GTD/GTN and Cancer in Pregnancy Flashcards
Patient with 1.4 mm melanoma at 23 weeks EGA s/p RLE and margins negative. What is the most appropriate next step in management?
Observation
(NOT interferon therapy or chemo)
Patient with late second trimester/early third trimester pregnancy, s/p USO c/w EST (endodermal sinus tumor) (unstaged). What is the most appropriate treatment?
A) observation
B) reoperation for staging
C) start BEP immediately
D) do MRI and start chemotherapy after delivery if no e/o disease on MRI
E) assess fetal lung maturity and start chemo after delivery
duplicate, and RED
C) start BEP immediately
- any stage endodermal sinus tumor, embryonal tumor or nongestational choriocarcinoma requires chemo
What chemo drug is least teratogenic in 1st trimester?
Cyclophosphamide or doxorubicin
NOT: MTX, 5-FU
What chemotherapy is the most teratogenic ?
MTX (less so 5FU)
Radiation within the first two weeks of pregnancy causes what?
Embryonic death
Radiation at 2-16 weeks EGA causes?
Microcephaly, growth retardation
Radiation at 16-20wks EGA causes?
Same as 2-16, but less severe (microcephaly, growth retardation)
Radiation at >30 weeks EGA causes?
Causes few issues
41 yo patient presents with GTN characterized by 7 pulm mets (no size given), antecedent molar pregnancy, interval 8 months, HCG 1,000. What treatment is most appropriate?
Single-agent MTX
WHO score of 6
Stage 3 (lung mets)
WHO score
know WHO scoring
What is the genetic make-up of a complete mole?
46XX paternal origin most common
Rarely 46XY
46XX (90%) (monoandric with replication in empty ovum of a single sperm’s haploid chromosomes) and 46XY (10%) (diandric - diaspermic fertilization of empty ovum)
“Daddy’s little girl”
What is the common genetic make-up of a partial mole?
69XXY
Sometimes 69XXX
Biparental and diandric origin (two sperm fertilize one egg)
Pregnant patient at 10wks GA with breast microcalcifications. What is best next step?
A) biopsy
B) termination
C) ultrasound
D) mammogram
2018 red Q
Biopsy
Pregnant patient at 10wks GA with palpable breast mass, best next step?
A) biopsy
B) termination
C) ultrasound
D) mammogram
Ultrasound
If patient has elevated serum HCG but no clinical evidence of GTD what is next step?
A) Urine assay
B) repeat serum HCG
C) check free subunit
Urine Assay
- if urine assay is. negative and serum levels do not decrease appropriately with parallel dilution, the molecule measures is likely a pseudogonadotropin or phantom hCG.
Which has the highest WHO score?
A) Liver mets
B) HCG 5000
C) mole as antecedent pregnancy
Liver mets
Stage IA G3 serous ovarian CA at 16wks preg?
6 cycles carbo/tax
WHO score - what has greatest impact?
A) HCG 10^4-5
B) interval >12 months from antecedent pregnancy
C) GI metastasis
Interval >12 months
What is the least likely cancer in a pregnant patient with no history of malignancy
a. lymphoma
b. melanoma
c. thyroid
d. colon
e. breast
Colon
most common
1 breast cancer
2 lymphoma
3 cervix
4 leukemia
5 melanoma
https://ascopubs.org/doi/10.1200/JCO.2009.23.2801#
ACS: The most common types of cancer found during pregnancy are, breast, cervical, thyroid, colon, and ovarian cancers, as well as melanoma, lymphoma, and leukemia
Other source: Thyroid cancer is the second most common malignancy during pregnancy, preceded only by breast cancer with an incidence of 14 per 100,000 live births
incidence of colorectal cancer (CRC) of 1 : 13,000
Tumor marker least likely to be affected by pregnancy
A) LDH
B) hCG
C) CA-125
D) inhibin
LDH
*CA-125, apha fetoprotein and bHCG are affected
*Anti-mullerian and inhibin B are not affected
Sixteen week pregnant patient has adnexal mass removed which is consistent with yolk sac tumor what do you do
A. start chemo
B. observe
C. other options
Start chemo
Pt with UPT+, hyperglycos hCG neg, hCG plateaus after 3 cycles MTX at 145-150. Next step?
