female pathology Flashcards
what are cervix problems?
endocervical polyp
SIL
Adenocarcinoma in situ
Cervical carcinoma
PAP smear
what are 2 types of cervix cells we have ?
Ecto cervix —> STRATIFIED SQUAMOUS EPITHELIUM —> if it would become cancer it would be squamous cell
Endocervix =Inner cervix = towards the utereus –> Mucus secreting columnar epithelium –> if it becomes cancer it would be adenocarcinoma
what is transformation zone?
aka squamocolumnar junction
the point where the 2 types of cells of the cervix meet
its very active and targeted by HPV
what is an endocervical polyp?
a polyp arising from the endocervical part of cervix
what is the clinical presentation of endocervical polyp?
40-60 years old
Abnormal vagina bleeding
what are the grossly features of endocervical polyp?
Polypoid mass with smooth surface
what are the microscopic features of polyp?
generally all polyps are projections lined by epithelium with a fibrovascular core
so here its endo so lined columnar epithelium secreting mucus –> ENDOCERVICAL GLANDS
with fibrous stroma and thick walled vessels
Note : the lining could be either squamous or columnar but the endocervical glands are present always
whats the difference between polyp and papillary?
polpy has smooth surface
papillary has projection
what is condyloma acuminatum?
Condyloma = mass
Acuminatum = pointed
its aka Genital wart
Genital cuz its in the genitalia
Wart = another name for papillae but for viral
it makes papillae
what causes Condyloma acuminatum ? genital wart
HPV TYPE 6 , 11
HPV affect human
and it attacks epithelial tissue especially sqamous and penetrate until basal cells then it lives there and lead to formation of papillae
type 6 and 11 are low risk so they have low chance of cancer cuz they dont reach DNA
SPREAD BY SKIN TO SKIN CONTANCT
what are the grossly features of condyloma acuminatum ?
Exophytic papillary lesion
what are the microscopic features of condyloma acuminatum ?
Papillary ( fingerlike ) lesion
Hyperkeratosis in case the virus affected a cell with keratin
Acanthosis –> increase epidermis thicking
Koilocytic changes :
viral effect on the cell , the nucleus shrink and hyperchromatic creating PERINUCLEAR HALOS ( chromophobe RCC )
what is squamous intraepithelial lesion? SIL?
aka Cervical intra epithelial neoplasia (CIN )
its a dysplasia = malignant transformation of cells = divide uncontrollably
notice the name squamous = affect squamous only
so it only affects the ectocervical region and not endo cuz endo is columnar and not squamous
what are 2 types of squamous intra-epithelial lesion ? or CIN?
Low grade SIL –> mild dysplasia
High grade SIL
what causes high grade SIL?
HPV = 16 and 18
6 and 11 were low risk so only polyps
here 16 and 18 are high risks = dysplasia
what are the grossly features of SIL/CIN?
normally dysplasia is something we only see under microscope but here we can see it :
using colposcopy appears as :
Discolored raised plaques
how do we confirm that the Plaques are SIL?
1st:
Apply acetic acid :
IF normal = retain pink color
IF abnormal = WHITE MOSAIC OR COBBLESTONE
2nd step :
Apply Lugol iodine :
If normal = Squamous epithelium become brown
If abnormal = Bright yellow non iodine uptake
what are the microscopic features of Low grade SIL? or CIN1?
Nuclear poleomorphism and hyperchromasia in lower 1/3 of epithelium
what are the microscopic features of HGSIL?
Nuclear pleomorphism and hyperchromasia in lower 2/3 –> CIN2
or
Nuclear pleomorphism and hyperchromasia in ENTIRE thickness = BECOMES CARCINOMA IN SITU -> CIN3
what is an important marker for High grade SIL?
P16 immunochimstery
Strong and diffuse nuclear and cytoplasmic positivity in the full thickness = forms block
ITS IMPO CUZ IT REACTES STRONGLY WITH CELLS IN CASES OF HIGH RISK HPV
if you see P16 = HIGH GRADE SIL = high risk HPV
what is the treatment of SIL/CIN?
Low grade = Most lesions regress but keep following up
High grade = Loop electrosurgical Excision procedures (LEEP ), conization , laser, cryosrugery, thermal ablation –> regardless of the way you need to remove it
what is Adenocarcinoma insitu?
Similar to SIL but this time its endocervix with the columnar gland cells ( dysplasia but in columnar gland cells )
its aka Cervical glandular intra-epithelial neoplasia
It can become invasive if not treated
what is the clinical presentation of ADC in situ?/ CGIN?
Asymptomatic
Cant even be seen grossly like SIL
what are the microscopic features of ADC in situ or CGIN?
Repalcement of endocervical epithelium on surface and glands by :
ABNORMAL ATYPICAL EPITHELIUM
what are the types of ADC in situ? CGIN?
HPV associated ( remember p16)
HPV independent
which ones are HPV associated?
Usual type
Intestinal type
have features of P16 cuz HPV dependent
what are the HPV independent types?
Gastric epithelium type
what are 2 types of cervical carcinoma?
