GU Flashcards
What is the vulva?
the skin and mucosa of the female genitalia external to the hymen, including the labia major, labia minor, mons pubis, and vestibule
The vulva is lined by what sort of epithelium?
squamous
Bartholin Cyst
- a dilation of the Bartholin gland
- arises as a unilateral, painful cystic lesion at the lower vestibule adjacent to the vaginal canal
- forms due to obstruction and inflammation
- most often in women of reproductive age
What are the Bartholin glands?
two glands, one present on each side of the vaginal canal, which produce a mucus-like fluid for lubrication
Condyloma
- a warty, often large, neoplasm of the vulvar skin
- most commonly due to HPV 6/11 or secondary syphilis
- histology is characterized by koilocytes
- rarely progress to carcinoma
What are the low risk types of HPV? What are the high risk types?
- low risk: those with low malignant potential, including 6 and 11
- high risk: those likely to progress to carcinoma, including 16, 18, 31, and 33
What is koilocytic change?
- a change in the cell morphology of HPV infected cells
- the nucleus takes on a wavy, raisin like shape
Lichen Sclerosis
- a thinning of the epidermis and fibrosis of the dermis of the vulvar skin
- presents as a leukoplakia (white patch), with “parchment-like” skin
- most common in post-menopausal women
- carries some degree of risk for squamous cell carcinoma (more than Lichen simplex chronicus)
Lichen Simplex Chronicus
- a hyperplasia of the vulvar squamous epithelium
- presents as a leukoplakia with thick, leathery skin
- associated with chronic irritation and scratchy
- benign and with no risk for squamous cell carcinoma
How does Lichen Sclerosis compare to Lichen Simplex Chronicus?
- Lichen Sclerosis is a thinning of the epidermis and fibrosis of the dermis that results in thinning of the skin and carries a risk for squamous cell carcinoma
- Lichen Simplex Chronicus is a hyperplastic thickening of the skin that poses no risk for carcinoma
Vulvar Carcinoma
- a carcinoma arising from the squamous epithelium lining the vulva
- presents as a leukoplakia and requires biopsy for diagnosis
- may be HPV or non-HPV related:
- HPV related is seen more often in young women with risk factors for HPV exposure and the carcinoma arises from pre-existing vulvar intraepithelial neoplasia, a dysplastic precursor lesion with koilocytic change
- non-HPV related is more often found in older women (>70) and arises from long-standing lichen sclerosis
What are two pathways for the development of vulvar carcinoma?
- HPV related: seen in younger women following vulvar intraepithelial neoplasia
- non-HPV related: seen in older women following long-standing lichen sclerosis
Extramammary Paget Disease
- the presence of malignant epithelial cells in the epidermis of the vulva
- it represents carcinoma in situ without underlying carcinoma (in contrast to Paget’s disease of the nipple , which is almost always associated with an underlying carcinoma)
- it presents as erythematous, pruritic, ulcerated vulvar skin
- must be distinguished from melanoma: Paget disease will be PAS+, keratin+ and S-100- while melanoma is keratin- and S-100+
How does Extramammary Paget disease differ from Paget disease of the nipple?
- extramammary Paget disease represents carcinoma in situ, usually without underlying carcinoma
- however, Paget disease of the nipple is almost always associated with an underlying carcinoma
What must extramammary Paget disease be differentiated from? How is this done?
- must be differentiated from melanoma
- Paget disease is keratin+ and S-100-
- melanoma is keratin- and S-100+
The vaginal mucosa is lined by what sort of epithelium?
non-keratinizing, stratified squamous epithelium
Adenosis
- a focal persistence of columnar epithelium in the upper vagina (the epithelium that was present during embryonic development from the Mullerian tubes but should have been resorbed)
- seen in females exposed to DES (diethylstilbestrol) in utero
- poses a risk for clear cell adenocarcinoma
What is diethylstilbestrol?
an estrogenic compound no longer used because it increased the risk of breast cancer in pregnant mothers and the risk for adenosis and clear cell adenocarcinoma in females exposed in utero
Clear Cell Adenocarcinoma
- a malignant proliferation of glands with clear cytoplasm
- a complication of DES-associated vaginal adenosis
Embryonal Rhabdomyosarcoma
- a malignant proliferation of immature skeletal muscle also known as sarcoma botryoides
- presents as bleeding and a grape-like mass protruding from the vagina or penis of a child (<5)
- rhabdomyoblasts are the characteristic cell and they exhibit cytoplasmic cross-striations as well as positive immunohistochemistry for desmin and myogenin
Which tumor presents as a grape-like mass protruding from the vagina or penis of a child?
embryonal rhabdomyosarcoma, consisting of rhabdomyoblasts
Vaginal Carcinoma
- a carcinoma arising from the squamous epithelium of the vaginal mucosa
- related to high-risk HPV (16,18, 31, 33)
- develops from a precursor, dysplastic lesion known as vaginal intraepithelial neoplasia
- in the lower ⅓ of the vagina, it spreads to the inguinal nodes, and in the upper ⅔, it spreads to the iliac nodes
To which lymph nodes does the vagina drain?
