Gynecologic Cancers Flashcards
What percentage of women get cancer?
1/3 women at some point in their lives
Relative incidence / mortality of gynecologic cancers
- Incidence: uterine > ovary > cervix
* Mortality: ovary > uterine > cervix
Risk factors for endometrial cancer (7)
•Mainly related to estrogen exposure: obesity (estrogen is unregulated by adipocytes), nulliparous, late menopause, unopposed estrogen, atypical hyperplasia, diabetes, HTN
Type I vs Type II endometrial cancer Association to estrogen Prevalence Population Aggression Mutation Histology
- Type I estrogen related. Type II not.
- 80% are type I, 15% are type II
- Pxs are younger / fatter in type I. Older / thinner in type II.
- Type I is less aggressive than type II
- Type I has mutation in PTEN and KRAS. Type II as mutation in p53.
- Type I has endometrioid histology (cells still columnar). Type II has serous histology (looks similar to ovarian cancer; cells not columnar, high N/C ratio, many mitoses)
Most common presentation of endometrial cancer
Most common complaint is abnormal post / peri-menopausal bleeding.
Indications for endometrial biopsy (5)
- Abnormal uterine bleeding – postmenopausal bleeding (always abnormal), perimenopausal intermenstrual bleeding, bleeding w/ hx of anovulation
- Postmenopausal women w/ endometrial cells on Pap test
- Thickened endometrial stripe via sonography
Staging endometrial cancer
- Surgical staging includes cytology, TAH / BSO, and pelvic / aortic lymph node dissection.
- Stage 1a: less than 50% of myometrium involved
- Stage 1b: >50% of myometrium involved
- Stage 2: cervix involved
- Stage 3: Uterine serosa, adnexae, vagina, or pelvic / aortic node metastases
- Stage 4: bladder / bowel involvement, inguinal node, or distant metastases.
Stage 1 is most common (70%)
Treating endometrial cancer (3)
- Surgery is primary treatment for endometrial cancer.
- Adjuvant postop therapy – used for stage II-IV
- Whole pelvic radiation + vaginal cuff boost: done for stage II / III
- Chemo
Risk factors for recurrent endometrial cancer (5)
High grade (II / III), depth of myometrial invasion, tumor size (>2cm), invasion of lymph / vascular space, aggressive histologic cell type (serous)
Treating recurrent endometrial cancer
Recurrent disease is considered incurable (except for isolated vaginal cuff recurrence in a woman who did not receive radiation). Recurrent disease is treated w/ platinum-based chemo
Risk factors (4) and preventative factors (5) for ovarian cancer
- Increasing risk factors – age (post-menopausal; biggest risk), family hx, infertility / low parity / uninterrupted ovulation, hx of cancer (esp breast)
- Decreasing risk factors – OCPs, pregnancy, tubal ligation, trans-tubal factor, breast feeding
Mutations in ovarian cancer
Low grade (4)
High grade
1 other
- Low grade tumors often have mutations in KRAS, BRAF, PTEN, and beta-catenin
- High grade tumors often have p53 mutation (most common mutation overall)
- BRCA 1 / 2 germline mutation associated w/ 35-65% lifetime risk
From where do most ovarian cancers originate?
70% originate from surface epithelial cells (mesothelium). Many are now thought to arise from the fimbriated end of the fallopian tube.
Ovarian cancer histology
Most are high grade, serous histology. High N/C ratio. Pyknotic. Stain for p53.
Ovarian cancer presentation (5)
Most common complaint is bloating and early satiety. Others include ascites, weight gain (from ascites), and bowel obstruction may be present.
Tumor marker for ovarian cancer
Efficacy
- CA 125 – elevated in 80% of advanced epithelial ovarian cancers.
- Poor sensitivity in stage I. Also poor specificity. NOT a screening test for general population.
Diagnosing ovarian cancer (3)
Often suggested by CT or US, but surgical exploration / pathology is definitive.
Staging ovarian cancer
- Staging is done surgically (like uterine cancer)
- I: confined to ovaries
- II: confined to pelvic organs
- III: spread to upper abdomen. Most common at presentation.
- IV: distant metastasis (lungs / liver).
Treating ovarian cancer (4)
- Optimal therapy is TAH/BSO (total abdominal hysterectomy / bilateral salpingo-oophorectomy) + staging. May include infracolic omentectomy and lymph node examination.
- Reproductive conservation therapy may be better for younger women. Remove just 1 ovary and leave uterus.
- Debulking increases survival.
- Chemotherapy required in all pxs except stage Ia – All pxs should receive a taxane and a platinum.
Prognosis of ovarian cancer after treatment
- 75% of women have a good response to chemo and are in remission after 6-8 cycles. Unfortunately, >50% of women in remission will recur w/in the first 3 years of completing treatment.
- Recurrent ovarian cancer is considered incurable.
Follow-up for ovarian cancer
- Rectovaginal pelvic exam and CA125 every 3-4 months for first 2 years, then 6 months for 3 more years.
- CT scan only if sxs are present
- Discuss HRT (mainly for premenopausal women, which is rare), diet, exercise
What is the most common cause of cancer death in women worldwide?
Cervical cancer
Which strains of HPV are high risk for cervical cancer?
16 and 18
Where does HPV virus most often infect?
Basal epithelium of mucosa. Transition b/w squamous and columnar epithelium is most susceptible.
How does HPV DNA disrupt cell control?
HPV DNA may get incorporated into host DNA, which usually disrupts E2 protein → disrupts normal feedback, so E6 / 7 get overproduced. E6 / 7 normally blocks p53 and Rb, which cause apoptosis. Overall, not enough apoptosis → cancer.
Signs / sxs of cervical cancer (6)
Abnormal / post-coital bleeding, foul vaginal discharge (tumor necrosis), pelvic pain, unilateral leg swelling / pain, pelvic mass, gross cervical lesion
Cervical cancer histology
Koilocytes w/ perinuclear halo (filled w/ virus)
Staging cervical cancer
- I: confined to cervix
- II: upper 2/3 of vagina / parametria involved
- III: lower 1/3 of vagina / parametria involved
- IV: distant disease, including bladder or rectal mucosa
Who is recommended to get the HPV vaccine?
Males / females age 9-26
Treating stage I a / b cervical cancer
- Stage Ia
- Conization – cut off abnormal part of cervix but leave normal cervix.
- Simple hysterectomy – used for micro invasive cancer
- Stage Ib
- Radical hysterectomy – removal of uterus, upper vagina, and pelvic lymph nodes. Preserve ovaries.
- Chemoradiation has equivalent survival to surgery. Used in pxs that can’t have surgery.
Treating stage 2+ cervical cancer (3)
- Chemoradiation is mainstay of tx. NOT surgery due to poor margins.
- 4-5 weeks of external radiation to pelvis.
- 2+ implants (brachytherapy)
- Concurrent cisplatin chemo. Acts as radiation sensitizer and controls metastases.
2 types of cervical cancer recurrence
Treatment
- Central pelvic recurrence – involves residual cervix, vagina, posterior bladder, or anterior rectum. Treat w/ radiation if this was not done before. If radiation was already done, may require en bloc removal of uterus, cervix, vagina, bladder, rectum, and sometimes vulva or peri-anal skin. Drastic, but has cure rates of 50%
- Others – chemotherapy is the only option. Very poor prognosis.