Ecto cervix –> squamous cell carcinoma
Endo cervix –> Adenocarcinoma
what are the risk factors of ectocervix squamous cell carcinoma?
Multiple sexual partners
First intercourse at young age
Infection with High risk HPV ( cuz it cause high grade SIL = can progress into carcinoma ) –> 16,18
What are the risk factors of adenocarcinoma ?
obesity
hypertension
Oral contraceptive
all these conditions raise estrogen
what are the gross features of cervical carcinoma?
Fungating cauliflower like mass invading into the vagina
Ulcerative lesion
Infiltrative mass -> diffuse enlargement , hardening of cervix –> barrel shaped cervix
what are the microscopic features of squamous cell carcinoma HPV associated?
Solid nest of maliganant squamous cells invading underlying stroma
NON KERATINIZING ( HPV = NO KERATIN )
P16 = STRONG DIFFUSE BLOCK like positivity
what are the microscopic features of squamous cell cervical carcinoma NON HPV associated ?
Solid nest of cells malignant squamous cell invading stroma
KERATINZED
p53 mutation
no p16 cuz no HPV
What are the microscopic features of adenocarcinoma cervical HPV associated?
Usual ADC : malignant cells arranged in glands
Mucinous ADC :
Malignant cells with mucinous secretion ( cuz gland )
Signet ring ( mucin escapes the gland )
what are the features of Cervical adenocarcinoma NON HPV associated?
Gastric adenocarcinoma type
Clear cell ADC -> Tumor has clear cytoplasm, with hobnail nulcei -> nucleis so big it bulges out of the cell
Endometrioid ADC
NO HPV Girls Can Eat
G = Gastric
C = clear cell
E= endometrium
what is the spread of cervical carcinoma ?
Direct to surrounding : Bladder, rectum ,vagina
Lympathic -> pelvic lymph nodes
Blood –> liver, bone, LUNG ( loves lung )
what are pap smear?
cytological screening
for cervical cancer screening
pap tests are cytological preparation of exfoliated cells from the cervix stained with papanicolau method
how are sample collected?
Conventional pap smear
Liquid base cytology
what is the routine done for a women younger than 21?
no screening regardless of sexual activity = young too young
what is the routine for women aged 21-29 ?
Pap smear alone every 3 years
HPV testing not recommended
what is the routine for women aged 30-65?
Pap test every 3 years
OR
HPV test alone every 5 years –> preferred
OR
HPV + Pap test every 5 years
what is the routine for women older than 65?
no need
what is the management for women 21-24 with ASCUS and LSIL?
ASCUS –> atypical squamous cells undetermined significance ( means mild atypia )
LSIL = LOW GRADE SIL
u js repeat the pap in 1 year
what is the management for women 25 and older with NILM but has HPV?
Negative for intra epithelial lesions or malignancy
if HPV is high risk (16,18 ) = Colposcopy
If not khalas
what is the management for women 25 and older with ASCUS ?
do HPV
if positive - colposcopy
if negative = routine ( pap smear every 3 years )
what is the management for women 25 and older with LSIL?
do HPV
if positive or not done = colposcopy
if negative = back to co testing ( pap + Hpv ) but in 1 year
what is the management of HSIL at any age ?
Colposcopy
what is the management of atypical glandular cells ?
Colposcopy with endo sampling + endometrial sampling
what are uterus problems?
Endometriosis
Adenomyosis
Endometrial hyperplasia
Uterine tumors
what are the cells found in the uterus ?
endometrium has glands = adenocarcinoma
Myometrium = SMOOTH MUSCLES
if benign = leiomyoma
Malignant =leimyosarcoma
what is endometriosis ?
you find endometrial tissue ( glands + stroma ) of the uterus in other locations other than uterus
where could the endometrial tissue be found?
Pelvic structures: ovaries, douglas pouch , Uterine ligament, tube, retovaginal septum
Peritoneal cavity or periumbilical tissue
Lymph nodes, lung , heart , skeletal muscles , bone
why does endometriosis happen?
unknown but 6 theories
3 says they came from uterus
3 says they didnt come uterus endometrium
what are the theories that says its from endometrial origin ( from uterus )?
Regurg theory :
During menstrual cycle, instead of getting flushed down, the shed endometrium goes back through the fallopian tube back to the ovaries and etc .
Stem cell implantation :
Similar to regurg theory, but this time instead of glands and stroma from endometrium that regurg its stem cells then those stem cells grew
Benign mestasis theory :
Cells of endometrium behave like cancer and invade blood vessels and go to other locations using blood somehow they developed this ability
what are the non endometrial origin theories ?
Extrauterine stem cells :
Stem cells from bone marrow leave bone marrow and go to different locations and grow there to become endometrium
Mullerian remnant abnormalities :
Abnormal migration of mullerian duct ( embryo origin of most of female genital system ) to different locations leading to development of endometrium in other orangs
Metaplastic theory:
Coelomic epithelium is a germinal epithelium from which genitalia and urinary system that can give raise anything from genitalia n urinary tract
how do endometrium maintain itself outisde the uterus ( in the different locations )?
