Primary Cervical Choriocarcinoma: Case Report and the Review of Literatures

doi:10.4236/jct.2013.48158

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Journal of Cancer Therapy, 2013, 4, 1335-1340

http://dx.doi.org/10.4236/jct.2013.48158 Published Online October 2013 (http://www.scirp.org/journal/jct) 1335

Primary Cervical Choriocarcinoma: Case Report and the

Review of Literatures

N. Behtash, M. Karimi Zarchi*, A. A. Shamshirsaz, A. A. Shamshirsaz,

Ashrafosadt Miratashi-Yazd, N. Mehrdad

Gynecological Oncology Fellowship, Shahid Sadoughi University of Medical Science, Yazd, Iran.

Email: *[email protected]

Received March 6th, 2013; revised April 6th, 2013; accepted April 14th, 2013

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

ABSTRACT

Background: Primary choriocarcinoma of the cervix is a very rare en tity. Case: A 35-year-old patient had been admit-

ted to our hospital with vaginal bleeding for 7 months. A cervical mass measured 4 × 4 cm was palpated on the anterior

surface of the cervix. Biopsy of the lesion demonstrated extensive necrosis and was in favor of squamous cell carci-

noma. Patient was accepted as FIGO stage Ib1-2 and underwent type II hysterectomy with bilateral salpingoopherectomy

and bilateral pelvic lymph node dissection was carried out. Post operative pathologic evaluation of the surgical speci-

men evinced that the case was primary cervical choriocarcinoma. Conclusion: Primary choriocarcinoma of the cervix

should be considered in patients in their reproductive years with cervical lesion and negative cervical cytology.

Beta-hCG assay and transvaginal color Doppler sonogra ph y are usefu l for earl y diagnosi s.

Keywords: Choriocarcinoma; Cervix; Primary

1. Introduction

Choriocarcinoma was categorized into two classes: ges-

tational and non gestational. Non gestational choriocarci-

noma is a rare germ cell tumor of the ovary that only

few cases are reported in literature. Gestational choriocarci-

noma belongs to the group of the gestational tropho-

blastic disease (GTD) and usually arises in the uterine

cavity. Extrauterine chorio carcinoma is rarely seen. Saito

et al. defined following diagnostic criteria for extrau-

terine choriocarcinoma in 1965: 1) absence of disease in

the uterine cavity, 2) exclusion of coexistence of normal

intrauterine pregnancy, 3) exclusion of molar pregnancy

and 4) pathologic confirmation of disease [1]. Most of

the extrauterine choriocarcinoma reported in literature,

originates in uterine cervix [2-7]. However, there are also

reports in the literature that choriocarcinoma located in

other regions outside the uterus in genital tract such as

ovary [8], tube [9], vulva [10] and vagina [11]. Our ob-

jective was to describe the clinical and pathologic find-

ings of one case of primary cervical choriocarcinoma in a

35-year-old woman and reviews of the literatures.

2. Materials and Methods

From January 1950 to December 2008, a PUBMED/

MEDLINE search performed using the key words chori-

ocarcinoma and cervix and primary. Totally 29 publica-

tions including 78 patients existed (Table 1), which 18

are in the PUBMED/MEDLINE. In our review, we ex-

cluded all papers other than English language. We got

information regarding age, gravida and parity, symptoms

and duration, preceding pregnancy, latent period from

preceding pregnancy, location, lesion size and hCG level

(Table 2). Also type of therapy and the outcomes were

attained and mentio ned in separate table (Table 3).

3. Case Presentation

A 35-year old woman, Gravid 3, Para 2 and Abortion 1,

had been experienced irregular vaginal bleeding for 7

months when she was referred to our clinic on June 2008.

Her first and second pregnancy ended in a full-term de-

livery by caesarean section in 37 and 38 weeks of gesta-

tion in 2002 and 2004, respectively. Her third pregnancy

ended in a missed abortion at 6 week’s gestation in 2005.

