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YR5 Histopathology > Gynaecological Pathology > Flashcards

Gynaecological Pathology Flashcards

1
Q

Describe the gynaecological tract from the outside in

A

Vulva

Vagina

Cervix

Uterine body

Fallopian tube

Ovaries

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2
Q

Name 2 forms of congenital anomalies in gynaecology

A

Duplication

Agenesis

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3
Q

What is the term for inflammation in each part of the Gynaecological Tract?

A

Vulva: vulvitis

Vagina: vaginitis

Cervix: cervicitis

Endometrium: endometritis

Fallopian tube: salpingitis

Ovary: oopheritis

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4
Q

Name 3 infections of the female genital tract that cause discomfort but no serious complications. What causes are each associated with?

A

Candida: DM, OCP + pregnancy enhance development of infection.

Trichomonas vaginalis: Protozoan.

Gardenerella: Gram -ve bacillus causes vaginitis

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5
Q

Name 4 infections of the female genital tract that can have serious complications.

A

Chlamydia: Major cause of infertility.

Gonorrhoea: Major cause of infertility.

Mycoplasma: Spontaneous abortion + chorioamnionitis.

HPV: Implicated in cancer.

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6
Q

What is PID?

A

general term for infection of the female upper genital tract, inc. womb, fallopian tubes + ovaries.

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7
Q

How do gonococci, chlamydia and enteric bacteria cause PID?

A

Usually starts from the lower genital tract + spreads upward via mucosal surface.

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8
Q

How do staph, strep, coliform bacteria and clostridium perfringens cause PID?

A

Secondary to abortion.

Usually start from the uterus + spread by lymphatics + blood vessels upwards.

Deep tissue layer involvement.

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9
Q

List 4 complications associated with PID

A

Peritonitis

Bacteraemia

Intestinal obstruction due to adhesions

Infertility (due to adhesions)

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10
Q

What is the sequence of events with salpingitis?

A

Usually direct ascent from the vagina.

Depending on severity + tx may result in resolution or complications.

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11
Q

List 7 complications associated with salpingitis

A

Plical fusion

Adhesions to ovary

Tubo-ovarian abscess

Peritonitis

Hydrosalpinx

Infertility: path of ovum disrupted

Ectopic pregnancy

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12
Q

What is an ectopic pregnancy?

A

Pregnancy occurring anywhere outside the uterus

Most commonly Fallopian tubes

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13
Q

What is this?

A

Salpingitis

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14
Q

List 3 pathologies which can occur in the cervix

A

Inflammation- acute/ chronic

Polyps

Dysplasia + carcinoma

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15
Q

Give 2 epidemiological facts about cervical cancer

A

2nd most common cancer affecting F worldwide

Mean age 45-50

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16
Q

List 5 risk factors for cervical cancer

A

Human Papilloma Virus: present in 95%

Many sexual partners

Sexually active early

Smoking

Immunosuppressive disorders

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17
Q

Which HPV types are low risk? What do they cause?

A

Most common: 6 + 11

Other types: 40, 42, 43, 44, 54, 61, 72, 73, 81

Genital + oral warts.

Low grade cervical abnormalities.

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18
Q

Which HPV types are high risk? What do they cause?

A

Most common: 16 + 18

Other types: 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68,82

Low + high grade cervical abnormalities.

Cervical cancer.

Vulval, vaginal, penile, + anal cancer.

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19
Q

What is cervical intraepithelial neoplasia (CIN)?

A

CIN= dysplasia in cervix.

Epithelial cells have undergone some phenotypic + genetic changes which are premalignant + preinvasive.

Basal membrane immediately deep to surface epithelium is intact.

Squamous epithelium (CIN) is involved more often than glandular epithelium (CGIN).

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20
Q

What do the precursors CIN and CGIN lead to?

A

CIN: Squamous cell carcinoma of the cervix

CGIN: Adenocarcinoma of the cervix

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21
Q

Briefly describe the progression from HPV to carcinoma

A

HPV infection: abnormal cells

CIN1: mild dyskariosis limited to most superficial ⅓ of epithelium

CIN2: moderate dyskariosis

CIN3: severe dyskariosis involves >⅔ epithelium

Carcinoma in situ: abnormal growth involves full thickness of epithelium + no penetration of surrounding tissue

Invasive malignancy: breeches basement membrane

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22
Q

What is cervical carcinoma?

A

Invasion through the BM defines change from CIN to invasive carcinoma.

2 types of cervical cancer:

  • Squamous cell carcinoma (most common)
  • Adenocarcinoma (20% of all invasive cases- HPV dependent or independent.)
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23
Q

What is this?

