Week 3 - Female GU Pathology

Question 1

What is ovarian torsion? How does it present?

Answer 1

• 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)

Question 2

What is seen on microscopy in a partial molar pregnancy?

Answer 2

Microscopy shows oedematous villi and subtle trophoblast proliferation

Question 3

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

Answer 3

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

Question 4

How are leiomyomas managed?

Answer 4

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

Question 5

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

Answer 5

• 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

Question 6

Describe the mechanism of action of pyrimidine analogues

Answer 6

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

Question 7

What are Krukenberg tumours?

Answer 7

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

Question 8

Give examples of benign pathology of the ovaries

Answer 8

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

Question 9

Describe the types of ovarian sex cord-stromal tumours

Answer 9

• 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

Question 10

How does fibrocystic change in the breast clinically present?

Answer 10

• Lumpy/bumpy
• Often multiple
• Worst before menstruation

Question 11

Define polycystic ovarian syndrome

Answer 11

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

Question 12

How prevalent is ovarian cancer?

Answer 12

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

Question 13

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

Answer 13

• 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

Question 14

How are granulomatous conditions of the breast characterised?

Answer 14

Formation of granulomas (aggregates of macrophages)

Question 15

Describe the pathogenesis of endometriosis

Answer 15

• 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

Question 16

Describe the embryological development of the gynaecological tract

Answer 16

• 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

Question 17

Describe the mechanism of action of tamoxifen

Answer 17

• 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

Question 18

What causes ovarian clear cell carcinomas?

Answer 18

Associated with endometriosis

Question 19

How are cervical cancers imaged?

Answer 19

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

Question 20

List the symptoms of periductal mastitis/mammary duct ectasia

Answer 20

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

Question 21

Describe the prevalence of breast cancer

Answer 21

• 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

Question 22

What is cGIN?

Answer 22

• 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)

Question 23

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

Answer 23

• 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

Question 24

How is the Nottingham prognostic index calculated?

Answer 24

• 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

Question 25

Describe pre-invasive/dysplastic lesions of the breast

Answer 25

* 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

Question 26

Describe the grading of CIN

Answer 26

CIN1 - low grade disease CIN 2/3 - high grade disease

Question 27

What is a leiomyosarcoma?

Answer 27

* 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

Question 28

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

Answer 28

* 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

Question 29

Describe the relationship between endometrial hyperplasia and adenocarcinoma

Answer 29

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

Question 30

Describe the malignancies which affect the fallopian tubes

Answer 30

* 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

Question 31

Describe the appearance of normal cervical cytology

Answer 31

* 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

Question 32

What is the most common pathology of the fallopian tube?

Answer 32

* 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

Question 33

Describe the mechanism of action of akylating agents

Answer 33

* 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

Question 34

What causes fibrocystic change in the breast?

Answer 34

* Probably an aberrant response of normal breast tissue to fluctuations in cyclical hormones - may not be a 'disease'

Question 35

What are endometrial stromal sarcomas?

Answer 35

* 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)

Question 36

List the main classes of anti-cancer drugs

Answer 36

* Alkylating agents * Antimetabolites * Cytotoxic antibiotics * Microtubule inhibitors * Steroid hormones and antagonists

Question 37

What are the symptoms of adenomyosis?

Answer 37

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

Question 38

Describe the appearance of endometrial polyps on microscopy

Answer 38

* 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

Question 39

What are the symptoms of a leiomyoma?

Answer 39

* Asymptomatic * Abnormal bleeding * Urinary frequency if large * Impaired fertility

Question 40

How does the lining of the cervix change during puberty?

Answer 40

* 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

Question 41

What are actinomyces?

Answer 41

* 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

Question 42

What is papillomatosis?

Answer 42

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

Question 43

How can prostate cancer be treated with hormonal therapy

Answer 43

* 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

Question 44

Describe the appearance of a serous ovarian carcinoma on imaging

Answer 44

* Large cystic mass * Benign - encapsulated, regular, clear edges * Metastatic - irregular, solid parts, in peritoneum

Question 45

Describe the types of molar pregnancies

Answer 45

* 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

Question 46

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

Answer 46

Microcalcification - small flecks of calcium (Benign lesions can calcify - more common in malignant cancers)

Question 47

Describe the side effects of chemotherapy

Answer 47

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.

