Female Pathology Flashcards
The two most important etiologies of PCOS are _ and _
The two most important etiologies of PCOS are increase in adipose tissue and increased LH
What is the consequence of increased adipose tissue in PCOS?
Increased adipose –> Increased estrogen –> Increased insulin resistance
What is the consequence of high LH in PCOS?
High LH –> disrupts the LH/FSH balance –> anovulation –> cyst formation
PCOS is also associated with an increase in androgen production by _ cells
PCOS is also associated with an increase in androgen production by ovarian theca interna cells
Explain how PCOS causes an increase in the free estrogens and androgens
PCOS is associated with insulin resistance –> this disrupts normal liver function –> decrease in sex hormone binding globulin –> increase in free estrogens and androgens
PCOS is associated with _ levels of estrogen and _ levels of progesterone
PCOS is associated with high estrogen and low progesterone
High estrogen and low progesterone causes _ to occur in PCOS
High estrogen and low progesterone causes endometrial hyperplasia to occur in PCOS
What is the “triad” of PCOS sx?
- Insulin resistance: obesity, acanthosis nigricans
- Increased estrogen, low progesterone: amenorrhea/oligomenorrhea, enlarged ovaries, infertility
- Increased androgens: hirsutism, acne
Though both LH and FSH are elevated in PCOS, (LH/FSH) are highest
Though both LH and FSH are elevated in PCOS, LH levels are highest
PCOS lab findings:
PCOS lab findings:
* High LH (very)
* High FSH
* High estrogen
* High testosterone
PCOS will appear as _ on ultrasound
PCOS will appear as enlarged ovaries with multiple cysts on ultrasound
* “String of pearls”
Hormonal contraceptives are often prescribed in the setting of PCOS for the purpose of _
Hormonal contraceptives are often prescribed in the setting of PCOS for the purpose of establishing estrogen/progesterone balance
* Prevent endometrial hyperplasia due to unopposed estrogen
Weight loss and metformin may be prescribed in the setting of PCOS to _
Weight loss and metformin may be prescribed in the setting of PCOS to decrease adipose tissue
Why is spironolactone used in for PCOS?
Spironolactone can be used as a steroid receptor antagonist –> androgen blocking effects
Finasteride inhibits _ which decreases the conversion of testosterone to DHT
Finasteride inhibits 5-alpha-reductase which decreases the conversion of testosterone to DHT
Letrozole is used for PCOS because it blocks the conversion of _ to _
Letrozole is used for PCOS because it blocks the conversion of androstenedione to estrone
Flutamide works as a _ and can be used in PCOS
Flutamide works as a androgen receptor antagonist and can be used in PCOS
* Can treat hirsutism
_ is a drug that promotes ovulation and may be used in the setting of PCOS
Clomiphene is a drug that promotes ovulation and may be used in the setting of PCOS
* Selective estrogen receptor modulator
Adenomyosis is _
Adenomyosis is hyperplasia of the endometrial basalis layer
The endometrium is composed of two “layers” the _ and the _
The endometrium is composed of two “layers” the stratum basalis and the stratum functionalis
Adenomyosis occurs when there is hyperplasia of the basalis layer that leads to invasion of endometrial tissue into the _
Adenomyosis occurs when there is hyperplasia of the basalis layer that leads to invasion of endometrial tissue into the myometrium
Adenomyosis is most likely to occur in women who have high _ levels
Adenomyosis is most likely to occur in women who have high estrogen levels
* Ex: PCOS, hormone replacement therapy, ovarian producing tumors
* Women aged 30-50
Describe the uterus in adenomyosis
Describe the uterus in adenomyosis:
soft, boggy, uniformly enlarged globular uterus
* May or may not present with tenderness
Adenomyosis may present with _ (painful periods) or _ (heavy or prolonged bleeding)
Adenomyosis may present with dysmenorrhea (painful periods) or menorrhagia (heavy or prolonged bleeding)
Adenomyosis can be treated with medication like _ or hysterectomy
Adenomyosis can be treated with medication like GnRH agonists (leuprolide) or hysterectomy
When high levels of estrogen cause enlargement of the endometrial glandular tissue we call this _
When high levels of estrogen cause enlargement of the endometrial glandular tissue we call this endometrial hyperplasia
* Increased estrogen relative to progesterone
* More common after menopause
* Causes AUB
* Diagnose with US and endometrial biopsy
What are the etiologies of endometrial hyperplasia?