A

Squamous cell carcinoma (cervical carcinoma)

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24
Q

What is this?

A

Adenocarcinoma (cervical carcinoma)

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25
Q

Give 4 factors affecting prognosis of cervical cancer

A

Tumour type

Tumour grade

Tumour stage: FIGO I (90%) - IV (10%) 5y S

Lymphovascular space invasion

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26
Q

What are the 2 distinct biological states of HPV?

A

Non productive/ Latent

Productive

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27
Q

How does HPV transform cells?

A

2 proteins E6 + E7 encoded by the virus have transforming genes.

E6 + E7 bind to + inactivate 2 tumour suppressor genes:

  • Retinoblastoma gene (Rb) (E7)
  • P53 (E6)

Interferes with apoptosis + increases unscheduled cellular proliferation, both of which contribute to oncogenesis.

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28
Q

What is the pathophysiology of HPV in non-productive/ latent phases?

A

HPV DNA continues to reside in basal cells.

Infectious virions NOT produced.

Replication of viral DNA is coupled to replication of the epithelial cells occurring in concert with replication of the host DNA.

Complete viral particles NOT produced.

Cellular effects of HPV infection NOT seen.

Infection only identified by molecular methods.

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29
Q

What is the pathophysiology of HPV in productive viral infection stages?

A

Viral DNA replication occurs independently of host chromosomal DNA synthesis.

Large no. viral DNA are produced + result in infectious virions.

Characteristic cytological + histological features

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30
Q

What happens for most people infected with HPV?

A

Nothing.

Immune system eliminates HPV
HPV undetectable within 2y in 90%

Relatively few develop Sx

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31
Q

What are the screening intervals for cervical cancer?

A

25: 1st invitation

25-49: Every 3y

50-64: Every 5y

65+: Only if 1 of last 3 was abnormal

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32
Q

What are the screening approaches for cervical cancer?

A

Cervical cytology (less used): 50-95% sens. 90% spec.

Hybrid Capture II (HC2) HPV DNA test: molecular genetics (used more)

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33
Q

What does HC2 HPV DNA test assess?

A

5 low risk HPV types

13 high risk HPV types

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34
Q

What cancers does the HPV vaccine help protect against?

A

Cervical

Some cancers of anal/ genital areas + genital warts

Some head + neck cancers

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35
Q

When are people offered the HPV vaccination?

A

Girls + boys aged 12-13

2nd dose 6-25m after

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36
Q

Which cancers are screened for in the UK?

A

Breast

Bowel

Cervical

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37
Q

Describe the layers of the uterus

A

Endometrium: lines uterus, contains glands + stroma. Shed in menstruation.

Myometrium: thick muscle layer, contracts in birth.

Perimetrium: smooth outer layer

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38
Q

What are endometrial indications for uterine biopsies?

A

Infertility

Uterine bleeding

Thickened endometrium on imaging

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39
Q

What are uterus/ related mass indications for biopsies?

A

Lesion identified on imaging

As part of a wider resection

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40
Q

What is endometrial hyperplasia? What is this usually driven by? What is the most common presentation?

A

irregular proliferation of endometrial glands with an increase in gland to stroma ratio

Driven by persistent oestrogen

Usual presentation: abnormal uterine bleeding

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41
Q

List 5 causes of endometrial hyperplasia

A

Peri-menopause

Persistent anovulation (persistently raised oestrogen)

PCOS

Ovarian Granulosa cell tumours

Oestrogen therapy

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42
Q

What is the most common gynaecological malignancy in developed countries? What is the most common subtype?

A

Endometrial cancer: Endometrioid

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43
Q

List 4 risk factors for endometrial cancer

A

Nulliparity

Obesity

Diabetes mellitus

Excessive oestrogen stimulation

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44
Q

Give 4 features of endometrioid carcinomas

A

Oestrogen dependent

Often a/w atypical endometrial hyperplasia

Low grade + high grade tumours

Develop through the accumulation of mutations of different genes.

45
Q

What is this?

A

Endometrioid Carcinoma

46
Q

What is this?

A

Endometrioid carcinoma

47
Q

Give 4 facts about serous and clear cell carcinomas

A

Older, postmenopausal

Less oestrogen dependent

Arise in atrophic endometrium

High grade, deeper invasion, higher stage

48
Q

Which mutations are associated with endometrial serous carcinomas?

A

P53 mutations in 90%

PI3KCA mutations in 15%

Her-2 amplification

49
Q

Which mutations are associated with endometrial clear cell carcinoma?

A

PTEN mutation

CTNNB1 mutation

Her-2 amplification

50
Q

What is this?

