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Phase 3 > Female GU and Breast > Flashcards

Female GU and Breast Flashcards

1
Q

Describe developmental abnormalities involving the breast

A
  • Ectopic (Heterotopic) Breast Tissue
    • Commonest congenital abnormality
    • Most often on ‘milk line’ between axilla and groin
  • Absent Nipple
  • Nipple with Little Glandular Development
  • Breast Hypoplasia
  • Macromastia
    • Stromal overgrowth leading to excessive breast size, occasionally begins at puberty (juvenile hypertrophy) or during pregnancy (gestational hypertrophy)
  • Nipple Inversion
  • Asymmetry
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2
Q

Describe periductal mastitis

A

Periductal Mastitis/Plasma Cell Mastitis/Duct Ectasia

A dilation of central lactiferous ducts, periductal chronic inflammation and scarring

Often asymptomatic but there may be discomfort, a mass, nipple retraction or inversion

Calcified luminal secretions may be seen on mammogram

It is commonest in middle age and is associated with smoking

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3
Q

Describe fat necrosis of the breast

A

The initial change is disruption of fat cells where vacuoles with the remnants of necrotic fat cells are formed

They then become surrounded by lipid-laden macrophages, multinucleated giant cells, and acute inflammatory cells

Fibrosis develops during the reparative phase peripherally enclosing an area of necrotic fat and cellular debris

Eventually, fibrosis may replace the area of degenerated fat with a scar, or loculated and degenerated fat may persist for years within a fibrotic scar

May follow trauma

Benign, but biopsy may be required to exclude cancer

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4
Q

Describe intraduct papilloma of the breast

A

A benign tumour of the epithelium lining of the mammary ducts

Solitary central papillomas are thought to be innocuous if there is no epithelial atypia

Multiple papillomas (papillomatosis) are thought to be slightly more likely to be associated with malignancy elsewhere in the same or the contralateral breast

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5
Q

Describe fibroadenoma of the breast

A

About 25% of asymptomatic women have at least one fibroadenoma in which there is characteristic overgrowth of epithelium and stroma

Symptomatic fibroadenomas are commonest in young women

Usually regarded as a benign neoplasm, hormone-sensitive and regress after the menopause

Usually firm, non-tender, mobile, usually <25-30mm

Rare fibroadenomas in adolescent girls may become very large

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6
Q

Describe the ranges of fibrocystic change in the breast

A

Very common and frequent benign breast condition

Tends to be multifocal and bilateral and may cause breast tenderness and nodularity

Ranges from small/large cysts, increased amounts of glandular tissue (adenosis), increased fibrous stroma, epithelial hyperplasia (of usual or occasionally atypical type)

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7
Q

State factors modifying breast cancer risk

A

Early Menarche

Late Menopause

Being Older at First Pregnancy

Oral Contraceptive Use

HRT

Obesity

Alcohol

Family History (BRCA1/BRCA2)

Protective factors include Exercise and Breast Feeding

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8
Q

Describe signs and symptoms of breast cancer

A
  • New lump or thickening in breast or axilla
  • Altered shape, size or feel of the breast
  • Pain
  • Skin changes:
    • Puckering
    • Dimpling
    • Skin oedema (orange peel)
    • Rash
    • Redness
  • Nipple changes:
    • Tethering/inversion
    • Discharge
    • Eczema-like change
  • Widespread inflammation
  • Redness
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9
Q

Describe the diagnosis of breast cancer

A
  • Clinical Examination
  • Imagine
    • USS
    • X-Ray Mammography
    • MRI
  • Fine Needle Aspiration Cytology
  • Core Biopsy
  • Excisional Biopsy
    • May be diagnostic, therapeutic or both
  • Women between 47 and 73 are invited for triennial 2-view mammography breast screening and may self-refer after 73
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10
Q

Describe the importance of steroid hormone receptors in breast cancer

A

About 80% of breast cancers overexpress oestrogen receptors (ER) and progesterone receptor (PR)