Endometrial hyperplasia is caused by high-estrogen states:
* PCOS
* Estrogen supplementation
* Nulliparity
* Late menopause
* Estrogen producing tumors
Endometrial hyperplasia may present as _
Endometrial hyperplasia may present as abnormal uterine bleeding or post menopausal bleeding
Endometrial hyperplasia can be identified as _ on histology
Endometrial hyperplasia can be identified as proliferation of glandular cells with atypical cells showing extensive loss of cell polarity
Endometrial hyperplasia can be medically managed with _ or hysterectomy if evidence of cellular atypia on biopsy
Endometrial hyperplasia can be medically managed with progesterone (progestin) supplementation or hysterectomy if evidence of cellular atypia on biopsy
* The idea behind giving progesterone is to improve hormone balance
Asherman syndrome is _
Asherman syndrome is failure of the endometrium to regenerate following uterine trauma
Explain the pathogenesis of Asherman syndrome
Uterine trauma –> destruction of the endometrial basalis layer –> adhesions/fibrosis –> failure of endometrial regeneration
Asherman syndrome may present as _
Asherman syndrome may present as amenorrhea, infertility, abnormal uterine bleeding, pelvic pain, recurrent pregnancy loss
The deepest layer of the endometrium is the _ , the more superficial layer of the endometrium before the myometrium is the _
The deepest layer of the endometrium is the stratum functionalis (gets shed) , the more superficial layer of the endometrium before the myometrium is the stratum basalis (regenerates)
Endometriosis is _
Endometriosis is extrauterine endometrial tissue
Overall the most common location for endometriosis is _ ; others include:
Overall the most common location for endometriosis is the ovaries ; others include: uterosacral ligaments, rectouterine pouch peritoneum
A predominant theory for the etiology of endometriosis is _
A predominant theory for the etiology of endometriosis is retrograde blood/ lymphatic flow
Endometriosis may present with _ (painful periods), _ (pain with sex), _ (difficulty pooping), and cyclic pelvic pain
Endometriosis may present with dysmenorrhea (painful periods), dyspareunia (pain with sex), dyschezia (difficulty pooping), and cyclic pelvic pain
* Can also cause infertility, abnormal uterine bleeding
Endometriosis can be visualized on ultrasound and may show a normal sized retroverted uterus with _
Endometriosis can be visualized on ultrasound and may show a normal sized retroverted uterus with nodular adnexa
Surgical pathology may reveal _ lesions of the peritoneum from endometriosis
Surgical pathology may reveal yellow-brown “powder burn” lesions of the peritoneum from endometriosis
Cystic, fluid filled lesions may result from endometriosis; we call this _
Cystic, fluid filled lesions may result from endometriosis; we call this endometrioma
Blood filled “chocolate cysts” on the ovaries is indicative of _
Blood filled “chocolate cysts” on the ovaries is indicative of endometrioma (endometriosis)
How do we manage endometriosis?
How do we manage endometriosis?
* NSAIDs (pain control)
* OCPs (inhibit LH surge –> decrease hormone fluctuation)
* GnRH agonists ie leuprolide (decrease LH/FSH)
* Progestins (suppress growth and implantation of ectopic endometrium)
* Danazol (inhibit LH/FSH surge)
* Surgical removal
Endometritis is _
Endometritis is inflammation/ infection of the endometrial lining from retained uterine contents
* Often occurs postpartum, after miscarriage, abortion, IUD, multiple cervical exams
Endometritis may present with:
Endometritis may present with:
* Fever, vaginal discharge, abdominal pain, uterine tenderness, foul smelling lochia (postpartum discharge)
Complications of endometritis include:
Complications of endometritis include: sepsis, surgical site infection, peritonitis
Acute endometritis is often caused by _ (pathogen)
Acute endometritis is often caused by group B streptococcus
Chronic endometritis is often caused by growth of _ or _
Chronic endometritis is often caused by growth of N. gonorrhoeae or A. israelii
* Also caused by chlamydia, IUD, TB
Endometriosis is the presence of estrogen-sensitive _ and _ outside of the uterine corpus
Endometriosis is the presence of estrogen-sensitive glands and stroma outside of the uterine corpus
* It responds to physiologic estrogen and continues to grow and bleed resulting in chronic inflammatory disorder
How does endometriosis present clinically?
