This document discusses endometrial cancer. It is the most common gynecologic malignancy in the US, with a 3% incidence rate that is increasing. Most cases are diagnosed early as abnormal vaginal bleeding prompts medical evaluation. Obesity, unopposed estrogen exposure, and genetics increase risk. Treatment depends on cancer stage, grade, and subtype, but commonly involves hysterectomy with or without additional therapies like radiation or chemotherapy. Outcomes are best for early stage, low grade endometrioid adenocarcinoma.

1. Endometrial Cancer
Hale Teka, M.D., OB-GYN Resident
Mekelle University,
College of Health Sciences, Dep't of OB-GYN

2. • Contents
1. Introduction
2. Endometrial Hyperplasia
3. Endometrial Cancer
Hale T., M.D., Resident PhysicianSaturday, January 7,
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3. • Epidemiology
– Most common gynecologic malignancy in US
– 3% in US
– Incidence is increasing
– Easily diagnosed
• Patients seek care early because of vaginal bleeding
• Endometrial biopsy leads quickly to diagnosis
– 4th leading cause of cancer in women
– 8th leading cause of cancer death
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4. • Management
– 75% stage I at diagnosis
– TAH + BSO + Staging lymphadenectomy
– Patients with more advanced disease typically require
postoperative combination chemotherapy,
radiotherapy, or both.
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5. • Risk Factor (An excessive estrogen environment)
– Advanced maternal age
• 60 years average age at diagnosis, 70 years the
incidence peaks
– Obesity
– Low parity
– Unopposed estrogen therapy
– Menstrual and reproductive factors
– Environment
– Family history
– Tamoxifen use
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6. • Obesity
– Excessive adipose tissue leads to aromatization of
androstenedione to estrone
– Excessive estrone leads to negative feedback inhibition
of HPO axis resulting oligo-anovulation
– Oligo-anovulation resutls in continuos estrogen
exposure without subsequent progestational effect
without menstrual withdrawal bleeding
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7. • Unopposed estrogen therapy
– Its effect recognized 3 decades a go
– Now estrogen alone not given to women with uterus
– For women with uterus estrogen and progesterone is
being given
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8. • Menstrual and reproductive factors
– Anoovulation and uninterrupted menstrual cycles
– Early age at menarche or late age of menopause
– PCOS
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9. • Environment
– Western women have higher chance of having
endometrial cancer than their black counter parts
• Animal fat
• Obesity
• Low parity
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10. • Age
– Less than 40 years: 5%
– Age > 55 years: 80%
– Average age at diagnosis: 60 years
– Age incidence peaks: 70 years
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11. • Family history
– Endometrial Ca is the most common extracolonic
manifestation of HNPCC
– “Sentinel cancer” for HNPCC
– Carries 40-60% risk
– More than colorectal cancer
– But only 5% of endometiral cancers are due to
HNPCC
– Slight risk of BRCA1 and BRCA2 carriers due to
frequent tamoxifen treatment
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12. • Tamoxifen use
– Unopposed estrogen use
– 2-3 fold higher risk
– In postmenopausal women
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13. • Coexisting diseases which are sequelae of obesity and
chronic estrogen exposure
– DM
– HTN
– Gallbladder disease
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14. • Protective Factors
– COC and Mirena users
• 1 year use: decrease risk by 30-50%
• Risk reduction extends for 10-20 years
• The progestin component has a chemopreventive
biologic effect on endometrial cancer
– Smoking
• Reduced levels of circulating estrogens through
weight reduction,
• An earlier age at menopause, and
• Altered hormonal metabolism
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15. Endometrial Hyperplasia
• The only known direct precursor of invasive disease
• Endometrial hyperplasia is defined as endometrial
thickening with a proliferation of irregularly sized and
shaped glands and an increased gland-to-stroma ratio
• In the absence of such thickening, lesions are best
designated as disorderly proliferative endometrium or
focal glandular crowding
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16. • World Health Organization Classification of Endometrial
Hyperplasia
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17. • Classification based on
– Glandular crowding
– Ratio of gland to stroma > 1
– Nuclear atypia
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18. • Endometrial intraepithelial neoplasia (EIN)
