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Year 3 > Week 4 Female GU and Breast > Flashcards

Week 4 Female GU and Breast Flashcards

1
Q

Pathology of vulva

A

Skin tags, melanocytic nevi common

Bartholin vestibular gland cysts: dilation of Bartholin gland (adjecent of vaginal canal) - becomes infected and forms abscess

Non infective inflammation:

Lichen planus

Lichen sclerosus (assoc. with increased risk of Vulva SCC) - white plaque, parchment-like skin

Vulva squamous cell carcinoma - HPV related and non-HPV related

HPV related: HPV 16/18 leading to dysplasia/vulva intraepithelial neoplasia (VIN). <60 yrs. Basaloid/warty cancers

Non HPV related (assoc. with dermatoses) - Lichen sclerosus, >60 yrs.

Extra mammary Paget’s disease (pic)

  • Malignant epithelial cells in the epidermis of vulva
  • Carcinoma in situ
  • Presents as erythematous, itchy, ulcerated skin
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2
Q

Pathology of vagina

A

NK stratified squamous epithelium

Atrophic vaginitis - decreased oestrogen due to menopause. Discomfort, bleeding.

Infections:

Bacterial vaginosis

Trachimonas vaginalis - STI (parasite)

Thrush (candida)

Vaginal carcnioma due to VAIN (vaginal intraepithelial neoplasia) rare. Primary cancers of cervix and vulva can spread to vagina.

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3
Q

Cervix epithelium

A

Exocervix (outer): NK stratified squamous epithelium (Right)

  • as cells migrate up to epithelial surface they accumualte glycogen, giving basket weave appearence)

Endocervix (inner): columnar (glandular) epithelium (Left)

Clear change between the two areas - transformation zone (where neoplasia of cervix commonly develops)

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4
Q

Cervical screening

A

Women 25-65 yrs

25-50 3 years

50-65 5 years

Detecting change in cells in transformation zone in cervix, for HPV infectiona and CIN

Features suggestive of malignancy:

High nuclear:cytoplasm ratio

Nuclear hyperchromasia (darker staining pattern in nucleus)

Nuclear pleomorphism

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5
Q

What does the current HPV vaccination cover?

A

HPV 6, 11 (genital warts) , 16, 18 (HPV that causes cervical cancer)

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6
Q

Cervical carcinoma

A

99% cervical carcinoma due to HPV (usually 16/18)

HPV leads to cervical intraepithelial neoplasia (CIN)

CIN characterised by dyskaryosis (nuclear abnoramlity)

HPV pathogenic for koilocytic change (perinuclear halo (clear area around nucleus) and nuclear enlargment, nuclear hyperchromasia (nucleus is stained darker)

Leads to squamous cell carcinoma

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7
Q
A

CIN II

Dyskaryosis 2/3 of epithelium

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8
Q
A

CIN I

If dyskaryosis involves first 1/3 of epithelium

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9
Q
A

CIN III

Dyskaryosis involving full-thickness epithelium

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10
Q

Cervical carcinoma symptoms

A

Middle aged women

Irregular vaginal bleeding

Post coital bleeding

Intermesntrual bleeding (between menstruation)

Pain

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11
Q

Adenocarcinoma of cervix

A

Endocervical glandular epthelium can also undergo pre-malignant change - cGIN (cervical glanduar intraepithepial neoplasia)

Glandular epithelium becomes adenocarcinoma

Also assoc. with HPV

Abnormalities:

Rosette: nuclei lines up and protrudes from edges (looks like rosette)

Pseudostratification: nuclei overalp

Can be picked up on smear (though difficult)

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12
Q

Koilocytic change

A

Pathogenic of HPV

  • High nucleus:cytoplasm ratio (nucleus larger)
  • nuclear hyperchromasia (nucleus darker staining)
  • perinuclear halo (pale area around nuelcus)
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13
Q

Uterus

A

Endometrium - consists of glands, stroma, changes in appearence depending on phase on menstrual cycle

  • Proliferative
  • Secretory
  • Menstruation

Myometrium - smooth muscle

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14
Q

Endometrium

A

Proliferative phase

Can see mitotic figures (dark cells)

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15
Q

Endometrium - what stage?

