Disorders of the Fallopian Tubes and Ovaries Flashcards
Where do the primordial germ cells come from and end up?
They migrate up the midline of the yolk sac through the dorsal mesentery of the hindgut until they reach the gonadal ridge, an outpouching of mesoderm on the posterior abdominal wall
What happens once the germ cells arrive at the gonadal ridge?
They are surrounded by three mesodermally-derived structures:
- Primitive sex cords - surround the germ cells -> will become granulosa cells
- Stroma -> surrounds the follicles, will become fibroblasts and theca cells
- Surface coelomic epithelium -> still derived from mesoderm, will become the mesothelium which covers the ovary
What causes streak or absent gonads?
When the germ cells do not migrate to the gonadal ridges properly -> as in Turner syndrome
-> ovaries are replaced by useless connective tissue with no follicles
How can abnormal migration cause ovaries with premature menopause?
If sex cords are not formed properly around germ cells, then the germ cells are not protected.
Protection from granulosa cells (primitive sex cord derived) is required to protect follicles
Where are the paramesonephric ducts located in development, and where do they fuse / not fuse?
Located lateral to the mesonephric duct in the outpuching called the “lateral urogenital ridge”
The ridges will come to fuse with eachother anterior to the hindgut. They fuse inferiorly, but remain slightly apart superiorly
What do the superior and inferior parts of the paramesonephric duct become?
Superior - unfused - Fallopian tubes
Inferior - fused - uterus, cervix, and upper 2/3 of vagina
Where does the urogenital sinus come from?
From the ventral portion of the distal endodermal tube, with a small contribution (mesodermal patch) from the mesonephric ducts which forms the trigone of the bladder.
What happens in the formation of the epithelium of the vagina?
Lower 1/3: From UG sinus - ectodermal origin - SSNK
Upper 2/3: From paramesonephric ducts - mesodermal origin - columnar epithelial cells
Lower 1/3 SSNK epithelium should spread to cover entire vagina and ectocervix
What is it called if there is persistence of columnar epithelium in the upper vagina? What increases your risk of this? What is the consequence?
Adenosis
Risk increased with in utero diethylstilbestrol
Increased risk of clear cell adenocarcinoma of the vagina
What does the mesonephric duct become in males?
SEED Seminal vesicles Epididymis Ejaculatory Duct Ductus deferens
What does the mesonephric duct become in females, even pathologically?
Epoophoron and paroophoron are remnants in the broad ligament
Can become Gartner duct cysts in the lateral vaginal wall if more distal portions of the duct do not involute
What is the order of areas in the Fallopian tube from the ovary to the uterus in females? Where does fertilization occur?
Fimbrae -> infundibulum -> ampulla -> isthmus -> ostium of uterus
Fertilization typically occursin the ampulla
What is the histological structure of the Fallopian tube wall?
Papillary structure filled with “mucosal plicae” lined with columnar cells
-> ciliated and move the egg down, most developed around time of ovulation
What do corpus lutea look like grossly in a female of reproductive age?
They look like large cystic structures with a hemorrhagic interior (lots of blood) which become progressive fibrotic.
Surrounded on outside by yellowish, luteinized (lipid-filled) granulosa and theca interna cells
What are corpora albicantia vs atretic follicles?
Corpora albicantia (sing. corpus albicans) - scars resulting from regressing corpus lutea
Atretic follicles - small, wavy, hyaline scars -> obliterative fibrosis. These are due to secondary follicles that never got selected for.
What would you expect to see in the ovaries of a young child vs post-menopausal women?
Young child - numerous primordial and early primary follicles, with many atretic follicles (never enough FSH to induce ovulation)
Postmenopause - atretic follicles and corpora albicantia (assuming she had been ovulating throughout her life)
What is the definition of endometriosis and the most common spot for it? Does the myometrium count?
Endometrial tissue, including both stroma and glands, outside the uterus
Most common spot is the ovary
->involvement of the myometrium is called adenomyosis, and does NOT count as a form of endometriosis
What are the theories of pathogenesis of endometriosis and how does this relate to endometriosis being found in the following locations: Ovarian cavity Abdominal cavity Abdominal scars Lungs Lymph Nodes Occurring in men
- Metastatic theory:
Retrograde menstrual flow through Fallopian tubes -> explains ovarian and abdominal cavity spreading.
