In the name of GOD

Gestational trophoblastic

Neoplasms (GTN)DanforthDr.F Behnamfar MD

GTN is divided into three histologic categories :

hydatidiform mole , invasive mole (chorioadenoma destruens) choriocarinoma .

Partial hydatidiform moles Placental site trophoblastic tumors (PSTT)

All derived from the human placental trophoblast and the paternal genome

Human chorionic gonadotropin (hCG) is secreted by these neoplasms and serves as a sensitive tumor marker that correlates well with the clinical course for all GTNs except PSTT.

The initial histologic features of any lesion identified as GTN are less important than the clinical data and hCG level.

Complete Hydatidiform MoleMacroscopically : Edema and swelling of virtually Villi without

identifiable fetal parts or amniotic membranes

Microscopically: The chorionic villi are hydropic with marked

interstitial edema . fetal vessels are absent Proliferation of cytotrophoblast and

syncytiotrophoblast

Complete moles: completely paternal chromosomal composition . most are 46,XX

An empty egg by a haploid sperm followed by reduplication

Empty ovum + 2323 endoreduplication 46xx Homozygous

Clinical finding :

1-one third to one half of uterine enlargement 2-Vaginal bleeding 3-Thecalutein cysts 20% 5-pregnancy – induced hypertension (PIH)4-pulmonary decompensation 6-hyperthyroidism 7-snowstorm (ultrasonography)

Partial mole partial moles often are associated with

identifiable fetal parts or amniotic membranes one haploid maternal and two haploid

paternal sets of chromosomes diagnosis : until after evacuation of the pregnancy

complete moles : 10% to 30% incidence of malignant

partial mole : fewer than 5% of the patients

Invasive mole

with invasion into the myometrium without intervening endometrial stroma

uterine perforation and hemorrhage

choriocarcinoma choriocarcinoma rapidly invades the

myometrium and uterine vessels , and systemic metastasis

no chorionic villi are identified hematogenous embolization (affinity of trophoblast cell for blood vessel) Most cases have no tissue for pathologic

study, hCG level has raise

50% of cases are preceded by hydatidform mole

Gestational choriocarcinoma has been observed several years after last known pregnancy .

Spontaneous regression of the primary uterine site

Placental site trophoblastic tumor (PSTT) Locally invasive neoplasms derived from

intermediate cells of the placenta HPL from cytotrophoblast cell small amounts of hCG rare systemic metastasis significantly more resistant to standard

chemotherapy than other forms of GTN hysterectomy is the initial therapy of choice

Risk factors for hydatidiform mole 1-prevous molar pregnancies 2-maternal age (advanced maternal age ,

younger women or adolescents) Animal fat Deficiency of folat –caroten and protein Low socioeconomic state

Management GTD complete physical and pelvic examinations complete blood count determination blood chemistry levels , including renal-liver baseline serum hCG level chest radiograph pelvic ultrasonography

Evacuation: suction dilation and curettage hysterectomy followed closely after hysterectomy incidence of malignant squeal:

20% after suction D&C to less than 5% after hysterectomy

Follow-up B-hCG levels every 1 to 2 weeks Until hCG

level is undetectable After the first normal level for 2 to 4 weeks Every then 1 to 2 months for 6 months Oral contraceptives

Hydatidiform mole

(compiete or parial )

Evacuation by suction D&C

(hysterectomy only sterllization

desired )

Monitor serum B-hCG

weekly Good contraception

hCG returns to negative

hCG levels q month X 6

May again attempt pregnancy if

desired

hCG plateaus or rises

Exclude new pregnancy

Stage and treat with chemotherapy

Algorithm for diagnosis and treatment of a patient with hydatidiform mole

Hysterectomy only if sterillzation desired After completion of 6 months of hCG normal

level pregnancy if desired

False – positive hCG Test Results The heterogeneity of hCG and the variability

between different hCG assays may in False – positive test results .

