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Medicine Year 3 > Week 3 - Female GU Pathology > Flashcards

Week 3 - Female GU Pathology Flashcards

1
Q

What is ovarian torsion? How does it present?

A
  • Ovary twists on its vascular pedicle
  • Affects young women
  • Presents with abdominal/pelvic pain, nausea and vomiting
  • Half of the time it is associated with an ovarian mass (e.g. Dermoid cyst - predisposes to torsion)
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2
Q

What is seen on microscopy in a partial molar pregnancy?

A

Microscopy shows oedematous villi and subtle trophoblast proliferation

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3
Q

What are the effects of hormone over-production in granulosa cell tumours?

A

Oestrogen over-production may lead to endometrial hyperplasia or endometrial carcinoma

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4
Q

How are leiomyomas managed?

A
  • Varies depending on number, size and symptoms
  • Medical - progesterone secreting IUS, hormonal therapies, tranexamic acid, GnRH agonists
  • Surgical - uterine artery embolisation, myomectomy, hysterectomy
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5
Q

Are tumours of the same size always detectable in different tissues?

A
  • A single cell, after 30 doublings, gives a cell mass of 109 cells - 2cm in diameter
    • Detectable in skin or breast
    • Non-detectable in e.g. liver
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6
Q

Describe the mechanism of action of pyrimidine analogues

A
  • E.g. Fluoro-uracil
  • Prevents thiamine formation
  • Stops DNA synthesis
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7
Q

What are Krukenberg tumours?

A

Metastases to the ovary from GI tract especially can mimic primary ovarian mucinous carcinomas (‘Krukenberg tumours’) - large unilateral tumours more likely to be primary

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8
Q

Give examples of benign pathology of the ovaries

A

Can have non-neoplastic cysts e.g. inclusion, follicular and luteal cysts

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9
Q

Describe the types of ovarian sex cord-stromal tumours

A
  • Include granulosa and theca cell tumours, which often secrete oestrogen, and (uncommonly) Sertoli-Leydig cell tumours, which may secrete androgens
  • Ovarian fibromas and thecomas are usually benign and not rare, can over produce oestrogens
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10
Q

How does fibrocystic change in the breast clinically present?

A
  • Lumpy/bumpy
  • Often multiple
  • Worst before menstruation
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11
Q

Define polycystic ovarian syndrome

A
  • Chronic anovulation syndrome associated with androgen excess
  • Clinical and/or biochemical hyperandrogenism
  • Polycystic ovarian morphology on ultrasound
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12
Q

How prevalent is ovarian cancer?

A

Ovarian cancer is the fifth most common cancer in women and fifth leading cause of cancer death in women

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13
Q

List the types of squamous cell carcinomas which can affect the vulva

A
  • SCC associated with vulval intraepithelial neoplasia
    • Occurs almost exclusively in females less than 60 y/o
    • Associated with high incidence of lower genital tract neoplasia particularly CIN and invasive cervical cancer
    • Usually related to high risk type HPV 16/18
    • Warty or basaloid cancer
  • SCC associated with dermatoses
    • Occurs in an older age group - most over 60, many over 70
    • Most of the cancers are well differentiated and keratinising
    • Not associated with HPV infection or VIN
    • Adjacent squamous hyperplasia and/or lichen sclerosus common
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14
Q

How are granulomatous conditions of the breast characterised?

A

Formation of granulomas (aggregates of macrophages)

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15
Q

Describe the pathogenesis of endometriosis

A
  • The metastatic theory - retrograde menstruation or surgical procedures introduce endometrium to sites outwith the uterine cavity
  • The metaplastic theory - endometrium arises directly from the coelomic epithelium (i.e. peritoneum) of the pelvis, as this is where endometrium originates from during embryological development
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16
Q

Describe the embryological development of the gynaecological tract

A
  • At approx. 6 weeks the coelomic lining epithelium forms the lateral Mullerian ducts, which grow downwards into the pelvis and fuse with the urogenital sinus
  • Fused portion of the Mullerian ducts becomes the uterus and remaining unfused parts become the fallopian tubes
  • Endometrial cavity, linings of the fallopian tubes and peritoneal covering of all the gynaecological organs are derived from the coelomic lining
  • Abnormalities of the uterus are related to abnormalities in the fusion of the Mullerian ducts
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17
Q

Describe the mechanism of action of tamoxifen

A
  • Tamoxifen - antagonist of oestrogen receptor
  • Some breast cancers
    • Are oestrogen dependent - oestrogen stimulates their growth
    • Can be treated with Tamoxifen
  • Tamoxifen is also an ovulatory infertility treatment
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18
Q

What causes ovarian clear cell carcinomas?

A

Associated with endometriosis

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19
Q

How are cervical cancers imaged?

A
  • MRI - local staging
  • US is not used in assessment
  • Key role of radiologist - determine staging to allow appropriate management
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20
Q

List the symptoms of periductal mastitis/mammary duct ectasia

A
  • Redness, swelling, tenderness around nipple
  • Sometimes a mass beneath the nipple
  • Sometimes nipple retraction
  • Sometimes nipple discharge
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21
Q

Describe the prevalence of breast cancer

A
  • Breast cancer is the most commonly diagnosed cancer in women in the UK (not highest mortality - lung cancer)
  • >55,000 women diagnosed with breast cancer each year in the UK, including 4,700 in Scotland
  • One in eight women in the UK will develop breast cancer in their lifetime
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22
Q

What is cGIN?

A
  • Cervical screening designed to pick up squamous lesions
  • Endocervical glandular epithelium also undergoes premalignant change - cervical glandular intraepithelial neoplasia (cGIN)
  • The malignant change from glandular epithelium is Adenocarcinoma
    • Adenocarcinoma more unpredictable, quick growth, aggressive tumours (small cell differentiation)
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23
Q

How can ultrasound be used to image the female reproductive organs?

A
  • Sonar beam into body, reflected by fat
    • Less beam to penetrate deeper tissues - less signal received back in those with more fat (may not be suitable in v obese patients)
  • To image the reproductive organs, can use
    • Transabdominal longitudinal ultrasound
      • Need full bladder - acts as window to see deeper structures
    • Transabdominal transverse ultrasound (turn probe 90 degrees)
    • Transvaginal ultrasound
      • Can be used to determine thickness of endometrium
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24
Q

How is the Nottingham prognostic index calculated?

A
  • NPI = [0.2 x S] + N + G

S is the size of the index lesion in centimeters

N is the node status: 0 nodes = 1, 1-3 nodes = 2, >3 nodes = 3

G is the grade of the tumour: Grade I = 1, Grade II = 2, Grade III = 3

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25
Q

Describe pre-invasive/dysplastic lesions of the breast

A
  • In breast dysplastic lesions are called carcinoma in-situ
  • Two types - both come from TDLU
    • Ductal carcinoma in-situ (DCIS) - risk of development of cancer higher
    • Lobular carcinoma in-site (LCIS)
  • Stage before invasive malignancy - malignant looking proliferation of epithelial cells within basement membrane (no extension into breast stroma)
  • No communication with blood vessels or lymphatics - no possibility of metastases
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26
Q

Describe the grading of CIN

A

CIN1 - low grade disease

CIN 2/3 - high grade disease

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27
Q

What is a leiomyosarcoma?

A
  • Uncommon malignant smooth muscle tumour of the myometrium (1-2% of uterine malignancies, commonest uterine sarcoma)
  • Peak incidence age 40-60 years, can be pre- or post-menopausal
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28
Q

What is another potential use for anti-folate drugs (aside from cancer therapy)?

A
  • Many of these are (potential) anti-parasitic drugs
    • Anti-folates used as anti-malarial drugs/in toxoplasmosis
  • Toxicity less acceptable in infectious disease than in cancer
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29
Q

Describe the relationship between endometrial hyperplasia and adenocarcinoma

A

Atypical endometrial hyperplasia is a known precursor of endometrioid adenocarcinoma, and 5-10% of those with this diagnosis will also have endometrioid adenocarcinoma in subsequent hysterectomy specimens

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30
Q

Describe the malignancies which affect the fallopian tubes

A
  • Primary adenocarcinomas involving and identifiable rising from the Fallopian tubes alone are rare, most common is papillary serous carcinoma. Endometrioid carcinomas are also seen
  • Fallopian tube carcinomas occur in women with BRCA1 mutations (about 10% occult malignancy present usually in fimbria of prophylactic salpingo-oophorectomias)
  • Fallopian tube carcinomas often involve omentum and peritoneal cavity at time of presentation
  • Some ‘ovarian’ carcinomas may be of fallopian tube origin
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31
Q

Describe the appearance of normal cervical cytology

A
  • Pink cells = superficial layer
    • Superficial squamous cells - small nucleus, lots of cytoplasm
  • Blue cells = intermediate/parabasal layer
    • Intermediate cells - slightly bigger nucleus
    • Endocervical cells (glandular/columnar) - tall columnar cytoplasm and basal nucleus
  • Some inflammatory cells
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32
Q

What is the most common pathology of the fallopian tube?

A
  • Salpingitis - part of the spectrum of pelvic inflammatory disease
  • Most commonly infective, mainly bacterial (chlamydia trachomatis, mycoplasma, coliforms, streptococci, staphylococci, neisseria gonorrhoeae)
  • Usually considered to be ascending infection (colonisation of vagina upwards)
  • Tuberculosis salpingitis uncommon, usually associated with tuberculosis of the endometrium
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33
Q

Describe the mechanism of action of akylating agents

A
  • Oldest chemotherapy drugs
  • Form covalent bonds with DNA (alkylate nucleotides)
  • Interfere with DNA polymerase transcription and replication
  • Most alkylating agents have two reactive groups, allows the drug to cross-link
    • Within one strand of DNA
    • Across the two strands of DNA
  • Cross-links don’t allow polymerase to function
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34
Q

What causes fibrocystic change in the breast?

A
  • Probably an aberrant response of normal breast tissue to fluctuations in cyclical hormones - may not be a ‘disease’
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35
Q

What are endometrial stromal sarcomas?

A
  • Group of tumours of the endometrial stroma
  • Rare - 0.2-1.5% of uterine malignancies and <10% of uterine sarcomas
  • Can be low grade (more common) or high grade (rare)
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36
Q

List the main classes of anti-cancer drugs

A
  • Alkylating agents
  • Antimetabolites
  • Cytotoxic antibiotics
  • Microtubule inhibitors
  • Steroid hormones and antagonists
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37
Q

What are the symptoms of adenomyosis?

