Pocket ObGyn – Gestational Trophoblastic Neoplasia

Dec 9, 2019 admin PHỤ KHOA, SẢN KHOA, SINH DỤC, UNG THƯ 0

Pocket ObGyn – Gestational Trophoblastic Neoplasia
See Abbreviations

Definition and Epidemiology

  • Originates from abn proliferation of placental Incid varies by geography (2/1000 in Japan, 0.6–1.1/1000 in Europe/North America) (NEJM 1996;335:1740)
  • GTN includes 4 types of related tumors: Complete & partial hydatidiform mole, invasive mole, placental site trophoblastic tumor, & Invasive GTN usually follows molar Preg, but can follow any gest.
Molar Pregnancy

 

Features of complete and partial hydatidiform moles
Feature Complete mole Partial mole
Karyotype 46XX (90%), 46XY (10%) 69 XXY (90–93%)
Fetal or embryonic tissue Absent Present
Hydatidiform swelling of chorionic villi Diffuse Focal
Trophoblastic hyperplasia Diffuse Focal
Scalloping of chorionic villi Absent Present
Trophoblastic stromal inclusions Absent Present
Implantation-site trophoblast Diffuse, marked atypia Focal, mild atypia
Risks Low dietary carotene.Vit A deficiency. Age >35 y. Prev SAB. Prev SAB. Irreg menses. OCP use >4 y.
From Berkowitz RS, Goldstein DP. Chorionic tumors. N Engl J Med. 1996;335(23):1740–1748.
  • Clinical presentation (NEJM 1996;335:1740)

Complete hydatidiform mole: Vaginal bleeding (89–97%); enlarged uterus for gestational age (38–51%);Theca lutein ovarian cysts (26–46%); hyperemesis gravidarum (20–26%); preeclampsia (12–27%); hyperthryoidism; respiratory distress (2–27%)

Partial hydatidiform mole: Signs & sx of incomplete or missed abortion; SGA or IUGR; less likely to present w/ medical complications

Diagnostic w/u pelvic US, serum hCG level, CBC, PT/PTT, renal & liver fxn studies, type & screen, pre-evacuation chest radiograph, if exhibiting sx of hyperthyroidism ® TSH, T3/T4; hyperemesis ® chemistry

 

Figure 21.1 Transverse uterus ultrasound image of a molar pregnancy with characteristic snowstorm pattern

 

Uterus

 

 

 

 

 

 

 

Molar pregnancy

(Courtesy of Patricia Johnson, University of Virginia)

•   Rx

Suction curettage followed by sharp curettage if pt desires future fertility. Rh immune globulin for RhD-negative women. Hysterectomy an option if pt desires sterilization.

Prophylactic chemo following molar Preg (Obstet Gynecol 1986;67:690) is controversial. Decreases postmolar GTN from 47–14% in high risk (WHO > 6; see below) complete moles. Can be used in high-risk moles or if f/u unreliable.

  • Post rx surveillance (Obstet Gynecol 2004;103:1365)

Serum hCG level w/i 48 h of evacuation

Serum hCG levels every 1–2 w until normalized (<5) Serum hCG level monthly for 6 mo once negative

Use of reliable hormonal contraception needed during surveillance

Invasive Mole (Chemo Research and Practice 2011;2011:1; Obstet Gynecol 2004;103:1365)

  • Risk of developing persistent/invasive GTN: 15–20% after complete hydatidiform mole; 1–4% after partial hydatidiform mole.
  • GTN diagnosed after molar gest if:

³4 hCG values plateau (±10%) over at least 3 w

³10% rise in hCG for ³3 values over at least 2 w Presence of histologic choriocarcinoma

Persistence of hCG 6 mo after molar evacuation (& rule out new Preg)

  • Metastatic GTN seen in 4% after evacuation for complete mole (Chemo Research and Practice 2011;2011:1)

Most common sites for metastases: Lung (80%), vagina (30%), brain (10%), & liver (10%)

Choriocarcinoma (Obstet Gynecol 2004;103:1365)

