Pathology Flashcards
What are the 2 main imaging modalities used to diagnose breast pathologies?
1) Mammogram
2) Ultrasound
What are the 2 main biopsy techniques used for laboratory testing of suspected breast cancers?
1) Fine needle aspiration biopsy
2) 14 gauge needle core biopsy
On a xray, a premenopausal breast appears (more/less) radiodense than a post-menopausal breast.
More
Why are inflammatory conditions of the breast most common in lactating women?
More milk
→ proliferation of Staphylococci in stagnant milk
→ Acute inflammation w neutrophils
→ Acute abscess formation
(Acute mastitis)
What are 4 examples of inflammatory conditions affecting the breast?
1) Acute mastitis
2) Periductal mastitis
3) Idiopathic granulomatous mastitis
4) Duct ectasia
5) Fat necrosis (usually trauma caused)
6) Inflammatory breast cancer
What are 3 Rx for a breast abscess?
1) Antibiotics
2) Excision
3) Incision and drainage
What is idiopathic granulomatous mastitis?
Rare inflammatory condition in parous women
- unknown etiology (might be HS rxn)
What are 2 Ddx of idiopathic granulomatous mastitis?
1) Malignancy
2) TB
What are 3 Rx for idiopathic granulomatous mastitis?
1) Steroids
2) Immunosuppressives
3) Surgery
What is a possible complication of breast augmentation such as paraffin injections, implants or autologous tissue?
Paraffinoma
- foreign-body type multinucleate giant cell reaction
What is an example of a common non-proliferative breast lesion?
Fibrocystic changes
Fibrocystic breast changes EPC:
Symptomatic in only _____% of women
Occurs during ______ age
Fibrocystic breast changes EPC:
Symptomatic in only 10% of women
Occurs during reproductive age
How does a breast with fibrocystic change present?
Surgeon: Lumpy bumpy breast on palpation
Radiologist: Dense breast with cysts
Characteristic microscopic findings:
1) Fibrosis
2) Cysts
3) Apocrine metaplasia
4) Epithelial hyperplasia
What is the main determinant of malignancy risk for a breast with fibrocystic change?
Degree of epithelial hyperplasia
(also look at:
i) proliferative/non-proliferative
ii) atypia
iii) Carcinoma in Situ)
What are the characteristic histological findings of fibrocystic changes in the breast?
1) Fibrosis
2) Cysts
3) Apocrine metaplasia
4) Epithelial hyperplasia
What are 2 epithelial tumours of the breast?
1) Papilloma
2) Carcinoma
What an example of a myoepithelial tumours of the breast?
Adenomyoepithelioma
What is an example of a mesenchymal tumour of the breast?
Lipoma
What are 2 examples of fibroepithelial tumours of the breast?
1) Fibroadenoma
2) Phyllodes
What is an example of a tumour of the nipple?
Paget’s
What are 2 examples of tumours in the male breast?
1) Gynaecomastia
2) Carcinoma
What are 3 examples of benign epithelial tumours of the breast?
1) Intraduct papilloma
2) Fibroadenoma
3) Phyllodes tumour
4) Nipple adenoma
Fibroadenoma EPC:
- (Common/Rare) benign lesion
- Highest prevalence in (young/old) women
- Peak prevalence around ____y
Fibroadenoma EPC:
- Common benign lesion
- Highest prevalence in young women
- Peak prevalence around 25y
What are the gross features of a breast fibroadenoma?
1) Firm, well-defined mobile lump
2) 1-6cm
3) May be multiple or bilateral
4) Can recur or regress spontaneously
What is the histological feature of a breast fibroadenoma?
Proliferation of glandular and stromal elements
What are 3 differences between a fibroadenoma and a phyllodes tumour?
1) Phyllodes have frond/leaf like architecture
2) Phyllodes can be malignant; fibroadenoma only benign
3) Phyllodes usually bigger and stromal proliferation is more common
What is the most common non-skin malignancy in women?
Breast carcinoma
What are 5 risk factors for developing breast cancer?
1) Caucasian/Jew/Parsi race
2) Perimenopausal age
3) High SES
4) Obesity
5) Previous breast disease
6) Family Hx
7) Early menarche/late menopause
What are 4 clinical/EPC characteristics of familial breast cancer?
1) Usually have several affected family members
2) Early onset
3) Bilateral breast cancers
4) Both breast and ovarian cancers
5) Germline mutations (eg. BRCA1/2, p53, PTEN)
How do breast cancers present on physical exam?
1) Palpable mass
2) Nipple discharge
3) Mammographic density
4) Mammographic calcification
What are 2 examples of non-invasive/in-situ carcinomas of the breast?
1) Ductal carcinoma in-situ
2) Lobular carcinoma in-situ
What are 3 examples of invasive carcinomas of the breast?
1) NST (no special type)
2) Special type (eg. mucinous, tubular, medullary, micropapillary, metaplastic, etc.)
3) Lobular carcinoma
What are 5 examples of malignant epithelial tumours of the breast?