She mentioned a regular menstrual cycle with 7 days

mean duration. She complained of bleeding 4 days before

her menses, and in the last month, she mentioned con-

*Corresponding a uthor.

Primary Cervical Choriocarcinoma: Case Report and the Review of Literatures

1336

Table 1. Eighty-seven cases of primary cervical choriocarcinoma recorded in literature.

Study Cases Journal Language/Country

Rashbaum M* (1952) 13 (12 from l it erature) Am J Obstet Gynecol 1952; 6 4: 451-5 English/Amer i ca

Saito M (1965) 18 (18 from literature) World Obstet Gynecol 1965; 17: 459-84 Japanese/Japan

Minegishi (1965) 6 Sanfujinka Jissai 1965; 14: 763 -7 Japanese/Japan

Koga (1966) 1 J Jpn Obstet Gynecol Soc 1966; 13: 245-9 Japanese/Japan

Ooguchi (1966) 7 J Jpn Obstet Gynecol Soc 1966; 18: 1083-92 Japanese/Japan

Danek (1969) 1 Minerva Ginecol 1969; 21: 1707-11 Italian/Italy

Momose (1970) 1 Obstet Gynecol Ther 1970; 21: 468-71 Japanese/Japan

Pavlica (1971) 1 Zentralbl Gynakol 1971; 93: 72- 4 German/Germany

Tsukamoto* (19 80) 1 Gynecol Oncol 1980; 9: 99-107 English/Japan

Tripathi* (1982) 1 Br J Obstet Gynecol 1982; 89: 267-9 English/India

Meriah (1983) 1 J Gynecolo Obstet Biol Reprod(Paris) 1983; 12: 51 9-24 French/France

Martin* (1983) 1 Am J Obstet Gynecol 1983; 147: 343-4 English/Americ a

Bogdanowicz (19 84) 1 Ginekol Pol 1984; 55: 527-30 Polish/Poland

Bhalla* (1987) 1 Indian J Pathol Microbiol 1987; 3 0: 51-3 English/India

Tsai*(1988) 4 Asia Oceania J Obstet Gynaecol 1988; 14: 285-9 2 English/Taiwan

Ben-Chetrit* (1990) 1 Am J Obstet Gynecol 19 90 ; 1 63: 1161-3 English/Israel

Lee* (1992) 1 Acta Obstet Gynecol Scand 1992; 71: 4 79-81 English/ Taiwan

Heyn (1993) 1 Geburtshilfe Frauenheilkd 1993; 53: 498-500 German/Germany

Herts* (1993) 1 J Ultrasound Med 1993; 12: 59-62 English/America

Abboud (1994) 1 J Gynecol Obstet Biol Reprod (paris) 1994; 23: 149- 51 French/France

Al Hassani* (1995) 1 Trop Geogr Med 1995; 47: 308-9 English/Qatar

Yahata* (1997) 1 Gynecol Oncol 1997; 64: 274-8 English/Japan

Lema* (1997) 1 East Afr Med J 1997; 74: 600-2 English / Malawi

Baykal* (2003) 1 Gynecol Oncol 2003; 90: 667-9 English/Turkey

Huang (2004) 2 Zhong Nan Da Xue Xue B ao Yi Xue Ban 2004; 29: 108-9 Chineese/China

Roopnarinesingh* (2004) 1 Ir Med J 2004; 97: 14 7-8 English/Irland

Peko (2005) 1 Med Trop 2005; 65: 498 French/France

Fu* (2007) 4 Int J Gynecol Cancer 20 07; 17: 715-719 English/China

Kairi-Vassilatou* (2007) 1 Int J Gynecol Cancer 2007; 17: 921-925 English/Greece

tinuous spotting for one month. On physical examination,

necrotic hemorrhagic polypoid mass protruding into cer-

vical canal, approximately 4 × 4 cm, was palpated. Va-

ginal fornices were normal. Digital examination demon-

strated no parametrial extension. Colposcopy was done

and punch biopsy was taken. During biopsy significant

bleeding from the lesion occurred and because of ob-

scured vision only eight specimens were excised. Patho-

logy reported that six of eight specimens were necrotic

tissue with atypia in favor of squamous cell carcinoma

and two specimens demonstrated dysplasia.

