Clinical: Gynecologic Oncology Flashcards
- Majority of ovarian cancers: 95%
- Average age at Dx: 63 years
- Most aggressive form of ovarian cancer
Epidemiology
Ovarian carcinoma
High-grade serous carcinona = most aggressive ovarian cancer
- 25% of all ovarian neoplasms; only 1% of cancers
- Account for 70% of ovarian tumors in ages 1-20
Epidemiology
GCT
- Account for 3% of all ovarian cancers
- Average age at Dx: 40s
Epidemiology
Sex cord-stromal cancers
TP53 mutation
Genetic Abnormalities
Associated with high-grade ovarian serous carcinoma, endometrial serous carcinoma
Inactivation of BRCA1/2
Genetic Abnormalities
Associated with high-grade ovarian serous carcinoma
Inactivation: mutation or hypermethylation
KRAS mutation
Genetic Abnormalities
Associated with low-grade ovarian serous carcinoma, ovarian mucinous carcinoma, endometrial endometrioid carcinoma
BRAF mutation
Genetic Abnormalities
Associated with ovarian mucinous carcinoma
PIK3CA mutation
Genetic Abnormalities
Associated with low-grade ovarian serous carcinoma, ovarian endometrioid carcinoma, ovarian clear cell carcinoma, endometrial carcinoma (types 1 & 2)
ARID1A mutation
Genetic Abnormalities
Associated with ovarian endometrioid carcinoma, ovarian clear cell carcinoma
PTEN mutation
Genetic Abnormalities
Associated with ovarian endometrioid carcinoma, endometrial endometrioid carcinoma
- Advancing age
- Obesity
- Nulliparity
- Endometriosis
- Early menarche / late menopause
- Genetic factors
Ovarian cancer
Risk Factors
- 40% lifetime risk of ovarian cancer
- 60-80% lifetime risk of breast cancer
Risk Factors: Genetic
Inactivation of BRCA1
Chromosome 17
- 20% lifetime risk of ovarian cancer
- 60-80% lifetime risk of breast cancer
Risk Factors: Genetic
Inactivation of BRCA2
Chromosome 13
- Increased risk of colon cancer
- 60-80% lifetime risk of endometrial cancer
- 10% lifetime risk of ovarian cancer (10%)
Risk Factors: Genetic
Lynch syndrome / HNPCC
HNPCC: hereditary non-polyposis colorectal cancer
- Oral contraceptive pills
- Multiparity
- Lactation
- Tubal ligation
- Opportunistic salpingectomy
Ovarian cancer
Protective Factors
- Bloating
- Abdominal pain
- Weight changes
- Early satiety
- Changes in stool caliber
- Constipation
- Vaginal discharge
Symptoms
Ovarian cancer
Endometriosis
Risk Factor
Increased risk: clear cell ovarian cancer; endometrioid ovarian cancer
LDH
Markers
Dysgerminoma
Schiller-Duval bodies
Histological Hallmarks
Endodermal sinus tumor
AFP
Markers
- Endodermal sinus tumor
- Embryonal carcinoma
- Immature malignant teratoma
B-hCG
Markers
Choriocarcinoma
Syncytioblasts produce B-hCG
Most common malignant GCT
* Most common in women age < 30
* Bilateral: 15-20% of cases
Epidemiology
Dysgerminoma
Most common ovarian GCT
* Bilateral: 12% of cases
Mature cystic teratoma (dermoid cyst)
Most common ovarian GCT
* Bilateral: 12% of cases
Mature cystic teratoma
Carl-Exner bodies
Histological Hallmarks
Granulosa cell tumor
Granulosa cell tumor
Risk Factor
Increased risk for endometrial carcinoma (10%)
Due to estrogenic effects
FOXL2 mutation
Genetic Abnormalities
Associated with granulosa cell tumor
Inhibin B
Markers
Granulosa cell tumor
- Lymphocytic infiltrate
- Multinucleated giant cells
Histological Hallmarks
Dysgerminoma
Coffee bean nuclei
Histological Hallmarks
Granulosa cell tumor
Reinke crystals
Histological Hallmarks
Leydig cell tumor
Rokitansky’s tubercle
