Endometrial Cancer
Endometrial cancer (Em. ca.)
1. Epidemiology and risk factor
1) 2 types of Em. ca.
¨ç estrogen-dependent tumor
- younger, perimenopausal woman
- hyperplastic Em. ¡æ Em. ca.
- better differentiated, more favorable prognosis
¨è estrogen-independent tumor
- older, postmeopausal, thin woman
- atrophic Em. ¡æ Em. ca.
- less differentiated, poorer prognosis
2) Risk factors (prolonged, unopposed estrogen stimulation of the Em.)
¨ç nullinparous woman
¨è infertility & Hx of irregular menses d/t anovulatory cycles
¨é menopause ¡Ã 52 y.o.
¨ê obesity : excess estrone as a result of peripheral conversion of adrenally derived ADD by aromatization in fat
¨ë PCOS & functioning ovarian tumors
¨ì estrogen replacement therapy (ERT) without progestin
¨í antiestrogen tamoxifen for treatment of breast ca.
¨î 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
¨ç abnormal uterine bleeding
¨è estrogen-producing ovarian tumors
¨é ERT
¨ê endometrial ca.
3) classification of Em. hyperplasia
¨ç simple hyperplasia
- dilated or cystic glands with round to slightly irregular shapes
- ¡è glandular-to-stromal ratio without glandular crowding
- no cytologic atypia
¨è complex hyperplasia
- architecturally complex : budding and infolding
- crowded glands with less intervening stroma without atypia
- no cytologic atypia
¨é atypical hyperplasia
- cytologic atypia (can be categorized as simple or complex)
- large nuclei of variable size and shape, ¡èN/C ratio, irregular clumped chromatin with parachromatic clearing, loss of polarity, prominent nucleoli
¨ê 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
¨ç Em. hyperplasia w/o atypia
- cyclical progestin therapy (medroxyprogesterone acetate 10~20mg/d for 14d/mo.)
- continuous progestin therapy (megestrol acetate 20~40mg daily)
¨è em. hyperplasia with atypia
- continuous progestin therapy (mesestrol acetate 40mg daily)
¨é F/U : periodic endometrial Bx, transvaginal US
5) Em. ca. screening (´ëºÎºÐ screeningÀ¸·Î¼ Å« ÀÇ¹Ì ¾øÀ½)
¨ç routine Pap smear, Em. cytologic assessment : low sensitivity and low specificity
¨è TVUS of uterus & Em. Bx.
¨é 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
¨ç È£¹ß¿¬·É : 50~60ÓÛ (average age : 60¼¼, >50¼¼ ÀÌ»óÀÌ 75%)
¨è cardinal symptom : vaginal bleeding or discharge (¾à 90% of pt.)
¨é ±âŸ
- pelvic pressure or discomfort : indicative of uterine enlargement or extrauterine spread
- hematometra, pyometra ¡æ purulent V/D & poor prognosis
¨ê 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
¨ë 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%)
¨ì premenopausal bleeding
- abnormal bleeding
: menometrorrhagia, oligomenorrhea, cyclical bleeding that continues past the usual age of menopause
2) signs (ÁÖ·Î metastasis ¿©ºÎ¸¦ ¾Ë¾Æº¸±â À§ÇÑ °Ë»ç)
¨ç peripheral LN, breast
¨è abdominal examination : ascites, hepatic or omental meta È®ÀÎ
¨é 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
¨ç endometrial aspiration biopsy : the first step in evaluating a patient with abnormal uterine bleeding or suspected endometrial pathology (Áø´Ü·üÀÌ 90~90%¿¡ À̸§)
¨è Pap test : unreliable diagnostic test
