This document summarizes information about uterine corpus tumors, specifically endometrial cancer. It discusses the epidemiology, etiology, risk factors, signs and symptoms, screening and diagnosis, pathology, staging and prognosis, and treatment of endometrial cancer. It notes that endometrial cancer is the most common female pelvic malignancy, with risk factors including obesity, unopposed estrogen exposure, and lack of parity. Diagnosis involves endometrial biopsy or dilation and curettage. Prognosis depends on staging which incorporates factors like tumor grade, myometrial invasion, and lymph node involvement. Treatment typically involves surgery including hysterectomy, with radiation therapy sometimes used as adjuvant treatment.

1. Uterine Corpus
Tumors
CREATED BY :-PATEL SABIR
GROUP NO:-601(2010-2016)

2. Endometrial Cancer
 Carcinoma of the epithelial lining (endometrium) of the uterine corpus is the
most common female pelvic malignancy, with 52,630 new cases estimated to
be diagnosed in 2014 and 8,590 deaths expected. Factors influencing its
prominence are the declining incidence of cervical cancer, longer life
expectancy, and earlier diagnosis.

3. Epidemiology
 Age
 Endometrial cancer is primarily a disease of postmenopausal women, although
25% of cases occur in premenopausal patients, with 5% of cases developing in
patients younger than 40 years.
 Geography
 The incidence of endometrial cancer is high in Western nations and very low in
Eastern countries.
 Immigrant populations tend to assume the risks of native populations,
highlighting the importance of environmental factors in the genesis of this
disease. Endometrial cancers tend to be more common in urban than in rural
residents. In the United States, the incidence of endometrial cancer is twice as
high in white women as in black women.

4. Etiology and Risk Factors
 Adenocarcinoma of the endometrium may arise in normal, atrophic, or
hyperplastic endometrium. Two mechanisms are generally believed to be
involved in the development of endometrial cancer. In approximately 75% of
women, there is a history of exposure to unopposed estrogen, either
endogenous or exogenous (type I). The tumors in these women begin as
endometrial hyperplasia and progress to carcinomas, which usually are better
differentiated and have a more favorable prognosis than tumors unrelated to
estrogens.
 In 25% of women, carcinomas appear spontaneously, are not clearly related to
a transition from atypical hyperplasia, and rather arise in a background of
atrophic or inert endometrium. These neoplasms tend to be associated with a
more undifferentiated cell type and a poorer prognosis (type II).

5. Unopposed Estrogen
 It has been hypothesized that long-term estrogenic stimulation of the endometrium unmodified by
progesterone has a role in the development of endometrial carcinoma. This hypothesis derives from
observations that women who are infertile or obese or who have dysfunctional bleeding due to anovulation are
at high risk for this disease, as are women with estrogen-secreting granulosa theca cell ovarian tumors. Also,
the recognition that atypical adenomatous (complex) hyperplasia is a precursor of cancer, and that it is
associated with unopposed estrogen use in women, underscores the importance of the association among
risk factors, estrogens, and cancer. In the late 1970s and early 1980s, several case-control studies
demonstrated that the risk of endometrial cancer is increased 4- to 15-fold in long-term estrogen users, as
compared with age-matched controls.
 It is well established that past use of oral contraceptives (OCs) protects against endometrial cancer. The use
of OCs with either high-potency progestin or low-potency progestin is associated with a decreased risk of
endometrial cancer. The potency of the progestin in most OCs appears adequate to provide a protective effect
against endometrial cancer. OCs with higher progestin potency may be more protective than OCs with lower
progestin potency among women with a larger body habitus.
 Sidebar: The Women's Health Initiative enrolled 16,608 postmenopausal women from 40 US clinical centers
into a randomized, double-blind, placebo-controlled trial. Women aged 50 to 70 with an intact uterus and
normal endometrial histology were assigned to once-daily 0.625-mg conjugated equine estrogen plus 2.5 mg
of medroxyprogesterone acetate or to placebo. After 6 years of the intervention and 7 years of additional
follow-up, endometrial cancer was diagnosed in 66 women in the combined-hormone–therapy group and in 95
women in the placebo group, which translated to a 35% reduction in risk (P = .007) (Chlebowski RT, Anderson
GL, Sarto G, et al: European Cancer Congress abstract LBA13, 2013).