Question 48

What treatments are available for cancer?

Answer 48

* 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

Question 49

What is a koilocyte?

Answer 49

* 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

Question 50

Describe the breast screening programme in Scotland

Answer 50

* 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

Question 51

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

Answer 51

* 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

Question 52

Describe the features of ovarian malignancy on ultrasound

Answer 52

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

Question 53

What is a leiomyoma?

Answer 53

* 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

Question 54

What kind of tumour is a fibroid? A: Lipoma B: Leiomyoma C: Angiolipoma D: Lipoleiomyoma E: Lymphangioma

Answer 54

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

Question 55

Describe the development of vulval squamous cancer

Answer 55

* 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

Question 56

How do breast fibroadenomas present?

Answer 56

* 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

Question 57

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

Answer 57

* 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

Question 58

Describe LETZ biopsy

Answer 58

* 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

Question 59

List stromal proliferations of the breast

Answer 59

* Diabetic mastopathy - type 1 diabetes, overproduction of fibrous stroma * Pseudoangiomatous hyperplasia

Question 60

List the phases in the normal menstrual cycle

Answer 60

1. Proliferative phase * Inner endometrium - simple columnar epithelium, long uterine glands * Coiled arteries, stratum functionalis --\> basalis * Stroma (connective tissue) 2. Secretory phase * Bigger more coiled glands, more secretions - nutrition of embryo (pre-implantation) 3. 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

Question 61

Describe the appearance of the uterus on CT

Answer 61

* 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

Question 62

List the signs/symptoms of ovarian malignancy

Answer 62

* Abdominal distention * Pelvic or abdominal pain * Feeling full and loss of appetite * Increasing urinary urgency or frequency * Irritable bowel disease \>50

Question 63

How thick should the endometrium be?

Answer 63

* Width varies with stage of cycle in premenopausal * Post-menopausal should be less than 5mm

Question 64

How is radiotherapy used in the treatment of breast cancer?

Answer 64

* To the breast following WLE to reduce risk of recurrence * Sometimes to the axilla if positive nodes have been found

Question 65

What clinical findings sugges a hydatidiform mole?

Answer 65

* On ultrasound * Larger uterus than expected for gestational age * Enlarged ovaries * Also may have hyperemesis, hypertension, high hCG

Question 66

What is the effect of HPV infection on the cervix?

Answer 66

* 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

Question 67

What is a radial scar?

Answer 67

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

Question 68

How do normal cells become cancer cells?

Answer 68

* 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

Question 69

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

Answer 69

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

Question 70

List the pathological features of radial scars

Answer 70

* 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

Question 71

Describe the mechanism of action of purine analogues

Answer 71

* Mercaptopurines * Converted into false nucleotides * Disrupts purine nucleotide synthesis * May be incorporated into DNA, disrupting helix

Question 72

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)

Answer 72

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)

Question 73

Which tumours can be discovered at breast screening?

Answer 73

* Asymptomatic * Small * Lower grade and stage than symptomatic tumours

Question 74

Describe the malignant surface epithelial ovarian tumours

Answer 74

* 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

Question 75

Describe the pathology of leiomyosarcomas

Answer 75

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

Question 76

Describe the mechanism of action of prednisone in cancer therapy

Answer 76

* Synthetic adrenocortical steroid hormone * Converted in the body to active form --\> Prednisolone - suppresses lymphocyte growth

Question 77

Describe the molecular subtypes of breast cancers

Answer 77

* 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

Question 78

Give examples of pathology which can affect the vulva

Answer 78

* 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

Question 79

Which conditions are associated with breast hypoplasia?

Answer 79

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

Question 80

Describe the prognosisof ovarian cancer

Answer 80

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

Question 81

When is the myometrium thickest?

