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MD3002 > Pathology of the Female Reproductive System 1 > Flashcards

Pathology of the Female Reproductive System 1 Flashcards

1
Q

Identify some common benign breast diseases.

A
  • Developmental abnormalities
  • Inflammatory lesions
  • Epithelial and stromal proliferations
  • Neoplasms.
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2
Q

What proportion of patients referred to breast units are diagnosed with a benign condition ?

A

About 90% of patients referred to breast units are diagnosed with a benign condition.

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3
Q

Benign breast disease

  • How common ?
  • Frequency with age ?
  • Differences clinically with breast cancer
A

Benign breast cancer

  • Common
  • Increases in frequency towards menopause then decreases
  • May be difficult to distinguish clinically from breast cancer
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4
Q

How is the diagnosis of benign breast disease accomplished ?

A
  • Mammography
  • Ultrasound (NOT for screening, for assessment)
  • MRI of the breast (NOT for screening, for assessment)
  • Needle biopsies

through these, the diagnosis of a benign breast disease can be accomplished without surgery in the majority of patients.

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5
Q

How is it preferable to avoid surgery for benign breast lesions ?

A

Because the majority of benign lesions are not associated with an increased risk for subsequent breast cancer, unnecessary surgical procedures should be avoided.

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6
Q

Distinguish between the US appearance of benign, and malignant lesions.

A

BENIGN

  • Oval/ellipsoid shape
  • Wider than deep
  • Smooth margins

MALIGNANT

  • Variable shape
  • Deeper than wide
  • Irregular or spiculated margins
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7
Q

Distinguish between normal, and malignant cells in cytology.

A

NORMAL

  • Large cytoplasm
  • Single nucleus
  • Single nucleolus
  • Fine chromatin

MALIGNANT

  • Small cytoplasm
  • Multiple nuclei
  • Multiple and large nucleoli
  • Coarse chromatin
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8
Q

Describe normal breast architecture in the adolescent.

A

Large and intermediate-size ducts are seen within a dense fibrous stroma. No lobular units are present.

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9
Q

Describe normal breast architecture in the postpubertal breast.

A

The terminal duct lobular unit consists of
small ductules arrayed around an intralobular duct. The two- cell-layered epithelium shows no secretory or mitotic activity. The intralobular stroma is dense and confluent with the interlobular stroma.

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10
Q

Describe normal breast architecture in the lactating breast.

A

The terminal duct lobular units are conspicuously enlarged, with inapparent interlobular and intralobular stroma. The individual terminal ducts, now termed acini, show prominent epithelial secretory activity (cytoplasmic vacuolization). The acinar lumina contain secretory material.

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11
Q

Describe normal breast architecture in the postmenopausal breast.

A

The terminal duct lobular units are absent. The remaining intermediate ducts and larger ducts are commonly dilated.

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12
Q

Define fibrocystic change.

A
  • Fibrocystic Change (FCC) is an exaggerated physiologic response.
  • Nonproliferative change that includes gross and microscopic cysts, apocrine metaplasia, mild epithelial hyperplasia, adenosis and an increase in fibrous stroma.
  • Typically multifocal and bilateral.
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13
Q

What proportion of women aged 20-50 are affected by FCC ? How does its frequency change postmenopause ?

A

FCC affects over one third of women 20–50 years old, then declines after menopause.

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14
Q

What are the main symptoms of FCC ?

A

Most women with FCC are asymptomatic, but some present with nodularity and pain.

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15
Q

Identify the main benign breast lesions histologically.

A
  • FCC (nonproliferative)
  • Proliferative Breast Disease (without atypia)
  • Atypical Ductal Hyperplasia
  • Fat necrosis
  • Benign Breast Tumours
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16
Q

How does having FCC affect risk of breast cancer ?

A

FCC doesn’t increase the risk of getting breast cancer, but it can make it more difficult to identify potentially cancerous lumps during breast examination and on mammograms

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17
Q

How does having proliferative breast disease affect risk of breast cancer ?

A

Proliferative disease without atypia entails a 2 fold increased risk of developing carcinoma over 5–15 years and is classified simply as proliferative breast disease.