On investigation, Biochemistry profile and chest X ray

(postero-anterior) were within normal limits. Computed

tomography of the abdomen and pelvic were normal. No

metastasis was found. Abdominal sonography showed

normal structures with uterus in normal size and normal

endometrium. Intravenous pyelography, cystoscopy and

proctoscopy were within normal as well. Then, the pa-

Primary Cervical Choriocarcinoma: Case Report and the Review of Literatures 1337

Table 2. Clinical featured of the patients with primary cervical choriocarcinoma in the literature.

Study Age Gravida

and Para Symptoms Preceding

Pregnancy

Latent Period

form Preceding

Pregnancy LocationLesion Size Serum or Urine

hCG

Rashbaum (1952) 38 G6P4

Vaginal Bleeding +

Abdominal pain

(2 weeks)

Induced

abortion 11 months Posterior

wall 6 * 8 * 4 cm

(macrography) -

Tsukamoto (198 0) 49 G4P2

Vaginal spotting +

lower abdominal

pain (2 weeks)

Elective

abortion 36 months - 4.5 * 3.5 cm

(Pelvic

angiography) 8000 U/L

Tripathi (1982) 28 G2P2 Menorrhagia (7

months) Term

delivery 7 months - 6 * 5 * 2.5 cm

(macrography) 540,000 i. u/24 h

Martin (1983) 35 G1P1 Menorrhagia

(3 months) Term

delivery 12 months - 4.0 * 3.5 * 2.5 cm

(macrography) Positive but not

mentioned

Bhalla (1987) 30 G4P3

Vaginal bleeding

(7 weeks) Induced

abortion 12 months - 6 * 5 * 4 cm

(macrography) Positive with

dilution 1/32

Case 1 46 G7P4 Menorrhagia with

occasionally massive

bleeding (2 months)

Elective

abortion 48 months - 9 * 7 * 4 cm

(macrography) 162,250 mIU/ml

Case 2 43 G1P1 Hemorrhagic shockTerm delivery29 years Posterior

wall 3 cm Positive but not

mentioned

Case 3 29 G4P3 Menorrhagia

(several months) Induced

abortion 48 months - - Positive but not

mentioned

Tsai

(1988)

Case 4 53 G7P5 - Hydatidiform

mole 3 months - - -

Ben-Chetrit (199 0) 33 G3P3 Menorrhagia

(1 month) Term delivery12 months - 0.5 * 1 cm (pelvic

examination) 3 2 mIU/ml

Lee (1992) 29 G2P1 Profuse vaginal

bleeding (6 hours)Hydatidiform

mole 9 months Left wall8.6 * 7.7 cm

(sonography) 150,580 mIU/ml

Herts (1993) 47 G1P1 Heavy vaginal

bleeding (6 days) Term delivery18 years - 5 cm

(sonography) 109,870 mIU/ml

al Hassani (1994) 40 G3P3(a) Post-coital bleeding

(2 months) Term delivery- Anterior

lip 2.5 * 2 cm

(macrography) 244 IU/L

Yahata (1997) 38 G4P2 Menorrhagia

(2 weeks) Term delivery4 months - 6 * 5 cm (Doppler

sonography an d

MRI) 128,000 IU/L

Lema (1997) 36 G11P10

Vaginal bleeding in

28 weeks of

gestation (2 days)Term delivery24 months Posterior

lip 4 * 2 cm

(macrography) -

Baykal (2003) 54 G5P4 Postmenopausal

bleeding Term delivery17 years - 3 cm (pelvic

examination)

45,000 IU/L

after pathology

report

Roopnarinesingh

(2004) 25 G1p0

Abdominal pain and

mild vaginal

bleeding (2 months)

