Bifocal intracranial tumors of nongerminomatous germ cell etiology: diagnostic and therapeutic implications

Abstract

Background: Patients presenting with synchronous bifocal intracranial tumors (masses in the pineal and neurohypophyseal region), detectable human chorionic gonadotropin (hCG) levels (5-100 mIU/mL), and normal alpha feto-protein (AFP) levels (≤10 ng/mL) are often diagnosed empirically with pure germinoma. In such scenarios, pathologic confirmation is often deferred, given that bifocal nongerminomatous germ cell tumors (NGGCTs) are considered rare and because available literature and research protocols support such an approach. We sought to characterize the association between bifocal intracranial tumors and NGGCT histology.

Methods: Seventy-one patients treated for intracranial germ cell tumors at Massachusetts General Hospital in 1998-2012 were identified. Patients presenting with synchronous bifocal disease were selected for further review.

Results: Of the 71 patients presenting with intracranial germ cell tumors, 14 (19.7%) had synchronous bifocal disease. Of these 14 patients, 7 (50.0%) had germinoma, 3 (21.4%) had NGGCT, and 4 (28.6%) had hCG levels <200 mIU/mL and normal AFP levels and were treated without pathologic confirmation. Of the 3 patients with confirmed bifocal NGGCT, 2 had detectable hCG levels with AFP <10 ng/mL and 1 patient had a detectable hCG level with a modest elevation in AFP.

Conclusions: NGGCTs should be considered in the differential diagnosis for patients presenting with bifocal intracranial tumors. Given differences in the management of germinomas and NGGCTs, clinicians should strongly consider a biopsy in patients presenting with bifocal masses and normal or modestly elevated biomarkers. Misclassification of such cases as germinomas could result in undertreatment and a possible increased risk for recurrence.

Keywords: NGGCT; bifocal; germ cell; multiple midline; nongerminomatous.

Fig. 1.

MRI at diagnosis for a patient with a bifocal, mixed NGGCT and germinoma. Displayed are sagittal (1a) T1 postcontrast and (1b) T2 weighted sequences, axial T1 postcontrast images of the (1c) pineal and (1d) neurohypophyseal regions, and coronal T1 postcontrast images of the (1e) pineal and (1f) neurohypophyseal regions. White arrowheads denote the neurohypophyseal mass; black arrowheads denote the pineal mass.

Fig. 2.

(2a) Hematoxylin and eosin stain of tissue (70× magnification) obtained from a pineal tumor of a patient presenting with synchronous bifocal masses, which displays a yolk sac component (left) and germinoma (right, labeled with arrowhead). (2b) Immunoperoxidase stain for beta hCG reveals the positive staining of cells in the germinomatous component (right, labeled with arrowhead) and only spotty staining in the yolk sac component (left).