Case presentation

DR. MOHAMMAD

ASHRAFUL AMIN(ASIF)

ID-927

NAME : SHILA RANI

AGE : 27YRS

RELIGION : HINDU

ADRESS : GUMGOAN,FULPUR,MYMENSHING

MARRIAL STATUS : MARRIED

HUSBAND’S NAME : RATAN CHANDRA

DOA : 16/9/14

CASE PROFILE

1) h/o amenorrhoea for 6weeks.

2) H/O vomiting several times for 12days.

3) H/O chest tightness for same duration.

4) H/O fever and weakness also same duration.

PATIENT HISTORY

M.CYCLE >>>>>> 3-4Days

M.Period >>>>>> Regular

LMP>>>>>> 1ST JULY, 2014

MENSTRUATION HISTORY

MARRIED FOR : 12 yrs.

PARA : 2(NVD)- 1(ND) + 1 (Ab)

GRAVITA : 4th

CONTRACEPTIVE HISTROY : nil

AGE OF LAST CHILD : 6yrs

NUMBER OF LIVING CHILD : 1

OBSTRUCTIVE HISTROY

Appearance : ill looking with resp distress

Pulse : 120/min

B/P : 90/60

Temp : 100 degree F

Resp. Rate : 24/min

Anaemia : Mild

Oedema : absent

Dehydration : absent

ON EXAMINATION

P/A/E : SOFT,TENDER,NOT

DISTENDED

P/V/E : NO ACTIVE BLEEDING

ON EXAMINATION

CBEWBC : 13500 /cu mm

N : 85%L :12%

HB : 10.2 gm/dlPlatelets : 210 k/cu mmESR : 58 mm in 1st hrBlood group : B+(ve)

ON INVESTIGATION

Microscopic examination :

E.C : 4-5/HPF

R.B.C : 1-2/HPF

P.C : 2-3/HPF

CAST : NIL

URINE R/M/E

Na+ : 136 mmol/L

K+ : 3.8 mmol/L

Cl- : 105 mmol/L

HCO3 : 20.3 mmol/L

pH : 7.38

SERUM ELETROLYTES

Uterus : is bulky in size and anteverted in position. AP diameter is 49mm.

Myometrium shows uniform echo texture all over. Endometrium is thickened

(16 mm)

Right ovary : normal

Left ovary : a cystic lesion with internal irregular echogenic area measuring

about (35*20) mm is seen in left ovary.

A mixed echogenic area measuring about (7.4*6.6)cm is seen in left adnexal

region.no definite gestational sac could be detected.

Mild pelvic collection is seen.

N.B : pelvi-calyceal systems of left kidney is moderately dilated. left ureter

is dilated.

IMPRESSION : 1) suggestive of ectropic pregnancy (left) with mild pelvic

collection

2) Left ovarian haemorrhagic cyst.

3)Left sided hyroureteronephrosis

USG

B-HCG – 1483100.00 mIU/ml

(Other hospital on 15/9/14)

B-HCG -1805.0 mIU/ml

( JIMCH – ON 17/9/14)

B-HCG

Trachea – normal in position

Diaphragm – both domes of the diaphragm are normal in

position, contour and definition. The costophrenic

angles are clear.

Heart : normal in transverse diameter.

Lungs – multiple variables size rounded opacity notes in

both lugs field.

Bony thorax – reveals no abnormality.

IMPRESSION : suggestive of secondary's

CHEST X-RAY

CHEST X-RAY(19/9/14)

Lungs – multiple variables size

rounded opacity notes in both lugs

field.

IMPRESSION : suggestive of

secondary's

Laparotomy followed by

biopsy taken from ovary ,

pelvic mass. Endometrial

curettage for

histopathology.

NAME OF OPERATION

DATE:17/9/14

there was no pelvic collection. Both tubes

were healthy, ovaries were polycystic.