Hydatidiform

mole 24 months Anterior

lip 4 * 3 * 5 cm

(MRI) 4150 U/L

Case 1 46 G6P4 Vaginal bleeding

(4 months) Induced

abortion 64 months Posterior

cervix 3 * 4 cm

(macrography) 20,000 U/L

Case 2 21 G1P0 Vaginal bleeding

(8 months) Hydatidiform

mole 20 months Posterior

cervix 5 * 7 cm

(macrography) 5344 U/L

Case 3 35 G4P2 Vaginal bleeding

(1 month) Induced

abortion 47 months Posterior

cervix 2 * 3 cm

(macrography) 4000 U/L

Fu (2007)

Case 4 30 G3P2 Vaginal bleeding

(3 months) Term delivery12 months Posterior

cervix 3.4 * 2.5 cm

(sonography) 2764 U/L

Kairi-Vassilatou

(2007) 43 G7P2 Amenorrhea

(2 months) Term delivery12 months Posterior

cervix 5 * 3 cm

(macrography) 7485 mIU/ml

(a): Patient had amenorrhea 3 years before her symptoms and D & C was performed for patient, but there was no report of the pathology. So the gravida is

subject to change (G4).

Primary Cervical Choriocarcinoma: Case Report and the Review of Literatures

1338

Table 3. Staging, treatment and outcomes of the patients with primary cervical choriocarcinoma in the literature.

Study Treatment Outcome

Rashbaum TAH + BSO Died (3 months after diagnosis)

Tsukamoto TAH + BSO followed by 3 courses of MTX Survived without recurrence

after 9 months

Tripathi Oral MTX for 2 days followed by TAH followed by 3 days MTX

followed by repe at course of MTX after 2 weeks Survived without recurre nce

after 10 months

Martin MTX + TAH + 3 postoperative courses of MTX -

Bhalla TAH + BSO followed by 1 course of MTX Recurrence with pulmonary metastasis

(after 3 months)

Case 1 TAH + BSO followed by 4 courses MTX + actinomycin D No Recurrence on follow up

Case 2 Radical Hysterectomy (suspicious for cervical cancer) Re c u rrence with pulmonary and brain

metastasis (1 month and 2 months)

Case 3 TAH + BSO Recurrence with pulmonary metastasis

(6 months) died (14 months)

Tsai

Case 4 Under Hydatidiform mole, subtotal hysterectomy + BSO performed.

Patient returned after 2 years with cervical choriocarcinoma and

pulmonary metastasis

Recurrence with pulmonary metastasis

and cervical choriocarcinoma (2 years)

Ben-Chetrit 2 course of MTX + folinic acid (patient desired future pregnan cy) Survived without recurrence

after 12 months

Lee Vaginal Hysterectomy + 4 courses actinomycin D (MTX

discontinued because of abnormal LFT) Survived without recurrence

after 20 months

Herts Vaginal Hysterectomy + Unilateral salpingo-oophorectomy Survived without recurrence

after 6 months

al Hassani TAH + BSO + chemotherapy -

Yahata 2 courses MAC followed by TAH followed by 6 cours es ACM Survived without recurrence

after 18 months

Lema TAH Missed on follow-up after surgery

Baykal Type III hysterect omy + BSO + Pelvic-paraaortic LAD followed by

EMA-CO chemotherapy -

Roopnarinesingh MTX for 8 weeks (alternate week) Survived with locally recurrence

after 12 months

Case 1 TAH + BSO followed by 2 course of ACM chemotherapy Survived without recurrence

after 17 years

Case 2 TAH followed by 2 courses of ACM after two courses of AF

performed at h e r h ome town Survived without recurrence

after 16 years

Case 3 3 courses of ACM after TAH + USO foll owed by 1 course 5-FU Survive without recurrence after 14 years

Case 4 1 course of ACM chemoth er apy following with TAH and 2 courses

of ACM Chemo t h erapy after TAH Survived without recurrence after 6 years

-: No information, ACM: Actinomycin D, cyclophosphamide and methotrexate; AF: Actinomycin D and 5-Fluouracil; BSO: Bilateral salpingo-oophorectomy;

EMA-CO: Etoposide-methotrexate-dactinomycin-cyclophosphamide-vincristine; 5-FU: 5-fluouracil; LAD: Lymphadenectomy; LFT: Liver function test; MTX:

Methotrexate; TAH: Total a bdominal hysterectomy; USO: Unilateral salpingo-oophorectomy.

tient was accepted as FIGO stage Ib1-2 cervical cancer.

