Neoplasms part 2 Flashcards
Type I endometrial CA
Caused by unopposed estrogen stimulation
Usually endometroid histology
Generally good prognosis- 90% cure stage I
About 70% diagnosed stage I
Type II endometrial CA
Unrelated to estrogen stimulation
Usually nonendometroid histology (clear cell, papillary serous)
Worse prognosis
RFs for endometrial CA
Obesity- extraovarian aromatization of androstenedione to estrone
Granulosa-theca cell ovarian tumors- about 15% have endometrial CA
Chronic anovulatory cycles (Stein-Leventhal syndrome)
Postmenopausal pts treated with unopposed ERT
Long-term tamoxifen
Alcohol intake: 2 or more drinks per day
Obesity and gynocologic CAs
BMI >35 is associated with increased mortality compared with nl wt in ovarian, cervical CA, and endometrial CA
What is the MC tx for endomtrial CA?
TAH with bilateral salpingo-oophorectomy
Endometrial carcinoma screening and prevention
In high risk pts- annual endometrial sampling and TVUS beginning at age 30-35
OCPs- possible chemoprevention
Risk-reducing hysterectomy for atypical endometrial hyperplasia
Endometrial adenocarcinoma
MC, typically postmenopause
Associated with excessive estrogen exposure
Often dx-ed with endometrial hyperplasia
Types of endometrial CA
Adenocarcinoma
Adenosquamous
Clear cell carcinoma
Serous carcinoma
Endometrial CA sx
Postmenopausal bleeding
Dysfunctional uterine bleeding (5% of endo CAs dx-ed
Name the types of endometrial hyperplasia from least risk of progression to CA to highest risk
Simple hyperplasia without atypia Complex hyperplasia without atypia Simple atypical hyperplasia Complex atypical hyperplasia -These pts also have significant risk for concurrent endometrial adenocarcinoma
Genetic risk factors for endometrial CA
Lynch syndrome
Cowden syndrome
-Characteristic benign mucocutaneous hamartomas
-Uterine fibroids-40% of pts
-Increased endometrial, breast, thyroid, colorectal, and renal CAs
Screening and prevention of endometrial CA in pts with genetic RFs
Annual endometrial sampling and TVUS beginning at age 30-35
Risk-reducing hysterectomy
Oral contraceptives for possible chemoprevention
Endometrial CA workup
TVUS to evaluate endometrial lining
Endometrial CA: stage and spread at dx
Majority of uterine adenocarcinomas are dx-ed at early stage:
- Confined to primary site (70%)
- Spread to regional organs and lymph nodes (20%)
- Distant metastases (10%)
Stage IA endometrial CA
Tumor confined to the endometrium
Stage IB endometrial CA
Invasion <1/2 myometrial thickness
Stage IC endometrial CA
Invasion >1/2 the myometrial thickness
Stage IIA endometrial CA
Endocervical glandular involvement only
Stage IIB endometrial CA
Cervical stromal invasion
Stage IIIA endometrial CA
Tumor invades serosa or adnexa, or malignant peritoneal cytology
Stage IIIB endometrial CA
Vaginal and/or parametrial metastasis
Stage IIIC1 endometrial CA
Metastasis to pelvic lymph nodes
Stage IIIC2 endometrial CA
Mets to P.A. nodes with or without pelvic lymph node metastasis
Stage IVA endometrial CA
Invasion of the bladder or bowel
Stage IVB endometrial CA
Distant metastasis, including intra-abdominal or inguinal LNs
Tx of endometrial CA: surgical
Surgical tx includes: Peritoneal fluid cytology
Abdominal exploration
Pelvic and para-aortic lymphadenectomy
Abdominal hysterectomy and bilateral salpingo-oophorectomy
Tx of endometrial CA: radiation and chemo
Commonly added for more advanced stage and high-risk features High-risk features include: Pathologic grade 3 Serous or clear-cell tumors Invasion of >1/2 the myometrium Extension to the cervix or adnexa
How are endometriosis and ovarian CA related?
They both involved the complement pathway
Current genetic testing research aims to separate women with benign endometriosis with endometriosis-associated ovarian CA
Normal ovary size in premenopausal women
3.5 x 2 x 1.5 cm
Nl ovary size in pt 2-5 yrs after menopause
1.5 x 0.7 x 0.5 cm
What are u/s findings in ovaries that are suspicious for malignancy
Cystic mass vs solid
Smooth capsule vs excrescences
Presence of internal septa or papillae
Presence of ascites is very suspicious for malignant process
Serum CA-125 and ovarian CA
Elevated in 80% of all pts with serous cystadenocarcinoma of the ovary but in only 50% of pts with stage I disease. Therefore not great for early dx and not for general screening.