Non-invasive:
1) Ductal carcinoma in-situ
2) Lobular carcinoma in-situ
Invasive:
3) NST (no special type)
4) Special type (eg. mucinous, tubular, medullary, micropapillary, metaplastic, etc.)
5) Lobular carcinoma
Others:
6) Paget’s
What are the common gross appearances of breast carcinoma?
Sites:
Upper outer > Subareolar > others
Growth pattern:
- comedo, circumscribes, infiltrating
Consistency:
- scirrhous, encephaloid, mucinous
Paget’s (nipple)
How are ductal and lobular carcinoma in-situ differentiated?
1) Location:
D: ducts
L: lobules
2) Cell size
D: M to L
L: S
3) Pattern
D: comedo, cribiform, micropapillary, papillary, solid
L: solid
4) Calcifications
D: present/absent
L: usually absent
5) Risk of subsequent invasive cancer
D: higher
L: lower
6) Location of metastasis
D: Ipsilateral
L: Ipsi/Contralateral
What is the distinctive feature of lobular carcinoma?
1) Loss of cellular adhesion
2) Characteristic arranged in discohesive or single file pattern
3) E-cadherin mutation
What is Paget’s disease?
Proliferation of malignant glandular epithelial cells (in-situ carcinoma) in nipple areolar epidermis
What are 5 prognostic factors of breast cancer?
1) Staging (TNM)
2) Grading (1-3)
3) Histological type (eg. NST, Special type, lobular)
4) ER/PR
- if +ve can use:
i) Tamoxifen → block tumours use of circulating estrogen
ii) Aromatase inhibitors → ↓estrogen in body
5) CerbB2/HER2
- can use Herceptin
6) Vascular invasion
When is breast screening for breast cancer recommended?
40-49y → 1 per year
>50y → once every 2 years
What are 3 determinants of breast cancer grading?
1) Tubule formation
2) Nuclear pleomorphism
3) Mitotic count
How is the staging of breast carcinomas done?
T:
<1cm → T1
2-5cm → T2
>5cm → T3
N:
no palpable → N0
ipsilateral axillary movable → N1
ipsilateral axillary movable → N2
ipsilateral internal mammary → N3
M:
M0 or M1
What are the typical molecular subtypes of breast carcinoma?
1) ER/PR
2) HER2
3) Proliferation gene (Ki67)
What are 5 causes of gynaecomastia?
Pubertal cause:
1) Hormonal imbalance (estrogen»_space; androgen)
Other:
2) Testicular atrophy (Klinefelter)
3) Cirrhosis
4) Estrogen secreting tumours of testes/adrenal gland
5) ↑Prolactin level
6) Drugs (eg. digoxin, anabolic steroids, etc.)
Carcinoma:
7) Any type (NST, special, lobular
BPH EPC:
(M/F)
Age:______
Men >50y
What is the definition of benign prostate hyperplasia?
Nodular hyperplasia of prostatic stromal and epithelial cells
What is the pathophysiology/pathogenesis of BPH?
1) Type 2 5α-reductase in the stromal cells convert testosterone into DHT
2) DHT bind to androgen receptors in epithelial and stromal cells → induce production of growth factors
3) ↑growth factors → ↑proliferation of stromal cells + ↓death of epithelial cells
Which part of the prostate does BPH occur?
Transitional zone
Why does BPH lead to urinary obstruction?
1) Enlarged prostate gland compress on prostatic urethra
2) ↑Prostatic smooth muscle tone (mediated via α1-adrenergic receptors)
What are 2 common clinical presentations of BPH?
Lower urinary tract symptoms:
1) Filling/storage problems
- frequency, urgency, nocturia
2) Voiding/obstructive symptoms
- hesitancy, terminal dribbling, incomplete voiding, urinary retention, overflow incontinence
How does BPH present on PE?
Enlarged rectal examination
- usually symmetrical and smooth
What is the histological appearance of BPH on (i) low power (ii) high power?
Low power:
- proliferation of both glandular and stromal tissue in nodular configuration
High power:
- hyperplastic prostatic glands w intact basal cell layer
What are 4 complications of BPH?
1) Acute urinary obstruction
2) Chronic urinary obstruction
3) Recurrent UTIs
4) Urolithiasis
5) Bladder hypertrophy, diverticulum, distension
6) Hydronephrosis, hydroureter
7) CKD
What are 3 forms of treatment for BPH?
1) Non-pharmacological:
- ↓fluid intake (esp before bedtime)
- ↓alcohol and caffeine intake
2) Medical:
- 5α-reductase inhibitors
- α-blockers
3) Surgical
- transurethral resection of prostate
Prostatic cancer EPC:
Age:
Top 3 cancers in M in SG
Men >50y
True or false: More men die with prostate cancer than from it as it has a wide range of biological behaviors.
True.
- from indolent to widely metastatic, fatal tumours
What is the most common form and type of prostatic malignancy?
Adenocarcinoma
- acinar adenocarcinoma (95%)
- ductal adenocarcinoma less common
What are 5 presentations of prostatic cancer?
1) Asymptomatic
2) Urinary symptoms
3) Symptoms of metastasis (eg. back pain)
4) Constitutional symptoms
5) DRE (enlarged, hard prostate)
6) ↑PSA levels
True or false: Clinically significant high of PSA is indicative of prostate cancer.