1- increased lvl of proinflammatory (PGE2) and agiogenic factor (VEGF) and matrix metalloprotinease (MMP )
2- Endometrium stromal cells make high lvls of AROMATASE leading to increased production of estrogen from androgen = estrogen maintain it
AROMASTE IS THE MOST IMP ONE = cuz this will increase estrogen = leading to infertility cuz hormonal imbalance
what are the grossly features of endometriosis ?
Dark red to bluish nodule
may form cystic structures ( chocolate cyst in ovary ) –> chocolate cuz of dark blood
they behave like normal endometrium like if women has increased thickness in uterus same will happen in other location, and when menstrual cycle happen , happen there as well
what are the microsocpic features of endometriosis ?
normal endometrium :
Endometrium glands
Stroma
Evidence of chronic hemorrhage –> HEMOSIDERIN LADEN MACROPHAGE
complications :
Malignancy + infertility
what is adenomyosis ?
presence of endometrial glands and storma WITHIN the myometrium
These are non function ( they dont work with menstrual cycle )
what is the cause adenomyosis ?
Instillation of endometrium with myometrium
what are the grossly features of adenomyosis ?
Trabeculated cut sruface of uterine wall
we took trabeculation of bladder in Benign prostate hyperplasia
what are the microscopic features of adenomyosis ?
Endometrial stroma and glands
within the myometrium
what is endometrial hyperplasia ?
Increased number of GLAND CELLS –> most imp
increased number of glands compared to stroma
what causes increased number of glands?
Prolonged excess of estrogen stimulation compared to progestin
Mutations
what causes increased estrogen?
Estrogen supplements ( without progestin)
Tamoxifen–> Hormonal treatment for breast cancer ( it blocks estrogen in the cancer but STIMULATE it in uterus )
PCOS ( increased androgen in blood so gets converted to estrogen )
Obesity ( aromatase enzyme activity increases in adipose tissue
Ovarian estrogen secreting stromal tumors , granulosa tumor, thecoma, sertoli-leydig cell
what is the mutation for endometrial hyperplasia?
PTEN
both for hyperplasia and carcinoma
what are types of endometrial hyperplasia ?
Hyperplasia without atypia
Hyperplasia with atypia –> Endomterial intra-epithelial neoplasia ( EIN )
what are grossly features of endometrial hyperplasia ?
Endometrial thickening with increased volume
what are the microscopic features of endometrial hyperplasia?
Increaed number of glands relative to stroma 3:1 ( its not consider hyperplasia if the ratio is the same )
STROMA TISSUE BETWEEN THE GLAND –> IMP –> if the glands fuse = cancer
Non- atypical hyperplasia : Mild glandular crowding and cystic gland dilation
Endomterial intra-epithelial neoplasia EIN :
Marked glandular crowding , cellular ATYPIA
Stratified cells with enlarged NUCLEI + NUCLEOLI ( nuclei and nucleoli megaly )—> PROSTATIC CARCINOMA same same
what is endometrial carcinoma?
carcinoma = arising from epithelium
what epithelium is found in endometrium = glands = so cancer of gland cells
Most common invasive cancer of female genital tract 55-65 years old
what are the types of Endometrial carcinoma ?
Type 1
Type 2
what are the characteristics of type 1?
55-65 years females
Caused by endometrial hyperplasia ( without atypia )
associated with increased estrogen
indolent –> not aggressive
what are the risk factors for type 1 endometrium carcinoma?
Unopposed estrogen stimulation
Obesity
Hypertension
Diabetes
All are associated with high estrogen
what are the mutuations associated with type 1 endometrium carcinoma ?
PTEN
KRAS
Microsatellite instability
what are the microscopic features of type 1?
Endometrioid adenocarcinoma —> very close to normal endometrium
what are the characteristics of type 2?
65-75
Atrophy of endometrium ( NOT INCREASED ESTROGEN )
Arise from endometrial intra-epithelial carcinoma ( EIC )–> ( hyperplasia with ATYPIA , type 1 wasnt associated with it )
AGGRESIVE
so notice type 1 = indolent, hyperplasia, estrogen
type 2 = aggressive, atypia with hyperpalsia, atrophy
what are the mutations of type 2 endometrial carcinoma ?
p53
Since one mutation it develops faster
what are the microscopic features of type 2 ?
2 types :
Serous –> fallopian tube like epithelium
or
Clear cell
what are the grossly features of endometrial carcinoma?
localized polyp tumor
Diffuse tumor involving endometrial surface
what are the microscopic features of endometrial carcinoma?
