Primary intracranial choriocarcinoma: a report of two cases and a review of the literature

Among 848 cases of primary intracranial malignancy seen during a 63-year period at a pediatric hospital, there were 2 cases of primary pineal choriocarcinoma. The clinical and laboratory findings of these 2 cases were similar to those of 33 cases of intracranial choriocarcinoma reported in the literature. In 1 patient with precocious puberty, the diagnosis was confirmed by labeling human chorionic gonadotropin (HCG) within the tumor, which had been stored for 25 years. In the other patient, who is alive and well 18 months after diagnosis, the response to cranial irradiation and intensive chemotherapy was monitored with serial measurements of serum, cerebrospinal fluid, and urinary HCG and with computed tomography. We conclude that intensive chemotherapy, radiation, and tumor resection, if feasible, offer the best chance of curing this otherwise fatal disease.     

Predictive factors for outcome in treatment of metastatic nonseminomatous germ cell tumors.

In recent years less intensive chemotherapy programs for patients with metastatic nonseminomatous germ cell tumors with high likelihood of cure have been proposed, and the use of innovative more intensive treatments for patients with less favorable prognosis is being explored. The development of validated prognostic classifications has thus become important. In 77 patients with metastatic nonseminomatous germ cell tumors treated with chemotherapy, the ability of various prognostic factors to predict outcome of treatment was assessed. The multifactorial prognostic classification (Indiana classification) and a mathematical predictive formula correctly allocated patients to low- or high-risk groups in 84.4 percent and 87.0 percent of cases. The multifactorial classification system (M.D. Anderson system) correctly allocated patients in 61 percent of cases. The presence of serum beta HCG levels over 1,000 mg/mL, a pure choriocarcinoma histology and possibly an extragonadal primary origin of tumor were found to predict an adverse outcome in a small number of patients. It is concluded that use of the Indiana classification or mathematical predictive formula is an accurate means of allocating patients with metastatic germ cell tumors to high- or low-risk groups and that allocation of patients with pure choriocarcinoma histology, very high beta HCG levels, or extragonadal primary origin of tumor to the poor prognosis category will improve the accuracy of prediction in a few cases.     

Intratumoral hemorrhage in choriocarcinoma during neuroendoscopic third ventriculostomy: case report

The authors report a case of intratumoral hemorrhage in a pineal region choriocarcinoma during neuroendoscopic third ventriculostomy. A 12-year-old boy who presented with headache and vomiting had precocious puberty. Neuroimagings revealed a pineal region tumor with obstructive hydrocephalus and his serum HCG level was 4,280 mIU/ml. He was diagnosed as having choriocarcinoma and underwent neuroendoscopic third ventriculostomy for obstructive hydrocephalus. There were many tumor vessels observed on the tumor surface, some of which bled subcapsularly. Postoperative CT scan showed the tumor increased in size with the intratumoral hemorrhage. After irradiation and chemotherapy, the tumor disappeared with normalization of serum HCG level. His symptoms improved and no additional neurological deficit was observed in his clinical course. We might infer from this case that the intratumoral hemorrhage was induced by the intracranial pressure change during neuroendoscopic surgery. Perioperative management is very important for avoiding fetal intratumoral hemorrhage.     

Choriocarcinoma-like lesions in patients with testicular germ cell tumors. Two histologic variants

Nine men with testicular germ cell tumors developed one of two types of histologically similar cystic lesions that had features of choriocarcinoma. In five cases, these choriocarcinoma-like lesions (CCLL) were felt to represent an unusual proliferation of teratomatous epithelium (teratomatous CCLL); whereas in four cases, the CCLL was felt to represent a nonbiphasic and cystic form of choriocarcinoma similar to the atypical choriocarcinoma described by Mazur et al. except for its cystic nature. Both types usually occurred as focal findings associated with teratomas. Eight of nine patients had received chemotherapy prior to excision of the CCLL. Teratomatous CCLLs often had a lacelike arrangement of atypical epithelium around cysts that contained homogeneous secretion. Mucicarmine stains were positive in four of five cases of teratomatous CCLLs. Cystic atypical choriocarcinoma consisted of stratified mononucleated cells lining cysts containing a coagulum of eosinophilic material. Stains for human chorionic gonadotropin (HCG) were positive in three of four cases of cystic atypical choriocarcinoma, although serum HCG elevations were either negative or just slightly elevated preoperatively. Five patients with a CCLL who were clinically free of disease following surgical excision and who received no additional chemotherapy remained well on follow-up (average, 1.9 years). We encourage the separate recognition of these lesions so that future studies may determine their clinical significance more precisely.     