6. Diet
 The high rate of occurrence of endometrial cancer in Western societies and the
very low rate in Eastern countries suggest a possible etiologic role for nutrition,
especially the high content of animal fat in Western diets. There may be a
relationship between high-fat diets and the higher incidence of endometrial
carcinoma in women with conditions of unopposed estrogen. Endogenous
estrogens rise in postmenopausal women because of increased production of
androstenedione or a greater peripheral conversion of this hormone to estrone.
In obese women, the extraglandular aromatization of androstenedione to
estrone is increased in fatty tissue.

7.  Obesity
 Phenotypically, the majority of women who develop endometrial cancer tend
to be obese. Women who are 30 lb over ideal weight have a threefold
increased risk of developing endometrial cancer, whereas those 50 lb or more
over ideal weight have a 10-fold increased risk.
 Parity
 Nulliparous women are at 2 times greater risk for developing endometrial
cancer, women who undergo menopause after age 52 are at 2.5 times greater
risk, and those who experience increased bleeding at the time of menopause
are at 4 times greater risk.
 - See more at: http://www.cancernetwork.com/cancer-
management/uterine-corpus-tumors/page/0/1#sthash.NoaQtR7D.dpuf

8. ENDOMETRIAL HYPERPLASIA
 Excessive proliferation of the endometrial glands & to a lesser extent endometrial
stroma
 Due to excessive estrogen stimulation
 Only 25% of Pt with E Ca have Hx of hyperplasia
CLASSIFICATION
1-Hyperplasia without atypia (not premalignant)
1-A-Simple
 Microscopically  crowding of the glands in the stroma
 Glands are cystically dilated & give a “Swiss cheese” appearance
 Commonly asymptomatic
 1% progress to Ca over 15 Y
 80% regress

9. ENDOMETRIAL HYPERPLASIA
1-B-Complex hyperplasia without atypia
 A complex crowded appearance of the glands with very little stroma
 Epithelial stratification & mitotic activity
 3% progress to Ca over 13 Y
 80% regress
 85% reversal with progestin Rx

10. ENDOMETRIAL HYPERPLASIA
2-Hyperplasia with atypia (premalignant)
 Histologically  endometrial glands are lined by enlarged cells with 
nuclear : cytoplasmic ratios
The nuclei are irregular with coarse chromatin clumping & prominent nucleoli
 50-94% regress with progestin therapy
 A higher rate of relapse after stopping Rx compared to that of lesions without
atypia
2-A-Simple
 Progression to carcinoma occur in 8%
2-B- Complex
 Progression to carcinoma occur in 29%

11. ENDOMETRIAL HYPERPLASIA
3-CARCINOMA IN SITU
Histologically differentiated from carcinoma by
 Presence of intervening stroma between abnormal glands
 There is no evidence of invasion
 It is difficult to differentiate from Ca

12. Signs and Symptoms
 Postmenopausal women
 Symptoms of early endometrial carcinoma are few but common. However, 90%
of patients complain of abnormal vaginal discharge, and 80% of these women
experience abnormal bleeding, usually after menopause. In the general
population, 15% of postmenopausal women presenting with abnormal bleeding
will be found to have endometrial carcinoma. Signs and symptoms of more
advanced disease include pelvic pressure and other symptoms indicative of
uterine enlargement or extrauterine tumor spread.
 Premenopausal women
 The diagnosis of endometrial cancer may be difficult to make in premenopausal
patients. The physician must maintain a high index of suspicion in this group of
patients and perform endometrial sampling in any women who complain of
prolonged, heavy menstrual periods or intermenstrual spotting.

13. Screening and Diagnosis
 Screening
 There is no role for screening of average-risk, asymptomatic patients for
endometrial cancer.
 Outpatient endometrial sampling
 These procedures, such as endometrial biopsy or aspiration curettage coupled
with endocervical sampling, are definitive if results are positive for cancer. The
results of endometrial biopsies correlate well with endometrial curettings, and
these biopsy procedures have the advantage of avoiding general anesthesia.
However, if sampling techniques fail to provide sufficient diagnostic information
or if abnormal bleeding persists, formal dilation and curettage is required.