A

Endometrial serous carcinoma

51
Q

What is this?

A

Endometrial clear cell carcinoma

52
Q

Which endometrial cancers are considered high grade?

A

Serous

Clear cell

Mixed

Undifferentiated

Dedifferentiated

Carcinosarcoma

53
Q

What system is used to grade endometrioid carcinomas?

A

FIGO 3 tier system depending on:

Architecture: % gland formation

Cytological atypic of individual cells

54
Q

What is the 2009 FIGO Staging for Carcinoma of the Endometrium?

A

Stage I: Tumour confined to corpus uteri.

Stage II: Tumour invades cervical stroma.

Stage III: Local +/- regional spread of tumour.

Stage IV: Tumour invades bladder +/- bowel mucosa, +/- distant metastases.

55
Q

What is this?

A

HMLH1 (A)

PMS2 (B)

MSH2 (C)

MH6 (D)

show strong nuclear expression in tumour cells of endometrioid carcinoma.

(mutations in mismatch repair genes)

56
Q

What are mesenchymal tumours (leiomyoma)?

A

Smooth muscle tumour of myometrium.

Commonest uterine tumour

20% of women >35y

AKA fibroid

Usually multiple

May be intramural, submucosal or subserosal

57
Q

What is this?

A

Leiomyoma

58
Q

What are leiomyosarcomas?

A

Malignant counterpart of leiomyoma: rare.

Usually solitary.

Usually postmenopausal.

Local invasion + blood stream spread.

5y survival 20-30%.

59
Q

What is this?

A

Leiomyosarcoma

60
Q

What is this?

A

Endometrial stromal sarcoma

61
Q

What is this?

A

Endometrial stromal sarcoma

62
Q

What is this?

A

Serous Epithelial Ovarian Tumour

63
Q

What is this?

A

Mucinous Epithelial Ovarian Tumour

64
Q

What is this?

A

Endometrioid Epithelial Ovarian Tumours

65
Q

What is this?

A

Clear cell Epithelial Ovarian Tumours

66
Q

What is this?

A

Brenner Epithelial Ovarian Tumours

67
Q

What is this?

A

Serous borderline tumour

68
Q

What is this?

A

Mucinous borderline tumour

69
Q

Give 4 features of high grade ovarian serous carcinomas

A

Most common type of malignant tumours (80%).

Aggressive.

  • Alteration in P53, in almost all.
  • BRCA1 or BRCA2 abnormalities (germline + somatic mutations; BRCA1 promoter methylation): encode proteins with important roles in DNA repair (homologous recombination).
70
Q

Which mutation is though to confer an overall survival advantage in high-grade serous ovarian cancer?

A

BRCA2 mutation

71
Q

Give 4 features of low grade ovarian serous carcinomas

A

Distinct pathogenesis from high grade serous carcinoma.

Low grade, relatively indolent, arise de novo or from borderline ovarian tumours.

Mutations in KRAS, BRAF.

No association with BRCA mutations.

72
Q

Give 5 features of Mucinous ovarian tumours

A

Very rare

Morphological features similar to mutinous tumours of GIT

KRAS mutations

If unilateral= primary

If bilateral: consider ovary as secondary

73
Q

Where are common origin sites for secondary ovarian tumours?

A

Metastatic colorectal carcinoma

Krukenberg tumours:

  • Bilateral mets composed of mucin producing signet ring cells.
  • Most often of gastric origin or breast.
74
Q

Give 3 facts about metastatic colorectal cancer spread causing secondary ovarian tumours

A
  • Ovaries= anatomic site prone to involvement by metastatic colorectal adenocarcinoma.
  • 4-10% of CRC go to ovary.
  • Ovarian lesions identified prior to primary tumor in 14-32% of cases.
75
Q

Give 2 facts about Krukenberg tumour spread causing secondary ovarian tumours

A

Causes bilateral mets composed of mucin producing signet ring cells

Often of gastric/ breast origin

76
Q

What are the 3 different categories of sex-cord stromal tumours?

A

Pure stromal tumours: Fibroma, Thecoma, microcystic stromal tumour.

Pure sex cord cells: Adult type + juvenile granulosa cell tumour.

Mixed sex cord-stromal tumours: Sertoli Leydig cell tumour.

77
Q

What is this?

A

Fibroma:

Fibroblasts

Benign, no endocrine production

78
Q

What is this?

A

Granulosa cell tumor:

Granulosa cells

Variable behaviour, may produce estrogen

79
Q

Give 3 facts about Thecomas

A

Derived from Thecal cells

Benign

May secrete Oestrogen or rarely androgens

80
Q

Give 2 facts about Sertoli-Leydig cell tumours

A

Variable behaviour

May be androgenic

81
Q

What somatic mutation is found in 97% of adult type granulosa cell tumours?

