Pathoma CH. 13 Female Genital System and Gestational Pathology Flashcards
What are the anatomical elements of the vulva?
Labia majora, labia minora, mons pubis, and vestibule
35 y/o patient presents with left sided painful cystic lesion adjacent to the vaginal canal. What type of cyst is most likely causing this unilateral pain and what causes this type of cyst?
Bartholin cyst—caused by inflammation and obstruction of the bartholin gland
What are the two most common causes of a bartholin cyst?
Infection and STDs
What are the 2 most common HPV strains causes a condyloma?
HPV 6 and 11
Warty neoplasm present in the vulvar skin…
Condyloma
A condyloma can occur secondary to what type of STD other than HPV?
Syphilis—less common
What histological characteristic does an HPV-associated condyloma have?
Koilocytes
Raisin/crinkled cells present in HPV-associated condylomas…
Koilocytes
Why are HPV strain 6 and 11 considered low risk HPV types?
The condylomas associated with these strains RARELY develop into carcinoma
Name the 4 most common high risk HPV types that can lead to dysplasia and carcinoma…
HPV 16, 18, 31 and 33
What disorder is associated with thinning of the epidermis and fibrosis of the dermis?
Lichen sclerosis
A postmenopausal patient presents with leukoplakia (white patch) and parchment-like vulvar skin. What disorder is associated with these findings?
Lichen sclerosis
Lichen sclerosis is a _____ tumor with an increased risk of ___________.
Benign
Squamous cell carcinoma
Hyperplasia of the vulvar squamous epithelium…
Lichen Simplex Chronicus
Patient presents with leukoplakia on thick, leathery vulvar skin and complains of constant irritation and scratching around the area. What is the most likely disorder this patient is presenting with?
Lichen Simplex Chronicus
Is Lichen Simplex Chronicus benign or malignant? Is there an increased risk of developing a carcinoma from this abnormality?
Benign—no increased risk of squamous cell carcinoma
Thinning of the vulvar skin is seen in what abnormality?
Lichen Sclerosis
Thickening of the vulvar skin is seen in what abnormality?
Lichen Simplex Chronicus
Squamous epithelium lining the vulva can develop into what type of cancer?
Vulcar carcinoma
What three vulvar disorders present with leukoplakia and why is a biopsy performed?
Lichen sclerosis
Lichen simplex chronicus
Vulvar carcinoma
Biopsy performed to distinguish each from one another and to determine if carcinoma
A 45 year old woman presents with leukoplakia of the vulvar and it was determined to be caused by vulvar carcinoma. Is the etiology HPV or non-HPV related? Why?
HPV— Seen primarily in premenopausal women btwn the ages of 40-50
A postmenopausal woman presents with vulvar carcinoma and has a history of lichen sclerosis. Is the etiology HPV or non-HPV related? Why?
Non-HPV related—this is due to long standing lichen sclerosis
HPV-related vulvar carcinoma is due to what HPV types?
High-risk—16,18,31, and 33
What are the most common risk factors for HPV related vulvar carcinoma?
Multiple partners
Early intercourse
Women of reproductive age
What vulvar disease is characterized by koilocytic change, disordered cellular maturation, nuclear atypia and increased mitotic activity? What cancer can develop from this disease?
Vulvar intraepithelial neoplasia
Vulvar carcinoma
Malignant epithelial cells in the epidermis of the vulva indicate what?
Extramammary Paget Disease
A female patient presents with erythematous, pruritic(itchy), ulcerated vulvar skin. What disease is most likely associated with this presentation?
Extramammary Paget disease
Extramammary Paget Disease of the breast will present with or without surrounding cancer?
With—Malignant epithelial cells of the nipple within the epidermis of the nipple will almost always present with underlying carcinoma—Paget disease of the vulva will NOT
Extramammary Paget disease of the vulva usually represents carcinoma _______ and will have no underlying carcinoma.
In situ
Name the stains used to distinguish Extramammary paget disease of the vulva from melanoma of the vulva…
PAS
Keratin
S100
PAS+, keratin+ and S100- will represent Paget cell carcinoma or melanoma?
Paget cells—PAS marks mucous, which only glandular tissue produces mucous—involves the epidermis—so PAS + → Paget
PAS-, keratin – and S100+ will represent Paget cell carcinoma or melanoma?