- lower ⅓ drains to the inguinal nodes
- upper ⅓ drains to the iliac nodes
What sort of epithelium lines the cervix?
- the exocervix is lined by non-keratinizing squamous epithelium
- the endocervix is lined by a single layer of columnar cells
Where along the female reproductive tract does HPV especially like to infect cells?
the transformation zone of the cervix
What happens in most cases of HPV infection?
the infection is resolved by acute inflammation
How is HPV type determined?
DNA sequencing
What makes high risk HPV types more likely to cause CIN and carcinoma?
- they express the E6 and E7 proteins
- E6 increases destruction of the p53 protein, which regulates the G1/S progression based on the presence of DNA damage, calling in repair mechanisms or inducing BAX to inhibit Bcl2 and induce apoptosis
- E7 destroys or inactives the Rb protein, which frees E2F and allows for unrestricted progression from G1/S
What are the functions of the E6 and E7 proteins expressed by high risk HPV?
E6 and E7 destroy or inhibit p53 and Rb proteins, respectively
How are CIN I, II, III and carcinoma in situ defined?
- CIN I involves less than ⅓ of the thickness of the cervical epithelium
- CIN II involves less than ⅔ the thickness
- CIN III involves slightly less than the entire thickness
- CIS involves the entire thickness
- in the progression to each, the chances of reversal diminish
What is the difference between CIN III and carcinoma in situ?
- CIN III involves slightly less than the entire thickness of the cervical epithelium while CIS involves the full thickness
- more importantly, however, is that CIN III may, although rarely, be reversed while CIS is irreversible in all cases
Cervical Carcinoma
- an invasive carcinoma arising from the cervical epithelium
- presents as vaginal bleeding, especially postcoital, or a with a cervical discharge, most often in middle-aged women (40-50)
- key risk factor is high-risk HPV infection, but secondary risk factors include smoking and immunodeficiency
- most common subtypes are squamous cell carcinoma (80%) and adenocarcinoma (15%), which are both related to HPV
- may invade through the anterior uterine wall into the bladder, blocking the ureters and causing hydronephrosis with post renal failure; a common cause of death in these patients
What is the most common type of cervical carcinoma?
squamous cell carcinoma, followed far behind by adenocarcinoma
What is a common cause of death in patients with cervical carcinoma?
invasion of the tumor through the anterior wall of the uterus, blocking the ureters and causing hydronephrosis with post-renal failure
What is the goal of Pap smears?
to catch dysplasia before it develops into carcinoma
The progression from CIN to carcinoma in situ usually takes how long? Why is this important?
10-20 years, making Pap smears an effective screening tool
When does screening begin for cervical carcinoma? How often is it performed?
- Pap smears begin at age 21
- repeated every three years
How do high grade dysplasias present on a pap smear?
the cells have hyperchromatic nuclei and high nuclear to cytoplasmic ratios
What is true about women who develop invasive cervical carcinoma today?
they have not undergone screening
An abnormal Pap smear is followed by what sort of test?
a colposcopy, in which the dysplasia is visualized by a magnifying glass and biopsied
What are the key limitations of the Pap smear?
- can result in false negatives if the transformation zone of the cervix isn’t sampled
- doesn’t appear to be efficacious in screening for adenocarcinoma even though it too is caused by HPV
Which sort of cervical carcinoma are Pap smears largely ineffectual at screening for?
adenocarcinoma
What HPV types does the vaccine cover?
types 6, 11, 16, and 18
Why should those who have received the HPV vaccine still receive Pap smears and monitoring?
because the vaccine only covers four HPV types
Growth of the endometrium is driven by what hormone?
estrogen
What hormonal change leads to shedding of the endometrium during menstruation?
loss of progesterone
Asherman Syndrome
- secondary amenorrhea due to loss of the basalis and scaring
- usually the result of overaggressive dilation and curettage of the uterus
What is the regenerative layer of the endometrium called?
the basalis
Anovulatory Cycle
- a lack of ovulation
- results in an estrogen-drive proliferative phase without a subsequent progesterone-driven secretory phase
- represents a common cause of dysfunctional uterine bleeding, especially during menarche and menopause
Acute Endometritis
- a bacterial infection of the endometrium
- most often associated with retained products of conception after delivery or miscarriage
- presents with fever, uterine bleeding, and pelvic pain
- treat with gentamicin + clindamycin +/- ampicillin
Chronic Endometritis
- chronic inflammation of the endometrium
- defined by the presence of plasma cells in the endometrium (never found there otherwise)
- usually related to retained products of conception, PID, IUD, or TB
- presents as abnormal uterine bleeding, pain, and infertility
Plasma cells in the endometrium are required for the diagnosis of what?
chronic endometritis
Endometrial Polyp
- a hyperplastic protrusion of endometrium
- most often caused by tamoxifen, which has weak pro-estrogenic effects on the endometrium
- presents with abnormal uterine bleeding
Tamoxifen has weak estrogenic effects in what tissue? What side effect does this often give rise to?
