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Flashcards in Pathology Deck (131):
1

What makes up the ovarian cycle?

Follicular phase
Ovulation
Luteal phase

2

What makes up the uterine cycle?

Menstrual phase
Proliferative phase
Secretory phase

3

When is the proliferative phase, and what hormone causes it?

D 1-14
Oestrogen

4

When is the secretory phase, and what hormone causes it?

D 16-28
Progesterone

5

What are some indications for endometrial sampling?

Abnormal uterine bleeding
Investigation for infertility
Spontaneous and therapeutic abortion
Assessment of response to hormonal therapy
Endometrial ablation
Work up prior to hysterectomy for benign indications
Incidental finding of thickened endometrium on scan
Endometrial cancer screening in high risk patients

6

What is menorrhagia?

Prolonged and increased menstrual flow

7

What is metrorrhagia?

Regular intermenstrual bleeding

8

What is polymenorrhoea?

Menses occurring at <21 day interval

9

What is polymenorrhagia?

Increased bleeding and frequent cycle

10

What is menometrorrhagia?

Prolonged menses and intermenstrual bleeding

11

What is amenorrhoea?

Absence of menstruation >6mo

12

What is oligomenorrhoea?

Menses at intervals of >35d

13

When does post menopausal bleeding become abnormal uterine bleeding?

1 year after cessation of menstruation

14

What are some causes of AUB in adolescence/early reproductive life?

DUB due to Anovulatory cycles
Pregnancy/miscarriage
Endometritis
Bleeding disorders

15

What are some causes of AUB in reproductive life/perimenopause?

Pregnancy/miscarriage
DUB: anovulatory cycles, luteal phase defects
Endometritis
Endometrial/endocervical polyp
Leiomyoma
Adenomyosis
Exogenous hormone effects
Bleeding disorders
Hyperplasia
Neoplasia: cervical, endometrial

16

What are some causes of AUB post menopause?

Atrophy
Endometrial polyp
Exogenous hormones: HRT, tamoxifen
Endometritis
Bleeding disorders
Hyperplasia
Endometrial carcinoma
Sarcoma

17

Endometrial thickness of what in postmenopausal women is taken as an indication for biopsy?

>4mm, 16mm is premenopausal

18

How can the endometrium be sampled?

Endometrial pipelle
Dilatation and curettage

19

What is DUB defined as?

Irregular uterine bleeding that reflects a disruption in the normal cyclic pattern of ovulatory hormonal stimulation to the endometrial lining (no organic cause for bleeding)

20

What happens in DUB de to anovulatory cycles?

Corpus luteum does not form
Continued growth of functionalis layer

21

In what conditions is DUB common in?

PCOS
Hypothalamic dysfunction
Thyroid disorders
Hyperprolactinaemia

22

What is luteal phase deficiency?

Insufficient progesterone or poor response by the endometrium to progesterone. Abnormal follicular development (inadequate FSH/LH) – poor corpus luteum

23

How is endometritis diagnosed histologically?

Recognising an abnormal pattern of inflammatory cells

24

What physiological barriers are there to endometritis?

Cervical mucous plug protects endometrium from ascending infection
Cyclical shedding

25

What organisms can cause endometritis?

Neisseria
Chlamydia
TB
CMV
Actinomyces
HSV

26

What can cause endometritis without specific organisms?

Intra-uterine contraceptive device
Postpartum
Postabortal
Post curettage
Chronic endometritis NOS
Granulomatous (sarcoid, foreign body post ablation)
Associated with leiomyomata or polyps

27

Describe chronic plasmacytic endometritis

Infectious unless proved otherwise
Associated with PID (neiserria gonorrhoea, chlamydia, enteric organisms)

28

Describe endometrial polyps

Usually asymptomatic, may present with bleeding or discharge
Occur around or after menopause
Almost always benign
Endometrial carcinoma can present as polyp

29

What are some causes of AUB related to the myometrium?

Adenomyosis- endometrial glands and stroma within myometrium, causes menorrhagia/dysmenorrhoea
Leiomyoma- benign tumour of smooth muscle, may be found elsewhere

30

How may leiomyoma present?

Menorrhagia
Infertility
Mass effect
Pain

31

Can there be multiple leiomyoma?

Yes: single or multiple, may distort uterine cavity

32

What is leiomyoma growth dependent on?

Oestrogens

33

What is seen in leiomyoma microscopically?

Interlacing smooth muscle cells

34

What are the normal cell layers of the ectocervix?

Exfoliating cells
Superficial cells
Intermediate cells
Parabasal cells
Basal cells
Basement membrane

35

Where is the transformation zone found?