A

FOXL2

(master transcription factor, regulates proliferation + apoptosis)

82
Q

What is DICER1 Syndrome?

A

Germline mutation in DICER1, a gene encoding an RNAse III endoribonuclease.

Familial multinodular goitre with sertoli/ leydig cell tumour + tumour susceptibility inc. pleuropulonry blastoma in childhood.

Found in up to 60% of sertoli-Leydig cell tumours.

83
Q

What is Peutz-Jegher’s Syndrome?

A

Germline mutations of STK11

Sex cord stromal tumour with annular tubules

Cases occurring in PJS usually show indolent behaviour.

84
Q

Give 3 facts about germ cell tumours

A

Account for 20% of ovarian tumours

95% benign

Predominantly occur in 1st + 2nd decade

85
Q

What are immature teratomas?

A

Indicates presence of embryonic elements.

Neural tissue particularly conspicuous.

Malignant neoplasm grows rapidly, penetrates the capsule + forms adhesions to surrounding structures.

Spreads in the peritoneal cavity by implantation.

Mets to LN, lung, liver + other organs.

86
Q

What is this?

A

Dysgerminoma

(germ cell tumour)

87
Q

What is this?

A

Yolk sac tumour

(germ cell tumour)

88
Q

What is this?

A

Embryonal carcinoma

(germ cell tumour)

89
Q

What is this?

A

Choriocarcinoma

(germ cell tumour)

90
Q

What is endometriosis?

A

Presence of endometrial glands + stroma outside of the uterus

10% of premenopausal women

Ectopic endometrial tissue is functional + bleeds at time of menstruation: pain, scarring + infertility

Can develop hyperplasia + malignancy

91
Q

What are the non-neoplastic functional ovarian cysts? What symptoms may these cause?

A

Follicular + luteal cysts

+/- Abdo pain/ mass

Self resolving

92
Q

What is an endometrioma?

A

Ovarian cyst in endometriosis

“Chocolate cyst”

Filled with old blood

93
Q

Describe the epidemiology of epithelial ovarian tumours

A

65% of all ovarian tumours

95% of malignant ovarian tumours

50% in 45-65y

94
Q

Describe the epidemiology of germ cell ovarian tumours

A

Bimodal distribution

15-21

65-69

95
Q

Describe the epidemiology of sex cord stromal ovarian tumours

A

Most commonly in post-menopausal women

Subtypes peak in 25-30y

96
Q

What is a ‘borderline’ tumour?

A

Tumour whose biologic behaviour- can’t be predicted on histologic grounds

Have very low but definite metastatic potential

Morphologically similar tumours may behave differently

97
Q

List 4 benign epithelial ovarian tumours

A

Serous Cystadenomas

Cystadenofibromas

Mutinous cystadenomas

Brenner tumour

98
Q

Give 2 statistics about malignant epithelial ovarian tumours

A

6th most common cancer in F worldwide

2nd most common cancer causing death in F

99
Q

List 5 risk factors for malignant epithelial ovarian tumours

A

Nulliparity

Infertility

Early menarche

Late menopause

FH: ovarian/ breast cancers

100
Q

List 3 familial syndromes associated with epithelial ovarian cancer

A

Familial breast-ovarian cancer syndrome a/w BRCA1+2

Site-specific ovarian cancer a/w BRCA1+2

Cancer family syndrome (Lynch type II)

101
Q

How are the familial syndromes associated with epithelial ovarian cancer transmitted?

A

Autosomal dominant

Hereditary ovarian cancer occurs at younger age than sporadic

102
Q

Which ovarian cancers are most common in patients with Lynch II syndrome?

A

Endometrioid

Clear cell

103
Q

Which is the most common ovarian malignancy in the general population?

A

Serous carcinoma

104
Q

Which cancer does endometriosis have a strong association with?

A

Clear cell ovarian carcinoma

105
Q

Which cancer does endometriosis have a weak association with?

A

Endometrioid ovarian carcinoma

(10-20% of endometrioid carcinoma cases)

106
Q

Give 2 facts about endometrioid carcinoma

A

Most thought to be derived from surface epithelium

Co-existance with endometrioid carcinoma in uterus is common

107
Q

Give 5 facts about mature teratomas (Dermoid)

A

Commonest germ cell tumour

Benign

Solid or cystic

May show many lines of differentiation but all mature adult type tissues

Teeth + hair v common

108
Q

Which part of the female genital tract is the most common site of metastasis?

A

Ovaries

YR5 Histopathology (27 decks)

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