ER/PR positive carcinomas are likely to respond to endocrine treatment (e.g. with Tamoxifen which in breast is predominantly an ER antagonist)

In endometrium and bone, Tamoxifen has a significant agonistic effect and there is elevation of endometrial cancer risk in women treated with Tamoxifen

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11
Q

Describe the importance of Her2 status in breast cancer

A

As a group, cancers which overexpress Her2 have a worse prognosis than other breast cancers

But treatment with the monoclonal antibody Trastuzumab (Herceptin) and other Her2 targeted therapies has improved outcomes

Adjuvant Herceptin reduces the risk of relapse in women with Her2 +ve breast cancer and prolongs survival in women with metastatic breast cancer

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12
Q

Describe the grading of breast cancers

A

Based on Nuclear Pleomorphism, Number of Mitoses per mm2 and Degree of Gland Formation by the Cancer Cells

Grade 1 - Well-Differentiated and Slow Growing

Grade 2 - In Between

Grade 3 - Poorly Differentiated and Fast Growing

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13
Q

Describe the Nottingham Prognostic Index

A

Prognostic index for breast cancer, following surgery

(Tumour Size x 0.2) + Grade + LN Involvement

0 Nodes = 1

1-3 Nodes = 2

4+ Nodes = 3

Higher the NPI, the lower the 5 Yr SR

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14
Q

Describe the molecular classification of breast cancer

A

The main distinction is still between ER -ve and ER +ve cancers

Luminal A ER+ cancers tend to be low grade, less proliferative and have a better prognosis

Luminal B ER+ cancers tend to be high grade, more proliferative and potentially do less well

In the ER- cancer group, there are three subtypes; normal breast-like, Her2 or basal-like

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15
Q

Describe the management options for breast cancer

A

Surgery (wide local excision plus radiotherapy or mastectomy for larger cancers)

Endocrine targeted treatment can help prevent relapse at distant sites

in triple negative cancers especially, adjuvant chemotherapy is important

1 in 3 potential episodes of metastatic relapse can be prevented by adjuvant chemotherapy

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16
Q

Describe cervical intraepithelial neoplasia (CIN)

A

Replacement of normal squamous epithelium by neoplastic squamous cells

Basement membrane remains intact

The neoplastic cells have the usual morphological features, abnormally intense staining (hyperchromasia), greater variability (pleomorphism) and fail to mature properly (and go on proliferating with mitotic cells visible) as they migrate from the base of the epithelium to its surface

Immature and dividing cells are confined to the basal 1/3 of the epithelium in CIN 1, the basal 2/3 in CIN 2 and persist into the surface 1/3 in CIN 3

Invasive squamous carcinoma of the cervix almost always develops from pre-existing CIN, but not all CIN will become squamous cancer

CIN 2 and CIN 3 are more likely to progress than CIN 1

17
Q

Describe squamous metaplasia of the cervical transformation zone

A

Prior to puberty, the ectocervix is covered by non-keratinising stratified squamous epithelium and the endocervix is lined by columnar (glandular) epithelium

With growth of the cervix after puberty, the squamo-columnar junction is everted into the vagina and the squamous epithelium adapts to the vaginal environment by squamous metaplasia in the ‘transformation zone’

These changes are reversed at the menopause

This zone of unstable differentiation is where most cervical neoplasia develop

18
Q

Describe the effect of HPV on the cervix

A

More than 99% of cervical carcinomas are associated with HPV infection

Even in the absence of CIN, HPV infection does visibly affect the cells of the cervical squamous epithelium

Even in the absence of productive infection, viral DNA can persist extra-chromosomally or integrated into the host’s cells

High risk HPV types 16 and 18 are strongly associated with CIN 2, CIN 3 and cervical cancer

19
Q

State the outcomes of cervical smear reporting

A
  • Negative
    • Repeat Routinely in 3 Years
  • Borderline Nuclear Abnormality
    • Repeat 6 Months
    • (If 3 x BNAs - Refer to Colposcopy)
  • Mild, Moderate or Severe Dyskaryosis
    • Refer to Colposcopy
  • Features SUggestive of Invasion
    • Urgent Referral to Colposcopy
20
Q