Melanoma—S100+→ melanoma
The mucosa of the vagina is lined by what type of epithelium?
Non-keratinizing squamous epithelium
This abnormality is characterized by focal persistence of columnar epithelium in the upper vagina…
Adenosis
The squamous epithelium from the lower 1/3 of the vagina is derived from what embryological structure?
Urogenital sinus
The columnar epithelium from the upper 2/3 of the vagina is derived from what embryological structure?
Mullerian ducts
The columnar epithelium of the upper 2/3 of the vagina is normally replaced by the lower 1/3 squamous epithelium. Name the disease where this replacement doesn’t occur and the columnar epithelium remains…
Adenosis
A female patient who was previously exposed to diethylstilbestrol (DES) in utero (because it can easily cross the placenta) is at risk for what vaginal disease?
Adenosis—can progress to clear cell adenocarcinoma
Malignant proliferation of glands with clear cytoplasm…
Clear cell adenocarcinoma
What precursor disease can lead to clear cell adenocarcinoma?
Complication of DES-associated vaginal adenosis
Malignant mesenchymal proliferation of immature skeletal muscle…
Embryonal Rhabdomyosarcoma
A 4 year old female patient presents with a grape-like mass protruding from the vagina with associated bleeding. What vaginal disorder does this patient most likely have?
Embryonal Rhabdomyosarcoma—also known as sarcoma botryoides—can occur in males and usually in children
What are the three characteristic features of Rhabdomyoblast seen in embryonal rhabdomyosarcoma?
1)Cytoplasmic cross-striations
Positive immunohistochemical staining for 2)desmin and 3)myogenin
Desmin—intermediate filament found in skeletal muscle
Myogenin—found in immature skin
What carcinoma arises form the squamous epitheliual lining of the vaginal mucosa?
Vaginal carcinoma
What HPV types are usually related to vaginal carcinoma?
High-risk—16,18,31, and 33
What is the dysplastic precursor for vaginal carcinoma?
Vaginal intraepithelial neoplasia (VAIN)
When cancer occurs in the lower 1/3 of the vagina, what regional lymph nodes can it spread to?
Inguinal nodes
When cancer occurs in the upper 2/3 of the vagina, what regional lymph nodes can it spread to?
Iliac nodes
What are the two division of the Cervix?
Exocervix and endocervix
What epithelium lines the exocervix?
Nonkeratinizing squamous
What epithelium lines the endocervix?
Single later of columnar cells
What is the junction btwn the exo and the endocervix?
Transformation zone
Within the cervix, what area is most susceptible to HPV?
Transformation zone
Persistent infection of HPV can lead to an increased risk of __________.
Cervical dysplasia—cervical intraepithelial neoplasia (CIN)
What are the high-risk HPV types for the development of cervical intraepithelial neoplasia (CIN)?
16,18,31 and 33
What are the low-risk HPV types for the development of cervical intraepithelial neoplasia(CIN)?
6 and 11
What 2 proteins are produced by high-risk HPV types and what do these proteins cause?
E6 and E7 proteins—cause increased destruction of p53 and Rb, respectively —loss of tumor suppressor proteins
The production of E6 from high-risk HPV types causes destruction of _____.
P53
The production of E7 from high-risk HPV types causes destruction of _____.
Rb
When high-risk HPV types produce E6 and E7, what cervical abnormality is the patient at an increased risk of developing?
Cervical intraepithelial neoplasia (CIN)
What is seen within the cervical epithelium when cervical intraepithelial neoplasia (CIN) occurs?
Koilocytic change
Disordered cellular maturation
Nuclear atypia
Increased mitotic activity
A grade of CIN I indicates involvement of…
A grade of CIN II indicates involvement of…
A grade of CIN III indicates involvement of…
Slightly less than the entire thickness of epithelium
Carcinoma in situ (CIS) of the cervical epithelium involves…
The entire thickness of the epithelium
What grades of CIN are reversible and which are not?
CIN I,II and III are all reversible—the higher the grade the less likely it is to regress. Carcinoma in situ (CIS) is NOT reversible and is considered metastatic
What is the average age range seen for women who develop cervical carcinoma?