A) Observe
B) actD
C) multidrug chemo
D) hyst
Observe - quiescent
hCG-Hyperglycosylated (%) appears to reliably identify active trophoblastic malignancy. It is a 100% sensitive marker for discriminating quiescent GTD from active GTN/choriocarcinoma. It is also a marker for the early detection of new or recurrent GTN/choriocarcinoma
Pt with elevated serum hCG no other signs of GTD, what is next step?
A) UPT
B) Repeat serum hCG
C) Measure free hcG
UPT - due to heterophilic antibodies that are not excreted in urine
Pt on tamoxifen x 2 years, 8 weeks pregnant: what do you recommend
Discontinue tamoxifen for pregnancy and breastfeeding
- while no specific congenital anomaly has been associated with tamoxifen and pregnancy, the following have been reported (Goldenhar’s syndrome, Pierre Robin sequence, ambiguous genitalia, clitoral hypertrophy). The medication should ideally be stoped at least 2 months before conception.
Pregnant pt, cone bx stage IA1 squamous cervical cancer neg margins. What next?
Observe
Pregnant pt cone bx CIS, + margins, pos ECC - what to do?
Observe
Characteristics of a PARTIAL MOLE
- PARTLY paternal
- triploid
- fetal PARTs
- focal PARTial edema (rather than diffuse)
- rare med complications (such as hyperthyroid, toxemia) (think partial risk)
- SGA
- < 5% malignant sequelae (think partial risk)
Most common ovarian tumor in pregnancy
Non-malignant teratoma
(tumor not cancer)
Most common ovarian cancer in pregnancy
Dysgerminoma - germ cell tumors make up 40% ovarian tumors in pregnancy
Quiescent vs active GTN
Persistent, unchanging low levels < 200 of real hcG for at least 3 months with hx of GTD or SAB but no detectable disease.
6-25% will develop active disease (increase in hyperglycosylated hCG with cytotrophoblastic invasion) and total hCG.
Only tx once sustained rise or overt clinical disease detected.
AGC-NOS during pregnancy, colpo neg at 22 weeks, what next?
Postpartum pap
41 yo with choriocarcinoma 7 months from pregnancy with pulm mets too numerous to count. How do you treat?
EMACO - high risk WHO score (7+)
Stage 3 (pulm mets)
32 weeks pregnant, 7 cm cystic adnexal mass - what do you do?
Ultrasound after delivery
14 weeks with ASCUS HPV +, no gross lesions, what do you do?
Colpo NOW
12 weeks pregnant, endodermal sinus tumor, next step?
Immediate chemo with BEP
* any stage endodermal sinus tumor, embryonal tumor or nongestational choriocarcinoma requires chemo
Do complete or partial moles have villous capillaries present?
Partial mole have villous capillaries intact
Which type of GTN is typically treated with hysterectomy?
Placental site trophoblastic tumor PSTT - because it is chemoresistant
*test for human placental lactogen, intermediate size cytotrophoblast is noted on pathology
Common cancers during pregnancy include?
Breast, cervix, lymphoma, ovary, melanoma, leukemia, thyroid, colorectal (most to least common)
Blood type associated with GTD?
Type A or AB
Common clinical features of GTD?
Vaginal bleeding
Excessive uterine size
Prominent theca lutein cysts
Toxemia (preeclampsia)
Hyperemesis
Hyperthyroidism
Trophoblastic emboli
Does p57/kip2 stain positive in partial or complete moles?
p57/kip2 is IHC marker for PARTIAL mole
Nuclear staining in cytotrophoblasts and villous stromal cells
p57 is paternally imprinted, maternally expressed gene CDKN1C (p57KIP2)
Also >90% expression in Choriocarcinoma
Risk factors for GTN?
