Diseases of the uterus

Dr Ismaiel Abu Mahfouz

Benign and pre-malignant diseases of the uterus

•Fibroids

•Endometrial hyperplasia

Fibroids • Smooth muscle tumours of the uterus

• Prevalence: variable (4.5% - 68%)

•Benign

• 0.2% : malignant transformations (leiomyosarcoma)

• Variable size from mm to many cm

• Increased risk: o African-Caribbean race (2X)

o Advancing age

o Premenopause

o HTN

o Family history (? Genetics)

•Reduced risk o Parity, smoking, COCP

Classification • Subserosal

• Intramural

• Submucous

Presentation

• Incidental finding

o In significant number of women

• Gynaecological

o AUB / HMB: due to increase surface area and vascularity

o Pelvic pain, dyspareunia, pelvic mass

• Anaemia due to HMB

• Obstetrics

o Sub-fertility / Miscarriage: ? Interference with implantation

o Abdominal pain, preterm labour, malpresentation and CS, PPH

• Compression of organ systems:

o Pressure effects on GIT and UT

Complications Hyaline degeneration

• Common

• Presents as painful enlarged fibroids due to hyaline/cystic degeneration

Red degeneration (necrobiosis)

• Typically during pregnancy at mid-term due to infarction

Calcification

• Usually in postmenopausal women

Sarcomatous change

• 0.2% risk

• Suspect if rapidly growing fibroids at advanced age

Infection

• Rare

Torsion

• Pedunculated fibroids

Investigations

Pelvic ultrasound

• First-line investigation

• TV or TA

MRI

• Useful when planning surgery

• Baseline prior to uterine artery embolisation (UAE)

Treatment

Individualised

Factors affecting choice of Rx

• Size

• location

• Number

• General medical health, age, BMI, previous surgery, previous fibroid Rx

• Desire for fertility preservation

• Women’s preference

Fibroid treatment Conservative :

Unlikely to be successful if large (>20w size) and multiple (if >5cm in size)

Options include

• Medical

• Myomectomy (Open, laparoscopic, hysteroscopic)

• Uterine artery embolisation

• MRI guided focused ultrasound

• Laparoscopic uterine artery occlusion

Radical

• Hysterectomy

Medical treatment COCP

• Reduce menstrual blood loss

• No change in fibroid size

LNG IUS system (Mirena IUS)

• Reduce menstrual blood loss > COCP

Ulipristal acetate (UPA)

• SPRM (selective progesterone receptor modulator)

• Reversibly blocks P receptor in endometrium and myometrium

• Orally active steroid

• Majority of women: reduction in size or prevention of further growth

• Used to treat HMB associated with uterine fibroids

Progestogens

• Cyclic P not recommended

Medical treatment

Preoperative GnRH agonist

3 – 4 month Rx prior to myomectomy / hysterectomy

• Reduces fibroid size and uterine volume

• Facilitates surgery through a low transverse abdominal incision in

women with large >24w sized multi-fibroids

• Improves preoperative haemoglobin levels

• Reduces perioperative blood loss and transfusion requirements

• Reduces hospital stay

Surgery for fibroid

Myomectomy and fertility Submucosal and intramural fibroids are associated with adverse fertility and

pregnancy outcomes

Therefore

• Removal of intracavitary part of submucous fibroid improves fertility

• Subserosal fibroids do not affect fertility outcome

Abdominal myomectomy

Hysteroscopic myomectomy

Uterine artery embolisation (UAE)

UAE Symptomatic fibroid

• Pt selection: multidisciplinary team ( Gynae, Interventional Radiology)

• Good outcome at short and medium term follow up

• Similar satisfaction rate to hysterectomy

Contraindication

• Active PID

• Pregnancy

• Women who may not accept a small risk of hysterectomy

MRI-guided focused ultrasound ablation

MRI-guided focused ultrasound ablation

• New innovation

• Effective and safe

• ? Fibroids less than 7-8 cm

• Improves QoL

• Adverse effects

• Low rate

• Abdominal pain, lumbar pain, first-degree burns, light vaginal bleeding

Surgery for fibroid

Hysterectomy can be considered as a first-step

• Severe symptoms (HMB, pressure effects, pain)