40-50 years
A 44 y/o female patient presents with postcoital vaginal bleeding with associated discharge. What carcinoma should be considered in this patient based on her presentation?
Cervical carcinoma
What are the primary risk factors for cervical carcinoma?
Exposure to high-risk HPVs
What are the secondary risk factors for cervical carcinoma?
Smoking and immunodeficiency (AIDS-defining illness)
Name the two most common subtypes of cervical carcinoma…
Squamous cell carcinoma (80%) and adenocarcinoma (15%)
* Both types related to HPV infections*
What is a common cause of death seen in advanced cervical carcinoma? Why?
Hydronephrosis with postrenal failure due to the advanced tumor invading the anterior uterine wall, entering the bladder, and blocking the ureters
The progression of CIN into carcinoma can take anywhere from _____ to _____ years.
10-20
What is the gold standard for screening of cervical carcinoma?
Pap smear
When performing a Pap smear, where are the cells scraped from?
Transformation zone of the cervix
List the low grade and high grade CINs…
Low grade—CIN I
High grade—CIN II and CIN III
What are the two characteristics of high-grade dysplasia (CIN)?
Cells with hyperchromatic nuclei
High nuclear to cytoplasmic ratios
What is indicated for confirmation after an abnormal Pap smear is discovered?
Confirmatory colposcopy and biopsy
What are the 2 major limitations to Pap smears?
Inadequate sampling of the transformation zone
Limited efficacy in screening for adenocarcinoma
What are the 4 HPV types that the vaccine covers?
6, 11, 16 and 18
What do antibodies against HPV type 6 and 11 protect against?
Condylomas
What do antibodies against HPV type 16 and 18 protect against?
CIN(cervical intraepithelial neoplasia) and Carcinoma
Why are Pap smears still necessary, even with the vaccine?
Because of the many different HPV subtypes that the vaccine does NOT cover
What hormone drives the proliferative phase/growth of the endometrium?
Estrogen
What hormone prepares the endometrium for implantation?
Progesterone
Loss of progesterone support causes what phase of the female cycle?
Menstrual (shedding) phase
Loss of the basalis and scarring causing amenorrhea…
Asherman syndrome
What is the cause of Asherman syndrome?
Overaggressive D&C—causing loss of basalis
How does an anovulartory cycle occur?
Estrogen-driven proliferative phase occurs WITHOUT a progesterone-driven secretory phase
Overgrowth occurs and the proliferative glands break down causing uterine bleeding
Common cause of dysfunctional uterine bleeding—during menarche and menopause
Bacterial infection of the endometrium…
Acute endometritis
A 25 year old 1 week post partum women presents with fever, abnormal uterine bleeding and pelvic pain. What is the most likely cause of her symptoms?
Acute Endometrities—due to retained products of conception
Chronic inflammation of the endometrium…
Chronic endometritis
What is necessary for the diagnosis of chronic endometritis?
Plasma cells—lymphocytes are also present, but are normally found in the endometrium
Retained products of conception, chronic pelvic inflammatory disease, IUDs and TB are all causes of chronic _________.
Endometritis
Chronic endometritis can present as…
Abnormal uterine bleeding, pain and infertility
Hyperplastic protrusion of the endometrium…
Endometrial Polyp
Endometrial polyp can arise as a side effect of what drug?
Tamoxifen—anti-estrogenic effects on the breast, BUT pro-estrogenic effects on the endometrium
Caused by retrograde menstruation and implantation at ectopic site…
Endometriosis
A 31 year old female patient presents with dysmenorrhea (pain during menstruation) pelvic pain and infertility. Upon ultrasound, fluid is found in the ovary and is describe as a ‘chocolate cyst’. What disorder does this patient most likely have?
Endometriosis
Where is the most common site of involvement with endometriosis?
Ovary—chocolate cyst
If a patient has endometriosis and presents with pelvic pain, what structure is most likely involved?
Uterine ligaments
If a patient has endometriosis and presents with pain with defecation, what structure is most likely involved?
Pouch of douglas
If a patient has endometriosis and presents with painful urination, what structure is most likely involved?
Bladder wall
If a patient has endometriosis and presents with abdominal pain and adhesions, what structure is most likely involved?
