Developing retroperitoneal anaplastic carcinoma with choriocarcinoma focus after ovarian non-gestastional choriocarcinoma : A case report

Introduction. Choriocarcinoma is a malignant form of gestational trophoblastic neoplasm (GTN). It is a rare event but also a curable malignancy. In the majority of instancies it developes after any gestational event. In some cases it developes as non-gestational extrauterine malignancy. Prognosis of choriocarcinoma is poor when invasion and metastases appear early and spread fast. This form of choriocarcinoma can lead to incurable and letal outcome. Case report. We presented a 20-year-old patient with abdominal and retroperitoneal malignancy – anaplastic carcinoma combined with choriocarcinoma metastases in. Tumor developed three months after left adnexectomy which had been done because of adnexal tumor. Choriocarcinoma was immunohistochemicaly confirmed in adnexal masses. Two courses of chemotherapy, metotrexate + folic acid (MTX+FA) regimen, were administrated. The initial serum beta human chorionic gonadotropin level stayed unknown as well as the last one after the treatment. The patient came from the other country and was hospitalized because of pelvic and abdominal pain and palpable abdominal masses in hypogastrium with progressive anemia. The human chorionic gonadotropin level was 38 mIU/L. Tumor biopsy was done and choriocarcinoma metastases were immunohistochemicaly confirmed with predominant anaplastic carcinoma. Five day course of MTX + cyclophosphamide regimen was administrated and the patient was prepared for operative treatment. Relaparotomy was perforemed and tumor completely exceeded. Tumor mass mostly developed retroperitonely and partialy in abdominal cavity infiltrating intestinal wall with rupture of sigmoid colon. Anaplastic carcinoma, with large fields of necrosis and bleeding, was confirmed after histological examination. Immunohistochemical examination excluded choriocarcinoma in tumor mass. After 20 blood units transfusion, one course of chemotherapy and tumor excision, the patient left hospital on the 9th postoperative day. The patient rejected chemotherapy which was recommended according to the protocol and died one month after the operation. Conclusion. Non-gestational metastatic choriocarcinoma complicated with another type of malignancy with early spread of the disease and low responsiriness to chemotherapy has poor prognosis and leads to lethal outocome.

caly confirmed with predominant anaplastic carcinoma.Five day course of MTX + cyclophosphamide regimen was administrated and the patient was prepared for operative treatment.Relaparotomy was perforemed and tumor completely exceeded.Tumor mass mostly developed retroperitonely and partialy in abdominal cavity infiltrating intestinal wall with rupture of sigmoid colon.Anaplastic carcinoma, with large fields of necrosis and bleeding, was confirmed after histological examination.Immunohistochemical examination excluded choriocarcinoma in tumor mass.After 20 blood units transfusion, one course of chemotherapy and tumor excision, the patient left hospital on the 9th postoperative day.The patient rejected chemotherapy which was recommended according to the protocol and died one month after the operation.Conclusion.Non-gestational metastatic choriocarcinoma complicated with another type of malignancy with early spread of the disease and low responsiriness to chemotherapy has poor prognosis and leads to lethal outocome.

Introduction
Gestational trophoblastic neoplasms (GTNs) can appear as benign GTNs (complete or partial hydatiform mole) as well as invasive mole, choriocarcinoma or placental site trophoblastic tumor as malignant GTNs.Among GTNs, choriocarcinoma is a highly potent malignancy of trophoblastic origin and usualy represents disturbance of fertilization.Choriocarcinoma is a rare event, highly malignant tumor and in the majority of instancies its localization is intrauterine and of gestational origine.Choriocarcinoma usually occurs after normal pregnancies, after term pregnancies and after molar pregnancies 1 .It can also occur after nongestational events 2, 3 .Serum beta human chorionic gonadotropin (HCG) elevation depends on hormone secretion component of choriocarcinoma (syncyciotrophoblast) 4,5 .Extrauterine localization of choriocarcinoma is rare and can develop on ectopic pregnancy.It is believed that some malignant non-gestational trophoblastic malignancies especially choriocarcinoma can develop from pluripotent germ cells in the gonads.If nongestational choriocarcinoma invades and metastatises early and rapidly without specific clinical manifestation it may have a poor prognosis.Diagnosis can be confirmed after histological and immunohistochemical examinations.This means that poorly differentiated carcinomas may show focal area of choriocarcinomatous differentiation 6,7 .

