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Gynae-Oncology > Endometrial Cancer > Flashcards

Endometrial Cancer Flashcards

1
Q

What is the pathophysiology of endometrial cancer?

A

Type 1: Stimulation of the endometrium by oestrogen, causing predictable progression through premalignant intraepithelial neoplasia.

Type 2: Genetic mutations (e.g. p53 tumour suppressor gene mutation in serous carcinoma)

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2
Q

What are risk factors for endometrial cancer?

A
  • Increasing age
  • Obesity
  • Diabetes mellitus
  • Atypical endometrial hyperplasia

Menstrual factors:

  • Early menarche
  • Late menopause
  • Nulliparity

Unopposed oestrogen:

  • PCOS
  • oestrogen only HRT
  • Oestrogen secreting ovarian tumours
  • Tamoxifen (E2 agonist at endometrium)
  • Lynch syndrome/HNPCC
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3
Q

What is the most common type of endometrial cancer?

A

Endometrioid carcinoma (80%)

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4
Q

What histopathological findings are found in endometrial hyperplasia WITHOUT atypia?

A

Increased glandular crowding
Increased gland:stoma ratio >3:1
Cystically dilated and irregularly shaped glands

No cytological atypia

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5
Q

What histopathological findings are found in endometrial hyperplasia WITH atypia?

A

Abnormal glands:

  • Cystically dilated
  • Budding/infolding of crowded glands
  • Increased gland:stroma ratio >3:1

Atypia:

  • Large, variable shape and size of nuclei
  • Loss of polarity
  • Increased nuclear to cytoplasmic ratio
  • Hyperchromatism,
  • Prominent nucleoli
  • Abnormal mitotic figures
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6
Q

What were the findings of the Cochrane Review into Laparoscopy vs Laparotomy for Early Endometrial Cancer?

A

No difference in risk of

  • death
  • cancer recurrence

Laparoscopy associated with less blood loss and earlier discharge from hospital

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7
Q

In endometrial hyperplasia without atypia, what is the progression to endometrial cancer over 20 years?

A

<5%

Spontaneous resolution in up to 80%
With progesterone, resolution rates up to 96%

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8
Q

In endometrial hyperplasia with atypia, what is the risk of concomitant carcinoma?

A

up to 43%
In patients undergoing hysterectomy

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9
Q

In endometrial hyperplasia with atypia, what is the risk of progression to endometrial cancer over 20 years?

A

27.5%

Spontaneous resolution in up to 30%

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10
Q

What % cases of endometrial cancer present premenopausally?

A

15%

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11
Q

What are two protective factors against endometrial cancer?

A

COCP/combined continuous MHT
Smoking!

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12
Q

What are the three main lymphatic trunks of the corpus uteri?

A

Utero-ovarian (infundibulopelvic)
Parametrial
Presacral

They collectively drain into the hypogastric (also known as internal iliac), external iliac, common iliac, presacral and para-aortic nodes.

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13
Q

What are the most common metastatic sites for endometrial / uterine cancer?

A

Vagina
Ovaries
Lungs

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14
Q

What are the seven histopathological types of endometrial carcinomas?

A
  1. Endometrioid carcinoma
  2. Mucinous adenocarcinoma
  3. Serous adenocarcinoma
  4. Clear cell adenocarcinoma
  5. Undifferentiated carcinoma
  6. Neuroendocrine tumours
  7. Mixed carcinoma
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15
Q

What are the five histopathological types of mixed epithelial and mesenchymal uterine tumours?

A
  1. Adenomyoma
  2. Atypical polyploid adenomyoma
  3. Adenofibroma
  4. Adenosarcoma
  5. Carcinosarcoma
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16
Q

What are the two traditional classifications of endometrial cancers?

A

Type 1 tumours (80%):

  • Grade 1 and 2 endometrioid carcinomas
  • Risk factor: unopposed oestrogen exposure
  • Arise from enodmetrial hyperplasia
  • Affects younger, peri-menopausal women

Type 2 tumours (10-20%):

  • Grade 3 endometrioid tumours
  • Non-endometrioid tumours: serous, clear cell, mucinous, squamous, transitional cell, mesonephric and undifferentiated
  • Arise from atrophic endometrium
  • Less hormone sensitive
  • Less differentiated, poorer prognosis.
  • Affects older, post-menopausal women
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17
Q

Who is screening recommended for, in the context of endometrial cancer?

