Endometrial Cancer

Endometrial cancer (Em. ca.)

1. Epidemiology and risk factor
1) 2 types of Em. ca.
① estrogen-dependent tumor
- younger, perimenopausal woman
- hyperplastic Em. → Em. ca.
- better differentiated, more favorable prognosis
② estrogen-independent tumor
- older, postmeopausal, thin woman
- atrophic Em. → Em. ca.
- less differentiated, poorer prognosis

2) Risk factors (prolonged, unopposed estrogen stimulation of the Em.)
① nullinparous woman
② infertility & Hx of irregular menses d/t anovulatory cycles
③ menopause ≥ 52 y.o.
④ obesity : excess estrone as a result of peripheral conversion of adrenally derived ADD by aromatization in fat
⑤ PCOS & functioning ovarian tumors
⑥ estrogen replacement therapy (ERT) without progestin
⑦ antiestrogen tamoxifen for treatment of breast ca.
⑧ others : DM, HTN, hypothyroidism

2. Endometrial hyperplasia
1) setting : proliferative endometrum as a result of protracted estrogen stimulation in the absence of progestin influence
2) clinical importance
① abnormal uterine bleeding
② estrogen-producing ovarian tumors
④ endometrial ca.
3) classification of Em. hyperplasia
① simple hyperplasia
- dilated or cystic glands with round to slightly irregular shapes
- ↑ glandular-to-stromal ratio without glandular crowding
- no cytologic atypia
② complex hyperplasia
- architecturally complex : budding and infolding
- crowded glands with less intervening stroma without atypia
- no cytologic atypia
③ atypical hyperplasia
- cytologic atypia (can be categorized as simple or complex)
- large nuclei of variable size and shape, ↑N/C ratio, irregular clumped chromatin with parachromatic clearing, loss of polarity, prominent nucleoli
④ classification of endometrial hypeplasia

4) progestin therapy is very effective in reversing endometrial hyperplasia w/o atypia but less effective for Em. hyperplasia with atypia
① Em. hyperplasia w/o atypia
- cyclical progestin therapy (medroxyprogesterone acetate 10~20mg/d for 14d/mo.)
- continuous progestin therapy (megestrol acetate 20~40mg daily)
② em. hyperplasia with atypia
- continuous progestin therapy (mesestrol acetate 40mg daily)
③ F/U : periodic endometrial Bx, transvaginal US

5) Em. ca. screening (대부분 screening으로서 큰 의미 없음)
① routine Pap smear, Em. cytologic assessment : low sensitivity and low specificity
② TVUS of uterus & Em. Bx.
③ most Em. ca. pt. present with abnormal perimenopausal or postmenopausal uterine bleeding early in the development of disease, when the tumor is still confined to the uterus

3. Endometrial cancer
1) symptom
① 호발연령 : 50~60代 (average age : 60세, >50세 이상이 75%)
② cardinal symptom : vaginal bleeding or discharge (약 90% of pt.)
③ 기타
- pelvic pressure or discomfort : indicative of uterine enlargement or extrauterine spread
- hematometra, pyometra → purulent V/D & poor prognosis
④ asymptomatic (<5%)
- investigation of abnormal Pap test
: malignant cells on Pap test are more likely to have a more advanced stage of disease
- discovery of cancer in a uterine removed for some other reasons
- evaluation of an abnormal finding on a pelvic US or CT scan
⑤ DDx. of postmenopausal bleeding
a. endometrial atrophy (60~80%)
b. ERT (15~25%)
c. endometrial polyp (2~12%)
d. endometrial hyperplasia (5~10%) : the source of excess estrogen should be considered
e. endometrial cancer (10%)
⑥ premenopausal bleeding
- abnormal bleeding
: menometrorrhagia, oligomenorrhea, cyclical bleeding that continues past the usual age of menopause

2) signs (주로 metastasis 여부를 알아보기 위한 검사)
① peripheral LN, breast
② abdominal examination : ascites, hepatic or omental meta 확인
③ gynecologic exam : vaginal introitus, suburethral area, entire vagina, cervix, bimanual examination
(uterus for size & mobility, adnexa for masses, parametria for induration, cul-de-sac for nodularity)
3) diagnosis
① endometrial aspiration biopsy : the first step in evaluating a patient with abnormal uterine bleeding or suspected endometrial pathology (진단률이 90~90%에 이름)
② Pap test : unreliable diagnostic test
③ hyteroscopy and DCB : cervical stenosis or low patient tolerance to aspiration biopsy 시 시행
a. a useful adjunct to endometrial biopsy for evaluating abnormal uterine bleeding and selecting patients for additional testing
b. F/E 필요한 경우
- endometrial thickness (≥5cm)
- a polypoid endometrial mass
- a collection of fluid within the uterus