Between ectocervical (squamous) and endocervical (columnar) epithelium

36

The position of TZ will alter during life as physiological responses to what?

Menarche
Pregnancy
Menopause

37

What is cervical erosion?

Exposure of delicate endocervical epithelium to acid environment of vagina leading to physiological squamous metaplasia

38

Describe cervicitis

Often asymptomatic: can lead to infertility due to simultaneous silent fallopian tube damage

39

What are the causes of cervicitis?

Non-specific acute/chronic inflammation
Follicular cervicitis- sub epithelial reactive lymphoid follicles preset in cervix
Chlamydia Trachomatis
HSV

40

Describe a cervical polyp

Localised inflammatory outgrowth
Bleeding cause, if ulcerated
Not premalignant

41

What are some neoplastic pathologies of the cervix?

Cervical Intraepithelial Neoplasia (CIN)
Cervical Cancer: squamous carcinoma, adenocarcinoma

42

What are risk factors for CIN/Cervical cancer?

Persistence of high risk HPVs, mostly types 16,18,31,33,35,45,48
Many sexual partners
Vulnerability of SC junction in early reproductive life- age at first intercourse, long term use of oral contraceptives, non-use of barrier contraception
Smoking: 3x risk
Immunosuppression

43

How much of all cervical cancers are caused by HPV 16 and 18?

70%

44

What is condyloma acuminatum?

Thickened papillomatous squamous epithelium with cytoplasmic vacuolation (koilocytosis)

45

What HPV's cause genital warts?

6 and 11

46

What epithelial changes may be seen in CIN?

Infected epithelium remains flat, but at show koilocytosis, which can be detected in smears

47

What does the virus do in HPV cervical cancer?

Integrates into host DNA

48

How long does an HPV infection take to become high grade CIN?

6 months to 3 years

49

How long does high grade CIN take to become invasive cancer?

5-20 years

50

What is the prevalence of HPV infection (pre-vaccination)?

15-25yo 30-50%
25-35yo 10-20%
>35yo 5-15%
80% cumulative prevalence in lifetime

51

Do most people develop immunity to HPV infection?

Yes

52

What does persistence of the HPV infection increase?

Risk of disease

53

Describe CIN

Pre-invasive stage of cervical cancer
Occurs at TZ
Can be large area
Dysplasia of squamous cells
Not visible to naked eye
Asymptomatic
Detectable by cervical screening

54

What delays in maturation/differentiation are seen in CIN?

Immature basal cells occupying more of epithelium

55

What nuclear abnormalities are seen in CIN?

Hyperchromasia
Increased nucleocytoplasmic ratio
Pleomorphism

56

Does excess mitotic activity occur in CIN?

Yes- abnormal mitotic forms
Situated above basal layers

57

How is CIN graded?

I-III depending on histological factors

58

What is seen in CIN I?

Basal, 1/3 of epithelium occupied by abnormal cells
Raised numbers of mitotic figures in lower 1/3.
Surface cells quite mature, but nuclei slightly abnormal

59

What is seen in CIN II?

Abnormal cells extend to middle 1/3
Mitoses in middle 1/3
Abnormal mitotic figures

60

What is seen in CIN III?

Abnormal cells occupy full thickness of epithelium
Mitoses, often abnormal, in upper 1/3

61

What percentage of CIN I,II,III lesions progress to invasion?

1,5, and >12% respectively

62

What percentage of CIN I and II progress to CIN III?

11 and 22% respectively

63

How many malignant cervical tumours are invasive squamous carcinoma?

75-95%

64

What is the 2nd commonest female cancer worldwide?

Invasive squamous carcinoma

65

What does invasive squamous carcinoma develop from?

Pre-existing CIN, therefore most cases are preventable by screening

66

Describe the staging of invasive squamous carcinoma

Stage 1A1 - depth up to 3mm, width up to 7mm
Stage 1A2 - depth up to 5mm, width up to 7mm: Low risk of lymph node metastases
Stage 1B - confined to the cervix
Stage 2 - spread to adjacent organs (vagina, uterus, etc..)
Stage 3 - involvement of pelvic wall
Stage 4 - distant metastases or involvement of rectum or bladder

67

What are the symptoms of invasive carcinoma of the cervix?

Usually none at microinvasive/early invasive stages
Abnormal bleeding: post coital, post menopausal, brownish or blood stained vaginal discharge, contact bleeding-friable epithelium
Pelvic pain
Haematuria/urinary infections
Ureteric obstruction/renal failure

68

What is the local spread of squamous carcinoma of cervix?

Uterine body, vagina, bladder, ureters, rectum

69

What is the lymphatic spread of squamous carcinoma of cervix?