- the endometrium
- endometrial polyp
Endometriosis
- the presence of endometrial glands and stroma outside the uterine endometrial lining
- current theory is that it is due to retrograde menstruation
- presents as dysmenorrhea and pelvic pain because it cycles just like normal endometrium
- most commonly involves the ovary and forms a “chocolate cyst”
- may also involve the uterine ligaments (pelvic pain), pouch of Douglas (pain with defecation), bladder wall (pain with urination), bowel serosa (abdominal pain and adhesion), or fallopian tube mucosa (scarring with increases risk for ectopic tubal pregnancy)
- adenomyosis is endometriosis within the myometrium
- risk for carcinoma at the site of endometriosis
- treat with NSAIDs, OCPs, progestins, GnRH agonists, danazol, or laparoscopic removal
What is a “chocolate cyst”?
- a cyst that forms in the ovary as a result of endometriosis
- fills with products of menstruation and has a chocolatey appearance
What site is most commonly affected by endometriosis?
the ovary
What is adenomyosis?
- endometriosis within the myometrium of the uterus
- treat with a GnRH agonist or hysterectomy
Why does endometriosis contribute to infertility?
because it can involve the Fallopian tubes and induce scarring
Endometrial Hyperplasia
- hyperplasia of the endometrial glands relative to stroma
- most often due to unopposed estrogen
- presents as postmenopausal bleeding
- classified according to its architectural (simple or complex) and whether or not there is cellular atypia
- the presence of atypia is the most important predictor of progression to carcinoma
What is the most significant predictor of whether endometrial hyperplasia will progress to carcinoma?
the presence or absence of cellular atypia
What causes endometrial hyperplasia?
unopposed estrogen
Endometrial Carcinoma
- a malignant proliferation of endometrial glands
- the most common invasive carcinoma of the female reproductive tract
- presents with postmenopausal bleeding
- may arise via either the hyperplastic or sporadic pathways:
- hyperplastic is more common and involves carcinoma arising from pre-existing endometrial hyperplasia; risk is related to estrogen exposure and the histology is endometroid
- sporadic arises in an atrophic endometrium without evidence of a precursor lesion; histology is usually serous and characterized by papillary structures as well as psammoma bodies; p53 mutation is common and these are aggressive tumors
What is the most common invasive carcinoma of the female reproductive tract?
endometrial carcinoma
Name and describe the two different pathways leading to endometrial carcinoma.
- hyperplastic: arising from pre-exisitng endometrial hyperplasia; most often due to unopposed estrogen; endometroid histology
- sporadic: arising from an atrophic endometrium; most often associated with a p53 mutation; histology is serous with papillary structures and psammoma bodies
Leiomyoma
- a benign proliferation of smooth muscle arising from the myometrium
- risk is related to estrogen exposure
- enlarge during pregnancy and shrink after menopause because they are estrogen sensitive
- usually asymptomatic but may lead to uterine bleeding, infertility, and a pelvic mass
- gross exam shows multiple, well-defined, white, whorled masses
What is the most common tumor in females?
leiomyoma
How can a leiomyosarcoma be distinguished form a leiomyoma on gross exam?
- leiomyoma is likely to be in multiple without necrosis or hemorrhage and found in premenopausal women
- leiomyosarcoma is likely to be singular with necrosis and hemorrhage and found in post-menopausal women
Leiomyosarcoma
- a malignant proliferation of smooth muscle arising from the myometrium
- arises de novo, not from leiomyomas
- usually seen in post-menopausal women
- gross exam reveals a single lesion with areas of necrosis and hemorrhage
Describe the basic structure of an ovarian follicle.
an oocyte surrounded by granuloma and theca cells
What is a corpus luteum?
the residual follicle that remains after ovulation, which secretes progesterone to drive the secretory phase
Polycystic Ovarian Disease
- multiple ovarian follicular cysts due to a hormone imbalance as hyperinsulinemia contributes to a rise in LH/FSH, which increases androgens
- androgens contribute to hirsutism, effect negative feedback on the HPO, which decreases the rate of follicular maturation resulting in enraptured follicles and anovulation, and gets converted to estrone (not estradiol) which increases risk for endometrial carcinoma
- presents as an obese young woman with infertility, oligomenorrhea, and hirsutism, often developing type 2 diabetes 10-15 years later; ovaries are bilaterally cystic
- treat with weight reduction, OCPs, clomiphene citrate, ketoconazole, spironolactone
- relatively common, affecting 5% of reproductive age women
Polycystic Ovarian Disease is driven by what?
an increase in LH which leads to excess androgens and estrone but reduces FSH
- androgens produce hirsutism and type 2 diabetes
- estrogen produces oligomenorrhea and risk for endometrial carcinoma
- low FSH produces cystic degeneration of ovarian follicles and infertility
Ovarian tumors arise from what three types of cells?
- surface epithelium
- germ cells
- sex cord stroma (granulosa, theca, fibroblast)
What is the most common type of ovarian tumor?
a tumor arising from surface epithelium
What sort of epithelium covers the ovary?
coelomic epithelium
Coelomic epithelium embryologically produces the epithelial lining of what structures?