• Significant pathology (>20 week sized uterus) that is unlikely to respond to other Rx

• Women’s preference for definitive Rx

• No desire for future fertility

Endometrial hyperplasia

Endometrial hyperplasia Definition • Proliferation of glands of irregular size and shape with an increase in the

glands/stroma ratio Classification • Simple endometrial hyperplasia with or without atypia • Complex endometrial hyperplasia with or without atypia

Atypia • Most important prognostic factor for progression to ca • Hyperplasia without atypia: < 2% progress to ca in “ mean duration of 10 years” • Hyperplasia with atypia : 23% progress to ca in “mean duration of 4 years” • Endometrial ca may co-exist with atypical hyperplasia in 25% of patient

Treatment

Without atypia

• Progesterone (including Mirena IUS)

• Follow up endometrial sampling

• ? TAH

With atypia

• TAH +/- BSO

Malignant diseases of the uterus

• Endometrial ca

• Sarcoma

Endometrial ca

Endometrial ca

• Increasing in incidence

• 25% increase in last decade

• Most common gynae ca in developed countries

• Strongly related to obesity

Endometrial ca; Risk factors

Advancing age

• Peak incidence: 65 - 75 years

• 2–5% < 40 years

Prolonged exposure to E2

• Late menopause

• Exogenous E2

Low parity

• 21– 34% are nulliparous

• Reduced by 30% after first birth & by 25% with each subsequent birth

• Why higher parity is protective?

o Sloughing off of the endometrium during delivery

o Breaks in exposure to unopposed E2 during pregnancy

Endometrial ca Risk factors

Obesity

• 3-10 fold increase

Hypertension and Type 2 DM

Cigarette smoking

• Decreases ca endometrium by 20–40% (anti-estrogenic effects of nicotine)

Unopposed estrogen therapy

• Increases by 6-8 times

• COCPs protective

Family history

• HNPCC (Lynch syndrome)

Others

• Previous pelvic irradiation

• Tamoxifen

Diagnostic assessments Trans-vaginal ultrasound

• ET: cut-off 5 mm in postmenopausal women: suggestive of ca

Endometrial biopsy

• Office based (Pipelle)

• GA

Hysteroscopy and endometrial biopsy

• The standard investigation for Dx

• Outpatient or inpatient

Screening

•No accepted technique for endometrial ca screening

• Identification of high-risk factors: early detection

Pathology of endometrial cancer

Adenocarcinoma

•Arises commonly from the fundus

• ? Difficult to distinguish between well-differentiated ca and atypical hyperplasia

• 25% of atypias have co-existing carcinomas

Pathology of endometrial cancer

Papillary serous carcinoma and clear cell carcinoma

• Similar to cell type in ovary and fallopian tube ca

• Spread in a similar fashion to ovarian ca

o Full-staging laparotomy and omentectomy is required

•Aggressive course and poor prognosis

• 50% of treatment failures

Pathology of endometrial cancer

Others types

•Mucinous adenocarcinoma: uncommon

• Squamous carcinoma : uncommon

•Undifferentiated carcinoma: very rare

Grading and spread for endometrial cancer Grading

Mode of spread in endometrial cancer

Differentiation Grade Spread Description

Well 1 Limit to endometrium, <10% involve

outer third of myometrium

98% glandular or papillary

formations

Moderate 2 2–50% solid areas

Poor 3 <10% limit to endometrium, cervical

extension 15%

>50% solid areas

Mode Description

Direct spread Through fallopian tubes to ovaries and peritoneal cavity

Most common route . Myometrial and eventually serosal involvement

Lymphatic To parametrial, vaginal, pelvic and para-aortic nodes (via infundibulopelvic ligament)

Haematogenous To liver, lung, central nervous system and bone is rare (late-stage disease)

