Abstract

BackgroundIntracranial germinoma (GEM) originates from primordial germ cells, more frequently in the pineal and suprasellar regions. Basal ganglia (BG) presentations are rare, especially associated with diabetes insipidus (DI) and without a neurohypophysis lesion or an “occult germinoma.” The management of GEM is controversial, although conventional wide-field irradiation with or without chemotherapy is the usual treatment. The potential role of radiosurgery in the management of these lesions remains unclear.

Case DescriptionA 15-year-old boy was admitted to the hospital, presenting with DI and right-hand dystonia. Magnetic resonance imaging (MRI) showed a paraventricular BG tumor near the left caudate nucleus. A stereotactic biopsy was performed, confirming the GEM diagnosis. The patient was treated by stereotactic radiosurgery (13 Gy), with remission of all symptoms. Eleven years after the onset of symptoms, the patient remained stable on a regular desmopressin regimen, maintaining normal water intake and urinary volume with improvement in the hand’s dystonia. The brain MRI performed annually during the past 10 years after radiosurgery revealed no tumor recurrence or other abnormalities at the neurohypophysis and pituitary stalk.

ConclusionBG GEM is rare and it may manifest with DI, a possible consequence of peritumoral edema surrounding the hypothalamus. Radiosurgery alone may be an effective treatment option. The occult GEM of the neurohypophysis could also cause DI preceding the radiological onset of GEM. Hence, it is mandatory to follow-up on patients with BG GEM presenting with central DI closely for a long time with periodic clinical and neuroimaging evaluations.

Keywords: Basal ganglia, Diabetes insipidus, Dystonia, Germinoma, Radiosurgery

INTRODUCTION

Intracranial germinoma (GEM), derived from primordial germ cells, predominantly affects the pineal and suprasellar regions but can arise in various brain locations, including the basal ganglia (BG), ventricles, thalamus, and cerebral hemispheres.[ 2 , 4 , 13 , 14 , 18 ] BG germinoma (BGGEM), a rare subtype representing only 2.9% of all GEM, may be associated with brainstem atrophy in up to 33% of cases.[ 1 , 2 , 18 , 20 ]

Patients with BG lesions may exhibit nonspecific symptoms, including hemiparesis, ataxia, and cognitive decline.[ 20 ] In a notable series, Kobayashi et al. found that diabetes insipidus (DI) occurred in 37.5% of patients with BGGEM.[ 8 ] Kato et al.[ 6 ] (1998) coined the term “occult GEM of the neurohypophysis” to describe cases where DI was the initial symptom of a GEM affecting the neurohypophysis, despite an initially normal magnetic resonance imaging (MRI) and the clinical-related lesion detection occurred months or years later.[ 6 ] Lesions in the hypothalamus-pituitary area are too subtle to be detected in the early stages, and the patient ends up diagnosed with idiopathic DI.[ 21 ]

The therapeutic approach for intracranial GEM remains a subject of ongoing debate.[ 1 , 4 , 14 ] Given their high sensitivity to radiotherapy and chemotherapy, these tumors generally exhibit favorable prognosis with 5-year survival rates exceeding 90%.[ 1 , 4 , 14 ] In this context, radiosurgery appears to be a viable treatment option for patients with localized disease who show no evidence of dissemination.[ 24 ]

We present a case of a pediatric patient with paraventricular BGGEM manifesting with DI and focal dystonia. We provide a comprehensive long-term follow-up, detailing the clinical manifestations and treatment with radiosurgery.

CASE PRESENTATION

A 15-year-old Caucasian boy previously healthy was admitted to the hospital in May 2009 with a diagnosis of central DI, presenting with polydipsia and polyuria. The symptoms had begun 5 months earlier, accompanied by right-hand dystonia.

The 24 h total urine volume was 8,648 mL, with an osmolarity of 175 mOsm/kgH₂O and sodium of 28.9 mEq. Pituitary hormones were normal. Assay of blood and cerebrospinal fluid (CSF) were negative for placental alkaline phosphatase (PLAP), alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (β-HCG). No tumor cells were found in CSF.

Central DI was diagnosed and treated with DDAVP (0.4 mg/day) with good control of symptoms.