Localization of alpha-fetoprotein and human chorionic gonadotropin to specific histologic types of nonseminomatous testicular cancer

We used an indirect immunoperoxidase technique to localize alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) to specific histologic types of testicular germ cell cancers. Among 20 nonseminomatous tumors studied, yolk sac tumor reacted for AFP in 13 of 15 cases, teratoma in 3 of 11 cases, and embryonal carcinoma in 3 of 14 cases. Syncytiotrophoblasts alone reacted for HCG in 14 of 15 cases, and syncytiotrophoblasts associated with choriocarcinoma reacted for HCG in 2 of 2 cases. There was a close correlation between the tissue demonstration of AFP and HCG and elevated serum levels of AFP and HCG, respectively. We conclude that in nonseminomatous testicular cancer yolk sac tumor is the primary site of synthesis of AFP, and syncytiotrophoblasts are the only site of synthesis of HCG.     

Extraneural metastasis of choriocarcinomatous element in pineal germ-cell tumor. Case report

A case of pineal germ-cell tumor producing human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) is reported in a 23-year-old man. Extraneural metastasis developed during a course of combined chemotherapy after radiation therapy. Postmortem examination revealed that the metastatic pulmonary tumor was a choriocarcinoma, producing only HCG.     

Salvage chemotherapy with methotrexate,etoposide and actinomycin D in men with metastatic nonseminomatous germ cell tumors with a choriocarcinoma component: A preliminary report

The objective of the present study was to assess the use of salvage chemotherapy using methotrexate, etoposide and actinomycin D (MEA) in men with nonseminomatous germ cell tumor (NSGCT) with a choriocarcinoma component. Nine patients were included. They had initially received bleomycin, etoposide and cisplatin, and high‐dose ifosfamide, carboplatin and etoposide as induction chemotherapies. However, they failed to achieve the normalization of β‐human chorionic gonadotropin (β‐HCG). Therefore, MEA therapy (methotrexate: 450 mg/body on day 1, actinomycin D: 0.5 mg/body on days 1–5, etoposide: 100 mg/body on days 1–5) was subsequently administered. After MEA therapy (median: 3 cycles), serum β‐HCG was normalized in five of the nine patients. Of these five, three achieved long‐term disease‐free survival and one died of disease unrelated to NSGCT, whereas the remaining patient developed disease recurrence and died of disease progression. All four patients who failed to achieve the normalization of β‐HCG died of disease progression. Although several severe toxicities greater than grade 3, which were mainly associated with bone marrow suppression, occurred in all patients, there was no treatment‐related death. Considering the current outcomes, MEA regimen could be an attractive option as a salvage chemotherapy for metastatic NSGCT patients with a choriocarcinoma component showing resistance to intensive conventional chemotherapies.     

Seminoma with elevated human chorionic gonadotropin. The case for retroperitoneal lymph node dissection

An elevated serum level of human chorionic gonadotropin (HCG) in a patient whose primary tumor histologically appears to be a pure seminoma implies the presence of syncytiotrophoblastic giant cells either detectable by careful step sectioning of the primary tumor or present in metastatic disease. Inasmuch as the malignant potential and radioresponsiveness of syncytiotrophoblastic giant cells are unknown and the serum elevation of HCG may signal metastatic embryonal carcinoma, retroperitoneal lymph node dissection with adjuvant chemotherapy dependent on pathologic staging should be considered for patients with seminoma and postorchiectomy elevated HCG levels. An illustrative case is herein reported.     

Primary intracranial malignant germ cell tumor associated with abnormal high value of alpha-fetoprotein and human chorionic gonadotropin

A case of primary suprasellar germ cell tumor that produced alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in a 8-year-old boy is reported. Partial removal of tumor and combination chemotherapy using cisplatin, vincristine, and bleomycin (modified PVB therapy) resulted in an almost definite regression of the tumor and improvement from clinical symptoms in this case. After the chemotherapy the concentrations of both serum AFP and serum HCG decreased to normal levels as well. Moreover by the immunoperoxidase method AFP, HCG, and placental alkaline phosphatase were found in this particular tumor tissue. In reviewing previous reports the immunohistochemical demonstration of three tumor markers in a single germ cell tumor is seemed to be extremely rare.     