A

May be asymptomatic or get dysmenorrhea, menorrhagia, dyspareunia, chronic pelvic pain

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38
Q

Describe the appearance of endometrial polyps on microscopy

A
  • Microscopy shows haphazardly arranged glands with preservation of low gland to stroma ratio, often thick walled blood vessels and fibrous stroma
  • Glands are usually inactive, but can also show proliferation, secretory changes or metaplasia
  • Occasionally cytological atypia or frank adenocarcinoma can be found in polyps
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39
Q

What are the symptoms of a leiomyoma?

A
  • Asymptomatic
  • Abnormal bleeding
  • Urinary frequency if large
  • Impaired fertility
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40
Q

How does the lining of the cervix change during puberty?

A
  • Prior to puberty - ectocervix is covered by non-keratinising stratified squamous epithelium and endocervix is lined by columnar (glandular) epithelium
  • With growth of 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’ - zone of unstable differentiation where most cervical neoplasia develop
  • These changes are reversed at the menopause
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41
Q

What are actinomyces?

A
  • Actinomyces - often seen in those using IUCD (coil)
  • Can be asymptomatic - no intervention required
  • If symptomatic (pelvic pain, bleeding, vaginal discharge, dysuria etc.) may need to remove coil and give antibiotics
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42
Q

What is papillomatosis?

A

Papillomas in small ducts at the periphery of the breast - this is not dysplasia as such but does slightly increase cancer risk for the patient

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43
Q

How can prostate cancer be treated with hormonal therapy

A
  • Most prostate cancers are dependent on testosterone
  • Treatment could be testosterone receptor antagonists
    • E.g. Flutamide (Drogenil)
    • Now replaced by Bicalutamide (Casodex)
  • Pituitary down-regulators
    • LHRH agonists (e.g. Prostap)
    • Inhibit release of Luteinising Hormone
    • LH normally stimulates the testes to produce testosterone
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44
Q

Describe the appearance of a serous ovarian carcinoma on imaging

A
  • Large cystic mass
  • Benign - encapsulated, regular, clear edges
  • Metastatic - irregular, solid parts, in peritoneum
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45
Q

Describe the types of molar pregnancies

A
  • Hydatidiform moles present w/ either spontaneous miscarriage or abnormalities detected on ultrasound
    • Partial mole - fertilisation of one egg by two sperm, resulting in triploid karyotype
    • Complete mole - fertilisation of an egg with no genetic material, usually by one sperm which duplicated its chromosomal material (10% occur when an egg with no genetic materal is fertilised by two sperm), diploid karyotype usually 46 XX
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46
Q

What feature is often seen on mammography which located breast cancers?

A

Microcalcification - small flecks of calcium

(Benign lesions can calcify - more common in malignant cancers)

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47
Q

Describe the side effects of chemotherapy

A

General toxic effects - affects rapidly dividing cell populations

  • Bone marrow suppression (blood cells)
  • Anaemia (RBC), immune depression/prone to infection (immune cells) e.g. lymphocytes, impaired wound healing (platelets)
  • Loss of hair
  • Damage to gastro-intestinal epithelium
  • Liver, heart, kidney
  • In children, depression of growth
  • Sterility
  • Teratogenicity (damage to embryo)

For most other disease these side effects would be completely unacceptable - no better drugs so have to accept side effects.

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48
Q

What treatments are available for cancer?

A
  • Surgical removal
    • Only for solid tumours
    • Dependent on location
    • Only if non-metastasised
  • Irradiation
    • Only if localised, non-metastasised
  • Chemotherapy with anticancer drugs
    • Often only treatment available, esp. if advanced cancer
    • Selective toxicity required
  • All three forms of treatment may be combined in patient care
  • Tumour may be advanced or metastasised before it is diagnosed
  • One treatment may not be effective enough
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49
Q

What is a koilocyte?

A
  • Koilocyte = squamous epithelial cell that has undergone structural changes, which occur as a result of HPV infection
  • Features of koilocytosis:
    • Nuclear enlargement (2-3x normal size)
    • Irregularity of the nuclear membrane
    • Hyperchromatic nucleus
    • Perinuclear halo
  • Koilocyte (‘hollow cell’) - likely HPV infection
    • Koilocyte characterised by a ‘clearing’ of the cytoplasm around the nucleus, recognisable on cytology and histology - reliable sign of HPV infection
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50
Q

Describe the breast screening programme in Scotland

A
  • Scottish breast screening programme invites women aged between 50 and 70 years old for screening every three years
  • Women over 70 years old are able to attend through self-referral
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51
Q

What are the general pathological changes seen in gestational trophoblastic disease?

A
  • Non-viable fertilised egg implants in the uterus, will fail to come to term
  • Gestational trophoblastic disease, which grows into a mass in the uterus that has swollen chorionic villi - grow in clusters that resemble grapes
  • Hyperplasia of trophoblastic tissue
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52
Q

Describe the features of ovarian malignancy on ultrasound

A
  • Irregular solid or mutli-loculated cystic mass
  • Solid components on cyst wall
  • Bilateral ovarian lesions
  • Ascites, peritoneal nodules, or other evidence of metastases
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53
Q

What is a leiomyoma?

A
  • Benign smooth muscle tumour of the myometrium
  • Very common - at least 25% of women, mostly of reproductive age, incidence is over 70% by age 50
  • May be single or multiple
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54
Q

What kind of tumour is a fibroid?

A: Lipoma

B: Leiomyoma

C: Angiolipoma

D: Lipoleiomyoma

E: Lymphangioma

A

Answer: B - leiomyoma

  • Leiomyoma is a benign smooth muscle tumour
  • Histologically normal and neoplastic smooth muscle are very similar
  • Clonal cytogenetic abnormalities in about 40% of leiomyomas e.g. trisomy 12, t12:14 support their neoplastic character
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55
Q

Describe the development of vulval squamous cancer

A
  • Although risk of malignancy in lichen sclerosus is generally low, in a minority of cases a subtle non-HPV entity called ‘differentiated VIN’ may have a much greater risk of progression
  • Unlike the cervix (almost all squamous cell cancer is HPV related) only about 2% of vulval cancer is thought to be HPV dependent
  • Like cervical intraepithelial neoplasia (CIN), vulval HPV-associated intraepithelial neoplasia (VIN) may –> invasive squamous carcinoma
  • Squamous epithelium of the vagina and perianal skin may also be affected by pre-neoplastic field change
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56
Q

How do breast fibroadenomas present?

A
  • Often asymptomatic but can cause a lump
  • Firm but not hard (cancers are v hard)
  • Mobile - so-called ‘breast mouse’
    • More than cancer - fixed and tethered
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57
Q

Give an example of a microtubule inhibitor and describe its mechanism of action

A
  • Vinca alkaloids (Vincristine)
  • Isolated from Madagascar periwinkles - local medicine for centuries
  • No oral absorption
  • Bind to microtubular protein, block tubulin polymerase, block normal spindle formation = disrupt cell division
  • Bad side effects - very unspecific
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58
Q

Describe LETZ biopsy

A
  • Loop excision of the transformation zone treats the abnormal epithelium and allows full assessment of the lesion by histopathology, confirmation of CIN, assessment of excision - make sure there is no invasive cancer
  • Doesn’t affect fertility, no significant consequences/side effects
  • Cone biopsy with scalpel is also effective and might be appropriate in a setting where LETZ is unavailable
  • Radical hysterectomy + radiotherapy for established disease
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59
Q

List stromal proliferations of the breast

A
  • Diabetic mastopathy - type 1 diabetes, overproduction of fibrous stroma
  • Pseudoangiomatous hyperplasia
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60
Q

List the phases in the normal menstrual cycle

A
  1. Proliferative phase
  • Inner endometrium - simple columnar epithelium, long uterine glands
    • Coiled arteries, stratum functionalis –> basalis
  • Stroma (connective tissue)
  1. Secretory phase
    * Bigger more coiled glands, more secretions - nutrition of embryo (pre-implantation)
  2. Menstrual phase
  • If fertilisation/implantation doesn’t occur
  • Surface layers shed in menstruation - stratum basalis remains as it has independent blood supply from straight arteries (source of artery regrowth in next cycle)
  • Stratum functionalis shrinks - death of corpus luteum (hormones maintain), spiral arteries are more coiled = vascular stasis –> tissue death
  • Active vasoconstriction then relaxation of arteries - flow of blood, carries away dying tissue
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61
Q

Describe the appearance of the uterus on CT

A
  • Uterus lies between bladder and rectum, intermediate grey soft tissue attenuation
  • Depending on how full the bladder is and retroverted the uterus is - can give it an unusual appearance at CT
  • Can be deviated to left or right - all normal variants
  • Tends to be low intensity band centrally of the endometrial canal - more distinct post contrast
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62
Q

List the signs/symptoms of ovarian malignancy

A
  • Abdominal distention
  • Pelvic or abdominal pain
  • Feeling full and loss of appetite
  • Increasing urinary urgency or frequency
  • Irritable bowel disease >50
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63
Q

How thick should the endometrium be?

A
  • Width varies with stage of cycle in premenopausal
  • Post-menopausal should be less than 5mm
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64
Q

How is radiotherapy used in the treatment of breast cancer?

A
  • To the breast following WLE to reduce risk of recurrence
  • Sometimes to the axilla if positive nodes have been found
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65
Q

What clinical findings sugges a hydatidiform mole?

A
  • On ultrasound
    • Larger uterus than expected for gestational age
    • Enlarged ovaries
  • Also may have hyperemesis, hypertension, high hCG
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66
Q

What is the effect of HPV infection on the cervix?

A
  • Persisting infection with an oncogenic strain of HPV is thought to be a necessary cause of cervical cancer and precancer
    • Increases risk of CIN - absence implies low risk at that time
  • Prevalent strains in Glasgow/Scotland are HPV 16 and 18 (there are other oncogenic strains)
  • Most HPV infection does not progress to CIN or cancer - other factors e.g. smoking
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67
Q

What is a radial scar?

A

Important form of ‘proliferative’ breast disease largely because mammographically they look like small cancers, have some of the architectural features of cancer too under the microscope

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68
Q

How do normal cells become cancer cells?

A
  • Normal cells become cancer cells though a change in DNA, multi-stage process
  • Two main categories of genetic change
    • Inactivation of tumour suppressor genes (stop proliferation)
    • Activation of proto-oncogenes to oncogenes (stimulate proliferation)
  • Usually regulatory genes become mutated
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69
Q

How can the sentinel lymph node be detected in breast cancer?