Answer 81

Proliferative stage - in preparation to deliver child

Question 82

What are the features of uterine fibroids on imaging?

Answer 82

* Hypoechoic (dark) mass on ultrasound * Often make the uterus look bulky/lobulated on CT

Question 83

What are the risks of a partial molar pregnancy?

Answer 83

Risk of invasive mole, which invades and destroys the uterus

Question 84

What is a uterine pipelle?

Answer 84

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

Question 85

How is cervical cytology screening carried out?

Answer 85

* Use speculum to access cervix * Cervical brush turned clockwise - spokes of brush have designed to collect cells when turned clockwise

Question 86

Describe a borderline nuclear abnormality of cervical cells

Answer 86

Enlargement of nucleus, abnormal chromatin

Question 87

How is cervical cancer managed?

Answer 87

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

Question 88

Describe the histology of the fallopian tube

Answer 88

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

Question 89

Give examples of benign developmental breast conditions

Answer 89

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

Question 90

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

Answer 90

* 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

Question 91

Describe the histological appearance of endometrial hyperplasia

Answer 91

* 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

Question 92

List the types of ovarian carcinomas

Answer 92

* 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

Question 93

Describe the mechanism of action of dactinomycin

Answer 93

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

Question 94

Describe the histology of a serous cystadenoma of the ovary

Answer 94

* Lined by ciliated columnar epithelial cells or cuboidal non-ciliated epithelium resembling ovarian surface epithelium * Fibrous stroma with spindly fibroblasts

Question 95

What investigations can be done to diagnose a breast lump?

Answer 95

* 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

Question 96

How can endometrial abnormalities be detected?

Answer 96

* Can be picked up on smear * Post-menopausal bleeding should always be referred to gynaecology for endometrial biopsy

Question 97

Describe the morphology of serous ovarian tumours

Answer 97

* 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

Question 98

Describe the mechanism of action of cisplatin

Answer 98

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

Question 99

What are Brenner tumours?

Answer 99

* 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

Question 100

Describe the invasion of a metastasising squamous carcinoma

Answer 100

Invades stromal tissue (BVs and lymphatics)

Question 101

Describe the appearance of ovarian torsion on ultrasound

Answer 101

* Enlarged ovary * Free fluid in pelvis * Ovary may show absent vascularity

Question 102

Give examples of akylating agents

Answer 102

* Nitrogen mustards * Derived from mustard gases of WW1 * Melphalan, chlorambucil, cyclophosphamide, ifosfamide * Cysplatin * Temozolomide * Lomustine - can penetrate brain * Busulpha - 'selective' effect on bone marrow

Question 103

List the risk factors for the development of breast cancer

Answer 103

* 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)

Question 104

What are the signs/symptoms of a breast malignancy?

Answer 104

* 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

Question 105

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

Answer 105

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

Question 106

Give examples of inflammatory condtions affecting the breast

Answer 106

* Acute mastitis * Granulomatous mastitis * Idiopathic * From systemic condition * Periductal mastitis * Fat necrosis

Question 107

Describe the appearance of ovarian follicles on ultrasound

Answer 107

* 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

Question 108

How are mucinous ovarian tumours diagnosed?

Answer 108

Diagnosis depends on architectural complexity and cytological atypia

Question 109

Are hyperplastic and dysplastic lesions of the breast always distinct?

Answer 109

* 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

Question 110

Give an overview of reproductive embryology

Answer 110

* 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

Question 111

Describe the appearance of normal squamous cells in cervical cytology

Answer 111

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

Question 112

Describe the role of HPV testing in cervical screening

Answer 112

* 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)

Question 113

What are mucinous ovarian tumours?

Answer 113

Tumours consisting of mucin-secreting cells

Question 114

Describe the pathological appearance of endometrial stromal sarcomas

Answer 114

* 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

Question 115

Describe the features of lobular carcinoma

Answer 115

* 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)

Question 116

Describe the appearance of polycystic ovaries

Answer 116

* 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)

Question 117

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

Answer 117

* 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

Question 118

What are the symptoms of acute mastitis?