Tumor marker levels in post-chemotherapy cystic masses: clinical implications for patients with germ cell tumors

PURPOSE: Increased tumor markers after induction chemotherapy for patients with germ cell tumor usually represent systemic disease and consequently second line chemotherapy is instituted, while retroperitoneal lymph node dissection (RPLND) is reserved for patients with marker normalization. We report the concentration of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in the fluid of post-chemotherapy cystic masses to evaluate this as a potential source for serum marker elevation. MATERIALS AND METHODS: From March 2002 to December 2002, 11 consecutive patients with post-chemotherapy cystic masses underwent RPLND. Following resection, aspirated fluid was analyzed for AFP and HCG. Only 5 post-chemotherapy RPLNDs were performed in patients with increased serum tumor markers, including the 3 patients in our study. Patients with increasing tumor markers and/or multifocal disease with noncystic residual masses after induction chemotherapy underwent salvage chemotherapy despite teratomatous elements in the primary tumor. RESULTS: All 11 patients had teratoma in the orchiectomy specimen and retroperitoneum, including one with malignant transformation. Cystic fluid markers were increased in all patients, 9 of 9 with HCG (range 7.0 to 6,880) and 9 of 11 with AFP (27.5 to 521.2). Two patients with an increased serum AFP before surgery (47.9 and 31.6) had cyst levels of 73.5 and 790.4 respectively. Both serum markers normalized postoperatively. One patient with increased pre-RPLND serum HCG (11.6) had a cyst level of 233. HCG continued to increase postoperatively and the patient died of disease. The remaining 10 patients remain disease free. CONCLUSION: Fluid from cystic teratoma contains variably elevated levels of HCG and AFP in all patients and appears to be independent of serum marker level or pathology. It is possible that a "slow leak" of fluid from cystic teratoma may explain elevated serum markers in selected patients with teratoma and thus may potentially avoid second line chemotherapy.     

Serum lactate dehydrogenase and human choriogonadotrophin in seminoma

The clinical significance of serum lactate dehydrogenase (LDH) and serum human choriogonadotrophin (HCG) as tumour markers was assessed in 105 patients with pure seminoma from whom 981 blood samples were analysed. The specificity of elevated HCG and LDH was 100 and 93% respectively. The comparable sensitivity was 32 and 47%. Serum LDH could not discriminate between patients with clinical stage I seminoma, prior to orchiectomy, and those with benign testicular lesions. In patients with advanced metastatic seminoma subjected to orchiectomy, serum LDH was increased in 82%, but elevated HCG was found in only 40%. After cisplatin-based chemotherapy, falsely elevated LDH was observed in 7 of 37 tumour-free patients, but HCG was normal in all patients with no evidence of disease. Six patients with residual tumour after chemotherapy had normal LDH and 4 of them had elevated HCG; 70% of the relapses in seminoma patients were associated with increased LDH (64%) and/or HCG (48%). In seminoma patients with comparable disease extension, elevated HCG seemed to be correlated with a high risk of relapse. Patients with normal pre-treatment LDH had a lower relapse-free survival rate than patients with elevated LDH. HCG is a highly specific tumour marker in seminoma with a rather low sensitivity. HCG is particularly useful for the primary diagnosis in patients with testicular lesions and during monitoring of chemotherapy in seminoma patients. LDH is less specific than HCG. Both markers should be analysed during follow-up of seminoma patients, since 70% of relapses are associated with an increase in one or both markers. Elevated pre-treatment HCG, but not elevated LDH, seems to indicate an increased risk of relapse in patients with seminoma.     

The intra-uterine contraceptive device--contraceptive or abortifacient?

Further to the investigation of the possible mode of action of the intra-uterine contraceptive device (IUCD), an assay for the beta-specific subunit of human chorionic gonadotrophin (HCG) has detected endogenous chorionic activity 21 days after menstruation. In 22 proven ovulatory cycles, 7 patients wearing an IUCD had demonstrable serum HCG levels in 45% of these cycles. Abnormal menstruation was associated with the majority of cycles in which there was HCG in the serum. Subsequent luteolysis occurred in all cases. The results of this study may support the hypothesis that IUCD exerts its effect on the fertilized, implanted blastocyst, thus causing possible 'micro-abortion'. Caution should be exercised in the interpretation of HCG values in the follow-up of patients with hydatidiform mole or choriocarcinoma who are bearing IUCDs, since positive HCG levels may be due to an early, fertilized and implanted blastocyst and not to invasive tissue.     

