repro pathology Flashcards
what is the triple test for breast cancer diagnosis?
- clinical examination
- radiology/imaging: ultrasound, mammogram
- pathology: fine needle aspiration, core biopsy, excision biopsy
acute mastitis pathogenesis and presentation
pathogenesis: cracked or inflamed nipple permits entry of microbe (s. aureus or other staphylococci) during nursing –> microbe proliferates in stagnant milk –> acute inflammation results in abscess formation
presentation: acute inflammation of the breast, erythematous red breast with concurrent fever
idiopathic granulomatous mastitis pathogenesis and presentation
pathogenesis: autoimmune disease targets secretory products of the breast - best controlled by steroids and immunosuppressants
presentation: lobulocentric granulomatous inflammation, ddx is TB
paraffinoma pathogenesis and presentation
pathogenesis: fibrosis around paraffin breast implant with foreign body-type inflammation
presentation: radiodense empty spaces surrounded by multinucleate giant cells and histiocytes
classical presentation of fibrocystic changes of the breast
• in women during reproduction decades (esp premenopausal decade)
• due to normal cyclic breast changes
• bilateral, multifocal soft lump
prognosis of fibrocystic changes of the breast
depends on the level of epithelial hyperplasia!
low: fibrosis, cystic changes, apocrine metaplasia
moderate: moderate hyperplasia, sclerosing adenosis (scar-like fibrous tissue in breast lobules)
high: atypical hyperplasia
changes involved in fibrocystic changes of the breast
non-proliferative:
cysts and apocrine metaplasia (cells have eosinophilic cytoplasm and round nuclei)
proliferative:
epithelial hyperplasia, fibrosis, (sclerosing) adenosis –> hard rubbery lump may be mistaken for breast cancer
fibroadenoma pathogenesis and presentation
pathogenesis: pleomorphic lesion of fibrous and glandular tissue
presentation:
- young women (25yo)
- MOUSE IN THE BREAST!!! firm well-defined slow-growing mobile tumour (1-6cm)
- tan white colour with yellowish specks
- glandular and stromal elements
- circumscribed and uniform
phyllodes tumour pathogenesis and presentation
pathogenesis: fibroepithelial tumour from intralobular stroma
presentation:
- presents in young women (25yo)
- risk of malignancy due to proliferating stromal elements (EXCISE A LARGE MARGIN)
- leaf like pattern = benign, stromal proliferation = malignant
- haematogenous metastasis to the lungs
- possible necrosis and/or haemorrhage
papilloma pathogenesis and presentation
pathogenesis: benign neoplastic papillary growth
presentation:
- premenopausal women
- commonly causes bloody nipple discharge
- solitary lesions/lumps but too small to see on mammogram
- necrosis of tips of papillae may cause haemorrhage, bloody nipple discharge, nipple retraction
risk factors for breast carcinoma
rich, obese, premenopausal woman who is Caucasian, Jew or Parsi with previous breast disease, who has never had children and doesn’t breastfeed, takes hormones, loves radioactive material, has positive family history (BRCA1, BRCA2, p53, PTEN genes) who had early menarche and will have late menopause
presentation of breast carcinoma
- palpable mass that is scirrhous, encephaloid or mucinous
- most commonly in upper outer quadrant > subareolar > others
- nipple discharge and retraction or Paget’s disease (erosion and redness)
- mammographic density and calcifications
- peau d’ orange appearance (tethered skin due to Cooper ligaments)
- lymph node metastases (esp palpable axillary nodes)
ductal carcinoma in situ presentation
- mammographic density, nipple discharge, Paget’s disease, palpable mass
- found in ducts (duh)
- medium or large sized cells with varied histological types (comedo, cribriform, solid, papillary, micropapillary)
- higher chance of malignant change and E-cadherin expression
- possible necrosis
lobular carcinoma in situ presentation
- incidental finding, not really any symptoms
- found in lobules (duh)
- small cells with solid histology
- low chance of malignant change
- may express ER, PR or HER2 receptors
Paget’s disease pathogenesis and presentation
pathogenesis: extension of DCIS along ducts in the epithelial layer to the nipple skin
presentation: eczematous scaly crusting/erosion/redness on the nipple unilaterally, causing ulceration of the nipple also