¨é hyteroscopy and DCB : cervical stenosis or low patient tolerance to aspiration biopsy ½Ã ½ÃÇà
¨ê TVUS
a. a useful adjunct to endometrial biopsy for evaluating abnormal uterine bleeding and selecting patients for additional testing
b. F/E ÇÊ¿äÇÑ °æ¿ì
- endometrial thickness (¡Ã5cm)
- a polypoid endometrial mass
- a collection of fluid within the uterus
4) pathology
¨ç Endometrioid adenocarcinoa
a. ¾à 80%ÀÇ endometrial carcinoma
b. FIGO Definition for Grading of Endometrial Carcinoma
¨è 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
¨é papillary serous carcinoma
- approximately 3~4% of endometrial carcinomas resemble serous carcinoma of the ovary and fallopian tuve
- aggressive nature and poor prognosis
¨ê clear cell carcinoma
- clear cell carcinoma accounts for less than 5% of all endometrial carcinomas
- papillary serous carcinoma¿Í ºñ½ÁÇϰųª ¾à°£ ´õ ³ª»Û ¿¹Èĸ¦ º¸ÀÓ (overall survival rate : 30~64%)
¨ë squamous carcinoma
- squamous carcinoma of the endometrium is rare
- cervial stenosis, chronic inflammation, pyometra µ¿¹ÝµÇ´Â °æ¿ì ¸¹À½
- poor prognosis (36% survival rate in clinical stage I disease)
5) simultaneous tumors of the endometrium and ovary
¨ç synchronous endometrial and ovarian cancer are the most frequent simultaneously occurring genital malignancies
(incidence : 1.4~3.8%)
¨è most commonly, both tumors are well-differentiated endometrioid adenocarcinomas of low stage that have an excellent prognosis
¨é ¾à 29%ÀÇ endometrioid ovarian adenocarcinoma´Â endometrial cancer¿Í °ü·Ã ÀÖÀ½
¨ê metastasisÀÎÁö double primary ÀÎÁö ¾Ë¾Æº¸±â À§ÇØ immunohistochemistry, flow cytometry, molecular study ÇÊ¿ä
6) pretreatment evaluation
¨ç complete history taking and physical examination
¨è CBC, blood chemistry (esp. LFT, RFT), blood type and screen, urinalysis
¨é chest x-ray, EKG
¨ê CA125 : advanced or metastatic endometiral cancer pt.¿¡¼ »ó½ÂµÇ¾î ÀÖÀ½
¨ë cystoscopy, sigmoidoscopy, IVP, barium enema, A-P CT´Â ȯÀÚÀÇ Áõ»ó, ¡ÈÄ, lab ¼Ò°ß¿¡¼ ÀÌ»ó ¼Ò°ß ÀÖÀ» ½Ã ½ÃÇà
7) clinical staging
8) surgical staging
¨ç 1971 FIGO Clinical staging for Endometrial Carcinoma
¨è 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 ¡Ã 1/2
- isthmus-cervix extension
- tumor size > 2cm
- extrauterine disease
¨é Prognostic variables in endometrial carcinoma
9) treatment
¨ç stage I & stage IIa disease
a. TAH & BSO (explo-lapa) : ¼ö¼ú °¡´ÉÇÑ ¸ðµç ȯÀÚ¿¡¼ TAH & BSO ½ÃÇà
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
¨è 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)
¨é 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
¨ç recurrent and metastasis
a. Ãʱâ Àڱ󻸷¾ÏÀ¸·Î Ä¡·á¹ÞÀº ȯÀÚÀÇ ¾à 1/4¿¡¼ Àç¹ß
b. Àç¹ß ºÎÀ§
- vaginal wall (33%)
- pelvis (20%)
- lung (17%)
- lymph node (2%)
¨è treatment : surgery, radiation therapy, chemotherapy µîÀÇ ´Ù¾çÇÑ modality¸¦ ÀÌ¿ëÇÒ ¼ö ÀÖÀ¸³ª, hormone therapy Ä¡·á°¡ »ó´ëÀûÀ¸·Î Áß¿äÇÔ
¨é Ä¡·áÈÄ È£¸£¸ó º¸Ãæ¿ä¹ý
a. Àڱ󻸷¾Ï ȯÀÚ¿¡¼ Ä¡·á ÈÄ HRT´Â ¿¹ÈÄ¿¡ ¿µÇâÀ» ÁÖÁö ¾ÊÀ½
b. HRTÀÇ ½ÃÀÛ ½Ã±â´Â ¼ö¼úÀ» ½ÃÇàÇϰí 1~3³â ÈÄ¿¡ ½ÃÇàÇÏ´Â °ÍÀÌ ¹Ù¶÷Á÷ÇÔ
c. Åõ¿© ¹æ¹ý : progesteroneÀ» Æ÷ÇÔÇÑ º´ÇÕÁö¼Ó¿ë¹ýÀÌ ±ÇÀåµÊ
1. Epidemiology and risk factor
1) 2 types of Em. ca.