A

Inject blue dye (radioactive) into skin of breast close to tumour, intraoperatively trace dye to lymph node which turns blue/radioactively detectable first

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70
Q

List the pathological features of radial scars

A
  • Fibrosis and elastic material at the centre
  • ‘Star shaped’ or ‘flower head’ appearance
  • Trapped glands only ‘pseudo-infiltrative’
  • Myoepithelial cells present in a way that is NOT seen in cancer
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71
Q

Describe the mechanism of action of purine analogues

A
  • Mercaptopurines
  • Converted into false nucleotides
  • Disrupts purine nucleotide synthesis
  • May be incorporated into DNA, disrupting helix
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72
Q

Koilocytes are a sign of viral infection in the epithelial cells of the squamous cervical mucosa, what virus is likely to be responsible?

A: Herpes simplex virus, type II
B: Herpes simplex virus, type I

C: Cytomegalovirus

D: Human papilloma virus

E: Human herpesvirus 8 (HHV-8)

A

Answer: D - Human papilloma virus

  • HPV infection very strongly associated with CIN and cervical cancer, especially ‘high risk’ types e.g. 16, 18
  • HSVI - cold sores
  • HSVII - common genital infection, no definite evidence it has a significant role in cervical cancer
  • CMV - member of herpes virus family, common infection, not involved in cervical cancer
  • HHV8 - member of herpes virus family, common infection, not involved in cervical cancer
  • Has a role in Kaposi’s sarcoma, usually in immunocompromised individuals (e.g. AIDS)
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73
Q

Which tumours can be discovered at breast screening?

A
  • Asymptomatic
  • Small
  • Lower grade and stage than symptomatic tumours
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74
Q

Describe the malignant surface epithelial ovarian tumours

A
  • Malignant epithelial tumours (carcinomas) may be cystic (cystadenocarcinoma) or solid (adenocarcinoma)
  • Carcinomas may be high grade serious (70%), endometrioid (10%), clear-cell (10%), low grade serous (5%) or mucinous (3%)
  • Similar carcinomas also occur in the uterus and some ‘ovarian’ carcinomas are now thought to be of endometrial or Fallopian tube origin with spread to ovary
  • HGSC are thought often to arise from epithelial precursor lesions in the ovarian end of the Fallopian tubes
  • Endometrioid and clear cell carcinomas probably arise from ovarian endometriosis
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75
Q

Describe the pathology of leiomyosarcomas

A
  • Macro - bulky invasive masses or polypoid, necrosis, haemorrhage and variable cut surface
  • Micro - overt cytological atypia, necrosis, mitotic activity, infiltrative margin
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76
Q

Describe the mechanism of action of prednisone in cancer therapy

A
  • Synthetic adrenocortical steroid hormone
  • Converted in the body to active form –> Prednisolone - suppresses lymphocyte growth
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77
Q

Describe the molecular subtypes of breast cancers

A
  • ER+
    • Luminal A - better prognosis
    • Luminal B - less good prognosis
  • ER -
    • Triple negative - HER2, PR, ER all negative
    • Basal type (aggressive) - includes some BRCA cancers
    • Normal breast type
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78
Q

Give examples of pathology which can affect the vulva

A
  • Inflammatory dermatoses and skin tumours occurring at other sites may also occur on the vulva
  • Skin tags, melanocytic nevi and benign cysts common
  • Candidiasis (thrush) is also common and may be associated with pregnancy or diabetes
  • Bartholin’s vestibular gland cystic may become infected with abscess formation
  • Lichen planus and lichen sclerosus et atrophicus are both non-infective inflammations
    • Lichen sclerosis is especially associated with anogenital skin in females - link with vulval squamous carcinoma
  • Vulval cancer
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79
Q

Which conditions are associated with breast hypoplasia?

A

Associated with ulnar-mammary syndrome, Poland’s syndrome, Turner’s syndrome and congenital adrenal hyperplasia

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80
Q

Describe the prognosisof ovarian cancer

A

Most women w/ ovarian cancer present late, many have poor prognosis - successful early diagnosis has not been achieved

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81
Q

When is the myometrium thickest?

A

Proliferative stage - in preparation to deliver child

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82
Q

What are the features of uterine fibroids on imaging?

A
  • Hypoechoic (dark) mass on ultrasound
  • Often make the uterus look bulky/lobulated on CT
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83
Q

What are the risks of a partial molar pregnancy?

A

Risk of invasive mole, which invades and destroys the uterus

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84
Q

What is a uterine pipelle?

A

Uterine pipelle = done on patient presenting with bleeding endometrial disorder, pipelle inserted into uterus through cervix to collect biopsy of endometrium

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85
Q

How is cervical cytology screening carried out?

A
  • Use speculum to access cervix
  • Cervical brush turned clockwise - spokes of brush have designed to collect cells when turned clockwise
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86
Q

Describe a borderline nuclear abnormality of cervical cells

A

Enlargement of nucleus, abnormal chromatin

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87
Q

How is cervical cancer managed?

A
  • Parametrium - a fibrous band that separates the cervix from the bladder
  • If this is NOT invaded - surgery
  • If this is invaded - chemotherapy/radiation
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88
Q

Describe the histology of the fallopian tube

A
  • Lined by ciliated columnar epithelium
  • Complex plicae
  • Layers of smooth muscle
  • Peritoneum
  • Smooth muscle layers and cilia assist with movement of oocyte down tube
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89
Q

Give examples of benign developmental breast conditions

A
  1. Ectopic breast tissue
  2. Breast hypoplasia
  3. Congenital nipple inversion
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90
Q

Describe the histological appearance of the normal squamous epithelium of the cervix

A
  • Population of cells proliferating to make enough new cells to supply the need for renewal of tissue = transit amplifying population
  • Proliferation usually restricted to lower 1/3 of cervical squamous epithelium, just above the basal layer - this is where dividing cells are likely to be seen
  • Towards the middle and surface of the epithelium, the cells develop more cytoplasm and their nuclei are relatively smaller
  • Cells flatten out towards surface
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91
Q

Describe the histological appearance of endometrial hyperplasia

A
  • Endometrial hyperplasia histologically characterised by an increase in gland:stroma ratio (greater than 1:1), can be seen with or without cytological atypia
  • Areas of gland crowding, small amounts of stroma between glands
  • Glands branch and vary in shape
  • Nuclear enlargement, coarse, irregularly distributed chromatin
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92
Q

List the types of ovarian carcinomas

A
  • Epithelial (90%)
    • Serous (80-85%) - high and low grade, usually stage 3-4, rarely stage 1
    • Mucinous (endocervical and intestinal phenotype)
    • Clear cell
    • Endometrioid
    • Brenners
    • Squamous
    • Benign, malignant, intermediate
  • Non-epithelial (10%)
    • Germ cell (first 2 decades)
      • Dysgerminoma, teratomas etc.
    • Sex chord
      • Granulosa cell - adults >50, or prepubertal
      • Sertoli, Leydig, thecoma, fibroma
    • Metastatic - uterus, stomach, colon, breast, lymphoma, pancreas
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93
Q

Describe the mechanism of action of dactinomycin

A
  • Inserts itself into the minor groove in the DNA helix
  • RNA polymerase function is disrupted - prevents separation of strands for replication
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94
Q

Describe the histology of a serous cystadenoma of the ovary

A
  • Lined by ciliated columnar epithelial cells or cuboidal non-ciliated epithelium resembling ovarian surface epithelium
  • Fibrous stroma with spindly fibroblasts
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95
Q

What investigations can be done to diagnose a breast lump?

A
  • Clinical - examination/palpation
  • Imaging - ultrasound, mammography, MRI
  • Tissue diagnosis - pathology (microscopy)
    • Fine needle aspiration - cytology (quick + easy)
    • Core biopsy - histology
    • Excision biopsy - diagnostic or therapeutic
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96
Q

How can endometrial abnormalities be detected?

A
  • Can be picked up on smear
  • Post-menopausal bleeding should always be referred to gynaecology for endometrial biopsy
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97
Q

Describe the morphology of serous ovarian tumours

A
  • Benign serous tumours -
    • Large, cystic (up to 30-40cm)
    • May be bilateral
    • Smooth shiny serosal covering
    • Cysts filled w/ clear serous fluid, lined by single layer of tall columnar epithelium, some cells ciliated
  • Borderline serous tumours -
    • More complex architecture
    • Mild cytologic atypia but no stromal invasion
    • Peritoneal implants may be present
  • Serous carcinoma -
    • Anaplasia of cells
    • Obvious stromal invasion
  • Psammoma bodies (concentrically laminated calcified concretions) common in the papillae of serous tumours in general
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98
Q

Describe the mechanism of action of cisplatin

A
  • Like other cross-linkers targets N7 of purine nucleotides
  • Resistance from - nucleotide excision repair mechanisms, efflux transporters for copper
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99
Q

What are Brenner tumours?

A
  • Uncommon mixed surface epithelial-stromal tumours
  • Usually benign, unilateral, size very variable, solid, circumscribed, yellowish
  • Often found incidentally
  • Histologically, nests of transitional epithelial cells with longitudinal nuclear grooves and abundant fibrous stroma
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100
Q

Describe the invasion of a metastasising squamous carcinoma

A

Invades stromal tissue (BVs and lymphatics)

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101
Q

Describe the appearance of ovarian torsion on ultrasound

A
  • Enlarged ovary
  • Free fluid in pelvis
  • Ovary may show absent vascularity
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102
Q

Give examples of akylating agents

A
  • Nitrogen mustards
    • Derived from mustard gases of WW1
    • Melphalan, chlorambucil, cyclophosphamide, ifosfamide
  • Cysplatin
  • Temozolomide
  • Lomustine - can penetrate brain
  • Busulpha - ‘selective’ effect on bone marrow
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103
Q

List the risk factors for the development of breast cancer

A
  • Reproductive - early menarche, late menopause, late 1st pregnancy
  • Hormonal - HRT therapy, oral contraceptive use
  • Anatomical/physiological - dense breast on mammography
  • Behavioural - alcohol, smoking
  • Genetic - positive family history, but also some rare genetic syndromes (BRCA 1&2, Li Fraumeni)
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104
Q

What are the signs/symptoms of a breast malignancy?