Biopsy from ovary was taken. Pelvic mass

in post.wall of urinary bladder. For this

assoc prof.dr.Rezaul islam took biopsy

from pelvic mass. then diagnostic D&C was

done & endometrial tissue was taken for

histopathology examination

FINDING

then she was sent to HDU on 17/9/14 in due to

respiratory distress and SPO2-50%

After on HDU (ON EXAMINATION) :

B/P : 125/78 mm Hg

Pulse : 84/min

Temp : N

SPO2 : 100% ( through BAIN circuit, 4-5L 02/min)

HDU

1. NPO-Till further order.

2. Bed rest with propped up position

3. 02 inhalation through BAIN circuit (4-6l/min)- cont

4. O-P, E-TT suction- Q1H

5. Chest and limb physiotherapy- Q1H

6. Close the both eyes with chloramphenicol eye drop-Q8H

7. Use oroclean mouth wash –Q8H

8. Inf DNS(1l) + inf DA(1L) +inf hartsol(1L)

I/V a 20drops/min-cont

9. Nebulization with windel plus –Q4H and SOS

10. Inj nutridex (100ml)

I/V over 1H-SOS (if RBS<6mmol/L)

HDU ORDER ON ADMISSION

17/9/14

INJ CEFTRON(1gm) – 1vial I/v –Q 12H

INJ METRYL (100ML) 1 bottle I/V – Q8H

INJ HYPNOFAST 3AMP(9cc) +N/S(36cc)=total 45cc,

I/V by S/P 1ml/H-Cont (stops if the BP falls)

INJ ESONIX(40mg) – 1vial I/V –Q12H

INJ EMISTAT (8mg) 1amp I/V –Q12H

INJ ANADOL (50mg)--½ Amp I/V – Q12H

PRE PAGE TREATMENT

ABG-

REPORT(18/9/14)

SUGGESTIVE : This is a patient of

choriocarcinoma with secondary

metastasis to lung’s and pt’s need

referred to oncologist for further

management.

OPINION ON MEDICINE WARD

DATE: 18/9/14

Pulse : 130/min

B/P : 100/60 mm Hg

R.R : 30/min

Temp : normal

Heart : s1,s2 HS audible

Lungs : VBS with Ronchi

FOLLOW UP

20/9/14

DATE DRUG AMOUNT

17/9/14 (1st dose) MTX 1 VIAL

21/9/14 (2nd dose) MTX 1 VIAL

23/9/14 (3RD dose) MTX 1 VIAL

MTX

LEUCOVORIN CALCIUM

Date Dose Route

22/9/14 1st I.V

(slowly)

24/9/14 2nd …..not yet

Appearance : ill looking with Resp distress

Pulse : 150/min

B/P : 100/60

Temp : 99 degree F

Resp. Rate : 28/min

Heart: s1,s2 audible (very loud)

Lungs: VBS on BL with crebs thoughout lungs.

Anaemia : Mild

Oedema : absent

Dehydration : absent

SPO2 : 66%

urine: high colour urine.

TODAY’S FOLLOW UP (24/09/14)

CHORIOCARCINOMA

DR. MOHAMMAD

ASHRAFUL AMIN(ASIF)

ID-927

SEMINAR ON:

• Gestational Trophoblastic Disease (GTD) is a

spectrum of proliferation abnormalities of

trophoblasts associated with pregnancy .

• GTD includes

- complete & partial H. mole

- invasive mole

- choriocarcinoma

- placental site trophoblastic tumour

Gestational Trophoblastic Disease

PATHOLOGIC CLASSIFICATION

CLINICAL CLASSIFICATION

Hydatidiform mole

*complete

*incomplete

Benign gestational trophoblastic disease

Invasive moleMalignant

trophoblastic diseaseNonmetastatic

Placental site trophoblastic tumor

Metastatic

Choriocarcinoma High risk Low risk

Pathologic and clinical classifications for

gestational trophoblastic disease

• Non metastatic ( confined to uterus)

• Metastatic

LOW RISK

-< 4 months duration

-initial serum HCG levels < 40,000miu/ml

-metastasis limited to lungs and vagina

-no prior chemotherapy

-no preceding term delivery

HIGH RISK

-duration > 4 months

-serum HCG levels > 40, 000

-brain or liver metastasis

-failure of prior chemotherapy

-Following term pregnancy

-WHO score>7

GTN(modified WHO classification

1998)

CHORIOCARCINOMA

DEFINITION

This is extremely malignant form of

trophoblastic tumour may be considered a

carcinoma of chorionic epithelium, although an

its growth and metastasis behave like sarcoma

• Characterized by abnormal trophoblastic

hyperplasia and anaplasia , absence of

chorionic villi

Pathology:

• Incidence: 1: 250-5000 pregnancies in Asia and 1:4000 in the west.

• Origin:

* Choriocarcinoma is a malignant tumour of the trophoblast.

1- About 50% of cases follow molar pregnancy.

2- 25% follow abortion

3- 23% follow normal pregnancy

4- 2% follow ectopic pregnancy.

