Benign and Malignant Tumors of the Female Reproductive System II Flashcards
Many “ovarian cancers” actually originate in the. . .
. . . fallopian tube
Peutz Jegher syndrome
- Mutation in SKT11
- 95% of patients develop mucucutaneous pigmented lesions
- 21% of patients develop a non-epithelial ovarian cancer, with a mean age of incidence of 27
- Also increased risk of GI and breast cancer
Lynch syndrome mutations
- In MMR or EPCAM genes
- Autosomal dominant
Due to our advances in tumor marker measurement and chemotherapeutics, the prognosis of GTN. . .
. . . is generally quite good.
Most women will be cured, and their reproductive capacity preserved.
Three types of GTN and major features
- Choriocarcioma: Neoplastic syncytiotrophoblast and cytotrophoblast without any chorionic villi
- Invasive mole: Edematous chorionic villi with trophoblastic proliferation that invade into the myometrium
- Placental site trophoblastic tumor: Absence of villi and with proliferation of intermediate trophoblast cells
Most important risk factors for GTN
Maternal age
History of prior GTD (benign or malignant)
Signs and symptoms of complete molar pregnancy
- Abnormal uterine bleeding
- Uterine enlargement with large, cystic ovaries (Lutein cysts)
- Hyperemesis gravidarum (extreme, persistent N/V)
- VERY high beta hCG (often with hyperthyroidism)
- Absence of fetal heart tones (remember, there is no fetus in these pregnancies!)
- On ultrasound: Luteid cysts and “snowstorm” pattern with hydropic villi.
Partial molar pregnancy presents very similarly to. . .
. . . misscarriage
There is abnormal uterine bleeding and an absence of fetal heart tones.
However, of course, in partial molar pregnancy the fetus was never viable to begin with.
Abnormal bleeding for more than 6 weeks following pregnancy raises suspicion for. . .
. . . malignant GTD arising from the pregnancy
These patients should be evaluated with serial beta hCG measurements. Elevated beta hCG in the absence of a pregnancy make the diagnosis.
Lutein cysts are generally indicative of. . .
. . . complete molar pregnancy
They are quite rare with partial molar pregnancy.
Standard of care for treating molar pregnancy
- Generally the treatment is suction dilation and curretage
- However, in women who do not wish to preserve child-bearing, hysterectomy is also an option.
-
All patients should have monitoring of beta hCG 48 hours post-evacuation, every 1-2 weeks while elevated, and then monthly for 6 months after levels return to normal.
- During this time contraception should be used.
Two pathways to vulvar carcinogenesis
Note: Chronic inflammation primarily indicates lichen sclerosis
Symptoms of vulvar neoplasm
- Vulvar itching
- Ulcerative or exophytic lesion on vulva
- Exophytic ulcer is pictured
Treatment for malignant GTN with no metastatic disease
Weekly intramuscular methotrexate has a cure rate close to 100%
Hysterectomy is also recommended for those who do not wish to preserve child-bearing and are good surgical candidates. However, it is not necessary for patients who wish to preserve child-bearing.
Bartholin’s gland carcinoma
- Rare form of vulvar cancer
- Any Bartholin gland mass in women over age 40 should be biopsied
Indications for vulvar biopsy
Note: “Suspicious” features include assymmetry, border irregularity, color variation, and bleeding or non-heaing ulceration
Use of acetic acid in assessment for cervical cancer
Causes cells with large nuclei to appear white to the naked eye. This allows one to visualize the transformation zone between the columnar and squamous epithelia.
Bethesda cervical cancer grading
LAST cervical cancer grading system
- Gets rid of “CIN” in final assessment
- CIN1 = LSIL
-
CIN2 is tested for p16:
- CIN2 p16- : LSIL
- CIN2 p16+: HSIL
- CIN3 = HSIL
90% of vulvar neoplasms are ___.
Most of the other 10% are ___.
90% of vulvar neoplasms are squamous cell carcinomas.
Most of the other 10% are melanomas.
Uterine fibroid
- aka leiomyoma
- Type of benign, hormonally-responsive tumor
- Estrogen stimulates growth (rapid growth in pregnancy, atrophy in menopause)
*
- Estrogen stimulates growth (rapid growth in pregnancy, atrophy in menopause)
The one risk factor for cervical cancer that is not like the others
Most cervical cancer risk factors are just risk factors for HPV infection
EXCEPT smoking.
Smoking makes cervical cancer more likely independent of HPV.