Endometriosis may present with:
* Adnexal mass
* Infertility
* Dysmenorrhea
* Dyspareunia
* Dyschezia
* Chronic pelvic pain
Endometritis can be diagnosed via:
- Clinical suspicion: pelvic pain, fever
- Blood cultures
- Endometrial biopsy: inflammatory cells in the endometrium
On endometrial biopsy, acute endometritis will reveal _ cells
On endometrial biopsy, acute endometritis will reveal neutrophils
On endometrial biopsy, chronic endometritis will reveal _ cells
On endometrial biopsy, chronic endometritis will reveal plasma cells
Endometrial hyperplasia has a risk for progression to _
Endometrial hyperplasia has a risk for progression to endometrial cancer
Endometrial hyperplasia is associated with a gland: stroma ratio _
Endometrial hyperplasia is associated with a gland: stroma ratio > 1:1
The most common benign tumor of the urogenital tract is _
The most common benign tumor of the urogenital tract is leiomyoma
* Most common in premenopausal patients
Leiomyomas may present with:
Leiomyomas may present with:
* Abnormal menstruation
* Mass effect
* Urinary tract symptoms
* Infertility
Medical management of leiomyomas:
A benign “well circumscribed white tan firm mass with whorled appearance” describes _
A benign “well circumscribed white tan firm mass with whorled appearance” describes leiomyomas
Microscopically, leiomyomas have bland smooth muscle arranged in bundles with _ nuclei
Microscopically, leiomyomas have bland smooth muscle arranged in bundles with cigar-shaped nuclei
_ is the most common cancer of the female reproductive tract
Endometrial cancer is the most common cancer of the female reproductive tract
* 75% of cases are postmenopausal patients
Risk factors for endometrial cancer involve _
Risk factors for endometrial cancer involve chronic estrogen exposure
* Early menarche
* Late menopause
* Estrogen replacement therapy without compensatory progesterone
* Obesity
* Nulliparity
75% of endometrial cancers are type 1 which are _
75% of endometrial cancers are type 1 which are endometrioid adenocarcinomas
(Type 1/ Type 2) endometrial cancer is well-differentiated with favorable prognosis and often caught at a lower stage
Type 1 endometrial cancer is well-differentiated with favorable prognosis and often caught at a lower stage
Type 1 endometrial cancers are often caused by unopposed estrogen and mutations in _ or _ tumor suppressor genes
Type 1 endometrial cancers are often caused by unopposed estrogen and mutations in PTEN or KRAS tumor suppressor genes
The most common Type 2 endometrial cancers are _ and _
The most common Type 2 endometrial cancers are serous and clear cell
* Type 2 only make up 20% of all endometrial cancers
Type 2 endometrial cancers are more aggressive, higher stage/grade and associated with _ mutations
Type 2 endometrial cancers are more aggressive, higher stage/grade and associated with TP53 mutations
(Leiomyosarcoma/ Leiomyoma) is more common in post-menopausal women
Leiomyosarcoma is more common in post-menopausal women
Risk factors of cervical cancer:
Risk factors of cervical cancer:
* HPV infection
* Diethystillbestrol (DES) exposure
* Smoking
* Immunocompromised state
Pap screening allows detection of dysplasia before progression to cancer
How are abnormal cells on pap test graded?