  • Arises from cytotrophoblasts & syncytiotrophoblasts. Does not contain chorionic villi. 50% arise from complete hydatidiform mole, 25% from nml pregnancies, 25% from spont abortion/ectopic Preg. Most aggressive.
Placental Site Trophoblastic Disease
  • Uncommon variant of choriocarcinoma. Predominantly composed of intermediate Tumor marker, HPL.
  • Secrete small amounts of bhCG ® tumor burden may be large before hCG levels detectable

Subseq Preg after GTN (NEJM 1996;335:1740)

  • 1% subseq pregnancies result in molar gest; women w/ GTN in remission have nml Preg rates following GTN; no ­ incid of spont abortion, congenital anomalies,

C-section

Survival after GTN
  • Prog depends on age, interval btw gest & dz, & serum bHCG
  • Low risk: 84% stage I GTN & 87% low-risk stages II–III ® complete remission w/ single-agent chemo (J Reprod Med 2006;51:835; Semin Oncol 1995;22:166; J Reprod Med 1992;37:461; Obstet Gynecol 1987;9:390; Gynecol Oncol 1994;54:76)

 

Treatment regimens for GTN
Protocol for low-risk GTN (stage I or low-risk stage II/III & WHO score £6)
Initial therapy Sequential methotrexate/actinomycin D

Hysterectomy if finished w/ childbearing (w/ adjunctive single-agent chemo)
Resistant therapy MAC

EMACO, if MAC fails

Hysterectomy (w/ adjunctive multiagent chemo) Local uterine resxn (to preserve fertility)
F/u 12 consecutive months of undetectable hCG levels Contraception for 12 mo
Protocol for high-risk GTN (stage II or stage III & WHO score ³7)
Initial therapy EMACO or EMAEP (etoposide, methotrexate, actinomycin D, carboplatin)
Resistant therapy VBP

Surg, as indicated
F/u 12 consecutive months of undetectable hCG levels Contraception for 12 mo
Protocol for Stage IV GTN
Initial therapy EMACO; w/ brain mets ® radiation, craniotomy for periph lesions; w/ liver mets ® embolization, resxn to manage complications
Resistant therapy EMAEP;VBP; experimental protocols; Surg, as indicated; hepatic artery infusion or embolization
F/u Weekly hCG levels until undetectable for 3 w, then monthly hCG ´

24 mo Contraception ´ 24 mo
From May T, Goldstein DP, Berkowitz RS. Current chemotherapeutic management of patients with gestational trophoblastic neoplasia. Chemother Res Pract. 2011;2011:806256.

 
  • High risk: 80% pts w/ stage IV dz achieve remission w/ multiagent therapy
Modified WHO prognostic scoring system as adapted by FIGO
Low risk, WHO score of 0–6; high risk, WHO score of ³7
Score 0 1 2 4
Age (yr) <40 ³40 – –
Antecedent Preg Mole Abortion Term –
Interval months from index Preg <4 4–6 7–12 ³13
Pretreatment serum bhCG <103 103–<104 104–<105 ³105
Largest tumor size – 3–<5 cm ³5 cm –
Site of metastases Lung Spleen, kidney GI Liver, brain
Number of metastases – 1–4 5–8 >8
Prev failed chemo drugs – – 1 ³2

 
  • Risk of relapse: 2% nonmetastatic GTN; 4% low-risk metastatic GTN; 13% pts high-risk metastatic GTN (Cancer 1996;66:978). Median time to relapse: 5 mo. Survival rate for relapsed GTN: 77.8% (J Reprod Med 2006;51:829).

 

FIGO staging of GTN, 2009
stage i Dz confined to uterus
stage ii GTN extends outside uterus but limited to genital structures (adnexae, vagina, broad ligament)
stage iii GTN extends to lungs, w/ or w/o known genital tract involvement
stage iv All other metastatic sites (brain, liver)
From Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia.

Int J Gynaecol Obstet. 2009;105(1):3–4.

See Abbreviations

BÀI LIÊN QUAN