Bowel serosa
If a patient has endometriosis and presents with ectopic tubal pregnancy, what structure is most likely involved?
Fallopian tube mucosa—scarring increases risk
Endometriosis in which the uterine myometrium is involved…
Adenomyosis
Occurs as a consequence of unopposed estrogen…
Endometrial hyperplasia
Endometrial hyperplasia usually presents as__________ uterine bleeding.
Postmenopausal
What two classifications are used when determining the prognosis of endometrial hyperplasia?
Growth pattern—simple or complex
Presence or absence of cellular atypia
What histological finding is the most important predictor for the progression of endometrial hyperplasia to carcinoma?
Presence of cellular atypia
Malignant proliferation of endometrial glands…
Endometrial carcinoma
Endometrial carcinoma most often presents in _____menopausal women.
Post—bleeding occurs
What are the two pathways in which endometrial carcinoma arises?
Hyperplasia (75%)
Sporadic (25%)
What are the risk factors for the hyperplasia pathway of endometrial carcinoma?
Estrogen exposure Early menarche/late menopause Nulliparity Infertility Anovulartory cycles Obesity
What is the average age for presentation of hyperplastic endometrial carcinoma?
Age 60
Describe the histological appearance of hyperplasia endometrial carcinoma…
Endometrioid→ normal endometrium-like
What is the mechanism for the sporadic pathway of endometrial carcinoma?
Carcinoma arises in an atrophic endometrium→ no precursor lesion
What is the average age for presentation of sporadic endometrial carcinoma?
Age 70
Describe the histological appearance of sporadic endometrial carcinoma…
Serous→ papillary structures with psammoma body formation
What is the common mutation that occurs in the sporadic pathway of endometrial carcinoma?
P53 mutation
Benign neoplastic proliferation of smooth muscle beginning in the myometrium…
Leiomyoma (fibroids)
Leiomyomas are related to ______ exposure.
Estrogen
Premenopausal women
Enlarge during pregnancy
Shrink after menopause
Multiple, well-defined, white, whorled masses found within the myometrium…
Leiomyoma (fibroids)
What are the symptoms associated with leiomyomas?
Usually asymptomatic, but when present→ abnormal uterin bleeding, infertility, and a pelvic mass
Malignant proliferation of smooth muscle beginning in the myometrium, usually present in postmenopausal women…
Leiomyosarcoma
Do leiomyosarcomas arise from leipmyomas?
NO—arise de novo
Single lesion in the myometrium with areas of necrosis and hemorrhage…
Leiomyosarcoma
What are the histological features of a leiomyosarcoma?
Necrosis
Mitotic activity
Cellular atypia
What acts on theca cells to induce androgen production?
LH
What cells act to convert androgen to estradiol and what induces this?
Granulosa cells stimulated by FSH
What two actions occur leading to ovulation?
Estradiol surge→ LH surge
After ovulation occurs what does the residual follicle become and what is secreted from this?
Corpus luteum→ secreting progesterone—driving the secretory phase (prep endometrium for possible pregnancy)
What occurs when there is degeneration of the follicles?
Follicular cysts
Multiple ovarian follicular cysts due to hormone imbalance…
Polycystic ovarian disease (PCOD)
What imbalance characterizes polycystic ovarian disease?
Increased LH and low FSH (LH:FSH >2)
Hirsutism (excess hair in a male distribution) occurs in women with polycystic ovarian disease. What causes this?
Increased LH inducing excess androgen production→ from the theca cells
What is androgen converted to in adipose tissue? What does this cause and what are woman at an increased risk of?
Estrone→ has feedback decreasing FSH→cystic degeneration of follicles
High levels of Estrone put women at increased risk of endometrial carcinoma
A 15 year old women presents with obesity, infertility, oligomenorrhea, insulin resistance and hirsutism. What is the most likely diagnosis and what is this patient at an increased risk of developing?
Polycystic ovarian disease
Increased risk of developing type 2 DM due to insulin resistance
What are the 3 cells types of the ovary that tumors can arise from?
Surface Epithelium (70%) Germ cells (15%) Sex cord-stroma
A surface epithelial tumor of the ovary is derived from what epithelium lining the ovary?