* In rare cases, the tumour arises as a teratoma in the ovary or testicle.

• Macroscopic appearnce:

The tumor arises in the endometrium as

1. a soft friable dark red hemorrhagic mass projecting into the uterine cavity and may from a polyp.

2. Malignant tissue may be buried within the myometrium , inaccessible to the curette, or hidden in a distant metastasis.

3. However, any of these tumor patterns secretes (hCG) which causes cystic changes of the ovaries in about 30% of cases..

Gross specimen of choriocarcinoma

• Microscopic appearance:

The tumour consists of cyto-and

synecytiotrophoblasts showing malignant

characters, invading the myometrium and blood

vessels. Chorionic villi are absentthis differentiates Choriocarcinoma from invasive

mole.

Microscopic image of choriocarcinoma

absence of chorionic villi

• Mode of spread:

1. direct spread: to the parametrium, tubes and

ovaries.

2. Blood spread: occurs early to distant organs.

The commonest sites are lunges (80%),

vegina (30%), brain (10%) and liver (10%)

Diagnosis:

• A- symptoms:

1- Persistent or irregular vaginal bleeding: it is the commonest symptom occurring after labor, abortion or evacuation of a vesicular mole. Bleeding can occur within days or months but rarely after 2 years.

2- Vaginal discharge: which is blood stained and offensive due to ulceration and infection of the growth .

3- amenorrhea: may be present due to continuous hCG production.

4- Acute abdominal pain: due to intraperitoneal haemorrhage as a result of perforation of the uterus by the growth.

5- Abdominal or vaginal swelling: may develop.

6- Symptoms of metastases: as dysponea, haemoptesis, jaundice and neurological symptoms as headache may be the first manifestation of the tumor.

7- pallor

8- vomiting.

• B- signs:

(1) cachexia and severe anaemia.

(2) fever may be present due to infection and

necrosis

(3) the uterus may be normal size or enlarged and

soft.

(4) the ovaries: may be enlarged and eystic.

(5) metaststic nodules: in the vulva or vagina

PATIENT MAY COMMONLY PRESENT WITH SIGN OF METASTASIS

Pulmonary metastasis

• 80% of patient with metastatic GTT lung involvement patient present with chest pain, cough, hemoptysis, dyspnea.

Principle of pulmonary pattern

• Alveolar or snow strom pattern.

• Discrete rounded densities- cannon ball appearance

• Embolic pattern caused by pulmonary arterial occlusion

Vaginal metastasis

• occur in about 30%

Liver metastasis

• Occur in about 10%

Central Nervous System

• Involve brain in 10% cases

C- investigations:

(1) uterine curettage: should be done in every case

of persistent or irregular uterine bleeding after

labour, abortion or molar pregnancy. However,

intramural tumour cannot be detected by

curettage.

(2) serum β- subunite of hCG: persistent or rising

titres in absence of pregnancy are indicative of

trophoblastic neoplasia.

(3) biopsy: from metastatic valvar or vaginal

lesions.

• (4) imaging:

a- plain X-ray chest: may show secondaries in the form of " cannon balls" or "snowstorm" appearance.

b- ultrasonography: to detect tumour, cystic ovaries and exclude remnants of conception.

c- CT scan: for lungs, liver, brain and bone.

• (5) lumbar puncture: plasma hCG/ CSF hCGratio less than 60 strongly CNS involvement my metastases

• (6) blood studies:

a- complete blood picture including platelet count

b- Renal, liver and thyroid function tests

c- Blood group.

Β-hCG VS hCG-H

Β-hCG

• Produced by

syncytiotrophoblasts

• Present through. out

the normal

pregnancy

•

• in all forms of GTD

• Method of action is endocrine

• Maintains progesterone

production

hCG-H

• Invasive cytotrophoblasts

• Present in implantation

phases of normal

pregnancy

GTN

• Paracrine

• Promotes trophoblastic

growth and invasion

WHO PROGNOSTIC SCORING SYSTEM

Score

Prognostic factor 0 1 2 4

Age(years) ≤39 >39 — —

Pregnancy historyHydatidiform mole

Abortion,

ectopic

Term pregnancy

—

Interval (months) of treatment

<4 4-6 7-12 >12

Initial hCG(mIU/ml) <103 103-104 104-105 >105

ABO Group O-A B-AB

Largest tumor(cm) <3 3-5 >5 —

Sites of metastasis Lung Spleen,

kidneyGI tract, liver Brain

No. of metastasis — 1-4 4-8 8

Previous (treatment) — — Single drug 2 or more

0-4 low risk, 5-7 intermediate risk, >8 high risk for death

Stage I confined to uterine corpus.