invasive ductal carcinoma presentation
desmoplastic change replacing normal breast fat and forming a firm palpable mass with an irregular border
invasive lobular carcinoma presentation
tumour cells invade stroma in a linear pattern forming strands (single file) with a loss of cellular adhesion, cells are E-cadherin negative
mucinous carcinoma presentation
rubbery soft tumour on a mucinous background, low grade and good prognosis tumour
medullary carcinoma presentation
high grade, poorly differentiated and well circumscribed tumour that initiates extensive lymphoplasmacytic/immune response and responds well to chemotherapy
no special type carcinoma presentation
indistinct tumour morphology but the most common type of breast carcinoma, basically for any tumour that doesn’t fit the others
causes of gynaecomastia
drug-induced, testicular atrophy, liver cirrhosis, estrogen-secreting tumours (testis, adrenal gland etc), hyperprolactinemia, hormonal imbalances from puberty
TNM staging of breast cancer
T: primary tumour (1-4)
N: lymphatic spread (0-3)
M: distant metastases (x, 0-1)
grading factors of breast cancer
histological grades (1-3) based on:
1. tubule formation
2. nuclear pleomorphism
3. mitotic count
benign prostatic hyperplasia pathogenesis
testosterone is converted into DHT by 5α-reductase and binds to androgen receptors on prostatic cells to produce growth factors (growth rate>death rate), leading to progressive hyperplasia of stromal and epithelial prostate cells especially in transitional zone
diagnosis of benign prostatic hyperplasia
- digital rectal examination for enlarged prostate
- ultrasound of testicles, prostate, kidney, bladder for associated pathologies
- prostate-specific antigen amt elevation
presentation of benign prostatic hyperplasia
- storage: increased frequency and urgency of urination, nocturia
- voiding: hesitancy or intermittent interruption of urine stream
- urinary tract obstruction: bladder distention and hypertrophy, hydronephrosis, urinary tract infections –> pyelonephritis
- urolithiasis and CKD
treatment for benign prostatic hyperplasia
- transurethral resection of the prostate
- α-blockers (Prazosin, Tamulosin) to relax the smooth muscle in the prostate and bladder neck
- lower fluid, alcohol and caffeine intake
prostatic cancer presentation
- asymptomatic
- urinary symptoms, similar to BPH
- back pain and other symptoms of metastases
- constitutional symptoms
- enlarged, hard, bumpy prostate gland on DRE
- elevated serum prostate specific antigen levels
pathogenesis of prostatic carcinoma
- usually found in acinar cells (95%) but may also be found in ductal cells
- in the peripheral zone of the prostate
- infiltrative malignant glands with nuclear atypia and absent basal cell layers
what is the Gleason grading?
grading for prostate cancer based on architecture of the two most undifferentiated/malignant looking parts of the prostate, can go up to 12
treatment for prostatic carcinoma
- radical prostatectomy for localised disease
- radiotherapy for localised/locally advanced disease
- androgen deprivation therapy for advanced/metastatic disease
condyloma acuminatum pathology and presentation
pathology: sexually transmitted via HPV 6/8
presentation: benign tumour on the inner surface of the prepuce, can be sessile/pedunculated
histologically: branching papillary stroma, covered by epithelium with superficial hyperkeratosis and acanthosis, enlarged and irregular hyperchromatic nuclei with perinuclear haloes
squamous cell carcinoma of the penis risk factors
uncircumcised, HPV 16 and 18, poor genital hygiene, smoking
features of squamous cell carcinoma of the penis
- slow growing locally invasive tumour, only painful after secondary ulceration and infection
- metastases to inguinal and iliac lymph nodes
- may be preceded by penile intraepithelial neoplasia (PeIN)
presentation of squamous cell carcinoma of the penis
- lesion on the glans of the inner surface of the prepuce near the coronal sulcus
- either papillary (like condyloma acuminatum) or flat (epithelial thickening with graying, fissuring mucosal surface)
pathogenesis of squamous cell carcinoma of the penis
- HPV genome E6 and E7 regions code for multiplication of viral genome and target tumour suppressor genes
- E6 –> p53, E7 –> Rb protein
- leads to nests of malignant squamous cells with nuclear pleomorphism and mitotic figures