Answer 118

Cellulitis, can develop into abscess

Question 119

Describe the staging of endometrial cancer

Answer 119

* 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

Question 120

Describe the mechanism of action of methotrexate

Answer 120

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

Question 121

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

Answer 121

* 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

Question 122

Describe the HPV vaccination programme in the UK

Answer 122

* 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

Question 123

What are the risks of a complete molar pregnancy?

Answer 123

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

Question 124

Describe the normal physiological function of the breast

Answer 124

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

Question 125

How do dermoid cysts develop?

Answer 125

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

Question 126

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

Answer 126

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

Question 127

How big is a punch biopsy of the cervix?

Answer 127

5mm

Question 128

What are the most common outcomes in borderline nuclear abnormality?

Answer 128

* 70% HPV * 20% CIN1 * 10% CIN2 * 5% CIN3

Question 129

Describe the benign surface epithelial ovarian tumours

Answer 129

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

Question 130

Describe the diagnostic features of a menstrual endometrium

Answer 130

* Blood and condensed stroma (stromal condensation) * Blood can be present for a variety of reasons

Question 131

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

Answer 131

* Oligomenorrhoea, hirsutism, infertility and obesity - usually after menarche * Insulin resistance may lead to type 2 diabetes

Question 132

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

Answer 132

* 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

Question 133

What are endometrial polyps?

Answer 133

* Exophytic masses of variable size which project into the endometrial cavity * Associated with tamoxifen in some cases

Question 134

What are the complications of treatment of CIN2/3?

Answer 134

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

Question 135

Describe the features of ovarian endometrioid carcinomas

Answer 135

* 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

Question 136

Describe the mechanism of action of cytotoxic antibiotics

Answer 136

* Often not used against infective diseases because not selective * Act mainly by a direct action on DNA as intercalators

Question 137

What are the symptoms of uterine fibroids?

Answer 137

Pain, infertility, menorrhagia

Question 138

Describe the morphology of mucinous ovarian tumours

Answer 138

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

Question 139

Describe the features of ductal carcinoma

Answer 139

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

Question 140

What is STIC?

Answer 140

* 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

Question 141

Describe the prognosis of leiomyosarcomas

Answer 141

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

Question 142

List the types of breast pathology

Answer 142

* 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

Question 143

Describe reproductive embryological development in males

Answer 143

* 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

Question 144

How does cervical cancer develop from CIN?

Answer 144

* 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

Question 145

Describe the appearance of PCOS on ultrasound

Answer 145

Multiple small follicles (no dominant)

Question 146

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

Answer 146

* 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

Question 147

What are the risk factors for epithelial ovarian cancers?

Answer 147

* Nulliparity * Family history * Prolonged OC use may reduce risk

Question 148

What percentage of serous ovarian carcinomas are malignant?

Answer 148

25% malignant (usually older women)

Question 149

Define endometriosis and adenomyosis

Answer 149

* Endometriosis - the presence of endometrial tissue outside the uterus * Adenomyosis - the presence of endometrial tissue within the myometrium

Question 150

Describe the lining of the cervix

Answer 150

* 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

Question 151

How is ovarian cancer treated?

Answer 151

* 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

Question 152

Describe the normal components of the breast

Answer 152

* 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

Question 153

Give examples of benign and malignant uterine pathology

Answer 153

* Benign * Fibroids * Adenomyosis * Malignant * Endometrial cancer

Question 154

What steps are taken following a sentinel lymph node biopsy if the biopsy is: 1. Negative 2. Positive

Answer 154

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

Question 155

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

Answer 155

* ​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

Question 156

How can breast cancers be classified molecularly?

Answer 156

* 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

Question 157

What is the aim of cervical cytology screening?

Answer 157

* 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

Question 158

Describe the genetic predisposition to ovarian cancers

Answer 158

* 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

Question 159

Describe the basic histological layers of the uterus

Answer 159

* 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

Question 160

Describe the staging of ovarian cancer

Answer 160

* 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

Question 161

Describe the features of a malignant serous ovarian carcinoma

Answer 161

* Thick septations, solid components * Ascites, peritoneal metastases, lymphadenopathy, distant metastases

Question 162

List the populations of cells which make up solid tumours

Answer 162

* 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

Question 163

What are the common prognostic factors in breast cancer?