The T1-weighted brain MRI sequence revealed a 1.3 × 0.7 cm hyperintense, heterogeneous, left-sided lesion in the paraventricular region of the caudate nucleus within the BG [ Figure 1a ]. The lesion appeared hyperintense on T2-weighted [ Figure 1b ] and fluid-attenuated inversion recovery sequences [ Figure 1c ], with contrast enhancement on T1-weighted images following gadolinium administration, as seen in coronal [ Figure 1d ], axial [ Figure 1e ], and sagittal [ Figure 1f ] planes. No leptomeningeal, pineal, or pituitary lesions were observed on the MRI. The pituitary stalk was centrally located and of normal thickness.

Figure 1:

(a) The T1-weighted brain magnetic resonance imaging sequence revealed a left-sided basal ganglia tumor in the paraventricular region of the caudate nucleus; (b) T2-weighted and (c) Fluid-attenuated inversion recovery sequences further characterized the lesion.; Contrast enhancement was observed on T1-weighted images in the (d) coronal, (e) axial, and (f) sagittal planes.

The patient underwent a stereotactic biopsy guided by a fusion of stereotactic computed tomography (CT) and MRI. Frozen section pathological examination was suggestive of a GEM.

Histopathological examination revealed the presence of undifferentiated cells with clear cytoplasm and irregular nuclei dispersed within a lymphoplasmacytic inflammatory reaction [ Figure 2a ]. Immunohistochemistry revealed tumor cells with strong membrane staining for c-kit and multifocal immunopositivity for anti-CD3, CD20, and bcl-2 oncoprotein antibodies. The tumor cells were negative for PLAP, AFP, β-HCG, as well as anti-CD1a and S100 protein antibodies, which confirmed the GEM diagnosis [ Figure 2b ].

Figure 2:

Photomicrograph (a) showing undifferentiated cells with clear cytoplasm and irregular nuclei, dispersed within a lymphoplasmacytic inflammatory reaction (Hematoxylin and Eosin, 400x); (b) Immunohistochemistry demonstrates strong membrane staining for c-kit in tumor cells, confirming the diagnosis of germinoma.

In 2010, a linear accelerator stereotactic radiosurgery (SRS) was performed with stereo-CT and MRI fusion. The patient received a single dose of 13 Gy to a conformally shaped 80% isodose shell encompassing the enhancing tumor margin [ Figure 3 ].

The postoperative period was uneventful, with improvement of symptoms and discontinuation of desmopressin therapy. A follow-up MRI performed 3 months after surgery revealed no residual tumor [ Figure 4 ].

Figure 3:

Stereotactic radiosurgery planning utilizing a fused stereo-computed tomography and magnetic resonance image for the delivery of a single dose of 13 Gy to a conformally shaped 80% isodose line.

Figure 4:

A follow-up brain magnetic resonance imaging performed 3 months after radiosurgery showed no evidence of residual tumor.

Seven months following radiosurgery, the patient experienced a recurrence of polydipsia and polyuria, although to a lesser degree than at the initial presentation. Laboratory tests demonstrated a urinary osmolarity of 328 mOsm/kgH₂O, urinary sodium of 20.5 mEq/24 h, an antidiuretic hormone (ADH) level below 1.31 pg/mL, and a baseline cortisol level of 37.10 mcg/dL. At the time of recurrence, CSF testing also ruled out leptomeningeal disease, and the MRI showed no evidence of tumor recurrence or other abnormalities related to radiosurgery, and neurohypophysis and pituitary stalk were normal [ Figure 5 ].

Figure 5:

Seven months after radiosurgery, brain magnetic resonance imaging revealed no evidence of tumor recurrence or abnormalities related to the procedure.

Desmopressin therapy was reinstituted, resulting in effective symptom management.

Eleven years after the onset of symptoms, the patient remained stable on a regular desmopressin regimen (0.2 mg/day), maintaining normal water intake and urinary volume. In addition, there was a noticeable improvement in the patient’s hand dystonia. The high-resolution brain MRI scans (3.0 tesla) performed annually during the past 10 years after radiosurgery revealed no evidence of tumor recurrence or other abnormalities, particularly within the neurohypophysis and pituitary stalk [ Figure 6 ].

Figure 6:

The T1-weighted brain magnetic resonance imaging sequence performed 10 years after radiosurgery: (a) axial view revealed no evidence of tumor recurrence; (b) sagittal view showed a normal neurohypophysis and pituitary stalk.