infections that typically cause orchitis and epididymitis
tuberculosis, mumps, gonorrhea, syphilis
pathogenesis and presentation of cryptorchidism
pathogenesis: failure of intra-abdominal testis to descend into scrotal sac, usually found in high scrotum but may also be found in abdomen or inguinal canal
presentation: empty scrotal sac, possibly testicular dysfunction/decreased fertility/ testicular cancer
hydrocele pathogenesis and presentation
pathogenesis: accumulation of serous fluid between the visceral and parietal layers of tunica vaginalis, due to excessive production/impaired absorption of serous fluid + obstruction of lymphatic drainage
presentation: enlarged, painless testicle illuminated by the transillumination test
testicular torsion pathogenesis and presentation
pathogenesis: twisting of spermatic cord cutting off venous drainage to testis
presentation: sudden onset testicular pain –> testicular infarction and eventual infertility
testicular torsion risk factors
- congenital: bell clapper abnormality, horizontal testis, spermatic cord with long intrascrotal component
- larger testis
- cryptorchidism
- trauma or exercise
types of male sex-cord stromal tumours
- Leydig cell tumours: may secrete androgens causing hormonal effects as clinical presentation
- Sertoli cell tumours: presents as usually (90%) benign testicular mass that is hormonally silent
lymphoma presentation in the male reproductive system
- in older patients
- non-Hodgkin B cell lymphomas
- in genitourinary tract as secondary involvement, or primary lymphoma of the urinary tract
- elevated serum LDH
testicular neoplasm risk factors
- youth (95% are germ cell tumours which are seen in young men)
- cryptorchidism
- genetic factors
- testicular dysgenesis syndrome
presentation of testicular neoplasms
- painless testis enlargement
- elevated markers: LDH, AFP (yolk sac tumours), β-HCG (choriocarcinoma)
presentation and types of seminomatous germ cell tumours
- localised for a long time (slow growing with good prognosis)
- very radiosensitive
- spread by lymphatics to para-aortic nodes
- usually seminoma (elevated serum LDH and β-HCG, sometimes OCT4 positive) or mixed tumour
–> histologically: polygonal tumour cells with clear cytoplasm and lymphocytic infiltrates, homogenous fleshy lobulated and tan-coloured tumour
presentation and types of non-seminomatous germ cell tumours (NSGCT)
- metastasize relatively earlier (more aggressive with poorer prognosis)
- radioresistant
- spreads via haematogenous route
- can be yolk sac tumour (common in infants, Schiller-Duval bodies on histology), choriocarcinoma (from trophoblastic tissue - nests of multinucleated syncytiotrophoblasts and mononucleated trophoblasts with early mets), teratoma (tissue from multiple cell layers), embryonic carcinoma (15-34yo)
developmental pathologies of the uterus
didelphys, arcuate, unicornate, bicornate, septate uteri
common gynaecological pathogens
Herpes virus, Molluscum contagiosum, Human Papilloma virus, Chlamydia trachomatis, Neisseria gonorrhoeae, Candida, Trichomonas
presentation of pathogen-infected uterus
bacterial vaginosis (thick, purulent exudate), protozoa (thin, greenish-yellow, bubbly discharge), fungus (patchy white adherent exudate)
pathogenesis and presentation of pelvic inflammatory disease
pathogenesis: an infection of the female reproductive organs when STD spreads from vagina to uterus/fallopian tube/ovaries
presentation: pelvic pain, adnexal tenderness, fever and vaginal discharge and COMPLICATIONS (peritonitis, adhesions, bacteremia, tubal pregnancy and infertility)
non-neoplastic vulval pathologies (3)
Bartholin cyst, Lichen sclerosus (thin, whitened epidermis), Lichen simplex chronicus (hyperkeratosis secondary to pruritis)
Paget’s disease of the vulva presentation
reddish “weeping” lesions visible on CK7 dye, neoplasm formed from squamous stratified epithelium
vulvar malignancy pathology
usually secondary to HPV, starts as vulva intraepithelial neoplasia and can become invasive –> squamous cell carcinoma (keratinisation and cell junctions)
clear cell adenocarcinoma of the vagina pathogenesis and presentation
pathogenesis: usually in-utero exposure of young women to diethylstilbestrol (DES) leading to vaginal adenosis
presentation: vacuolated tumour cells in clusters and gland-like structures