14. Screening and Diagnosis
 Dilation and curettage
 This is the gold standard for assessing uterine bleeding and diagnosing endometrial carcinoma.
Before dilating the cervix, the endocervix should be curetted. Next, careful sounding of the
uterus is accomplished. Dilation of the cervix is then performed, followed by systematic
curetting of the entire endometrial cavity. Cervical and endometrial specimens should be kept
separate and forwarded for pathologic interpretation.
 The American Cancer Society (ACS) has concluded that there is insufficient evidence to
recommend routine screening for endometrial cancer for average-risk women. However, the
ACS recommends that at the time of menopause, all women should be informed about the risks
and symptoms of endometrial cancer and strongly encouraged to report any unexpected
bleeding or spotting to their physicians. Women at elevated risk for endometrial cancer from
tamoxifen therapy should be informed about the risk and symptoms of endometrial cancer and
strongly encouraged to report any unexpected bleeding or spotting to their physicians.
 Women who carry the HNPCC abnormality should be considered for a prophylactic total
abdominal hysterectomy bilateral saphingo-oophorectomy, especially after childbearing and
when contemplating abdominal surgery for any reason. Additional investigation is needed to
determine the appropriate monitoring for endometrial cancer in HNPCC carriers.

15. Pathology
Adenocarcinoma
 Endometrioid adenocarcinoma is the most common form of endometrial
carcinoma, accounting for 75% to 80% of cases. It varies from well
differentiated to undifferentiated. The former demonstrates well-preserved
glands in at least 95% of the tumor, whereas in the latter, less than half of the
neoplasm shows glandular differentiation. Squamous differentiation can be
seen in 30% to 50% of cases.
 Adenocarcinoma with benign squamous differentiation has been termed
"adenoacanthoma" and generally has a good prognosis.
 If the squamous component resembles squamous carcinoma, the tumor is
designated an adenosquamous carcinoma. These lesions tend to have a worse
prognosis because of their association with a poorly differentiated glandular
component.

16. Serous carcinoma
 This is an aggressive form of endometrial cancer that accounts for fewer than
10% of these tumors. Serous cancer of the endometrium closely resembles
serous carcinoma of the ovaries and fallopian tubes and is usually found in an
advanced stage in older women.

17. Clear-cell carcinomas
 Clear-cell carcinomas of the endometrium closely resemble their counterparts
in the cervix, vagina, and ovaries. As with serous cancers, these tumors
generally occur in older women and have a poor prognosis because of their
propensity for early intraperitoneal spread

18. Secretory adenocarcinoma
 This is an uncommon endometrial cancer that resembles secretory
endometrium with its associated progestational changes. These cancers tend to
be of low grade and have a good prognosis.

19. Staging and Prognosis
 Two large prospective GOG surgical staging trials reported in 1984 and 1987
helped define the prognostic factors for endometrial carcinoma and the current
treatment approaches. In addition to evaluating the predictive value of such
factors as age, race, and endocrine status, the studies confirmed that prognosis
is directly related to the presence or absence of easily determined uterine and
extrauterine risk factors. Uterine prognostic factors include histologic cell type,
tumor grade, depth of myometrial invasion, occult extension of disease to the
cervix, and vascular space invasion. Extrauterine prognostic factors include
adnexal metastases, intraperitoneal spread of disease to other extrauterine
structures, positive peritoneal cytology, pelvic lymph node metastases, and
aortic node involvement. The revised staging system takes into account the
nearly equivalent survival rates among low to intermediate grade IA and IB
tumors, the lack of prognostic significance of endocervical gland involvement,
and the marked survival differences of pelvic node or para-aortic node
involvement. A revised staging system can be seen in Table 1.