¨ç estrogen-dependent tumor
- younger, perimenopausal woman
- hyperplastic Em. ¡æ Em. ca.
- better differentiated, more favorable prognosis
¨è estrogen-independent tumor
- older, postmeopausal, thin woman
- atrophic Em. ¡æ Em. ca.
- less differentiated, poorer prognosis
2) Risk factors (prolonged, unopposed estrogen stimulation of the Em.)
¨ç nullinparous woman
¨è infertility & Hx of irregular menses d/t anovulatory cycles
¨é menopause ¡Ã 52 y.o.
¨ê obesity : excess estrone as a result of peripheral conversion of adrenally derived ADD by aromatization in fat
¨ë PCOS & functioning ovarian tumors
¨ì estrogen replacement therapy (ERT) without progestin
¨í antiestrogen tamoxifen for treatment of breast ca.
¨î 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
¨ç abnormal uterine bleeding
¨è estrogen-producing ovarian tumors
¨é ERT
¨ê endometrial ca.
3) classification of Em. hyperplasia
¨ç simple hyperplasia
- dilated or cystic glands with round to slightly irregular shapes
- ¡è glandular-to-stromal ratio without glandular crowding
- no cytologic atypia
¨è complex hyperplasia
- architecturally complex : budding and infolding
- crowded glands with less intervening stroma without atypia
- no cytologic atypia
¨é atypical hyperplasia
- cytologic atypia (can be categorized as simple or complex)
- large nuclei of variable size and shape, ¡èN/C ratio, irregular clumped chromatin with parachromatic clearing, loss of polarity, prominent nucleoli
¨ê 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
¨ç Em. hyperplasia w/o atypia
- cyclical progestin therapy (medroxyprogesterone acetate 10~20mg/d for 14d/mo.)
- continuous progestin therapy (megestrol acetate 20~40mg daily)
¨è em. hyperplasia with atypia
- continuous progestin therapy (mesestrol acetate 40mg daily)
¨é F/U : periodic endometrial Bx, transvaginal US
5) Em. ca. screening (´ëºÎºÐ screeningÀ¸·Î¼ Å« ÀÇ¹Ì ¾øÀ½)
¨ç routine Pap smear, Em. cytologic assessment : low sensitivity and low specificity
¨è TVUS of uterus & Em. Bx.
¨é 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
¨ç È£¹ß¿¬·É : 50~60ÓÛ (average age : 60¼¼, >50¼¼ ÀÌ»óÀÌ 75%)
¨è cardinal symptom : vaginal bleeding or discharge (¾à 90% of pt.)
¨é ±âŸ
- pelvic pressure or discomfort : indicative of uterine enlargement or extrauterine spread
- hematometra, pyometra ¡æ purulent V/D & poor prognosis
¨ê 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
¨ë 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%)
¨ì premenopausal bleeding
- abnormal bleeding
: menometrorrhagia, oligomenorrhea, cyclical bleeding that continues past the usual age of menopause
2) signs (ÁÖ·Î metastasis ¿©ºÎ¸¦ ¾Ë¾Æº¸±â À§ÇÑ °Ë»ç)
¨ç peripheral LN, breast
¨è abdominal examination : ascites, hepatic or omental meta È®ÀÎ
¨é 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
¨ç endometrial aspiration biopsy : the first step in evaluating a patient with abnormal uterine bleeding or suspected endometrial pathology (Áø´Ü·üÀÌ 90~90%¿¡ À̸§)
¨è Pap test : unreliable diagnostic test