ASCUS: atypical squamous cells of undetermined significance
LSIL: low-grade squamous intraepithelial lesion
HSIL: high-grade squamous intraepithelial lesion
HPV high risk testing is screening for subtypes _ and _
HPV high risk testing is screening for subtypes 16,18
* Both of these make E6 and E7 gene products
E6 inhibits _
E7 inhibits _
E6 inhibits TP53
E7 inhibits pRb
High-grade squamous intraepithelial lesion (HSIL) has _ abnormalities due to increased DNA from HPV integration
High-grade squamous intraepithelial lesion (HSIL) has high nuclear to cytoplasm ratios abnormalities due to increased DNA from HPV integration
The vaccine used in the US to protect against HPV is _
The vaccine used in the US to protect against HPV is Gardasil 9
* HPV 6, 11, 16, 18, 31, 33, 45, 52, 58
LEEP procedure is _
LEEP procedure is loop electrosurgical excision procedure
* This is a local procedure
Follicular cysts are common ovarian cysts which arise from _ cells
Follicular cysts are common ovarian cysts which arise from sex cord/stromal cells (ie the granulosa/theca cells)
* Most common type
* Unruptured follicle
Epithelial cysts are ovarian cysts that arise from the _
Epithelial cysts are ovarian cysts that arise from the surface epithelium
_ cysts are caused by large amounts of hCG
Theca lutein cysts are caused by large amounts of hCG
* Cyst wall is composed of luteinized theca cells (no granulosa cells)
* Elevated androgen levels
* Tend to be bilateral
Neoplastic cysts are malignant or benign ovarian tumors most commonly of _ origin
Neoplastic cysts are malignant or benign ovarian tumors most commonly of surface epithelial origin
Corpus luteum cyst
Epithelial ovarian cyst
_ is a benign cystic ovarian epithelial neoplasm with smooth external surface
Cystadenoma is a benign cystic ovarian epithelial neoplasm with smooth external surface
* The most common ovarian neoplasm in all ages
Cancer antigen marker _ is used in postmenopausal patients to evaluate for ovarian cancer (recurrence)
Cancer antigen marker CA-125 is used in postmenopausal patients to evaluate for ovarian cancer (recurrence)
PCOS is defined as having at least 2/3 of the following:
PCOS is defined as having at least 2/3 of the following:
1. Polycystic ovaries (follicular cysts)
2. Irregular menstruation/ infertility
3. Elevated androgen levels
PCOS pathophysiology
Ovarian cancer may present with non-specific symptoms like:
Ovarian cancer may present with non-specific symptoms like:
* Constipation
* Abdominal/pelvic pain
* Bloating
Three categories/ “layers” of ovarian tumors:
Three categories/ “layers” of ovarian tumors:
1. Epithelial
2. Sex cord stromal
3. Germ cell
The vast majority (95%) of ovarian neoplasms are of _ origin
The vast majority (95%) of ovarian neoplasms are of epithelial origin
_ is the most common histological subtype of epithelial neoplasms
Serous is the most common histological subtype of epithelial neoplasms
Serous carcinoma is associated with _ gene mutations
Serous carcinoma is associated with TP53, BRCA1, BRCA2
Benign ovarian epithelial tumors are called _
Malignant tumors are called _
Benign ovarian epithelial tumors are called cystadenoma
Malignant tumors are called cystadenocarcinoma
Serous (ovarian epithelial) tumors are characterized by _
Serous (ovarian epithelial) tumors are characterized by secretion of thin serous fluid and CA-125
Serous cystadenocarcinoma
Mucinous (ovarian epithelial) tumors are characterized by _
Mucinous (ovarian epithelial) tumors are characterized by thick mucus and secretion of carcinoembryonic antigen (CEA)
Mucinous ovarian tumor
Clear cell carcinoma
* Almost always malignant
Sex cord tumors come from _ cells
Sex cord tumors come from granulosa cells
Stromal tumors come from _ cells
Stromal tumors come from fibroblasts and theca cells
(Fibromas/thecomas) produce estrogen
Thecomas produce estrogen
* Thecomas are a benign sex cord stromal tumor in postmenopausal women
Meigs syndrome (3) elements
Meigs syndrome (3):
1. Ovarian fibroma
2. Ascites
3. Pleural effusion
Granulosa cell tumors are malignant and will overproduce _ and _
Granulosa cell tumors are malignant and will overproduce estrogen and inhibin
* Postmenopausal bleeding in women in 50s
Sertoli-leydig tumors secrete _
Sertoli-leydig tumors secrete testosterone –> abrupt and rapid virulization
