Flashcards in Module 3: Ovaries: General Info and Cysts and Surface Epithelial Tumors Deck (44):
First before we talk about the various tumors of the ovaries lets first discuss the basic physiology of the female hormones. What is the role of LH and FSH?
LH: acts on theca cells ---- androgen production
FSH: acts on granulosa cells --- convert androgens ---- estradiol (proliferative phase) --- LH surge ---- ovulation (secretory stage) --- corpus luteum ---- progesterone --- degenerate follicles ---- follicular cysts
What happens to the cell if you have a chronically high LH?
Multiple cysts lined by granulosa cells and hypertrophied theca interna cells
Now before discussion on the ovarian tumors lets first touch on the cysts diseases. The first is a Simple Cyst (physiological cyst, non-neoplastic cyst). What are some general features?
No dysplasia seen (hence its non-neoplastic)
No chance of malignancy
Women of reproductive age
Best investigation: Ultrasound
Now there are two types of Simple Cyst that are named according to the time of your menstrual cycle. First is the Follicular Cyst. what are some Features?
During the Estrogen (Follicular) Phase
--before ovulation is called follicular phase in the ovary and proliferative phase in the uterus.
--lined by cuboidal granulosa cells
--Women that hasn't been menstruating is going to be stuck in the estrogen phase so therefore this cyst predominates.
The second type of Simple Cyst is the luteal cyst. What are some features
During Progesterone (luteal) phase
--after ovulation you have luteal phase in the ovary and secretory phase in the uterus
--most common symptom is asymptomatic.
--Prego patients will have these types of cysts because they have high progesterone levels as well as hydatiform moles and gestational choriocarcinoma.
--Lipid laden cells called Theca cells
Seen when lots of betaHCg is being produced
What is the major complications for Simple (non-neoplastic) cysts?
More than 7cm increased risk of rupture and torsion and if on the right side then mimics acute appendicitis.
Moving on to the next female ovarian cysts are the Chocolate Cysts of the ovaries. What is the etiology?
Etiology: Endometrosis (repeated cyclical hemorrhage) --- induces fibrosis, adhesions, and severe pain
What is the morphology seen for patients with chocolate cysts of the ovary?
Morphology: normal endometrial glands amidst stroma with hemorrhages (hemosiderin laden macrophages)
What is a complication of chocolate cysts of the Ovary?
May extend along pelvic ligaments and associated with infertility (Due to tubal scars)
--needs to be distinguished from corpus luteum cysts
Finally the last of the cysts of the ovaries is Polycystic Ovarian Disease (Stein-Leventhal Syndrome). Who present with this?
Black women of reproductive age that are obese
All due to increased estrogen levels
What is the pathogenesis for polycystic ovarian disease?
LH stimulates theca cells --- Androgen Production ---- converted to estrogen in the adipose tissue by aromatase --- increased estrogen levels ---- negative feedback on the anterior pituitary ---- decreased FSH --- no negative feedback on hypothalamus -- Elevated GNRH --- Stimulates LH production by anterior pituitary (Should stimulate FSH, but estrogen keeps it low) --- LH stimulates theca cells -- cycle continues
What levels are elevated and what levels are reduced in Polycystic Ovarian Disease?
Elevated: Estrogen, LH, GNRH, Androgen, Insulin and Glucose
Low: FSH and progesterone (Because you are not ovulating)(no neg feedback from progesterone to LH)
What is the presentation for patients that have polycystic ovarian disease?
Women of reproductive age
Obesity --- peripheral insulin resistance -- type II diabetes
*amenorrhea, infertility -- due to persistently high LH (No LH spike)
Slide 2 is a picture of the cysts. Explain the appearance of the cysts in polycystic ovarian disease
Multiple Cysts in BOTH ovaries:
--subcapsular or subcortical cysts
--Follicular cysts (patients arent ovulating)
Both ovaries are enlarged
--thickened (hypertrophied) stroma in both ovaries due to constant stimulation by LH
Necklace like appearance of the cysts
What are the best investigations for polycystic ovarian disease?
Most accurate: Hormone Profile
--LH to FSH ratio most accurate test 3:1
Can do ultrasound: necklace like appearance of the cysts with a hypertrophied stroma
Finally what are the complications for polycystic ovarian disease?
1. Type II diabetes (metabolic syndrome)
4. Fatty Liver and NASH (non alcoholic steatohepatitis) due to the obesity
5. Endometrial hyperplasia --- endometrial carcinoma
What treatments are used for polycystic ovarian disease?
1. Chlormiphine: Induces ovulation (regularizes cycle)
2. Metformin for obesity and diabetes
Now moving onto the primary ovarian tumors. First lets list the classifications based on origin.
4 surface epithelial tumors:
Serous, Mucinous, Endometrioid and Brenner's
4 Germ Cell Tumors:
Choriocarcinoma, endodermal sinus (yolk sac), dysgerminoma (oocytes) and teratoma (fetal tissues: mature, immature and specialized)
3 Sex Cord Stromal Tumors:
Granulosa-theca, sertoli-leydig and fibrothecoma
Before we get into the specifics for each lets just go over some general basics and rules. What are the pre-disposing factors for developing a primary ovarian tumor?
