Trophoblastic diseases (gestational trophoblastic tumour) KANNUR MEDICAL COLLEGE

Trophoblastic diseases ► Comprises a spectrum of diseases including benign vesicular mole at one end to the choriocarcinoma at the other end

Hydatidiform mole ► Partial mole ► complete mole

Hydatidiform mole ► Incidence UK, USA 1:2000 to 1:3000 UK, USA 1:2000 to 1:3000 India& Middle East 1:160 to 1:500 India& Middle East 1:160 to 1:500 China 1:150 China 1:150 Taiwan 1:82 Taiwan 1:82

Hydatidiform mole ► Etiology 1. blood group A 2. Age - 40 yrs more prone 3. repeat mole 2%after 1molar preg &28% after 2 molar preg 4. Dietary deficiency of protein, FA, iron

Trophoblastic diseases ► Vesicular mole partial complete complete ► Invasive mole ► Placental site trophoblastic tumor ► choriocarcinoma

GTT contd ► Signs &symptoms bleeding 97% &passage of vesicles/anemia 5% bleeding 97% &passage of vesicles/anemia 5% abdominal pain abdominal pain uterine size >MA 50% cases uterine size >MA 50% cases <MA 25% cases <MA 25% cases =MA 25% cases =MA 25% cases hyper emesis gravidarum 8% hyper emesis gravidarum 8% gestational hypertension/PET 27% gestational hypertension/PET 27% hyperthyroidism 7% hyperthyroidism 7% trophoblastic embolisation 2% trophoblastic embolisation 2% theca lutein ovarian cysts 50% cases of comp. mole theca lutein ovarian cysts 50% cases of comp. mole

Hydatidiform mole ► Cytogenetics partial mole partial mole single ova +2 sperms → triploid karyotype single ova +2 sperms → triploid karyotype ova sperms ova sperms ie 23x + 23x → 69xxx ie 23x + 23x → 69xxx 23x 23x 23x + 23y → 69xyy 23x + 23y → 69xyy 23y 23y 23x + 23x → 69xyy 23x + 23x → 69xyy 23y 23y 69yyy -nonviable 69yyy -nonviable

Hydatidiform mole contd ► Complete mole(cytogenetics) ova +sperm/s → complete mole ova +sperm/s → complete mole empty ova+ 23x → 23x → endoreduplication → 46xx empty ova+ 23x → 23x → endoreduplication → 46xx or or empty ova+ 23x → 46xx +23x +23x or or empty ova+ 23x → 46xy +23y +23y

Hydatidiform mole contd ► Pathology -complete & partial mole differs in morphological,histological &karyotypic findings ► partial mole morphological features morphological features malformed fetus, placenta with focal hydropic changes and proliferation, malformed fetus, placenta with focal hydropic changes and proliferation,

Hydatidiform mole contd ► Pathology complete mole complete molemorphology resembles bunches of grape like vesicles, pearly white, translucent containing watery fluid(size from few mm to 2-3 cm),attached to main stalk by thin pedicles,heamorrhagic areas. resembles bunches of grape like vesicles, pearly white, translucent containing watery fluid(size from few mm to 2-3 cm),attached to main stalk by thin pedicles,heamorrhagic areas. fetus,amniotic sac and normal placenta are absent fetus,amniotic sac and normal placenta are absent ovaries contains theca lutein cyst in 60% of cases ovaries contains theca lutein cyst in 60% of cases

Hydatidiform mole contd ► Complete mole histology histology absence of tertiary villous absence of tertiary villous proliferation of both the trophoblast proliferation of both the trophoblast hydropic changes hydropic changes

Invasive mole ► Some hydatidiform mole erode myometrium,or may burst into peritoneal cavity ► Locally malignant ► Invasive mole: benign mole -1:12 ► Intermediate between benign mole and malignant mole ► Chorionic villi present

Invasive mole contd ► Trophoblastic tumor following a full term pregnancy is always choriocarcinoma;but that following abortion or molar preg is invasive mole or choriocarcinoma ► Trophoblastic tumor diagnosed for upto 6mths following abortion or mole is often an invasive mole, but later than 6 mths is usually choricarcinoma

hydatidiform mole contd hydatidiform mole contd ► 80% of H.mole resolves with treatment 15% develops PTD 15% develops PTD 2-5% develops choriocarcinoma 2-5% develops choriocarcinoma