- fallopian tube (serous cells)
- endometrium
- endocervix (mucinous cells)
Ovarian Surface Epithelial Tumor
- a tumor arising from the coelomic epithelium overlying the ovary, which normally give rise to the epithelial lining of the fallopian tube, endometrium, and endocervix
- classified as mucinous or serous based on the fluid it contains and as benign (cystadenoma), borderline, or malignant (cystadenocarcinoma)
- cystadenomas are usually a simple cyst with a smooth lining whereas cystadenocarcinomas are complex cysts with shaggy linings
- preset late with vague abdominal symptoms or signs of compression such as urinary frequency and the prognosis is generally poor
- tend to spread locally and produce “omental caking”
- CA-125 is a useful serum marker but not used for screening
How do ovarian cystadenomas compare to cystadenocarcinomas?
- cystadenomas are benign, composed of a single cyst with a simple, flat lining, and are most common in premenopausal women
- cystadenocarcinomas are malignant, composed of complex cysts with a thick, shaggy lining, and most common in postmenopausal women
- both are derived from the surface epithelium of ovaries and can be of the mucinous or serous type
Endometroid Tumor of the Ovary
- a malignant tumor derive from the coelomic epithelium of the ovary
- composed of endometrial-like glands, which sometimes arises form endometriosis
- 15% are associated with a second, independent endometrial carcinoma (of the hyperplastic/endometroid variety)
- preset late with vague abdominal symptoms or signs of compression such as urinary frequency and the prognosis is generally poor
- tend to spread locally and produce “omental caking”
- CA-125 is a useful serum marker but not used for screening
Those with an endometroid tumor of the ovary should be screened for what other condition?
an endometroid carcinoma of the endometrium
Brenner Tumor
- a benign tumor derived from the coelomic epithelium of the ovary composed of bladder-like epithelium
- preset late with vague abdominal symptoms or signs of compression such as urinary frequency
- tend to spread locally and produce “omental caking”
- CA-125 is a useful serum marker but not used for screening
How does the prevalence of the varying types of ovarian cancers change with age? Which age groups are most likely to experience each kind?
- germ cell tumors affect younger women (15-40)
- benign surface epithelial tumors tend to affect middle-aged premenopausal women
- malignant surface epithelial tumors tend to affect older, post-menopausal women
Germ cell tumors generally arise during what age range?
15-40 years of age
Cystic Teratoma
- a cystic tumor composed of fetal tissue derived from two or three embryologic layers
- the most common germ cell tumor in females
- bilateral in 10% of cases
- typically benign; however, the presence of immature tissue or somatic malignancy within the teratoma indicates malignant potential
- may present in females with pain secondary to torsion or enlargement of the ovary
- struma ovarii is a special teratoma that is composed mostly of thyroid tissue and may induce hyperthyroidism
What is the most common type of immature tissue found in a teratoma?
neural ectoderm
What is the most common type of somatic malignancy found in a teratoma?
squamous cell carcinoma of the skin
What is struma ovarii?
a teratoma composed primarily of thyroid tissue, leading to hyperthyroidism
What endocrine dysfunction is most likely to arise in females with a teratoma?
hyperthyroidism if the teratoma represents a struma ovarii
Dysgerminoma of the Ovary
- a germ cell tumor composed of large, clear cells with central nuclei (resembling oocytes)
- the most common malignant germ cell tumor
- has a good prognosis as it responds well to radiotherapy
- serum LDH (lactic acid dehydrogenase) may be elevated
Endodermal Sinus Tumor
- a malignant germ cell tumor seen in men (as a nonseminoma) and women that mimics the yolk sac
- the most common germ cell tumor in children
- serum AFP is often elevated
- histology is likely to reveal Schiller-Duval bodies (glomeruloid-like structures)
What are Schiller-Duval bodies?
glomeruloid-like structures seen on histology of an endodermal sinus tumor
Which germ cell tumor is most common in female children?
endodermal sinus tumor
Choriocarcinoma
- a malignant germ cell tumor composed of cyto- and syncytiotrophoblasts
- mimics placental tissue but villi are absent
- it spreads via the hematogenous route early (makes sense because the usual function of trophoblasts is to establish fetal blood flow) and goes to the lungs
- high B-hCG is characteristic and may lead to theca cysts in the ovary or hyperthyroidism (since the a subunit of B-hCG resembles that of FSH, LH, and TSH)
- in women it can arise as a complication of gestation (following hydatidiform mole, spontaneous abortion, etc.) or as a spontaneous germ cell tumor
- when it arises from the gestational pathway it tends to respond well to chemotherapy; but those that arise spontaneously do not
- in men, it is classified as a nonseminoma
Granulosa-Theca Cell Tumor
- a neoplastic proliferation of granuloma and/or theca cells
- often produces estrogen leading to precocious puberty, menorrhagia/metrorrhagia, or endometrial hyperplasia with postmenopausal bleeding depending on the women’s stage of life
- histology shows Call-Exner bodies (granulosa cells arranged around collections f eosinophilic fluid, resembling primordial follicles)
- malignant but with minimal risk for metastasis
Sertoli-Leydig Cell Tumor of the Ovary
- a sex cord-stromal tumor composed of Sertoli cells that form tubules and Leydig cells
- Leydig cells have characteristic Reinke crystals on histology
- may produce androgens, leading to hirsutism and virilization
Meigs syndrome
- a syndrome of ovarian fibroma, pleural effusions, and ascites
- entire syndrome resolves with removal of the tumor
Krukenberg Tumor
- a bilateral metastatic mucinous tumor of the ovaries
- most often due to metastasis of a diffuse type gastric carcinoma; as such, signet cells are common
- bilateral nature helps distinguish it from a mucinous cystadenocarcinoma
A Krukenberg Tumor must be distinguished form what other ovarian carcinoma? How is this done?
