Uterine choriocarcinoma: A gynaecological masquerader case report and review of the literature

doi:10.4236/mc.2013.24009

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Vol.2, No.4, 69-72 (2013) Modern Chemotherapy

http://dx.doi.org/10.4236/mc.2013.24009

Uterine choriocarcinoma: A gynaecological

masquerader case report and review of the literature

Eguzo Kelechi1, Chisara C. Umezurike1*, Emmanuel Akwuruoha2

1Nigerian Christian Hospital, Aba, Nigeria; *Corresponding Author: [email protected]

2Abia State University Teaching Hospital, Aba, Nigeria

Received 9 July 2013; revised 15 August 2013; accepted 1 September 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Choriocarcinoma is a rare clinical

condition, and its diagnosis may be difficult, es-

pecially in resource-limited settings. Case Pre-

sentation: A 38-year old para 2 woman is with a

4-month history of intractable vaginal bleeding

and offensive vaginal discharge, but without

antecedent pregnancy. She had previously been

managed at various tertiary medical institutions

where several pelvic ultrasound scans and even

histology of endometrial curette could not clinch

the diagnosis. The diagnosis of choriocarcino-

ma was made by a serial strip-based pregnancy

testing, which was still positive at 1:200 dilu-

tions. She was treated with chemotherapy in-

volving Adriamycin, Cyclophosphamide, Meth-

otrexate and Folinic acid. Conclusion: The di-

agnosis of choriocarcinoma may be difficult

especially when it develops ab initio without

preceding abortion, molar or term pregnancy. In

settings where serum hCG assay may be not

available, the simple strip-based pregnancy test

in dilution could be helpful in its diagnosis and

treatment m oni tor ing .

Keywords: Choriocarcinoma; Chemoth erapy;

Human Chorionic G onadotropin; Resource-Limited

Settings

1. INTRODUCTION

According to the World Health Organization Science

Group in 1983 [1] on histopathological and clinical termin-

ology, gestational choriocarcinoma is a carcinoma arising

from the trophoblastic epithelium that shows both cyto-

trophoblastic and syncytiotrophoblastic element. It may

arise from conceptions that give rise to a live birth, a still

birth, and abortion at any stage, an ectopic pregnancy or

a hydatidiform mole, or it may arise from ab initio.

Gestational trophoblastic diseases (GTD) comprise a

variety of biologically interrelated co nditio ns which form

a clinical spectrum consisting of four distinct clinical

pathological entities namely, molar pregnancy, invasive

mole, placental site trophoblastic tumours, and chorio-

carcinoma [2-4]. Serum human chorionic gonadotropin

(h’CG) assay has remained the main stay of diagnosis,

prognosis and monitoring of the co ndition.

The purpose of this report is to illustrate how difficult

the diagnosis of choriocarcinoma could be and to show

how a simple and “technology free” pregnancy test could

still be relevant in its diagnosis and treatment in resource-

poor settings.

2. CASE PRESENTATION

A 38-year old para-2 Nigerian woman was presented

in our centre with 4 months history of intractable vaginal

bleeding. The bleeding was said to be heavy and was

associated with passage of big blood clots. It was associ-

ated with offensive vaginal discharge, weight loss, fever

and antecedent menorrhagia. It was not however associ-

ated with any history of amenorrhea, termination of preg-

nancy, lower abdominal swelling, post-coital or contact

bleeding. Her last confinement was four years prior to

presentation. There was no history of cough, hemoptysis,

jaundice, unusual behaviour, convulsion, urinary or gas-

tro-intestinal symptoms. Prior to her presentation at our

center, the patient had been managed at the various terti-

ary hospitals (both in northern and south-eastern Nigeria),

where various abdominal ultra-sound scan report sus-

pected uterine fibroids, cervical cancer and endometrial

cancer respectively. A histopathological report from one

of the centres queried ch roni c endo metritis. Th ere was no

definite diagnosis, but she had been transfused with

many units of bl ood.

Initial evaluation revealed severe anaemia, with high

grade fever, tachycardia (120 beats/minute) and low

E. Kelechi et al. / Modern Chemotherapy 2 (2013) 69-72

blood pressure (80/50 mmHg). Her chest was clinically

clear, while she had suprapubic tenderness and offensive

vaginal discharge associated with altered blood and cer-

vical excitation tenderness. There was no suburethral or

cervical lesion. Due to her previous conflicting investi-

gation reports, the patient was booked for examination

under anesthesia, where she had torrential bleeding that

was coming from uterine cavity. Thus, a pregnancy test

was ordered that led to the diagnosis of choriocarcinoma.