A
  • In the breast
    • Lump, thickening
    • Skin changes - ‘peau d’orange’ (rare), redness (remember so called ‘inflammatory carcinoma’)
  • At the nipple
    • Skin changes - rash, redness
    • New inversion
    • Discharge
  • In the axilla
    • As a lump
  • Pain is an unusual symptom of breast cancer
  • Discovered at breast screening - can be completely asymptomatic
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105
Q

Describe the stages of abnormality in cervical cells which can be seen with cervical cytology

A
  1. Borderline nuclear abnormality
  2. Low grade dyskaryosis with koilocytosis (CIN1)
  3. High grade (moderate) squamous dyskaryosis (CIN 2/3)
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106
Q

Give examples of inflammatory condtions affecting the breast

A
  • Acute mastitis
  • Granulomatous mastitis
    • Idiopathic
    • From systemic condition
  • Periductal mastitis
  • Fat necrosis
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107
Q

Describe the appearance of ovarian follicles on ultrasound

A
  • Common, benign, asymptomatic
  • Look like cyst on ultrasound
  • Most don’t need follow up
    • <3cm premenopausal is normal, <5cm no follow up, 5-7cm may need annual follow up
    • Postmenopausal <1cm normal, <3cm no follow up, 3-5cm can be followed up with ultrasound and Ca125 for one year
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108
Q

How are mucinous ovarian tumours diagnosed?

A

Diagnosis depends on architectural complexity and cytological atypia

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109
Q

Are hyperplastic and dysplastic lesions of the breast always distinct?

A
  • Boundary between what is ‘hyperplastic’ and what is ‘dysplastic’ is blurred
  • There are some ‘hyperplastic’ lesions that have increased risk of cancer or might be related to dysplasia including
    • Some types of columnar cell change
    • ‘Atypical’ forms of ductal hyperplasia
    • In-situ lobular neoplasia
  • If seen on biopsy further investigation/biopsy may be required
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110
Q

Give an overview of reproductive embryology

A
  • Reproductive development diverges after approx. 7 weeks gestation
  • With testis determining factor/sex determining region Y (SRY) on Y chromosome, development proceeds as male
  • Without SRY, development proceeds as female
  • Gonads arise from embryonic urogenital ridges
  • Genital ducts arise from the paired mesonephric and paramesonephric ducts
  • The mesonephric (Wolffian) ducts –> male structures
  • The paramesonephric (Mullerian) ducts –> female structures
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111
Q

Describe the appearance of normal squamous cells in cervical cytology

A
  • Varying keratinisation - different colour (nuclear changes are more important)
  • Nuclei same shape/size/colour - small + regular
  • Abundant cytoplasm
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112
Q

Describe the role of HPV testing in cervical screening

A
  • HPV testing easier with liquid based cytology, more sensitive than cytology
    • Could be used effectively in primary screening in women aged >30
  • HPV tests are very sensitive, which at present reduces specificity and in women >30 limits its usefulness in screening
  • This may change in HPV immunised women as we should no longer see high positive rates with reduction of HPV 16/18
  • In 2020 HPV testing will be used for primary screening
  • Primary HPV screening may allow longer screening rounds (5 years)
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113
Q

What are mucinous ovarian tumours?

A

Tumours consisting of mucin-secreting cells

114
Q

Describe the pathological appearance of endometrial stromal sarcomas

A
  • Both low and high grade have a diffusely infiltrative ‘worm like’ growth pattern macroscopically (and microscopically)
  • Microscopy
    • Low grade tumour cells resemble cells of proliferating endometrial stroma, with mitoses
115
Q

Describe the features of lobular carcinoma

A
  • 10-15% of all breast cancer
  • More likely to be bilateral + multifocal
  • Does not have classical features of malignancy
    • Small
    • Bland - monomorphic
    • Discohesive cells - loss of cell adhesion molecule E-cadherin (can test for)
116
Q

Describe the appearance of polycystic ovaries

A
  • Enlarged ovaries, multiple subcortical cysts 5-15mm in diameter
  • Thickened, fibrotic outer surface over cysts lined by granulosa cells with a hypertrophic and hyperplastic luteinised theca interna
  • Absence of corpora lutea, corpora albicantes (ovulation not occurring)
117
Q

What changes occur in the cervix with hormonal changes throughout a woman’s life?

A
  • Prepubertal girls - functional squamocolumnar junction is just within the cervical canal
  • Post-puberty, due to hormonal influence and during pregnancy the columnar epithelium extends outwards over the ectocervix and the cervix everts - squamocolumnar junction moves out to the vaginal portion of the cervix
    • Exposed to the acidic vaginal environment - undergoes physiological metaplasia to tougher squamous cells in days-weeks
    • New squamocolumnar junction is more internal, zone of unstable epithelium between two epitheliums is the transformation zone
  • After menopause - uterine structures involute and functional squamocolumnar junction moves into the cervical canal
118
Q

What are the symptoms of acute mastitis?

A

Cellulitis, can develop into abscess

119
Q

Describe the staging of endometrial cancer

A
  • Stage 1 - carcinoma in uterus
  • Stage 2 - spread to cervix
  • Stage 3 - outside uterus, but within the lesser ‘true’ pelvis
  • Stage 4 - beyong the pelvis
120
Q

Describe the mechanism of action of methotrexate

A
  • Higher affinity for Dihydrofolate reductase than folic acid
  • Inhibition of dihydrofolate formation
  • Inhibition of purine/pyrimidine nucleotide synthesis
  • Ultimately, halt to DNA/RNA synthesis
121
Q

What is the body’s main anti-cancer defense and how is this utilised in anti-cancer therapy?

A
  • Cancer cell: uncontrolled growth
  • Immune system - doesn’t always recognise at the cells present as ‘self’
  • Apoptosis of transformed cells is best defence
    • Failure to pass checkpoint in cell division –> programmed cell death
  • Growth is target of chemotherapy
  • Most anti-cancer drugs attack cell division
  • They do not reverse de-differentiation, invasiveness or metastasis
  • This therefore potentially attacks all rapidly dividing cells
122
Q

Describe the HPV vaccination programme in the UK

A
  • Started in 2008
  • Aimed at 12/13 year old girls (in school in S1), catch up programme for older girls
  • Going to start vaccinating boys (with no catch up programme)
    • Increases herd immunity, some throat cancers seem to be HPV driven in young men
  • Scotland us now using a quadrivalent vaccine to cover against HPV 6, 11, 16, 18
    • 6/11 - genital warts
    • 16/18 - cervical cancer
  • HPV vaccination is important but can’t assume it will eradicate all cervical cancer
123
Q

What are the risks of a complete molar pregnancy?

A
  • Carries a 10% risk of invasive mole and 2.5% risk of choriocarcinoma (frankly malignant, rapidly invasive and metastasises widely, treatable with chemotherapy)
124
Q

Describe the normal physiological function of the breast

A

Breast responds to hormonal stimuli throughout life

  • Puberty - ducts sprout from the breast bud, in females puberty initiates further development establishing the adult mammary gland
  • Pregnancy/lactation - increase in the number and size of lobular epithelial cells. Vacuolated cytoplasm. Secretions in lactation.
  • Menopause - lobules atrophic and less fibrous stroma
125
Q

How do dermoid cysts develop?

A

Totipotent germ cells differentiate into mature tissues of all 3 germ cell layers: ectoderm (skin, hair, teeth), endoderm (GI, respiratory, epithelium), mesoderm (fat, muscle)

126
Q

Describe the appearance of moderate dyskaryosis (likely CIN2) on cytology

A

Some normal looking nuclei and enlarged nuclei with abnormally coarse looking chromatin - dyskaryosis which alerts the cytologists to possible presence of CIN

127
Q

How big is a punch biopsy of the cervix?

A

5mm

128
Q

What are the most common outcomes in borderline nuclear abnormality?

A
  • 70% HPV
  • 20% CIN1
  • 10% CIN2
  • 5% CIN3
129
Q

Describe the benign surface epithelial ovarian tumours

A
  • Benign lesions usually cystic (cystadenoma) with or without solid stromal component (cystadenofibroma)
130
Q

Describe the diagnostic features of a menstrual endometrium

A
  • Blood and condensed stroma (stromal condensation)
    • Blood can be present for a variety of reasons
131
Q

What are the symptoms of polycystic ovaries (Stein-Leventhal syndrome)?

A
  • Oligomenorrhoea, hirsutism, infertility and obesity - usually after menarche
  • Insulin resistance may lead to type 2 diabetes
132
Q

How is hormonal therapy used in the treatment of breast cancer?

A
  • In tumours with high levels of residual hormone receptors (oestrogen receptor/progesterone receptor +) the use of drugs which block hormone function such as tamoxifen may be used
  • These are often used after surgery for ER, PR + tumours
  • In post-menopausal women there is no endogenous oestrogen from the ovaries but oestrogen can be produced in soft tissue (fat etc.)
  • Aromatase inhibitors such as Letrozole can inhibit this process in post-menopausal wome
133
Q

What are endometrial polyps?

A
  • Exophytic masses of variable size which project into the endometrial cavity
  • Associated with tamoxifen in some cases
134
Q

What are the complications of treatment of CIN2/3?

A
  • Immediate
    • Pain - abdominal/uterine cramp
    • Haemorrhage
  • Delayed
    • Secondary haemorrhage (1-2%)
    • Infection
    • Cervical stenosis (approx. 1%)
    • No good evidence of impact on fertility
135
Q

Describe the features of ovarian endometrioid carcinomas

A
  • Microscopically characterised by neoplastic tubular glands, similar to those of the endometrium
  • Benign and borderline forms exist, but usually malignant
  • Bilateral in about 30% of cases: 15-20% of women with these ovarian tumours also have an endometrial carcinoma
  • Most are low grade and many are thought to arise from endometriosis
136
Q

Describe the mechanism of action of cytotoxic antibiotics

A
  • Often not used against infective diseases because not selective
  • Act mainly by a direct action on DNA as intercalators
137
Q

What are the symptoms of uterine fibroids?

A

Pain, infertility, menorrhagia

138
Q

Describe the morphology of mucinous ovarian tumours

A

Morphology: large, multilocular, no psammoma bodies, crypts lined by cells with abundant mucinous cytoplasm

139
Q

Describe the features of ductal carcinoma

A
  • Around 70-80% of all breast cancer
  • Also called invasive carcinoma NST (no special type)
  • Classic histological features of malignancy
140
Q

What is STIC?