Germ cell tumors arise from cells that make up the _
Germ cell tumors arise from cells that make up the ovum
* Teratomas
* Dysgerminomas
* Yolk sac tumors
* Choriocarcinomas
_ is a germ cell tumor that occurs most often in adolescent patients, increases serum LDH, and has fried egg appearance on histology
Dysgerminoma is a germ cell tumor that occurs most often in adolescent patients, increases serum LDH, and has fried egg appearance on histology
Yolk sac tumors secrete _ and are characterized by _ bodies on histology
Yolk sac tumors secrete alpha-fetoprotein and are characterized by Schiller-Duval bodies on histology
Teratoma
(Mature/Immature) teratomas are benign
Mature teratomas are benign –> called “dermoid cyst”
* Immature are malignant
Teratomas are _
Teratomas are differentiated cells of one or more 3 germ layers
* Endoderm, mesoderm, ectoderm
_ is a mature cystic teratoma that contains predominantly thyroid tissue
Struma ovarii is a mature cystic teratoma that contains predominantly thyroid tissue –> hyperthyroidism
The most common immature tissue in an immature (malignant teratoma) is _
The most common immature tissue in an immature (malignant teratoma) is neural
An enlarged, asymmetric, nontender uterus in the setting of abnormal uterine bleeding is indicative of _
An enlarged, asymmetric, nontender uterus in the setting of abnormal uterine bleeding is indicative of leiomyoma (fibroid)
* Females aged 20-40
* Multiple discrete tumors with “whorled well-demarcated smooth muscle bundles”
Prolonged estrogen exposure leading to discrete collection of benign endometrial tissue describes _
Prolonged estrogen exposure leading to discrete collection of benign endometrial tissue describes endometrial (uterine) polyps
* Most common in post-menopausal women with history of estrogen exposure
Explain the pathophysiology of endometrial polyps
High estrogen –> increased growth of the uterine myometrium –> benign smooth muscle tumor
_ is a malignant neoplasm of the myometrium which presents as a single tumor with areas of necrosis
Leiomyosarcoma is a malignant neoplasm of the myometrium which presents as a single tumor with areas of necrosis
Endometrial carcinoma can be distinguished into two histological subtypes _ and _
Endometrial carcinoma can be distinguished into two histological subtypes endometriod type and serous type
Endometrial atrophy that undergoes transformation describes (endometrioid/serous) type endometrial carcinoma
Endometrial atrophy that undergoes transformation describes serous type endometrial carcinoma
Histology of serous type endometrial carcinoma will show _
Histology of serous type endometrial carcinoma will show papillae, tufts +/- psammoma bodies
Endometrioid type endometrial carcinoma is caused by unopposed estrogen + loss of _
Endometrioid type endometrial carcinoma is caused by unopposed estrogen + loss of PTEN/ mismatch repair protein
* Histology will show abnormally arranged endometrial cells
Overaggressive dilation and curettage (D&C) can cause loss of the basalis layer leading to secondary amenorrhea called _ syndrome
Overaggressive dilation and curettage (D&C) can cause loss of the basalis layer leading to secondary amenorrhea called Asherman syndrome
Tamoxifen can cause endometrial polyps due to its _ effects on the endometrium
Tamoxifen can cause endometrial polyps due to its pro-estrogenic effects on the endometrium
* Tamoxifen treats breast cancer due to its anti-estrogenic effects on the breast, however, it has pro-estrogenic effects on the endometrium
Endometriosis carries an increased risk of carcinoma, especially in _ site
Endometriosis carries an increased risk of carcinoma, especially in ovaries
* Ovaries are the most common site of involvement
The most important predictor for progression of endometrial hyperplasia to carcinoma is _
The most important predictor for progression of endometrial hyperplasia to carcinoma is presence of cellular atypia
The most common invasive carcinoma of the female genital tract is _
The most common invasive carcinoma of the female genital tract is endometrial carcinoma
Endometrial carcinoma arises via two different pathways _ and _
Endometrial carcinoma arises via two different pathways hyperplasia and sporatic
* 75% of the time it is the hyperplasia pathway