Answer 163

* 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

Question 164

Describe the histological appearance of leiomyomas

Answer 164

* 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

Question 165

What is an endometrioma?

Answer 165

* AKA chocolate cyst, localised form of endometriosis, usually in ovary

Question 166

Describe the pathogenesis of periductal mastitis/mammary duct ectasia

Answer 166

* Central ducts become inflamed, blocked and dilated * Associated with chronic inflammation and scarring * Known relationship to smoking

Question 167

How are endometrial polyps treated?

Answer 167

Via hysteroscope in outpatient clinic

Question 168

What are the causes of bilateral ovarian masses?

Answer 168

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

Question 169

Describe the hormonal changes which cause menstruation

Answer 169

* No fertilisation/failure of implantation = corpus luteum degeneration * Lack of progesterone - endometrium breakdown

Question 170

What are the symptoms of endometrial hyperplasia/adenocarcinoma?

Answer 170

Usually only postmenopausal bleeding

Question 171

Describe the prevalence of granulosa cell tumours

Answer 171

* Usually occur in post-menopausal women * Fairly common

Question 172

List types of invasive malignancies of the breast

Answer 172

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

Question 173

What are the treatment options for breast cancer?

Answer 173

* Surgical treatment * Wide local excision * Mastectomy * Oncological treatment * Radiotherapy * Chemotherapy * Hormonal therapy

Question 174

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

Answer 174

* 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

Question 175

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

Answer 175

* 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

Question 176

List the types of surface epithelial ovarian tumours

Answer 176

* 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

Question 177

What is a haemorrhagic ovarian cyst?

Answer 177

* Haemorrhage into a dominant follicle/functional cyst * Asymptomatic or might present with pain

Question 178

Describe the patient pathway in breast cancer

Answer 178

* Presentation * Investigation * Treatment * Surgical * Oncological * Pathology report * Diagnostic categories * Prognostic features

Question 179

Describe congenital abnormalities of the uterus

Answer 179

* 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

Question 180

Describe the hormonal control of the menstrual cycle before menstruation

Answer 180

* 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)

Question 181

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

Answer 181

* 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

Question 182

From where do surface epithelial ovarian tumours arise?

Answer 182

Coelomic mesothelium on the surface of the ovary

Question 183

What is 'inflammatory cancer'?

Answer 183

* 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)

Question 184

Describe the appearance of an endometrioma on imaging

Answer 184

* Ultrasound * Variable, cyst with haemorrhagic debris * Won't go away after 6 weeks * MRI * Shows it contains haemorrhage

Question 185

What pathological processes can affect the vagina?

Answer 185

* 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

Question 186

Describe the microscopic appearance of fibrocystic change in the breast

Answer 186

* 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

Question 187

Where can endometriosis occur?

Answer 187

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.

Question 188

What is seen on microscopy in a complete molar pregnancy?

Answer 188

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

Question 189

What are the symptoms of salpingitis?

Answer 189

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

Question 190

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

Answer 190

* 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)

Question 191

Describe reproductive embryological development in females

Answer 191

* 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

Question 192

Who should be offerred cervical cytology screening?

Answer 192

* 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

Question 193

How is surgical treatment used in breast cancer?

Answer 193

* 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

Question 194

What is fat necrosis? What causes it?

Answer 194

* 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

Question 195

How is chemotherapy used in breast cancer treatment?

Answer 195

* 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

Question 196

What are the possible complications of salpingitis?

Answer 196

* 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

Question 197

When are products of conception sent to pathology for analysis?

Answer 197

* 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

Question 198

How is colposcopy carried out?

Answer 198

* 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

Question 199

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

Answer 199

1/3 thickness change in epithelium

Question 200

What are the main causes of breast abscesses?