A
  • Serous tubal intraepithelial carcinoma - recent concept
  • Abnormal epithelium distal fallopian tube
  • Limited by basement membrane (B) so in situ
  • Nuclear atypia (N) clearly seen
  • Likely precursor for high grade serous carcinoma
  • Similar mutations to invasive tumour including p53
141
Q

Describe the prognosis of leiomyosarcomas

A

Prognosis - spread to lungs, liver and brain, 40% 5 year survival

142
Q

List the types of breast pathology

A
  • Inflammatory conditions - pathologies caused by the results of the bodies reaction to an antigen - often a microorganism or virus (i.e. an infection)
  • Hyperplasia - pathologies caused by an increase in the amount of cells - will cease when stimulus removed
  • Neoplasia - pathologies caused by an increase in the amount of cells - will NOT cease when stimulus removed. Both benign and malignant neoplasms exist.
  • Dysplasia -
    • Dysplasia/carcinoma in-situ/in-situ neoplasia = all the same process in different sites
    • Describes tissue which
      • Is not normal
      • Is not invasive malignancy (yet) - often still within the epithelium it arose in
      • No capacity to metastasise
      • Is somewhere between the two

Breast pathology can be benign, dysplastic or malignant

143
Q

Describe reproductive embryological development in males

A
  • SRY directs the gonad to become testes, with spermatogonia, Leydig and Sertoli cells
    • Testosterone from Leydig cells stimulates development of mesonephric duct structures - without it, mesonephric ducts atrophy
    • Dihydrotestosterone promotes development of prostate, penis and scrotum
    • Anti-Mullerian hormone/Mullerian inhibiting substance from Sertoli cells induces regression of paramesonephric ducts (without it they persist)
  • Mesonephric ducts –> rete testis, efferent ducts, epididymis, vas deferens, seminal vesicle, trigone of bladder
  • Urogenital sinus –> bladder (except trigone), prostate gland, bulbourethral gland, urethra
144
Q

How does cervical cancer develop from CIN?

A
  • Invasive squamous carcinoma of the cervix almost always develops from pre-existing CIN, but not all CIN will become squamous cancer
  • CIN II and CIN III are more likely to progress than CIN I
145
Q

Describe the appearance of PCOS on ultrasound

A

Multiple small follicles (no dominant)

146
Q

How do the external genitalia develop embryologically in males and females?

A
  • In both sexes (genital tubercle, genital folds, genital swellings) are indistinguishable up to approx. week 12
  • In males –> body and glans penis, corpora cavernosum
  • In females –> body and glans clitoris, labia
147
Q

What are the risk factors for epithelial ovarian cancers?

A
  • Nulliparity
  • Family history
  • Prolonged OC use may reduce risk
148
Q

What percentage of serous ovarian carcinomas are malignant?

A

25% malignant (usually older women)

149
Q

Define endometriosis and adenomyosis

A
  • Endometriosis - the presence of endometrial tissue outside the uterus
  • Adenomyosis - the presence of endometrial tissue within the myometrium
150
Q

Describe the lining of the cervix

A
  • Endocervix lined by columnar mucous cells, contains numerous tubular mucous glands, which emptying viscous alkaline mucous into the lumen
  • Ectocervix lined by non-keratinised stratified squamous epithelium (resembles the lining of the vaginal canal)
  • Junction between ecto- and endocervix is the squamocolumnar junction
151
Q

How is ovarian cancer treated?

A
  • In patients with extensive spread, surgery is not indicated or can be deferred if they have one or more of the following
    • Multiple liver metastases
    • Lymphadenopathy in the porta hepatis
    • Suprarenal para-aortic lymph nodes
    • Diffuse mesenteric disease
    • Evidence of pleural or parenchymal lung disease
  • These patients are treated with neoadjuvant chemotherapy (e.g. with carboplatin plus paclitaxel), surgery can sometimes be done after initial chemotherapy
152
Q

Describe the normal components of the breast

A
  • What is inside the breast:
    • Fat - majority of breast tissue by volume (90%), pathologically largely inert
  • Epithelium
    • Lobules - clusters of glands that make milk during lactation
    • Ducts - the plumbing that takes the milk to the nipple
    • Together form a tree-like network in the breast
    • At the tips of the ‘branches’ is the terminal duct lobular unit (TDLU), where the ducts join the lobules - most breast pathology and neoplasms arise here
153
Q

Give examples of benign and malignant uterine pathology

A
  • Benign
    • Fibroids
    • Adenomyosis
  • Malignant
    • Endometrial cancer
154
Q

What steps are taken following a sentinel lymph node biopsy if the biopsy is:

  1. Negative
  2. Positive
A
  1. Negative - no further treatment required
  2. Positive
  • Further surgery - clearance
  • Axillary radiotherapy
  • No futher treatment - as long as there are oncological treatments in play to mop up any residual carcinoma
155
Q

What effect to anti-cancer drugs have on cells in various stages of the cell cycle?

A
  • ​If a anti-cancer drug targets DNA synthesis it will only target cells in the S phase - have to give it for a long time + repeat to target all cells
  • Actively dividing cells are sensitive to many anticancer drugs
    • Drugs that are active only on dividing cells - cell-cycle specific drugs
  • Resting (G) phase cells are less sensitive to anticancer drugs
    • Drugs also active on resting cells - cell cycle-non specific
    • E.g. hormone specific for breast/prostate cancer
156
Q

How can breast cancers be classified molecularly?

A
  • Modern molecular techniques have offered alternative ways to classify breast cancer rather than classic morphology
  • Techniques used in gene profiling and microarray analysis - large numbers of genes assessed and patterns detected
  • Not routinely given in most UK pathology reports, give an alternative scheme for classifying breast cancer which complements and overlaps traditional morphology
  • ER and PR status still however is the critical molecular test in use in practice - ‘predictive’ of response to hormone therapy
157
Q

What is the aim of cervical cytology screening?

A
  • Cytological screening samples cells from the cervical transformation zone - designed to detect changes associated with HPV infection and Cervical Intraepithelial Neoplasia (CIN)
  • CIN - precancerous squamous epithelial changes - asymptomatic
  • The presence of dyskaryosis (nuclear abnormalities - cytological) suggestive of CIN prompts referral to colposcopy clinic for biopsy to detect CIN
158
Q

Describe the genetic predisposition to ovarian cancers

A
  • About 5-10% of ovarian cancers are familial, mostly related to BRCA1/2 gene mutations
  • Lifetime risk of ovarian cancer is approx. 30% in BRCA1 carriers, lower in BRCA2
  • Genetic alterations in sporadic ovarian cancer
    • BRCA mutations only present in 9% ovarian cancers
    • HER2 overexpressed in 35% of ovarian cancers (= poor prognosis)
    • KRAS mutations in 30% of ovarian tumours, mostly mucinous cystadenocarcinomas
    • P53 mutated in approx. 50% of all ovarian cancers, esp. in high grade serous cancers
159
Q

Describe the basic histological layers of the uterus

A
  • Endometrium - consists of glands and stroma and has a variety of normal appearances depending on the phase of the menstrual cycle, menopausal status etc.
  • Myometrium - smooth muscle comprising much of the uterus
  • Perimetrium - outer serosal layer, derived from visceral peritoneum
160
Q

Describe the staging of ovarian cancer

A
  • Stage 1A - tumour localised to 1 ovary, capsule intact
  • Stage 1B - tumour localised to both ovary, capsule intact
  • Stage 1C - capsule ruptured, surgical split, malignant cells in astasis
  • Stage 2A - infiltration of tumour into fallopian tube, infiltration of tumour into fallopian tube and uterus
  • Stage 2B - infiltration of tumour into urinary bladder, infiltration of tumour into rectum
  • Stage 3 - spread of the tumour to retroperitoneal lymph nodes, spread of tumour to peritoneum, in form of peritoneal deposits
  • Stage 4 - spread of tumour to pleura, causing pleural effusion, spread to the tumour to lung parenchyma as lung nodules, spread of the tumour to liver/spleen
161
Q

Describe the features of a malignant serous ovarian carcinoma

A
  • Thick septations, solid components
  • Ascites, peritoneal metastases, lymphadenopathy, distant metastases
162
Q

List the populations of cells which make up solid tumours

A
  • Dividing cells - progressing through cell cycle
    • Sensitive to cell cycle specific drugs
  • Resting cells - not dividing but could do so
    • Insensitive to many drugs
    • Cause many relapses - have to give many chemo doses to reach desired toxicity
  • Cells which can no longer divide but contribute to tumour size
    • Not a problem
163
Q

What are the common prognostic factors in breast cancer?

A
  • Hormone receptor status - ER, PR
    • Predicts behaviour and sensitivity to hormonal treatments
  • HER 2 status - HER 2 amplification generally predicts poorer prognosis but will allow treatment with Herceptin and similar drugs
  • Stage
    • A measure of how far a tumour has spread
    • TNM is the most common in use and is used in breast
      • T - Tumour - in breast determined by size in mm
      • N - Nodes - how many axillary nodes involved
      • M - Metastasis - present or not
  • Grade
    • Measures the intrinsic ‘aggressiveness’ of the tumour
    • How fast will this grow?
    • Different in different sites?
    • In breast - count tubules, mitoses and estimate nuclear size to get a score 1-3
      • Grade 1 - slow growing
      • Grade 2 - intermediate
      • Grade 3 - fast growing
  • Nottingham prognostic index
    • Way of combining grade and stage together into a single number that can be used as a shorthand to stratify prognosis
164
Q

Describe the histological appearance of leiomyomas

A
  • Whorled (fascicular) pattern of smooth muscle bundles separated by well vascularised connective tissue
  • Smooth muscle cells elongated with eosinophilic or occasional fibrillar cytoplasm and distinct membranes
  • Lymphocytes and mast cells
165
Q

What is an endometrioma?

A
  • AKA chocolate cyst, localised form of endometriosis, usually in ovary
166
Q

Describe the pathogenesis of periductal mastitis/mammary duct ectasia

A
  • Central ducts become inflamed, blocked and dilated
  • Associated with chronic inflammation and scarring
  • Known relationship to smoking
167
Q

How are endometrial polyps treated?

A

Via hysteroscope in outpatient clinic

168
Q

What are the causes of bilateral ovarian masses?

A
  • Primary ovarian malignancy metastases
  • Metastases from other sources
    • E.g. Krukenberg tumours - look for GI tract lesions
  • Diagnosis - CT guided biopsy
169
Q

Describe the hormonal changes which cause menstruation

A
  • No fertilisation/failure of implantation = corpus luteum degeneration
  • Lack of progesterone - endometrium breakdown
170
Q

What are the symptoms of endometrial hyperplasia/adenocarcinoma?