A

High risk groups ONLY, such as those with Lynch Syndrome

Pipelle and TV USS annually from the age of 35 until hysterectomy
Prophylactic TH+BSO should be discussed at the age of 40

(FIGO, 2018)

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18
Q

What was the key finding of the ASTEC study?

A

Large multi centre RCT.
Randomised women with stage I endometrial cancer to TAH-BSO/washings versus TAH-BSO washings and pelvic lymphadenectomy.

Findings: Removing pelvic nodes add staging information but no recurrence free or overall survival benefit was seen.

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19
Q

What is the definition of endometrial hyperplasia?

A

Irregular proliferation of the endometrial glands with an increase in the gland to stroma ratio when compared with proliferative endometrium

(RCOG GTG)

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20
Q

Why have people advocated that progestogens be used to treat endometrial hyperplasia?

A

The progestogens modify the proliferative effects oestrogen on the endometrium.

There is evidence of 96% rate of regression when progestogens used.

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21
Q

Discuss the management of endometrial hyperplasia WITHOUT atypia:

A

Identify and correct reversible risk factors:

  • Weight loss
  • Stop oestrogen only HRT or switch to combined HRT.

Observe alone OR commence progestogen treatment (indicated if failure to regress with observation alone or symptomatic with AUB):

  • Mirena (1st line): at least 6 months duration; ideally up to 5 years.
  • Continuous oral progestogen: at least 6 months duration,

Follow-up:

  • Endometrial biopsy every 6 months.
  • Need 2 x consecutive negative biopsies before discharging.
  • Advise to seek review if abnormal bleeding occurs after completion of treatment.
  • High risk women e.g. BMI >=35 or treatment with oral progestogens should have biopsy every 6 months; once 2 x consecutive negative biopsies obtained, increased biopsy interval to every year.

Indications for hysterectomy:

  • Progression to atypia
  • No regression after 12 months of treatment
  • Relapse of hyperplasia after completion of treatment
  • Persistence of bleedding
  • Declines surveillance / non-compliance with medical treatment.

Choice of surgical approach:
- Laparoscopy preferred: shorter stay, less pain, quicker recovery
- If postmenopausal: offer total hysterectomy with BSO
- If premenopausal: offer total hysterectomy with BS
(RCOG, GTG)

22
Q

What is the management for a patient with endometrial hyperplasia with atypia?

A

Surgery (first-line):

  • Postmenopausal: total hysterectomy + BSO
  • Premenopausal: total hysterectomy + BS; individualise choice of oophorectomy

Fertility sparing treatment OR not suitable for surgery:

  • Exclude invasive endometrial cancer, co-existing ovarian cancer
  • Medical treatment: Mirena (1st line) or oral progestogens (2nd line)
  • Follow-up usually biopsy every 3/12 until 2 x consecutive negative biopsies then increase interval to every 6- 12 months until hysterectomy performed.
  • When fertility is no longer desired, offer hysterectomy.
23
Q

How does Tamoxifen increase the risk of endometrial cancer?

A
  • Selective oestrogen receptor modulator
  • Indicated in treatment of breast cancer: Inhibits proliferation of breast cancer by competitive antagonism of oestrogen receptors
  • Partial AGONIST action on other tissues, including the vagina and the uterus
    Estrogenic effect may promote the development of fibroids, endometrial polyps and hyperplasia and in turn, increase the risk of endometrial cancer
24
Q

What is a woman’s life-time risk of developing endometrial cancer?

A

2-3%

25
Q

What is the peak age of incidence of endometrial cancer?

A

70-79 yrs

26
Q

What is the lymphatic drainage of the uterus?

A
  • Utero-ovarian (infundibulopelvic
  • Parametrial
  • Presacral

These collective drain into the following lymph nodes:

  • Hypogastric (internal iliac)
  • External iliac
  • Common iliac
  • Presacral
  • Para-aortic
27
Q

Define stage I endometrial cancer.

Define stage IA, IB and IC

A

Stage I: tumour confined to uterus

Stage IA: confined to the endometrium or non-aggressive histological type. (Has 1-3 categories)

Stage IB: invasion equal to or more than half of myometrium of non-aggressive histological types

Stage IC: aggressive histological types confined to the endometrium or a polyp

28
Q

Define stage II endometrial cancer:

A

Tumour invades cervical stroma but does not extend beyond the uterus.

29
Q

Define stage III endometrial cancer.