False.
Does not correlate with presence/absence of prostatic cancer
- can be elevated in eg. prostatitis
How is prostate cancer staged and graded?
Staging
i) confined to prostate
ii) invasion beyond prostate (eg. extraprostatic extension, seminal vesicle, bladder)
Grading:
i) Based on architecture
ii) Gleason grading and scoring
What is the histological appearance of prostatic cancer?
Infiltrative/malignant glands/cells with nuclear atypia and absent basal cell layers
How is the Gleason score of prostatic cancer calculated?
Most predominant Gleason pattern + Most common Gleason pattern
What is a “grade group” of prostatic cancer?
Prognostic category based on Gleason score
What are 3 Rx for prostatic cancer?
1) Radical prostatectomy
- good for localised (low stage)
2) Radiotherapy
- good for localised or locally advanced (low stage)
3) Androgen deprivation therapy
- for advanced, metastatic disease
i) Medication (eg. synthetic analogues of LHRH, androgen receptor blockers)
ii) Surgical castration (orchidectomy)
What is condyloma acuminatum?
Sexually transmitted wart caused by HPV (commonly low risk types HPV-6, HPV-11) that occurs on external genitalia or perineal area
What is the gross appearance of condyloma acuminatum?
Pedunculated or sessile papillary tumours
- on external genitalia or perineal area
- on penis, most commonly (i) around coronal sulcus (ii) inner surface of prepuce
What is the histological appearance of condyloma acuminatum?
1) Papillary proliferation of thickened epidermis (acanthosis)
2) a/w Koilocytosis (squamous cells w enlarged irregular hyperchromatic nuclei w perinuclear haloes)
What genital pathology is caused by HPV 6 and 11?
HPV 6 and 11 → Low risk
→ Condyloma acuminatum
What genital pathology is caused by HPV 16 and 18?
Squamous cell carcinoma
What are 3 a/w of penile SCC?
1) HPV 16 or 18 infection
2) Poor genital hygiene
3) Smoking
(Circumcision in early life a/w lower risk)
Penile SCC is usually (fast/slow) growing and (locally/widely) invasive.
Slow growing, locally invasive
- so metastasis to inguinal/iliac lymph nodes → grim prognosis
Penile SCC may be preceded by a non-invasive precursor lesion known as ____________________.
Penile intraepithelial neoplasia (PeIN)
Both invasive penile SCC and PeIN can be classified into ________________ via ____________________.
HPV-associated and HPV-independent
- by p16 IHC
How does HPV act as a carcinogenic virus?
1) E6 oncogene:
- targets p53 → degradation → loss of tumour suppression
2) E7 oncogene:
- targets Rb → inactivation → uninhibited cell proliferation
What is the appearance of penile SCC?
Same as most other SCCs:
- nests of malignant squamous cells
- nuclear pleomorphisms and mitotic figures
- keratin pearls
Cryptorchidism:
Presentation:
Treatment:
Histology if untreated:
Cryptorchidism:
Presentation: empty scrotal sac
Treatment: orchidopexy (by 1y)
Histology if untreated: (i) arrest of germ cell development (ii) testicular atrophy
What are the 3 common sites of cryptorchidism?
1) High Scrotal (60%)
2) Inguinal canal (25%)
3) Abdominal (15%)
A hydrocoele is caused by the accumulation of serous fluid between the _________________ of the ___________________.
Visceral and parietal layers of tunica vaginalis
What are 3 causes of hydrocoele?
1) Primary/idiopathic
Secondary:
2) Patent processus vaginalis
3) Infections (eg. filariasis, epididymorchiditis)
4) Tumour
5) Iatrogenic (eg. disruption of lymphatics after hernia repair)
How does a hydrocoele present?
1) Painless
2) Enlarged testis/scrotum
3) Transilluminative scrotum
What are 4 complications of hydrocoele?
1) Rupture
2) Infection → pyocoele
3) Acute haemorrhage → haematocoele
4) Testicular atrophy (long-standing)
How is hydrocoele usually treated?
Most spontaneously resolve
- if need, treat underlying secondary cause
- SOME cases require surgical treatment
What is the clinical definition of testicular torsion?
Twisting of spermatic cord that cuts off venous drainage of testis
What is the typical presentation of testicular torsion?
Adolescent males presenting with sudden onset testicular pain
True or false: Testicular torsion is a medical emergency.
True.
Torsion <6 hours probably will not cause infarct
Torsion >24 hours will certainly cause an infarct
What are 4 risk factors for testicular torsion?
1) Larger testes
2) Cryptorchidism
3) Trauma/exercise
Congenital factors:
4) Bell-clapper abnormality (90%)
5) Horizontal lie of testes
6) Spermatic cord w long intrascrotal component
What is Bell-clapper abnormality?
Abnormally high insertion of the tunica vaginalis on spermatic cord
→ ↑mobility of testes
- usually bilateral and orchidopexy will be done during surgical correction to ↓risk of reccurence
What are the common causative organisms for UTIs in male children?