21. Uterine size
 The size of the uterus was previously believed to be a risk factor and was part
of the older clinical staging system. However, recent information indicates that
uterine size is not an independent risk factor but rather relates to cell type,
grade, and myometrial invasion

22. Surgical staging
 Cell type and grade can be determined before hysterectomy, although in some
series, grade, as determined by dilation and curettage, has an overall
inaccuracy rate of 31% compared with grade in the hysterectomy specimen,
and grade 3 tumors have an inaccuracy rate of 50%. Recognition of all of the
other factors requires an exploratory laparotomy, peritoneal fluid sampling, and
hysterectomy with careful pathologic interpretation of all removed tissue. This
primary surgical approach led the International Federation of Gynecology and
Obstetrics (FIGO) to define endometrial cancer as a surgically staged disease
in 1988, incorporating many of the prognostic factors into th

24. Treatment
 Surgery
 Approximately 90% of patients with a diagnosis of endometrial cancer are
medically able to undergo surgery. Preparation for this surgery should include
evaluation of such concurrent medical problems as hypertension and diabetes,
which are frequently found in patients with endometrial cancer.

25. Open surgical procedure.
 The operative procedure is performed through an adequate abdominal incision
that allows for thorough intra-abdominal exploration and retroperitoneal lymph
node removal if necessary. On entry into the peritoneal cavity, fluid samples are
obtained for subsequent cytologic determination (intraperitoneal cell washings).
Next, thorough intra-abdominal and pelvic exploration is undertaken, with
biopsy or excision of any suspicious lesions. In particular, the uterus should be
observed for tumor breakthrough of the serosal surface. The distal ends of the
fallopian tubes are clipped or ligated to prevent possible tumor spillage during
uterine manipulation.
 These procedures should be followed by total extrafascial hysterectomy and
bilateral salpingo-oophorectomy. The excised uterus is opened away from the
operating table, and the depth of myometrial penetration is determined by
clinical observation or microscopic frozen section. The depth of myometrial
invasion can be accurately assessed in more than 90% of cases.

26. Laparoscopic surgery
 An alternative method of surgically staging patients with clinical stage I
endometrial cancer is gaining in popularity. This approach combines
laparoscopically assisted vaginal hysterectomy with laparoscopic
lymphadenectomy.

27. Treatment
 Lymph node evaluation
 Lymphadenectomy
 Surgical staging
 Adjuvant radiation therapy
 Brachytherapy
 Vaginal irradiation

29. Uterine Sarcomas
 Carcinosarcomas and other uterine sarcomas are uncommon tumors,
accounting for less than 4% of all cancers of the uterine corpus.
Carcinosarcomas, the most common histologic subtype, demonstrate both
epithelial and stromal differentiation. Endometrial stromal sarcomas and
leiomyosarcomas are characterized by differentiation toward one or more
stromal tissues. Leiomyosarcomas occur at an earlier age than do
carcinosarcomas, with a plateau observed in middle age. There is strong
epidemiologic evidence that prior exposure to pelvic irradiation may increase
the risk for the development of uterine sarcomas. Generally, these tumors are
characterized by aggressive growth, with early lymphatic or hematogenous
spread. The overall survival rate is poor, with the majority of deaths occurring
within 2 years of diagnosis.

30. Patterns of Spread
 Lymphatic metastases are a significant route of spread for carcinosarcoma, with
a reported incidence of 40% to 60% occurring with stage I disease.
Leiomyosarcoma has a propensity for extra-abdominal spread, often involving
the lungs. For carcinosarcoma, the initial site for recurrence after surgical
resection is likely to be the pelvis or abdomen, whereas leiomyosarcomas tend
to fail to recur distantly. In a prospective surgical staging trial by the GOG, the
recurrence rate for early-stage carcinosarcoma was 53% and for
leiomyosarcoma, 71%.