A

Secretory phase

Spiral glands are more irregular, luman larger, secrete mucus (looks eosinophilic (pink))

Blood vessels prominent (spiral arteries)

Oedematous stroma

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16
Q

Endometrium - stage?

A

Menstrual phase

Glands have collapsed

Lots of blood

Stroma was previously oedematous has now shed

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17
Q

Endometriosis

A

Presence of endometrial tissue (glands and stroma) outside of uterus

Adenomyosis: presence of endometrial tissue in myometrium

Aeitology:

Retrograde theory: retrograde menstruation leading to endomtrium outside of uterine cavity

Metastatic theory: endoemtrial tissue arises from coelomic epithelium e.g. peritoneum

Sites of endometriosis:

Ovaries (leads to chocolate cyst), small/large bowel, appendix, vagina

Histology:

Glands

Stroma

Processed blood (by macrophages) - sign of chronic haemorrhage

Symptoms:

Pelvic pain (endometrial tissue in uterine ligaments), Dysmenorrhea (pain during menstruation), pain with bowel movements (as endometrial tissue can be in pouch of douglas), infertility (endometrial tissue in fallopian tubes)

Diagnosis: Laparoscopy

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18
Q

What happens to endometriosis after menopause?

A

Graudal regression

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19
Q

Example of an developmental abnormality of the uterus

A

Bicornuate uterus

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20
Q

Endometrial polyps

A

Exophytic mass projecting into endometrial cavity

Assoc. with tamoxifen (as has pro-esotrogenic effect on endometrium)

Decreaesd gland:stroma ratio (more stroma than gland)

Fibrous stroma (looks pinker) and thick walled blood vessels

Presents irregular uterine bleeding

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21
Q

Endometrial hyperplasia

A

Increased gland:stroma ratio (increased endometrial glands compared to stroma) due to prolonged oestrogenic stimulation

Causes:

PCOS, obesity, HRT

Clinical features: post-menopausal bleeding (as during menopause, ovaries stop secreting oestrogen but fat converted to oestrogen)

Atypical endometrial hyperplasia:

Precursor of endometrioid adenocarcinoma (looks like normal endometrium)

Treatments:

Hyerplasia - mirena IUD

Endometrioid Adenocarcinoma - hysterectomy

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22
Q
A

Leiomyoma - benign proliferation of smooth muscle of myometrium

Common, usually pre-menopausal women

Assoc. with trisomy 12

Symptoms:

Usually asymptomatic

  • abnormal bleeding (as endomtrial lining is stretched), increased urinary frequency
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23
Q

Leiomyoma vs Leiomyosarcoma

A

Leiomyoma:

Pre-menopausal women

Multiple, distinct, white whorled mass

Microscopically resembles normal smooth muscle tissue

Leiomyosarcoma: malignant smooth muscle tumor of myometrium. Arises de novo (does not come from leiomyoma)

Post-menopausal women

Single mass, can be necrotic and haemorrhagic

Microscopically: atypical cytology, mitotic figures

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24
Q
A
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25
Q
A

Endometrial stromal sarcoma

Group of tumors from endomtrial stroma

Diffuse worm-like pattern

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26
Q

Gestational trophoblastic disease

A

Umbrella term for group of diseases including hydatidiform mole, and malignant tumors e.g. choriocarcinoma (tumour of trophoblasts)

Hydaditiform mole

Complete - empty egg fertilised by one/two sperm

46 chromosomes

Enlarged oedematous villi

Circumferential trophoblastic proliferation

Increased risk of choriocarcinoma

Partial - normal egg fertilised by two sperm

69 chromosomes

Oedematous villi

Partial trophoblastic proliferation

Minimal risk choriocarcinoma

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27
Q

Ovary

A

Covered by flat, coelomic epithelium

Cortex: follicles containing occytes, stroma

Medulla: blood vessels, nerves, hilar cells

In follicle, oocyte surrounded by granulosa cells, and theca cells (outer)

LH acts on theca cells to secrete androgens

FSH acts on granulosa cells to convert androgens to oestrogen

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28
Q

What is this?