Used for monitoring response to therapy
Malignant adnexal lesions may be _____ or _______ dz from the uterus, breast, or gastrointestinal tract
Primary
Metastatic
PE of adnexal neoplasm
Cervical, supraclavicular, and/or inguinal LAD and/or the presence of pleural effusions or ascites
Breast exam is especially important bc the ovary is a common site of metastasis from breast carcinoma
Serum CA-125 in benign conditions
Normal value
Rarely greater than 100 to 200 U per mL
<35 U/mL
Screening for ovarian CA
Do not screen women at average risk
Screen women at increased risk- women with familial ovarian CA syndromes, who have not undergone prophylactic oophorectomy
Screen with a combo of CA 125 and TVUS. Start at age 30 or 5-10 years earlier than the earliest age of 1st dx of ovarian CA in the family
Screen every six months.
Human epididymis protein 4
An antigen derived from human epididymis protein, a product of the WFDC2 gene that is overexpressed in pts with serous and endometrioid ovarian carcinoma
Used to monitor recurrent or progressive dz in pts with EOC
Lab reference range for human epididymis protein 4
Less than or equal to 150 pM
Types of epithelial ovarian CA from most common to least common
High-grade serous CA Endometrioid CA Clear cell CA Mucinous CA Low-grade serous CA
Epithelial ovarian carcinoma
CAs thought to arise from ovaries, but current thought is many of these CAs arise from Fallopian tubes or from Mullerian epithelium
Prevention of ovarian Ca in women with familial CA syndromes and genetic predispositions for ovarian CA
These women may have risk-reducing surgery-BSO or hysterectomy and BSO
Genetic mutations with increased risk of ovarian CA and other CAs
BRCA 1 and 2 gene mutations
Lynch syndrome
What is the risk for developing ovarian CA related to?
Cause is unknown
Risk is related to parity
The more children a woman has and the earlier in life she gives birth, the lower her risk of ovarian CA
Sx of ovarian CA- general
Often vague and non-specific
Women and their doctors often blame the sx on other, more common conditions.
Has usually spread beyond the ovaries by the time CA is dx-ed
Sx of ovarian CA- specific
Sense of pelvic heaviness Vague lower abdominal discomfort Vaginal bleeding Wt gain or loss Abnl menstrual cycles Unexplained back pain that worsens over time Increased abdominal girth Non-specific GI sx
Carcinosarcoma ovarian CA
Mean age dx 75 years
Histology is mixture of malignant epithelial and stromal tissues
Borderline/LMP ovarian CA
Termed semimalignant, good prognosis
Surgery without chemo is current tx
Age at dx tends to be around 10 yrs younger than the other epithelial ovarian CAs
Serous and mucinous (serous more common) subtypes
CA-125 not helpful in dx or f/u
Sex cord stromal tumors-ovarian CA
Composed of Granulosa cells Theca cells Sertoli cells Leydig cells Fibroblasts of stromal origin, single cell type or in various combinations CA-125 not useful in dx or f/u Chemo tx usually bleomycin, etoposide, and cisplatin
Granulosa-theca cell tumor
Often hormonally active and can produce large amounts of estrogen: pt may initially present with bleeding from endometrial hyperplasia
Cause of 1/3 of pts with Sertoli-Leydig tumors
Virilized from androgens and androgen precursors, causing: Oligomenorrhea Amenorrhea Breast atrophy Hirsutism Deepening voice Male pattern baldness Acne Clitoral enlargement
What are the most common malignant ovarian tumors in young women?
Dysgerminoma and immature teratoma
Tumor markers for ovarian CA germ cell tumor
LDH (best)
HCG
AFP
S/sx of ovarian germ cell tumor
Prognosis
Tx
Tend to occur in young women and girls: swelling, possible abd pain
Curable if dx-ed and treated early
Tx is surgery then chemo
Tx of ovarian CA
Surgical tx may be sufficient for malignant tumors that are well-differentiated (grade 1) and confined to the unruptured ovary (stage 1)
Addition of chemo is required for more aggressive tumors (grade 2 or 3) that are confined to the ovary
Pts with advanced disease (stage 2, 3, 4) standard of care is maximal cytoreductive surgery combined with multiagent chemo. Current favored regimen is carboplatin, Taxol, and Avastin
Stage I ovarian CA
Limited to one or both ovaries
Stage IA ovarian CA
Involves one ovary
Capsule intact
No tumor on ovarian surface
No malignant cells in ascites or peritoneal washings
Stage IB ovarian CA
Involves both ovaries
Capsule intact
No tumor on ovarian surface
Negative washings
Stage IC ovarian CA
Tumor limited to ovaries with any of the following: capsule ruptured, tumor on ovarian surface, positive washings
Stage II ovarian CA
Pelvic extension or implants
Stage IIA ovarian CA
Extension or implants onto uterus or fallopian tube
Negative washings
Stage IIB ovarian CA
Extension or impolants onto other pelvic structures
Negative washings
Stage IIC ovarian CA
Pelvic extension or implants with positive peritoneal washings