Gram neg rods
- a/w congenital genitourinary abnormalities
What are the common causative organisms for UTIs in male <35/sexually active young men?
STDs (eg. chlamydia, gonorrhoea)
What are the common causative organisms for UTIs in male >35?
Common UTI pathogens (eg E. coli, pseudomonas)
How does gonorrhoea usually spread to the testis?
Only in late stage
Urethra → prostate, seminal vesicles → epididymis → testes
Mumps usually affects ______________ and acute orchiditis usually follows __________________.
School-aged children
Acute orchiditis follows 1wk after onset of parotid gland swelling
Tuberculous orchiditis usually starts in the ____________ before spreading to the testes.
Epididymis
In syphilitic orchiditis, the testes are usually involved (before/after) the epididymis.
Before
- epididymis may be spared
What are 5 germ cell testicular tumours?
Seminomatous:
1) Seminoma
2) Spermatocytic seminoma
Non-seminomatous
3) Embryonal carcinoma
4) Yolk sac tumour
5) Choriocarcinoma
6) Teratoma
7) Neuroendocrine tumour
Testicular tumours are mostly ___________, less commonly _______ and least commonly _______________.
Germ cell (95%) > Sex cord stromal tumours > Lymphomas (in older px) > Epithelial tumours (very rare)
How do post-puberty testicular tumours differ from paediatric tumours?
Most post-pubertal tumours originate from germ cell neoplasia in-situ
What are 3 risk factors for testicular germ cell tumours?
1) Genetic factors (familial predisposition)
2) Cryptorchidism
3) Testicular dysgenesis
What special form of testicular tumours are almost exclusive found in older patients?
Lymphomas
Germ cell testicular tumours are usually seen in which demographic?
young men
What are 4 differences between seminomatous and non-seminomatous germ cell testicular tumours?
1) Cell type
S: resemble primordial germ cells/early gonocytes
NS: undifferentiated/other lineages
2) Progression
S: slow, good prognosis
NS: more aggressive, poor prognosis
3) Treatment
S: S to radiotherapy
NS: R to radiotherapy
4) Spread
S: lymphatic first
NS: earlier and haematogenous
What are 4 clinical features of testicular germ cell tumours?
1) Painless enlargement of testis
2) ↑LDH (seminomas/lymphomas but also any with high tumor burden)
3) ↑AFP (yolk-sac tumours)
4) ↑ß-HCG (choriocarcinoma)
What is the commonest testicular germ cell tumour?
Seminoma (~50%)
What are the serum tumour markers for seminoma?
Serum LDH
(ß-HCG mild ↑ in cases w admixed synctiotrophoblasts)
What is the most common age group for seminomas?
30-40s
What is the gross appearance of a seminoma?
Relatively homogenous, fleshly, lobulated, tan to cream-coloured tumour
What is the histological appearance of a seminoma?
Polygonal cells w clear cytoplasm (containing glycogen)
- admixed with lymphocytic infiltrates
- ± granulomas
What is the use of IHC in seminoma diagnosis/managment?
Seminoma is OCT4+
OCT4 can highlight background Germ cell neoplasia in-situ
What is the second most common testicular germ cell tumours?
Embryonal carcinoma
What is the most common age group for embryonal carcinomas?
15-34y, peak at 30
True or false. Embryonal carcinoma is most commonly a/w ↑serum AFP.
False. Not usually a/w elevated tumour markers.
- ↑serum AFP seen in yolk sac tumours
What is the histological appearance of embryonal carcinoma?
1) Solid glandular and papillary growth pattern
2) Pleomorphic polygonal tumour cells w high grade nuclear features
What is the most common testicular tumour in infants?
Yolk sac tumour
What is the characteristic tumour marker for yolk-sac tumours?
Serum AFP
True or false. Though rare, yolk sac tumours usually occur solitarily in adults.
False.
usually occurs as part of a mixed germ cell tumour
True or false. Elevated serum AFP in neonates as young as 4mths of age is indicative of a yolk sac tumour.
False.
Neonates have physiologically elevated AFP up to 6mths of age
What is the histological appearance of yolk sac tumour?
Remarkably heterogenous: reticular, microcystic, myxomatous, spindle cells, solid, granular, endodermal sinus, hepatoid, etc.
- ± Schiller-Duval bodies (central vessel surrounded by cuboidal to columnar tumour cells)
Where do choriocarcinomas arise from?
Trophoblastic tissue
What is the characteristic tumour marker for choriocarcinomas?
Serum ß-HCG
What is the gross appearance of choriocarcinoma?
Necrotic and haemorrhagic (early haematogenous metastasis)
What is the histological appearance of choriocarcinoma?
1) Nests and sheets of (i) multinucleated syncytiotrophoblasts and (ii) mononucleated trophoblasts
2) a/w haemorrhage and necrosis
3) Lymphovascular invasion
What are the components of a teratoma?
Variety of mature/immature tissue types, most often from >1 germ layer
- may exist in combination w other germ cell tumours as mixed GCT
How do pre and postpubertal type teratomas differ?