A

Corpus albicans - scarring left when corpus luteum degenerates, if an egg is not fertilised

Shows patient has finished menstrual cycle but is peri- menopause, as no follicles

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29
Q

PCOS

A

Includes symptoms of annovulation (oligomenorrheoa - few periods) and increased androgen levels (hirsutism, infertility)

Typically in young, obese women

Pathophysiology:

Gonadotropins:

Increased LH - supports theca cells - makes more androgens

Decreased FSH (less conversion of androgens to oestrogen)

Leads to degeneration of follicles forming mulitple sub-cortical cysts

Inreased androgens:

  • Due to theca cells producing androgens
  • Decreased steroid hormone binding globulin (produced in liver, binds testosterone so won’t be active)

Insulin resistance:

Inuslin stimulates theca cells, reduces SHBG, increased androgens

Increased risk of endometrial carcinoma

Treatment: Weight loss, metformin, clomifene (anti-oestrogen, leading to increased FSH due to negative feedback)

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30
Q

Ovarian neoplasms

A
  1. Coelomic epithelium
  2. Germ cells
  3. Sex cords/stromal cells (cells which support oocyte e.g. granulosa, theca cells

Clinical presentation:

Aymptomatic, pain, irregular menstruation, hirsutism, ascites (bloated abdomen)

Investigations:

physical examination, bloods: CA-125, ultrasound

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31
Q

Surface epithelial ovarian tumours

A

Benign - cystadenoma (cystic) or cystadenofibroma (without solid stromal component)

Borderline - has malignant potential but better prognosis

Malignant - cystadenocarcinoma (cystic) or solid adenocarcinoma

Carcinomas can be high grade serous, low grade serous, mucinous, endometrioid (assoc. with endometriosis), clear-cell (assoc with endometriosis),

High grade serous: BRCA1/2 genes, p53

Low grade serous: KRAS

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32
Q

Surface epithelial ovarian tumors - serous ovarian tumours

A

Benign: women 30-40yrs. Large, bilateral, smooth, shiny covering. Cysts are filled with serous fluid, lined by single columnar epithelium. Some cells cilaited.

Borderline: cellular atypia, no stromal invasion

Malignant: older women. Anaplasia (lack of differentiation) of cells. Stromal invasion.

Psammoma bodies (pic) - concentric calcifications, in papillae of serous tumours. (Also in papillary thryoid carcinoma)

33
Q

Surface epithelial ovarian tumours: Mucinous

A

Tumour consists of mucin secreting cells

Most benign. Borderline. Malignant.

Krukenberg tumours - Cancer from GI metastases to ovary. Can mimic primary ovarian mucinous tumour (usually unilateral)

Morphology: large, no psammoma bodies, cysts lined with mucinous cytoplasm

34
Q

Benign or Malignant?

Serous or malignant?

A

Malignant mucinous ovarian tumour

Nuclei more atypical, lost polarity, mitotic figures, irregular shaped glands, cells contain mucus

35
Q

Ovarian endometrioid carcinoma

A

Histologically characterised by appearence of tubular glands, resembles normal endometrium

Usually malignant (though can be benign, malignant)

Arises from endometriosis

Some have ovarian tumour and endometrium carcinoma (due to loss of PTEN tumour supressor gene)

36
Q

Germ cell tumour

A

Young women

Found as ovarian mass or incidentally on abdominal scans

95% are mature cystic teratomas (dermoid cysts) - benign

Germ cells differentiate into 3 germ cells layers: ectoderm (skin, hair), mesoderm (muscle, fat), endoderm (GI, respiratory epithelium)

Morphology - smooth, hair, teeth, bone, GI epithelium

Malignant:

5% immature cystic teratomas (Immature tissue - neuroectoderm)

1%: tissue elements e.g. skin can become malignant. Skin - squamous cell carcinoma

Cystic teratomas prone to torsion

Yolk sac tumour, choriocarcnioma (placental tissue) rare

37
Q

Ovarian sex cord/stromal cell tumours

A

Resemble normal sex cord stromal tissue of ovary (granulosa, theca, cells, fibrous tissue, Sertoli, Leydig cells)

Granulosa and theca cell tumours: secrete oestrogen

Sertoli-Leydig cell tumours - secrete androgens

Granulosa cell tumours - not rare. Post-menopausal women. Can lead to endometrial hyperplasia, endometrial carcinoma