Early>pelvic, para-aortic nodes

70

What is the haematogenous spread of squamous carcinoma of cervix?

Late> liver, lungs, bone

71

How are squamous carcinomas of the cervix graded?

Well differentiated
Moderately differentiated
Poorly differentiated
Undifferentiated / anaplastic

72

Describe cervical glandular intraepithelial neoplasia (CGIN)

Origin from endocervical epithelium
CGIN is preinvasive phase of endocervical adenocarcinoma
More difficult to diagnose on cervical smear than squamous
Screening less effective
Sometimes associated with CIN

73

Describe endocervical adenocarcinoma

5-25% of cervical cancer
Increasing incidence, particularly young women
Some are mixed, arise from common cell of origin
Worse prognosis than squamous

74

What are the RFs for endocervical adenocarcinoma?

Higher socio-economic class
Later onset of sexual activity
Smoking
HPV-particularly 18

75

What other HPV driven neoplasias exist?

Vulvar Intraepithelial Neoplasia
Vaginal Intraepithelial Neoplasia
Anal Intraepithelial Neoplasia

76

What is associated with VIN?

Paget's disease

77

Describe the bimodal presentation of VIN

Young- often multifocal recurrent or persistent causing treatment problems
Older- greater risk of progression to invasive squamous carcinoma

78

Is VIN HPV related?

Often, but not always

79

What often occurs with VIN?

Synchronous CIN and VaIN

80

How does vulvar invasive squamous carcinoma usually present (VISC)?

Elder women- ulcer or exophytic mass

81

What can VISC arise from?

Normal epithelium or VIN

82

Are VISC's well differentiated?

Yes (verrucous are an extremely well differentiated type)

83

What is the most important prognostic factor in VISC?

Inguinal LN spread

84

What is the surgical treatment of VISC?

Radical vulvectomy and inguinal lymphadenectomy

85

What are the 5 year survival rates of VISC?

90% if node -ve
<60% if node +ve

86

Describe vulvar Paget's disease

Crusting rash
Tumour cells in epidermis, contain mucin
Mostly no underlying cancer, tumour arises from sweat gland in skin

87

Who does vaginal squamous carcinoma commonly present in?

Elderly

88

How many vaginal melanoma appear?

As a polyp

89

What are the 3 stages of endometrial hyperplasia?

Simple
Complex
Atypical (precursor of carcinoma)

90

What are the causes of endometrial hyperplasia?

Often unknown
May be persistent oestrogen stimulation

91

How does endometrial hyperplasia present?

Abnormal bleeding (DUB or PMB)

92

Describe the distribution, component, glands and cytology for simplex endometrial hyperplasia

General
Glands and stroma
Dilated not crowded
Normal

93

Describe the distribution, component, glands and cytology for complex endometrial hyperplasia

Focal
Glands
Crowded
Normal

94

Describe the distribution, component, glands and cytology for atypical endometrial hyperplasia

Focal
Glands
Crowded
Atypical

95

What is the peak incidence of endometrial carcinoma?

50-60yo, uncommon under 40

96

What should be considered in young women with endometrial carcinoma?

Consider underlying predisposition e.g. PCOS or Lynch syndrome

97

What are the two main groups of endometrial carcinoma?

Endometrioid carcinoma (type 1 tumour 80%): precursor atypical hyperplasia
Related to unopposed oestrogen
Serous carcinoma (type 2): precursor serous intraepithelial carcinoma
Not associated with unopposed oestrogen, affects elderly postmenopausal women, TP53 often mutated

98

How does endometrial carcinoma usually present?

Abnormal bleeding

99

What are the macroscopic findings of endometrial carcinoma?

Large uterus
Polypoid

100

What are the microscopic findings of endometrial carcinoma?

Most are adenocarcinomas
Most are well differentiated

101

What is the spread of endometrial carcinoma?

Directly into myometrium and cervix
Lymphatic
Haematogenous

102

Describe type 1 endometrial carcinomas

Endometrioid and mucinous phenotypes
PTEN, KRAS, PIK3CA mutations
Associated with atypical hyperplasia as precursor lesion
Microsatellite instability
Germline mutation of mismatch repair genes (Lynch syndrome)

103

Why is obesity a known RF for endometrial cancer?

Excess risk associated with endocrine and inflammatory effects of adipose tissue
Adipocytes express aromatase that converts ovarian androgens into oestrogens, which induce endometrial proliferation
Insulin/IGF exert proliferative effect on endometrium
Sex hormone binding globulin levels are lower in obese women, and therefore the level of unbound, biologically active hormone is higher

104

What is Lynch syndrome?