MUST THERE BE INVASION TO :
Endometrial stromal invasion
Lymphovascular invasion
Myometrial invasion
what are the microscopic features endometroid adenocarcinoma? TYPE 1
Architecture :
Gland fusion, No stroma in between, solid sheats
Cytologic features:
Similar to EIN -> Stratified cells with NUCLEI AND NUCLEOLI MEGALY
what are the microscopic features of serous carcinoma?
this was type 2
Papillae
Cells with HIGH grade cytologic ATYPIA ( cuz type 2 was raised from EIN )
PSAMMOMA BODIES
P16 + P53 ( We said p53 was associated with type 2 )
we have p16 even though we dont have HPV
what are the features of clear cell carcinoma of endometrial cancer?
type 2 as well
Glands
Cell have clear cytoplasm
Hobnail nuclei –> nucleus protrudes beyond boundaries of cell
Similar to clear cell adenocarcinoma of cervix
what is the clinical presentation of endometrial carcinoma ?
post menopausal bleeding
US endometrial thickness
Dilation and curretage
any vaginal bleeding women come u suspect the cancer until proven otherwise
how does endometrial carcinoma spread?
Direct :
Myometrium + Cervix
Lymphatic : Fundus, para aortic lymph node
Lower part – common iliac lymph node
Blood :
LBLB= LUNG, BONE, LIVER,BRAIN
what is leimoyoma ?
clinically known as fibroids
smooth muscle benign tumor from the myometrium
characteristics of leiomyoma ?
Most common benign tumor in female
at reproductive age
respond to hormones –> Estrogen, progesterone stimulate its gorwth
what are chromosomes rearrangements ?
chromosome 6 and 12
mutation in MED12 gene
leiomyoma make 6-12 smooth moves ( 6 and 12 chromosomes, Med12
what are the sites where it can leiomyoma arise from ?
from myometrium directly –> Intramural
Beneath endometrium = submucosal
Serosa = Sub serosal –> aka parasitic cuz it can extend to nearby structures for blood supply like parasite
what are the grossly features of leiomyoma ?
Well circumscribed
Firm
Gray white
WHORLED cut surface
similar to seminoma
what are the microscopic features of leiomyoma ?
Bundle of smooth muscles
Low mitotic rate
NO ATYPIA
NO NECROSIS
multiple lesions ( opposite to leiomyosarcoma everything will be opposite )
what are the prognosis of leiomyoma ?
rarely transform into sarcoma
the presence of multiple lesions doesnt increase the risk of malignancy
what are the characteristics of leiomoyosarcoma ?
Post menopausal
metastasize : usually to lung
what mutation is for leiomyosarcoma ?
p53
what are the grossly features of leiomyosarcoma ?
Solitary ( leiomyoma was multiple )
Large
Hemorrhagic ( opposite to leiomyoma )
Necrotic mass ( ooposite to leiomyoma )
Invading into myometrial wall
Porject to lumen
what are the microscopic features of leiomyosarcoma ?
Triad :
Marked ATYPIA
Increased mitosis
Cell necrosis
all these are opposite to the leiomyoma
what endometrial stromal neoplasms ?
Tumor composed of cells similar to proliferative phase of endometrial stroma
what are the types of endometrial stromal neoplasm ?
Endometrial stromal nodule
Low grade endometrial stromal sarcoma
High grade endometrial stromal sarcoma
Undifferentiated uterine sarcoma
4 types
Went from nodule to sarcoma
what are the features of endometrial stromal nodule ?
Gross :
WELL CICRUMSCRIBED YELLOW NODULE ( single )
Microscopic :
Uniform endometrial stromal cells
NO INVASION
CD10+
What are the features of LOW grade endometrial stromal sarcoma ?
POOORLY circumscribed ( cuz sarcoma )
Yellow + MULTIPLE nodules
Extending from endometrium and INVADING myometrium
Microscopic :
MULTIPLE nodules from endometrial stromal cells with :
Mild nuclear ATYPIA
LOW MITOTIC ACTIVITY
invade myometrium
CD10+
What are features of HIGH grade endometrial stromal sarcoma ?
POORLY circumscribed MASS
Extending from ENDOMETRIUM and invading myometrium
HEMORRHAGE + NECROSIS ( there was none in low grade )
Microscopic features :
stroma cells with :
MARKED NUCLEAR ATYPIA—> opposite to low grade
HIGH MITOTIC ACTIVITY —> opposite to low grade
Invading myocardium
NEGATIVE FOR CD10 ( everything else had it )
what is pelvic inflammatory disease ?
Infection of the upper reproductive tract organs
by pelvic we mainly mean FALLOPIAN TUBE
Somewhat resemble pyelonephritis
what are the types of pelvic inflammatory disease?
Acute PID : acute infection from cervix to tubes then ovaries
Chronic PID : Chronic pelvic infection that can follow acute episodes of PID
what causes PID?
Bacteria ascending from the lower female genital tract :
N. gonorrhea
Chlamydia trachomatis
what are the routes of infection in PID?
Ascending infection : Frond endocervicitis
Blood or lympathic extension : From appendicitis, colitis , diverticulitis
what is the clinical presentation of PID?
Fever, lower abdominal or pelvic pain
pelvic masses -> distention of tubules with exudate
when we do a vaginal smear :
more than 3 WBCs per high power field –> very characteristics
you would see abscess in the form of cysts
what are the complications of PID?
