GESTATIONAL TROPHOBLASTIC DISEASE

OBSTETRICS II
  Dr. Anna Lisa Tan
 

GESTATIONAL  TROPHOBLASTIC  DISEASE   Chromosomal  composition:  

o Triploid  (69XXX,  69XXY,  69XYY)  
 
o Composed  of  1  maternal  and  2  paternal  haploid  sets  of  
Definition   chromosomes  
o Spectrum   of   pregnancy-­‐related   trophoblastic   proliferative   o Non-­‐viable  fetus  of  a  triploid  partial  mole  has:    
abnormalities  
• Multiple  malformation,    
o Abnormal   growth   and   development   of   trophoblast   continue  
• Abnormal  growth  is  common,  82%  have    
beyond  the  end  of  pregnancy  
• Symmetric  growth  restriction  
Outline  
• Diploid  (2%),  Tetraploid  (4%),  unknown  (8%)  
1. Hydatidiform  mole  
o Twin  gestation  of  a  complete  mole  and  a  normal  fetus  and  
• Complete    
placenta  is  sometimes  misdiagnosed  as  a  diploid  partial  mole  
• Partial    
 
2. Gestational  Trophoblastic  Neoplasia  (GTN)  
• Invasive  mole  
SUBSTANTIAL  RISK  OF  DEVELOPING  SUBSEQUENT  GTN:  
• Complete:  20%  
• Chriocarcinoma  
• Partial:  0.5%  
• Post  molar  GTN  
 
3. Placental  Site  Trophoblastic  Tumor  (PSTT)  
4. Epitheloid  trophoblastic  tumor   FEATURES  OF  PARTIAL  AND  COMPLETE  MOLES  
  FEATURE   PARTIAL   COMPLETE  
HYDATIDIFORM  MOLE  (H.  MOLE)   Karyotype   Usually  69XXX  or   46XX  or  46XY  
  69XXY  
o Characterized  histologically  by  abnormalities  of  the  chorionic   PATHOLOGY  
villi   Embryo-­‐fetus   Often  present   Absent  
o In  the  form  of:   Amnion-­‐  fetal  RBC   Often  present   Absent  
• Trophoblastic  proliferation   Villous  edema   Variable,  focal   Diffuse  
• Edema  of  villous  stroma   Trophoblastic   Variable,  focal,  slight   Variable,  slight  to  
o Occupy  uterine  cavity,  occasionally  develop  in  oviduct  and   to  moderate   severe  
ovary   CLINICAL  PRESENTATION  
o Types:  Based  on  the  morphologic,  cytogenic  and   Diagnosis   Missed  abortion   Molar  gestation  
clinicopathologic  effects   Uterine  size   Small  for  dates   50%  large  for  dates  
• Complete  H.  Mole  –  67%  (POGS)  
Theca-­‐lutein  cysts   Rare   25-­‐30%  
• Partial  H.  Mole  –  14%  
Medical  complication   Rare   Frequent  
 
GTN   <5-­‐10%   20%  
 
THECA  LUTEIN  CYSTS  
o Ovaries  contain  multiple  cysts  
o Microscopic  size  to  >/=10  cm  in  diameter  
o Smooth,  often  yellowish,  lined  with  lutein  cells  
o Incidence:  25-­‐60%  associated  with  complete  moles  
o Overstimulation   of   lutein   elements   by   large   amounts   of   hCG  
                                secreted  by  proliferating  trophoblastic  cells  
 
o May  be  associated  with  
COMPLETE  HYDATIDIFORM  MOLE   • fetal  hydrops    
o Chorionic  villi  transform  into  a  mass  of  clear  vesicles  
• placental  hypertrophy  
o Vary  in  size  (barely  visible  to  few  cm)  and  often  hang  in  
• multifetal  pregnancy  
clusters  from  thin  pedicles  
o Histology  
 
• Luteinized   cells   forming   the   inner   cyst   lining   with  
Histology:  
adjacent  surrounding  theca  cells  
o Hydropic  degeneration  and  swelling  of  villous  stroma  
o My  undergo  torsion,  infarctions  or  haemorrhage  
o Absence  of  blood  vessels  in  swollen  villi  
o Cysts   regress   after   delivery,   oophorectomy   should   NOT   be  
o Proliferation  of  trophoblastic  epithelium  to  a  varying  degree  
performed  unless  ovary  is  extensively  infarcted  
o Absence  of  fetus  and  amnion  
o Large  ovarian  cysts  may  be  decompressed  if  symptomatic  
 