Prepubertal:
- benign, not a/w GCNIS
Postpubertal:
- malignant, derived from GCNIS
What are 3 Rx for testicular germ cell tumours?
1) Surgical (radical orchidectomy)
- initial treatment
2) Adjuvant radiotherapy for some seminomas (depends on stage and other factors)
3) Chemotherapy
- standard for non-seminomatous and metastatic disease
What are 2 sex-cord stromal tumours?
1) Leydig cell tumours
2) Sertoli cell tumours
How do leydig and sertoli cell tumours differ?
Leydig:
1) Secrete androgens, estrogens and even corticosteroids
2) Hormonal effects → clinical presentation
Sertoli:
1) Most benign, 10% malignant
2) Present as testicular mass, hormonally silent
What kind of testicular lymphomas typically present in older px?
Non-hodgkin’s B cell lymphomas
What biochemical can be raised in testicular lymphoma?
Serum LDH
What are 5 common female genital infections?
1) Herpes
2) Molluscum contagiosum
3) HPV
4) Chlamydia trachomatis
5) Neisseria gonorrhoeae
6) Candida
7) Trichomonas
What is the typical (i) source of herpes in a female genital infection and (ii) where and how does it usually manifest?
Herpes:
i) STD
ii) Vulva (herpetic ulcers)
What is the typical (i) source of Molluscum contagiosum in a female genital infection and (ii) where and how does it usually manifest?
Molluscum contagiosum:
i) STD
ii) Molluscum lesions
What is the typical (i) source of HPV in a female genital infection and (ii) where and how does it usually manifest?
HPV:
i) STD
ii) Vulva, vagina, cervix, corpus, adnexa
- genital warts, intraepithelial neoplasia, invasive carcinoma
What is the typical (i) source of Chlamydia trachomatis in a female genital infection and (ii) where and how does it usually manifest?
Chlamydia:
i) STD
ii) Vagina, cervix, corpus, adnexa
- follicular cervicitis, endometritis, invasive carcinoma
What is the typical (i) source of Neisseria gonorrhoeae in a female genital infection and (ii) where and how does it usually manifest?
Gonorrhoeae:
i) STD
ii) Vulva (skene gland adenitis)
Vagina (vaginitis in children)
Cervix (acute cervicitis)
Corpus and adnexa (acute endometritis and salpingitis)
What is the typical (i) source of Candida in a female genital infection and (ii) where and how does it usually manifest?
Candida:
i) Endogenous
ii) Vulvovaginitis
What is the typical (i) source of Trichomonas vaginalis in a female genital infection and (ii) where and how does it usually manifest?
Trichomonas:
i) STD
ii) Vagina
- cervicovaginitis
What are 3 typical presentations of female pelvic inflammatory disease?
1) Pelvic pain
2) Adnexal tenderness
3) Fever and vaginal discharge
What are 5 complications of female pelvic inflammatory disease?
1) Peritonitis
2) Adhesions
3) Bacteremia
4) Tubal pregnancy
5) Infertility
What is the typical appearance of discharge in a female bacterial genital infection?
Yellow and purulent
- histo: bacteria and acute inflammatory cells
What is the typical appearance of discharge in a female protozoal genital infection?
Bubbly, frothy discharge
What is the typical appearance of discharge in a female fungal genital infection?
White discharge
What would vesicles aroudn the male penis or female vulva that shows “Ground glass” appearance on histology be indicative of?
Herpetic ulcers
What are 2 forms of acquiring pelvic inflammatory diseases?
1) Primary infection
a) Postpartum endometritis
b) Intrauterine device
c) Curettage/Abortion
2) Spread through intercourse
a) Gonococcus
b) Strep
c) Staph
d) Actinomyces
e) Mycoplasma
f) Chlamydia
What is the cellular origin of Vulva-Paget’s disease?
Primitive epithelial progenitor cells
What are 2 non-neoplastic epithelial disorders of the vulva?
1) Lichen sclerosus
- autoimmune
- whitish plaques along labia
- atrophic skin
- thinned epithelium w chronic inflammation and fibrosis in stroma
2) Lichen simplex chronicus
- secondary to pruritis
- thickening of squamous epithelium
What are 2 benign neoplasm of the vulva
1) Hidradenoma
2) Condyloma
What are 3 malignant neoplasms of the vulva?
1) VIN
2) VAIN
3) CIN
How are glandular neoplastic cells differentiated from normal epithelial cells in Vulva-Paget’s disease?
IHC w CK7
True or false. The most common malignant neoplasm of the vulva is SCC due to high risk (16, 18) HPV infections.
False.
SCC is most common but most arise from lichen sclerosus or VIN
What is the histological appearance of clear cell adenocarcinoma of the vagina?
Vacuolated tumour cells in clusters and gland-like structures
Vaginal clear cell adenocarcinoma EPC:
Age: ________
Most common in those whose mothers had ________________.
Vaginal clear cell adenocarcinoma EPC:
Age: 15-20y
Most common in those whose mothers had been treated with DES during pregnancy
What is the probable precursor of Clear Cell Adenocarcinoma of the vagina?