– Using this system, anovulatory or prolonged estrogen-
exposed endometria without atypia are generally
designated as endometrial hyperplasias
• Polyclonal diffusely responding to hormone
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19. – In contrast, endometrial intraepithelial neoplasia
(monoclonal intrinsically proliferating) is used to
describe all endometria delineated as premalignant by
a combination of three morphometric features that
reflect
• Glandular volume,
• Architectural complexity, and
• Cytologic abnormality
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20. • Clinical Features
– 2/3rd present with postmenopausal bleeding
– Thickened endometrium (>10 mm)
• Warrants biopsy
– Endometrium <5 mm
• Bleeding secondary to endometrial atrophy
– Features of the endometrium
– Adnexal mass
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21. • The following are not indicated
– Further work up for premenopausal women who have
endometrial thickness < 10 mm with AUB
– Hysteroscopy
• Hyperplastic endometrium is not distinctive so
hysteroscopy is inaccurate
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22. • Endometrial abnormal echostructural changes on
sonography
– Cystic endometrial changes suggest polyps,
– Homogeneously thickened endometrium may indicate
hyperplasia, and
– A heterogeneous structural pattern is suspicious for
malignancy
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24. • Occasionally, an adnexal mass may be palpable on
examination
– Most likely is a benign ovarian cyst,
– Any solid features noted during transvaginal
sonography should raise the possibility of a coexisting
ovarian granulosa cell tumor
– These tumors produce an excessive estrogenic
environment that results in up to a 30-percent risk of
endometrial hyperplasia or less commonly, carcinoma
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25. • Management
– Depends on
• Patient’s age
• Presence or absence of cytologic atypia
• Risks for surgery
– Option relies on clinical judgment
– Options
• Surgical
• Nonsurgical
– Inherently risky
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26. • Nonatypical endometrial hyperplasia
– Premenopausal
• Provera  given orally for 12 to 14 days each
month at a dose of 10 to 20 mg daily
• Mirena
• COC
– Menopausal
• Be sure first!
• Annual endometrial biopsy follow up
• Low dose provera: 2.5 mg daily regimen
• Simple hyperplasia: Follow without treatment
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27. • Indications for biopsy
– New bleeding after treatment
– Postmenopausal women
• Pipelle sampling  usually sufficient sample is not
obtained through this method
• D & C
• Biopsy can be taken with IUD in-situ
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28. • Response of nonatypical hyperplasia to progestins
– Exceed 90%
– Persistent disease: shift to high dose regimen
• MPA: 40 – 100 mg daily
• Megestrol acetate (Megace) : 160 mg daily
– Hysterectomy for refractory cases
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29. • Atypical Endometrial Hyperplasia
– High dose progestin therapy
• Highly motivated patients who does not compelete
their family size
• Unfit for surgical removal
– Hyterectomy
• Main stay
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30. Endometrial Cancer
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31. • Prevention
– No screening needed for low risk women
– For high risk women
• Screening starting at 35 years
• Prophylactic hysterectomy
– +BSO  10-12% of life time risk of ovarian Ca
– Criteria for screening
• Colorectal or other Lynch syndrome-associated
cancers in three first-degree relatives, occurring in at
least two successive generations, and in one
individual under the age of 50 years
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32. • Lynch syndrome cancers include
– Colon,
– Endometrium,
– Small bowel,
– Renal pelvis and ureter, and
– Ovary, among others
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33. • Diagnosis
– Historically
• Irregular vaginal bleeding
• Abnormal vaginal discharge
• Pelvic pressure and pain in advanced cases
• Signs and symptoms of advanced disease
– Pap smear  Not sensitive
– Endometrial sampling
– Lab workup
– Imaging studies
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34. • Pap smear
– Sensitivity 50%
– Three possible findings
• Normal
• Benign endometrial cells
• Atypical glandular cells  concerning
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35. • Endometrial sampling
– Office Pipelle biopsy
– D & C
– Outpatient hysteroscopy not sensitive for hyperplasia
and may increase risk of peritoneal contamination
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36. • Lab
– CA-125
