Endometrial carcinoma

Endometrial hyperplasia
Endometrial hyperplasia is a premalignant
condition, that can predispose to, or be associated
with, endometrial carcinoma. It is characterized by
the overgrowth of endometrial cells and is caused
by excess unopposed oestrogens, either
endogenous or exogenous, similar to endometrial
cancer, with which it shares a common aetiology
Presentation
Endometrial hyperplasia was commonly
diagnosed on endometrial biopsies and it is now
most commonly diagnosed in women over 40yrs
old with irregular menstruation or in those with
post-menopausal bleeding.
Management of endometrial hyperplasia (no atypia)
Depends on age of patient, histology, symptoms, and desire for retaining
fertility.
• Exclude treatable causes of unopposed oestrogens:
• oestrogen-only HRT
• oestrogen-secreting tumour (e.g. granulosa cell tumour of ovary).
• Treat with progestagens, e.g.:
• continuous oral progestagens daily for 3–6mths: 5mg
norethisterone (premenopausal); 10mg medroxyprogesterone
acetate (MPA) (perimenopausal); 20mg MPA (post-menopausal)
• levonorgestrel intrauterine device if post-menopausal.
• Risk of progression to cancer:
• simple hyperplasia ~1%
• complex hyperplasia 3.5%.
• Rebiopsy only if abnormal bleeding continues
Classification of endometrial hyperplasia
Endometrial hyperplasia:
• simple
• complex (adenomatous).
• A typical endometrial hyperplasia
ENDOMETRIAL HYPERPLASIA
Atypical endometrial hyperplasia
- 46% of women with atypical hyperplasia will have a concurrent
adenocarcinoma and, if not concurrent, there is a very high risk the woman
will develop adenocarcinoma.
- Counsel about high risk of developing endometrial carcinoma.
- Unless fertility is desired or unacceptably high operative risk, recommend
TAH (+ BSO if >45yrs). bilateral salpingo-oophorectomy
If conservative treatment, then treat with high-dose progestagens,
e.g. MPA 100mg daily. Rebiopsy every 3–6mths until progression or
regression, and continue with long-term surveillance. Mirena ® coil often
used for maintenance treatment (if not trying to conceive).
Strongly consider hysterectomy once fertility not requir
Endometrial cancer: aetiology and histology
Endometrial cancer predominantly affects post-menopausal women (91%
of cases in >50yr olds).
Aetiology
Presence of unopposed oestrogen (i.e. no protective effect progesterone),
whether endogenous or exogenous.
• Endogenous:
• peripheral conversion in adipose tissue of androstenedione to oestrone
• oestrogen-producing tumour (granulosa cell tumour)
• polycystic ovarian syndrome or anovulatory cycles at menarche or
during climacteric period (lack of progesterone as no luteal phase).
• Exogenous:
• oestrogen-only HRT
• tamoxifen (oestrogen agonist in endometrial tissue).
Risk factors
• Obesity and conditions predisposing or associated with obesity
(including type II diabetes mellitus, hypothyroidism, hypertension).
• Reduced endogenous progesterone production:
• nulliparity (pregnancy associated with high progesterone levels)
• PCOS (anovulatory cycles—no corpus luteum, no progesterone)
• early menarche/late menopause (anovulatory cycles).
• Genetic predisposition: HNPCC (Lynch II syndrome) with high risk of
colorectal, endometrial, and ovarian tumours (40–60% lifetime risk
of endometrial cancer; inherited as autosomal dominant condition
• Breast cancer (shared lifestyle risk factors and tamoxifen usage).
Protective factors
• Parity (high progesterone dose in pregnancy).
• COCP (50% decrease with up to 4yrs of use up to 72% with 12 or more
years ) (progesterone effect).
• Histological types of endometrial cancer
• Adenocarcinoma
• Endometrial adenocarcinoma 87%.
• Adenosquamous carcinoma* 6%.
• Clear cell or papillary serous carcinoma* 6%.
• MMMT* 1%. malignant mixed mullerian tumor
• * High risk of advanced disease at presentation and
recurrence—all G3.
• Grading
• Well differentiated (G1).
• Moderately differentiated (G2).
• Poorly differentiated or high risk cell type (G3
• Endometrial biopsy endometrial tumor

