CASE SUMMARY

• 18 years , primi presented in ER with complain of amenorrhoea for 3 months followed by PV bleeding for 2 days with passage of grape like vesicles ,on examination uterus 24 weeks size and vitals stable and hemoglobin 8gm /dl %.

• WHAT COULD BE THE DIAGNOSIS?

Molar Pregnancy

Dr Hem Nath SubediIInd year Resident

OBGYNCOMSTH

CONTENTS

• DEFINITION• INCIDENCE• TYPES • CLINICAL FEATURES • INVESTIGATIONS • DIAGNOSIS• MANAGEMENT • COMPLICATIONS

DEFINITION

• Gestational Trophoblastic Disease (GTD) is a spectrum of abnormal growth and proliferation of the trophoblasts that continue even beyond the end of pregnancy

INCIDENCE

• The reported incidence of GTD varies widely worldwide, from a low of 23 per 100,000 pregnancies (Paraguay) to a high of 1,299 per 100,000 pregnancies (Indonesia).

• The malignant potential of GTD is also higher in South Asia (10-15%) compared to western countries (2-4%)

Types

• Gestational trophoblastic disease – Molar pregnancy (hydatidiform mole) or

premalignant• Complete mole • Incomplete or partial mole

– Gestational trophoblastic neoplasia or malignant• Invasive mole • Choriocarcinoma • Placental site trophoblastic tumor• Epitheloid trophoblastic tumor

COMPLETE VS INCOMPLETE HYDATIDIFORM MOLE

Spectrum of Gestational Trophoblastic Disease

• Premalignant Malignant

COMPLETE MOLE INVASIVE MOLE

PARTIAL MOLE CHORIOCARCINOMA

PLACENTAL SITE TROPHOBLASTIC TUMOR

ABORTION OR NORMAL PREGNANCY

15%*

0.5%*

Seckl mj, fisher RA. Choriocarcinoma and partial partial hydatidiform mole . Lancet 2000;356:688

Genetic basis of developing Gestatinal Trophoblastic Disease

• Defective locus at 19q13.4 in five families and this abnormalities excitingly, been localized to a single gene NALP7.

• Choriocarcinoma has been found to be developed after delation of 7p12-q11.2,amplification of 7q21-q31, and loss of 8p12-p21.

Murdoch S,djuric U et al . Mutation I NALP7 cause hydatidiform moles and reproductive wastage in human.

Mustada T ,sasaki M et al .human Chromosome 7 carries a putative tumor suppressor gene(s) involved in choriocarcinoma . Oncogene 1997;15: 2773-2781

Clinical features • Vaginal bleeding • Excessive uterine growth• Hyperemesis gravidarum• Hyperthyroidism• Preeclampsia • Embolization of trophoblastic tissue• Theca lutein cyst• Metastatic features

– pulmonary- cough, chest pain, hemoptysis, dyspnoea, chest x ray finding -80%

– Vaginal – growth in vagina irregular bleeding per vagina - 30%– Hepatic- Epigastric pain -10%– CNS – acute focal neurologic deficit. - 10%

-Gestational Trophoblastic Disease,in Bereks And Novaks Gynecology ,15th Edition, Walter Wilkinson, Newyork 2012, Pp ,

VAGINAL METASTASIS

LUNG METASTASIS

Diagnosis

• Clinical features • History• Physical examination• Investigation– Lab investigation – Beta-hCG, LFT, RFT, CBC, urine R/E– USG abdomen and pelvis– Chest x ray – CT scan – Histopathological examination

USG Showing snow strom patttern

Staging of Gestational Trophoblastic Neoplasia

• Stage I - Disease confined to uterus• Stage II -GTN extending outside uterus but limited

to genital structures (adnexa, vagina, broad ligament)

• Stage III -GTN extending to lungs with or without known genital tract involvement

• Stage IV -All other metastatic sites

Goldstein DP, Vzanten-Przybysz I, Bernstein MR, et al. Revised FIGO staging system for gestational trophoblastic tumors: recommendations regarding therapy. J Reprod Med 1998;43:37–43.