• The only lab work up which is helpful
• Preoperatively, an elevated level indicates the
possibility of more advanced disease
• It is most useful in patients with advanced disease
or serous subtypes to assist in monitoring response
to therapy or during posttreatment surveillance
• However, even in this setting, its utility in
the absence of other clinical findings is limited
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37. • Imaging
– Chest x-ray
– CT (to see advanced disease) and MRI (to see origin)
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38. • Role of the generalist
– Grade 1 type I  Hysterectomy
– Consultations
• Preoperative consultations for advanced disease
• Intraoperative consultations for cancers extending
to the cervix
• Postoperative consultations for hysteroectomy
done for other indications and biopsy proving
endometrial cancer
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39. • Histopathologic Criteria for Assessing Grade
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40. • In addition to percent of solid growth nuclear atypia
raises the grade by 1
• The simplicity of dividing tumors into low-grade lesions
and high grade lesions based on the proportion of solid
growth ( ≤50 percent or >50 percent, respectively) is
attractive and appears to have value
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41. • World Health
Organization
Histologic
Classification
of
Endometrial
Carcinoma
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42. • Endometroid adenocarcinoma
– The most common (75% of cases)
• Hyperplastic endometrium  low grade
• If glandular component decreases and
endometrium is atrophic  high grade
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43. • Serous carcinoma
– 5-10%
– Highly aggressive, even the mixed ones
– Commonly referred to as uterine papillary serous
carcinoma (UPSC), its histologic appearance resembles
epithelial ovarian cancer, and psammoma bodies are
seen in 30 percent of cases
– Exophytic
– Omental caking
– Secrete CA-125
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44. • Clear cell carcinoma
– < 5%
– High aggressive
– Poor prognosis
– Microscopically it can be
• Solid
• Cystic
• Papillary or
• Tubular
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45. • Mucinous carcinoma
– 1-2%
– Almost all are stage I grade 1 lesions with a good
prognosis
– The main diagnostic dilemma is differentiating this
tumor from a primary cervical adenocarcinoma
– Immunostaining may be helpful, but MR imaging may
be required to further clarify the most likely site of
origin
– For defining anatomy, MR imaging tool offers superior
contrast resolution at soft-tissue interfaces
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46. • Mixed Carcinoma
– An endometrial cancer may demonstrate combinations
of two or more pure types
– To be classified as a mixed carcinoma, a component
must comprise at least 10 percent of the tumor
– Except for serous and clear cell histology, the
combination of other types usually has no clinical
significance
– As a result, mixed carcinoma usually refers to an
admixture of a type I (endometrioid adenocarcinoma
and its variants) and a type II carcinoma
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47. • Undifferentiated Carcinoma
– In 1 to 2 percent of endometrial cancers, there is no
evidence of glandular, sarcomatous, or squamous
differentiation
– These undifferentiated tumors are characterized by
proliferation of medium-sized, monotonous epithelial
cells growing in solid sheets with no specific pattern
– Overall, the prognosis is worse than in patients
with poorly differentiated endometrioid
adenocarcinomas
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48. • Rare Histologic Types
– Fewer than 100 cases of squamous cell carcinoma of
the endometrium have been reported
– Diagnosis requires exclusion of an adenocarcinoma
component and no connection with the squamous
epithelium of the cervix
– Typically, the prognosis is poor
– Transitional cell carcinoma of the endometrium is also
rare, and metastatic disease from the bladder or ovary
must be excluded during diagnosis
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49. • Pathology
– Degree of differentiation is important
– Tumors that arise following pelvic radiation
• High stage
• High grade
• High risk histologic subtype
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50. • Type II serous and clear cell carcinomas have a particular
propensity for extrauterine disease, in a pattern that
closely resembles epithelial ovarian cancer
• Patterns of Spread (for type I endometrioid tumors)
– Direct extension
– Lymphatic metastasis
– Hematogenous dissemination, and
– Intraperitoneal exfoliation