Infertility -> tubal obstruction
Ectopic pregnancy –> in narrow tube cases cuz ovum migration is disturbed
what are tubal lesions?
pre malignant tubal lesions
at FALLPOIAN TUBE FIMBRIA ( close to ovaries )
what are the risk factors for tubal lesions?
Patients with hereditary BRCA mutations ( also seen in breast cancer )
what are the grossly features of tubal lesions ?
NONE
what are the microscopic features of tubal lesions?
STIC –> very imp –> Serous tubal intraepithelial carcinoma ( its cancer but not invading yet )
ATYPIA
Mutant P53- -> we said in endometrial carcinoma we have type 2 serous and it was associated with p53 and here we have serous so p53
HIGH ki-67
what are the ovary problems?
Cystic problems :
Follicular cysts
Corpus luteal cyst
Poly cystic ovarian disease
Ovarian tumors
what is follicular cyst?
A normal follicle with granulosa cells and theca cells
BUT IT FAILED TO BURST AND RELEASE THE OVUM
So it enlarges and become a cyst
what are the grossly feature of follicular cyst ?
Thin walled cyst
Unilocular ( one lobule )
Smooth inner cells
Clear fluid
what are the microscopic features of follicular cyst ?
normal components of a follicle since its js an unruptured follicle :
Inner layer of granulosa cells
Outer layer of theca cells
what is corpus luteal cyst ?
Corpus luteal fail to regress
become enlarged with fluid and blood
( another cyst was filled with blood was endometriosis but it was dark chocolate )
what are the grossly features of corpus luteal cyst?
Thin walled cyst
Unilocular –> one lobule
Smooth inner surface
HEMORRHAGIC CONTENT ( cuz we mentioned it was filled with fluid and blood )
what are the microscopic features of corpus luteal cyst?
normal components of corpus luteum :
Markedly luteinized granulosa and theca cells
IF you see a cyst in ovary filled with red blood = corpus luteal cyst
if its dark brown blood = endometriosis
what is polycystic ovary diseae/ syndrome? stein leventhal syndrome ?
a women with 2 of the following features :
1- Oligoovulation or anovulation –> irregular or absent menstrual period
2- Clinical and/or biochemical signs of HYPERANDROGESIM –> hirsutism, acne, elevated serum androgen levels
3- Polycystic ovaries on Ultra sound
any 2 if the above
VERY VERY COMMON
what is the pathogenesis of it?
Starts off with high LH why? = UNKOWN
LH will go to ovary –> stimulate the theca cells and thus Increase androgen production
Inhibit granulosa cells –> DECREASE estrogen production from ovary
Increased androgen will lead to :
Follicular atresia + atrophy
Physical changes and symptoms such : hirsutim , acne
Will go to adipose tissue and then there we have aromatase = convert the androgens to estrogen
so we have decreased estrogen from ovaries but INCREASED IN BLOOD due to this conversion
This increased estrogen will cause endometrium hyperplasia –> risk of cancer
also stimulate LH
N cycle repeats
what happens if women is obese?
women with PCOS are usually obese? why ? we dont know
the increased adipose tissue will make more estrogen but will also lead to DECREASED insulin sensitivity leading to INCREASED Insulin release cuz tissue is not responding
Hyperinsulinemia will lead to :
Ancathosis nigricans ( black thickness of skin )
Increased androgens ( from theca cells and adrenal gland )
INCREASE LH secretion –> Increase the LH/FSH ratio
this disturbed ratio will lead to follicles hyperplasia of theca cells acummulation of follicular fluid forming cyst like structure s
what are the investigations for PCOS?
Pelvic ultrasound
Lab :
HIGH LH , normal FSH
HIGH estrogen, androgen, free testerone
High plasma insulin
what are the grossly features? of PCOS?
large ovaries
numerous cortical cysts ( Arrested follicles )
what are the microscopic features of pcos?
Multiple cystic follicles with LUTEINIZED THECA CELLS
no granulosa cuz they are inhibited by LH
what are the risk factors for ovarian tumors?
benign = more common in young
malignant = more common in older
Age –> after menopause
Genetics and family history
Hormonal replacement therapy
Oral contraceptive use = lower risk
Why? cuz we give hormones postmenopause ( body wont use it = harm ) , Oral contraceptive = given during reproductive years =body is using them
Smoking
Endometriosis
Reproductive history = no pregnancy and women with low parity have higher risk
Ovulation= more ovulation = higher risk
Pregnancy and breastfeeding = reduce risk when ur pregnant no ovulation for 9 months so less ovulation less risk
what are the genetic risk factors for ovarian tumors?
lynch syndrome –> MLH1,MH2,MSH6,PSMS2
Hereditary breast and ovarian cancer syndrome –> BRCA1 and BRCA2
what are the classification of ovarian tumor?
According to place of origin
if primary from the ovaries themselves
if primary could arise from :
Surface epithelium which is derived from celomic epithelium ( could be any type of cell from genito, urinary system, glands like endocervix, urothelial like bladder, serous like fallpon tube, etc )
Germ cells ( similar to tumors in testis –> Yolk sac tumor , Teratoma, Mixed, Embryonal , chorio) ( only new one is dysgerminoma which similar to seminoma)
Sex cord/stroma of ovary ( leydig, sertoli, granulosa, theca)
Secondary –> metastatic
what are the surface epithelium tumor??