Stage II metastases to pelvis and

vagina

Stage III metastases to lung

Stage IV metastases to other organs.

FIGO CLASSIFICATION:

FIGO STAGING SYSTEM FOR GESTATIONAL TROPHOBLASTIC TUMOUR

Stage I : Disease confined to uterus

Ia : Confined to uterus with no risk factor

Ib : Confined to uterus with 1 risk factor

Ic : confined to uterus with 2 risk factor

Stage II : GTT extending outside uterus but

limited to genital str. (adenexa vagina broad

ligaments)

IIa : GTT involving genital tract with out risk

factor

Iib : GTT involving genital tract with 1 risk factor

IIC : GTT involving genital tract with 2 risk factor

FIGO STAGING SYSTEM FOR GESTATIONAL TROPHOBLASTIC TUMOUR

Stage III : GTT extending of lung with or without

Known genital tract involvement

IIIa : GTT extending to lung with no risk factor

IIIb : GTT extending to lung with 1 risk factor

IIIc : GTT extending to lung with 2 risk factor

Stage IV: All other metastatic sites

IVa : All metastatic sites other site with out risk

factor

IVb : All metastatic sites other site with out 1 risk

factor

IVc: All other metastatic sites site with out 2 risk

factor

Risk Factor ; HCG > 100;000mIU/ml

Diagnostic Evaluation All Patients with persistent GTT should undergo

careful pretreatment evaluation including the

following –

•Complete history and physical examination .

•Measurement of serum HCG value.

•. Hepatic, thyroid and renal function test.

•Determination of baseline peripheral WBC and

platelet count.

•Once the diagnosis established the further

examination should be done to determine the extent

of disease (Chest X- ray, CT scan of abdomen, pelvis

and Head, MRI, USG)

Management

1. Preventive and Curative

a. Preventive – Prophylactic CT in at risk women

following evacuation of molar pregnancy.

Risk Women –

• Age of patient >35 years.

• Level of HCG > 100,000 IU/ 24 Hours.

• Histological diagnosed infiltrative mole.

• Previous history of molor pregnancy.

- Meticulous follow up following evacuation of H. mole of

at least one years to detect early evidence of

trophoblastic reactivation.

Single agent chemotherapy is highly effective in case of

persistent trophoblastic disease.

- Selective hysterectomy in H. mole in patients of

age>35years.

Treatment:

The treatment of choice

chemotheraphy

Chemotherapy:

(I) low- risk group score ≤ 4:

Single cytotoxic drug either methotrexate or

actinomycin D

(II) High-risk group score >8 :

Multiple cytotoxic drugs

Hysterectomy may be indicated in the following

conditions:

• severe uterine bleeding

• perforation of the uterus with intraperitoneal

haemorrhage.

• Massive haemorrhage from the bowel

• Torsion of a theca lutein cyst.

• Durg resistance or toxicity.

• Persistant localised metastases in the vagina,

lung or brain after chemotherapy

Those who want to retain fertility

1. Single agent CT is preferred treatment in patients

with stage I disease who want to retain fertility.

• When patients are resistant to single agent

chemotherapy and desire to retain fertility

combination chemotherapy should be

administered.

• Stage II & III – Vaginal and pelvic metastatics.

Vaginal – In low risk cases.

Single agent chemotherapy have 80% rate of

remission.

High risk patients managed with primary intensive

combination chemotherapy.

Curative Management -

• Chemotherapy.

• Surgery.

• Radiation.

Management of various stages-

Stage I:

Initial – single agent chemotherapy or hysterectomy

with adjunctive chemotherapy .

Resistant – Combination chemotherapy

Hysterectomy with adjunctive chemotherapy.

Local resection, pelvic infusion.

Stage II & III-

Low risk –

Initial - Single agent chemotherapy.

Resistant – Combination chemotherapy.

High Risk –

Initial – Combination chemotherapy.

Resistant – second line combination chemotherapy

Stage IV-

Initial - Combination Chemotherapy.

Brain – Whole heat irradiation (3000 CGY)

craniotomy to manage complications.

Liver – Resection to manage complications.

Resistant – second line combination chemotherapy

hepatic arterial infusion.

Adjuvant chemotherapy is administered for

three reasons

1. To reduce the likelihood of disseminating

viable tumour cell at surgery.