¨é hyteroscopy and DCB : cervical stenosis or low patient tolerance to aspiration biopsy ½Ã ½ÃÇà
¨ê TVUS
a. a useful adjunct to endometrial biopsy for evaluating abnormal uterine bleeding and selecting patients for additional testing
b. F/E ÇÊ¿äÇÑ °æ¿ì
- endometrial thickness (¡Ã5cm)
- a polypoid endometrial mass
- a collection of fluid within the uterus
4) pathology
¨ç Endometrioid adenocarcinoa
a. ¾à 80%ÀÇ endometrial carcinoma
b. FIGO Definition for Grading of Endometrial Carcinoma
¨è 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
¨é papillary serous carcinoma
- approximately 3~4% of endometrial carcinomas resemble serous carcinoma of the ovary and fallopian tuve
- aggressive nature and poor prognosis
¨ê clear cell carcinoma
- clear cell carcinoma accounts for less than 5% of all endometrial carcinomas
- papillary serous carcinoma¿Í ºñ½ÁÇϰųª ¾à°£ ´õ ³ª»Û ¿¹Èĸ¦ º¸ÀÓ (overall survival rate : 30~64%)
¨ë squamous carcinoma
- squamous carcinoma of the endometrium is rare
- cervial stenosis, chronic inflammation, pyometra µ¿¹ÝµÇ´Â °æ¿ì ¸¹À½
- poor prognosis (36% survival rate in clinical stage I disease)
5) simultaneous tumors of the endometrium and ovary
¨ç synchronous endometrial and ovarian cancer are the most frequent simultaneously occurring genital malignancies
(incidence : 1.4~3.8%)
¨è most commonly, both tumors are well-differentiated endometrioid adenocarcinomas of low stage that have an excellent prognosis
¨é ¾à 29%ÀÇ endometrioid ovarian adenocarcinoma´Â endometrial cancer¿Í °ü·Ã ÀÖÀ½
¨ê metastasisÀÎÁö double primary ÀÎÁö ¾Ë¾Æº¸±â À§ÇØ immunohistochemistry, flow cytometry, molecular study ÇÊ¿ä
6) pretreatment evaluation
¨ç complete history taking and physical examination
¨è CBC, blood chemistry (esp. LFT, RFT), blood type and screen, urinalysis
¨é chest x-ray, EKG
¨ê CA125 : advanced or metastatic endometiral cancer pt.¿¡¼ »ó½ÂµÇ¾î ÀÖÀ½
¨ë cystoscopy, sigmoidoscopy, IVP, barium enema, A-P CT´Â ȯÀÚÀÇ Áõ»ó, ¡ÈÄ, lab ¼Ò°ß¿¡¼ ÀÌ»ó ¼Ò°ß ÀÖÀ» ½Ã ½ÃÇà
7) clinical staging
8) surgical staging
¨ç 1971 FIGO Clinical staging for Endometrial Carcinoma
¨è 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 ¡Ã 1/2
- isthmus-cervix extension
- tumor size > 2cm
- extrauterine disease
¨é Prognostic variables in endometrial carcinoma
9) treatment
¨ç stage I & stage IIa disease
a. TAH & BSO (explo-lapa) : ¼ö¼ú °¡´ÉÇÑ ¸ðµç ȯÀÚ¿¡¼ TAH & BSO ½ÃÇà
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
¨è 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)
¨é 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
¨ç recurrent and metastasis
a. Ãʱâ Àڱ󻸷¾ÏÀ¸·Î Ä¡·á¹ÞÀº ȯÀÚÀÇ ¾à 1/4¿¡¼ Àç¹ß
b. Àç¹ß ºÎÀ§
- vaginal wall (33%)
- pelvis (20%)
- lung (17%)
- lymph node (2%)
¨è treatment : surgery, radiation therapy, chemotherapy µîÀÇ ´Ù¾çÇÑ modality¸¦ ÀÌ¿ëÇÒ ¼ö ÀÖÀ¸³ª, hormone therapy Ä¡·á°¡ »ó´ëÀûÀ¸·Î Áß¿äÇÔ
¨é Ä¡·áÈÄ È£¸£¸ó º¸Ãæ¿ä¹ý
a. Àڱ󻸷¾Ï ȯÀÚ¿¡¼ Ä¡·á ÈÄ HRT´Â ¿¹ÈÄ¿¡ ¿µÇâÀ» ÁÖÁö ¾ÊÀ½
b. HRTÀÇ ½ÃÀÛ ½Ã±â´Â ¼ö¼úÀ» ½ÃÇàÇϰí 1~3³â ÈÄ¿¡ ½ÃÇàÇÏ´Â °ÍÀÌ ¹Ù¶÷Á÷ÇÔ
c. Åõ¿© ¹æ¹ý : progesteroneÀ» Æ÷ÇÔÇÑ º´ÇÕÁö¼Ó¿ë¹ýÀÌ ±ÇÀåµÊ