Serous
mucinous
Endometroid
Clear cell
Transitional cell ( urothelial )
MOST IMP cuz coelemia can differentiate into any cell from genito urinary tract
how do we classify the tumors of surface eptihelial tumors? malignant or benign
Benign –> NO epithelial proliferation + NO atypia + NO invasion
Borderline –> Epithelial proliferation + ATYPIA + NO invasion
Malignant —> Epithelial proliferation + ATYPIA + INVASION
any tumor end with oma is benign
malignant = sarcoma/carcinoma
If borderline will be mentioned
what are the types of surface epithelium ovarian tumor?
type 1
Type 2
what are the characteristics of type 1 surface epithelium tumor?
often detected in early stage
arise from borderline tumors
or
Endometriosis
generally better prognosis
what are the types of type 1 surface epithelial tumor?
Low grade serous
Endometroid
Clear cell
Mucinous
what are the mutations in type 1 surface epithelium ovarian cancer?
similar to type 1 endometrial cancer :
PTEN
KRAS
in addition to BRAF
what are the characteristics of type 2 surface epithelium ovarian cancer?
Usually diagnosed at advanced stage
ARISE FROM : STIC –> SEROUS TUBAL INTRAEPITHELIAL CARCINOMA –> ATYPICAL. P53, HIGH KIA64
Poor prognosis despite chemo response
what are the types of type 2 surface epithelium ovarian cancer?
only 1
HIGH GRADE SEROUS ( low grade was type 1)
what are the mutation of type 2 surface epithelium ovarian cancer?
similar to type 2 endometrial cancer
P53
in addition to BRCA1/2 ( cuz we said STIC is due to BRCA )
How do surface epithelium ovarian cancer happen?
after ovulation happen
the follicle breaks the surface as its pushing out the ovum
this makes a hole in the surface
now this HOLE is the problem:
If STICS from the fallopian fimbriae gets shed off and fall on this hole —> will grow there and become TYPE 2 –> HIGH GRADE SEROUS
IF the women didnt have STICS –>other surface epithelial cells might fall into it and develop and proliferate forming type 1 ( mucinous, low grade serous, endometroid, etc )
thats why ovulation is a risk for ovarian cancer as everytime ovulation happen a hole forms
so if you see a female with high grade ovarian serous cancer –> check fallopian tube for STIC + check for brca gene
What are the features of benign serous tumor ?
Grossly :
Could be bilateral
Cyst unilocular
Contains Serous fluid
Microscopic :
Single Layer of epithelium
No atypia
what are the features of borderline /atypical proliferative serous tumor ?
Grossly :
Could be bilateral
Cyst with many papillary projections
Microscopic features :
Multilayering of epithelium
NO STROMAL INVASION
what is special about borderline= atypical proliferative serous tumor ?
Implants :
Most important prognostic factor
Could be non invasive
or
Invasive
what are the features of malignant serous tumor ?
could be low grade or high grade ( but each is different from each others , low grade was type 1 and high grade was type 2 )
Grossly :
Mostly BILATERAL -> maligant is bilateral mostly
SOLID ( no longer cyst ) NECROSIS , HEMORRHAGE ( like corpus luteum cyst and endometriosis )
Microscopic :
Malignant cells
ARRANGED IN GLANDS, PAPILLAE, SHEETS WHATEVER
INVADE THE STROMA ( in borderline there was no invasion )
Psammoma bodies –> like Papillary RCC, Papillary urothelial carcinoma , Endomterium serous tumor
High grade has extra :
HIGH NUCLEAR ATYPIA
P53 MUTATION
Fallopian tube with STIC
what are the features of BENIGN of MUCINOUS tumors?
Type 1
Grossly :
Could be bilateral
MULTILOCULAR CYSTS –> only one no other is
Contains MUCINOUS FLUID
Microscopic features:
Single layer of epithelium
No atypia
What are the benign mucinous tumor associated with ?
Dermoid cysts –> Was seen in teratoma ( prepubertal )
Brenner tumor
what are the features of borderline/atypical proliferative mucinous tumor ?
Grossly :
Could be bilateral
Benign tumor but MANY PAPILLARY PROJECTIONS ( like serous borderline )
Microscopic features:
Multi layer epithelium
Atypia
No stromal invasion ( cuz its borderline )
no implants here like serous
what are the features of malignant mucinous tumor?
Grossly :
UNILATERA –> serous bilateral
Mostly solid, necrotic, hemorrhagic
Microscopic :
Malignant cells
arranged in glands, papillae, solid sheets, etc
Infiltrating stroma
Abundant mucin —> leading to formation of sigent right ( ADC in cervix hpv associated)
NOTE if the mucinous ovarian cancer is not primary meaning its metastasis it would be BILATERAL smaller and IF IT WAS primary it would be big and unilateral
ho w to differentiate between primary mucinous and secondary mucinous ovarian tumor ?