Guide to pap smear screening recommendations
- Age 21-29: Pap smear every 3 years, no HPV testing
- Age 30-64: Pap smear and HPV test every 5 years OR Continue as above
- Age 65+ : If last few paps negative and no history of CIN3, there is no longer a need for pap smear screenings
Uterine artery embolization procedure diagram
(For fibroids)
Histologic types of endometrial hyperplasia
Note that in simple hyperplasia, the gland to stroma ratio is preserved, but in complex hyperplasia, it is primarily the glands that are proliferating.
What type of endometrial hyperplasia is pictured here?
Simple endometrial hyperplasia without atypia
What type of endometrial hyperplasia is pictured here?
Complex endometrial hyperplasia with atypia
___ on ultrasound indicates a low probability of endometrial cancer
Endometrial stripe < 4 mm on ultrasound indicates a low probability of endometrial cancer
The endometrial stripe is the “stripe” visualized on the ultrasound screen representing the endometrium.
When a pap smear is abnormal, __ is the next step.
When a pap smear is abnormal, colposcopy (for histology) is the next step.
Treatment for cervical intraepithelial neoplasia (CIN)
- LSIL: Monitoring and followup
- HSIL: Immediate therapy
- Ablation: Cryotherapy or laser ablation
- Excision: Cone or LEEP (iodine staining and excision of iodine-negative cells)
Major causes of post-menopause vaginal bleeding and workup for these patients
- Workup:
- Endometrial biopsy (endometrial cancer)
- Pap smear (cervical cancer)
- Careful physical and pelvic exam
Signs and symptoms of cervical cancer
- Highly variable and nonspecific
- Watery vaginal discharge
- Intermittent spotting
- Post-coital bleeding
- Cervix may appear normal, but is often friable
Signs and symptoms of uterine fibroids
-
Heavy periods
- Due to disruption of mucosa. Serosal fibroids least likely to present this way
- Pelvic pressure/sensation of pelvic mass
- Dysmenorrhea / painful menses
How do we diagnose uterine fibroids?
Through physical exam and imaging studies (pelvic ultrasound, sonohysterogram, MRI if ultrasound insufficient)
Biopsy is not necessary unless to rule out malignancy
Contraindications to OCP
- Age over 35
- Smoking
- Migraines
Management of uterine fibroids
- Medical management: (Remember, they are hormonally responsive)
- OCP (if not contraindicated)
- Progestins
- Prostaglandin synthetase inhibitors (NSAIDs)
- GnRH agonists / leuprelide (only as temporizing measure prior to surgery or to bridge to menopause)
- Surgical management:
- Uterine artery embolization (really IR)
- Myomectomy (abdominal or hysteroscopic)
- Hysterectomy
Which type of ovarian tumor increases the risk of endometrial hyperplasia and endometrial cancer?
Granulosa cell tumors
Since they secrete estrogen!
Management of endometrial hyperplasia
- Depends upon the type of hyperplasia
- For simple and complex w/o atypia:
- Low risk of progression
- Medical therapy w/ progesterone (oral methoxyprogesterone acetate)
- For somple and complex w/ atypia:
- High risk of progression
- Definitive therapy w/ hysterectomy once fertility is no longer desired
- Long term high-dose progesterone therapy with freqeunt endometrial sampling may bridge to hysterectomy in those who still wish to have children
Type 1 vs Type 2 endometrial cancer
- Type 1:
- Estrogen dependent
- 90% of cases
- Type 2:
- Estrogen independent
- 10% of cases
- Tend to have aggressive, high-grade nuclei or clear cell histology
Ovaries should only be palpable in. . .
. . . 50% of women of reproductive age
Not in pre-menarchal girls
(Usually) not in post-menopausal women
Primary evaluation of an adnexal mass
Pelvic ultrasound
Main classifications of adnexal masses
- Funcitonal cysts (physiologic and resolve spontaneously)
- Benign ovarian neoplasms
- Malignant ovarian neoplasms
Management of functional ovarian cysts
- Generally none, they will typically resolve on their own and are not concerning for malignancy
- If they become symptomatic (usually due to size, but also torsion or hemorrhage into the cyst), surgery is indicated
__-derived ovarian cancers are most associated with paraneoplastic syndromes
Stroma-derived ovarian cancers are most associated with paraneoplastic syndromes:
- Thecomas and fibromas (benign) are associated with Meig’s syndorme
- Granulosa cell tumors (malignant) are associated with hyperestroginemia
- Sertoli Leydig cell tumors (malignant) are associated with hyperandrogenemia
Most common symptoms for ovarian cancer
-
GASTROINTESTINAL:
- Abdominal bloating
- Early satiety
- Abdominal distension
- Abdominal or pelvic pain
- Note that ovarian tumors often do not present with any gynecologic symptoms, so index of suspicion must remain high in women over the age of 40.