One week later the patient underwent type II hysteric-

tomy with bilateral salpingoopherectomy and pelvic

lymph node dissection. At operation, a soft necrotic

hemorrhagic mass, approximately 4 × 5 cm, was found

on the anterior surface of the cervix.

On gross examination, the hysterectomy specimen

presented with a soft, brown-colored mass of 3.5 cm in

the largest diameter which was intramural and did not

involve the lumen. The tumor formed a necrotic hemor-

rhagic mass confined to the lower part of cervix without

extending to the endometrium or myometrium.

On microscopic examination sections revealed a ne-

crotic hemorrhagic tumor that is distinct from the epithe-

lial surface of both endocervix and ectocervix. So, this

distinction proved that tumor had not had epithelial ori-

Primary Cervical Choriocarcinoma: Case Report and the Review of Literatures 1339

gin and we could exclude Squamous cell carcinoma or

adenocarcinoma. On magnification Malignant tropho-

blastic tumor composed of atypic bizarre polygonal tro-

phoblasts with nucleolated nuclei, High nuclear to cyto-

plasm ratio (N/C ratio) and atypic mitotic figures which

are strongly positive for B-HCG and pancytokeratin.

Human placental lactogen (HPL) was weakly positive in

few cells. There was also hemorrhage (Blood Lake) in

tissue and for this reason, the pathologist performed Im-

munohistochemistry of CD31 and VIII Factor to exclude

tumor with endothelial origin like angiosarcoma. Based

on these findings, choriocarcinoma was diagnosed for the

patient. An extensive sectioning of the endometrium,

myometrium, parametrial tissues and lymph nodes con-

firmed that these areas were free of neoplastic cells or

any other site of trophoblastic cells.

Patient discharged with good condition four days later

and postoperative B-hCG was 6 mIU/ml after 2 weeks of

operation. According to the FIGO staging system of

GTD, the patient was classified as stage I, but because

there was no preoperative B-hCG level we could not de-

termine the risk score of the patient [12]. The patient is

under follow-up and has had serial B-hCG measurement,

which has been declining through 4 weeks. She is doing

well without any complain so far.

4. Discussion

Gestational intrauterine choriocarcinoma has higher inci-

dence rate in Asia, Africa and Latin America in com-

parison to United States and Europe, may be due to so-

cioeconomic status [13]. However, the overall incidence

of choriocarcinoma in recent years has been decreased

parallel to improving socioeconomic conditions [13]. Pri-

mary choriocarcinoma of the cervix is an extremely rare

disease; however, most of the case reports in literatures

demonstrate that extrauterine choriocarcinoma mostly

originates in cervix rather than other sites in genital tract

[2 -7] . O ur ca se fulfilled the criteria defin ed by Saito et a l.

[1]. So, it is an ectopic choriocarcinoma originates from

the cervix.

The median age was 37 with the range of 21 - 54 year s

old (two patients were postmenopausal). 9 patients were

less than 35 years old. The latent period from preceding

pregnancy had a range of 3 - 348 months with 62% less

than or equal to 24 months. Long latency of choriocarci-

noma after the preceding pregnancy is not common [14].

Choriocarcinoma is heterochronic if the latent period is

more than two years [15]. Choriocarcinoma occurred in

our patients 3 years after the preceding pregnancy, which

was terminated by induced abortion. There was limited

data regarding the location of tumor with mostly origi-

nated from posterior cervix.

Gestational choriocarcinoma may follow any type of

pregnancy, which most preceded by molar pregnancy

(50%), 25% developed after abortion and 25% follow an

apparently normal pregnancy. The more common gesta-

tional variety is associated with a coincident and antece-

dent pregnancy. In this review primary cervical chorio-

carcinoma preceded by 50% normal pregnancy, 32%

abortion and 18% de vel o ped after hydatidi f orm mole.