Answer 200

* Periductal mastitis/mammary duct ectasia * Acute (lactational) mastitis

Question 201

How are dermoid cysts usually diagnosed?

Answer 201

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

Question 202

Describe the prevalence of breast fibroadenomas

Answer 202

* Commonest benign breast neoplasm * Commoner in young patients

Question 203

What is an intraduct papilloma?

Answer 203

* 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

Question 204

What is the terminal duct lobular unit?

Answer 204

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

Question 205

Describe the more aggressive forms of ovarian teratomas

Answer 205

* 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)

Question 206

How does squamous carcinoma appear on colposcopy/cytology?

Answer 206

Bleeds easily On cytology - blood polymorphs, bizarre shaped squamous cells

Question 207

Describe the pathology of ductal carcinoma in-situ

Answer 207

* 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

Question 208

Describe the prevalence of serous ovarian tumours

Answer 208

* 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

Question 209

How is the risk of ovarian malignancy calculated?

Answer 209

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)

Question 210

Describe the prognosis of serous ovarian tumours

Answer 210

* 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

Question 211

List the types of benign breast pathology

Answer 211

1. Developmental 2. Inflammatory 3. Hyperplastic 4. Benign neoplasms

Question 212

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

Answer 212

* 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

Question 213

How are endometrial hyperplasia/adenocarcinoma treated?

Answer 213

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

Question 214

What is Meig's syndrome?

Answer 214

* 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

Question 215

Give examples of hyperplasia in the breast

Answer 215

* Fibrocystic change * Radial scar * Stromal proliferations

Question 216

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

Answer 216

* 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

Question 217

How prevalent are are mucinous ovarian tumours?

Answer 217

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

Question 218

Give examples of common benign ovarian pathologies

Answer 218

* Ovarian follicles * Dermoid cysts * Haemorrhagic cysts * Endometriomas * Polycystic ovarian syndrome * Ovarian torsion

Question 219

How can cystic teratomas present acutely?

Answer 219

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

Question 220

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

Answer 220

* 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

Question 221

What is ectopic breast tissue?

Answer 221

* 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

Question 222

How do ovarian tumours typically clinically present in general?

Answer 222

* 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

Question 223

What causes acute mastitis?

Answer 223

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

Question 224

Give examples of rare ovarian germ cell tumours

Answer 224

Dysgerminoma, embryonal carcinoma, yolk-sac tumour, choriocarcinoma

Question 225

Define gestational trophoblastic disease

Answer 225

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

Question 226

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

Answer 226

* 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)

Question 227

List the symptoms of cervical cancer

Answer 227

* Post coital bleeding * Intermenstrual bleeding * Irregular vaginal bleeding * Pain * None

Question 228

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

Answer 228

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

Question 229

When is mastectomy used to treat breast cancer?

Answer 229

* 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

Question 230

List non-carcinoma breast malignancies

Answer 230

* Sarcomas - stromal * Lymphoma - lymphoid cells * Malignant phyllodes * All very rare but can occur

Question 231

What is a nipple adenoma?

Answer 231

* Benign condition, can be mistaken for cancer * Alongside nipple

Question 232

Describe the appearance of endocervical glandular abnormalities

Answer 232

* Rosette * Psuedostratification, multiple nuclei * cGIN - darker, cells abnormal, smaller spaces between glands

Question 233

Describe the histology of the ovaries

Answer 233

* Flat surface epithelium * Cortex: compact ovarian stroma, small functional cysts, germ cells * Medulla: hilus cells, vessels, nerves

Question 234

How is CIN2/3 treated?

Answer 234

* 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

Question 235

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

Answer 235

* 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

Question 236

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

Answer 236

* 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

Question 237

Describe the microscopic appearance of a breast fibroadenoma

Answer 237

* 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

Question 238

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

Answer 238

* 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

Question 239

What is the most common ovarian germ cell tumour?

Answer 239

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

Question 240

Which cells of the ovary can be affected by tumours?