Define stage IIIA, IIIB and IIIC:

A

Local and/or regional spread of tumour.

Stage IIIA: tumour invades serosa of uterus and/or adnexae

Stage IIIB: vaginal involvement and/or parametrial involvement

Stage IIIC: metastases to pelvic and/or para-aortic lymph nodes

30
Q

Define stage IV endometrial cancer.

Define stage IVA and IVB:

A

Stage IV: tumour invades bladder and/or bowel mucosa and/or distant metastases.

Stage IVA: invasion of bladder and/or bowel mucosa.

Stage IVB: distant metastasis including intra-abdominal metastases and/or inguinal nodes.

31
Q

List the 4 main histopathologic criteria for high risk disease:

A
  • Grade 3 tumour (poorly differentiated)
  • LVSI
  • Non-endometrioid histology
  • Cervical stromal invasion
32
Q

A postmenopausal woman has a TVUSS showing an endometrial thickness <4 mm; what is her probability of having endometrial cancer?

A

<1%

33
Q

How would you screen a woman with Lynch syndrome for endometrial cancer?

A

TVUSS + pipelle surveillance starting age 35 annually until hysterectomy.

Perform hysterectomy by age 40 once family complete.

34
Q

What is the sensitivity and specificity of endometrial pipelle in detecting endometrial cancer?

A
  • Sensitivity 73%
  • Specificity 99%
35
Q

What is the combined negative predictive value of TVUSS and curettage in excluding endometrial cancer?

A

Negative predictive value 96%

36
Q

List the investigations you would order in the work up of a woman you suspect has endometrial cancer:

A

Pipelle biopsy

Imaging:

  • TVUSS: ET, uterine cavity fluid
  • CXR: lung metastases
  • MRI pelvis: depth of invasion, cervical involvement and lymphadenopathy
  • CT chest, abdo pelvis or PET-CT: for high risk patients to evaluate lymph nodes and distant metastases

Endoscopy:

  • Hysteroscopy D&C: to assess uterine cavity and obtain biopsy
  • Cystoscopy: suspected bladder extension
  • Proctoscopy: suspected rectal extension

Bloods:

  • FBC
  • LFTS
  • Renal function
37
Q

When should a woman with endometrial hyperplasia but wishing to conceive start trying?

A

At least one biopsy should show regression before trying.
Advise her regression is associated with higher implantation and pregnancy rates.

38
Q

Is letrozole (aromatase inhibitor) associated with endometrial hyperplasia and cancer?

A

No

39
Q

Describe the steps involved in full surgical staging for endometrial cancer management:

A
  • Midline laparotomy
  • Peritoneal washings for cytology
  • TAH-BSO (based on stage-see below)
  • Careful examination +/- biopsy of possible metastases:
  • Omentum (consider omentectomy)
  • Liver
  • Pouch of Douglas
  • Adnexae
  • Pelvic and para-aortic nodes
  • Complete pelvic lymphadenectomy and resection of any enlarged para-aortic nodes

By stage:

  • *Stage Ia:**
  • total hysterectomy and BSO and washings
  • consideration of ovarian preservation in premenopausal women with low risk cancer
  • Full surgical staging not required
  • *Stage Ib:**
  • total hysterectomy and BSO
  • SLNB OR pelvic and selective para-aortic lymphadenectomy
  • *Stage II:**
  • Simple hysterectomy OR modified radical hysterectomy and BSO
  • AND pelvic and selective para-aortic lymphadenectomy

Stage III: Radical Hysterectomy, pelvic and para-aortic lymphadenectomy

Stage IV: Cytoreductive surgery , pelvic and para-aortic lymphadenectomy

40
Q

What is the indications for performing sentinel lymph node mapping?

What are the benefits of SLNM?

A

Indications:

  • Clinical stage Ib / uterine-confined disease
  • If considering lymphadenectomy, you can do SLNM first.