o Regression:  8-­‐10  weeks  post  evacuation  
Chromosomal  composition:  
 
o 85%  46XX  
o Androgenesis   INCIDENCE  
• Both  chromosomes  of  paternal  origin   o 1-­‐2:  1000  pregnancies  (worldwide)  
• Ovum  has  been  fertilized  by  a  haploid  sperm,  
o More  common  in  parts  of  Asia  
which  duplicates  its  own  chromosomes  after   o Philippines:  2.4  per  1000  pregnancies  (POGS  2002-­‐2008)  
meiosis   o UP  PGH:  14/1000  pregnancies  
• Chromosomes  of  ovum  are  either  absent  or    
inactivated   RISK  FACTORS  
o Dispermy:  46  XY   o Maternal  age  
o Least  common:  45X   • Most  consistent  risk  factor  
  • Compared   to   women   between   25   and   29   years  
PARTIAL  HYDATIDIFORM  MOLE   gravid  females  
o Hydatidiform  changes  are  focal  and  less  advanced   § <20  years  old:  3  fold  increased  risk  
o Some  element  of  fetal  tissue  is  seen   § >45  years  old:  19  fold  increased  risk  
o Progressive  swelling  within  stroma  of  characteristically   § >50   years   old:   200-­‐400   fold   increased  
avascular  chorionic  villi   risk  
  o Gravidity  
        

2-­‐fold   increased   risk   among   women   with   >/=   5   § Snowstorm  appearance  

OBSTETRICS II: Gestational Trophoblastic Disease|Dr. Anna Lisa Tan

•
pregnancies   § Diffuse  hydropic  changes  and  swelling  
o Previous  molar  pregnancies  
• 1.3%  frequency  of  recurrent  moles  
§ Complete  mole:  1.5%  
§ Partial  mole:  2.7%  
• More   than   2   molar   pregnancies   =   greater   risk   of  
developing  another  molar  pregnancy  
o Nutrition  
• 2-­‐fold  increased  risk  in  mild  malnutrition  
 
• 7-­‐fold  increased  risk  in  severe  malnutrition   • UTZ  of  Partial  H-­‐mole  
• Increase   in   carotene   and   animal   fat   intake   § Presence  of  abnormal  fetus  or  abnormal  
increases  risk  for  H.  mole   gestational  sac  
o OCP   o Serum  hCG  levels  greater  than  expected  at  AOG  
o Previous  miscarriage   • Measurement   of   a   high   hCG   (>100,   000   mIU/ml)  
o Smoking   suggests  complete  hydatidiform  mole  
o Increased   paternal   age:   >45   years   old   increased   risk   for   • In   contrast,   Partial   H-­‐mole   is   less   commonly  
complete  mole   associated  with  markedly  elevated  hCG  levels  
  o Pre-­‐eclampsia-­‐eclampsia  developing  <24  weeks  
CLINICAL  COURSE   o Hyperemesis  gravidarum  in  15-­‐25%  of  cases  
1. Symptoms   are   more   dramatic   in   complete   mole   than   partial    
mole   HISTOPATHOLOGIC  EXAMINATION  
Bleeding  (89-­‐97%)   COMPLETE  
Ø Spotting  to  profuse  haemorrhage   o Large,   avascular,   generally   hydropic   villi   with   cistern  
Ø May   begin   just   before   abortion,   or   more   often,   formation  
may  bleed  intermittently  for  weeks  to  months   o Various   degrees   of   trophoblastic   proliferation,   generally  
2. Uterine  size   circumferential  
Ø 50%  are  larger  than  expected  for  gestational  age   o Absence  of  an  embryo  or  fetal  parts  
Ø 25%  are  appropriately  sized  
Ø 25%  are  small  for  dates  
3. Fetal  activity  
Ø Even   if   uterus   is   enlarged   sufficiently,   no   fetal  
heart  motion  is  detected  
Ø Sometimes,  incomplete  molar  degeneration  in  the  
placenta   accompanied   by   a   living   fetus   (twin  
pregnancy)  
4. Gestational  Hypertension  (12-­‐27%)  
Ø Pre-­‐eclampsia  that  develops  before  24  weeks  may  
 