Hematogenous / lymphatic dissemination -> endometriosis appears in lungs / lymph nodes
Iatrogenic - surgeon moves it there accidentally -> explains abdominal laparotomy scars with it
- Metaplastic theory - multipotent stem cells become endometrium -> explains occurrence rarely in men
How can endometriosis appear grossly in the ovaries, serosa of pelvis / abdomen, and intestines?
Ovaries - “chocolate cysts” - blood-filled endometrioma
Serosa - “powder burns” - black spots on serosa
Intestines - induce fibrosis leading to adhesions and even mural-thickening of smooth muscle (Crohn’s like presentation)
How does endometriosis appear different than adenocarcinoma histologically?
There is proliferation of both the glands and the stroma
In endometrial adenocarcinoma -> Just the glands are proliferating
What symptoms can endometriosis present with?
Cyclic pelvic pain and dysmenorrhea, dyspareunia, dyschezia (pain with defecation, if colon involved), and even infertility
What is the cause of pelvic inflammatory disease?
Infection of fallopian tubes and ovaries, usually by gonorrhea or chlamydia. Other bacteria can do it.
-> vaginal or cervical infection alone won’t do it
What are the initial acute manifestations of PID?
- Acute suppurative salpingitis - acute inflammation of fallopian tube with epithelial injury
- Salpingo-oophoritis - extension to involve ovary
What are the later possible acute manifestations of PID?
- Pyosalpinx - fallopian tube gets filled with purulent exudate if it gets clogged at both ends
- Tubo-ovarian abscess - extensive mass involving both the Fallopian tubes and ovaries
What are the acute complications of PID? What complications could occur later because of these?
Peritonitis and bacteremia
-> the infection can spread to the body
-> may result in intestinal obstruction due adhesions formed by peritoneum
After the infection has been eradicated in PID, what are the possible sequellae? What complications can occur because of this?
- Chronic salpingitis -> chronic inflammation and fibrosis of fallopian tubes, with fusion of plicae
- > can lead to infertility and increased risk of ectopic pregnancy - Hydrosalpinx -> occur following pyosalpinx -> fimbriae fuse and accumulate tubal secretions making a large mass
What are the classical signs and symptoms of PID?
Pelvic pain / dysmenorrhea,
leukorrhea (purulent vaginal discharge), possible acute abdomen
Chandelier sign - cervical motion tenderness on pelvic exam -> patient jumps as if trying to touch a chandelier
Where does ectopic pregnancy usually occur and what are the risk factors?
Usually occurs in ampulla of Fallopian tube
Risk factors: Previous pelvic surgery History of PID Peritubal adhesions due to endometriosis or appendicitis Tubal diverticula (plicae form holes) IUD use.
What is the common presentation for ectopic pregnancy? What is it often mistaken for?
Pelvic pain, and frequently an acute abdomen -> fallopian tube ruptures since trophoblast is invasive, and the epithelium is not properly decidualized
Often mistake for appendicitis
How is diagnosis of ectopic pregnancy confirmed?
Increased serum beta-HCG as well as ultrasound examination showing no pregnancy, and likely ultrasound will show mass in the fallopian tube
What is the most common cause of ovarian enlargement and what are three types?
Ovarian cysts
- Epithelial inclusion cysts - small cysts formed by invagination of ovarian surface epithelium (single layer)
- Follicle cysts
- Corpus luteum cysts
What are follicle cysts and are they functional?
“Follicular cysts”
- > upruptured Graafian follicles
- > lined by granulosa and theca cells
- > are functional -> can be lined by granulosa cells and produce estrogen
What are corpus luteum cysts and are they functional? What’s on the ddx?
Corpus luteum with blood in them which have a delayed resolution -> taking forever to turn into corpus albicans
DDx: Chocolate cyst from endometriosis
What do the ovaries look like in Stein-Leventhal syndrome?
This is also called Polycystic Ovarian Disease
-> look like bilaterally enlarged, smooth ovaries (no corpora lutea or albicantia) with numerous follicle cysts and hyperplastic theca-interna cells (LH levels are high) which appear luteinized
What are the three broad types of ovarian neoplasms and which is the most common?