4) pathology

① Endometrioid adenocarcinoa
a. 약 80%의 endometrial carcinoma
b. FIGO Definition for Grading of Endometrial Carcinoma

② mucinous carcinoma
- approximately 5% of endometrial carcinomas have a predominant mucinous pattern in with more than 50% of the tumor is composed of cells with intracytoplasmic mucin
- good prognosis
③ papillary serous carcinoma
- approximately 3~4% of endometrial carcinomas resemble serous carcinoma of the ovary and fallopian tuve
- aggressive nature and poor prognosis
④ clear cell carcinoma
- clear cell carcinoma accounts for less than 5% of all endometrial carcinomas
- papillary serous carcinoma와 비슷하거나 약간 더 나쁜 예후를 보임 (overall survival rate : 30~64%)
⑤ squamous carcinoma
- squamous carcinoma of the endometrium is rare
- cervial stenosis, chronic inflammation, pyometra 동반되는 경우 많음
- poor prognosis (36% survival rate in clinical stage I disease)

5) simultaneous tumors of the endometrium and ovary
① synchronous endometrial and ovarian cancer are the most frequent simultaneously occurring genital malignancies
(incidence : 1.4~3.8%)
② most commonly, both tumors are well-differentiated endometrioid adenocarcinomas of low stage that have an excellent prognosis
③ 약 29%의 endometrioid ovarian adenocarcinoma는 endometrial cancer와 관련 있음
④ metastasis인지 double primary 인지 알아보기 위해 immunohistochemistry, flow cytometry, molecular study 필요

6) pretreatment evaluation
① complete history taking and physical examination
② CBC, blood chemistry (esp. LFT, RFT), blood type and screen, urinalysis
③ chest x-ray, EKG
④ CA125 : advanced or metastatic endometiral cancer pt.에서 상승되어 있음
⑤ cystoscopy, sigmoidoscopy, IVP, barium enema, A-P CT는 환자의 증상, 징후, lab 소견에서 이상 소견 있을 시 시행

7) clinical staging

8) surgical staging
① 1971 FIGO Clinical staging for Endometrial Carcinoma

② Indications for selective pelvic and para-aortic lymph node dissection in endometrial cancer
- tumor histology : clear cell, serous papillary, squamous or grade 3 endometrioid
- myometrial invasion ≥ 1/2
- isthmus-cervix extension
- tumor size > 2cm
- extrauterine disease

③ Prognostic variables in endometrial carcinoma

9) treatment
① stage I & stage IIa disease
a. TAH & BSO (explo-lapa) : 수술 가능한 모든 환자에서 TAH & BSO 시행
b. vaginal hysterectomy
c. laparoscopic management
d. radical hysterectomy
e. radiation therapy
f. postoperative adjuvant therapy
g. oservation
h. vaginal vault irradiation
i. external pelvic irradiation
- external pelvic irradiation decreases the risk of recurrence of pelvic disease after hysterectomy in certain high-risk groups
- Ix

j. extended field irradiation
- Ix

k. whole abdomen irradiation
l. progestin
m. chemotherapy : cisplatin, doxorubicin, cyclophosphamide

② stage II disease (2 main approaches have usually been taken to the treatment of stage II disease)
a. Radiacal hysterectomy, BSO, and bilateral pelvic lymphadenectomy
b. Combined radiation and surgery (external pelvic irradiation and intracavitary radium or cesium followed in 6 weeks by TAH and BSO)

③ Clinical stages III and IV disease
a. stage III
- surgical eradication of all macroscopic disease should be the goal
- postoperative radiotherpay can then be tailored to the extent of disease
b. stage IV
- Treatment of stage IV disease depends on the individual patient but usually involves a combination of surgery, radiation therapy, and systemic hormonal therapy or chemotherapy

10) recurrent disease
① recurrent and metastasis
a. 초기 자궁내막암으로 치료받은 환자의 약 1/4에서 재발
b. 재발 부위
- vaginal wall (33%)
- pelvis (20%)
- lung (17%)
- lymph node (2%)
② treatment : surgery, radiation therapy, chemotherapy 등의 다양한 modality를 이용할 수 있으나, hormone therapy 치료가 상대적으로 중요함
③ 치료후 호르몬 보충요법
a. 자궁내막암 환자에서 치료 후 HRT는 예후에 영향을 주지 않음
b. HRT의 시작 시기는 수술을 시행하고 1~3년 후에 시행하는 것이 바람직함
c. 투여 방법 : progesterone을 포함한 병합지속용법이 권장됨