be   from   H   mole   or   extensive   molar   degeneration    
(hydropic  or  molar  degeneration)   PARTIAL  
5. Hyperemesis  gravidarum   o Hydropic  villi  admixed  with  normal  sized  villi  
Ø Elevated  hCG:  Nausea  and  vomiting   o Scalloping   of   villous   outline   resulting   in   trophoblastic  
Ø 12-­‐25%   inclusions  
Ø Associated  with  electrolyte  imbalance   o Less  trophoblastic  proliferation  
6. Thyrotoxicosis   o Small   blood   vessels   and   fetal   nucleated   blood   cells   within   the  
Ø Serum   free   thyroxine   is   elevated   due   to   villous  stroma  
thyrotropin-­‐like  effect  of  hCG  
Ø Alpha  subunit  of  TSH  and  hCG  are  similar  
Ø Cross  stimulation  can  lead  to  hyperthyrotoxicosis  
7. Embolization  or  trophoblastic  deportation  
Ø Dreaded  complication  
Ø Variable   amounts   of   trophoblastic   cells   with   or  
without   villous   stroma   escape   from   the   uterus   into  
the  venous  outflow  at  time  of  molar  evacuation  
Ø Uncommonly  may  produce  signs  and  symptoms  of  
acute   pulmonary   embolism   or   edema,   metastasis,  
death  
 
 
CLINICAL  AND  DIAGNOSTIC  FEATURES    
o Spontaneous  expulsion  is  most  likely  around  16  weeks  and  is   PROGNOSIS  
rarely  delayed  beyond  28  weeks   o Reduced  to  zero  mortality  
o Continuous   or   intermittent   brown   or   bloody   discharge   at   o 20%  GTN  
about  12  weeks   o Majority  regresses  
o Uterus  large  for  dates  in  50%  of  cases    
o Absence  of  fetal  parts  and  fetal  heart  motion   MANAGEMENT  
• Fetal   heart   tone   is   usually   heard   on   Doppler   at   10   o As  a  result  of  better  technology,  moles  are  now  terminated  
MED2017

weeks   earlier  
o Characteristic  UTZ  appearance      
• Complete  H.  mole  

2  
 
        