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18
Q

How does having atypical ductal hyperplasia affect risk of breast cancer ?

A

Proliferative lesions with atypia involve even greater relative risk (5 fold) than simple proliferative disease. Such patients require close clinical monitoring.

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19
Q

Describe the overall pathogenesis of breast cancer.

A

Normal epithelium –> Proliferative disease without atypia –> Atypical hyperplasia –> DCIS –> Invasive breast cancer

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20
Q

How may cysts (e.g. in FCC) be distinguished from solid masses ?

A

Cysts cannot reliably be distinguished from solid masses by clinical breast examination or mammography; in these cases, ultrasonography and fine needle aspiration (FNA) cytology, which are highly accurate, are used.

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21
Q

To what extent can men develop benign breast conditions ?

A

Men can also develop benign breast conditions and the most common in men is Gynaecomastia (hyperplasia of the male breast stromal and ductal tissue)

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22
Q

What are the main causes of Gynecomastia in men ?

A

• It is usually caused by a relative increase in the oestrogen to androgen ratio in the circulation or breast tissue.
• The most common cause is secondary to drugs.
• In older patients, it involves cardiovascular and prostate drugs, and in younger patients, cannabis, anabolic steroids, anti-ulcer drugs and antidepressants
• Other pathological causes include undiagnosed
hyperprolactinaemia, liver failure, alcohol excess, obesity and malignancy (testes and lung).

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23
Q

Can gynecomastia present physiologically ?

A

Gynaecomastia can also be physiological and present spontaneously in a trimodal age pattern; neonates,
pubertal and senescence. These cases are usually self-
limiting.

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24
Q

Identify the main types of benign breast tumors.

A
  • Fibroadenoma
  • Duct papilloma
  • Adenoma
  • Connective tissue tumours
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25
Q

FIBROADENOMAS

  • Which cells do they arise from ?
  • Appearance
  • Clinically
A

FIBROADENOMAS

  • arise from breast lobules and are composed of fibrous and epithelial tissue
  • well circumscribed, oval shaped, and highly mobile lump (easily identifiable on US), because of the encapsulation and pliability of young breast tissue
  • clinically, difficult to differentiate from Phyllodes Tumours, which is a distinct pathology
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26
Q

What is a Phyllodes Tumour ? What are the main differences between Phyllodes Tumours and Fibroadenomas ?

A

Phyllodes tumours are sarcomas which rapidly enlarge and have variable degrees of malignant potential.

1) Larger than fibroadenomas and tend to occur in an older age group
2) Different appearance (fibroadenomas are smooth, well circumscribed, oval shaped, highly mobile)

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27
Q

Clinically, how may we diagnose between a fibroadenoma and a phyllodes Tumor ?

A
  • Young patients (less than 25 years) with clearly benign clinical and imaging findings are usually spared a core biopsy (traumatic and can give rise to bleeding/fat necrosis so only if necessary)
  • In older patients we have to rule out occult malignancy / Phyllodes tumour (so biopsy)
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28
Q

Distinguish between FCC and fibroadenoma.

A

FCC

  • May be painful
  • Needle aspiration shows straw-colored or green fluid
  • Most common benign breast condition

FIBROADENOMA

  • Typically painless
  • Benign solid tumor containing glandular and fibrous tissue
  • Core biopsy may be required (esp if older patient)
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29
Q

Describe the management for fibroadenomas.

A

Can be followed clinically or surgically excised

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30
Q

How does fat necrosis of the breast present ? How may this be diagnosed ?

A

Fat necrosis presents as a soft, indistinct lump that develops a few weeks after a traumatic incident, and often in older women with fatty breasts.

Using imaging, some are difficult to distinguish from breast cancer and a core biopsy is often indicated

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31
Q

What proportion of all cancers in women does breast carcinoma make up ?
What proportion of all breast carcinomas occur in men ?

A

20% of all cancers in women.

1% of tumours occur in men.

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32
Q

In the UK, what is the lifetime risk of breast carcinoma in women ?

A

In the UK, lifetime risk for women is 1 in 9.