Presence of heterophilic antibodies

After evacuation of hydatidiform mole;(9% to 36%) of patients requiring therapy

Pattern of hCG regression If hCG level plateau or raise for 3 or more

consecutive weekly levels appearance of metastatsis

higher frequency of post molar malignant GTN

1- Trophoblastic proliferation 2- Uterine enlargement 3- Theca lute in cysts 4- RDS after molar evacuation 5- post evacuation uterine hemorrhage

Persistent GTD irregular vaginal bleeding Thecalutein cysts Uterine subinvolution Persistently elevated serum hCG level

Clinical classification of malignant gestational trophoblastic neoplasia

Nonmetastatic GTN A. Not defined in terms of good versus poor

prognosis

Metastatic GTN

Good prognosis (absence of high-risk factors )1. Pretreatment serum B-hCG level < 40,000 IU/ml2. Less than 4-month duration of symptoms

attributable to disease3. No evidence of brain or liver metastasis4. No significant prior chemotherapy 5. No antecedent term pregnancy

Poor pregnosis (any single high-risk factor )1. pretreatment serum B-hCG level >40,000 Iu/ml 2. more than 4-month duration of symptoms

attributable to disease 3. brain or liver metastasis or both4. failed prior chemotherapy 5. antecedent term pregnancy

Malignant GTN distant metastases

Gastrointestinal urologic hemorrhage Hemoptysis Neurological symptoms due to cerebral

hemorrhage Clinical hyperthyroidism

Four principal pulmunary radiologic patterns snowstorm pattern (Alveolar pattern )

Discrete rounded densities Plural effusion Embolic pattern

Management :

Physical and pelvic examinations Baseline hCG level Chest radiograph Pelvic ultrasonography

CT of brain , chest , and abdomen –pelvis Exclude an uterine pregnancy

Stage IStage II

Stage III

Stage IV

Strictly confined to uterine corpus Extends outside the uterus , but limited to genital structures Extends to the lungs with or without genital tract involvement All other metastatic sites

Sub stages assigned for each stage as follows : A: no risk factors present B: One risk factor C: Both risk factors Risk factors used to assign substages :1- pretherapy serum hCG> 100,000 mIU/ml 2- Duration of disease > 6 months

Who Orgnaization prognostic scoring system for gestational trophoblastic neoplasia

Prognostic factor 0 1 2 4

Age <39 >39 _ -

Antecedent pregnancy Hydatidiform Abortion , ectipic Term pregnancy -

Interval (months) <4 4-6 7-12 >12

hCG level (IU/liter) <10 10-10 10-10 >10

ABO blood groups (female/male)

O/A B A/O AB

Largest tumor (cm) <3 3-5 >5 _

Site of metastasis _ Spleen, kidney Gastrointestinal tract, liver Brain

Number of metastases _ 1-3 4-8 >8

Prior chemotherapy _ _ Single drug Multiple druge

The total score is obtained by adding the individual scores for each prognostic factor . Total score :<4 , low risk ; 5-7 , intermediate risk ;>8 , high risk .Interval :between antecedent pregnancy and start of chemotherapy.

WHO Scoring systemScore :

<4,low risk 5-7 mid risk>8 , high risk

Chemotherapy alone is successful in curing 85% of patients with non metastatic and good-

prognosis

Hysterectomy rarely is indicated as Initial therapy for women with malignant GTN

Persistence of a lung nodule after hCG normalization Should not necessarily surgery

Whole-brain and whole-liver irradiation in conjunction with chemotherapy

protocol for treatment of GTDStage I single agent chemotherapy Resistant combination chemotherapy or

hysterectomy with adjuvant chemotherapy

Stage II,III low risk single agent chemotherapy high risk combination chemotherapy Resistant second line chemotherapy

Stage IV combination chemotherapy radiotherapy Resistant second line chemotherapy

liver 2,000 rd therapy prevent hepatic hemorrhage selective occlusion of the hepatic artery

Response during therapy

Weekly intervals during therapy After remission hCG levels in the normal level Every 1 month First year of surveillance .

Follow up

Molar pregnancy 6 month GTN 1 year

Metastatic GTN except lung 2 year

Recurrence rates after therapy for GTN have been 3% to 26%

Late complication

Slight increase in the incidence of spontaneous abortion

Repeat molar 1% ovarian failure as a result of prolonged multi

drug chemotherapy

Low incidence of congenital malformations The incidence of placenta accreta particular ,

appears to be increased

After first pregnancy

We should be a chest radiography . Serum BhCG after 6-8 weeks of post partum Placenta should be undergo pathology

Towards a safe motherhood