Cancer predisposition syndrome- Hereditary non-polyposis colorectal cancer
High risk of endometrial cancer (28%) and increased probability of developing ovarian cancer
AD Inheritance

105

What kind of tumour staying for mismatch repair proteins can help identify tumours due to Lynch syndrome?

Immunohistochemistry

106

What characteristic of defective mismatch repair do Lynch syndrome tumours show?

Microsatellite instability

107

Describe type 2 endometrial carcinomas

Serous and clear cell phenotypes
TP53 mutation and overexpression
Precursor lesion serous endometrial intraepithelial carcinoma
More aggressive than endometrioid/mucinous carcinoma

108

Describe the spread of type 2 endometrial carcinomas

Spreads along fallopian tube mucosa and peritoneal surfaces so can present with extrauterine disease

109

What is serous carcinoma characterised by?

Characterised by a complex papillary and/or glandular architecture with diffuse, marked nuclear pleomorphism

110

Why does endometrioid carcinoma have a good prognosis?

As usually confined to uterus at presentation

111

What is the treatment for endometrial carcinoma?

Hysterectomy
Chemo/radiotherapy

112

How is endometrial carcinoma staged?

I-IV
Prognosis depends on:
Stage
Histological grade
Depth of myometrial invasion

113

Describe endometrial carcinoma grading

Based on architecture
Grade 1 5% or less solid growth
Grade 2 6-50% solid growth
Grade 3 >50% solid growth

114

Are serous and clear cell carcinoma graded?

Not formally

115

Describe stage I-IV of endometrial cancer

Stage I Tumour confined to the uterus
IA- No or < 50% myometrial invasion
IB- Invasion equal to or > 50% of myometrium
II- Tumour invades cervical stroma
III- Local and or regional tumour spread
IIIA- Tumour invades serosa of uterus and/or adnexae
IIIB- Vaginal and/or parametrial involvement
IIIC- Metastases to pelvic and/or para-aortic lymph nodes
IV- Tumour invades bladder and or bowel mucosa (IVA) and/or distant metastases (IVB)

116

Describe endometrial stromal sarcoma

Low and high grade (high has increased atypical, proliferative activity)
Rare, cells resemble endometrial stroma
Infiltrate myometrium and often lymphovascular spaces

117

How does endometrial stromal sarcoma present?

With AUB but initial may be as mets (commonly ovary or lung)

118

What is the most important prognostic factor in endometrial stromal sarcoma?

Stage

119

Describe carcinosarcoma

<5% of uterine malignancies
High grade carcinomatous and sarcomatous elements
Heterologous elements seen in about 50% (rhabdo/chrondro/osteosarcoma)
Usually associated with poor outcome

120

The present of what component has the worst prognosis in carcinosarcoma?

Rhabdomyosarcomatous

121

Describe leiomyosarcoma

Malignant smooth muscle tumour commonly displaying spindle cell morphology
Most common uterine sarcoma
1-2% uterine malignancies
Most >50yo

122

What are the commonest symptoms of leiomyosarcoma?

Abnormal vaginal bleeding
Palpable pelvic mass
Pelvic pain

123

Does leiomyosarcoma have a good prognosis?

No

124

How is leiomyosarcoma staged?

Same staging system as endometrial stromal sarcoma, different to that for endometrial cancer

125

When can follicular cysts form?

When ovulation doesn't occur (polycystic ovaries)

126

What are the possible sites of endometriosis?

Ovary (‘chocolate’ cyst)
Pouch of Douglas
Peritoneal surfaces, including uterus
Cervix, vulva, vagina
Bladder, bowel etc

127

What are some complications of endometriosis?

Pain
Cyst formation
Adhesions
Infertility
Ectopic pregnancy
Malignancy (endometrioid carcinoma)

128

How are epithelial ovarian tumours categorised?

Benign- no cytological abnormalities, proliferative activity (absent or scant), no stromal invasion
Borderline- cytological abnormalities, proliferative, no stromal invasion
Malignant- stromal invasion

129

What are most cases of high grade serous carcinoma?

Tubal in origin

130

What % of ovarian tumours do germ cell tumours make up?

15-20%

131

Describe Figo staging of ovarian cancer?

1A tumour limited to one ovaries
1B tumour limited to both ovaries
1C Cancer involving ovarian surface/rupture/surgical spill/tumour in washings
2A Extension or implants on uterus/fallopian tube
2B Extension to other pelvic intraperitoneal
3A Retroperitoneal lymph node
Metastasis or microscopic extrapelvic peritoneal involvement
3B Macroscopic peritoneal metastasis beyond pelvis up to 2cm in dimension
3C Macroscopic peritoneal metastasis >2cm in dimension
4 Distant metastasis