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Solid Tumour Section
Mini Review
Ovary: Choriocarcinoma
Eiko Yamamoto
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsurumai-cho
65, Showa-ku, Nagoya city, Aichi pref 466-8550, Japan (EY)
Published in Atlas Database: September 2008
Online updated version : http://AtlasGeneticsOncology.org/Tumors/OvaryChoriocarcID5219.html
DOI: 10.4267/2042/44571
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology
and primary gestational ovarian choriocarcinoma which
arises from ectopic pregnancy in the ovary.
The nongestational type is as a component of a mixed
germ cell tumor and a pure ovarian choriocarcinoma is
a very rare malignant tumor.
Identity
Alias
Choriocarcinoma
of
the
ovary;
Ovarian
choriocarcinoma
Note
Choriocarcinoma of the ovary is a highly malignant
ovarian tumor which is characterized pathologically by
the presence of trophoblastic malignant cells, and
biochemically by the production of the pregnancy
hormone human chorionic gonadotrophin (hCG) in the
absence of an ongoing pregnancy. Choriocarcinoma
tends to be invasive and to metastasize early and
widely through both the venous and lymphatic systems.
This disease is classified two types in origin,
gestational choriocarcinoma and nongestational germ
cell tumor. Nongestational pure choriocarcinoma is so
rare that the prognosis, chemo-sensitivity, and genetics
analysis of nongestational type have not been decided
compared with that of gestational type. It is necessary,
but
difficult
to
distinguish
nongestational
choriocarcinoma from gestational choriocarcinoma
except by DNA analysis.
Clinics and pathology
Etiology
By far the most important risk factor for gestational
choriocarcinoma is the nature of the preceding
pregnancy. A hydatidiform mole carries with it a 1,000
- to 2,000 fold increased risk of choriocarcinoma, one
of the most striking cancer risk factors identified in
humans. In nongestational choriocarcinoma, no factors
have been associated with the etiology of germ cell
tumor, apart from an increased incidence associated
with dysgenetic gonads.
Epidemiology
Gestational type
Women over the age of 40 are at increased risk for
gestational choriocarcinoma. The reported prevalence
of choriocarcinoma varies widely throughout the world,
being greatest in Asia, Africa, and Latin America and
substantially lower in North America, Europe, and
Australia. Choriocarcinoma occurs with a frequency of
1:20,000 to 1:40,000 pregnancies in the United States
and Europe. Estimates for the incidence in Asia, Africa,
and Latin America have generally been higher; rates as
high as 1 per 500 to 1,000 pregnancies have been
reported, although marked regional variations do occur.
Gestational choriocarcinoma follows normal pregnancy
(25%), spontaneous abortion (25%), and hydatidiform
mole (50%), but only about 3-5% of all molar
pregnancies eventuate in choriocarcinoma. Gestational
Classification
Classification of choriocarcinoma of the ovary is based
on gestational or not. It is very difficult to differentiate
a pure ovarian carcinoma with a non-gestational origin
from a gestational one using histopathological
investigation. It can be diagnosed with only in a patient
who is sexually immature, unable to conceive, or has
never had sexual intercourse, unless DNA analysis is
not performed.
The gestational type includes an ovarian metastasis
from primary uterine choriocarcinoma which occurs in
association with a normal pregnancy or spontaneous
abortion, complete hydatidiform mole, or partial mole,
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(9)
683
Ovary: Choriocarcinoma
Yamamoto E
primary ovarian choriocarcinoma is extremely rare,
with an estimated incidence of 1 in 3.7 x 108
pregnancies.
Nongestational type
Nongestational choriocarcinoma arises in women under
40 years old because of germ cell tumor, and the
frequency is reported less than 0.6% of all ovarian
tumors. Goswami et al. reported the mean age 13.6 +/6.9 years old.
stage I germ cell tumors can be treated with
conservative surgery, i.e., unilateral oophorectomy or
salpingo-oophorectomy. Postoperative chemotherapy is
recommended by combination chemotherapy with the
BEP (bleomycin, etoposide and cisplatin) or
methotrexate-based regimen.
Prognosis
The prognosis of gestational choriocarcinoma is getting
better by advances of combination chemotherapy. The
survival rate is increasing and 96.4% in 15 years since
1985. Nongestational pure choriocarcinoma of the
ovary is so rare that it is not known whether the
prognosis is worse than gestational choriocarcinoma or
not. Some papers reported that nongestational
choriocarcinoma of the ovary has worse prognosis and
is
less
sensitive
to
methotrexate-based
chemotherapeutic regimens than gestational neoplasm.
But they did not diagnose definitely by DNA
polymorphism analysis. It is important to clarify
whether the tumor arose from a gestational or
nongestational origin in order to understand the
prognosis of this disease accurately.
Clinics
Clinical symptoms are variety in gestational type,
because choriocarcinoma is likely to metastasis to
multiple organs, such as lung, liver, and brain. More
than 90% of patients with extrauterine gestational
choriocarcinoma will have lung metastasis. In
nongestational type, predominant presenting symptom
is lower abdominal pain. Common complains includes
atypical genital bleeding, amenorrhea, nausea, and
vomiting because of high level of hCG.
Choriocarcinoma is often diagnosed by the finding of
an elevated hCG level in association with metastatic
lesion detected radiaographically. The levels of serum
or urine beta-hCG are good tumor marker for the
progression or remission of disease.
Genetics
Pathology
Note
To differentiate gestational from nongestational tumors,
it is necessary to determine whether a paternal
contribution is present in the genome of the tumor.