o 2  phases:   perimenopausal   since   the   risk   for   ovarian  

OBSTETRICS II: Gestational Trophoblastic Disease|Dr. Anna Lisa Tan

1. Immediate  evacuation   metastasis   is   rare   and   most   ovarian   cysts   are   theca  
2. Evaluation  for  persistent  trophoblastic   lutein  cysts  
proliferation  or  malignant  change  (Post-­‐hCG   • Intervention   for   theca   lutein   cysts   is   unnecessary  
monitoring)   since   these   spontaneously   resolve   within   8-­‐12  
o Recognition  and  treatment  of  medical  complication   weeks  after  molar  evacuation  
• Anemia   o Identification  of  women  at  risk  for  malignant  degeneration  
• Pre  eclampsia   • Administration  of  chemoprophylaxis  
• Hyperthyroidism   § Methotrexate  –  IV  route  (ideal)  
• Electrolyte  imbalance   -­‐ If   hypersensitive   to  
• Hyperemesis  gravadarum   Methotrexate   and   liver  
• Pulmonary  insufficiency   toxicity:  Actinomycin  D  
• Disseminated  intravascular  coagulopathy  (DIC)   • Prophylactic  Chemotherapy  
o Baseline  laboratory  examinations   § Controversial  role  
• CBC  with  differential  and  platelet  count   § Does  not  improve  long  term  prognosis  
• Blood  typing   § Toxicity   may   be   significant,   including  
§ Possibility  of  blood  transfusion   death  
§ May   be   considered   in   high   risk   complete  
• Pre-­‐evacuation  diluted  serum  beta  hCG  (RIA)  
moles,  especially  if  serum  hCG  testing  is  
• Liver  profile  (ALT,  AST)  
unavailable  or  follow  up  is  poor  
§ Because  of  possible  chemoprophylaxis   –  
§ Indications  
nephrotoxic  and  hepatotoxic  
-­‐ Age  >/=  35  years  old  
• Renal  profile  (BUN,  Creatinine)  
-­‐ Gravidity  of  4  or  more  
• Urinalysis  
-­‐ Uterine   size   >6weeks   larger  
• Chest  X-­‐ray  
than  AOG  
§ For  complications  of  chemoprophylaxis:  
-­‐ Theca  lutein  cysts  >/=  6  cm  
pulmonary  
-­‐ Medical  complications  
§ Possible  metastasis  to  lungs  
-­‐ Recurrent  molar  pregnancies  
§ Pulmonary   hemorrhage,   infection   or  
-­‐ Beta  hCG  >  100,  000  mIU/ml  
congestion  
-­‐ Poor   follow-­‐up/distant  
o Other  exams  (if  indicated)  
geographic  location  
• Free  T4,  TSH  for  symptomatic  patients   § Contraindications  
• Serum  electrolytes   -­‐ Hemoglobin   <100   mg/dl,  
• 12  lead  ECG   hematocritt  <0.30  
• Arterial  blood  gas   -­‐ WBC  <3  x  10  
o Evacuation  of  molar  products   -­‐ Absolute   neutrophil   count  
Suction  curettage   (ANC)  </=  1.5  
• Treatment   of   choice   of   H-­‐moles   regardless   of   -­‐ Platelet  count  <100  
uterine  size   -­‐ Any  active  infection  
• Uses  suction  machine   -­‐ Presence   of   liver   or   renal  
• For  large  moles,  blood  should  be  available   dysfunction  
• Cervix  may  be  further  dilated  under  anesthesia   o Follow  up  evaluation  of  molar  pregnancies  
• After   most   molar   tissue   is   removed   by   aspiration   • Prevent  pregnancy  for  a  minimum  of  1  year  during  
oxytocin   is   started   (Oxytocin   can   cause   embolism   hormonal  contraception  
if  used  prior  to  evacuation)   § 1  year  monitoring  of  hCG  levels  
• After   myometrium   is   contracted,   gentle   sharp   § You   wouldn’t   know   if   the   rise   in   hCG   is  
curettage  is  performed   due  to  the  pregnancy  or  progression  to  
• Intraoperative   ultrasonographic   exam   to   ensure   GTN  
uterine  cavity  has  been  emptied   • Monitor   serum   hCG   levels   every   2   weeks   –   should  
• All   specimens   obtained   are   submitted   separately   progressively  fall  to  an  undetectable  level  
(suction  and  sharp  curettage)   • Once  hCG  falls  to  normal  level,  hCG  monthly  for  6  
Hysterectomy  with  mole  in  situ   months,   then   every   2   months   for   the   next   6  
• An   option   if   further   pregnancies   is   no   longer   months  
desired  with  completed  family  size   • Chemotherapy   is   not   indicated   as   long   as   levels  
§ Offers  added  advantage  of  sterilization   continue  to  regress  
§ Decreases  risk  of  local  invasion   • Rise,   plateau   >10%–   demands   evaluation   for  
§ Does   not   obviate   need   for   close   follow   persistent  GTD  and  usually  treatment  
up    
• Logical   procedure   in   women   aged   >/=   40   years,   POST  MOLAR  HCG  REGRESSION  CURVE  
because  at  least  1/3  develop  GTN   o Average  of  14  weeks  post  evacuation:  hCG  normalizes  
• Reduces  likelihood  of  recurrent  disease   o Median  weeks  for  Partial  H-­‐mole  to  regress:  7  weeks  
• Important  adjunct  to  treatment  of  chemoresistant   o Median  weeks  for  Complete  h  mole:  9  weeks  
tumors    
o Important  points   COMPARATIVE  REGRESSION  OF  HCG  TITER  
• Hysterotomy   and   induction   of   labor   by   Oxytocin   or     REGRESSION   MEAN  
Prostaglandin   to   allow   spontaneous   expulsion   are   H-­‐mole   60-­‐170  days    
associated  with:  
Term   10-­‐120  days   14  days  
§ Incomplete  evacuation  
Ectopic   31  days   8.5  days  
MED2017

§ Significant  haemorrhage  
§ Higher  incidence  of  postmolar  GTD   Spontaneous  abortion   9-­‐35  days   19  days  
• Adnexae   are   not   removed   unless   the   patient   is   Induced  abortion   16-­‐60  days   30  days  

3  
 
        

FOLLOW  UP  EVALUATION  OF  MOLAR  PREGNANCIES   Vagina:  50%  

OBSTETRICS II: Gestational Trophoblastic Disease|Dr. Anna Lisa Tan

•
o Estrogen-­‐Progesterone  contraceptive  or  DMPA   • Vulva,  kidneys,  liver,  ovaries,  brain,  bowels  
• Low   dose   (<50   mcg)   of   estradiol   content   –   o Presence  of  ovarian  theca  lutein  cystà  1/3  of  cases  
contraception  of  choice    
§ Suppresses   the   endogenous   luteinizing  
hormone   which   can   interfere   in   the  
interpretation  of  results  
• OCPs  are  found  to  be  superior  to  barrier  methods  
or  IUD  
 
