Although uncommon, germ cell tumors remain one of the principal diagnostic considerations in the evaluation of a sellar region mass, particularly in the pediatric population (20). In North American and UK series, germ cell tumors account for only 1% of all intracranial tumors; however, approx 35% of these will involve the suprasellar regions. Why these tumors should be far more common in Japan, where they account for 10% of all intracranial tumors, remains an epidemiologic curiosity. Germ cell tumors typically occur during childhood and adolescence, having their peak incidence within the first two decades of life. Whereas those arising in the pineal region have a predilection for males, germ cell tumors of suprasellar origin appear notably more common in females.
It is important to recognize that germ cell tumors represent a collection of embryologically interrelated entities, each differing in germinal composition, degree of differentiation, and overall biological malignancy (21,22). At the most benign extreme is the mature teratoma—a well-differentiated lesion composed of mature tissues derived from all three germ cell layers. The remaining germ cell tumors are fully malignant lesions, exhibiting both local invasiveness and meta-static capability. In order of increasing biologic aggression, germ cell tumors include germinoma, immature teratoma, embryonal carcinoma, endodermal sinus tumor, and choriocarcinoma (196).
From practical and prognostic standpoints, malignant germ cell tumors are distinguished as being either germinomas or non-germinomatous germ cell tumors. The former account for 60% of all germ cell tumors and generally have a more favorable prognosis. By contrast, nongerminomatous germ cell tumors, being neoplastic counterparts of the most primitive of primordial tissues, can be considered among the most extreme examples of human malignancy—ones that usually prove fatal despite multimodality therapy. Mixed germ cell tumors composed of both germinomatous and nongerminomatous elements have also been increasingly recognized.
Germ cell tumors involving the sellar region are usually situated in the suprasellar cistern, tenaciously adherent to, if not frankly invasive of, the basal brain surface, hypothalamus, optic nerves, and pituitary stalk (23-25). Larger lesions may extend upward into the anterior third ventricle and, less frequently, downward into the sella. Germ cell tumors of primary intrasellar origin are rare, although they have been known to cause sellar expansion, chiasmal compression, and cavernous sinus invasion in a fashion similar to pituitary adenomas (26-28). Synchronous lesions occurring in both suprasellar and pineal locations are present in fewer than 10% of cases (196).
The well-known clinical triad of DI, visual disturbance, and panhypopituitarism frequently characterizes the presentation of suprasellar germ cell tumors. DI is an important diagnostic feature—one that may occasionally antedate other clinical or radiological evidence of the tumor by years (29). Panhypopituitarism is generally the result of hypothalamic or stalk compression and is usually manifested as delay or regression of sexual development or growth failure. Occasionally, a prepubertal child may present with precocious puberty, a phenomenon related to either hypothalamic compression/damage or the liberation of P-human chorionic gonadotropin (P-hCG) by the tumor (30). Hydroceph-alus, the result of third ventricular obstruction, is generally a late finding. MRI is the radiological investigation of choice; however, germ cell tumors lack any specific radiologic features that unequivocally distinguish them from other lesions (craniopharyngioma, chiasmatic glioma, hypothalamic hamartoma/ glioma) occurring in the region.
Acknowledging the limitations of imaging to reliably predict tumor histology, practitioners have made use increasingly of various tumor markers as more accurate predictors of tumor histology (20,22-25,31,32). a-Fetoprotein (AFP), P-hCG, and placental alkaline phosphatase (PLAP), as measured in both the blood and CSF, are most commonly measured. AFP elevations suggest an endodermal sinus tumor or a mixed tumor containing endodermal sinus elements. P-hCG elevations suggest a choriocarcinoma or a mixed tumor containing choriocarcinoma elements. When neither AFP nor P-hCG is elevated, a diagnosis of pure germinoma or teratoma is suspected. However, germinomas may also show variable elevations of P-hCG. High levels of PLAP suggest a diagnosis of germinoma; however, lesser elevations are compatible with any of the various germ cell entities. Despite their theoretic use, these tumor markers lack sufficient sensitivity and specificity to be routinely informative, and although they are frequently suggestive of tumor histology, only occasionally are they diagnostic. When elevated, however, these tumor markers are helpful in ongoing patient follow-up.
Although there is ongoing controversy over the optimal management of intra-cranial germ cell tumors in general, opinion appears less divided concerning suprasellar germ cell tumors (23,25). The inability of MRI or tumor markers to distinguish reliably the radiosensitive germinomas from the aggressive nongerminomatous germ cell tumors (or, for that matter, other more common lesions occurring in the region, such as craniopharyngiomas) has placed increasing importance on obtaining a precise tissue diagnosis before instituting therapy. Accordingly, and after correction of any endocrine deficits, surgery plays both a diagnostic and a therapeutic role. Except for the rare germ cell tumors of intrasellar origin that have been successfully approached transsphenoidally (26,28,33), most suprasellar germ cell tumors require craniotomy, usually through a subfrontal or subfrontal-pterional approach. Generous tissue sampling is obtained, the optic apparatus is decompressed, and a nonradical debulking procedure is undertaken. Except in the benign mature teratoma, where attempts at gross total excision may effect cure, there is little evidence that radical resection of malignant germ cell tumors supports any survival advantage.
Postoperatively, all malignant germ cell tumors require some form of adjuvant therapy, the nature of which is based on the histologic diagnosis and the degree of disseminated disease. The frequency of metastatic dissemination among these tumors has been variably reported between 10% and 57% (22).
The majority of metastatic deposits occur within the neuroaxis; only 3% of all metastases occur systemically. The most important objective of staging is to exclude clinically occult subarachnoid deposits, the presence of which can be determined by studies of CSF cytology and spinal MRI. Germinomas, given their exquisite radiosensitivity, are treated with 1500 cGy to the tumor field, with additional craniospinal boosts should multifocal disease or positive CSF cytology be demonstrated. The prognosis of suprasellar germinomas is favorable, and contemporary series show that patient survival approaches 90% at 5 yr and longer (34,35). On the other hand, nongerminomatous germ cell tumors continue to fare far worse despite surgery and radiation therapy; only exceptional cases are alive at 5 yr, as most patients succumb to local recurrence within 18 mo of diagnosis (23,25). The effectiveness of chemotherapy for nongerminomatous germ cell tumors of the gonads has rejuvenated interest in applying the same to their intracranial counterparts. Postoperative neoadjuvant chemotherapy (cisplatin and VP-16), followed by craniospinal radiation, and followed again with chemotherapy (vinblastine, bleomycin, carboplatin, and VP-16), resulted in an encouraging tumor responses (20,23-25). The evolution of aggressive chemotherapeutic regimens holds much promise in the management of nongerminomatous germ cell tumors—lesions that otherwise portend a uniformly terrible prognosis (36).
Was this article helpful?