Protective factors against ovarian cancer
- History of OCP for at least 5 years
- History of tubal ligation
- Hysterectomy
When is CA125 most helpful in evaluating a pelvic mass?
In post-menopausal women
Many pre-menopausal women will have nonspecifically elevated CA125 (assc w/ fibroids, PID, endometriosis)
Patient presents with symptoms and history suspicious for ovarian cancer. Pelvic ultrasound shows a lesion on the right ovary with malignant features, and CA125 is elevated. What is the next step in evaluation?
Surgical exploration
Any vaginal bleeding in a post-menopausal patient should raise a big red flag for. . .
. . . endometrial cancer
95% of cases of endometrial cancer are __.
95% of cases of endometrial cancer are symptomatic
This makes screening for endometrial cancer not very worthwhile, since patients will come to you when they have it!
Anyone that you think might have atrophic vaginitis should always be worked up for ___ as well.
Anyone that you think might have atrophic vaginitis should always be worked up for endometrial cancer as well.
Endometrial cancer in patients on tamoxifen
While the risk is increased, we still don’t screen patients on tamoxifen for endometrial cancer because endometrial cancer declares itself.
Again, we do NOT screen for endometrial cancer.
Treating vaginal atrophy
You can treat vaginal atrophy with topical estrogen, AFTER you rule out endometrial cancer as a cause of post-menopausal vaginal bleeding,
Endometrial cancer is a ___-staged cancer.
Endometrial cancer is a surgically-staged cancer.
FIGO staging
For cervical cancer
“Brachytherapy” vs “Teletherapy”
Brachytherapy: Radioactive substance is placed inside of a patient in order to kill cancer cells
Teletherapy: Radioactive light is transmitted through the patient inorder to kill cancer cells
Intracavitary brachytherapy
Radiotherapy for cervical cancer
The radiation source is placed in a device in the vagina (and sometimes in the cervix)
The radioisotopes used have produce radiation that acts only locally, with the main effects being on the cervix and walls of the vagina
What to do for each FIGO stage
“Carcinomatosis”
A condition in which multiple carcinomas develop simultaneously, usually after dissemination from a primary source.
Often seen in ovarian neoplasms since they are open to the peritoneal cavity
“Workflow” of cervical cancer screening and diagnosis
- Pap smear
- If abnormal, colposcopy and biopsy
- If abnormal, LEEP or cone biopsy
With regards to cervical cancer, any progression further than simply microscopic invasion (<3mm) indicates. . .
. . . radical hysterectomy and lymph node biopsy
Why are HPV guidelines so different in younger women?
Because there is a chance that if you are younger than age 30, you may clear even advanced HPV on your own.
Type of hysterectomy in cervical cancer
Abdominal!!!
NOT minimally invasive. This is because the uterine manipulator can spread cervical cancer intraoperatively in laporoscopic surgery.
Standard chemotherapy for most ovarian cancer is ___.
For most endometrial cancer, it is ___.
Standard chemotherapy for most ovarian cancer is carboplatin + taxol.
For most endometrial cancer, it is carboplatin alone.
“Parametrium”
Tissue just lateral to the cervix.
PET-CT in cervical cancer
Can be useful for visualizing involved lymph nodes
Any cervical cancer beyond stage I B2 requires ___.
Any cervical cancer beyond stage I B2 requires chemotherapy.
PARP inhibitors
- Target poly-ADP polymerase, the initial step in the homologous recombination repair pathway
- Several forms of cancer are more dependent on PARP than regular cells, making PARP an attractive target for cancer therapy
- Specifically, if a tumor has a mutation in homologous repair pathways, PARP therapy can be effective regardless of the origin of the tumor
Unlike most other cancers that require surgical therapy, in cervical cancer if there is recurrence at the same location. . .
. . . repeat surgery is still indicated
This usually involves radical cystectomy, vaginectomy, rectectomy, and colostomy.
This is curative in 50% of cases.
BRCA1 vs BRCA2 syndromes
-
BRCA1:
- Average age of onset 50
- 80% breast, 30% ovarian
-
BRCA2:
- Average age of onset 60
- 80% breast, 20% ovarian, also pancreas, prostate
- Male breast cancer
Cowden disease
PTEN overexpression
Associated with thyroid, breast, and uterine cancer
LVSI
Lymphovascular space invasion
Poor prognostic sign for cancers. Evaluated on histology and often relevant for staging.
“Velvety” vulvar lesion
Buzzword for Paget’s disease of the vulva
Treatment for microinvasive cervical cancer
Cone biopsy is. . . diagnostic AND curative
Abnormally high HPL suggests. . .
. . . placental site trophoblastic tumor
Reinke crystals
Seen exclusively in a Sertoli-Leydig cell tumor
