Gynecology 5th year, 7th lecture/part two (Dr. Sindus)

Premalignant and Premalignant and malignant disorders of the malignant disorders of the

uterine corpusuterine corpus

Most common malignant diseases affecting the uterus Most common malignant diseases affecting the uterus is endometrial carcinoma, which arises from the lining is endometrial carcinoma, which arises from the lining of the uterus. However, sarcoma also arise from the of the uterus. However, sarcoma also arise from the stroma of the endometrium or from the myometrium. stroma of the endometrium or from the myometrium.

Epidemiology :Epidemiology :• The median age of presentation is just over 60 years The median age of presentation is just over 60 years

of age, however it can occur in their 20s, but the vast of age, however it can occur in their 20s, but the vast majority of cases occur in women over 45 years of age.majority of cases occur in women over 45 years of age.

with less than with less than 55 ％％ diagnosed under diagnosed under 4040 years of age years of age．．

Highest incidence is in white north americans. Highest incidence is in white north americans.

Aetiology :Aetiology : The exact cause is unknown, however risk factors in The exact cause is unknown, however risk factors in

postmenapausal and premenapausal women include postmenapausal and premenapausal women include the following :the following :

1 1 –– Obesity. Obesity. 2 2 –– Impaired carbohydrate tolerance.Impaired carbohydrate tolerance. 3 3 –– Nulliparity. Nulliparity. 4 4 –– Late menopause.Late menopause. 5 5 –– Unopposed oestrogen therapy.Unopposed oestrogen therapy. 6 6 –– Functioning ovarian tumors.Functioning ovarian tumors. 7 7 –– Previous pelvic irradiation.Previous pelvic irradiation. 8 8 –– Sequential oral contraceptives with dimethisteroneSequential oral contraceptives with dimethisterone 9 9 –– Family history of carcinoma of breast, ovary or Family history of carcinoma of breast, ovary or

colon.colon. 10 10 –– Polycystic ovary disease.Polycystic ovary disease. 11 11 –– Tamoxifin therapy which has weak oestrogen Tamoxifin therapy which has weak oestrogen

effects on the endometriumeffects on the endometrium

* * Many of the factors are related to an increase in Many of the factors are related to an increase in oestrogen levels.oestrogen levels.

* * In post In post –– menopausal period, the majority of menopausal period, the majority of circulating oestrogen is derived from aromatization of circulating oestrogen is derived from aromatization of peripheral androgens. This conversion take place peripheral androgens. This conversion take place principally in adipose tissue. Also post principally in adipose tissue. Also post –– menopausal menopausal women with diabetes have increased oestrogen levels.women with diabetes have increased oestrogen levels.

* * Nulliparity and late menopause are both associated Nulliparity and late menopause are both associated with increased risk of endometrial cancers, which may with increased risk of endometrial cancers, which may be explained by the prolonged oestrogenic effect on the be explained by the prolonged oestrogenic effect on the endometrium.endometrium.

* * Women who use oral contraceptive or progesterone Women who use oral contraceptive or progesterone have up to a 50 % reduction in the incidence of have up to a 50 % reduction in the incidence of endometrial cancer and protection lasts for many years endometrial cancer and protection lasts for many years after the discontinuation of these treatments. Cigarette after the discontinuation of these treatments. Cigarette smoking has also been associated with the reduced risk smoking has also been associated with the reduced risk of endometrial cancer. of endometrial cancer.

There is no effective screening programmeThere is no effective screening programme，， but occasionally cervical smears contain but occasionally cervical smears contain endometrial cancer cells or double endometrial cancer cells or double thickness endometrial ultrasonic thickness thickness endometrial ultrasonic thickness of 4mm or more indicates a need for of 4mm or more indicates a need for

endometrial samplingendometrial sampling．．

Classification :Classification :

A A Endometrialhypeplasia :Endometrialhypeplasia :

Glandular hyperplasia of the endometrium are benign Glandular hyperplasia of the endometrium are benign conditions that may produce symptoms clinically conditions that may produce symptoms clinically indistinguishable from early endometrial carcinoma. indistinguishable from early endometrial carcinoma. Some of hyperplasias, even though reversible, are Some of hyperplasias, even though reversible, are considered premalignant lesions. Divided into:considered premalignant lesions. Divided into:

1/ 1/ Hyperplasia without atypia Hyperplasia without atypia

which is subdivided into either simple ( cystic ) which is subdivided into either simple ( cystic ) hyperplasia and complex ( adenomatous ) hyperplasia.hyperplasia and complex ( adenomatous ) hyperplasia.

2/ 2/ Hyperplasia with atypia, these hyperplasia are Hyperplasia with atypia, these hyperplasia are generally considered premalignant.generally considered premalignant.