Endometrial hyperplasia –> endometrial carcinoma will normally have _ histology
Endometrial hyperplasia –> endometrial carcinoma will normally have endometrioid histology
In the sporatic pathway, endometrial carcinoma arises in an atrophic endometrium with no precursor lesions; histology will be _
In the sporatic pathway, endometrial carcinoma arises in an atrophic endometrium with no precursor lesions; histology will be serous
* Characterized by papillary structures
Serous endometrial carcinoma is often associated with _ mutations
Serous endometrial carcinoma is often associated with p53 mutations
Increased LH in PCOS induces excess androgen production, resulting in _
Increased LH in PCOS induces excess androgen production, resulting in hirsutism
The most common type of ovarian tumor is a _
The most common type of ovarian tumor is a surface epithelial tumor
The two most common type of surface epithelial tumors are _ and _
The two most common type of surface epithelial tumors are serous and mucinous
* Can be benign or malignant
* Less common subtypes are endometrioid and brenner
_ are surface epithelial ovarian tumors composed of bladder-like epithelium and are usually benign
Brenner tumors are surface epithelial ovarian tumors composed of bladder-like epithelium and are usually benign
* Coffee bean nuclei
Epithelial ovarian carcinomas tend to be aggressive and spread locally, especially to the _
Epithelial ovarian carcinomas tend to be aggressive and spread locally, especially to the peritoneum
_ is a germ cell tumor that mimics fetal tissue
Teratoma is a germ cell tumor that mimics fetal tissue
* Often benign but can contain immature tissue (neural) or somatic malignancy (squamous cell carcinoma of skin) –> malignant
The female equivalent of a seminoma is a _
The female equivalent of a seminoma is a dysgerminoma
* Most common malignant germ cell tumor in adolescents
_ is a tumor composed of large cells with clear cytoplasm and central nuclei that resemble oocytes
Dysgerminoma is a tumor composed of large cells with clear cytoplasm and central nuclei (“fried egg”) that resemble oocytes
* May have increased LDH levels
_ is a germ cell tumor that mimics the yolk sac and is most common form in children
Endodermal sinus tumor is a germ cell tumor that mimics the yolk sac and is most common form in children
Yolk sac tumors will often have elevated _
Yolk sac tumors will often have elevated serum AFP
Yolk sac tumors classically show glomerulus-like structures called _ on histology
Yolk sac tumors classically show glomerulus-like structures called Schiller-Duval bodies on histology
_ is a malignant tumor composed of cytotrophoblasts and syncytiotrophoblasts that mimics placental tissue
Choriocarcinoma is a malignant tumor composed of cytotrophoblasts and syncytiotrophoblasts that mimics placental tissue
* Vili are absent
Choriocarcinomas are often associated with high _ levels
Choriocarcinomas are often associated with high beta-hcg levels
Name three types of sex cord-stromal tumors that can occur in females:
Name three types of sex cord-stromal tumors that can occur in females:
1. Granulosa-theca cell tumor
2. Sertoli-Leydig cell tumor
3. Fibroma
Granulosa-theca cell tumors cause high _ levels and will have a presentation consistent with this
Granulosa-theca cell tumors cause high estrogen levels and will have a presentation consistent with this
* Prior to puberty- precocious puberty
* Reproductive age- menorrhagia
* Postmenopause- endometrial hyperplasia + AUB
Sertoli-Leydig cell tumors in a female may result in _
Sertoli-Leydig cell tumors in a female may result in excess androgen, hirsutism, virilization
A _ is a benign tumor of fibroblasts
A fibroma is a benign tumor of fibroblasts
* Type of sex cord-stromal tumor
* “Bundles of spindle-shaped fibroblasts”
Fibromas are associated with _ and _ ; this is called Meigs syndrome
Fibromas are associated with pleural effusions and ascites; this is called Meigs syndrome
Theca-lutein cysts are associated with _ malignancy
Theca-lutein cysts are associated with choriocarcinoma
Dysgerminoma tumors markers are _ and _
Dysgerminoma tumors markers are hCG and LDH
Call-Exner bodies may be seen in _ sex cord stromal tumors
Call-Exner bodies may be seen in granulosa cell tumors
