Primary Intracranial Choriocarcinoma: MR Imaging Findings

Discussion

Choriocarcinoma is a highly malignant neoplasm composed of biphasic cellular components of mononuclear cytotrophoblasts and multinucleated syncytiotrophoblasts. It usually develops within or outside the uterus following a gestational event, referred to as gestational choriocarcinoma. Nongestational choriocarcinoma can arise from germ cells in gonadal or extragonadal midline locations (mediastinum, retroperitoneum, or pineal gland) and is always mixed with other elements of GCTs.¹² PICCC belongs to the category of primary intracranial GCTs and is the most malignant of all primary intracranial GCTs. The incidence of PICCC is quite rare, with an estimated ratio of 3%–5%^9,13,14 among all intracranial GCTs, similar to that in our series of 2.8%. A relatively high incidence of PICCC has been reported in Asia, especially in the Japanese population. A statistical analysis published by the Committee of Brain Tumor Registry of Japan demonstrated that the incidence of PICCC was 3.2% of all 1127 primary intracranial GCTs.¹³

Clinically, PICCC presents between 3 and 22 years of age (mean age, 11.8 years) and has a male predominance (male-to-female ratio, 74:19).⁶ In the present study, our patients' ages ranged from 7 to 19 years (mean, 11.9 years), and there was also a predilection for males, with the male-to-female ratio of 6:1. The patients' clinical presentations were nonspecific, depending on the location of the tumors. Precocious puberty, which results from the production of HCG, is the most common specific symptom of PICCC occurring in males, especially in patients younger than 12 years of age, and our findings were in accordance with this observation.^3,15,16

Various sites of PICCC have been reported, including the pineal region^3,5,17–21 and the suprasellar or parasellar region.^5,15,22,23 Less common sites include the lateral ventricle,² pituitary fossa,²⁴ basal ganglia,^2,25 and septum pellucidum.⁶ In our study, all tumors were located in the pineal (6/7) and suprasellar (1/7) regions. Although several studies have reported CSF dissemination of PICCC at the time of diagnosis,² most of the PICCCs in our series were single lesions and only 1 case was multifocal. This discrepancy is likely due to the location of the lesions in our series, because most (6/7) of our patients' lesions were located in the pineal region, leading to hydrocephalus, despite the small size of the mass; therefore, they presented at an earlier stage.

Correct pretreatment diagnosis is important for determining a therapeutic plan. HCG/β-HCG is a useful biologic tumor marker characteristic of choriocarcinoma. Markedly elevated serum HCG/β-HCG levels are strongly suggestive of choriocarcinoma or mixed GCTs with choriocarcinoma elements. In the series described by Matsutani et al,⁹ all patients with choriocarcinoma or mixed GCTs with choriocarcinoma elements had highly elevated levels of serum HCG of >2000 IU/L, whereas the serum HCG levels in patients with GCT without choriocarcinoma elements were <770 IU/L. In this study, serum β-HCG levels were assayed in 6 cases, and all demonstrated serum β-HCG levels >5000 IU/L (range, 5498–85,303 IU/L; mean, 24,623.3 IU/L). It appears, therefore, that a patient with a markedly elevated serum β-HCG level of >5000 very likely has choriocarcinoma.

Imaging features aid the pretreatment diagnosis when PICCC is suspected. However, most cases of PICCC reported in the literature are case reports with rather nonspecific radiologic findings. According to previous reports, PICCC is frequently seen as a solitary mass with heterogeneously increased attenuation on noncontrast CT scans.^5,18 Our CT findings in 3 patients with PICCC were similar to these previous case report findings. Although the presence of calcification has been described in several cases,¹⁸ it is usually not a dominant feature of PICCC. In our study, only 1 lesion contained punctate calcification in the 3 patients who underwent CT evaluation.

MR imaging has provided improved localization, preoperative evaluation, and characterization of the tumor. In the few published reports,^{2,3,6,20,23,26} the tumor has been described as an ovoid or irregular mass with a large hemorrhagic component on MR imaging. The presence of hemorrhage is a characteristic feature of PICCC. After the administration of contrast, the tumors usually show markedly heterogeneous enhancement. Our results confirm these findings.