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33
Q

What is the commonest cause of death in women in 35-55 age group ?

A

Breast carcinoma

34
Q

What is the most common cancer in the UK ?

A

Breast carcinoma

35
Q

What are the main risk factors for breast cancer ?

A
  • Alcohol
  • Estrogen-progesterone contraceptives
  • Estrogen-progesterone menopausal therapy
  • X radiation and Gamma radiation
  • Body fatness (post-menopausal breast cancer only)
36
Q

What are some factors which decrease risk of breast cancer ?

A
  • Physical activity

- Body fatness (pre-menopausal breast cancer only)

37
Q

Identify the main non-invasive precursors of breast cancer. Where are they typically found ?

A

Tumour cells confined to ducts or acini.

Two forms:

1) Ductal carcinoma in situ.
- Often unilateral.

2) Lobular carcinoma in situ.
- Often bilateral, can be multifocal.

38
Q

How are non-invasive precursors of breast cancer usually identified ?

A

Usually identified coincidentally.

39
Q

Describe the histological appearance of high grade ductal carcinoma in situ.

A
  • Breast duct filled with atypical, crowded cells with a high mitotic rate and areas of cell death (apoptosis).
  • The lumen of the duct is filled with dead cells, inflammatory cells and fine calcium granules.
  • There is no invasion of cells beyond the duct.
  • Possible micro-calcifications present (mainly for medium grade DCIS)
40
Q

Define high grade in the context of tumors.

A

Poorly differentiated

41
Q

Describe the X-ray appearance of DCIS.

A

Micro-calcifications

42
Q

What are the main types of invasive carcinoma of the breast ? State the proportion of each relative to total number of invasive carcinomas of the breast.

A
  • Most are of ‘No Special Type’ (old term ‘ductal’) 75 - 90%.
  • Infiltrating lobular carcinoma (10%), may be multifocal.
  • There are some special types (less common).
43
Q

What are the main kinds of breast cancer ?

A

1) Carcinomas (majority)
2) Phyllodes Tumours
3) Paget’s Disease of the nipple

44
Q

What is Paget’s Disease of the nipple ?

A
  • Leads to erosion of the nipple that resembles eczema

* Associated with underlying in situ or invasive carcinoma

45
Q

How does breast cancer spread ?

A
  • Direct
  • Lymphatics
  • Blood stream (e.g. to lungs, bone, breast)
  • Transcoelomic
46
Q

Describe the method of SLNB for confirmation/exclusion of metastatic spread of tumour to axillary nodes ?

A

LNB helps to ascertain if it is necessary to perform an axillary clearance and helps in planning of further therapy. It can also provide prognostic information about the patient’s survival and tumour recurrence. The theory behind SLNB is that cells from the primary tumour are likely to spread to the first node to receive lymph from the involved area. This node is known as the sentinel node. SLNB involves the use of a radioactive tracer (technetium-99m) and a blue dye. Prior to surgery, breast tissue around a tumour is injected with a small amount of radioactive fluid which migrates to the sentinel node over minutes to hours. During surgery, a blue dye is then injected into the breast tissue close to the tumour. This will also track to the sentinel node.
The sentinel node is then detected via a radiation detection probe (gamma sensor). A small incision is made in the skin at the site of the sentinel node and the node should also have turned blue, this is used for visual confirmation of the sentinel node. After identification, the node is removed and examined. If the sentinel node is free of tumour then removal of the remaining lymph nodes is not necessary.

47
Q

Identify the main prognostic factors in breast cancer.

A 
♦ Tumour type
♦ Tumour grade (A) 
♦ Tumour stage
– Tumour size
– Node metastasis (B) 
– Other metastases

♦ Oestrogen receptor (C) (if positive or not)
♦ HER-2 amplification

48
Q

Identify the main factors that have led to steady improvements in the long-term survival rates for breast cancer.

A

Better diagnosis
Improved treatments
Screening programmes
Public awareness

49
Q

What proportion of women with breast cancer will survive for at least five years after diagnoses ? 10 year after diagnosis ? 20 years ?