- it is a mucinous tumor from gastric carcinoma
- as such it must be distinguished from a mucinous cystadenocarcinoma of the ovary
- this is accomplished because the Krukenberg tumor is most often bilateral while the primary ovarian carcinoma is unilateral
Pseudomyxoma Peritonei
massive amounts of mucus in the peritoneum due to a mucinous tumor of the appendix, often with metastasis to the ovary
What is the most likely place for an ectopic pregnancy?
the lumen of the fallopian tube
What is the major risk factor for ectopic pregnancy?
scarring secondary to PID or endometriosis
Ectopic pregnancy
- a pregnancy outside the uterine lining
- most often found in the lumen of the fallopian tube
- risk factors include prior ectopic pregnancy, history of infertility, PID (salpingitis), endometriosis, ruptured appendix, or prior tubal surgery
- presents as lower quadrant abdominal pain a few weeks after a missed period and lower-than-expected hCG
- is a surgical emergency as it may rupture or bleed into the Fallopian tube
How do we define a spontaneous abortion?
miscarriage of a fetus occurring before 20 weeks gestation
What percentage of recognized pregnancies end in spontaneous abortion?
about 1/4
Teratogens can have a wide array of effects. How do their affects vary based on the point at gestation at which the exposure occurred?
- if exposure occurs in the first 2 weeks, it usually leads to spontaneous abortion
- between weeks 3-8 it is likely to lead to organ malformation
- after 8 weeks, the most likely outcome is organ hypoplasia
What are the most common causes of spontaneous abortion?
- chromosomal anomalies, especially trisomy 16
- hypercoagulable states as in antiphospholipid syndrome
- congenital infection
- exposure to teratogens in the first two weeks of gestation
Placenta Previa
- implantation of the placenta in the lower uterine segment with the placenta overlying the cervical os
- risk factors include multiparty or prior C-section
- presents as third trimester bleeding
- requires delivery by C-section to avoid compressing the arteries in the placenta during vaginal delivery
Placental Abruption
- separation of the placenta from the decider prior to delivery
- risk factors include trauma, smoking, hypertension, and cocaine abuse
- presents with abrupt pain and third-trimester bleeding (bleeding may be concealed if the separation doesn’t extend to the cervical os)
- may cause DIC, maternal shock, or fetal distress; life threatening to both the mother and fetus
- examination of the placenta after delivery/removal will reveal a very blood maternal surface with lots of clots
Placenta Accreta
- improper implantation of the placenta onto the myometrium with little or no intervening decidua
- risk factors are prior C-section, inflammation, or placenta previa
- presents with difficult delivery of the placenta and postpartum bleeding
- often requires a hysterectomy to control the bleeding
- placenta increta and percreta are varying degrees of penetration
Pre-Eclampsia
- pregnancy-induced hypertension with either proteinuria or end-organ dysfunction after the 20th week gestation
- due to an abnormality of the maternal-fetal vascular interface in the placenta
- usually presents in the third trimester and affects 5% of pregnancies
- more common in those with pre-existing hypertension, diabetes, chronic renal disease, or autoimmune disorders
- may border on malignant hypertension with severe headaches and visual abnormalities
- treatment is with anti-hypertensives and IV magnesium to prevent seizures but definitive treatment is delivery
How does eclampsia compare to pre-eclampsia?
- eclampsia is pre-eclampsia (HTN, proteinuria, edema) plus seizures
- may cause maternal death due to stroke, intracranial hemorrhage, or ARDS
What is HELLP?