Histological Hallmarks
Mature cystic teratoma (dermoid cyst)
Psammoma bodies
Histological Hallmarks
Ovarian papillary serous carcinoma
Hobnail cells
Histological Hallmarks
Ovarian clear cell carcinoma
Ovarian mucinous carcinoma
Associations
Associated with pseudomyxoma peritonei
MLH1 mutation
Genetic Abnormalities
Associated with HNPCC
MLH1: DNA MMR gene
MSH2 mutation
Genetic Abnormalities
Associated with HNPCC
MSH2: DNA MMR gene
- Obesity
- Genetic syndromes (e.g., Lynch)
- Endometrial hyperplasia
- Tamoxifen use
Endometrial cancer
Risk Factors
- Smoking
- Combined oral contraceptive
- Intrauterine contraceptive device
Endometrial cancer
Protective Factors
MSI mutation
Genetic Abnormalities
Associated with endometrial cancer
- Accounts for 80% of uterine cancers
- Clinical setting: excess unopposed estrogen & endometrial hyperplasia
- Well-differentiated / low-grade
- Favorable prognosis
Epidemiology
Type 1 endometrial carcinoma: endometrioid
- Accounts for 20% of uterine cancers
- Non-estrogen dependent
- Clinical setting: atrophic endometrium or polyps
- Poorly-differentiated / high-grade
- Poor prognosis
Epidemiology
Type 2 endometrial carcinoma: papillary serous, clear cell or carcinosarcoma (MMMT)
* High-risk histologies
MMMT = malignant mixed mesodermal tumor
Uterine tumor containing a malignant epithelial component & a malignant mesenchynal component
Pathology
Carcinosarcoma (MMMT)
Atypical endometrial hyperplasia
Treatment
- Fertility-sparing: progesterone; oral, Mirena IUD
- Non-fertility sparing: simple hysterectomy
Related to high-risk HPV infection
1. Early onset of sexual activity
2. Multiple / high-risk sexual partners
3. History of STIs
4. Immunosuppression
5. History of VIN / VAIN
6. Smoking
Cervical cancer
Risk Factors
- Associated with high-risk HPV infection
- Risk factors: smoking; immunosuppression
- HPV-16 most common
- More common in younger women: 40s-50s
- Progresses to warty & basaloid carcinoma
- High-grade
- Long time to progression
Epidemiology
VIN, usual type
- Often associated with lichen sclerosis
- 5% of LS will develop SCC within 10 years
- Usually not associated with HPV infection
- More common in older women: 70s
- Progresses to invasive SCC
- Well-differentiated
- Short time to progression
Differentiated VIN
VIN, keratinizing type
Vulvar Paget’s Disease
Treatment
Wide local excision
Drains to inguinal lymph nodes first, followed by pelvic lymph nodes
Pathology
Vulvar cancer
Early stage vulvar cancer
Treatment
Vulvectomy with lymph node dissection (LND)
VIN
Treatment
Wide local excision
Most common site of extramammary Paget’s disease
Epidemiology
Vulva
2nd most common vulvar malignancy
Epidemiology
Vulvar melanomoa
Most common finding in vulvar melanoma
Epidemiology
Pigmented lesion
- Asians
- Diet low in animal fat, carotene, Vit A
- Extremes of reproductive years
- History of infertility / many abortions
- Blood type A / AB
Gestational trophoblastic disease
Risk Factors
HPL
Markers
Gestational trophoblastic neoplasia (GTN)
Low-risk GTN
Approach to Therapy
Single agent CTX w/ methotrexate or actinomycin D
* If no response to MTX, can switch to act-D
* Rx for GTD if pt. has renal insufficiency: act-D
High-risk GTN or choriocarcinoma
Approach to Therapy
Multi-agent CTX w/ EMA-CO
* E = etoposide
* M = methotrexate
* A= actinomycin D
* C = cyclophosphamide
GTD
Approach to Therapy
Surgical: D&C