POST  MOLAR  GTN  
o Plateau   of   serum   hCG   level   (+/-­‐   10%)   for   four   measurements  
during  a  period  of  3  weeks  or  longer  –  days  1,  7,  14,  21  
o Rise   of   serum   hCG   >10%   during   3   weekly   consecutive    
measurements  or  longer  during  a  period  of  2  weeks  or  more  –    
days  1,  7,  14   INVASIVE  MOLE  
o Serum  beta  hCG  remains  detectable  6  months  or  more   o Excessive  trophoblastic  overgrowth  and  extensive  
o Histological  criteria  for  choriocarcinoma   penetration  by  trophoblastic  cells  including  whole  villi  
o Persistently  elevated  beta  hCG  titer  14  weeks  post  evacuation   o Structures  penetrate  into  depths  of  myometrium,  sometimes  
o Elevation   of   a   previously   normal   beta   hCG   titer   after   involving  the  peritoneum,  parametrium,  and  vaginal  vault  
evacuation  provided  the  diagnosis  of  pregnancy  is  excluded   o Almost  always  arise  from  partial  or  complete  mole  
o Clinical  or  histological  evidence  of  metastasis  at  any  site   o Locally  invasive,  does  not  have  the  tendency  for  widespread  
  metastasis  
GESTATIONAL  TROPHOBLASTIC  NEOPLASIA    
  CLINICAL  PRESENTATION  
o A  disease  state  wherein  there  is  clinical  evidence  of:   o Patients  may  present  with  any  of  the  following  
• Invasive  mole   • Vaginal  bleeding:  most  common  symptom  
• Choriocarcinoma   • Uterine  enlargement  and  irregularity  
o May  follow  molar  pregnancy  or  normal  pregnancy   • Due  to  its  invasive  nature,  tumor  may  perforate  
  through  the  myometrium  producing  an  
ETIOLOGY   intraperitoneal  bleed  that  may  present  as  an  acute  
o 50%:  H.  mole   abdomen  
o 25%:  abortion   • Profound  anemia  
o 25%:  normal  pregnancy   o Signs  and  symptoms  of  hemorrhage  in  metastatic  sites  
  • Pulmonary  involvement  may  cause  cough,  
PATHOLOGY   dyspnea,  hemoptysis  and/or  pleuritic  chest  pain  
o Diagnosis   is   made   primarily   by   persistently   elevated   serum   • Abdominal  pain  if  visceral  involvement  
beta  hCG  levels   • Neurological  manifestations  may  include  
o In  most  cases,  there  is  no  tissue  to  submit  for  histopathology   headaches,  seizures,  loss  of  consciousness  and  
o Clinical   management   is   not   always   dictated   by   histological   paralysis  
findings   o Important  point  
  • Clinicians  should  be  alert  to  the  possibility  of  GTN  
CHORIOCARCINOMA   in  any  reproductive  age  woman  with  bizarre  CNS  
o Extremely  malignant  form     symptoms,  post  partum  cerebrovascular  accidents  
  or  radiographic  evidence  of  metastatic  tumor  of  
Gross:   unknown  primary  origin  
o Rapidly   growing   mass   invading   the   myometrium   and   blood    
vessels  that  causes  hemorrhage  and  necrosis   DIAGNOSIS  
o Tumor  is  dark  red  or  purple  and  ragged  or  friable   o Clinical  presentation  
o Endometrium   o Serum  beta  hCG  titer  
• Bleeding,   sloughing,   infection   of   the   surface   may   o Ultrasound  
occur   § Most  accurate  non-­‐invasive  diagnostic  
o Myometrium   procedure  
• Composed   of   masses   of   tissue   may   extend   o Color  Doppler  
outward   as   dark,   irregular   nodules   that   penetrate   § Alert  you  on  the  hypervascular  nature  of  
the  peritoneum   disease  
  § Can  define  regions  of  increased  vascularity  
Incidence:     representative  of  invasive  disease  and  
o 1  in  30,  000  pregnancies   enhanced  uterine  perfusion  distinct  from  that  
o 2/3  after  normal  delivery   seen  in  conditions  related  to  pregnancy  or  
o 1/3  after  molar  gestation   abortion  
  o Transvaginal  sonography  is  especially  helpful  for  
Histology:   diagnosing  and  subsequently  following  GTT  lesions  
o Columns   and   sheets   of   trophoblastic   cells   penetrate   the   during  chemotherapy  
muscle  and  blood  vessels   o Histopathologic  confirmation  is  not  necessary  
o Absence  of  a  villous  pattern   o In  the  presence  of  vaginal  lesions,  biopsy  should  NOT  be  
  performed  as  this  will  induce  torrential  bleeding  
Metastasis  (hematologic):    
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o Trophoblastic  cells  have  greater  affinity  to  form  blood  vessels    

o Most  common  sites:      
• Lungs:  75%  

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MANAGEMENT   § Antecedent  term  pregnancy  