Treatment of hydatidiform mole ► Suction evacuation &thorough gentle curettage pre requisites pre evacuation HCG chest Xray ABG (if HCG > 1 lakch IU/L) Laparotomy set, O2 ready Laparotomy set, O2 ready

hydatidiform mole contd hydatidiform mole contd ► Post evacuation monitoring (follow up) Wkly s. HCG till 3 consecutive values are normal(<5 IU/L) then monthly s. HCG for 6mths then monthly s. HCG for 6mths

Hydatidiform mole ► Diagnosis history history examination examination HCG HCG TFT TFT Chest X Ray Chest X Ray USG - snow storm appearance USG - snow storm appearance CT scan CT scan MRI scan MRI scan

Hydatidiform mole ► Differential diagnosis wrong dated preg wrong dated preg multiple preg multiple preg acute hydramnios acute hydramnios fibroid complicating preg fibroid complicating preg

Hydatidiform contd ► Complications haemorrhage, anemia haemorrhage, anemia infection infection thyroid storm thyroid storm Tropho. Embolisation with a/c pulmonary insuff. & CCF Tropho. Embolisation with a/c pulmonary insuff. & CCF uterine perforation –spontaneous/follo. Suction evacuation uterine perforation –spontaneous/follo. Suction evacuation development of PTD development of PTD -invasive mole -invasive mole - choriocarcinoma - choriocarcinoma

Persistent trophoblastic disease ► 15% of comp.mloe &4% of partial mole → PTD ► High risk factors for PTD pre evacuation beta HCG > IU/L pre evacuation beta HCG > IU/L uterine size > MA uterine size > MA Presence of TLC >6cm Presence of TLC >6cm ► Diagnosis –platauing or doubling of s. betaHCG

Persistent trophoblastic disease contd ► Signs &Symptoms - irreg.vag.bleeding following molar evacuation - irreg.vag.bleeding following molar evacuation -TLC -TLC - uterine sub involution or asymmetric enlargement - uterine sub involution or asymmetric enlargement -persistently elevated beta HCG -persistently elevated beta HCG -Histologically features s/o either hydatidiorm mole /chorioca/ placental site tropho.tr -Histologically features s/o either hydatidiorm mole /chorioca/ placental site tropho.tr

Persistent trophoblastic disease contd ► Types metastatic PTD metastatic PTD (follo. molar evacuation of 4% cases of complete mole ) (follo. molar evacuation of 4% cases of complete mole ) Non metastatic PTD Non metastatic PTD (follo. 15% cases of complete mole ;but seen more frequently follo. non molar preg) (follo. 15% cases of complete mole ;but seen more frequently follo. non molar preg)

Persistent trophoblastic disease contd ► Metastasis at the time of diagnosis of PTD pulmonary 80% pulmonary 80% vaginal 30% vaginal 30% liver 10% liver 10% brain 10% brain 10%

Persistent trophoblastic disease contd ► FIGO staging of GTT STAGE 1 confined to uterus STAGE 1 confined to uterus STAGE 11 GTT extending outside uterus but limited to genital structures(adnexa, vagina, broad lig) STAGE 11 GTT extending outside uterus but limited to genital structures(adnexa, vagina, broad lig) STAGE 111 GTT extending to lungs with/ without genital structures involvement STAGE 111 GTT extending to lungs with/ without genital structures involvement STAGE 1V all other metastasis STAGE 1V all other metastasis

Persistent tropho. disease contd WHO prognostic scoring system Factors Age<39 >39 > Ante.premoleabortion Term preg Term preg - Interval <4 mths 4-6 mths 7-12 mths 7-12 mths >12 mths >12 mths Pre Rx betaHCG < lakh lakh>1lakh Size of tr <3cm 3-5 cm >5cm

Persistent tropho. disease contd WHO prognostic scoring system factors0124 Site of mets - Spleen, kidney GI,liverBrain No.of mets >8 Blood gp AB Previous failed chemo -- Single agent chemo combinat ion

Persistent tropho. disease contd WHO prognostic scoring system ► SCORE <4 LOW RISK 5-8 MIDDLE RISK 5-8 MIDDLE RISK >8 HIGH RISK >8 HIGH RISK