Primary is less common :
BIGGER + UNILATERAL
Secondary/metastasis = MOST COMMON
Smaller , BILATERAL
describe endometrioid surface epithelium type 1 cancer?
Most are malignant
Associated with endometriosis
describe clear cell tumors of surface epithelium type 1 ovarian cancer?
Most are malignant
ASSOCIATED WITH ENDOMETRIOSIS + LNYCH SYNDROME (MSH2 )
COME WITH PARA ENDOCRINE HYPERCALCEMIA? cuz it secretes PTH–> what else secrete PTH? RCC and now this
describe brenner tumors of type 1 superficial ovarian cancer?
Most are benign
Mimic urothelium cells ( bladder )
3 types :
Benign
Borderline
Malignant –> TO BE MALIGNANT U MUST FIGHT :
1- STROMAL INVASION
2- benign or borderline components
if you dont find its no longer brenner its js urothelial cancer
describe dysgerminoma?
Seminoma of females same everything :
Most common malignant germ cell tumor of ovary
Pure or mixed with GCT
20-30 years old
HIGHLY MALIGNANT
Treated by EXCISION + RADIATIO +CHEMO
what is the chromosomal abnormality of dysgerminoma ?
Isochromosome 12
KIT
like seminoma
whats positive in dysgerminoma?
like seminoma
PLAP ( GCIN )
CD117
what are the grossly features of Dysgerminoma ?
same as seminoma
Soft
Well define
Grey White
Multinodular
Replaces ovary
what are the microscopic features of dysgerminoma ?
same as seminoma
Clear cells –> MONOTONUS ( same in everything )
Large clear glycogen rich cytoplasm
Nests
WITH LYMPHOCYTES INFILRTATION
describe embryonal carcinoma in females?
same as male
common component of mixed germ cell tumor ( rarely occurs alone )
Very aggressive
whats raised in the serum
AFP , BHCG, in females
in male = LDH
what positive in embryonal carcinoma ?
CD30
what are the grossly features of Embryonal carcinoma?
same as male
Poorly circumscribed cuz aggressive
Grey-whitis mass –> hemorrhage and necrosis
Does not replace entire tests ( as its small mass )
what are the microscopic features of embryonal carcinoma?
Anaplastic epithelial cells –>most imp
arranged in solid sheets , tubules glands, papillary
Necrosis cuz hemorrhage
describe yolk sac tumor in females?
Same as males
occurs as pure form or rarely as part of mixed germ cell tumor
what is the serum marker for yolk sac tumor?
AFP
whats positive in yolk sac tumor?
AFP
grossly features ?
yellow white, mucinous soft
microscopic features of yolk sac tumor? ?
Cuboidal to columnar cells epithelial that come in many different shapes :
Microcyst –> most imp
glands, sheets, papillae, etc
SCHILLER DUVAL BODY –> papillary projection with central blood vessel surrounded by thick layer of basement membrane covered by layer of embryonic epithelial cells
HYALINE GLOBULES –> eosinophilic PAS positive globules ( AFP )
what is teratoma in females?
aka ovarian ghoul
germ cell tumor composed of all 3 types of germ layers :
Ectoderm–> skin neural tissue
Endoderm –> glandular tissue
Mesoderm –> fibrous, cartilage, fat,smooth muscles
VERY AGGRESSIVE IN FEMALES VERY
sites where teratoma could occur?
Gonads –> testis, ovaries
Extra gonadal –> arise from midline embryonic rests, mediastinum , retroperitoneum
what are the classification if teratoma in females?
different than males ( post pube ( mali ) pre pub ( benign ) , teratoma with mali )
1- Mature benign tumor
2- Immature malignant teratoma
3- Monodermal teratoma
4- Teratoma with malignancy–> elder women
describe mature benign teratoma ?
all the tissues are well developed and differentiated
You can tell what everything is
most of the time its cystic since its benign
Young women
describe immature malignant teratoma ?
All tissues are IMMATURE you cant tell what is what
small blue round cells
MOSTLY SOLID cuz malignant and in young women
How do we determine how severe it is ? neuroeptihelial –> more neuroepithelial = more malignant and thats how they grade it
describe monodermal teratoma ?
here the teratoma takes in one type of tissue
usually its thyroid functioning tissue
what is the clinical presentation of teratoma ?
Infertility
IF it has neural tissue :
Limbic ENCEPHALITIS
Gliomatosis peritonii
limbic encephalitis usually accompany which type of teratoma?
Mature benign teratoma
gliomatosis peritonni usually accompany which type of teratoma ?
Immature malignant teratoma
what are grossly features of mature benign teratoma?
Mature cyst ( Dermoid cyst )
Unilocular cysts
Smooth outersurface
Contains cheesy sebaceous material with hair , tooth
what are the microscopic features of mature benign teratoma ?
Mature elements from all 3 germ layers
Mature ectoderm –> skin ,neural tissue
Mature mesoderm —> cartilage, bone ,fat
Mature endoderm –> Respiratory tract epithelium, gut, thyroid wall
what are the grossly features immature malignant teratoma ?
happen in young women,prepubertal
SOLID ( not cyst cuz its malignant )
areas of necrosis
Hemorrhage
microscopic features of immature malignant teratoma ?