Fibroma - benign tumour of fibroblasts

Meigs syndrome - fibroma, ascites and pleural effusion

Ovarian tumour with ascites - usually carcinoma

38
Q

Brenner tumour

A

Mixed surface epithelium-stromal tumour

Benign, unilateral, yellowish

Contains urothelium (transitional epithelial cells) with fibrous stroma

39
Q

Fallopian tube

A

Ciliated columnar epithelium

Plicae

Layers of smooth muscle

40
Q

Common conditions of Uterus

A

Endometriosis

Uterine fibroids (leiomyomas)

Uterine cancer

Clinical presentation: pain, post menopausal bleeding

41
Q

Uterine fibroids (leiomyomas)

A

Clinical presentation: heavy periods, pain, pressure, anaemia

42
Q

Normal structure of breast

A

Derived from milk line (imaginary line from axilla down to vulva)

Terminal duct lobular unit: functional unit

All ducts (grandular tissue) and lobules are lined by: inner luminal cells and myoepithelial cells (contractile function)

Adolescent breast - ducts in a dense stroma

After puberty - lobules develop, breast expands

Pregnancy - hyerplasia, TDLU enlarged

Lactating - epithelial secretory activity (cytoplasic vacuoles)

Menopause - Atrophy -of TDLU. Ducts are dilated.

43
Q

Common conditions of Fallopain tube

A

Tubo-ovarian abcess: pelvic pain, increased CRP/WCC, temperature

Ectopic pregnant: pelvic pain, bHCG increased, missed periods

44
Q

Developmental abnormalities

A

Ectopic breast tissue - commonest congenital breast abnormality, usually on milk line

Brest hypoplasia - assoc. with Turner’s syndrome

45
Q

Inflammtory breast conditions

A

Infectious:

Acute mastitis - cellulitis of breast, assoc. with breast feeding. Bacteria (S.aureus) enters through cracked nipple

  • presents as warm, red breast with purulent discharge
  • can form abscess

Non-infectious/inflammatory:

Granulomatous inflammation of breast can occur in systemic diseases e.g. sarcoidosis, TB

Idiopathic granulomatous mastitis: Non-necrotising granulomatous inflammation centred on loubles. Distinct, hard mass. Usually parous (previously pregnant). May repsond to steroids.

  • Need to exclude TB, sarcoid, vasculitis

Periductal mastitis - inflammation of subaerolar ducts, leading to dilation of sub-aerolar ducts. Assoc. with smoking. Presents as sub-aerolar mass and nipple retraction (due to granulation tissue which contains myofibroblasts which pull in skin). Multiparous post menopausal women.

Ductal ectasia - Inflammation of duct leading to dilatation of duct. Duct becomes blocked. Debris leads out leading to, peri-aerolar mass with green/brown nipple discharge.

Fat necrosis: related to trauma. Benign. Presents as mass or calcification on mammogram. Biopsy shows necrotic fat with calcifications and giant cells.

46
Q

Fibrocystic change

A

Most common breast condition

Development of fibrosis and cysts

Presents as bilateral, diffuse breast lumpiness

Includes:

Fibrosis (increased fibrous stroma)

Cystic

Adenosis (increased glandular tissue) (can show calcifications on MMG)

Apocrine metaplasia (large, epithelial cells with granular eosinophilic cystoplasm and apical projections)

Sclerosing adenosis - benign proliferation of glandular tissue. Can show microcalcifications on US. 2x risk of br. ca

Radial scars - sclerosing lesions, with fibrotic and elastic core >10mm. Myoepithelail cells present (whereas tubular carcinoma doesn’t)

Epithelial hyperplasia (ductal, lobular) - **2x risk of br. ca**
Epithelial hyperplasia with atypia - **4x risk of br. ca**

Papillomas also included

47
Q

Intraductal papilloma

A

Papillary lesion: finger like projection with epithelial lining

Papillary growth (benign) into a large duct, lined by epithelal and myoepithelial cells with fibrovascular core

Multiple papillomas (papillomatosis) - assoc. with malignancy

Presents as bloody discharge in pre-menopausal (benign)

If malignant (papillary carcinoma) - has no myoepithelial cells (more common in post-menopausal women)

48
Q

Benign neoplasms: Fibroadenoma

A

Tumour of fibrous tissue and glands. Characteristically, proliferation of epithelium and mesenchyme.