- pre-eclampsia with thrombotic microangiopathy of the liver
- characterized by Hemolysis, Elevated Liver enzymes, and Low Platelets
- can lead to hepatic sub capsular hematomas, which may rupture and lead to severe hypotension
Sudden Infant Death Syndrome
- death of a health infant (1 month to 1 year old) without obvious cause, typically during sleep
- associated with sleeping on the stomach, exposure to cigarette smoke, and prematurity
What are the teratogenic effects of cocaine?
intrauterine growth retardation and placental abruption
What are the teratogenic effects of thalidomide?
limb defects
What are the teratogenic effects of cigarette smoke?
intrauterine growth retardation
What are the teratogenic effects of isotretinoin?
spontaneous abortion or hearing and visual impairment
What are the teratogenic effects of tetracycline?
discolored teeth
What are the teratogenic effects of warfarin?
fetal bleeding
What are the teratogenic effects of phenytoin?
digit hypoplasia and cleft lip/palate
Hydatidiform Mole
- an abnormal conception that yields growth of abnormal placental tissue instead of a child
- characterized by swollen, edematous villi with proliferation of trophoblasts
- the uterus expands as if a normal pregnancy but the uterus is much larger and B-hCG much higher than expected
- without prenatal care, it presents in the second trimester as passage of grape-like masses
- with prenatal care, it is diagnosed via routine US since fetal heart sounds are absent and there is a “snowstorm” appearance
- can be classified as complete or partial depending on whether the two sperm fertilized an empty or normal egg
- treatment is suction curettage and subsequent monitoring of B-hCG to ensure adequate removal
- poses a risk for choriocarcinoma and requires monitoring
What sets a partial hydatidiform mole apart from a complete mole?
- partial arises from fertilization of a normal egg by two sperm (69 chromosome)
- some fetal tissue is present (hence the term partial)
- some villi are hydropic and some are normal
- focal proliferation is present around the hydropic villi
- the risk for choriocarcinoma is minimal
What sets a complete hydatidiform mole apart form a partial mole?
- complete arises from fertilization of an empty egg by two sperm (46 chromosome)
- no fetal tissue is present (hence the term complete)
- most villi are hydropic and there is diffuse, circumferential proliferation around hydropic villi
- the risk for choriocarcinoma is 2-3%, which is higher than that of partial
Hypospadias
- an opening of the urethra on the inferior surface of the penis due to failure of the urethral folds to close properly
- associated with inguinal hernia and cryptorchidism
Epispadias
- an opening of the urethra on the superior surface of the penis due to abnormal position of the genital tubercle
- associated with bladder exstrophy
Lymphogranuloma Venereum
- a necrotizing granulomatous inflammation of the inguinal lymphatics and lymph nodes in a male
- results from sexual transmission of Chlamydia trachomatis, serotypes L1-L3
- eventually heals with fibrosis, which may cause rectal stricture if there was perianal involvement
Squamous Cell Carcinoma of the Penis
- a malignant proliferation of squamous cells of the penile skin
- risk factors include those that increase the risk for a high risk HPV as well as lack of circumcision which serves as a nidus for chronic inflammation and irritation
- arises from precursor in situ lesions like Bowen disease or Erythroplasia of Queyrat
Bowen Disease
an in situ carcinoma of the penile shaft or scrotum that presents as leukoplakia and serves as a precursor lesion for squamous cell carcinoma
Erythroplasia of Queyrat
an in situ carcinoma of the penile glands that presents as erythroplaki and serves as a precursor lesion for squamous cell carcinoma
Bowenoid Papulosis
- an in situ carcinoma of the penile skin that presents as multiple reddish papule
- seen in younger patients than Bowen disease or Erythroplasia of Queyrat
- does not progress to invasive carcinoma
What is the difference between Bowen disease, Erythroplasia of Queyrat, and Bowenoid Papulosis.
- all are forms of in situ carcinoma involving the skin of the penis, but only Bowen disease and erythroplasia progress to squamous cell carcinoma
- Bowen disease is a leukoplakia of the shaft
- Erythroplasia of Queyrat is a erythroplakia of the glands
- Bowenoid papulosis is presents as multiple reddish papules
Cryptochidism
- failure of the testicle to descend into the scrotal sac after developing in the abdomen
- it is the most common congenital male reproductive anomaly and is more common in premature infants
- most cases resolve spontaneously, but if it hasn’t by age 2 it requires surgical correction
- after age 2, germ cells begin to be damaged by the lack of proper thermoregulation resulting in testicular atrophy with infertility and risk for seminoma
What happens if cryptochidism doesn’t resolve and isn’t corrected by age 2?
- germ cells are damaged by the lack of proper thermoregulation
- results in testicular atrophy with infertility
- also increases the risk for seminoma
What are the four most common causes of orchitis?
- Chlamydia or Neisseria in younger males (via sexual activity)
- E. coli and Pseudomonas in older adults (spread of UTI)
- mumps virus
- autoimmune orchitis
Chlamydia trachomatis Orchitis
- an inflammation of the testicle due to infection with serotypes D-K
- seen primarily in young adults with highest STD risk
- may cause sterility but libido is unaffected because Leydig cells are spared
Which cell type is affected by Chlamydia trachomatis and Neisseria gonorrhoea orchitis?