- Surface epithelial tumors - most common - formed from coelomic epithelium
- Germ cell tumors
- Sex cord-stromal tumors
What are risk factors for ovarian malignancies?
- Inherited mutations in BRCA1/2 or Lynch syndrome (HNPCC)
- Nullparity / low parity -> more ovulations without pregnancy = more need to regrow surface epithelium and thus cancer risk
- PCOS
What are protective factors against ovarian malignancies?
- Tubal ligation
- OCPs - less ovulation
- Multiparity - less ovulation
Why do ovarian neoplasms have such a poor prognosis?
They are often discovered very late - symptoms are nonspecific GI / GU discomfort
Vaginal bleeding will only occur if the neoplasm secretes estrogen
Why are surface epithelial tumors of the ovary so heterogeneous?
They are derived from the ovarian surface epithelium which has the same origin as Mullerian duct epithelium -> can be fallopian, endometrial, or endocervix type endothelium based
What are the three major histologic subclassifications of surface epithelial tumors of the ovary? Which is most common?
- Serous neoplasms - most common
- Mucinous neoplasms
- Endometrioid neoplasms
What is the most common malignant ovarian neoplasm overall? What is the differentiation towards? What does it look like histologically?
Papillary serous cystadenocarcinoma -> papillary pattern means it’s differentiated towards Fallopian tube
Columnar epithelial cells, and since it is papillary carcinoma -> psammoma bodies are frequently seen
What do mucinous ovarian tumors differentiate towards? What mutation is associated?
Endocervix or intestinal mucinous columnar epithelium
-> KRAS mutations are often seen
What type of ovarian cancer arises in the setting of endometrial cancer and are they related?
Ovarian endometrioid carcinoma
-> often arises in the setting of endometriosis, but the uterine endometrial cancer is independent (not the same tumor)
What are the three forms in which each subtype of ovarian neoplasm can be found?
- Adenoma - benign -> minimal epithelial proliferation
- Borderline - inbetween benign and malignant (malignant, but much better prognosis)
- Adenocarcinoma - marked epithelial proliferation and STROMAL INVASION
What are two gross features you look at to differentiate between benign and malignant ovarian neoplasms?
Solid areas -> more solid areas = more likely to be malignant. (More cystic = likely benign)
Bilateral = more likely malignant than benign
What is pseudomyxoma peritonei and what is likely to cause it?
Mucinous material from ovarian tumor leaks into abdomen and causes mucinous ascites
Mucinous cystadenocarcinomas are most likely to cause it, can also be due to appendiceal tumor
How do ovarian adenocarcinomas typically disseminate?
Disseminate locally and have massive peritoneal involvement
-> present with ascites
May also disseminate in lymphatics or even hematogenously
-> poor prognosis
What tumor marker is useful for ovarian adenocarcinoma?
CA 125 -> much like CEA tumor marker for colorectal carcinoma
-> good for serous and endometrioid
What is a Brenner tumor and why is it unique?
It is a Benign tumor that is actually solid (rather than cystic) and is composed of Bladder epithelium (urothelial / transitional type)
Who tends to get benign vs malignant surface epithelial ovarian tumors in terms of age?
Benign - usually in premenopausal women - aged 30-40
Malignant - usually in postmenopausal women - aged 50-60
What is the most common germ cell tumor of females, what age group tends to get them, and where do they arise?
Mature cystic teratomas (benign)
Tend to occur in younger age group than benign surface epithelial tumors -> ages 10-30
Often arise in the ovary, but can arise anywhere along line of migration of germ cells (along the midline)
Give another name for mature cystic teratoma and tell me what the mass contains? What will a little solitary protuberance contain?
Dermoid cyst
It is a cystic mass composed of all matured structures from all three germ cell layers, but often with ectodermal predominance (skin / hair).
A little solitary protuberance often contains the little mesoderm / endoderm derivatives, rest is ectoderm
What is struma ovarii an example of and how does it present?
A monodermal teratoma which is mostly composed of mature thyroid tissue -> benign variant, but presents clinically as hyperthyrodism
What germ layer most commonly predominates in immature teratoma, and is it benign or malignant? What is seen histologically?