Describe the features and effects of Salpingitis

A

Part of the spectrum of pelvic inflammatory disease

Most commonly infective (mainly bacterial - chlamydia trachomatis, mycoplasma, coliforms, streptococci, staphylococci, Neisseria gonorrhoea)

Usually considered to be an ascending infection

Symptoms include fever, lower abdominal/pelvic pain and pelvic mass (if tubes distended with exudate or secretions)

Complications: Adherence of tube to ovary (tubo-ovarian abscess); Adhesions involving tubal plicae increase risk of ectopic pregnancy; Damage or obstruction of tube lumen may produce infertility which may be difficult to treat

21
Q

Describe the features and effects of non-neoplastic cysts of the ovaries

A

Non-neoplastic cysts include inclusion, follicular and luteal cysts

Symptoms include oligomenorrhoea, hirsutism, infertility, over-production of androgens by cystic follicles, high LH and low FSH

Effects include enlarged ovaries, multiple subcortical cysts (5-15mm), thickened and fibrotic outer surface, absence of corpus lutea and corpus albicans (as ovulation is not occurring) and insulin resistance (which may lead to T2DM)

22
Q

Describe the processes, features and effects of ovarian surface epithelial tumours

A

Thought to arise from coelomic mesothelium on the surface of the ovary

Benign lesions usually cystic (cystadenoma) with or without a solid stromal component (cystadenofibroma)

Malignant epithelial tumours (carcinomas) may be cystic (cystadenocarcinoma) or solid (adenocarcinoma)

Carcinomas may be high grade serous (HGSC), endometroid, clear-cell, low grade serous (LGSC) or mucinous

HGSC is closely associated with p53 and BRCA1 mutations

Most women with ovarian cancer present late and in many the prognosis is poor

(Surface epithelial tumours also have an intermediate, borderline category called tumours of low malignant potential which have limited invasive potential and a much better prognosis)

23
Q

Describe ovarian sex cord/stromal tumours

A

These include granulosa and theca cell tumours which often secrete oestrogen and (uncommonly) Sertoli-Leydig cell tumours which may secrete androgens

Granulosa cell tumours usually occur in post-menopausal women and are not rare (oestrogen overproduction may lead to endometrial hyperplasia or endometrial carcinoma)

Ovarian fibromas and thecomas are usually benign and not rare

24
Q

Describe the features of ovarian germ cell tumours

A

95% of ovarian germ cell tumours are mature cystic teratomas (dermoid cysts)

Totipotent germ cells differentiate into mature tissues of all 3 germ cell layers

Mostly found in young women as ovarian masses or found incidentally on abdominal scans

May contain foci of calcification associated with bone or teeth

Approx. 10% are bilateral

Grossly they appear smooth, filled with sebaceous secretions and matted hair

Sometimes foci of bone and cartilage, nests of bronchial or GI epithelium, teeth and other recognisable lines of development may be present

About 5% of ovarian teratomas in adult are immature cystic teratomas, associated with more aggressive behaviour

25
Q

Describe endometrial carcinoma

A

Usually in older women, over 50 years of age

May be accompanied by background endometrial hyperplasia and oestrogen excess

Lynch syndrome is also a risk factor

Must be excluded in cases of post-menopausal bleeding

Investigations include endometrial biopsy, transvaginal ultrasound or hysteroscopy

Bilateral salpingo-oophorectomy is usually appropriate as well as hysterectomy

Prognosis is stage dependent, but other factors include grade, lymphovascular space invasion and tumour cells in peritoneal washings

Carcinosarcoma (Malignant Mixed Mullerian Tumour) are high grade serous carcinomas of the endometrium with a worse prognosis

26
Q

Describe leiomyomas (fibroids) of the uterine smooth muscle

A

Extremely common, often multiple, almost always benign smooth muscle tumours of the uterine body