OBSTETRICS II: Gestational Trophoblastic Disease|Dr. Anna Lisa Tan

o Little  distinction  between  invasive  mole  and  choriocarcinoma   o Brewer  Scoring  System  (1991)  
in  terms  of  the  way  that  treatment  strategy  is  planned   • Number  of  metastases  
o More   important   than   the   type   of   GTN   is   the   accurate   and   • Metastatic  sites  other  than  lungs  and  vagina  
rapid   diagnosis   so   that   treatment   may   be   administered   • Previous  failed  chemotherapy  
promptly   • Points:  
o Diagnose  and  treat  concomitant  medical  complications   Lung  and/or  Vaginal  metastases  
o Order  necessary  lab  and  diagnostic  exam   0  
No  prior  chemotherapy  
• Include  metastatic  work  up   1-­‐4  metastases  
• Baseline  examinations  include:   1   Metastases  other  than  lung  and/or  vagina  
§ Diluted  serum  beta  hCG  (RIA)   Prior  chemotherapy  
§ Complete   Blood   Count   with   differential   2   5-­‐8  metastases  
and  platelet  count   3   >8  metastases  
§ Blood  typing   • Survival  
§ Liver  profile  (SGOT,  SGPT)   § 1=100%  
§ Renal  profile  (BUN,  Creatinine)   § 2=88%  
§ Urinalysis   § 3=63%  
§ Chest  X-­‐ray   § 4=29%  
-­‐ To  detect  lung  metastasis   o FIGO  Staging  
-­‐ Used  to  count  the  number  of   Stage  I   Disease  confined  to  the  uterus  
metastases   for   risk   score   Stage   Disease  extending  outside  of  the  uterus  but  
assessment   II   limited  to  the  genital  structures  
-­‐ In   the   presence   of   a   normal   Stage  
Disease  extending  to  the  lungs  
chest   X-­‐ray,   patients   should   III  
undergo   Chest   CT   scan   to   Stage  
Other  metastatic  sites  
detect  occult  metastases   IV  
Ø Used   only   for   • Combination  of  WHO  prognostic  system  and  FIGO  
monitoring   of   the   staging  is  presently  being  used  
disease   and   NOT   • A  patient’s  stage  and  score  is  expressed  by  
for   risk   score   allotting  a  roman  numeral  to  the  stage  and  an  
assessment   Arabic  numeral  to  the  risk  score  separated  by  
-­‐ All   patient   with   pulmonary   colon  (Eg:  GTN  III:8)  
metastases   having   an    
aggregate   diameter   of   >/=   3   TREATMENT  
cm   should   undergo   CT   scan   o Cornerstone  is  chemotherapy  
of  the  brain   • Single   agent:   Methotrexate,   Actinomycin,   5FU,  
§ Pelvic/Transvaginal   Ultrasound   with   Etoposide  
Doppler  studies   • Multiple  agents:  MAC,  EMACO  
§ CT   scan   of   abdomen   (Ultrasound   is   o Majority  have  excellent  prognosis  
acceptable)   o Surgery  –  Hysterectomy  
o All   patients   with   a   diagnosis   of   gestational   trophoblastic   o Thoracotomy  with  pulmonary  wedge  resection  
neoplasia   (GTN),   with   or   without   histopathological   findings,   o Craniotomy  
should  be  staged  and  scored  using  the  FIGO  staging  and  risk   o Whole  brain  or  liver  radiotherapy  
factor  system   Stage   Low   High  
  I   Single  agent   Single  agent  
PROGNOSIS   II   Single  agent   Multiple  agent  
o WHO   III   Single  agent   Multiple  agent  
• Low  risk  <  7   IV   Multiple  agent   Multiple  agent  
• High  risk  =  7  or  more   o Surgery  is  only  an  adjunct  to  chemotherapy  
Prognostic  Factor   0   1   2   4   • Hysterectomy  may  be  performed  for  appropriately  
Age   <39   >39       selected  patients  to  decrease  the  tumor  load  and  
Antecedent   H-­‐ Abortion   Term     the  number  of  chemotherapeutic  courses  to  be  
pregnancy   mole   given  
Interval   <4   4-­‐6   7-­‐12   >12   • Hysterectomy  is  indicated  in  the  following  cases  
Beta  hCG   <103   103-­‐104   104-­‐105   >105   § Control  of  profuse  uterine  bleeding  
§ >/=35  year  old  and/or  complete  family  
Largest  tumor  (cms)     3-­‐5   >5    
size  
Site  of  Metastasis     Spleen   GIT   Liver  
§ Inability  to  repair  a  tumor  perforation  
Kidney   Brain   § Drug  resistance  
Number  of  Metastasis     1-­‐4   4-­‐8   >8    
Prior  chemotherapy       Single   2  or   FOLLOW  UP  
drug   more   o Serum  hCG  every  month  after  treatment  up  to  6  months,  
o Hammond’s  Criteria   then  every  2  months  for  another  6  months,  every  3  months  
• Low  risk  (no  risk  factors)   for  the  second  year  of  follow  up  and  every  6  months  
• High  risk  (any  of  the  ff  risk  factors   thereafter  
§ hCG  >  100,  000  mIU/ml  in  24  hour  urine   o Pregnancy  should  be  avoided  for  a  span  of  2  years  from  the  
or  >40,  000  mIU  in  serum   first  normal  hcg  titer  
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§ Symptoms  present  >4  months   • Monitoring  of  hCG  levels  lasts  for  2  years  
§ Brain  or  liver  metastases  
• A  safe  and  effective  form  of  contraception  should  
§ Prior  chemotherapy  failure  
be  given  