IMMATURE tissue + little mature tissue
GRADING IT IS BASED ON IMMATURE NEUROEPITHELIAL TISSUE
what are the types monodermal teratoma ?
Ovarian carcinoid –> maybe functioning producing serotonin
Struma ovarii –> mature thyroid tissue
describe teratoma with malignant transformation ?
Tend to occur in older women
Come with any cancer :
Squamous cell carcinoma, thyroid caricnoma, melanoma , etc
describe choriocarcinoma in females?
Same as males
usually mixed germ cell tumor
HIGHLY MALIGNANT
Surgery with chemotherapy
Most aggressive NSGCT
spreads rapidly by blood
composed of varying amounts of syncyiotrophoblast cells
Cytotrophoblasts cells
what is the serum marker for choriocarcinoma n what is it positive for ?
hCG
what do you see in the microscopic features of choriocarcinoma?
Snyciotrophoblasts –> large multinucleated
Cytotrophblasts
hemorrhage
what are the types granulosa cell tumor ?
sex cord tumor
Adult type –> middle aged women + low malignant potential
Juvenile –> children and young adults + low malignant potential
Both have low malignancy
what does granulosa cell tumor secrete?
estrogen so : ( leybig secrete androgen, sertoli secrete both estrogen and androgen but more estrogen )
in case of tumor it would lead to
Vaginal bleeding in adults
Precocious puberty in children
what is the serum marker for granulosa cell tumor?
INHIBIN
what is granulosa cell tumor positive for ?
INHIBIN
what are the grossly features of Granulosa cell tumor?
Solid cystic
Cut surface :
Yellow due to intracellular lipids
what is the microscopic features of
Cells :
Small GROOVED NUCLEI ( coffe bean like )
ARRANGED IN FOLLCILES WITH EOSINOPHILIC MATERIAL –> CALLED CALL EXNER BODIES
describe leydig cell tumor in females?
same as males
most common sex cord stromal tumor
MAINLY PRODUCE ANDROGEN
Grossly : Well circumscribed , MAHOGY brown cut surface ( like chromophobe RCC and oncocytoma )
Microscopic features :
Solid sheets ( sertoli are tubules )
Polygonal cells with abdundant eosinophilic
Cytoplasm contain :
Lipofuscin pigment ( lipid droplets in it )
Reinke crystals ( red rods in the cytoplasm )
describe sertoli cell tumor in females?
SAME as male
produce both estrogen and androgen but mainly ESTROGEN
Grossly :
Well circumscribed, solid, white nodule
Microscopic :
Tubules not sheets
Cells with clear or pale eosinophilic cytoplasm
Cytoplasm Contain :
Lipids
Charcot bottcher filaments
Characteristics of FIBROMA?
occur at reproductive age
NO endocrine manifestation cuz it doesnt produce hormones
GREY WHITIS MASS
what is meigs syndrome ?
Women at reproductive age
come with 3 things :
Fibroma ( ovarian mass )
RIGHT pleural effusion
Ascites
MEIGS SYNDROME
what links all of these? no one knows
what are the ccharacteristics of thecoma?
tumor from theca cells
OCCUR AT POST MENOPAUSAL WOMEN ( opposite to fibroma where it occurred at reproductive age )
It secretes estrogen ( also opposite to fibroma which didnt secrete anything )
features of thecoma ?
GROSSLY :
YELLOW like granulosa
Microscopic :
Yellow lipid laden theca cells with reticulin fibers around each tumor
what are metastatic tumors in the ovaries?
Could be from :
Genital tumors : Uterus, fallopian , contralateral ovary
Extra-genital tumor –> BREAST and GIT , pancreas , biliary tract
what are krukenberg tumors?
source of primary tumors :
Stomach 75% of case
large inestines
breast
Microscopically :
Nests of mucin producing signet ring cancer cell
how does ovarian tumors spread?
Local to adjacent rogans
Transcelomic : exofoliation of cells into peritoneal cavity deposit in :
Contralateral ovary
Douglas pouch
Surface intestine
Omentum
Umbilical metastasis
Lymphatic :
Retrograde para aortic nodes
Inguinal LN
BLOOD : LBLB
what are the markers released by epithelial ovarian cancer ?
CA-125
What does mucinous ovarian cancer release in serum?
CEA
whats the marker for embryonal carcinoma and choriocarcinoma in females?
HCG
what marker is released by granulosa cell tumor?
inhibin
what marker is released by Dysgerminoma ?
LDH
Seminoma also release this
what marker is released by Yolk sac tumor? Endoermal sinus tumor?
AFP
what is oval risk of ovarian malignancy algorthm? ROMA?
something done to women with ovarian mass and scheduled for surgery to indicate if them mass is benign or malignant
this is not accurate at all but its something better than nothing
vero cell assay?
a way used to detected shiga toxin in the stool
thyroidization ?
chronic nephritis