Case report
A 20-year-old patient presented with abdominal and retroperitoneal malignancy -anaplastic carcinoma (gravida 1, parity 1).The tumor developed three months after left adnexectomy because of cystic tumor 8 7 9 cm.CA 125 levels were 16 U/mL (< 35 U/mL ref. value).Immunohistochemical examination was done and tumor cells were identified as CK7, CK20 and beta HCG positive and diagnosis of choriocarcinoma was confirmed.The patient was treated in another country.Two courses of chemotherapy, methotrexate 50 mg/m 2 im on the days 1, 3, 5, 7 + folic acid 30 mg iv on the days 2, 4, 6, 8 (MTX + FA), were administrated without checking initial HCG level.
The patient came to our hospital with a history of pelvic pain and developing abdominal and left retroperitoneal tumor 3 months after left adnexectomy and 2 courses of chemotherapy.Right adnexectomy was done one year before this operation and histopathological findings confirmed borderline cystadenoma ovarii.
On admission to hospital the patient had palpable abdominal masses, pelvic and abdominal pain and progressive anemia.The tumor that developed 3 months after left adnexectomy and 2 courses of chemotherapy because of the confirmed non-gestational choriocarcinoma spreaded retroperitonealy and also in the abdominal cavity.We checked HCG and it was 38 mlU/L.Tumor marker CA-125 and alpha-fetoprotein (AFP) levels were in normal ranges.Transvaginal Doppler ultrasonographic examination was done and normal uterus without pelvic masses was seen.Hyperechogenic masses were suspected on the left lateral and back retroperitoneal and invaded to the left subphrenium (Figure 1).This was confirmed on computed tomography (CT) scans of abdomen and pelvis.CT scans of the pelvis showed the normal uterus without pathological masses and there was a heterogenous mass dimenssions 25 39 37 cm partly in ab- dominal cavity and mostly invaded left retroperitonealy (Figure 2).Brain and lung metastases were excluded after Xray examination.
To prevent multiorganic failure, endotoxic shock or/and disseminated intravascular coagulation caused by hemorrhage and infection in tumor mass we decided to exceede the tumor mass.Because of the great risk of hemorrhage biopsy of metastasis is not recommended in patients with metastatic choriocarcinoma.We decided to do it inspite of the risks, so we could make the right decision for the final treatment and to find the source of hemorrhage and suspected developing infection.Tumor biopsy was done and metastatic choriocarcinoma with predominant anaplastic carcinoma was confirmed (Figure 3).According to this and also ultrasonographic and CT findings we prepared the patient for radical tumor excision.Preparation included administrating appropriate chemotherapy regimen.Suggested chemotherapy regimens for choriocarcinoma treatment include the following: MAC regimen -metotrexate (MTX) + actinomycin-d + cyclophosphamid, then EMA/CO -etoposide + metotrexate + actinomycin-d + cyclophosphamid + vincristin.Unfortunately, these protocols could not be administrated in Serbia because actinomycin-d is not registrated.
That means that chemotherapy regimen was modified and 5 days metotrexate + cyclophosphamid regimen was administrated before total tumor excision.This therapy showed to be effective and one week later beta HCG was 2 mlU/L.Because of immunohistochemically confirmed meta-static focus of choriocarcinoma in predominant anaplastic carcinoma and only one positive HCG level of 38 mlU/mL, 5 day chemotherapy (methotrexate 15 mg IV + cyclophosphamide 300 mg IV) was administrated according to the protocol.
One week after chemotherapy serum HCG was below 5 mlU/mL.During and after chemotherapy the patient got 8 blood units and 9 units of FFP.Broad spectrum antibiotics continued administrating.The operative treatment was done in collaboration with vascular surgeon.Rupture of sigmoid colon and hemorrhage in tumor mass were found.The tumor had been exceeded in toto (Figure 4).On the day before and during the operation, 12 doses of blood were transfused and 6 doses of FFP.Immunohistochemical examination excluded metastases of choriocarcinoma in the exceeded tumor mass.After chemotherapy and total tumor excision anaplastic carcinoma was confirmed with intestinal infiltration and large fields of necrosis and bleeding.Tumor cells were CK7, The patient had early and extensive development of anaplastic carcinoma with choriocarcinoma foci complicated with ruptured sigmoid colon, infection and hemorrhage in tumor tissue.This explains progressive anemia, infection and febrile state.Nine days after the operation the patient went home recovered but died one month later becouse had rejected chemotherapy recommended according to the protocol.

Discussion
Non-gestational choriocarcinoma is a rare trophoblastic malignancy.If diagnosed on time and treated it can also be curable.If it does not invade nor metastatize early the prognosis can be better and the treatment more successful.Sometimes it spreads in the abdomen and also retroperitonealy.Non-gestational choriocarcinoma are followed with significantly lower serum beta HCG than in postgestatinal choriocarcinoma.That is the reason for poor prognosis in the time of diagnosis with following complications and letal outcome 8,9 .Because of the great risk of hemorrhage biopsy of metastases is not recommended in patients with metastatic choriocarcinoma.Destruction of local tissue and organs can be followed with progressive anemia caused by local hemorrhage in tumor, abdomen or retroperitoneum.Concommitent infection with high temperature needs antibiotic treatment and supportive therapy 10,11,12 .
Chest and brain X-ray have to be done to exclude metastases in non-gestational as well as in gestational choriocarcinoma.Ultrasonography and CT are also of a great diag-nostic value 13 .Suggested chemotherapy regimens for choriocarcinoma treatment include following: MAC regimenmetotrexate (MTX) + actinomycin-d + cyclophosphamid, then EMA/CO -etoposide + metotrexate + actinomycin-d + cyclophosphamid + vincristin.Unfortunately, these protocols could not be administrated in Serbia because actinomycin-d is not registrated.
In the presented patient the effective chemotherapy regimen was a modified one: 5 days metotrexate 15 mg iv + cyclophosphamid 300 mg iv were administrated before the operation and tumor excission.This therapy showed to be effective for choriocarcinoma foci in anaplastic carcinoma and one week later beta human chorionic gonadotropin was 2 mlU/L.Prognosis of non-gestational metastatic choriocarcinoma depends on the diagnosis as well as on treatment response.Delayed diagnosis and low responsiveness to chemotherapy and early extensive spread of disease mean poor prognosis and lead to letal outcome.

Conclusion
Non-gestational metastatic choriocarcinoma complicated with another type of malignancy with early spread of the disease and low responsiveness to chemotherapy has poor prognosis and leads to lethal outcome.