2. To maintain cytotoxic level of chemotherapy

in the blood stream and tissue in case viable

tumour cells are disseminated at surgery .

3. To treat any occult metastasis that may

already present at the time of surgery.

Chemotherapy

Single agent chemotherapy with either actinomycin D

or methotrexate has achieved comparable and excellent

remission rates in both non metastatic and low risk

metastatic GTN.

single drug regimen in low rate case –

Drug Dosage Route Days

Methotrexate 1-15 mg/kg IM/IV 1,3,5,7.

Folonic acid 1-015 mg/kg IM 2,4,6,8.

Actinomycin D 12 mg/kg IV 1-5

Cyclophosphamide 3mg/kg IV 1-5

EMA- CO protocol in poor prognosis

metastatic disease

The course will restart after 7-14 days. If possible, Generally 2

additional courses are given after the hCG levels become normal.

Days Drug Dose

Day-1 Etoposide 100mg /m2in 200 ml saline infused over 30 minutes.

Actinomycin D 0.5 mg IV bolus

Methotrexate 100mg /m2 bolus folllowed by 200mg /m2 IV infusion over 12 hours.

Day -2 Etoposide 100mg /m2in 200 ml saline infused over 30 minutes.

Actinomycin D 0.5 mg IV bolus

Folinic acid 15mg IM every 12 hrs for 4 doses begnning 24 hours after starting methotrexate.

Day-8 Cycolphosphamide 600mg/m2 IV in saline over 30 min.

Vincristine (oncovin) 1mg/m2 bolus

• Myelosuppression

• Nausea,vomiting

• Mucositis

• Alopecia

• Neuropathy

• Second malignancy AML, breast and colon

cancer.

SIDE EFFECTS

Leucovorin is used to prevent harmful effects of

methotrexate. when methotrexate is used to treat

certain types of cancer. Leucovorin is also used to

treat people who have accidentally received an

overdose of methotrexate or similar medications.

Leucovorin is in a class of medications called folic

acid analogs. It works by protecting healthy cells

from the effects of methotrexate or similar

medications while allowing methotrexate to enter

and kill cancer cells.

Leucovorin

(Folinic acid )

• Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

1. diarrhoea

2. rash

3. Hives (Urticaria, also known as hives, is an outbreak of swollen, pale red bumps or plaques)

4. itching

5. difficulty breathing or swallowing

side effects can this

medication cause

• Patients with brain metastasis require whole

brain radiation therapy(3000cGY ocer 10 days)

• In liver metastasis hepatic artery ligation or

embolisation or whole liver radiation (2000 c GY

over 10 days)along with chemotherapy may be

effective.

RADIATION

Follow up-

All patients with stage I through stage III disease

should receive follow up with-

1. Weekly measurement of HCG level until they

are normal for 3 consecutive weeks.

2. Monthly measurement of HCG value until level

are normal for 12 consecutive months.

3. Effective contraception during the entire

interval of hormonal follow up.

PROGNOSIS

• Cure rates should approach 100% in

nonmetastatic and low-risk metastatic GTD

• Intensive multimodality therapy has resulted in

cure rates of 80-90% in patients with high-risk

metastatic GTD

FOLLOW-UP AFTER SUCCESSFUL

TREATMENT

• Quantitative serum hCG levels should be

obtained monthly for 6 months, every two

months for remainder of the first year, every 3

months during the second year

• Contraception should be maintained for at

least 1 year after the completion of

chemotherapy. Condom is the choice.

SUMMARY OF PATIENT

FIGO classification:

Stage III metastases to lung.

According WHO Prognostic Scoring System to

this patient

Score

Prognostic factor 0 1 2 4

Age(years) ≤39

Pregnancy historyAbortion,

ectopic—

Interval (months) of treatment

<4

Initial hCG(mIU/ml) >105

ABO Group B

Largest tumor(cm)

Sites of metastasis Lung

No. of metastasis 1-4

Previous (treatment) — —

0-4 low risk, 5-7 intermediate risk, >8 high risk for death

TOTAL SCORE : 8 ( or 5)

Prognostic factorScore

Age(years) 0

Pregnancy history 1

Interval (months) of treatment 0

Initial hCG(mIU/ml) 4 ( if 1st HCG is count, if not then score:1)

ABO Group 2

Largest tumor(cm) ?

Sites of metastasis 0

No. of metastasis 1

Previous (treatment) 0

THANK

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