Most common benign tumour of breast

Most common tumour in pre-menopausal women

Well circumscribed, mobile, marble-like mass

Hormone-sensitive - can shrink during menopasue

Juvenile adenomas can be very large

No increase risk of cancer

49
Q

Phyllodes tumour

A

Fibroadenoma-like tumour with overgrowth of fibrous stroma

Overgrowth pushes out “leaf-like” projections

Post-menopausal women

Can be malignant

Needs to be surgically excised with margin

50
Q

Pure adenomas

A

Pure adenomas: Tubular or lactating, lack prominent stroma of fibroadenomas

51
Q

Nipple adenomas

A

Nipple adenomas:

Presents as erosive lesion on nipple +/- nipple discharge

  • Benign but can mimic Paget’s disease of the nipple (malignant)

Paget’s disease of nipple: Ductal carcioma in situ that has gone up to skin of nippple

  • Presents as red, scaly rash on nipple (like eczema) , and darker area surrounding nipple. Can be a sign of breast cancer
52
Q

Harmatoma of breast

A

Discrete, smooth, painless mass of glandular, fatty, fibrous tissue

53
Q

Breast cancer

A

Most common cancer in women

Usually 40-70 yrs

Risk factors:

Earlier menarche, late menopause, obesity, OC use, HRT, alcohol, BRACA1/2, Li Fraumeni Syndrome (p53), pTEN. nulliparity, first child after 30 yrs.

Symptoms: new lump, altered shape/size

skin changes - peau d’orange (resembles skin of an orange, due to lymphatic infilitration), rash

nipple changes - inversion, ezcema-like rash (Paget’s)

Investigations:

Clinical examination

MMG, US (microcalcification often present in invasive carcinoma)

FNA

Core biospy, excisional biopsy

UK women invited from 50-70 every 3 yrs

Treatment

Local excision and radiotherapy

Mastectomy

Sentinel node biopsy

Axillary clearence - if sentinel node positive. However, can cause limitation of arm movement, lymphoedema

54
Q

Pseudo Angiomatous Stromal Hyperplasia (PASH)

A

Hard, palpable lump. Radily enlarging mass with skin changes.

Premenopausal

Dense stroma lined with channels lined by myofibroblasts

Differential: angiosarcoma

55
Q

Breast cancer pharmacology

A

Tamoxifen: ER (oestrogen receptor) antagonist (80% breast cancers overexpress oestrogen and progesterone receptors)

However, has agonist activity in endometrium so can cause increase risk of endometrial cancer

Aromatase inhibitors - Letrazole (prevents conversion of androgens to oestrogen) - only for post-menopausal women

Transtuzumab (Herceptin) - Those who express HER2 have worse prognosis. Transtuzumab has improved survival

Chemotherapy

56
Q

Prognostic factors for breast cancer

A

Size, grade (based on tubules, pleomorphism, mitoses) and lymph node

Type does not add much if take grade into account

Hormone receptor status - important in repsonse to certain treatment

57
Q

Nottingham Prognostic Index

A

Estimates prognosis, and determines treatment

Grade of tumour - Grade 1 = 1 pt, Grade 3 = 3 pts

Nodes - 0 nodes = 1 pt, 1-3 nodes = 2 pts, 4+ nodes = 3 points

Size (size x 0.2cm)

Higher, poor prognosis

58
Q

In situ carcinoma of breast

A

Malignant epithelial proliferation within basement membrane

Has not expanded into breast stroma

Has not communication with blood vessels, lymphatics

No possibility of metastases

59
Q

Axillary staging

A

Need to US axilla in all invasive carcinoma

Sentinel node biopsy - SN (first node which the cancer will spread to from primary tumour). If neg, suggests cancer has not spread to lymph nodes or other organs.

Inject blue dye, assess first lymph nodes

Axillary clearence - if SN postive

60
Q

Ductal carcinoma in situ

A

Malignant proliferation of cells in ducts within basement membrane

Most commonly shows calcification on MMG

Presents as lump, nipple discharge, Paget’s disease of breast (DCIS which extends up ducts to skin of nipple)

10x increased risk of breast ca

Histologically - necrosis dystrophic calcificaiton in centre

Treatment

Complete excision

Local excision and radiotherapy

Mastectomy+/-reconstruction

61
Q

Invasive ductal carcinoma

A

Forms duct-like structures

Most common invasive carcinoma

Presents as mass detected by physical examination or MMG

May show nipple retraction, skin dimpling

Biopsy: ductal like structures with desmoplastic stroma

62
Q

Special subtypes of invasive ductal carcnioma

A

Tubular carcinoma - produces tubules. Desmoplastic stroma (connective tissue which grows with tumour so very dense). No myoepithelial cells

Mucinoid carcinoma - malignant cells flooded in pool of mucus. Usually over 75 yrs.