- Sertoli cells are affected, potentially causing sterility
- Leydig cells are spared, leaving testosterone and libido in tact
Mumps Virus Orchitis
- a potential complication of mumps virus usually only seen in those that contract mumps after the age of ten
- risk for infertility
Autoimmune Orchitis
granulomatous inflammation of the testicles involving the seminiferous tubules
Testicular Torsion
- a twisting of the spermatic cord
- causes the thin-walled veins to collapse while the arteries remain open, resulting in congestion and hemorrhage infarction
- usually due to congenital failure of the testes to attach to the inner lining of the scrotum via the processes vaginalis
- presents in adolescents with sudden testicular pain and an absent cremasteric reflex
Describe the cremasteric reflex.
when you scrap upward on the inner thigh of a male, the scrotum should ascend
Varicocele
- a dilation of the spermatic vein due to impaired drainage
- usually left sided because the left vein drains into the left renal vein while the right vein drains directly into the IVC
- presents as a “bag of worms” appearance upon standing examination and will not be transilluminated
- seen in a large percentage of infertile males because it leaves lots of warm blood in the sac for longer periods
Varicoceles are associated with what neoplasia?
left renal cell carcinoma, which tends to invade and obstruct the left renal vein, impairing drainage of the left spermatic vein
Hydrocele
- a collection of fluid within the tunica vaginalis (a serous membrane covering the testicle and internal surface of the scrotum)
- when it presents in infants, it is often associated with incomplete closure of the processus vaginalis, leaving communication between the scrotum and peritoneal cavity
- in adults, it is more often associated with blocked lymphatic drainage
- presents as a scrotal swelling that can be transilluminated
What does a testicular mass that can be transilluminated suggest about that mass?
that it is not solid and is, instead, likely a hydrocele
What causes hydroceles in infants?
failure of the processes vaginalis to close completely, leaving a duct between the peritoneal cavity and tunica vaginalis
What structure fills with fluid in a hydrocele?
the tunica vaginalis, a remnant of the processus vaginalis
Testicular tumors arise from what two sources?
germ cells and sex cord-stroma (there are no surface epithelial tumors as in ovaries)
How are testicular masses biopsied?
they aren’t because this risks seeding of the scrotum
Why aren’t testicular masses biopsied?
because this risks seeding the scrotum with tumor cells and most testicular tumors are malignant germ cell tumors
What is the most common testicular tumor?
a malignant germ cell tumor
What should be done when you suspect a testicular tumor.? Explain the logic behind this decision.
- do not biopsy because most testicular tumors are malignant germ cell tumors and biopsy risks seeding the scrotum with malignant cells
- instead, proceed with a radical orchiectomy
What are the risk factors for testicular germ cell tumors?
- cryptorchidism
- Klinefelter syndrome
How do we divide testicular germ cell tumors?
as seminomas or nonseminomas
How do seminomas and nonseminoma testicular germ cell tumors compare?
- seminomas are more common, highly responsive to radiotherapy, metastasize late, and have a good prognosis
- nonseminomas are slightly less common, show a variable response to treatment, and often metastasize early
Seminoma
- a malignant testicular germ cell tumor and the most common testicular tumor
- comprised of large cells with clear cytoplasm and central nuclei, resembling an ovarian dysgerminoma
- grossly, it form s homogenous was without hemorrhage or necrosis
- it has the potential but rarely produces B-hCG
- responds well to radiotherapy
Embryonal Carcinoma of the Testicle
- a malignant nonseminoma (testicular germ cell tumor)
- comprised of immature, primitive cells that may produce glands
- in contrast to a seminoma, it forms a hemorrhagic mass with necrosis
- it is aggressive with early hematogenous spread
- may see increases in AFP or B-hCG
- chemotherapy may result in differentiation into another type of germ cell tumor
What reproductive tumor may respond to chemotherapy by differentiating into another type of tumor?
embryonal carcinoma
Embryonal Carcinoma of the Ovary
- a malignant germ cell tumor composed of immature, primitive cells
- aggressive with early hematogenous spread and a poor response to treatment
Why do choriocarcinomas often induce hyperthyroidism?
because they produce B-hCG, which has an alpha subunit mimicking that of LH, FSH, and TSH, which can stimulate the receptors for those substances
How do teratomas seen in men differ from those seen in women?
they are malignant in males, not in females (unless there are signs of immature tissue or somatic malignancy in the teratoma)
How do we determine the prognosis of a mixed germ cell tumor?
the prognosis is based on that of the worst component
Leydig Cell Tumor
- a benign sex cord-stromal tumor seen in men, which produces androgen
- because of this it causes precocious puberty in children or gynecomastia in adults
- characteristic Reinke crystals are seen on histology and gross exam reveals a golden brown mass
Sertoli Cell Tumor
- a benign sex cord-stromal tumor seen in men
- the tumor is comprised of tubules and is clinically silent
What is the most common cause of a testicular mass in males over the age of 60?
lymphoma
Testicular Lymphoma
- the most common cause of a testicular mass in males over the age of 60
- often bilateral and usually of the DLBC type
Prostatic glands are composed of what cells?
an inner layer of luminal cells and an outer layer of basal cells
What sort of fluid does the prostate secrete?
an alkaline fluid
Acute Prostatitis
- usually bacterial; Chlamydia trachomatis and Neisseria gonorrhoeae are common in younger males while E. coli and Pseudomonase are common in older adults (from spread of UTI)
- presents with dysuria, fever, and chills, urgency, and low back pain
- the prostate will feel warm, tender, boggy, and enlarged on digital rectal exam
- prostatic secretions will show WBCs and culture will reveal bacteria
Chronic Prostatitis
- chronic inflammation of the prostate
- presents with dysuria and pelvic or low back pain
- prostatic secretions show WBCs but cultures are usually negative
How does the presentation of acute prostatitis differ from that of chronic prostatitis?