• In general, the various patterns of spread are interrelated
and often develop simultaneously
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51. • Lymphatic spread
– Haphazard
– No pattern identified
• Hematogenous
– Lung and less commonly liver , brain and bone
• Retrograde transtubal and serosal perforation
– Mechanisims by which malignant cells reach the
peritoneal cavity
• Port-site metastatis
– After laparascopy
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52. • Treatment
– TAH + BSO
– Extrafacial or type I hysterectomy is sufficient for early
diseases
– Type III hysterectomy may be required if there is
cervical extension
– TVH with or without BSO is an option in selected
cases
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53. • Steps of surgical staging
– Vertical abdominal incision is preferred
– Collect ascites upon entry or peritoneal washing with
50-100 mL of saline
– Systematic exploration
– Hysteroectomy with BSO
– Frozen dissection
– Pelvic and para-aortic lymphadenectomy
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54. • Contraindications for surgery
– A desire to preserve fertility,
– Massive obesity,
– High operative risk, and
– Clinically unresectable disease
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55. FIGO Staging of Carcinoma of the Endometrium
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57. Saturday, January 7,
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58. Distribution of Endometrial Cancer by FIGO Stage (n
5281 patients)
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59. – Surveillance
• Pelvic examination every 3 to 4 months for the first
2 years and twice yearly for an additional 3 years
before returning to annual visits
• Pap tests are not a mandatory part of surveillance
since they identify an asymptomatic vaginal
recurrence in less than 1 percent of patients and are
not cost effective
• Women who have more advanced disease that
requires postoperative radiation or chemotherapy
or both warrant more aggressive monitoring.
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60. • Serum CA-125 measurements may be valuable,
particularly for UPSC
• Intermittent imaging using CT scanning or MR
imaging may also be indicated
• In general, the pattern of recurrent disease depends
on the original sites of metastasis and the treatment
received
– Chemotherapy (Primary, Adjuvant)
– Radiotherapy (Primary, Adjuvant)
– Hormonal (Primary, Adjuvant)
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61. • Chemotherapy
– Paclitaxel (Taxol), doxorubicin (Adriamycin), and
cisplatin (TAP) chemotherapy is the adjuvant
treatment of choice for advanced endometrial cancer
following surgery
– In practice, cytotoxic chemotherapy is frequently
combined, sequenced, or sandwiched with
radiotherapy in patients with advanced endometrial
cancer following surgery
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62. • Radiation therapy
– Primary radiation
• Poor surgical candidates
• Intracavitary brachytherapy such as Heyman
capsules
• 10-15% less success than surgical management
– Adjuvant
• Controversial for early stage disease
• Indicated for advanced disease
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63. • Hormonal therapy
– Primary treatment
• For excessively high operative risk
• Should be used with caution
– Adjuvant
• Tamoxifen modulates the expression of the
progesterone receptor and is postulated to thereby
improve progestin therapy efficacy
• Clinically, high response rates have been noted with
tamoxifen used adjunctively with progestin therapy
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64. • Fertility sparing management
– Hormonal therapy without hysterectomy is an option
in carefully selected young women with endometrial
cancer who desperately wish to preserve their fertility
– ART may be required
– High dose progestin
– 3-4 months D &C biopsy follow up
– Delivery of healthy infant is the expectation
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65. Poor Prognostic Variables in Endometrial Cancer
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66. • Relapse
– Site of relapse is the most important factor
– If not previously irradiated  good prognosis
– Vaginal relapse is curable
– Combinations of options available
– Palliation may be the goal for some of the patients
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67. References
1. Barbara L. Hoffman, et al., Williams Gynecology 2ed
2012: The McGraw-Hill Companies, Inc.
2. James R. Scott, 2008. Danforth’s Obstetrics and
Gynecology, 9th edition
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68. Saturday, January 7,
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69. Thank you for listening!
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