Genetics: BRCA 1 and 2, p53, p10 and HER2neu
Increase Estrogen: nulliparity, obesity and Etcetera
--oral contraceptives are protective
Describe the spread of the malignant primary ovarian tumors ?
Lymph Nodes: iliac and paraaortic
Peritoneum: ascites and omental caking via seeding
Blood: Liver, lungs, Brain, Bone, Kidney
Most primary ovarian tumors are unilateral but can be bilateral. If you see a bilateral primary tumor which one is it most likely going to be?
All cystic ovarian tumors are benign and all solid ovarian tumors are malignant. What are the exceptions to these rules?
Brenner's: solid but benign
Fibrothecoma: Solid but benign
Most primary ovarian tumors are asymptomatic why?
Because there is so much room for them to grow
--so by the time they present with pain they will have metastasized as well as had mass effect on the rectum and bladder
Most of the primary ovarian tumors are asymptomatic because they are non functional. However some are functional, which ones are functional?
1. Choriocarcinoma makes betaHCG (patients will have intense morning sickness and amenorrhea)
2. Sertoli-Leydig: makes testerone and therefore man like symptoms
3. Granulosa-Theca: makes estrogen causes endometrial hyerplasia and leads to vagina bleeding.
As stated earlier ovarian carcinomas go through the lymph nodes first. what is the exception to this real?
A patient presents with intestinal obstruction and US shows mucinous implants with distended bellies, where do you look first? (aka jelly belly)
--note that mucinous cyst of the ovaries do give you jelly belly but not the most common cause
What is the most common ovarian tumor in kids?
What is the most common ovarian tumor in post menopausal women?
Now starting with the surface epithelial tumors (65-70%). First is serous cystadenoma. explain the histology and gross for this
MOST COMMON OVARIAN TUMOR
---Looks like epithelium of fallopian tubes
**tall columnar ciliated epithelium with papillary projections and psammoma bodies
As you go from benign (3a) to borderline (3b) to malignant (3c). What is the progress in terms of histology?
3a: Benign: Single layer of tall columnar ciliated epithelium and completely cystic
3b: gross more solid papillary projections and histology: multiple layers of tall columnar ciliated epithelium, more psammona bodies, complex branching papillae; BM still intact
3c: gross: very solid histology: invasion into stroma and more complex papilla
What gene mutations are considered high grade vs low grade in terms of serous cystadenoma?
Low grade: KRAS and BRAF
High grade: p53 and BRCA
Again what is the presentation for serous cystademoma?
Long time to present (b/c there is room for it grow), but can cause mass affect (bladder and rectum)
What are Psammoma Bodies?
Calcium concretions seen at tips of papilla
What tumors show Psammoma bodies?
Serous ovarian tumor (most common)
Serous endometrial carcinoma
Papillary renal cell carcinoma
Papillary thyroid carcinoma
Moving onto the next surface epithelial timor is mucinous tumor, what are some general features?
Usually unilateral but can be bilateral
--only mucinous primary ovarian tumor so use PAS
--epithelium looks like endocervix/intestinal epithelium with tall columnar non ciliated with goblet cells
Pictures 4a and 4b go through the progression of Mucinous tumor from benign to malignant. What is the gross and histology of these changes?
4a: Benign: Gross--Cystic with multiloculations (many little cysts within one large cyst). Histology: single layer of tall columnar with goblet cells
not pictured: borderline: more solid and histology: multiple layers of tall columnar with goblet cells but again no invasion of BM
4b: Malignant: Gross: Solid. Histology: tall columnar with goblet that has invaded the stroma and back to back glands producing mucin
What are the complications with Mucinous tumor?
Cystic: Torsion or Rupture
Solid: only torsion
Metastasis: lymph nodes
Pseudomyxoma Peritonei (jelly belly)
--malignant invades and metastasizes into peritoneum --- intestinal obstruction --- distended abdomen that hasnt passed stool for the past 3-4 days
(remember appendix is most common)
Next surface epithelial tumor is endometrioid. What is the etiology?
PTEN, KRAS, Beta-catenin, MSI
What is the gross and histology image of endometrioid tumor?
Gross: Solid and cystic, velvety surface
Histology: resembles endometrial carcinoma (not normal endometrium) as seen in endometriosis. Simple columnar epithelium
Finally the last surface epithelial tumor is Brenner's Tumor. What are some general features?
Solid but benign!
Seen in post menopausal women
What is the histology and gross as seen on slide 5?
Gross: Solid Mass
Histology: Nests of spindles cell with well differentiated transitional (urothelium) epithelium with coffee-bean nucleus (granuloma)
What are the complications of Brenner's Tumor?
Torsion but not rupture because solid tumors do not rupture
very small chance of malignant
What tumor marker do all surface epithelial tumors use?