Neuroectodermal derived -> contains immature fetal tissue.
It is an aggressive malignancy typically, and is embryonal tissue intermixed with necrosis and hemorrhage
If a mature teratoma becomes malignant, how does this usually happen?
Usually occurs due to a squamous cell carcinoma arising within the mature tissue (due to it being mostly ectodermal)
What is the most common malignant ovarian germ cell tumor? How do the cells appear?
Dysgerminoma (analogous to seminoma in males)
Cells appear large with clear cytoplasm and central nuclei (resembling oocytes or friend eggs)
What are the useful tumor markers in dysgerminoma and what is the prognosis?
Lactate dehydrogenase (LDH) is most useful.
hCG is also sometimes useful if syncytiotrophoblasts are intermixed
Excellent prognosis with radiation to chemotherapy (similar to seminoma, completely opposite to non-seminoma germ cell tumors)
What does histology of yolk sac tumor show and what is the serum marker?
Schiller-Duval bodies (glomeruloids structures) -> remember these are the “endodermal sinus”
-> alpha-fetoprotein is tumor marker (yolk sac)
What aggressive germ cell malignancy is often mixed with other types? What is its histologic pattern?
Embryonal carcinoma
-> Solid sheets and nests of large, pleomorphic cells, often making a pseudoglandular pattern
What is the tumor marker and prognosis of nongestation choriocarcinoma? What will be seen histologically?
Tumor marker is beta-HCG
Invasive cytotrophoblasts / syncytiotrophoblasts, but villi are ABSENT (unlike invasive mole)
Prognosis is god awful with early hematogenous spread (does not respond well unlike gestational choriocarcinoma)
What are sex cords vs stroma in “sex cord-stromal” tumors?
Derivative of:
1. Sex cords -> granulosa or Sertoli cells
- Stroma -> fibroblasts, theca cells, Leydig cells
If sexcord-stromal tumors are functioning, who tends to get estrogenic vs androgenic versions?
Estrogenic - older women
Androgenic - younger women
But obviously there are exceptions to rules
What is the most common malignant sex cord-stromal tumor? Who tends to get it gets it? What is their presentation?
Granulosa cell tumors
- > estrogen-secreting, thus adult-type (women in their 50s, postmenopausal)
- > presents as abnormal uterine bleeding due to endometrial hyperplasia
What can happen if granulosa cell tumors occur in pre-adolescents? What tumor marker is used to track it?
Sexual precocity
Tumor marker is inhibin -> made by granuloma cells to inhibit FSH
What is seen histologically in granulosa cell tumors? Do these have good prognosis?
Call-Exner bodies
- > granulosa cells arranged around collections of eosinophilic material
- > follicular pattern which resembles primordial follicles (they think they are around germ cells)
Yes, they are a low-grade malignancy with good prognosis
What is a fibroma-thecoma and who tends to get it? What hormone is secreted?
Benign tumor of varying amounts of fibroblasts and theca cells (epithelial derived) -> actually produce estrogen (rather than testosterone, they go the next step)
Thus, like granulosa cell tumors, presents as abnormal uterine bleeding in postmenopausal women
What is Meigs syndrome? What might you confuse it for?
Triad of ovarian fibroma, ascites, and hydrothorax
-> might confuse for ovarian carcinoma ascites, but actually fibromas / thecomas are benign
Who is the androgenic sex cord-stromal neoplasm which usually occurs in younger women? What does it look like histologically?
Sertoli-Leydig cell tumor (yes! this can occur in the ovaries!)
Sertoli cells will form tubes, and the Leydig cells will be the stroma between the tubules.
Reinke crystals can be seen on histology in Leydig cells (as in male Leydig cell tumors)
What happens to women with Sertoli-Leydig cell tumor?
Defeminization - amenorrhea, decreased breast size
Virilization / hirsutism
What is a Krukenberg tumor? How can you differentiate this from primary ovarian malignancy?
Mucinous, signet-ring cell adenocarcinoma which has metastasized to ovary
-> usually due to diffuse gastric adenocarcinoma
-> typically metastases will be bilateral, whereas primary mucinous cystadenocarcinoma is unilateral usually
What are the most common tumor locations to metastasize to the ovary?
Genital tract, GI tract, or breast