Although a titrated serum hCG could not be done, an

analysis of urine hCG was positive at 1:200 d ilution. Her

blood group was B+, while her husband’s was O+. Her

PCV on admission was 12% and her total white blood

cell count, platelet count, serum electrolytes and urea

were within normal limits.

She was successfully resuscitated with antibiotics and

massive blood transfusion (20 units). Further evaluation

did not show any evidence of lung, liver or brain metas-

tases. Meanwhile, prognostic scoring of the patient was

uncertain as she was not “pregnant” and the serum hCG

could not be assayed, but she was placed at clinical stage

I (tumour confined to the uterus). She was then com-

menced on cancer chemotherapy.

Therapy was instituted using Methotrexate 50 mg on

days 1, 3, 5 and 7; Folinic acid 7 mg on days 2, 4, 6 and

8; Cyclophosphamide 650 mg daily for 5 days (in sa-

line), and Adriamycin 75 mg stat on day 1. Following

the first course of chemotherapy, the bleeding ceased and

the patient made tremendous clinical improvement. The

course was repeated on day 21, while the patient was

consistently monitored for signs of toxicity. Pregnancy

test became negative at the end of the second course. She

was scheduled to receive one more course of chemo-

therapy but she defaulted due to high cost of the cyto-

toxic drugs and the apparent relief of her symptoms. She

presented three months later with relapse and features of

metastasis and died.

3. DISCUSSION

Gestational trophoblastic disease most commonly fol-

lows molar pregnancy and may also occur following

normal or ectopic pregnancies and spontaneous or thera-

peutic abortions. Its incidence varies with figures as high

as 1 in 120 pregnancies in some areas of Asia and South

America, compared to 1 in 1200 in United States [5]. In

the United Kingdom, it has a calculated in cidence of 1 in

714 live births [3]. Metastatic gestational trophoblastic

disease occurs in 4% patients after local management of

Hydatidiform mole [5]. The incidence of choriocarci-

noma after complete hydatidiform mole is about 1000

times greater than after a normal pregnancy . It may oc-

cur ab initio as in the case presented [1,6]. Choriocarci-

noma is a rare tumour. In western countries, the inci-

dence is 1 in 45,000 to 50,000 pregnancies [5,7]. Higher

incidence is reported from, Africa, Asia and South Ame-

rica [8]. Majority of cases occur in women aged less than

35 year s of age [5].

Choriocarcinoma is suspected when there is persistent

or irregular uterine haemorrhage, following abortion or

hydatidiform mole. However, as illustrated in this case, it

could also be suspected in cases of undiagnosed vaginal

bleeding, even in the absence of pregnancy. Rapid growth

and haemorrhage make the tumour a gynecological

emergency. Metastasis may occur in lung, pelvis and

vagina. Rare sites include gastrointestinal tract, spleen,

and kidney. The central nervous system is seldom in-

volved in the absence of pulmonary metastasis [2]. Meta-

static disease occurs in 4% of patients after local man-

agement of hydatidiform mole and very rarely after term

pregnancies or abortions [1]. Sometimes they may be

combined with malignant germ cells components; and it

may be difficult to differentiate a primary tumour from a

metastasis. For females in non reproductive age group,

the tumours may arise from ovarian germ cells, which is

histologically similar to gestational uterine choriocarci-

noma [6].

Hitherto, serum hCG assay has remained the key fac-

tor in diagnosis and monitoring of the progression of the

disease. This has made clinical prognostic scoring easy

and objective, as the serum hCG provides a sensitiv e and

reliable indicator of the body burden of the tumour, its

progression and regression in response to treatment [1].

However, in resource-limited settings, like ours, serial

dilution test for urine hCG has also proven to be a useful

diagnostic tool. The emphasis, however, should be to

correlate the urine titers with serum values. This will

enhance prognostication of patients for appropriate che-

motherapy. According to I.A. McNeish et al. [9], proper

classification of patients (as low risk) did not compro-

mise outcome, but rather prevented undue exposure to

potentially carcinogenic chemotherapy.