sarcoma botryoides (embryonal rhabdomyosarcoma) presentation
grapelike tumour clusters, normal stratified squamous epithelium with undifferentiated sarcoma underneath
histological changes in cervical intraepithelial neoplasia
higher N:C ratio, increased mitosis, nuclear irregularity (multinucleation, perinuclear haloes, crinkled nuclei) –> ranked mild/moderate/severe dysplasia as CIN1/2/3
risk factors for cervical intraepithelial neoplasia
- HPV: HPV16 (assoc with amplification of 3q) and 18 especially
- early age intercourse
- multiple sexual partners
- increased parity
- exposure to oral contraceptives and nicotine
- genital infections
3 steps to cervical cancer development
- HPV infection
- progression to cervical intraepithelial neoplasia
- invasion and mets (locally: uterus, vagina, bladder, rectum, lymphatic, haematogenously: lung, liver, bone, brain)
gross presentation of cervical carcinoma
intermenstrual bleed, post coital bleed, post menopausal bleed, dyspareunia, fungating/ulcerative/infiltrative tumour
histological presentation of cervical carcinoma
75-90%: squamous cell carcinoma aka keratin pearls, intercellular bridges, eosinophilic cells with intracellular keratin, polygonal cells
rest: adenocarcinoma (gland formation invading underlying stroma), adenosquamous, undifferentiated
endometrial hyperplasia pathogenesis and presentation
pathogenesis: increase in the number of glands relative to the stroma, due to unopposed estrogen secretion
presentation: abnormal vaginal bleeding, may progress from simple hyperplasia to complex hyperplasia (loss of PTEN, glandular overcrowding, irregular shape)
endometrial carcinoma types
1: caused by prolonged estrogen stimulation –> endometrial hyperplasia, ovarian estrogen-secreting tumours, estrogen replacement therapy
2: p53 mutation with no preexisting hyperplasia, poorly differentiated serous type, poor prognosis
endometriosis pathogenesis and presentation
pathogenesis: endometrial glands and stroma found outside of the uterus (usually abdominal cavity)
presentation: dysmenorrhea, pelvic pain, infertility
leiomyoma risk factors and presentation
risk factors: VERY COMMON!! IN >30yo woman (but regresses after menopause), high amounts of estrogen and progestins / being pregnant (causes rapid size increase and haemorrhagic degeneration)
presentation: beefy red tumour located subserosal/intramural/uterine cavity/pedunculated/submucosal, histologically bundles of spindle cells with elongated blunt-ended nuclei and cigar-shaped bland appearance
adenomyosis pathogenesis and presentation
pathogenesis: ectopic endometrial deposits in the myometrium with accompanying overgrowth of muscle and connective tissue
presentation:
1. diffuse: deposits are confined to inner part of myometrium, foci of endometrium is brownish
2. localised: resembles fibroid with brownish foci
causes to exclude in dysfunctional uterine bleeding:
- uterine lesions
- pelvic inflammatory disease
- adenomyosis
- ectopic pregnancy
- hydatid mole
- uterine leiomyoma
- endometriosis
- trauma and sexual abuse
- medication
- foreign bodies
causes (by age group) of uterine bleeding
prepuberty: precocious puberty
adolescence: anovulatory cycle, coagulation disorders
reproductive age: complications of pregnancy, anatomic lesions
postmenopausal: endometrial atrophy, anatomic lesions
types of fallopian tube inflammation
- paratubal cyst (hydatids of Morgagni)
- hydrosalpinx
- pyosalpinx
- actinomycotic salpingitis: eosinophilic structures with peripheral radiation aka Hippelis syndrome
fallopian tube benign neoplasms
adenomatoid tumour: asymptomatic invagination of visceral mesothelium
salpingitis isthmica nodosa: diverticulum enters fallopian tube wall and causes swelling
types of ovarian cysts
follicular cysts (physiologic), corpus luteal cyst (formed from corpus luteum), polycystic ovary syndrome
polycystic ovary syndrome (PCOS) presentation
- obesity, hirsutism, acne due to hormonal irregularities (way too much estrogen)
- amenorrhoea
- multiple cysts and stromal hyperplasia
- persistent anovulatory state
types of germ cell neoplasms
dysgerminoma (monotonous tumour cells with clear glycogen-filled cytoplasm), teratoma (2-3 germ layers of cells), endodermal sinus tumour (forms sac-like structures/Schiller-Duval bodies and rich in α-fetoprotein)
