIN can mean:* Cincinnati, Ohio** The Cincinnati Reds, an MLB franchise.** The Cincinnati Bengals, an NFL franchise.* An alternative spelling of Qin.* Cervical intraepithelial neoplasm...
by periodic cytologic examinations.
It appears most frequently between ages of 55 and 65, and uncommon below 40.
There are two pictures of this disease, perimenopausal women with estrogen excess and in older women with endometrial atrophy.
External links