A

Usually only postmenopausal bleeding

171
Q

Describe the prevalence of granulosa cell tumours

A
  • Usually occur in post-menopausal women
  • Fairly common
172
Q

List types of invasive malignancies of the breast

A
  1. Ductal carcinoma
  2. Lobular carcinoma
  3. The ‘special types’ - rare breast cancers e.g. papillary/micropapillary, tubular, medullary, mucinous
  4. Non-carcinoma malignancy
173
Q

What are the treatment options for breast cancer?

A
  • Surgical treatment
    • Wide local excision
    • Mastectomy
  • Oncological treatment
    • Radiotherapy
    • Chemotherapy
    • Hormonal therapy
174
Q

How can steroid hormones and antagonist be used in cancer therapy?

A
  • Hormones are key regulators physiological functions including growth
  • Tumour may be responsive to a specific hormone which makes it regress e.g. prednisone
  • Tumour may be dependent on a hormone to grow - an antagonist of the hormone will suppress growth e.g. tamoxifen in breast cancer
175
Q

Why is the distinction of nipple inversion from birth from new nipple inversion important?

A
  • Nipple inversion from birth is a benign congenital anomaly
  • New nipple inversion in someone who has never had an inverted nipple may be a sign of cancer
176
Q

List the types of surface epithelial ovarian tumours

A
  • Benign lesions
  • Tumours of low malignant potential - intermediate borderline category
    • Limited invasive potential and much better prognosis than overtly malignant ovarian carcinomas
  • Malignant epithelial tumours
177
Q

What is a haemorrhagic ovarian cyst?

A
  • Haemorrhage into a dominant follicle/functional cyst
  • Asymptomatic or might present with pain
178
Q

Describe the patient pathway in breast cancer

A
  • Presentation
  • Investigation
  • Treatment
    • Surgical
    • Oncological
  • Pathology report
    • Diagnostic categories
    • Prognostic features
179
Q

Describe congenital abnormalities of the uterus

A
  • Class U0 - normal uterus
  • Class U1/dysmorphic uterus - T-shaped, infantile
  • Class U2/septate uterus - partial, complete
  • Class U3/bicorporeal uterus - partial, complete, bicorporal septate
  • Class U4/hemi uterus - with rudimentary cavity, without rudimentary cavity
  • Class U5/aplastic uterus - with rudimentary cavity, without rudimentary cavity
180
Q

Describe the hormonal control of the menstrual cycle before menstruation

A
  • Ovary stimulated by FSH/LH from HPO axis
    • FSH stimulates maturation of a dominant follicle and production of oestrogen by granulosa follicular cells
    • LH stimulates production of progesterone by the ovary
  • Proliferation stimulated by oestrogen
  • Secretions stimulated by progesterone (in general makes things looser and more secretory - retains water and so progesterone based drugs can make patients feel bloated)
181
Q

What is the importance of the pathology report in breast cancer?

A
  • Following surgery the breast tissue removed is assessed pathologically using microscopy and other techniques
  • The pathology report contains a wealth of data all of which is important to clinicians and patients - diagnosis and prognosis
182
Q

From where do surface epithelial ovarian tumours arise?

A

Coelomic mesothelium on the surface of the ovary

183
Q

What is ‘inflammatory cancer’?

A
  • Not actually a type of cancer, unusually way that any type of breast cancer may present
  • Lots of lymphatics blocked by tumour, breast becomes diffusely oedematous, red and tender (mimics inflammatory conditions)
184
Q

Describe the appearance of an endometrioma on imaging

A
  • Ultrasound
    • Variable, cyst with haemorrhagic debris
    • Won’t go away after 6 weeks
  • MRI
    • Shows it contains haemorrhage
185
Q

What pathological processes can affect the vagina?

A
  • Low oestrogen after the menopause may lead to atrophic vaginitis with discomfort, dyspareunia and bleeding. Polyps and cysts are not uncommon.
  • VAIN (vaginal intraepithelial neoplasia) and squamous carcinoma of the vagina are uncommon, but primary cancers of the cervix or vulva can involve the vagina
  • Infections including bacterial vaginosis, thrush and trichomonas vaginalis are sometimes identified in smears
    • Trichomonas vaginalis is sexually transmitted, sensitive to hetronidazole
186
Q

Describe the microscopic appearance of fibrocystic change in the breast

A
  • Small and large cysts (dilated cavities lined by epithelium)
  • Adenosis - more glands/lobular tissue (even sclerosing adenosis where the glands are small and squashed)
  • More fibrous stroma
  • Epithelial hyperplasia - where the duct or lobular epithelium gets thicker and forms unusual shapes
  • Apocrine metaplasia - where the epithelial cells of cysts changes to look like apocrine sweat glands
  • Microcalcification - important as calcifications seen on mammography and are one way to detect cancer
  • Columnar cell changes
    • Recently recognised part of the fibrocystic spectrum
    • Associated with calcification - seen on mammography
    • Tall cells with apical snouts line cysts
    • Some variants of columnar cell change increase (very slightly) cancer risk
187
Q

Where can endometriosis occur?

A

Sites of endometriosis - ovaries, peritoneal surfaces (including uterine ligaments and rectovaginal septum), large and small bowel, appendix, mucosa of cervix, vagina and fallopian tubes, laparotomy scars etc.

188
Q

What is seen on microscopy in a complete molar pregnancy?

A

Microscopy shows markedly enlarged oedematous villi with central cisterns and circumferential trophoblast proliferation

189
Q

What are the symptoms of salpingitis?

A

Fever, lower abdominal or pelvic pain and pelvic masses if tubes distended with exudate or secretions

190
Q

Compare lobar carcinoma in-situ and ductal carcinoma in-situ

A
  • LCIS
    • Less of a clinical concern than DCIS
    • Behaves more like a risk factor for malignancy than true dysplasia
  • DCIS
    • More significant and usually requires treatment
    • Up to between 14-50% of patients with DCIS will develop invasive cancer if left untreated
    • May not be a small lesion - can be extensive and form a significant mass or lesion without progression to invasive cancer
    • Can co-exist with invasive malignancy
    • Is usually treated with surgery but without axillary surgery (by definition pure DCIS will not metastasise)
191
Q

Describe reproductive embryological development in females

A
  • Without SRY, the gonad develops into an ovary with oogonia and stromal cells; without testosterone, mesonephric ducts regress
  • Without AMH/MIS, the paramesonephric ducts give rise to the oviducts, uterus, cervix and upper 1/3 of the vagina
  • Urogenital sinus –> bulbourethral glands, lower 2/3 of vagina, bladder (except trigone), urethra and vestibule
  • Mesonephric ducts –> trigone of bladder
192
Q

Who should be offerred cervical cytology screening?

A
  • The current policy in Scotland is that women aged 25-65 are invited - inclusive of those who have been vaccinated
    • Age 25-50 three yearly
    • Age 50-65 five yearly
193
Q

How is surgical treatment used in breast cancer?

A
  • Surgery aims to excise the malignancy and leave none behind
  • Type of surgery offered depends on
    • Size and type of tumour(s)
    • Size of breast
    • Location of tumour
  • Multiple tumours - difficult to conserve breast tissue
  • Small breast - hard to conserve breast tissue
194
Q

What is fat necrosis? What causes it?

A
  • Relatively common inflammatory reaction caused by damage to breast fat
  • Can be caused by any trauma
    • External trauma - history important
    • Previous surgery
    • Other inflammatory conditions
195
Q

How is chemotherapy used in breast cancer treatment?

A
  • Neoadjuvant - before surgery to reduce the size of a tumour
  • Adjuvant
    • After surgery to reduce the risk of metastasis at a distant site. Not all patients will benefit and stratification of risk is important using various prognostic factors (grade, stage etc.) to identify ‘high risk’ tumours
    • Particularly useful in ‘triple negative’ breast carcinoma which lack targets for usual hormonal therapies (ER, PR, HER2 negative) and are difficult to treat
196
Q

What are the possible complications of salpingitis?

A
  • Include adherence of tube to ovary, tubo-ovarian abscess
  • Adhesions involving tubal plicae increase risk of tubal ectopic pregnancy
    • Ruptured tubal ectopic pregnancy can be potentially life-threatening
  • Damage or obstruction of tube lumen may produce infertility which may not be easy to treat
  • Ovarian tubes also commonly involved when endometriosis is present and this may also compromise ovarian tube function
197
Q

When are products of conception sent to pathology for analysis?

A
  • Usually to confirm intrauterine pregnancy, pathologist looks for placentally derived chorionic villi or an implantation site
  • Also important to identify any cases of gestational trophoblastic disease - partial and complete hydatidiform moles and choriocarcinoma
198
Q

How is colposcopy carried out?

A
  • Cervix visualised
  • Washed with acetic acid
  • Application of iodine
  • Green light filter
  • Abnormal area can be biopsied (stains white w/ acetic acid or is non-iodine staining) or treatment performed at the time or at further appointment
199
Q

How thick are the changes seen in the epithelium in CIN1?

A

1/3 thickness change in epithelium

200
Q

What are the main causes of breast abscesses?

A
  • Periductal mastitis/mammary duct ectasia
  • Acute (lactational) mastitis
201
Q

How are dermoid cysts usually diagnosed?

A

Most found in young women as ovarian masses or incidentally on abdominal scans, may contain foci of calcification associated with bone/teeth, approx. 10% bilateral

202
Q

Describe the prevalence of breast fibroadenomas

A
  • Commonest benign breast neoplasm
  • Commoner in young patients
203
Q

What is an intraduct papilloma?

A
  • The other relatively common benign breast neoplasm
  • A frond-like growth usually in large ducts below the nipple
  • Patients present often with nipple discharge
  • Benign but often excised to ensure nothing worse lurking
204
Q

What is the terminal duct lobular unit?

A
  • Epithelial structures that produce milk during lactation
  • 2 layers around them
    • Luminal
    • Myoepithelial - lost in breast malignancy (can test for to diagnose)
205
Q

Describe the more aggressive forms of ovarian teratomas

A
  • About 5% ovarian teratomas in adults are immature cystic teratomas with immature neuroectodermal elements, associated with more aggressive behaviour
  • Teratomas in children rare but often more immature than in adults
  • In 1% there is malignant transformation of one of the tissue elements (squamous carcinoma, adenocarcinoma, sarcomas etc)
206
Q

How does squamous carcinoma appear on colposcopy/cytology?