In our series, the internal architecture was best displayed on T2-weighted images, in which all lesions displayed heterogeneous hypointensity and hyperintensity. Correlating the MR imaging appearance and the microscopic findings, the heterogeneous signal intensity seen on MR images reflects the various components contained within the lesion, such as intratumoral hemorrhage, fibrosis, cysts, necrosis, or vascular proliferation. Frequent hemorrhage is seen in PICCC due to the fragility of vessels perfusing these trophoblastic tumors and due to the innate capacity of trophoblastic cells to invade and erode vessel walls. Marked striplike or patchy areas of hypointense signal intensity on T2-weighted images corresponded histologically to intratumoral blood products such as hemosiderin and fibrosis; this correspondence was a feature seen in all our patients. On T1-weighted images, these foci of high signal intensity were assumed to correlate with small foci of hemorrhage.

On gadolinium-enhanced T1-weighted images, the heterogeneous, ringlike, and intratumoral nodular enhancement was an additional feature seen in our study. To our knowledge, this varying enhancement pattern has not been described previously. Heterogeneous and intratumoral nodular enhancement is most likely due to the sheet- or cordlike arrangement of the trophoblastic cells, which undergo vascular proliferation. The ringlike enhancement may be attributed to plentiful blood vessels on the peripheral rim of the tumor. Consequently, cystic necrosis is more likely to occur in the central area of the tumor. In most of the tumors (5/7), enhancement on T1-weighted images was seen in the isointense or slightly hyperintense areas on T2-weighted images.

Before one suggests the diagnosis of a PICCC, it is important to exclude a hemorrhagic metastasis from the genital system because extracranial choriocarcinoma, especially arising from the gonad, is known to spread via a vascular route. It also often metastasizes to the central nervous system in 3%∼28% of patients.²⁷ The differential diagnosis of a primary intracranial lesion in the pineal or suprasellar region includes other GCTs (germinoma, teratoma, embryonal carcinoma, and endodermal sinus tumor), meningioma, astrocytoma, aneurysm, or venous malformation. The patients' age and biochemical markers, such as serum HCG/β-HCG, carcinoembryonic antigen, and α-fetoprotein, can be useful in differentiating the lesions from a PICCC. From the standpoint of the MR imaging findings, intratumoral hemorrhage of other GCTs is rare, except for mixed GCTs with a choriocarcinoma element. Although some germinomas may have cystic components,²⁶ they demonstrate relatively homogeneous enhancement. Teratomas often show fatty and calcified components.^4,20 Embryonal carcinoma and endodermal sinus tumor tend be larger than PICCCs and irregular in shape.⁴ In addition, the signal intensity of PICCCs on T1- and T2-weighted images tends to mimic meningiomas, though most PICCCs show heterogeneous enhancement, whereas meningiomas most often have homogeneous enhancement and thickening of the adjacent dura. Astrocytomas tend to show hyperintensity on T2-weighted images,²⁰ while PICCCs demonstrate heterogeneous signal intensity with marked hypointense areas. A partially thrombosed aneurysm or venous malformation with blood products demonstrates intrinsic T2 hypointensity and can be excluded on the basis of MR imaging or CT angiographic findings.

The treatment of PICCC remains controversial because the tumor is highly resistant to standard treatment. Although several studies^2–4 have reported cases of successfully treated PICCCs by using a combination of surgery, chemotherapy, and radiation therapy, the disease is usually fatal and there is no established treatment. Some investigators^4,8,9 recommend surgery as the first-line therapy when the tumor is small enough to resect completely.

The clinical outcome in patients with PICCC is very poor, which is probably due to their high risk for fatal hemorrhage and their propensity for extraneural/CSF metastasis. Such extraneural metastases usually occur in the lung in one-third or more of patients.^16,28 The median survival time is 22 months and the 1- and 2-year survival rates are 61.2% and 49.8%, respectively.³