Patient evaluation History

• Abnormal uterine bleeding (PMB, HMB) 90% of women

• Vaginal discharge

• LUTS

• Weight loss, general weakness, abdominal swelling

Physical examination • Frequently normal

• Inspection and palpation of the vulva and vagina

• Suburethral area is common for metastatic deposits

• Exclude other causes for vaginal bleeding

• Bimanual rectal and vaginal examination to assess pouch of Douglas, parametria

Preoperative workup

• Full blood count

•Blood Glucose

• Liver and renal functions

•Consider Cystoscopy

•Consider Sigmoidoscopy

•CT scans: pelvis, abdomen

Staging assessments Imaging studies

CXR

• Essential

MRI

• Degree of myometrial invasion

• Stage of disease (particularly cervical involvement)

• Pelvic & para-aortic lymph node involvement

TVS

• Alternative for evaluating degree of myometrial invasion

• Less accurate than MRI

CT scan

• Indicated in cases of non-endometroid ca

PET–CT

• Useful for detecting distant disease suspected but not detected on CT scan

FIGO staging 2014 update

Stage I Tumour confined to the corpus uteri

IA: Tumour confined to the uterus. No or less than half myometrial invasion

IB: Tumour confined to the uterus. More than half myometrial invasion

Stage II Cervical stromal invasion but not beyond the uterus

Stage III Local and/or regional spread of the tumour

IIIA: Tumour invades serosa or adnexa

IIIB: Vaginal and/or parametrial involvement

IIIC1: Pelvic node involvement

IIIC2: Para-aortic involvement

Stage IV Tumour invades bladder and/or bowel mucosa and/or distant metastases

IVA: Tumour invasion of the bladder and/or bowel mucosa

IVB: Distant metastases: abdominal metastases and/or inguinal lymph nodes.

Treatment of ca endometrium

Surgery

• The main treatment

Radiotherapy

• If patient is unfit for surgery

•Adjuvant

Hormonal treatment

•High dose progesterone

Treatment of ca endometrium • Stage I:

Total hysterectomy (abdominal or laparoscopic) and BSO

• Stage II :

Radical hysterectomy +/- postoperative Radiotherapy

• Stage III :

Surgery (TAH& BSO and aim to debulk disease) +

Adjuvant pelvic irradiation

• Stage IV:

Individualised: aim to achieve local control

Combination of surgery, RT for palliative local control, and CT for distant control

Prognostic factors

•Cell type

•Grade

•Depth of myometrial invasion

• Endocervical involvement

Recurrent disease

• Majority: within the first 36 months

• 75% of local recurrences present with vaginal bleeding or pelvic pain

• Always check for systemic spread

Treatment for recurrence

• Pelvic RT: appropriate If no previous RT

• Pelvic Exenteration: Prior radiation with isolated central pelvic recurrences with no evidence of LN involvement

• Progestogens & Tamoxifen: clinical response in 20%

• Doxorubicin, platinum-based & placitaxel: response rates: 30–40%

Sarcoma

Uterine sarcomas

•A rare group of heterogeneous neoplasms arising from the uterine corpus

•Mainly of carcinosarcomas, leiomyosarcomas, endometrial stromal sarcomas

•Aggressive clinical behaviour & poor prognosis

•High risk of local recurrence and distant spread

Epidemiology and prognostic factors Epidemiology

• 4–9% of all invasive uterine ca

• Black women had twice the risk

• Median age at diagnosis o Leiomyosarcoma: 48–54 years o Endometrial stromal sarcoma: 41–63 years o carcinosarcoma: 62–67 years

Prognostic factors

• Stage is the most important prognostic factor

• Poor prognostic factors: o High grade o Adnexal spread o Lymph node metastasis

FIGO: Sarcoma staging IA Tumor limited to uterus < 5 cm

IB Tumor limited to uterus > 5 cm

IIA Tumor extends to the pelvis, adnexal involvement

IIB Tumor extends to extra-uterine pelvic tissue

IIIA Tumor invades abdominal tissues, one site

IIIB More than one site

IIIC Metastasis to pelvic and/or para-aortic lymph nodes

IVA Tumor invades bladder and/or rectum

IVB Distant metastasis

Treatment

Surgical resection

• The mainstay of Rx

• TAH & BSO is the standard surgical Rx

• Pelvic and/or para-aortic lymphadenectomy

• There is a limited role for adjuvant radiotherapy / chemotherapy