A

Bleeds easily

On cytology - blood polymorphs, bizarre shaped squamous cells

207
Q

Describe the pathology of ductal carcinoma in-situ

A
  • Previously existing spaces are expanded by a proliferation of atypical epithelial cells
  • Don’t invade through epithelial basement membrane
  • Focal necrosis commonly associated with DCIS - in centre
208
Q

Describe the prevalence of serous ovarian tumours

A
  • Most frequent ovarian tumours - 60% benign, 15% borderline, 25% malignant
    • Benign most common in 30-40 y/o
    • Malignant most common in 45-65 y/o
209
Q

How is the risk of ovarian malignancy calculated?

A

Risk of malignancy index:

  • RMI - ultrasound score x menopausal score x CA 125
  • Menopausal score
    • Premenopausal - 1
    • Postmenopausal - 3
  • Ultrasound score
    • 0 = none
    • 1 = one abnormality
    • 3 = two or more abnormalities
  • RMI > 200 concerning for malignancy - referral to specialist gynaecological cancer service, and staging CT advised if >200 (look for metastatic disease)
210
Q

Describe the prognosis of serous ovarian tumours

A
  • Benign and borderline tumours have an excellent outcome (borderline tumours almost 100% survival, even with peritoneal involvement nearly 75%)
  • Invasive serous carcinomas have poor prognosis, depends on stage at diagnosis
211
Q

List the types of benign breast pathology

A
  1. Developmental
  2. Inflammatory
  3. Hyperplastic
  4. Benign neoplasms
212
Q

How is axillary surgery used in the treatment of breast cancer?

A
  • Like carcinomas at other sites breast cancer has a tendency to spread to local nodes for the breast are in the axilla
  • Formerly the only option was to excise all of the nodes in the axilla to ensure that all the nodes with cancer were removed
  • This ‘axillary clearance’ sometimes caused poor post-op arm function or gross arm oedema
  • The modern alternative is sentinel node biopsy
213
Q

How are endometrial hyperplasia/adenocarcinoma treated?

A
  • Hyperplasia - progesterone therapy such as Mirena IUS or hysterectomy
  • Endometrial adenocarcinoma - hysterectomy, with subsequent management depending on tumour grade + stage
214
Q

What is Meig’s syndrome?

A
  • Combination of an ovarian fibroma with ascites and pleural effusion = Meig’s syndrome
  • Removal of the tumour is curative
  • Pathophysiology not clear but ovarian tumour with ascites is more likely to be a carcinoma
215
Q

Give examples of hyperplasia in the breast

A
  • Fibrocystic change
  • Radial scar
  • Stromal proliferations
216
Q

How does HPV infection make the cervix genetically susceptible to cancer?

A
  • More than 99% of cervical carcinomas are associated with HPV infection
    • Have a genome of only 8kb but >150 types associated w/ different biological properties
  • Early genes E1-7 interact with intracellular molecules to interfere with cell proliferation machinery to replicate the virus
  • Late genes L1/2 encode capsid proteins
  • Disruption of cell cycle checkpoints may contribute to accumulation of oncogenic mutations and carcinogenesis
217
Q

How prevalent are are mucinous ovarian tumours?

A

About 10% of malignant (cystadenocarcinomas), 10% of low malignant potential (borderline), 80% benign

218
Q

Give examples of common benign ovarian pathologies

A
  • Ovarian follicles
  • Dermoid cysts
  • Haemorrhagic cysts
  • Endometriomas
  • Polycystic ovarian syndrome
  • Ovarian torsion
219
Q

How can cystic teratomas present acutely?

A

Cystic teratomas are prone to torsion (presentation of 10-15% of cases), producing an acute surgical emergency

220
Q

Describe the effectiveness of cytotoxic anti-cancer drugs and how this impacts dosing

A
  • A therapeutic course of a cytotoxic drug kills a constant fraction of the malignant cells
  • If a dose kills 99.999% of all dividing cells in a tumour of 109 cells - leaves 10,000 cells
  • Host immune system does not destroy these cells, and they will divide again - must aim for total kill
  • Prolonged treatment required to reduce chance of relapse from resting cells –> severe cumulative toxicity
221
Q

What is ectopic breast tissue?

A
  • Breast tissue outside the breast
    • Usually in ‘milk line’ - embryological structure between axilla and groin - can be elsewhere
  • Sometimes with nipple
  • Sometimes glandular material only
  • ALL other types of breast disease can happen in ectopic breast tissue
222
Q

How do ovarian tumours typically clinically present in general?

A
  • Often asymptomatic until well advanced
  • Clinical presentation often similar despite biological diversity: local pressure symptoms (e.g. pain, gastrointestinal complaints, urinary frequency)
  • Sometimes they become twisted on their pedicles (torsion) producing severe abdominal pain (acute abdomen)
  • Functioning ovarian tumours often come to attention because of the hormones they produce
  • Abdominal swelling due to ascites is a common presentation of ovarian malignancy but ascites also seen with benign tumours
223
Q

What causes acute mastitis?

A
  • Often associated with breast feeding - fissuring of skin (due to baby feeding) allows access to organisms
  • Stagnant milk allows growth
224
Q

Give examples of rare ovarian germ cell tumours

A

Dysgerminoma, embryonal carcinoma, yolk-sac tumour, choriocarcinoma

225
Q

Define gestational trophoblastic disease

A

Gestational trophoblastic disease = umbrella term for several conditions including hydatidiform moles (partial and complete) and frankly malignant tumours including choriocarcinoma

226
Q

Give examples of nitrogen mustards and their use as anti-cancer drugs

A
  • Mechlorethamine - not in use anymore
    • First anticancer chemotherapy drug
    • Blister agent
    • Used to treat Hodgkin’s lymphoma, non-Hodgkin’s lymphoma - destroys blood
    • Highly reactive - must be given IV
  • Melphalan
    • Fusion of mechlorethamine with phenylalanine - precursor for melanin
    • Melphalan might accumulate specifically in melanomas? - didn’t work but
    • Much more stable, less aggressive
    • Absorption and distribution possible without extensive alkylation
    • Oral drug
    • Used to treat multiple myeloma, ovarian and breast cancer (still used)
  • Cyclophosphamide
    • Prodrug, requires activation by phosphoramidase - high phosphoramidase activity in some tumours (specific in situ activation?)
    • Didn’t work but
    • Prodrug with activation in liver
    • Much less toxic
    • Aldehyde dehydrogenase (ALDH) in hepatocytes protects liver against toxicity of drug
    • ALDHs also present in large concentrations in bone marrow cells and intestinal epithelium
    • Used to treat many cancers (not those with ALDH e.g. liver)
227
Q

List the symptoms of cervical cancer

A
  • Post coital bleeding
  • Intermenstrual bleeding
  • Irregular vaginal bleeding
  • Pain
  • None
228
Q

What does a whorled ‘water silk’ appearance of a uterine mass suggest?

A

Description typical of uterine fibroids (leiomyomas) - almost always benign lesions but can be large, often multiple and may be symptomatic

229
Q

When is mastectomy used to treat breast cancer?

A
  • Some tumours are large, multiple or extensive
  • Neo-adjuvant chemotherapy can shrink some of these large tumours to make WLE possible
  • Other tumours size, extent or location may mean that mastectomy is clinically safest
230
Q

List non-carcinoma breast malignancies

A
  • Sarcomas - stromal
  • Lymphoma - lymphoid cells
  • Malignant phyllodes
  • All very rare but can occur
231
Q

What is a nipple adenoma?

A
  • Benign condition, can be mistaken for cancer
  • Alongside nipple
232
Q

Describe the appearance of endocervical glandular abnormalities

A
  • Rosette
  • Psuedostratification, multiple nuclei
  • cGIN - darker, cells abnormal, smaller spaces between glands
233
Q

Describe the histology of the ovaries

A
  • Flat surface epithelium
  • Cortex: compact ovarian stroma, small functional cysts, germ cells
  • Medulla: hilus cells, vessels, nerves
234
Q

How is CIN2/3 treated?

A
  • Diathermy - loop dependent on size of cervix/lesion, lesion sent to pathology
  • ‘Cold-coagulation’ - uses heat to destroy abnormal cells
    • Dead tissue will slough off
    • Don’t have tissue to examine - might have microinvasion which can’t be identified
  • Treatment done in clinic under local anaesthetic
235
Q

Describe the changes seen in high grade (moderate) squamous dyskaryosis

A
  • 1:2 to 2:3 nuclear to cytoplasmic ratio
  • CIN2 - 2/3 thickness change in epithelium
  • Nuclear enlargement with dense hyperchromasia and coarse chromatin clumping
  • CIN3 - invaded endocervical glands
  • Full thickness epithelial cell change CIN3
236
Q

Describe the genetic mutations most commonly associated with low/high grade serous carcinoma of the ovary

A
  • In HGSC, p53 and BRCA1 are typically abnormal and ovarian carcinomas in patients with BRCA1 mutations are almost always HGSC
    • Inability to repair double stranded DNA breaks leads to chromosomal instability and genomic chaos
  • LGSC (KRAS, BRAF typically abnormal) is often associated with a borderline serous component and is a quite different disease
237
Q

Describe the microscopic appearance of a breast fibroadenoma

A
  • Like a ‘giant lobule’ - all the TDLU tissue expanded and distorted
  • Ducts, glands, and lots of variably cellular fibrous tissue
  • Rare fibroadenomas in adolescent girls may become very large (100mm+ - giant fibroadenoma)
    • Juvenile fibroadenoma is a related entity in girls <18 years of age and often large
238
Q

Describe the changes which occur due to cystic atrophy of the endometrium

A
  • Multiple cystic spaces (dilated glands) lined with atrophic epithelium are present within a dense fibrous stroma
  • Can be mistaken for diffuse or focal areas of endometrial thickening e.g. endometrial polyp or endometrial hyperplasia
239
Q

What is the most common ovarian germ cell tumour?

A

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

240
Q

Which cells of the ovary can be affected by tumours?

A
  1. Surface (coelomic) epithelium
  2. Germ cells
  3. Sex cord/stromal cells

Each cell type gives rise to various tumours

241
Q

Describe the mechanism of action of antimetabolites

A
  • Interfere with nucleotide synthesis or DNA synthesis
    • Nucleotide synthesis - antifolates
      • Methotrexate
      • Ralitrexed
      • Pemetrexed
    • Nucleotide analogues
      • 5-fluorouracil
      • Cytarabine
      • Gemcitabine
      • Fludarabine
      • Capecitabine
  • Deprive cell of metabolites needed for DNA synthesis e.g. nucleotides
  • Antifolates - deprive cell of folate, needed for thiamine production
  • Nucleotide analogues - disrupt function of DNA by interfering with helix
242
Q

What is a phyllodes tumour?