3/ 3/ Carcinoma insitu Carcinoma insitu

BB Endometrial carcinoma : Endometrial carcinoma : Characterized by obvious hyperplasia and anaplasia of Characterized by obvious hyperplasia and anaplasia of

glandular element, with invasion of underlying stroma, glandular element, with invasion of underlying stroma, myometrium or vascular spaces. myometrium or vascular spaces.

* * Endometrial cancer can spread by 4 possible routs :Endometrial cancer can spread by 4 possible routs :1 1 –– Direct extension. Direct extension. 2 2 –– Lymphatic metastasis. Lymphatic metastasis.3 3 –– peritoneal implants after transtubal spread. peritoneal implants after transtubal spread.4 4 –– haematogenous spread. haematogenous spread.

* * Pathologist recognized 3 major histological types of Pathologist recognized 3 major histological types of endometrial carcinoma: endometrial carcinoma:

1 1 –– Adenocarcinoma. Adenocarcinoma. 2 2 –– Adenocarcinoma with squamous differentiation. Adenocarcinoma with squamous differentiation.3 3 –– Adenosquamous carcinoma. Adenosquamous carcinoma.

2003-10-272003-10-27 Carcinoma of the EndometriumCarcinoma of the Endometrium 88

All 3 types have identical presenting symptoms and All 3 types have identical presenting symptoms and signs, patterns of spread, and general clinical behavior.signs, patterns of spread, and general clinical behavior.

* * Papillary serous and clear cell carcinoma of the Papillary serous and clear cell carcinoma of the endometrium are other unusual histological subtypes endometrium are other unusual histological subtypes that carry a poor prognosis even when apparently that carry a poor prognosis even when apparently confined to the superficial myometrium. confined to the superficial myometrium.

Clinical presentation :Clinical presentation : 1 1 –– About 75 About 75 –– 80 % of women with endometrial 80 % of women with endometrial

carcinoma will present with carcinoma will present with postmenopausal bleedingpostmenopausal bleeding. . Sometimes bloody stain postmenopausal vaginal Sometimes bloody stain postmenopausal vaginal discharge may be associated with endometrial discharge may be associated with endometrial carcinoma.carcinoma.

2 2 –– In premenopausal period, most women with In premenopausal period, most women with endometrial carcinoma present with endometrial carcinoma present with intermenstrual intermenstrual bleedingbleeding. Although 1/3 may present with heavy . Although 1/3 may present with heavy periods only.periods only.

33 - - Postmenopausal discharge Postmenopausal discharge from pyometra from pyometra carries a 50carries a 50 ％ ％ risk of associated malignancyrisk of associated malignancy . .

44 – – Pain Pain may occur with pyometra or metastatic may occur with pyometra or metastatic spreadspread．．

Diagnosis :Diagnosis :

Traditionally, post menopausal bleeding was Traditionally, post menopausal bleeding was investigated by a dilatation and curettage.investigated by a dilatation and curettage.

Fractional curettage : dilatation and fractional Fractional curettage : dilatation and fractional curettage is the definitive procedure for diagnosis of curettage is the definitive procedure for diagnosis of endometrial carcinoma. It should be performed with the endometrial carcinoma. It should be performed with the patient under anesthesia and by first curetting the patient under anesthesia and by first curetting the endocervical canal followed by dilatation of the canal endocervical canal followed by dilatation of the canal and circumferential curettage of the endometrial cavity. and circumferential curettage of the endometrial cavity.

More recently diagnosis has shifted to outpatient More recently diagnosis has shifted to outpatient setting with :setting with :

a a –– Pap smear. Pap smear.

b b –– Ultrasound determination of endometrial Ultrasound determination of endometrial thickness, also any ovarian pathology may be detected.thickness, also any ovarian pathology may be detected.

In post menopausal woman 5 mm is the cutoff for a In post menopausal woman 5 mm is the cutoff for a normal unilateral endometrial strip. Color flow imaging normal unilateral endometrial strip. Color flow imaging may increase specificity. may increase specificity.

c c –– Out Out –– patient endometrial sampling using patient endometrial sampling using instruments such as a pipelle Sampler.instruments such as a pipelle Sampler.

d d –– Out Out –– patient hysteroscopy. patient hysteroscopy.

2003-10-272003-10-27 Carcinoma of the EndometriumCarcinoma of the Endometrium 1414

2003-10-272003-10-27 Carcinoma of the EndometriumCarcinoma of the Endometrium 1515

Staging :Staging :

The FIGO classification and staging of endometrial The FIGO classification and staging of endometrial carcinoma are ( it is surgical staging ) : carcinoma are ( it is surgical staging ) :

Stage I : Stage I : The carcinoma is confined to the corpus.The carcinoma is confined to the corpus.

Ia : Ia : Tumor limited to the endometrium.Tumor limited to the endometrium.

Ib : Ib : Invasion to less than Invasion to less than ½½ of the myometrium. of the myometrium.