Traditionally, patients with uterine choriocarcinoma

have been categorized as low risk (score of 0 to 5), me-

dium risk (score of 6 to 9) and high risk (score > 9), us-

ing the prognostic scoring system [1]. This enables ra-

tional use of chemotherapy with emphasis on the risk of

developing resistance. However, I.A. McNeish et al. [9]

have proposed a new scoring system: Charing Cross

scoring system (Table 1), which is intended to further

reduce the risk of undue exposure to chemotherapy. This

new system proposes the use of Methotrexate-Folinic

acid regimen for low risk disease (score 0 - 8), while

EMA/CO (Etoposide, Methotrexate, Actinomycin D,

Cyclophosphamide and Oncovin) is reserved for high

risk disease (score > 8). An algorithm (Figure 1) has also

been developed to enhance case management.

Initial treatment for those with low-risk disease was

Methotrexate (MTX) (50 mg intramuscularly on days 1,

E. Kelechi et al. / Modern Chemotherapy 2 (2013) 69-72

3, 5, and 7 wit h Folinic acid (FA) 7.5 mg ora lly on days 2,

4, 6, and 8, repeated every 2 weeks. [1] Whereas for

those with medium-risk disease, the chemotherapy regi-

men consisted of MTX as above, plus oral Hydroxyurea

1 g on day 1, oral mercaptopurine 75 mg on the same day

as the FA, alternating with courses of either intravenous

Etoposide 250 mg/m2 on days 1 and 3, or courses of in-

travenous Actinomycin 0.5 mg daily for 5 days. 2 Treat-

ment for high-risk disease was infusional chemotherapy

according to the Etoposide, Methotrexate, and dActino-

mycin (EMA)/Cyclophosphamide and Vincristine (CO)

regimen 3 (Table 2) [9].

Our case typically illustrates the frustration associated

with cancer chemotherapy in Nigeria and indeed other

developing countries where prevalent poverty makes

procurement and sustenance of the drugs impossible.

Meanwhile, several complications of both uterine

choriocarcinoma and its management have been docu-

men ed. Being a highly malignant disease, metastases

may occur in lung, pelvis and vagina. Rare sites include

gastrointestinal tract, spleen, and kidney. The central

nervous system is seldom involved in the absence of

pulmonary metastasis [5]. There are reports describing

Figure 1. Treatment pathway for low-risk gestational tropho-

blastic disease.

Table 1. Charing cross scoring system for gestational trophoblastic disease1.

Charing Cross Scoring Sy stem2

Variable 0 1 2 6

Age, years <39 >39

Antecedent pregnancy Male Abortion or unknownTerm

Interval

(end of antecedent pregnancy to start treatment), months<4 4 - 7 6 - 12 >12

hCG, IU/L 103 - 104 <103 104 - 105 105

ABO (male x female) A × O B × A/O

O × A AB × A/O

O/A X unknown

No. of metastases 0 1 - 4 4 - 8 >8

Site of metastases Nil or lungs or vaginaSpleen, kidney GI tract CNS, liver

Largest tumor mass, cm <3 3 - 5 >5

Previous chem otherapy Nil Nil Single agent Two or more drugs

1Low risk, 0 to 8; high risk, >8. 2The patient’s Charing Cros s score is calcul ated at the start of treatment. All p atients are asses sed with clinical history, serum

hCG, chest radiograph, and uterine ultrasound. If there is evidence of metastatic disease on radiograph, computed tomographic scan of the chest, abdomen and

pelvis and a cranial magnetic imaging scan are obtained. The largest tumor mass measurement usually derives from the uterine ultrasound scan.

Table 2. Dactinomycin and EMA/CO chemotherapy regimens.

Regimen Dosage

Dactinomycin 0.5 mg IV daily × 5 Repeated every 2 weeks

EMA/CO EMA Day 1 Dactinomycin 0.5 mg IV bolus Etoposide 100 mg/m2 over 30 mi nut es

Methotrexate 300 mg/m2 over 12 hours

Day 2 Dactinomycin 0.5 mg IV bolus Etoposide 100 mg/m2 over 30 mi nut es

Folinic acid 15 mg PO bid over 2 days commencing 24 hours after start of methotrexate

CO Vincristine 0.8 mg/m2 (maximum 2 mg) bolus Cyclophospham ide 600 mg/m2

over 30 minutes EMA and CO alternatively weekly

OPEN ACCESS

E. Kelechi et al. / Modern Chemotherapy 2 (2013) 69-72

metastasis to large intestine from choriocarcinoma pre-

senting as pseudo-obstruction and metastasis to stomach.