There are some theories expressed for developing of

cervical choriocarcinoma [16,17]. It is possible that it can

be a metastatic tumor from a vanishing intrauterine cho-

riocarcinoma or it could be a transformation of a cervical

pregnancy. The pathologic examination ruled out these

possibilities, as we demonstrated that no trophoblastic

cell was observed in endothelium and myometriu m of the

uterus. Another theory expresses the role of therapeutic

abortion in the implantation of trophoblasts in the cervix

and lower genital tract. Trauma to the cervix during D &

C may be a predisposing factor [6]. Our case was pre-

ceded by an abortion and it supports the later theory.

There was no pathological examination of the curetted

material as this was performed in another city and we did

not have access to the pathology.

The clinical diagnosis of primary choriocarcinoma is

very difficult. In this review all patients except one,

complained of vaginal bleeding with different period of

time ranged from 6 hours to 8 months, with different

severity that one patient referred with hypovolemic shock.

Only one patient complained of amenorrhea. The predo-

minant symptom is abnormal vaginal bleeding which is

due to angiogenesis and neovasculirization of this tumor.

There are few differential diagnoses which include uter-

ine cervical pregnancy, threatened abortion, a cervical

polyp and malignancy [4]. In the present case, choriocar-

cinoma was presented with vaginal bleeding and misdi-

agnosed as malignancy. For this reason, we should con-

sider choriocarcinoma as differential diagnosis in any

patient in their reproductive years with a cervical lesion

with high vascul ari t y and pr o fuse bleeding.

How can we suspect and diagnose cervical choriocar-

cinoma? As we mentioned above, in cervical lesions in

women of child-bearing age with profuse bleeding,

measurement of serum and urinary B-hCG is useful for

diagnosis. Color Doppler transvaginal ultrasonography

and MRI with con trast detect the abundan t blood flow in

the tumor [4]. Transvaginal Doppler sonography allows

detection of tumoral vessels, which manifests high dia-

stolic blood flow and low impedance resulting in ne-

ovasculirization [4]. Contrast-enhanced MRI can demon-

strate tumoral vascularity and in cases of necrosis hy-

pointensity of the necrotic areas are perceptible [4].

Diagnosis of such a kind of cervical tumor is very dif-

ficult for pathologist both in biopsy and surgical resec-

tion. In our case, the first pathologist misdiagnosed

choriocarcinoma with squamous cell carcinoma as Ben-

Primary Cervical Choriocarcinoma: Case Report and the Review of Literatures

1340

Chetrit [18]. Necrosis is a predominant feature of these

neoplasms, often to such an extent that the viable tissue

is obscured. So, we should consider immunohistochemi-

cal staining in extend necrotic tissue obtained from cer-

vix for more information, because there is the chance for

more limited surgery and more successful chemotherapy

for choriocarcinoma if it is diagnosed in the first step. In

our case, massive necrosis of the tumor and arising of

tumor from non-epithelial origin motivate the pathologist

to perform immunohistochemical staining. As we show-

ed the specimen was markedly positive fo r B-hCG.

The treatment of choice as in our patient was total ab-

dominal hysterectomy and bilateral salpingoopherectomy

with or without chemotherapy. In terestingly, Ben-Chetrit

and his co-worke rs in one report and Roopnarinesingh et

al. in other report, documented conservative management

of primary cervical choriocarcinoma [4,18].

5. Conclusion

In conclusion, cervical choriocarcinoma should be con-

sidered in the differential diagnosis of cervical lesions in

their child-bearing years, especially lesions with promi-

nent vascularity. A beta-hCG assay, transvaginal color

Doppler sonography or contrast-enhanced MRI may

form part of pre-operative investigation in such a patient.

A detailed correlation between histologic findings and

patient’s clinical history, lab studies and radiologic data

is always required to preclude diagnostic pitfalls and de-

signates the appropriate treatment.

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