Vaginal adenosis
- metaplasia of squamous epithelium → glandular adenocarcinoma
What is Sarcoma Botryoides?
Embryonal Rhabdomyosarcoma
How does Sarcoma Botryoides usually present?
Grape-like clusters in vagina of infants and children
How is Sarcoma Botryoides usually treated?
Surgery (vaginectomy) + Chemotherapy
What are 5 risk factors for cervical neoplasia?
1) Early age at first intercourse
2) Multiple sex partners
3) Increased parity
4) Male partner w multiple previous sexual partners
5) Presence of cancer-associated HPV
6) Certain HLA and viral subtypes
7) Oral contraceptives and nicotine
8) Genital infections (Chlamydia)
True or false. The risk of developing cervical neoplasia can be reduced via inoculation with a HPV vaccine in Singapore.
True
What is Cervical Screen Singapore (CSS)?
National cervical cancer screening programme
- 25-69y F who ever had sex
- 25-29y → Pap test every 3 years
- >30 → HPV test every 5 years
What are the histological features of HPV?
1) Multinucleation
2) Perinuclear haloes
3) Crinkled nuclei
4) HPV IHC
5) Koilocytosis-CIN I
What are 2 screening tests for cervical cancer?
1) PAP
2) HPV test
What is the pathogenesis of HPV-induced cervical neoplasia?
10-15 years:
HPV infection → CIN → Cancer
Why is cervical cancer screening so important?
Early detection of HPV-infected cervix and treatment can prevent progression to CIN and thus full blown carcinoma
What is the gross appearance of cervical carcinoma?
Fungating, ulcerating or infiltrative
What are the typical presentations of cervical carcinoma?
1) Intermenstrual bleed
2) post-coital bleed
3) Postmenopausal bleed
4) Dyspareunia
What are 6 histological subtypes of cervical carcinoma?
SCC: (75-90%)
1) Large cell non-keratinising
2) Large cell keratinising
3) Small cell (<5%)
Others:
4) Adenocarcinoma
5) Adenosquamous
6) Undifferentiated
How are cervical carcinomas staged?
Stage I: Cervix only
- 90% 5yS
Stage II: Upper vagina or parametrium
- 75% 5yS
Stage III: Pelvic wall or lower vagina
- 30% 5yS
Stage IV: Rectum/Bladder, extrapelvic
- 10% 5yS
What are the modes of spread in cervical carcinoma?
1) Direct local invasion
- uterus, vagina
- bladder, rectum (fistula)
2) Lymphatics
3) Hematogenous
What is the clinical definition of endometrial hyperplasia?
Increase in the number of glands relative to stroma, often w abnormal shapes
- #1 caused by unopposed estrogen stimulation
- impt cause of abnormal vaginal bleeding
What are the 2 types of endometrial hyperplasia and how do they differ?
1) Non-atypical/Simple
- Cystic hyperplasia
- irregularly dilated glands
- uncommonly progresses to adenocarcinomas
2) Complex
- Glandular crowding and irregular shape
- epithelial stratification
- loss PTEN
- high risk of cancer
In which demographic is endometrial carcinoma most commonly seen?
Postmenopausal women
What are the 2 subtypes of endometrial carcinoma and how do they differ?
1) Type 1
- Prolonged estrogen stimulation
- endometrial hyperplasia
- ovarian estrogen secreting tumours
- estrogen replacement
2) Type 2
- No a/w estrogen
- no pre-existing hyperplasia
- p53 mutation
- poorly differentiated serous type
- poor prognosis
What are the differences in the stepwise development of type 1 vs 2 endometrial carcinoma?
Type 1:
Proliferative endometrium
→ PTEN loss → Non-atypical hyperplasia
→ KRAS mutation + Microsatellite instability → Atypical hyperplasia
→ Further mutations → Carcinoma
Type 2:
Atrophic endometrium
→ p53 mutations → Serous endometrial intraepithelial carcinoma
→ further mutation → Serous carcinoma
How are cervical carcinomas graded?
Degree of architectural differentiation via solid or not:
Grade 1: <5% non-squamous/morular solid growth pattern
Grade 2: 6-50%
Grade 3: >50%
How are cervical carcinomas graded?
Stage 1: Corpus only
Stage 2: Corpus + Cervix
Stage 3: Invasion into pelvis
Stage 4: Outside pelvis
What is the most common uterine neoplasm?
Leiomyoma
Leiomyoma are _____ dependent and thus increase in size with nuclear ________ receptor and regress after menopause, with __________ and ____________ causing rapid increase in size and haemorrhagic degeneration.
Oestrogen-dependent
- ↑size w nuclear receptor
- progestins and pregnancy may cause rapid ↑size
What are 4 possible locations of leiomyoma formation in the uterus?
1) Within uterine cavity (pedunculated)
2) Submucosal
3) Intramural
4) Subserosal
5) Cervix
What are 4 symptoms and complications of leiomyoma?
1) Abnormal bleeding
2) Bladder compression
3) Sudden pain
4) Infertility
5) Spontaneous abortion
What is “red degeneration” in leiomyomas?