Answer 240

1. Surface (coelomic) epithelium 2. Germ cells 3. Sex cord/stromal cells Each cell type gives rise to various tumours

Question 241

Describe the mechanism of action of antimetabolites

Answer 241

* 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

Question 242

What is a phyllodes tumour?

Answer 242

* 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

Question 243

What causes the symptoms associated with polycystic ovaries?

Answer 243

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

Question 244

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

Answer 244

* Inflammatory cells (neutrophils) * Dyskaryotic cells

Question 245

Describe the cell division cycle

Answer 245

* 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

Question 246

Describe the histological appearance of endometrial adenocarcinoma

Answer 246

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

Question 247

Describe the appearance of endometrial cancer on imaging

Answer 247

* Transvaginal US initial investigation- endometrial thickening (\>5mm) * MRI - local invasion * CT - distant metastases

Question 248

Why does cystic atrophy of the endometrium occur?

Answer 248

* Benign process that can occur as part of tamoxifen-associated endometrial change * Post-menopausal women for breast cancer

Question 249

Describe the appearance of an ovarian endometrioma

Answer 249

Chocolate cyst

Question 250

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

Answer 250

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

Question 251

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

Answer 251

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.

Question 252

What is the most common congenital abnormality of the breasts?

Answer 252

Ectopic breast tissue

Question 253

Describe the mechanism of action of nucleotide analogues

Answer 253

* 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

Question 254

Which demographic is most commonly affected by breast cancer?

Answer 254

* 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

Question 255

Describe the appearance of adenomyosis on imaging

Answer 255

Thickening of the junctional zone

Question 256

How can endometrial polyps present?

Answer 256

Abnormal bleeding

Question 257

Describe the gross appearance of dermoid cysts

Answer 257

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

Question 258

Describe the mechanism of action of doxorubicin

Answer 258

* 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)

Question 259

Describe the pathogenesis of fat necrosis

Answer 259

* 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

Question 260

Describe the prognosis of malignant mucinous ovarian tumours

Answer 260

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

Question 261

What causes endometrial hyperplasia/adenocarcinoma?

Answer 261

* 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

Question 262

Describe the appearance of a normal uterus on MRI

Answer 262

* Endometrium bright * Junctional zone dark * Myometrium in the middle * Easiest to see the 3 layers of the uterus on T2

Question 263

How are haemorrhagic cysts diagnosed/managed?

Answer 263

* Ultrasound * Variable, cyst with haemorrhagic debris * Follow up in 6 weeks - check its getting smaller/gone

Question 264

List the clinical symptoms of endometriosis

Answer 264

* Dysmenorrhoea * Pelvic pain * Infertility

Question 265

Describe wide local excision of a breast cancer

Answer 265

* 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

Question 266

Why is correct diagnosis of benign breast neoplasms important?

Answer 266

* 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

Question 267

What causes granulomatous conditions of the breast

Answer 267

* 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

Question 268

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

Answer 268

* 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

Question 269

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

Answer 269

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

Question 270

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

Answer 270

* 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

Question 271

How can fat necrosis present?

Answer 271

* May cause a lump and clinically or mammographically be mistaken for cancer

Question 272

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

Answer 272

* 40% fibrocystic change * 30% no disease * 10% cancer * 7% fibroadenoma * 13% miscellaneous benign Majority of women who present with breast lumps have benign conditions

Question 273

How is invasive cervical squamous carcinoma diagnosed?

Answer 273

* 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

Question 274

Is cervical screening working?

Answer 274

* 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

Question 275

Give examples of cytotoxic antibiotics

Answer 275

* Dactinomycin * Doxorubicin Both isolated from streptomyces

Question 276

List common benign neoplasms of the breast

Answer 276

* Fibroadenoma * Intraduct papilloma * Nipple adenoma

Question 277

Describe the prognosis of endometrial stromal sarcomas

Answer 277

* 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

Question 278

What are the symptoms of a leiomyosarcoma?

Answer 278

Symptoms - initially none, then bleeding or pain

Question 279

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

Answer 279

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

Question 280

Describe the division of the cervical epithelial stem cells

Answer 280

* 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