Metastasis to gastrointestinal tract and presentation as

perforation of small intestine is very rare [10]. Also, it

has been reported that exposure to combination, but not

single-agent, chemotherapy is associated with an in-

creased incidence of second tumors, especially myeloid

leukemia and colon cancer [11]. In addition, combination

chemotherapy, more than single agent Methotrexate,

increases the risk of an early menopause [12].

4. CONCLUSION

Although uterine choriocarcinoma, a rare form of ges-

tational trophoblastic disease, usually follows a molar

pregnancy, term deliveries or abortions, it can also pre-

sent ab initio. Its diagnosis can often pose a dilemma in

resource-limited settings, but a high ind ex of suspicion is

helpful. The high cost of cytotoxin, which contributed to

the default in treatment and eventual death of the patient,

should be revisited. There is a need to make the cytotoxic

drugs available and affordable across the world. Finally,

although urin e hCG assay is no t the go ld standard for the

diagnosis and monitoring of this disease, it is useful in

resource-limited settings. Further studies, however, should

be done to correlate urine hCG titres with serum hCG

levels in order to enhance the diagnosis and management

of choriocarcinoma in low-resource settings.

REFERENCES

[1] James, F.H., et al. (1993) Cancer medicine. 3rd Ed, Lea

& Febinger, Philadelphia, 704, 1691-1694.

[2] Muggia, F.M., Eifel, P.J. and Burke, T.W. (1997) Gesta-

tional trophoblastic diseases. In: de Vita Jr., V.J., Hellman,

S. and Rosenberg, S.A., Eds., Cancer Principles and Prac -

tice of Oncology, Lippincott-Raven, Philadelphia, 1427-

1539.

[3] Roya l College of Obstetricians and Gynaecolog ists (2010)

The management of gestational trophoblastic disease.

RCOG, London.

[4] Ng, T.Y. and Wong, L.C. (2003) Diagnosis and manage-

ment of gestational trophoblastic neoplasia. Best Practice

& Research Clinical Obstetrics and Gynaecology, 17,

893-903.

http://dx.doi.org/10.1016/S1521-6934(03)00098-1

[5] Paradinas, F.J. (1992) Pathology and classification of

trophoblastic tumours. In: Coppleson, M., Ed., Gynaeco-

logic Oncology, 2nd Edition, Churchill Livingstone, Lon-

don, 1013-1026.

[6] Acosta-Sison, H. (1959) Ab initio choriocarcinoma: Two

unusual cases. Obstetrics & Gynecology (New York), 13,

350-352.

[7] Seckl, M.J., Sabire, N.J. and Berkowitz, R.S. (2010) Ge-

stational trophoblastic disease. The Lancet, 376, 717-729.

http://dx.doi.org/10.1016/S0140-6736(10)60280-2

[8] Fox, H. and Buckley, C.H. (1992) The female genital

tract and ovaries. In: McGee, J.O.D., Isaacson, P.G. and

Wright, N.A., Eds., Oxford Text Book of Pathology, 2nd

Edition, Oxford University Press, New York, 1565-1639.

[9] Balagopal, P.G., et al. (2003) Unusual presentation of

choriocarcinoma. World Journal of Surgical Oncology,

2003, 1, 4. http://dx.doi.org/10.1186/1477-7819-1-4

[10] McNeish, I.A., et al. (2002) Low-risk persistent gesta-

tional trophoblastic disease: Outcome after initial treat-

ment with low-dose methotrexate and folinic acid from

1992 to 2000. Journal of Clinical Oncology, 20, 1838-

1844. http://dx.doi.org/10.1200/JCO.2002.07.166

[11] Rustin, G.J.S., Newlands, E.S., Lutz, J.M., et al. (1996)

Combination but not single-agent Methotrexate chemo-

therapy for gestational trophoblastic tumors increases the

in ci de nce of second tu mors. Journal of Clinica l On co lo gy ,

14, 2769-2773.

[12] Bower, M., Rustin, G.J.S., Newlands, E.S., et al. (1998)

Chemotherapy for gestational trophoblastic tumours has-

tens menopause by 3 years. European Journal of Cancer,

34, 1204-1207.

http://dx.doi.org/10.1016/S0959-8049(98)00059-8