A

More than 8 out of 10 women with breast cancer will survive for at least five years after diagnoses.

More than three-quarters of women diagnosed with breast cancer now survive for at least 10 years or more.

Almost two out of three women with breast cancer now survive their disease beyond 20 years.

50
Q

What are the main screening strategies of breast cancer ?

A
  • Breast self examination.
  • Clinical breast examination.
  • Mammography.
  • Ultrasonography.
  • Magnetic Resonance Imaging (MRI).

The selection of women can be based on:
• Risk factor based, or universal
• Age

51
Q

What number of women in the UK undergoes breast cancer screening ?

A

2 Million

52
Q

Describe NHS Breast Screening Program.

A

-Invites all women aged between 50 and 70 for screening every 3 years.
-You need to be registered with a GP to receive the invitations.
• Around 4 out of 100 women (4%) are called back for further investigation.

53
Q

What is the significance of the NHS Breast Screening Program ?

A

Breast cancers found by screening are generally at an early stage. Very early breast cancers are usually easier to treat, may need less treatment, and are more likely to be cured.

As a result, decreased mortality thanks to screening

54
Q

Is screening for breast cancer effective ?

A

Evidence from randomised trials suggests that screening is effective. Screening saves about one life from breast cancer for every 200 women who are screened.

BUT

For every one woman who is saved, about three women are diagnosed with a cancer that would never have become life threatening, so offered treatment they did not need.

55
Q

Identify the main genetic mutations associated with familial breast cancer.

A

TP53 mutations

BRCA1 and 2 mutations

56
Q

What are the recommendations of NICE concerning screening for women with familial history of breast cancer.

A

NICE recommend yearly MRI scans from:

  • Age 20 for women with a TP53 mutation
  • Age 30 for women with a BRCA1 or BRCA2 mutation.
57
Q

What proportion of all breast cancers are thought to be familial ?

A

About 5% of all patients with breast cancer are thought to be affected by breast cancer genes.

58
Q

What signs/symptoms are red flags for breast cancer ? (Ie. refer urgently for suspected breast cancer )

A

Refer urgently for suspected breast cancer when:
• aged 30 and over and have an unexplained breast lump with or without pain.
• aged 30 and over with an unexplained lump in the axilla.
• with skin changes that suggest breast cancer.
• aged 50 and over with any of the following symptoms in one nipple only: discharge / retraction / other changes of concern e.g. rash, dripping, dimpling

Consider non-urgent referral in people aged under 30 with an unexplained breast lump with or without pain.

59
Q

Identify the main pathologies of the female reproductive system (beside breast pathologies).

A

MALIGNANCIES
-Cervical Squamous Neoplasia (includes invasive cervical cancer, which are mainly SCCs, but a minority includes adenocarcinomas)

60
Q

What are the main causes of Cervical Squamous Neoplasia ?

A
  • Human papillomavirus main aetiological factor.

* Immune modulation: smoking, HIV infection.

61
Q

How may Cervical Squamous Neoplasia be diagnosed ?

A

• Pre-invasive phase detectable by cervical cytology.

62
Q

Describe the classification system for pre-invasive Cervical Squamous Neoplasia.

A

• Grading systems for pre invasive disease: Bethesda classification:
- Cervical intraepithelial neoplasia (CIN) grades 1 to 3 (squamous intraepithelial lesions are precursors of invasive cancer)
- ‘Low grade squamous intraepithelial
neoplasia’ (LSIL, = grade 1) versus ‘high grade’ (HSIL, = grades 2,3)

63
Q

Do condoms eradicate risk of HPV tranmission ?

A

Condoms offer some protection but do not eradicate risk of transmission.

64
Q

Describe the pathophysiology of Cervical Cancer.

A

1) HPV infection becomes persistent (usually transient and cleared without clinical consequences) (normal tissue becomes LSIL)
2) the virus may incorporate its DNA into the host cell’s genome (LSIL becomes HSIL)
3) once incorporated, the production of viral oncoproteins can go on unchecked, and the host’s genes that suppress tumours (p53 and pRb) can be inactivated.
4) Damaged DNA is replicated without being checked and repaired, and malignantly transformed cells proliferate uncontrollably.