- Age >40
- Prior molar pregnancy
- Asian or American Indian ancestry
Risk factors for Molar Pregnancy?
- Extremes of maternal age (< 15 or > 35)
- Prior molar pregnancy
How do PSTT and ETT differ from choriocaricnoma?
- consist predominantly of intermediate trophoblast
— PSTT: neoplastic proliferation of intermediate trophoblasts at placental implantation site
— ETT: neoplastic chorionic type intermediate trophoblasts
[— vs choriocarcinoma, composed of syncytiotrophoblast, cytotrophoblast and intermediate trophoblast] - low HCG and HPL
- tend to remain in uterus
- chemoresistant
Surgical management, PLND if appears contained to uterus (5-15% risk nodal mets)
GTN pretreatment evaluation
- H&P
- HCG level
- Hepatic, thyroid, renal function tests
- CBC, T&S (Rhogam if Rh-)
- CXR
- Pelvic US
If metastatic disease is found:
- CT chest/abd/pelvis
- MRI head
- can consider PET per UTD
- CSF HCG level (if head imaging neg and still suspicious, normal value plasma to CSF ratio < 60:1)
Young patient with an initial WHO score 5 being treated with MTX. Now with two weeks of rising HCG, what should you do?
A) switch to actinomycin-D
B) switch to EMA-EP or EMA-CO
C) CT scan
D) hysterectomy
E) D&C
Per NCCN: If HCG <1000, switch to weekly actinomycin-D. If HCG >= 1000, repeat workup to check for mets (i.e. CT scan)
NCCN: Pulse Act-D should not be used as secondary therapy for failed MTX, nor primary therapy for those with CCA (use fixed daily dose Act-D x5 days)
Risks factors for GTD
extremes maternal age, OB hx prior molar pregnancy or SAB, diet low in animal fat/carotene/vitA, blood type A or AB
Do complete or partial moles have villous capillaries present?
Partial moles
Which is not associated with GTD risk?
A) Extremes of age
B) prior mole
C) low beta carotene
D) High animal fat intake
E) NLRP7 gene mut
F) Asian
D) High animal fat intake
Low animal fat intake is associated with increased GTD risk
Cervical cancer and pregnancy - outcomes, stage at diagnosis?
Stage for stage, the course of disease and prognosis of cervical cancer in pregnant patients are similar to those of nonpregnant patients
Most patients are diagnosed at an early stage of disease. This is probably a result of routine prenatal screening, but it is also possible that advanced stage disease interferes with conception
Staging lymphadenectomy during pregnancy may provide the most definitive information on lymph node status. This information is important, as patients diagnosed with high-risk (node-positive) disease should be counseled about the importance of initiating immediate definitive therapy, including pregnancy termination.
Per UTD
Patient with GTN with lung mets and otherwise no other significant risk factors - best treatment?
Single agent MTX (multi-day dosing)
(lung mets get 0 points)
What are the subsequent pregnancy outcomes of patient with complete molar pregnancy followed by GTN that was treated with chemotherapy?
Expect normal reproduction (no increased risk of prenatal/intrapartum complications)
Increased risk of future molar pregnancy (1/100 patients will have at least 2 molar pregnancies)
So after 1 mole, risk of second is 1-2%
After 2 moles, risk of third is ~15%
Familial repetitive mole: missense mutation in NLRP7 on chromosome 19
What confers a worse prognosis in PSTT?
- advanced stage
- older age
- longer interval from previous pregnancy
- previous term pregnancy
- higher serum hCG level
- higher mitotic rate
- coagulative tumor necrosis
- clear cytoplasm
- PSTT is chemoresistant - so if distant metastasis outsie of uterus, this is bad because limited options.
70% PSTTs act in a benign manner and 30% are aggressive with distant mets
PSTT may have a higher free-beta subunit of HCG