Multiple liver metastases of a suprasellar germ cell tumor treated with combined chemotherapy of cisplatin and etoposide

A 23-year-old man was admitted with progressively disturbed vision and easy fatigability. CT scans demonstrated an enhanced mass in the sellar region. Physical and endocrinological examinations revealed atrophy of both optic nerves, temporal field cuts in both eyes, and panhypopituitarism. Concentrations of human chorionic gonadotropin (HCG) in the serum and cerebrospinal fluid were 12 and 33IU/L, respectively. On November 11, 1987, the tumor was partially removed using the transsphenoidal approach. The histological diagnosis was germinoma with syncytiotrophoblastic giant cells. Following postoperative craniospinal irradiation (whole brain, 30Gy; local, 18Gy; spinal canal 28Gy), CT scans showed no residual tumor and the HCG levels decreased until they were undetectable. Eighteen months later, the patient complained of abdominal pain. His serum HCG level had increased to 2,554 IU/L. CT scans of the abdomen revealed multiple low density areas in the liver. Chest X-ray was negative. A Ga scintigram disclosed only liver metastasis. Administration of a chemotherapy was started on June 26, 1989. Cisplatin and etoposide in doses of 20mg and 40mg respectively were given for 5 consecutive days in one course. Following four courses of the combined chemotherapy, the tumor entirely disappeared on CT scans and the HCG level returned to normal. The patient is now able to work well without evidence of recurrence. Multiple liver metastases of an intracranial germ cell tumor had been fatal in previous reports. This may be the first case with liver metastases in which the victim is still alive. The present case indicates that combined chemotherapy with cisplatin and etoposide is effective for extraneural metastases of an intracranial germ cell tumor.     

Choriocarcinoma arising from the pituitary fossa with extracranial metastasis: A review of the literature

Since Askanazy's first report on a case of primary intracranial choriocarcinoma in 1906, more than 60 cases have been reported so far. We add to that a case of intrasellar choriocarcinoma with suprasellar extension: A 12-year-old girl showed cranial nerve palsies, hypopituitarism, and abnormally high titers of human chorionic gonadotropin (HCG) in blood and in cerebrospinal fluid (CSF). She died 3 months after surgery. At autopsy, an intra- and suprasellar choriocarcinoma, which penetrated through the clivus into the cerebellopontine angle and metastasized remotely to the lungs, was confirmed. This rare case is presented with a thorough review of the literature.     

False positive beta-human chorionic gonadotropin in testicular cancer

Persistent elevations in serum markers after chemotherapy for germ cell testicular carcinoma indicate residual disease. We report on a patient with advanced seminoma with choriocarcinoma who had elevated serum beta-human chorionic gonadotropin (beta-HCG) and residual masses on computerized tomography scan after chemotherapy. Wedge liver resection and retroperitoneal node dissection yielded only necrotic tissue which assayed and immunoperoxidase stained positively for beta-HCG. Serum beta-HCG fell to undetectable levels postoperatively, and the patient remains disease-free after three years. Phagocytosis of necrotic tumor apparently released entrapped beta-HCG resulting in a false positive tumor marker.     

Comparison of human chorionic gonadotrophin concentrations in the sera of patients with normal and abnormal pregnancy measured by radio-immunoassay and immunoradiometric assay

Human chorionic gonadotrophin (HCG) concentrations were measured in the serum of 40 patients with normal pregnancy, 18 with ectopic pregnancy, 36 with incomplete abortions and 24 patients with gestational trophoblastic disease using a radio-immunoassay (RIA) and immunoradiometric assay (IRMA). There were no significant differences in HCG concentrations measured by the two assays with regard to the first three groups but the patients with gestational trophoblastic disease had consistently higher results on RIA, probably reflecting increased circulating free beta-subunit of HCG. It was concluded that measurement of HCG using IRMA for the intact molecule gives equivalent results to RIA in patients with normal and ectopic pregnancy as well as after abortion. However, monitoring of patients with choriocarcinoma and hydatidiform mole requires an assay that detects free beta-HCG.     