PTD ► Treatment stage 1, stage2, stage3(low risk) stage 1, stage2, stage3(low risk) single agent chemo +/-hysterectomy single agent chemo +/-hysterectomy resistant cases combination chemo resistant cases combination chemo stage 3( high risk case) & stage 4 stage 3( high risk case) & stage 4 combination chemo+/- hysterectomy=/- radiation+/- surgery depending on site of mets combination chemo+/- hysterectomy=/- radiation+/- surgery depending on site of mets

PTD ► SINGLE AGENT CHEMO - Methotexate(MTX),Folinic acid (FA)rescue regimen - Methotexate(MTX),Folinic acid (FA)rescue regimen mtx mg/kg IM/IV on D1,3,5,7 mtx mg/kg IM/IV on D1,3,5,7 FA mg/Kg IM on D2,4,6,8 repeat 2 wkly till 3 consecutive s. HCG values are normal FA mg/Kg IM on D2,4,6,8 repeat 2 wkly till 3 consecutive s. HCG values are normal -Actinomycin-D /kg IM daily or 5 days rpt 2wkly till 3 consecutive s. HCG values are normal Etoposide 200 mg orally daily for 5 daysrpt 2wkly till 3 consecutive s. HCG values are normal

PTD ► COMBINATION CHEMO E M A –C O E M A –C O Etoposide(E) Etoposide(E) Methotrexate(M) Methotrexate(M) ActinomycinD (A) ActinomycinD (A) Cyclophosphomide(C) Cyclophosphomide(C) Vincristine (O) Vincristine (O)

PTD ► FOLLOW UP low& intermediate risk low& intermediate risk Wkly s.HCG till 3 consecutive values are normal, then monthly s.HCG for 12 months Wkly s.HCG till 3 consecutive values are normal, then monthly s.HCG for 12 months high risk high risk Wkly s.HCG till 3 consecutive values are normal, then monthly s.HCG for 24 months Wkly s.HCG till 3 consecutive values are normal, then monthly s.HCG for 24 months

choriocarcinoma ► Rare malignant growth of body of uterus ► Non gestational choriocarcinoma occurs as part of germ cell gonadal neoplasm both in male and female ► Incidence 1:50000to 1:70000 in US& UK and is 10 times more common in South East Asia ► 50% cases following hydatidiform mole,25% following abortion,20% following full term labour,5% following ectopic preg

choriocarcinoma ► Morphologically :purple friable mass projecting into uterine cavity,ulcerates and gives blood stained /purulent discharge/presents with haemorrhage, erode uterus may cause uterine perforation projecting into uterine cavity,ulcerates and gives blood stained /purulent discharge/presents with haemorrhage, erode uterus may cause uterine perforation ► Metastasis :by blood stream ► Histology :anaplastic cyto&syncytiotrophoblast,absence of chorionic villi

choriocarcinoma ► Symptoms&signs -persistent or irregular uterine bleeding -persistent or irregular uterine bleeding -offensive vaginal discharge -offensive vaginal discharge -pyrexia,cachexia -pyrexia,cachexia -amenorrhoea due to very high level of HCG -amenorrhoea due to very high level of HCG -rupture of uterus with intraperitoneal hrges -rupture of uterus with intraperitoneal hrges -symptoms of distant site metastasis-like haemoptysis,hemiplegia, epilepsy, -symptoms of distant site metastasis-like haemoptysis,hemiplegia, epilepsy, - bluish red vaginal nodules, enlarged uterus,palpable TLC - bluish red vaginal nodules, enlarged uterus,palpable TLC

choriocarcinoma ► D/d : placental polyp ectopic preg ectopic preg ► RX combination chemotherapy combination chemotherapy surgery if indicated surgery if indicated

Role of surgery in GTT ► HYSTERECTOMY when? high risk multiparous patients >40 yrs high risk multiparous patients >40 yrs chemotherapy ineffective chemotherapy ineffective hrge due to uterine perforation hrge due to uterine perforation placental site trophoblastic tr placental site trophoblastic tr ► if TLC causes a/c abdomen due to hrge or torsion then laparotomy is indicated ► Bleeding mets in lung may require thoracotomy & at brain mat require craniotomy ► (even after surgery patient should be under follow up and may require chemo )

Placental site trophoblastic tumour ► Variant of chorioca,consists mainly of intermediate tropho. ► Non responsive to chemotherapy ► Hysterectomy is the TOC ► hPL is the tumor marker