Modifiers such as HIV, smoking, immunodepression, STD, can contribute to this further.

65
Q

What is the latency incubation period to cancer, from HPV ?

A

15 years

66
Q

Which part of the cervix are neoplastic changes most likely to occur in ?

A

The cervix transformation zone (columnar epithelium of endometrial lining transitions into squamous epithelium of lining of vagina)

67
Q

Identify screening strategies for cervical cancer.

A

Screening:
• Cytology
- Spatula, Cytobrush, Glass slide, Liquid based
• HPV detection (16, 18, others)
• Visual inspection with acetic acid or iodine
• Colposcopy and biopsy

• Vaccination!

68
Q

Describe the process of cytology for cervical cancer screening.

A
  • The first stage in cervical screening is taking a cervical sample using liquid based cytology (LBC), which has replaced the conventional Pap smear.
  • National policy of not starting screening to age 25 and thereafter screening every three years until the age of 49 years and every five years from age 50-64 years
69
Q

How does malignant breast disease change in frequency over time.

A

Increases over time, even further after menopause (BUT more aggressive and inherited forms tend to be at younger age)

70
Q

What is the most common form of cervical cancer ?

A

The commonest cervical cancer is an invasive tumour of epithelial origin with squamous differentiation.

71
Q

Why have we stopped using Pap smears as much in cervical cancer ?

A

Because the slides used included a lot of debris and mucus which were difficult to interpret. This does not occur with liquid based cytology.

72
Q

Identify management options for cervical cancer.

A
  • Local excision (Large Loop Excision of the Transformation Zone (LLETZ), using Loop Electrosurgical Excision procedure (LEEP))
  • Cryotherapy (destroying cells of the transition zone)
73
Q

What is the precursor lesion for invasive cervical adenocarcinoma ?

A

Cervical Glandular Intraepithelial Neoplasia (CGIN)

74
Q

Identify the classical symptoms of invasive cervical cancer.

A

Post coital bleeding, but many asymptomatic in the early

stages.

75
Q

Describe treatment of invasive Squamous cell carcinoma of the Cervix.

A
  • Radical hysterectomy is favoured for localized tumour, especially in younger women.
  • For tumours larger than 4 cm or spread beyond the cervix, radiotherapy with concurrent platinum based chemotherapy is the mainstay of treatment.
76
Q

What proportion of adolescent girls need to be vaccinated against HPV to prevent cervical cancer in the population ?

A

80%

77
Q

Describe the delivery of HPV vaccine in the UK.

A
  • A routine immunisation programme for HPV started across the UK in September 2008 for 12-13 year old girls (school year eight).
  • As well as routine immunisation of girls in school year eight, in the first three years there was an initial phased catch up of girls currently aged up to 18 years.
  • Gardasil is used
  • Boys aged between 12 and 13 in England, Scotland and Wales will be offered immunisation against HPV.
  • A vaccination programme for men aged 45 or younger who have sex with other men was also announced in 2018 in England, and was introduced in 2017 in Scotland.
78
Q

What was the effect of the HPV vaccine on prevalence of cervical cancer ?

A

Prevalence dropped

79
Q

What is the mean age at which women develop SIL (CIN) ?

A

25-30 years

80
Q

Out of all LSILs (CIN 1), how many regress, how many progress into HSILs (CIN 2 and 3) ? how many progress into invasive cancers ?

Contrast these stats with the proportion of HSILs that progress into invasive squamous carcinoma.

A

70%
6%
1%

Progression of HSIL (CIN 2 & 3) to invasive squamous carcinoma occurs with greater frequency and over a shorter interval (10% to 20% of cases of HSIL (CIN 2 and 3) progress to invasive carcinoma if untreated)

81
Q

Describe the ease of detection of breast cancer, compared to cervical cancer.

A

Breast cancer: pre malignant phase less obvious, may not be invariably present and difficult to detect by screening as no lump is present.

Cervical cancer: well understood pathway from HPV infection through CIN to invasive cancer; readily accessible for screening.

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