Symptoms include dysmenorrhoea, menorrhagia and discomfort

Most active during the reproductive years and involute following the menopause

Hormonal treatments may relieve symptoms but occasionally surgery is appropriate

Uterine artery embolisation by interventional radiology is an alternative option

27
Q

Describe leiomyosarcomas of the uterus

A

Rare, but the most common non-epithelial malignancy

Soft mass, poorly circumscribed outline

May cause haemorrhage and necrosis

Much more abnormal histology

Vascular invasion may spread via the bloodstream to the lungs

Poor long-term prognosis

28
Q

Describe adenomyosis

A

Basal endometrium extends abnormally into hyperplastic myometrium

May co-occur with endometriosis

Peaks between 35 and 50

Pts often present with dysmenorrhoea and menorrhagia

May be focal or diffuse

In diffuse involvement, the uterus becomes bulky and heavier

29
Q

Describe endometriosis

A

Presence of endometrial glands and stroma outside the body of the uterus

Mechanisms are not fully understood but include retrograde menstruation, local metaplasia of surface epithelium and dissemination via the bloodstream

Inflammation, cysts and scarring associated with endometriosis can cause significant symptoms and compromise fertility

30
Q

Describe Gestational Trophoblastic Disease

A

A group of conditions characterised by excessive proliferation of trophoblasts

The classical hydatidiform mole is a mass of large oedematous chorionic villi

Complete Mole - No Foetus - Unispermis or dispermic fertilisation of an ‘empty’ egg (genotype 46XX or 46XY)

Partial Mole - Foetus Usually Present - Haploid egg fertilised by one sperm which reduplicates, or by 2 sperm (genotype 69XXY or 92XXXY)

Risk of progression to chorioncarcinoma

Requires monitoring of hCG levels

31
Q

Describe the Alkylating Agent class of chemotherapy drug

A

e.g. Cyclophosphamide, Cysplatin, Melphalan

Form irreversible covalent bonds with DNA to interfere with transcription and replication

Used in a range of cancers from lymphoma (mechlorethamine), multiple myeloma, ovarian and breast cancer (melphalan)

32
Q

Describe the Anti-Metabolite class of chemotherapy drug

A

e.g. Methotrexate, 5-Fluorouracil, Mercaptopurines, Cytarabine

|nterfere with nucleotide or DNA synthesis

Methotrexate - Folate Antagonist

5-Fluoriuracil - Pyrimidine Analogue

Mercaptopurines - Purine Analogues

33
Q

Describe the Cytotoxic Antibiotic class of chemotherapy drug

A

e.g. Dactinomycin, Doxorubicin

Act mainly by direct action on DNA as intercalators

Dactinomycin disrupts function of RNA polymerase by inserting itself into the minor groove of the DNA helix

Doxorubicin inserts itself between base pairs to impair DNA and RNA synthesis

34
Q

Describe the Microtubule Inhibitor class of chemotherapy drug

A

e.g. Vincristine

Binds to microtubular protein, blocks tubulin polymerisation and normal spindle formation to disrupt cell division

35
Q

Describe the Steroid Hormone and Antagonist class of chemotherapy drug

A

Tumours may be responsive to a hormone which make it regress, or it may be relient on a hormone to grow, in which case an antagonist of the hormone will suppress growth

Prednisolone - Suppressed lymphocyte growth

Tamoxifen - Oestrogen receptor antagonist used in ER+ve breast cancers

Casodex (Bicalutamide) - Testosterone receptor antagonist used in prostate cancers which are testosterone dependent

36
Q

Describe the principles of cancer chemotherapy

A

Cell cycle drugs are only effective on the subset of the cell population currently undergoing cell division

Resting (G) phase cells are therefore less sensitive to these drugs and care the cause of many relapses

The aim must be for a total kill and prolonged treatment is required to reduce the chance of relapse from resting cells

Chemotherapy drugs do not reverse de-differentiation, invasiveness or metastasis

General side effects include bone marrow suppression, hair loss, damage to GI epithelium, organ damage, sterility, teratogenicity and depression of growth in children

Phase 3 (14 decks)

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