Intracranial germ-cell tumors. Immunohistochemical study of three autopsy cases

Histological and immunohistochemical findings in three cases with primary intracranial germ-cell tumors are reported. Based on histological examination, they were diagnosed, respectively, as an endodermal sinus tumor with immature teratoid differentiation, teratoma and embryonal carcinoma, and choriocarcinoma and germinoma. The first case was presumed to be a combination of endodermal sinus tumor and germinoma. An immunohistochemical examination showed positive reactions to alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) in the endodermal sinus tumor, and to human chorionic gonadotropin (HCG) in the choriocarcinoma, but showed no reaction in the embryonal carcinoma. Human chorionic gonadotropin was demonstrated in syncytiotrophoblastic cells and CEA in a gland-like structure. The value of measuring CEA in cases of germ-cell tumors, in addition to AFP and HCG assays, is stressed, and the characteristics of CEA-positive tissue are discussed.     

Serum and tissue tumour markers in seminomas

The serum expression of the tumour markers hydroxybutyric dehydrogenase (HBD), beta human chorionic gonadotrophin (beta HCG), alphafetoprotein (alpha FP) and placental alkaline phosphatase (PLAP) has been assessed in a consecutive series of 50 patients with pure seminoma. In pre-orchiectomy sera from 15 patients with stage I disease, HBD was elevated in 5, beta HCG in 3, alpha FP in 1 and PLAP in 1 (of 3 only). In 27 patients with stage 2 or 3 disease, prior to chemotherapy, serum HBD was elevated in 19, beta HCG in 11, alpha FP in 2 and PLAP in 10 (of 18). The presence of beta HCG was investigated immunocytochemically in primary tumour tissue from 39 patients. It was demonstrated in 6 of 21 tumours from patients with stage I disease and 5 of 18 with stage 2 or 3 disease.     

Primary intracranial germ cell tumor in the right basal ganglia and its vicinity area--a report of the case with germinoma and choriocarcinoma histologically

A case of intracranial germ cell tumor in the right basal ganglia and it's vicinity area was presented and previous reported cases were reviewed. The patient was a 11-year-old boy with precocious puberty. His illness started with left hemiparesis and mental disturbance, i.e. behavioral and emotional change one year prior to admission. Enhanced CT demonstrated a round lesion of high density, with relatively low density in the center portion. The tumor developed from the right putamen to thalamus, and involved toward hypothalamic region on coronary CT. Hormonal studies revealed abnormal levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), human chronic gonadotropin (HCG), and testosterone. In addition to excessively high levels of HCG in the urine, serum and CSF, high elevation of plasma LH and low of plasma FSH were revealed. On 3 June 1980, right temporal craniotomy was performed and a piece of the tumor was removed. Tumor's tissue was diagnosed as germinoma by pathohistological examination. As the effect of postoperative Co-60 radiation, high density area on CT disappeared and remained as well margined low density area. On repeated CTs and HCG-measurements on further, recurrent sign was not noted up to now. However, as a result of pathohistological studies in details, syncytiotrophoblast generally seen in the choriocarcinoma seem to be presented in it's tissue. Therefore, by means of peroxidase labeled antibody method, the authors proved HCG in syncytial cells of the tumor's tissue. There are very little reports on quantification of HCG in primary intracranial germ cell tumor with precocious puberty. Serial measurements of HCG are useful for following the diagnosis and therapy of primary intracranial germ cell tumors. In this report, the authors provide evidence that the syncytial cell mixed in intracranial germinoma secrets HCG.     

Pineal choriocarcinoma presenting massive ventricular hemorrhage--a case report

A case of primary choriocarcinoma in the pineal region is reported. A six-year-old boy showing precocious puberty, suddenly developed coma by massive ventricular hemorrhage. He recovered gradually up to akinetic mutism, but whose clinical, hormonal and neuroradiological studies failed to demonstrate any pathological lesions. Four years later a small tumor was detected by CT in the pineal region. At the same time increased serum-HCG level was shown. Subtotal removal of the tumor was carried out by Stein's supracerebellar infratentorial approach. The pathology of the tumor showed the characteristics of choriocarcinoma, consisting of major necrotic area and of tumor cells, syncytiotrophoblast and cellular trophoblast. The former revealed strong activity of HCG by immunoperoxidase study. Postoperative chemotherapy with actinomycin-D and methotrexate was given for a month. In the course of these treatments, serum-HCG recovered within normal range. This patient shows no signs and symptoms of the recurrence 6 months after operation. Early diagnosis with aids of neuroradiology as well as hormonal studies and the early initiation of the treatment may prevent major complications like massive tumoral bleeding, also might achieve the favorable outcome of this tumor.