Coelomic epithelium
What does the coelomic epithelium produces embryologically?
Fallopian tube
Endometrium
Endocervix
What are the two most common subtypes of surface epithelial tumors?
Serous and mucinous
Benign surface epithelial tumors (cystadenomas) are most common in…
Premenopausal women age 30-40
Describe the histology of a benign surface epithelial tumor (cystadenoma)
Single cyst with a simple, flat lining
Malignant surface epithelial tumors (cystadenocarcinomas) are most common in…
Postmenopausal women age 60-70
Describe the histology of a malignant surface epithelial tumor (cystadenocarcinoma)
Complex cysts with a thick, shaggy lining
What mutation carries an increased risk for the development of serous carcinoma in the ovary and fallopian tube?
BRCA1 mutation
Name two subtypes of surface epithelial tumors that a uncommon…
Endometrioid—usually malignant
Brenner tumor
What is an endometrioid surface epithelial tumor associated with?
Endometriosis
What type of surface epithelial tumor is composed of bladder-like epithelium and is usually benign?
Brenner tumor
What is CA-125 tumor marker useful for?
Useful serum marker used to monitor treatment response and screening for recurrence
What are the age ranges in which women are most likely to develop a germ cell tumor?
15-30 y/o-→ reproductive age
Name the 4 germ cell tumor subtypes…
Fetal tissue→ cystic teratoma and embryonal carcinoma
Oocytes→ dysgerminoma
Yolk sac→ endodermal sinus tumor
Placental tissue→ choriocarcinoma
Cystic tumor composed of fetal tissue derived from 2/3 embryologic layers…
Cystic teratoma
A cystic teratoma is most often benign, however the presence of what two aspects will indicate malignant potential?
Immature tissue
Somatic malignancy→squamous cell carcinoma of the skin
Teratoma composed primarily of thyroid tissue…
Struma ovarii
A tumor composed of large cells with clear cytoplasm and a central nuclei and is the most common malignant germ cell tumor…
Dysgerminoma
What is the testicular counterpart to a dysgerminoma?
Seminoma
The serum level of what substance may be elevated due to a dysgerminoma?
LDH
A malignant tumor that mimics the yolk sac and is the most common germ cell tumor is young children…
Endodermal sinus tumor
The serum level of what substance is often elevated in the presence of an endodermal sinus tumor?
Serum AFP
What structures are classically seen on histology where an endodermal sinus tumor is present?
Schiller-Duval bodies (glomerulus-like structures
Malignant tumor composed of cytotrophoblasts and syncytiotrophoblasts mimicking placental tissue and does NOT response well to chemotherapy…
Choriocarcinoma→ small hemorrhagic tumor with early hematogenous spread
What substance is elevated in the presence of a Choriocarcinoma and what can this lead to?
Elevated B-hCG—produced by the syncytiotrophoblasts, which may lead to thecal cysts in the ovary
Sex cord-stromal granulosa-theca cell tumors will often present with signs of estrogen excess, why and what will this cause for pre-puberty, reproductive age, and postmenopausal women.
These tumors often produce estrogen
Pre-puberty→ precocious puberty
Reproductive age→ menorrhagia or metrorrhagia
Post menopausal (most common)→ endometrial hyperplasia with postmenopausal uterine bleeding
What sex cord-stromal tumor can produce androgen, which can lead to hirsutism and virilization in women?
Sertoli-Leydig cell tumor
What sex cord-stromal tumor is characterized by Reinke crystals?
Sertoli-Leydig cell tumor
A benign tumor of fibroblasts…
Fibroma
Meigs syndrome is associated with a fibroma. What is Meigs syndrome?
Pleural effusions and ascites
Metastatic mucinous tumor involving both ovaries→ commonly due to metastatic gastric carcinoma…
Krukenberg tumor→ usually seen bilaterally—which helps distinguish it from primary mucinous carcinoma of the ovary (seen unilaterally)
What helps distinguish a Krukenberg tumor of the ovaries from a primary mucinous carcinoma of the ovary?
Krukenberg tumor of the ovaries is bilateral
Primary mucinous carcinoma of the ovary is unilateral
Large amount of mucus in the peritoneum caused by a mucinous tumor of the appendix…
Pseudomyxoma
Implantation of fertilized ovum at a site other than the uterine wall…
Ectopic Pregnancy
Where is the most common site for an ectopic pregnancy to occur?