Beefy red appearance due to rapid growth and infarction with subsequent haemorrhagic degeneration
What are the histological characteristics of leiomyosarcoma?
1) Increased mitosis
2) Necrosis
3) Atypia
Where does leiomyosarcoma commonly metastasise to?
Lung and Brain
What gross feature of leiomyosarcoma hints at its differentiation from leiomyoma?
Haemorrhage
What is endometriosis?
Presence of endometrial glands and stroma in abnormal locations outside the uterus
What are the common presentations of endometriosis?
1) Dysmenorrhea
2) Pelvic pain
3) Infertility
True or false. Endometriosis can lead to carcinoma.
True.
Endometrioid and cell clear carcinoma
What is adenomyosis?
Ectopic endometrial deposits in myometrium with overgrowth of muscle and connective tissue.
What are the 2 forms of adenomyosis?
1) Diffuse
- deposits confined to inner part of myometrium
- more common
2) Localised
- Resemble fibroids
- rarer
Name 1 possible cause(s) of abnormal per-vaginal bleeding in a prepubescent girl.
Precocious puberty
(hypothalamic, pituitary, ovarian origin)
Name 2 possible cause(s) of abnormal per-vaginal bleeding in an adolescent girl.
1) Anovulation
2) Coagulation disorders
Name 3 possible cause(s) of abnormal per-vaginal bleeding in a woman of reproductive age?
1) Pregnancy complication (eg. abortion, ectopic pregnancy)
2) Anatomic lesion (eg. leiomyoma, polyps)
3) Dysfunctional uterine bleeding (eg. anovulatory cycle, ovulatory dysfunctional bleeding)
Name 2 possible cause(s) of abnormal per-vaginal bleeding in a perimenopausal woman.
1) Dysfunctional uterine bleeding (eg. anovulatory cycle)
2) Anatomic lesions (eg. carcinoma, hyperplasia, polyps)
Name 2 possible cause(s) of abnormal per-vaginal bleeding in a postmenopausal woman?
1) Endometrial atrophy
2) Anatomic lesions (eg. carcinoma, hyperplasia, polyps)
What are 6 differentials for dysfunctional uterine bleeding/abnormally heavy uterine bleeding with no underlying anatomical cause?
1) Uterine lesions (eg. fibroids, polyps, cancer)
2) Pelvic inflammatory disease
3) Adenomyosis
4) Ectopic pregnancy
5) Hydatid mole
6) Uterine leiomyoma
7) Endometritis
8) Trauma and sexual abuse
9) Medication
10) Foreign bodies (eg. tampons, condom)
What is a paratubal cyst (hydatids of Morgagni)?
Benign, pedunculated cystic structures arising from the fimbrial end of the fallopian tubes
- Mullerian duct remnants
What is hydrosalpinx?
Blocked fallopian tube filled with fluid
What are 2 causes of hydrosalpinx?
1) Previous pelvic infection (eg. pelvic inflammatory disease)
2) Endometriosis
What are 4 causative organisms of pyosalpinx?
1) Chlamydia
2) Neisseria gonorrhoeae
3) Escherichia coli
4) Staphylococci
5) Streptococci
How does pyosalpinx present?
Pelvic pain and fever
How is pyosalpinx treated?
Antibiotics/surgery
What is the main complication of pyosalpinx?
Infertility
What are 5 sequelae of salpingitis?
1) Resolution
2) Spread → Tubo-ovarian abscess
3) Healing w fibrosis → Tubo-ovarian mass
4) Blocked fimbria → pyosalpinx → mass/hydrosalpinx (abs of pus)/hydrosalpinx follicularis (distension)
What is the histological appearance of actinomycotic salpingitis?
1) Eosinophilic structures with peripheral radiation
2) Filamentous branched clubbed organism
- Gram positive
- non-acid fast
What form of salpingitis have in increased incidence in IUCD px?
Actinomycotic salpingitis
What is the most common benign tumour of the fallopian tube?
Adenomatoid tumour
What is the histological appearance of an adenomatoid tumour?
1) Invagination of visceral mesothelium
2) Tubular spaces of varying sizes composed of flattened cells
True or false. An adenomatoid tumour usually has a good prognosis as px present very early with complaints of acute pelvic and abdominal pain.
False.
Usually asymptomatic
What is salpingitis isthmica nodosa?
Diverticulae that communicate with oviduct lumen to cause swellings
- usually bilateral w nodular swellings
What are 4 forms of non-neoplastic ovarian cysts?
1) Follicular cysts
2) Multiple follicular cysts (polycystic ovary syndrome)
3) Corpus luteal cysts
4) Endometriotic cysts
What is a follicular cyst?
Arise from unruptured follicles/follicles that ruptured and sealed immediately
- filled w serous fluid
- mostly physiologic
Corpus luteal cyst:
Gross appearance:
a/w:
Corpus luteal cyst:
Gross appearance: yellowish thick cyst lining
a/w: menstrual irregularities
How does polycystic ovary syndrome/Stein-Leventhal syndrome usually present?