A
  • Very similar to fibroadenoma but commoner in older patients
  • They are more cellular, more mitotic and more atypical than fibroadenoma, also often larger
  • ALL fibroadenomas are benign only MOST phyllodes behave in a benign fashion
  • SOME phyllodes are frankly malignant
243
Q

What causes the symptoms associated with polycystic ovaries?

A

Over-production of androgens by multiple cystic follicles in the ovaries (reasons unclear) - LH high, FSH low

244
Q

Describe the appearance of severe dyskaryosis (likely CIN3) on cytology

A
  • Inflammatory cells (neutrophils)
  • Dyskaryotic cells
245
Q

Describe the cell division cycle

A
  • S phase - DNA synthesis
  • G2 - pause before separation of chromosomes in mitosis
  • After mitosis the cell usually differentiates (–> G0 phase), if not –> G1 (cell matures and grows ready for next division)
  • Restriction point at end of G1 checks cell is ready to divide again
246
Q

Describe the histological appearance of endometrial adenocarcinoma

A
  • Atypical glandular proliferation, tubular glands lined by columnar cells
  • Nuclei are oval/elongated, large
  • Neutrophils within and around cysts
247
Q

Describe the appearance of endometrial cancer on imaging

A
  • Transvaginal US initial investigation- endometrial thickening (>5mm)
  • MRI - local invasion
  • CT - distant metastases
248
Q

Why does cystic atrophy of the endometrium occur?

A
  • Benign process that can occur as part of tamoxifen-associated endometrial change
    • Post-menopausal women for breast cancer
249
Q

Describe the appearance of an ovarian endometrioma

A

Chocolate cyst

250
Q

What is the significance of PAX8 and Wnt1 markers in ovarian cysts?

A
  • Positive - of embryologically Mullerian origin
  • If negative, tumour is metastases of a primary tumour from another tissue e.g. GI
251
Q

An administrator (29) attends her GP for routine cervical cytology. A sample of cells is reported with squamous cells showing ‘moderate dyskaryosis’.

Q. What should the GP do?

A: Refer patient for colposcopy

B: Reassure and arrange routine recall for repeat cytology in 3 years

C: Reassure and repeat cytology within 6 months

D: Request urgent referral for likely cervical cancer

E: Arrange HPV vaccination

A

A - refer for colposcopy

‘Dyskaryosis’ implies definitely abnormal nuclei and the most likely reason for their presence is significant CIN. Detecting CIN is main reason for cervical screening - pre-malignant lesion which can be treated before it becomes a cancer. Colposcopy + biopsy required to evaluate the situation further.

252
Q

What is the most common congenital abnormality of the breasts?

A

Ectopic breast tissue

253
Q

Describe the mechanism of action of nucleotide analogues

A
  • Sugar moiety of cytidine is arabinosine rather than ribose
  • Isolated from the sponge Cryptothethya crypta
  • Cellular activation to ara-CTP
  • S-phase cell cycle specific, inhibits DNA polymerase
  • Incorporation into DNA causes chain termination
254
Q

Which demographic is most commonly affected by breast cancer?

A
  • Around 350 men are diagnosed with breast cancer every year in the UK, including around 30 in Scotland
  • Rare in women in their 20s and uncommon in the 30s
  • Incidence rises steadily from later 30s to about 60, after which it does not change much
  • Median age for breast cancer diagnosis is mid-60s
255
Q

Describe the appearance of adenomyosis on imaging

A

Thickening of the junctional zone

256
Q

How can endometrial polyps present?

A

Abnormal bleeding

257
Q

Describe the gross appearance of dermoid cysts

A

Smooth capsule, often filled with sebaceous secretion and matted hair, sometimes foci of bone and cartilage, nests of bronchial or gastrointestinal epithelium, teeth and other recognisable lines of development also present e.g. thyroid

258
Q

Describe the mechanism of action of doxorubicin

A
  • Inserts itself between base pairs -strong interaction w/ DNA bases because it is aromatic
  • Binds to the sugar-phosphate DNA backbone
  • Local uncoiling
  • Impaired DNA and RNA synthesis
  • Now approx. 2000 doxorubicin analogues (anthracyclines)
259
Q

Describe the pathogenesis of fat necrosis

A
  • Necrotic fat (trauma causes fat cells to swell and burst, releasing contents) with chronic inflammation and multinucleated giant cells
  • Pathologically
    • Spaces - fat cells, without nuclei
    • Speckles - chronic inflammatory cells
260
Q

Describe the prognosis of malignant mucinous ovarian tumours

A

Prognosis of mucinous cystadenocarcinoma slightly better than serous, but stage is more important than histological type

261
Q

What causes endometrial hyperplasia/adenocarcinoma?

A
  • Conditions associated with prolonged oestrogenic stimulation of the endometrium
  • Possible underlying causes
    • Anovulatory cycles
    • Endogenous sources of oestrogen - obesity, PCOS, oestrogen secreting ovarian tumours
    • Exogenous sources of oestrogen only HRT
262
Q

Describe the appearance of a normal uterus on MRI

A
  • Endometrium bright
  • Junctional zone dark
  • Myometrium in the middle
  • Easiest to see the 3 layers of the uterus on T2
263
Q

How are haemorrhagic cysts diagnosed/managed?

A
  • Ultrasound
    • Variable, cyst with haemorrhagic debris
  • Follow up in 6 weeks - check its getting smaller/gone
264
Q

List the clinical symptoms of endometriosis

A
  • Dysmenorrhoea
  • Pelvic pain
  • Infertility
265
Q

Describe wide local excision of a breast cancer

A
  • Aim to take just the tumour with a rim of normal tissue in order to preserve the remaining breast
  • Usually combined with radiotherapy in order to minimise the risk of recurrence
  • Pathological assessment of margins is important
266
Q

Why is correct diagnosis of benign breast neoplasms important?

A
  • Benign neoplasms will form a mass and keep growing despite removal of the initiating stimulus
  • Will not metastasise - BUT patients will feel a lump and be anxious
267
Q

What causes granulomatous conditions of the breast

A
  • Systemic granulomatous disease e.g. TB, sarcoidosis
  • Idiopathic granulomatous mastitis - when infection has been clinically excluded - treat with steroids (would make infection worse)
  • Reactions to ruptured implants can be granulomatous
268
Q

What are the possible outcomes of a cervical smear and what are the next steps for each outcome?

A
  • Negative
    • Repeat routinely in 3 years
  • Borderline nuclear abnormality
    • Repeat in 6 months (x3 BNA refer for colposcopy)
  • Low grade dyskaryosis
    • 2x refer for colposcopy
  • High grade dyskaryosis (moderate)
    • Refer for colposcopy
  • High grade dyskaryosis (severe)
    • Refer colposcopy
  • Glandular abnormality (smear is designed to see squamous lesions but can detect glandular)
    • Refer to colposcopy - endocervical cells
    • CGIN –> adenocarcinoma
  • Features suggestive of invasion
    • Urgent referral to colposcopy
269
Q

Where are mitoses (dividing cells) most likely to be seen in normal cervical stratified squamous epithelium?

A: In the basal layer of the epithelium

B: Just above the basal layer

C: Near the surface of the epithelium

D: At all levels from basal to surface

E: In the basal 2/3 of the epithelium

A

Answer: B

  • Mitoses (dividing cells) most likely to be seen in proliferative zone just above the basal layer in normal cervical stratified squamous epithelium
  • Basal layer itself includes stem cells and does not proliferate very rapidly
  • Mitoses in basal 2/3 of epithelium - seen in CIN2
  • Mitoses at all levels from basal to surface - seen in CIN3
270
Q

How can sentinel lymph node biopsy be used in the treatment of breast cancer?

A
  • The sentinel node is the node that cancer will likely spread to first before it involves any other axillary nodes
  • Identifying and removing the sentinel node allows pathologists to asses whether or not there is tumour in the sentinel node
271
Q

How can fat necrosis present?

A
  • May cause a lump and clinically or mammographically be mistaken for cancer
272
Q

What are the most common findings in women presenting with breast lumps?

A
  • 40% fibrocystic change
  • 30% no disease
  • 10% cancer
  • 7% fibroadenoma
  • 13% miscellaneous benign

Majority of women who present with breast lumps have benign conditions

273
Q

How is invasive cervical squamous carcinoma diagnosed?

A
  • Inflammation and necrosis can be a clue on cervical cytology to the presence of invasive squamous carcinoma
  • Diagnosis can be difficult on cytology - colposcopy and biopsy required for definitive diagnosis
  • Dirty looking smear reflects necrosis and inflammation which can be a clue to the presence of an invasive carcinoma
274
Q

Is cervical screening working?

A
  • The biggest risk factor for cervical cancer is not attending for a smear test
  • Introduced in 1998, HPV vaccination introduced in 2008 in UK - diagnosis of cervical cancer has declined
  • Diagnosis spiked in 2009 after Jade Goody died
275
Q

Give examples of cytotoxic antibiotics

A
  • Dactinomycin
  • Doxorubicin

Both isolated from streptomyces

276
Q

List common benign neoplasms of the breast

A
  • Fibroadenoma
  • Intraduct papilloma
  • Nipple adenoma
277
Q

Describe the prognosis of endometrial stromal sarcomas

A
  • Slow clinical progression with 50% local recurrence rate, and death from metastases in 15%
  • Recurrence or metastasis can occur many years after primary tumour and is not predictable
278
Q

What are the symptoms of a leiomyosarcoma?

A

Symptoms - initially none, then bleeding or pain

279
Q

What genetic mutation is thought to predispose to ovarian endometrioid cancer?

A

Like endometrial cancer, endometrioid carcinomas have often lost PTEN (phosphatase and tensin homolog’) tumour suppressor gene

280
Q

Describe the division of the cervical epithelial stem cells

A
  • Stem cells in basal layer divide asymmetrically to yield:
    • A cell which will remain as a stem cell
    • A cell which will proliferate (divide several times) to supply the new cells which will mature as they migrate from the bottom of the epithelium to the top, where the differentiated cells are finally shed

Medicine Year 3 (15 decks)

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