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o Clinical  exam  is  performed  every  follow  up  

OBSTETRICS II: Gestational Trophoblastic Disease|Dr. Anna Lisa Tan

• Pelvic  exam  –  enlargement  of  uterus,  adnexal  
pathology  
o If  at  time  of  completing  treatment,  there  is  still  radiographic  
evidence  of  residual  tumor,  further  radiographs  are  required  
yearly  
o For  patients  who  have  not  undergone  a  hysterectomy,  a  
transvaginal  ultrasound  is  required  every  6  months  
   
 
POST  MOLAR  GTN  
Management:  
o Plateau  of  serum  hCG  level  (+/-­‐  10%)  for  four  measurements  
o Recognition  and  treatment  of  concomitant  medical  problems  
during  a  period  of  3  weeks  or  longer  –  days  1,  7,  14,  21  
o Laboratory  examinations  and  metastatic  work  up  
o Rise  of  serum  hCG  >10%  during  3  weekly  consecutive  
o Non-­‐metastatic  PSTT  
measurements  or  longer  during  a  period  of  2  weeks  or  more  –  
• Not  desirous  of  pregnancy  
days  1,  7,  14  
§ Hysterectomy   with   adjuvant   single  
o Serum  beta  hCG  remains  detectable  6  months  or  more  
agent   chemotherapy   using  
o Histological  criteria  for  choriocarcinoma  
Methotrexate  
o Persistently  elevated  beta  hCG  titer  14  weeks  post  evacuation  
o Elevation  of  a  previously  normal  beta  hCG  titer  after   • Desirous  of  pregnancy  
evacuation  provided  the  diagnosis  of  pregnancy  is  excluded   § EMACO  
o Clinical  or  histological  evidence  of  metastasis  at  any  site   § Options  
  -­‐ Hysteroscopic  resection  
-­‐ Curettage  
PLACENTAL  SITE  TROPHOBLASTIC  TUMOR  
o Total   hysterectomy   with   or   without   bilateral   salphingo-­‐
o Neoplastic   proliferation   of   intermediate   trophoblasts   that  
oophorectomy   and/or   multiagent   chemotherapy   preferably  
invade   the   myometrium   at   the   placental   site   after   a  
EMACO  
pregnancy  
 
