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 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. |
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. |
Pathology | 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. |
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, 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. |
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