1) Amenorrhoea
2) Multiple cysts and stromal hyperplasia
3) Persistent anovulatory state
4) >estrogen and androgen
- usually in obese, hirsute, acne
What are 5 ovarian germ cell tumours?
1) Seminoma
2) Dysgeminoma
Embryonal carcinomas (totipotent cells):
3) Yolk sac tumour
4) Choriocarcinoma
5) Teratoma
What is the gross appearance of dysgerminoma?
Large, firm, bosselated external surface
- soft & fleshy
What is the histological appearance of dysgerminoma?
1) Nests of monotonous tumour cells with clear glycogen-filled cytoplasm
2) Fibrous septa with lymphocytes
True or false: Dysgerminomas are mainly treatable by radiotherapy.
True.
- dysgerminomas are highly radiosensitive
What is the main difference between a mature and immature teratoma?
Mature:
- can be both benign (cystic teratoma, struma ovarii) and malignant (SCC, thyroid)
Immature:
- all malignant
How are immature/malignant teratomas graded?
Grade 1: rare foci of immature neuroepithelial tissue occupying <1/LPF (40x) in any slide
Grade 2: 1-3 LPF/slide
Grade 3: Large amounts
Female germ cell tumours EPC:
- Germ cell tumours constitute _____% of ovarian tumours
- majority type: ________________ in women _________y
- minority type: ______________ in women _____________y
Female germ cell tumours EPC:
- Germ cell tumours constitute 15-20% of ovarian tumours
- majority type: mature cystic teratomas in women of reproductive age
- minority type: malignant/immature teratoma in young women and children
How are immature teratomas distunguished from mature teratomas?
Prescence of immature elements (eg. primitive neuroepithelium)
What form of cell differentiation do mucinous tumours exhibit?
Endocervical
What form of cell differentiation do serous tumours exhibit?
Tubal
What form of cell differentiation do endometrioid tumours exhibit?
Endometrial
What form of cell differentiation do cell cell type tumours exhibit?
Endometrial
What form of cell differentiation do Brenner tumours exhibit?
Transitional/urothelial
How do the pathogenesis of type 1 ovarian epithelial tumours (eg. low grade serous, endometrioid, mucinous) differ from that of type 2 (eg. high grade serous)?
Type 1:
- progress from benign → borderline → low-grade carcinoma
Type 2:
- from inclusion cysts/fallopian tube epithelium that show high grade features (serous)
What are the 4 histological criteria for borderline ovarian neoplasms?
1) Epithelial hyperplasia
- stratification, tufts
2) Atypia
- mild to moderate
3) Minimal mitotic activity
4) Absence of destructive stromal invasion
Endometrioid ovarian tumours EPC:
- ____% of all ovarian cancers
- most are (benign/malignant)
- 15% coexist with __________
- (better/worse) prognosis than serous carcinoma
Endometrioid ovarian tumours EPC:
- 20% of all ovarian cancers
- most are malignant
- 15% coexist with endometriosis
- better prognosis than serous carcinoma
What is the key histological feature of endometrioid ovarian tumours?
Tubular glands resembling endometrium
What is the gross and histological appearance of clear cell ovarian adenocarcinoma?
Grossly solid/cystic
Histo: large sheets of epithelial cells with clear cytoplasm and tubules with hobnail nuclei
What is the histological appearance of Brenner tumours?
1) Nests of urothelial-like cells in a dense fibrous stroma
2) Coffee bean nuclei
What are the categories of the 3 major histological types (serous, mucinous, and endometriod)?
1) Benign
2) Borderline
3) Malignant
What is the histological appearance of female fibroma/thecomas?
Stromal tumours with fibroblasts (fibroma) or plump spindle cells with lipid droplets (thecoma)
What is Meig’s syndrome?
Triad for ovarian fibroma-thecomas
1) Fibromas
2) Ascites
3) Pleural effusion
What is the histological appearance of granulosa cell tumours?
1) Large, focally cystic to solid
2) Yellow areas of lipid-laden luteinized cells
3) Follicular pattern (Call-Exner bodies)
4) Cleaved, elongated nuclei (coffee bean)
5) Strong positivity for inhibin
Why do granulosa cell tumours commonly lead to/present with endometrial hyperplasia and carcinoma?
75% are estrogen secreting
What is a Arrhenoblastoma?
Sertoli-Leydig cell tumours
- rare mesenchymal tumour of low-grade malignant potential
- resemble embryonic testis
- androgen secretion
- common in young women
Why do px with arrhenoblastomas present with maculinisation?
Secrete androgen
What is the most common malignant sex-cord stromal tumours in females?
Granulosa cell tumours
What are 4 methods of spread of malignant ovarian neoplasms?
1) Local infiltration into broad ligament
- urethral obstruction, bladder involvement
2) Peritoneal spread
- ascites with malignant cells in fluid, peritoneal nodules
3) Lymphatic spread
4) Hematogenous spread
- lung nodules
What is a Krukenberg tumour?
2° tumour from primary site
- bilateral
- friable and necrotic with vascular invasion
- ovarian surface involvement
- 2 types:
i) Mullerian (uterus, FT, peritoneum)
ii) Extramullerian (breast, GIT)