o Histologically:  
Follow  up:  
predominant  
o Same  as  GTN  
cytotrophoblastic  cells  
• Beta  hCG  
o Serum  hCG  may  be  
• Clinical  pelvic  exams  
normal  or  elevated  
o Human  placental   • Avoidance  of  pregnancy  
lactogen   • Transvaginal  Ultrasound  
  • Chest  X-­‐ray  
Diagnosis:   • Family   planning   methods   –   low   dose   OCPs   for   2  
Clinical  presentation   years  
o Seen  mostly  in  women  of  reproductive  age    
o Presents  with  vaginal  bleeding  (79%)  and  amenorrhea  of   EPITHELIOID  TROPHOBLASTIC  TUMOR  
varying  duration  (90%)   o Recently   described   trophoblastic   neoplasm   felt   to   be   a  
o Asymmetric  enlargement  of  uterus   malignant   counterpart   of   the   intermediate   trophoblasts   of  
o Other  symptoms  relating  to  metastasis   the  chorion  lavae,  which  have  an  epithelioid  appearance  
o 53-­‐78%  follow  a  term  delivery,  the  rest  after  abortion  or  molar    
pregnancy   Clinical  presentation:  
o 44-­‐69%  present  as  Stage  I  disease   o Age  ranges  from  15-­‐48  years  old  
  o Antecedent  pregnancy:  full  term  in  majority  of  cases  
Sonographic  picture   o Interval  between  antecedent  pregnancy  and  diagnosis  is  1  to  
o Appear   as   heterogenous,   hyperechoic   mass   with   multiple   18  years  
cystic  spaces  within  myometrium  of  enlarged  uterus   o Abnormal  vaginal  bleeding:  common  
o On   Doppler,   both   hypervascular   and   hypocvascular   forms   of   o Extrauterine  epithelioid  trophoblastic  tumors  can  develop  
the   disease   have   been   described   with   or   without   cystic   after  long  latent  period  without  evidence  of  disease  
masses,  but  none  are  diagnostic  of  PSTT    
Beta  hCG  titer   Diagnosis:  
o Low   levels   of   hCG   plus   a   relatively   large   tumor   should   raise   o Beta  hCG  titer  
suspicion  of  PSTT   • Serum   beta   hCG   levels   are   nearly   always   elevated  
Histopathologic  examination   at  time  of  diagnosis  
o Gross    
• Most   are   well   circumscribed,   polypoid   projecting   Histopathology:  
into   the   uterine   cavity   or   may   predominantly   o Location:  
involve  the  myometrium   • 30%  uterine  corpus  
o Microscopic   • 50%  LUS  
• PSTT   is   characterized   by   a   monomorphic   cell   • 20%  Extrauterine  
population   of   implantation   site   intermediate   • Small  bowels  
trophoblastic  cells  that  separate  muscle  bundles  as   • Lungs    
they  invade  the  myometrium   o Gross  
o Immunostain  with  human  placental  lactogen  is  confirmatory   • Solitary,  discrete  nodules  deeply  invading  the  
cervix  and  myometrium  
• Cut  surface  is  either  solid  or  cystic  
• Solid  areas  are  typically  tan  to  brown,  with  
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hemorrhage  and  necrosis  

o Microscopic  

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Monomorphic,  chorionic  type  intermediate  

OBSTETRICS II: Gestational Trophoblastic Disease|Dr. Anna Lisa Tan

•
trophoblastic  cells  in  nests,  cords  and  masses  of  
cells  are  eosinophilic,  fibrillar,  hyaline  like  material  
and  necrotic  debris  
• Typically,  small  blood  vessels  located  within  the  
center  of  tumor  
• Apoptotic  cells  and  bodies  diffusely  distributed  
throughout  tumor  
 
Management:  
o Recognition   and   management   of   associated   medical  
problems  
o Baseline  laboratory  exams  and  metastatic  work  up  -­‐   same  as  
GTN  
o May  not  be  responsive  to  chemotherapeutic  agents  
o Hysterectomy  and  lung  resection  have  been  used  successfully    
o Effectiveness   of   curettage   and   chemotherapy   for   treatment  
of  early  lesion  require  further  evaluation  
 
Follow  up:  Same  as  GTN  
 
CLINICAL  FEATURES  OF  PSTT,  ETT  AND  CHORIOCARCINOMA  
Feature   PSTT   ETT   Choriocarcinoma  
Abnormal  
Clinical   Missed   Persistent  GTD  
vaginal  
Presentation   abortion   after  H-­‐mole  
bleeding  
Last  known  
Variable,  can  be   Variable,  can  be  
pregnancy  or   Months  
remote   remote  
GTD  
History  of  
5-­‐8%   14%   50%  
mole  
Serum  beta   Low  (<2000   Low  (<2000   High  (>100,  000  
hCG   mIU/ml)   mIU/ml)   mIU/ml)  
Self-­‐limited   Self-­‐limited  
Aggressive  if  
Behavior   Persistent  or   Persistent  or  
untreated  
aggressive   aggressive  
Response  to  
Variable   Variable   Good  
chemotherapy  
Surgery   Surgery  
Treatment   Chemotherapy  
(Hysterectomy)   (Hysterectomy)  
 
PREGNANCY  AFTER  GTD  
o Follow  up  
• H  mole  =  1  year  
• GTN  =  years  
o No   difficulty   with   fertility   or   normal   pregnancy   outcome  
following  successfully  treated  GTD  
o Women   given   chemotherapy   do   not   have   increased   risk   of  
anomalous  foetuses  
o 1.3%  developed  second  molar  pregnancy  
o Incidence  of  third  molar  pregnancy  –  15-­‐20%  
 

[Team OB]
MED 2017
 
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