WHO PROGNOSTIC SCORING SCORES 0 1 2 4

AGE IN YRS <40 >40 - -

ANTECEDENT PREGNANCY

H.MOLE ABORTION TERM -

INTERVAL SINCE LAST PREGNANCY

<4 MONTHS 4-6 7-12 >12

BHCG <1000 10^3-10^4 10^4-10^5 >10^5LARGE SIZE TUMOR 3-4 5 - -

SITE OF METATSTASIS

SPLEEN,KIDNEY GI LIVER, BRAIN

NUMBER OF METASTASIS

1-4 5-8 >8

PREVIOUS FAILED CHEMO

SINGLE DRUG TWO OR MORE DRUG

Adapted from FIGOLow risk score <6 ,High risk score >7

Management of gestational trophoblastic diseaseHydatidiform mole

Evacuation

Serial hCG levels

FIGO scoring

GTN

LOW RISK

SINGLE AGENT CHEMO

HIGH RISK

COMBINATION OF CHEMO

SERAIL HCG MONITORING

RELAPLSED AND RESISTANT DIEASE SECOND LINE CHEO THARAPY

Resolution 6 months HCG follow up

RESOLUTION LIFE LONG Hcg follow up

Adapted from , management of trophoblastic disease ,in resent advances in obstetrics and gynecology, 24th edition,jeypee brothers , india pp 135-151

Indications for chemotherapy in GTD• Histological evidence of choriocarcinoma• Evidence of metastases in brain, liver or gastrointestinal tract or

radiological opacities >2 cm on chest x ray.• Pulmonary , vulval or vaginal metastates unless hcg falling• Heavy Vaginal Bleeding Or Evidence Of Gasrointestinal Or

Intraperitoneal Hemorrhage• Rising Hcg After Evacuation• Serum Hcg >20,000 Iu/L More Than 4weeks After Evacuation,

Because Of Risk Of Uterine Perforation.• Elevated hcg 6months after evacuation even if still falling.

Adapted from , management of trophoblastic disease ,in resent advances in obstetrics and gynecology, 24 th edition,jeypee brothers , india pp 135-151

Low risk treatment regimen

• Methotrexate 1mg/kg /day for 1st , 3rd ,5th,7th day.• Folinic acid rescue 0.1mg/kg/day for 2nd ,4th ,6th,8th

day• Typical side effects– Stomatitis– Conjunctivitis– Abdominal pain– Chest pain

Alazzam M, Tidy J, Hancock BW, et al.: First line chemotherapy in low risk gestational trophoblastic neoplasia. Cochrane Database Syst Rev (1): CD007102, 2009

High risk treatment regimen• EMA/CO

– Etoposide– Methotrexate– Actinomycin d– Cyclcophosphamide– Oncovin/vincristine

• Week 1, Days 1-2: EMA With Folinic Acid Rescue.• Week 2, Day 8: CO• Typical Side Effects

– Myelosuprpression-granulocyte Colony Stimulatin Factor Used To Prevent Neutropenia And Maintain Dose Intensity

– Nausea/Vomiting– Mucositis– Reversible Alopecia – NeuropathyBagshawe KD, Harland S. Immunodiagnosis and monitoring of gonadotropin-producing

metastases in the centraL nervous system . Cancer 1976;38:112–118.

Follow up of patient

Year 1 2-weekly serum and urine hCG for 1-6 months

2 weekly urine hCG for 7-12 months

Year 2 4 weekly urine hCGYear 3 8 weekly urine hCGYear 4 3-monthly urine hCGYear 5 4-monthly urine hCGYear 6-life 6-monthly urine hCG

Available at: http://www.hmole-chorio.org.uk/clinicians_info_post_chemo_followup.html

Pregnancy after GTN

• Live births (66.9%),• Preterm deliveries (6.7%),• Ectopic pregnancies (1.1%),• Stillbirths (1.4%)• Repeat molar pregnancies (1.7%)

Garrett LA, Garner EO, Feltmate CM, et al. Subsequent pregnancy outcomes in patients with molar pregnancy and persistent gestational trophoblastic neoplasia. J Reprod Med 2008;53:481–486.

Recurrence rate of GTN

• 1.5 % of patient with prior complete mole .• 2.7 % of patient with prior partial mole. • 23% of patient with two prior molar pregnancies.• 2.5% of patients with no metastatic disease.• 3.7% of patients with good-prognosis metastatic

disease.• 13% of patients with poor-prognosis metastatic

disease.Mutch DG, Soper JT, Babcock CJ, et al.: Recurrent gestational trophoblastic disease. Experience of the Southeastern Regional Trophoblastic Disease Center. Cancer 66 (5): 978-82, 1990

Gestational trophoblastic disease in: Williams obstetrics, 24th edition, newyork, magraw hill.

COMPLICATIONS

• IMMEDIATE– Massive hemorrhage– Early onset preeclampsia and Eclampsia – Hyperemesis Gravidarum – Pulmonary embolism– Uterine perforation– IUGR of viable pregnancy– Still birth – Preterm birth

• REMOTE – Choriocarcinoma

Questions

• Define types of molar pregnancy and write difference between complete hydatidiform mole and partial mole?

• What are the clinical features of molar pregnancy how will you manage a case of molar pregnancy?

• Write complications of molar pregnancy.