Both have good prognosis

63
Q

Lobular carcinoma in situ (LCIS)

A

Malignant proliferation of cells in lobules, within basement membrane

Usually detected incidentally, no mass or calcification

Bilateral, multi-focal

Dyscohesive cells (not stuck together), loss of E-cadherin

Management:

Follow up (as low risk of become invasive)

Bilateral mastectomy

64
Q

Invasive lobular carcicnoma

A

No duct formation, grows in single file (signet ring cells)

65
Q

Tumor grading

A

Blood and Richardson

Grade 1-3 (Grade 1: well differentiated, slow growing, Grade 3: poorly differentiated, fast growing)

Tubules (less no. of cells that form tubule, worse)

Pleomorphism

Mitoses

66
Q

Cancer chemotherapy

A

Alkylating agents: cross-links DNA between one strand, and across two strands

  • Nitrogen mustards: Melphalan, Cyclophosphamide
  • Cysplatin
  • Busulphan
  • Lomustine

Antimetabolites: interferes with DNA/nucleotide synthesis

  • Methotrexate

Nucleotide analogues:

  • Pyrimidine analogues: Flouro-uracil
  • Purine analogues: Mercaptopurines
  • Cytarabine (inhibits DNA polymerase)

Cytotoxic antibiotics: acts by direct action on DNA as intercalators

  • Dactinomycin:

disrupted RNA polymerase

  • Doxorubicin:

impairs RNA/DNA synthesis

Vincristine - Microtubule inhibitors

  • Disrupts cell division

Steroid hormones:

Prednisolone - supresses lymphocyte growth

Hormone antagonists:

Tamoxifen - oestrogen antagonist

Flutamide - testosterone antag

Prostap - LH release inhibitors

67
Q

Salpingitis

A

Salpingitis: Inflammation of fallopian tubes

Part of inflammtory pelvic disease

Due to bacteria e.g. Chalmydia trachomatis, mycoplasma, coliforms

Fever, low abdo pain, pelvic mass if tube distended with exuate

Complications: tubo-ovarian abcess (adherence of tube to ovary), damage of tube leading to infertility, tubal ectopic pregnancy

68
Q

Fallopian tube malignancies

A

Papillary serous carcinoma

BRCA1 mutations

69
Q

Pseudo angiomatous stromal hyperplasia

A

Hard palpable lump

Premenopausal

Presents as rapidly expanding mass with skin changes

70
Q

Diabetic mastopathy

A

Ill-defined hard mass

Assoc with TMD1

<30 yrs

Keloid like stroma

71
Q

What kind of cells would you see if you do a FNA of cyst, abscess or lipoma in the breast

A

Abscess: neutrophils (soft, tender)

Cyst: macrophages (doesn’t appear solid on US)

Lipoma: mature fat cells (soft to palpate, less mobile than fibroadenoma)

72
Q

Which cancers are signet ring cells present in?

A

Cell which nucleus is pushed to side due to mucin

Lobular carcinoma of breast

Gastric adenocarcinoma (diffuse)

73
Q

Pagets disease of breast

A

DICS that has extended up ducts to kin of nipples

Red, scaly rash

74
Q

What does this IHC stain show?

A

That the breast cancer is ER positive (when oestrogen binds to receptor, moves to nucleus)

Brown colour is positive

Progesterone would look similar

75
Q

What does this IHC stain show?

A

Breast cancer which is Her2+ (Her2 receptor on cell surface)

Brown colour is positive

76
Q

Features of heridatry br. cancer

A

Fx history

Pre-menopausal age

Mulitple tumours

77
Q

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

A

Colposcopy: Looking at the cervix

LETZ Biospy (loop excision of transformation zone)

78
Q

TNM

A

Tumour size or depth

N - spread to regional lymph nodes

Metasteses - distant metastasis (most important factor)

Year 3 (15 decks)

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