Lumen of the fallopian tube
What is the classic presentation of an ectopic pregnancy?
Lower quadrant abdominal pain occurring a few weeks after a missed period
A miscarriage occurring before 20 weeks gestation…
Spontaneous abortion
A women who is 14 weeks pregnant presents to her OB/GYN with vaginal bleeding, crampy pain and spotting. What is the most likely complication that occurred?
Spontaneous abortion
What are some common causes of a spontaneous abortion?
Chromosomal anomalies (especially trisomy 16)
Hypercoagulable states
Congenital infection
Exposure to teratogens
Name the teratogen that is the most common cause of mental retardation…
Alcohol
Name the teratogen that can lead to facial abnormalities and microcephaly…
Alcohol
Name the teratogen that can lead to IUGR and placental abruption…
Cocaine
Name the teratogen that an lead to limb defects…
Thalidomide
Name the teratogen that can lead to IUGR…
Cigarette smoke
Name the teratogen that can lead to a spontaneous abortion…
Isotretinoin
Name the teratogen that can lead to hearing and visual impairment…
Isotretinoin
Name the teratogen that can lead to discolored teeth…
Tetracycline
Name the teratogen that can lead to fetal bleeding…
Warfarin
Name the teratogen that can lead to digit hypoplasia and cleft lip/palate…
Phenytoin
Implantation of the placenta in the lower uterine segment overlying the cervical os…
Placenta previa—presents as 3rd trimester bleeding and often requires c-section
Separation of the placenta form the decidua prior to delivery…
Placental abruption—3rd trimester bleeding and fetal insufficiency
Implantation of the placenta into the myometrium with little or no intervening decidua presenting with difficult delivery of the placenta…
Placenta accreta
Pregnancy-induced HTN, proteinuria and edema…
Preeclampsia
Fibrinoid necrosis occurs due to the HTN
What is the cause of preeclampsia?
Abnormality of the maternal-fetal vascular interface in the placenta
What signals the beginning of eclampsia?
Seizures
What is HELLP syndrome?
HELLP is preeclampsia with thrombotic microangiopathy involving the liver
Hemolysis/Elevated Liver enzymes/Low Platelets
Death of a healthy infant 1 month→1 year old…
Sudden Infant Death Syndrome
What are risk factors for SIDS (Sudden Infant Death Syndrome)?
Sleeping on stomach
Exposure to cigarette smoke
Prematurity
Swollen and edematous villi with proliferation of trophoblasts seen during an abnormal pregnancy…
Hydatidiform mole
A normal ovum fertilized by two sperm creates what type of molar pregnancy and how many chromosomes are present?
Partial—has 69 chromosomes
An empty ovum fertilized by two sperm creates what type of molar pregnancy and how many chromosomes are present?
Complete—has 46 chromosomes
In what type of molar pregnancy in fetal tissue present? Absent?
Partial→ present
Complete→ absent
Describe the villous edema in a partial mole pregnancy…
Some villi are hydropic and some are normal
Describe the villous edema in a complete mole pregnancy…
Most villi are hydropic
What are the risks of developing choriocarcinoma from a partial mole pregnancy and a complete mole pregnancy?
Partial—minimal
Complete—2-3%
What two aspects of a pregnancy are abnormal when a molar pregnancy occurs?
Uterus is much larger
B-hCG is much higher than expected for date of gestation
A patient with a molar pregnancy who has had no prenatal care will usually present…
In second trimester after passage of a grape-like mass through the vaginal canal
A patient with a molar pregnancy who has had prenatal care will usually present…
In first trimester for routine ultrasound and fetal heart sounds will be absent and a snowstorm appearance will be seen on ultrasound
What is the treatment for a molar pregnancy?
Suction curettage
Why is B-hCG monitoring important after D&C of molar pregnancy?
Ensure adequate removal
Screen for development of choriocarcinoma
When will choriocarcinomas respond well to chemotherapy and when will they NOT?
When they arise from gestational pathway (molar pregnancy) they respond well to chemo
When they arise from the germ cell pathway they do not respond well