types of ovarian surface epithelial tumours
mucinous cystadenoma/cystadenocarcinoma, serous cystadenoma, endometroid ovarian tumours (mimics endometrium), clear cell ovarian adenocarcinoma (large sheets of epithelial cells with clear cytoplasm and tubules with hobnail nuclei), Brenner tumour (nests of urothelial cells in a dense fibrous stroma with coffee bean nuclei)
types of sex cord/stromal tumours in women
- fibrothecomas: stromal tumours with fibroblasts and plump spindle cells with lipid droplets (thecomas)
- granulosa cell tumour: large, focally cystic with lipid-filled luteinised cells, coffee bean nuclei and inhibin positive
- Sertoli - Leydig cell tumour: resembles embryonic testes and secretes androgens
Krukenberg tumour presentation
- usually bilateral
- friable and necrotic with vascular invasion
- ovarian surface involvement
- due to metastasis from a different site
- signet ring cells
causes of spontaneous abortion (loss of pregnancy before 20 weeks of gestation without outside intervention)
- uterine defects (fibroids, polyps)
- endocrine factors
- hypertension, diabetes
- fetal chromosomal anomalies
- TORCH infections
predisposing factors for ectopic pregnancy
- chronic salpingitis
- peritubal adhesions
- leiomyomas
- previous surgery
- benign cysts and tube tumours
- intrauterine device (IUD)
presentation of ectopic pregnancy
- amenorrhea
- abdominal pain
- vaginal bleeding
- rupture of fallopian tube
- haemorrhage (haematosalpinx, haematoperitoneum) –> haemorrhagic shock
- spontaneous regression of pregnancy
- tubal abortion
placental abnormalities
- placenta previa: implantation of placenta over/near internal os
- abruptio placentae: premature separation of normally positioned placenta from uterine wall before delivery
- placenta accreta/increta/percreta: adhesion of normal placental villi to uterine wall (aka no decidual plate between villi and myometrium)
preeclampsia triad
- hypertension
- proteinuria
- oedema
eclampsia sequentae
decreased uteroplacental perfusion –> arterial vasoconstriction (–> systemic hypertension) + endothelial injury + activation of intravascular coagulation –> disseminated intravascular coagulation –> proteinuria in the kidneys, seizures and coma in the CNS, abnormal liver function test, ischaemia and fibrin thrombosis
risk factors for gestational trophoblastic diseases
- asian, african, latin american
- extremes of reproductive age
- previous moles (specifically for choriocarcinomas)
hydatiform mole presentation and complications
presentation: vaginal bleeding, large uterus, molar vesicles, hyperemesis, pulmonary embolization, hyperthyroidism
complications: uterine haemorrhage, coagulopathy, infection, continued trophoblastic activity leading to invasion and choriocarcinoma
complete vs partial hydatiform mole pathogenesis
complete: fertilisation of egg when the nucleus is lost/inactivated, leading to 46XX or 46XY (paternal X chromosomes) mole
partial mole: egg chromosomal content is normal but egg is fertilized by 2 sperm, leading to 69XXX or 69XXY mole
invasive mole pathogenesis and presentation
pathogenesis: hydatiform mole where hydropic villi invade the myometrium and are transported to extrauterine sites (blood vessels, distant site mets)
presentation: locally aggressive mole with low metastatic risk, highly chemosensitive but may cause death due to uterine perforation or intraperitoneal bleeding
choriocarcinoma possible pathogeneses
arise from trophoblast of any gestational event likely due to biphasic proliferation of synctio-cytotrophoblast, 50% from complete mole, 25% after abortion, 25% from normal pregnancy, 3% ectopic
presentation of choriocarcinoma (female)
haemorrhagic friable mass in uterine cavity causing haemorrhage, necrosis, anaplastic trophoblast and vascular invasion, presenting clinically with abnormal uterine bleeding, haematogenous metastasis and raised HCG levels
common investigations for infertility
- hormonal assay
- endometrial sampling
- laparoscopy
- hysteroscopy
- hysterosalpingography
- microbiologic studies
common causes of infertility
- hypothalamus-pituitary hormones
- gonadotropin deficiency, hyperprolactinemia
- pelvic inflammatory disease
- endometritis
- endometriosis
- polycystic ovarian syndrome
- anti-sperm antibodies
- chronic cervicitis
- endometrial adhesions
- premature menopause