- acute is usually bacterial so prostatic secretions contain WBCs and are culture positive; however, secretions from those with chronic prostatitis are likely culture negative
- additionally, acute presents with dysuria, fever, and chills whereas chronic presents with dysuria and pelvic or low back pain
Benign Prostatic Hyperplasia
- hyperplasia of prostatic stroma and glands
- an age related change, and seen in most men over 60
- poses no increased risk for cancer
- driven by the androgen DHT
- occurs the central periurethral zone of the prostate
- presents with problems starting and stopping urination as well as overflow incontinence, which poses a risk for hydronephrosis
- the obstruction causes hypertrophy of the bladder wall smooth muscle and increase risk for bladder diverticula
- microscopic hematuria may be present
- PSA is often slightly elevated (4 < PSA < 10)
- treatment involves an a1- antagonist, which has the added benefit of lowering BP, or an a1A-antagonist for normotensive patients
- another treatment option is a 5a-reductase inhibitor, to reduce conversion of testosterone to DHT
What portion of the prostate is affected by BPH? What about by prostatic adenocarcinoma?
- BPH: the central, periurethal zone
- adenocarcinoma: the posterior peripheral area
What complications arise from BPH?
- there is no risk for cancer
- but the obstruction may cause overflow incontinence, hypertrophy of the bladder wall smooth muscle, or bladder diverticula
What hormone drives BPH?
dihydrotestosterone (DHT)
How is DHT synthesized in vivo?
testosterone is converted to DHT by 5a-reductase expressed by stromal cells in the prostate
What is the function of PSA?
it is made by prostatic glands to liquefy semen
What is a normal PSA? What level would be consistent with BPH or adenocarcinoma?
- normal is < 4
- BPH is between 4-10
- adenocarcinoma is often above 10
Describe two treatment options of BPH.
- usually start with an a1-antagonist like terazoin, which relaxes smooth muscle to improve bladder function and blood pressure
- if the patient is normotensive, however, consider an a1A-antagonist like tamsulosin, which will act only at the bladder
- can also consider a 5a-reductase inhibitor, which blocks conversion of testosterone to DHT, the hormone that drives the hyperplasia; but this takes months to produce results and may cause gynecomastia or sexual dysfunction
Prostate Adenocarcinoma
- a malignant proliferation of prostatic glands
- risk factors include age, race (AA most and Asians least), and a diet high in saturated fats
- most often, it is clinically silent as it arises in the peripheral, posterior region and does not affect the ureter until late
- screening begins at age 50 with PSA and digital rectal exams
- histology reveals small, invasive glands with prominent nucleoli
- graded on Gleason system which is based solely on architecture (not nuclear atypia) as determined in two areas on a score of 1-5, which is then combined to determine prognosis
- spreads to the lumbar spine or pelvis, forming osteoblastic metastases; at this point, PSA, prostatic acid phosphatase, and serum alkaline phosphatase are all likely elevated
- prostatectomy is performed for localized disease and advanced disease is treated with hormone suppression to reduce testosterone and DHT
At what age and via what methods do we begin screening for prostate cancer?
begin at age 50 with PSA levels and digital rectal exams
What kind of PSA does adenocarcinoma make?
bound PSA, so low percentage free-PSA is suggestive of cancer
What is the Gleason grading system?
- a system for grading prostatic adenocarcinoma
- it takes into account only architecture and not nuclear atypia
- two areas are assessed and scored from 1-5 with the combined score determining the prognosis
When prostatic adenocarcinoma spreads, where is it most likely to go?
the lumbar spine or pelvis
Metastatic prostate adenocarcinoma is likely to have what signs of labs?
- elevated PSA (mostly bound)
- low % of free PSA
- elevated prostatic acid phosphatase
- elevated alkaline phosphatase
How is prostate adenocarcinoma treated?
- prostatectomy is used in cases of localized disease
- advanced disease is treated with hormone suppression aimed at reducing testosterone and DHT levels; this includes continuous GnRH analogs like leuprolide and androgen antagonists like flutamide
The breast is a modified ___ gland.
sweat
Where can breast tissue develop?
anywhere along the milk line between the axilla and the vulva
What is the functional unit of the breast called and what does it consist of?
it is called the terminal duct lobular unit and it is composed of a lobule filled with glands, which drain into a common terminal duct
Describe the ductal epithelium within the breast.
- there is the luminal cell layer, the inner layer which is responsible for milk production
- and there is the myoepithelial layer, which has contractile ability and propels milk towards the nipple
Describe breast tissue before puberty.
male and female breast tissue at this point consists of large ducts under the nipple
Describe development after menarche.
- driven by estrogen and progesterone
- lobules and small ducts form
Where in the breast is the highest density of terminal duct lobular units?
in the upper outer quadrant