Benefits:

  • Reduces morbidity associated with comprehensive pelvic lymphadenectomy and selective para-aortic lymphadenectomy
  • Gives prognostic information from lymph node status
  • Sensitivity >90%
41
Q

Describe the key surgical principles of sentinel lymph node mapping:

A
  • Superficial and deep cervical injection of technetium radioisotope or blue dye
  • Complete evaluation of peritoneal cavity
  • Dissection to evaluate retroperitoneal spaces and identify sentinel drainage pathways from the parametria.
  • Excision of most proximal lymph nodes in sentinel pathway.
  • Remove any suspicious looking lymph nodes
  • Use frozen section analysis if available.
  • May perform hemipelvic side-specific lymphadenectomy for mapping failure to reduce false-negative staging.
42
Q

Describe the role of radiotherapy in the treatment of endometrial cancer:

A

Stage Ib & II with intermediate and high risk factors (at least 2 of):
- Age >60 years
- Deep myometrial invasion
- Grade 3
- Serous or clear cell histology
- LVSI
OR positive LN on histology
OR close surgical margins

Combination adjuvant chemoradiation therapy indicated for stage III disease to maximise recurrence-free survival.

For symptom management in stage IV disease - for vaginal bleeding or mass effect (incl. lymphoedema) due to large primary mass of lymphadenopathy

For treatment of cancer recurrence.

Palliation of brain or bone mets.

43
Q

How should a woman desiring fertility with grade 1 endometrioid endometrial carcinoma be managed?

A

Fertility preservation only if STAGE 1a GRADE 1 or 2 endometrioid cancer.

High dose progestogens:

  • Megestrol acetate 160-320 mg/day
  • MPA 400-600 mg/day

Refer to fertility clinic and encourage trying to conceive once remission obtained.

Hysterectomy once childbearing completed.

44
Q

What are the management options for stage II disease?

A
  • Radical hysterectomy, BSO, bilateral pelvic lymphadenectomy and selective aortic node dissection.
  • Simple or modified radical hysterectomy, BSO, bilateral pelvic lymphadenectomy and selective aortic node dissection.
  • Full surgical staging
  • Adjuvant radiotherapy: 1) involved nodes, 2) adverse prognostic factors or 3) close or involved surgical margins
  • If surgery not feasible (tumour extension or medically comorbid: EBRT pelvic radiotherapy and intracavitary brachytherapy.
45
Q

What are the management options of stage III disease?

A
  • Full surgical staging with radical hysterectomy, resection of all pelvic nodes and selective para-aortic nodes
  • Followed by EBRT and/or chemotherapy.
  • If surgical resection not possible: neoadjuvant pelvic radiotherapy +/- chemotherapy, followed by exploratory laparotomy.
46
Q

What is the follow-up intervals and duration for low risk disease (stage IA, grade 1 and 2)?

A
  • 6 monthly reviews up to 2 years (alternate between GP and surgeon).
  • Discharge at 2 years if no symptoms or concerns.
47
Q

What is the follow-up intervals and duration for intermediate risk disease (stage IA G3, stage IB grades 1 and 2)?

A
  • 6 monthly reviews with surgeon +/- rad onc up to 3 years.
  • Discharge at 3 years if not symptoms or concerns.
48
Q

Describe radical hysterectomy.

A

Radical hysterectomy refers to the excision of the uterus en bloc with the parametrium (ie, round, broad, cardinal, and uterosacral ligaments) and the upper one-third to one-half of the vagina. The surgeon usually also performs a bilateral pelvic lymph node dissection.

49
Q

What is the role of progesterone therapy in endometrial cancer?

A

1) Stage 1a, grade 1/2 in women wanting fertility preservation
2) For women not suitable for surgery and radiotherapy
3) Recurrence in women not suitable for surgery and radiotherapy

50
Q

What are the options for women not suitable for surgical resection?

A
  • Combined EBRT and brachytherapy
  • +/- chemotherapy
  • High dose oral progestogen if not suitable for radiotherapy
51
Q

How is recurrence of endometrial cancer managed?

A

Localised recurrence
- EBRT and brachytherapy first line

Larger recurrence may be amenable to cytoreductive surgery

  • +/- radiotherapy as EBRT and/or brachytherapy
  • Neoadjuvant chemotherapy is considered to increase chance of curative cytoreductive surgery
  • In well selected patients survival can be as high as 50%

If not amenable to radiotherapy or surgery, or distant metastases:

  • Chemotherapy with carboplatin and paclitaxel
  • If ER/PR positive high dose progesterone (megestrol 80mg bd-qds) as long as disease in remission or stable - if progressive stop and move to palliation
52
Q

what chemotherapy agents can be used for endometrial cancer?

A

Carboplatin and paclitaxel

  • Less toxic, better tolerated and fewer treatment related deaths than with doxorubicin/cisplatin/paclitaxel (TAP) combination therapy

Gynae-Oncology (14 decks)

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