• Perform endometrial sampling if ET ≥ 4mm or

persistent bleeding in woman with ET <4mm
(in which case consider formal hysteroscopy).
• Blind outpatient sampling (e.g. pipelle, vabra).
• Hysteroscopy: under LA as outpatient or GA as
inpatient
• Endometrial cancer: presentation and investigation
• Presentation post menopausal bleeding
• Most commonly presents with PMB. Younger women present with
menstrual disturbance (heavy or irregular periods). 1% are picked
up on routine cervical smear tests.
• 1 in 10 women with PMB will have endometrial cancer or atypical
hyperplasia.
• Endometrial sampling required for women >45yrs with abnormal
menstrual symptoms. pus in uterus
• - PV discharge and pyometra may occur instead of bleeding—have
increased index of suspicion in post-menopausal women with
increased PV discharge (50% of post-menopausal women with
pyometra have underlying carcinoma).
History
• Presenting symptoms.
• Menstrual history.
• Parity.
• Comorbidities.
• Drug history (COCP, HRT, tamoxifen, antihypertensives, oralhypoglycaemics).
• Family history.
Examination
• Rule out other causes of bleeding (vulval, vaginal, and cervical pathology)
with vulval, vaginal, and speculum examination.
• Bimanual examination: uterine size, mobility, adnexal masses.
Haematological investigations
• FBC, U&E, LFTs
• Imaging investigations
• • TVUSS: <4mm endometrial thickness (ET) very low
risk of endometrial pathology in post-menopausal
women (96% NPV)—no requirement for endometrial
sampling.
• CT chest/abdomen/pelvis: G3 disease for preoperative
staging as increased risk of disease outside of uterus.
• MRI pelvis: can be used to determine local extent of
tumour and presence of grossly involved pelvic lymph
nodes
• C XR (staging).
• Endometrial cancer: treatment
• Treatment
• Surgery
• TAH and BSO and pelvic washings : this can be
performed via a transverse or midline incision.
Increasingly, laparoscopic hysterectomy is gaining
popularity
• Pelvic lymphadenectomy
Role in low-grade early disease is controversial
 • Adjuvant radiotherapy
• Adjuvant radiotherapy limited to vault brachytherapy, if
intermediate risk
external beam radiation therapy
(EBRT ± vault brachytherapy boost for high risk (G3, stage Ib) or locally
advanced disease.
• Role of adjuvant chemotherapy in addition to ERBT in high risk
disease being examined in clinical trial .
• Radiotherapy reduced pelvic recurrences, but gave no survival
advantage to women with stage Ib endometrial cancer and
intermediate risk histology
.
• pelvic recurrences were amenable to radiotherapy
in previously non-irradiated patients.
• Vault brachytherapy reduced risk of pelvic recurrence
• Hormonal
• High dose progesterone used for advanced
and recurrent disease.
• Largely aiming for palliation of symptoms
(bleeding)—no survival advantage
demonstrated.
• Palliative radiotherapy
• EBRT given at lower dose and in few fractions
to control local symptoms (e.g. bleeding).
• FIGO staging of endometrial cancer
• Stage Extent of disease 5-year survival
• I Tumour limited to uterine body 85%
• Ia <1/2 myometrial depth invaded
• Ib >1/2 myometrial depth invaded
• IIa Tumour limited to uterine body and cervix 75%
• II b Invasion into cervical stroma
• III Extension to uterine serosa, peritoneal cavity,
and/or lymph nodes 45%
• IIIa Extension to uterine serosa, adnexae, or positive peritoneal
fluid (ascites or washings)
• IIIb Extension to vagina
• IIIc Pelvic or para-aortic lymph nodes involved
• IV Extension beyond true pelvis and/or involvement of
bladder/bowel mucosa
25%
• Iva Extension to adjacent organs
• Ivb Distant metastases or positive inguinal lymph nodes

*Endocervical involvement without stromal invasion now included in

stage I.
• Rare uterine malignancies
• Uterine sarcomas
• Uterine sarcomas are very rare, accounting for 3–
5% of uterine cancers and have an incidence of
2:100 000 women.
• Abnormal bleeding is the most common
presenting feature; other symptoms include pain
and a pelvic mass. Polypoid masses may protrude
through the cervical os.
• - Uterine corpus sarcomas account for 3–5% of all
uterine cancers, but cause 26% of the mortality.
• Types of uterine sarcomas
• Leiomyosarcoma (46%).
• Endometrial stromal sarcoma (12%).
• Carcinosarcoma (27%).
• Not specified/others (15%).