Examination of genetic polymorphisms from the tumor
and comparison with those found in the patient and her
partner should define the presence or absence of
paternal DNA and establish whether or not a tumor is
gestational. An extensive literature search including
Medline demonstrated only five reported cases of
nongestational ovarian pure choriocarcinoma diagnosed
with DNA polymorphic analysis from 1985 to 2007.
There is no difference in pathological appearances
between gestational type and nongestational pure
choriocarcinoma.
On
gross
examination,
a
circumscribed hemorrhagic mass is observed.
Microscopically, hemorrheage and necrosis are found,
and tumor cells resemble placental trophoblastic cells:
cytotrophoblast (CT), intermediate trophoblast (IT),
and syncytiotrophoblast (ST). The CT and IT tend to
grow in clusters and sheets separated by ST. The
typical pattern of choriocarcinoma has been called "two
cell pattern", "biphasic"-terms that reflect the relatively
regular, alternating arrangement of CT and ST in the
tumor interspread with intermediate trophoblast.
Nuclear plemorphism, hyperchromasia and nuclei are
prominent. Immunohistochemically, beta-hCG is
expressed in syncytiotrophoblastic cells, but not
cytotrophoblastic cells.
Cytogenetics
Note
Gestational choriocarcinoma shows wider variations in
karyotype, most being aneuploid, with some in the
hyperdiploid and hypotetraploid range. Many forms of
chromosomal gains, losses and rearrangements are
observed, but no specific chromosomal abnormality has
yet been identified.
Treatment
Gestational choriocarcinoma is treated
with
methotrexate-based chemotherapy, for example MEA
(methotrexate,
etoposide
and
actinomycin-D),
EMA/CO (methotrexate, etoposide, actinomycin-D,
cyclophosphamide and vincristine), or EP/EMA
(etoposide, cisplatin, methotrexate and actinomycin-D).
However, nongestational ovarian choriocarcinoma
(germ cell tumor) is so rare that there is lack
information on therapeutic options. Germ cell tumors
of the ovary are treated with total abdominal
hysterectomy and bilateral salpingo-oophorectomy. A
complete staging operation is indispensable for
management and prognostication. In young patients,
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(9)
Cytogenetics Morphological
Gestational type
A study by Matsuda et al. suggested that chromosome 7
contained a putative tumor suppressor gene for
choriocarcinoma. Furthermore, by using a panel of
microsatellite markers located on chromosome 7, they
identified the critical region on chromosome 7 (7p127q11.23) which was biallelically deleted in
choriocarcinomas. Another study by Ahmed et al.,
using the comparative genomic hybridization
684
Ovary: Choriocarcinoma
Yamamoto E
technique, demonstrated amplification of 7q21-q31 and
loss of 8p12-p21 in choriocarcinomas which did not
occur in hydatidiform moles.
Suryanarayan K, O'Hanlan KA, Surti U, Ishwad CS, Nowels K,
Letourneau D, Marina N. Nongestational choriocarcinoma in
the postpartum period: a case report. J Pediatr Hematol Oncol.
1998 Mar-Apr;20(2):169-73
Genes involved and proteins
Ahmed MN, Kim K, Haddad B, Berchuck A, Qumsiyeh MB.
Comparative genomic hybridization studies in hydatidiform
moles and choriocarcinoma: amplification of 7q21-q31 and loss
of 8p12-p21 in choriocarcinoma. Cancer Genet Cytogenet.
2000 Jan 1;116(1):10-5
Note
Gestational type
In the tumor suppressor genes, p53 (located on
chromosome 17 and encodes for a 53 kDa nuclear
phosphoprotein that binds to DNA and inhibits the
progression of the cell cycle from G1 to S phase), the
p21WAF1/CIP1 (a downstream effector of p53 and
mediates growth arrest by inhibiting the G1 cyclindependent kinase), the retinoblastoma (Rb) gene (a
reaction to the inactivation of Rb protein by forming a
complex with over-expressed mdm2 proteins) were
upregulated in choriocarcinoma than in normal
placenta, and the DOC-2/hDab2 gene was
downregulated. In oncogenes, the expression of c-myc,
c-erb-B-2, c-fms and bcl-2 oncoproteins were studied
in normal placenta, partial and complete moles, and
choriocarcinoma. The study suggested that synergistic
up-regulation of c-myc, c-erb-B-2, c-fms and bcl-2
oncoproteins may be important in the pathogenesis of
complete mole and choriocarcinoma.
Inaba H, Kawasaki H, Hamazaki M, Okugawa T, Uchida K,
Honzumi M, Komada Y, Ito M, Toyoda N, Sakurai M. A case of
metastatic
ovarian
non-gestational
choriocarcinoma:
successful treatment with conservative type surgery and
myeloablative chemotherapy. Pediatr Int. 2000 Aug;42(4):3835
Matsui H, Suzuka K, Iitsuka Y, Seki K, Sekiya S. Combination
chemotherapy with methotrexate, etoposide, and actinomycin
D for high-risk gestational trophoblastic tumors. Gynecol
Oncol. 2000 Jul;78(1):28-31
Shigematsu T, Kamura T, Arima T, Wake N, Nakano H. DNA
polymorphism
analysis
of
a
pure
non-gestational
choriocarcinoma of the ovary: case report. Eur J Gynaecol
Oncol. 2000;21(2):153-4
Goswami D, Sharma K, Zutshi V, Tempe A, Nigam S.
Nongestational pure ovarian choriocarcinoma with contralateral
teratoma. Gynecol Oncol. 2001 Feb;80(2):262-6
Matsuda T, Wake N. Genetics and molecular markers in
gestational trophoblastic disease with special reference to their
clinical application. Best Pract Res Clin Obstet Gynaecol. 2003
Dec;17(6):827-36
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Yamamoto E. Ovary: Choriocarcinoma. Atlas Genet Cytogenet
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685