Ic : Ic : Invasion more than Invasion more than ½½ of the myometrium. of the myometrium.

Stage II : Stage II : The carcinoma has involved the corpus and The carcinoma has involved the corpus and the cervix but has not extended outside the uterus. the cervix but has not extended outside the uterus.

IIa : IIa : Endocervical glandular involvement only.Endocervical glandular involvement only.

IIb : IIb : Cervical stromal invasion.Cervical stromal invasion.

Stage III : Stage III : The carcinoma has extended outside the The carcinoma has extended outside the uterus but not outside the true pelvis.uterus but not outside the true pelvis.

Stage IV : Stage IV : The carcinoma has extended outside the true The carcinoma has extended outside the true pelvis or has obviously involved the mucosa of the pelvis or has obviously involved the mucosa of the bladder or rectum.bladder or rectum.

2003-10-272003-10-27 Carcinoma of the EndometriumCarcinoma of the Endometrium 1717

2003-10-272003-10-27 Carcinoma of the EndometriumCarcinoma of the Endometrium 1818

2003-10-272003-10-27 Carcinoma of the EndometriumCarcinoma of the Endometrium 1919

* * Surgical stage I tumor account for 75 % of all Surgical stage I tumor account for 75 % of all endometrial carcinoma which explain the relative good endometrial carcinoma which explain the relative good overall prognosis. overall prognosis.

Prognosis :Prognosis :

Prognosis of the disease is related to stage, which now Prognosis of the disease is related to stage, which now include grade of disease, myometrial invation and LN include grade of disease, myometrial invation and LN involvement. Other factors such as age and body involvement. Other factors such as age and body morphology are also important.morphology are also important.

It is believed that the presence of malignant squamous It is believed that the presence of malignant squamous component ( adeno squamous carcinoma ) is thought to component ( adeno squamous carcinoma ) is thought to be associated with a poorer outcome.be associated with a poorer outcome.

2003-10-272003-10-27 Carcinoma of the EndometriumCarcinoma of the Endometrium 2222

Stage 5 year survivalStage 5 year survival

I 85%I 85%

II 68%II 68%

III 42%III 42%

IV 22%IV 22%

Differential diagnosis :Differential diagnosis : Clinically the differential diagnosis of endometrial Clinically the differential diagnosis of endometrial

carcinoma include all the causes of abnormal uterine carcinoma include all the causes of abnormal uterine bleeding. bleeding.

* * In premeopausal patient the following should be In premeopausal patient the following should be excluded :excluded :

1 1 –– Complication of early pregnancy. Complication of early pregnancy. 2 2 –– Liomyoma. Liomyoma. 3 3 –– Endometrial hyperplasia and polyps. Endometrial hyperplasia and polyps. 4 4 –– Cervical polyps. Cervical polyps. 5 5 –– Various genital or metastatic cancers. Various genital or metastatic cancers. * * In the postmenopausal age group, the following In the postmenopausal age group, the following

should be considered :should be considered : 1 1 –– Atrophic vaginitis. Atrophic vaginitis. 2 2 –– Exogenous oestrogen ( HRT ) Exogenous oestrogen ( HRT ) 3 3 –– Endometrial hyperplasia and polyps. Endometrial hyperplasia and polyps. 4 4 –– Various genital neoplasma. Various genital neoplasma.

Treatment :Treatment :

Stage I : Stage I : - The treatment of choice is total abdominal - The treatment of choice is total abdominal hysterectomy and bilateral salpingoopherectomy.hysterectomy and bilateral salpingoopherectomy.

- Radiotherapy is also necessary if invasion of - Radiotherapy is also necessary if invasion of the myometrium has occurred to more than the inner the myometrium has occurred to more than the inner half of the myometrium.half of the myometrium.

Stage II : Stage II : - If patient is surgically fit, do radical - If patient is surgically fit, do radical hysterectomy and bilateral lymphadenectomy with hysterectomy and bilateral lymphadenectomy with para-aortic node sampling should be performed.para-aortic node sampling should be performed.

- If patient unfit surgically then radiotherapy - If patient unfit surgically then radiotherapy may be used.may be used.

Stage III : Stage III : If node suggest spread of disease then surgery If node suggest spread of disease then surgery with adjuvant radiotherapy.with adjuvant radiotherapy.

Stage III & IV : Stage III & IV : Treatment needs to be individualized to Treatment needs to be individualized to the patient, but surgery is not usually the first line of the patient, but surgery is not usually the first line of treatment. treatment.

Treatments

Radiotherapy is performed and then occasionally Radiotherapy is performed and then occasionally

residual disease may be involved by surgical residual disease may be involved by surgical intervention.intervention.

Progesterone :Progesterone :

Some believe that progesterone may be helpful in Some believe that progesterone may be helpful in preventing recurrence after treatment of early stage preventing recurrence after treatment of early stage disease. disease.