Accelerated Unilateral Radiographic Huntingtonian Changes Following Neoadjuvant Chemotherapy for a Nongerminomatous Germ Cell Tumor Leading to Identification of Occult Disease in the Dorsal Striatum

Summary:

Basal ganglia nongerminomatous germ cell tumors comprise 10% to 15% of germ cell tumor and have substantial morbidity at the time of local failure. In this submitted image we present a case where neoadjuvant chemotherapy unmasked a unilateral caudate head loss consistent with Huntingtonian changes. Careful review of the patient’s imaging identified disease within the dorsal striatum that was not previously identified at the time of diagnosis. Review of the diffusion tensor fractional anisotropy imaging identified progressive white matter likely secondary to the occult disease within the dorsal striatum. Although this patient was asymptomatic and had no signs of a movement disorder, similar findings have been noted to be a prelude to such findings several months later. The occult disease was incorporated into the patient’s radiotherapy planning target volume as oversight of these changes would have led to a marginal miss and potential early disease relapse.

A 7-year-old boy presented with diabetes insipidus, precocious puberty, visionloss, and right-sided cranial nerve palsies (III, IV, VI). A magnetic resonance imaging (MRI) was completed, which demonstrated a unifocal heterogenously enhancing suprasellar mass (Fig. 1C, superior margin indicated by black arrow) with intratumoral hemorrhage (white arrows). The lesion invaded the upper clivus (black arrows) and both displaced and invaded the chiasm/bilateral cavernous sinus (Fig. 1B). An axial T2WI at presentation demonstrated symmetric basal ganglia (BG) (Fig. 1A, *right caudate head). Serum markers were consistent with (AFP +) a nongerminomatous germ cell tumor (NGGCT). He underwent resection using a transsylvian approach into the supraoptic space. Pathology demonstrated lobules of necrotic tumor cells with round nuclei, prominent nucleoli, and abundant clear cytoplasm in a background of mature lymphocytes. Neoplastic cells stained positive for c-kit and placental alkaline phosphatase. The tumor was negative for AE1/AE3, human chorionic gonadotropin, alpha fetoprotein, and CD30. Postoperative MRI revealed no residual or disseminated disease. He went on to receive alternating cycles of carboplatin/etoposide and ifosfamide/etoposide per ACNS1123.¹ After chemotherapy, an MRI demonstrated unilateral loss of the right caudate head (*) and atrophy (white arrows) in the right dorsolateral prefrontal cortex (dlPFC) (Fig. 1D, T2WI) similar to the pattern seen in Huntington’s disease, except in a unilateral distribution. This triggered more intensive investigation of an axial T1WI that illustrated changes suggestive of the resolution of occult “type 1” disease in the anteromedial right striatum (Fig. 1E, white arrowheads).²

FIGURE 1.

Representative images taken from the time of diagnosis (A, B, C) and following neoadjuvant chemotherapy (D, E, F).

CONCLUSIONS

Although the cause of increased T1 signal is uncertain, calcium and/or other paramagnetic mineral deposition has been implicated and may explain CT hyperdensities in cases of basal ganglia non-germinomatous germ cell tumor.³ An axial fractional anisotropy map showed unilateral degeneration of the right anterior limb of the corona radiata and anterior superior thalamic radiations (Fig. 1F, white triangles). The team was unaware of the BG disease until the caudate atrophy was noted. Although the patient was planned to receive craniospinal radiotherapy to 36 Gy, the new MRI findings triggered modification of the 54 Gy involved field boost volume to reflect the prechemotherapy extent and the occult findings in the right striatum as they would not have otherwise been included resulting in a potential “marginal miss.”

Unilateral caudate atrophy may be the presenting sign of occult disease in 10% to 15% of patients with type 1 BG NGGCT that show faint or no contrast enhancement, and may otherwise be mistaken for benign findings. Although this patient had no identifiable movement abnormalities, many patients will develop progressive motor deterioration.³ Our hypothesis is that subclinical disease within the BG leads to disruption of the dlPFC-BG-thalamocortical circuit leading to cell body loss in the caudate and dlPFC.⁴