31. Treatment
 Surgery
 Surgery is the mainstay of treatment for uterine sarcomas. For carcinosarcoma,
this usually consists of total abdominal hysterectomy and bilateral salpingo-
oophorectomy, with washings to be obtained for peritoneal cytology. The GOG
prospective staging study reported a 17% incidence of nodal metastasis for this
histologic subtype, so retroperitoneal nodes should be sampled as for poorly
differentiated endometrial cancers. For patients with advanced/recurrent
disease, aggressive surgical debulking does not appear to improve outcome.
 Hysterectomy with oophorectomy is also standard therapy for uterine
leiomyosarcoma

32. Treatment
 Adjuvant irradiation
 Radiotherapy
 Chemotherapy

33. Gestational Trophoblastic Diseases
 Gestational trophoblastic diseases (GTDs) encompass a spectrum of neoplastic
disorders that arise from placental trophoblastic tissue after abnormal
fertilization. In the United States, GTDs account for less than 1% of gynecologic
malignancies. Forty years ago, women with choriocarcinoma had a 95%
mortality rate. Today, with the advent of effective chemotherapy and the
development of a reliable tumor marker (β-subunit human chorionic
gonadotropin [β-hCG]), the cure rate for choriocarcinoma is 90% to 95%.

34. Clinical Presentation
 Complete mole
 The classic signs of a molar pregnancy include the absence of fetal heart sounds, physical
evidence of a uterus that is larger than expected for gestational age, and vaginal bleeding.
Although an intact fetus may coexist with a partial mole, this occurs in fewer than 1 in 100,000
pregnancies.
 The most common presenting symptom of molar pregnancy is vaginal bleeding, reported in up
to 97% of patients. Intrauterine clots may undergo oxidation and liquefaction, producing
pathognomonic prune juice–like fluid. Prolonged or recurrent bleeding may result in iron
deficiency anemia. Symptoms of anemia occur in approximately 50% of patients at the time of
diagnosis. Early toxemia (hypertension, proteinuria, and edema) presenting during the first or
second trimester is common (20% to 30% of cases) in molar pregnancy.
 Hyperthyroidism is seen clinically in approximately 7% of molar pregnancies. An elevation of
triiodothyronine and thyroxine (T4) levels is observed more commonly than are the clinical
manifestations of tachycardia, sweating, weight loss, and tremor. These hormonal elevations
are presumed to be secondary to the structural similarity of hCG to thyroid-stimulating
hormone.

35. Partial mole
 Patients with partial mole have clinical features different from those with
complete mole. Fewer than 10% of patients with partial mole have uterine
enlargement. Patients with partial mole do not have prominent theca-lutein
cysts, hyperthyroidism, or respiratory insufficiency. They experience toxemia
only rarely. The diagnosis of partial mole is usually made after histologic review
of curettage specimens.

36. Diagnostic studies
 Laboratory studies. Thyroid function studies should be performed in all
patients with a clinical history or physical examination suggestive of
hyperthyroidism. Abnormal thyroid function, manifested as an elevated T4 level,
is common in GTD. Metastatic deposits in the kidneys or GI tract may reveal
themselves by hematuria or hematochezia.
 Tumor markers. A well-characterized glycoprotein hormone secreted by the
syncytiotrophoblast, hCG is essential to maintaining normal function of the
corpus luteum during pregnancy. Because all trophoblastic tumors secrete β-
hCG, this hormone serves as an excellent marker for tumor activity in the
nonpregnant patient. Serial β-hCG levels should be monitored during therapy to
ensure adequate treatment. The level of β-hCG is roughly proportional to the
tumor burden and inversely proportional to the therapeutic outcome.

37. Treatment
 Molar pregnancy. For patients with complete or partial hydatidiform mole,
evacuation of the mole by suction and sharp curettage should be performed.
Oxytocics also are given to produce uterine involution and to control bleeding.
However, these agents should be used judiciously because they may cause
hyponatremia and fluid overload. A baseline chest radiograph and β-hCG
measurement should be obtained before surgery. After molar evacuation, 80%
of patients will need no further intervention

38. Reference
 On Endometrial Cancer
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39. On Uterine Sarcomas
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40. On Gestational Trophoblastic Diseases
 Lurain JR: Gestational trophoblastic disease I: Epidemiology, pathology,
clinical presentation and diagnosis of gestational trophoblastic disease, and
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high-risk gestational trophoblastic neoplasia. J Reprod Med 57:219–224, 2012.
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