DISCUSSION

Germinomas primarily originate in the suprasellar and pineal regions [ 2 , 9 , 21 , 24 ] from totipotent cells of the rostral neural tube, which migrate along the midline during embryonic development. However, in 5–10% of cases, these cells may deviate from the midline, resulting in their localization in regions such as the BG and thalamus.[ 9 10 , 13 , 16 ]

PLAP is a marker of primordial germ cells and is detected in approximately 82.6% of GEM. However, interpreting PLAP staining can be challenging in small biopsy samples, inflammatory-rich tissues, and specimens that have undergone prior freezing [ 19 ], as observed in our case. In contrast, c-kit and OCT3/4 are highly sensitive markers for GEM, demonstrating a detection rate of 100%.[ 26 ]

The association between DI and GEM can be attributed to three primary mechanisms. The most common mechanism is the involvement of the pituitary or suprasellar region.[ 1 , 3 , 7 , 23 ] In rare instances, BG or thalamus involvement may lead to atypical DI, potentially secondary to peritumoral edema affecting the hypothalamus.[ 7 , 22 ] In addition, hidden tumors within the neurohypophysis or pituitary stalk should also be considered as a potential cause.[ 1 , 2 , 7 , 18 , 23 ]

The relationship between BG lesions and DI appears to be complex.[ 3 , 5 , 12 , 13 ] The proximity of the BGGEM to critical functional hypothalamic pathways may have disrupted hypothalamic circuits responsible for ADH regulation, leading to DI rather than direct involvement or occult GEM. In addition, the presence of involuntary hand movements aligns with known associations between BGGEM and focal dystonia, attributed to the disruption of neurological circuits within the caudate nucleus caused by tumor compression. In the present case, 11 years after the onset of symptoms, without the appearance of a pituitary lesion, the most likely explanation for the DI is hypothalamic involvement, although this theory cannot be definitively confirmed. These findings underscore the need for further studies to elucidate the interplay between BG tumors and hypothalamic function.

Occult GEM of the neurohypophysis should always be considered a differential diagnosis for idiopathic DI. These lesions typically manifest within 12–66 months from symptom onset,[ 22 , 23 ] often presenting with thickening of the pituitary stalk or other neurohypophyseal changes.[ 15 , 23 ] The sustained recurrence-free follow-up over 11 years, without evidence of neurohypophyseal involvement, strongly argues against the hypothesis of an occult GEM.[ 15 , 23 ]

Kobayashi et al. highlighted instances of occult neurohypophyseal GEM, where central DI preceded tumor detection.[ 8 ] Such cases emphasize the importance of prolonged monitoring in patients presenting with DI. Tamaki et al. explored atypical GEM locations, including the BG, underscoring the variability in clinical presentation.[ 22 ] Ramelli et al. examined the significance of DI as an early manifestation, reinforcing the need to consider GEM in the differential diagnosis of unexplained DI. BGGEM has a longer delay in diagnosis, which was identified as a significant independent prognostic factor.[ 15 , 26 ]

GEM is highly sensitive to both radiotherapy and chemotherapy, offering the potential for cure.[ 3 , 9 , 14 , 17 , 25 ] Routine ventricular irradiation is widely recommended for GEM due to the risk of occult CSF seeding, particularly in ventricular tumors located in the pineal or suprasellar regions.[ 11 ] Hao et al. described a case of BGGEM treated with radiation therapy, achieving long-term remission.[ 4 ] Local SRS for ventricular lesions may be less efficient in controlling CSF dissemination compared to whole-ventricular irradiation.[ 11 , 17 ] This limitation arises because SRS targets localized tumor masses but does not address microscopic tumor spread within the ventricular system.[ 11 , 17 ] For lesions outside the ventricles, such as BGGEM, SRS might be a viable standalone option, as these locations are less prone to CSF seeding. However, careful patient selection and long-term monitoring are crucial to ensure the absence of occult dissemination. The prognosis for children with nonmetastatic GEM is generally favorable, with survival rates ranging from 90% to 100%.[ 1 , 5 , 13 , 18 ]

CONCLUSION

BG GEM presenting with central DI in children is rare but should not be overlooked. Long-term follow-up, including regular clinical and neuroimaging evaluations, is essential to monitor for the potential development of occult GEM. This case report highlights the potential for SRS as a treatment option for patients with BGGEM, particularly in the absence of other lesions in the neurohypophysis. This case highlights the efficacy of SRS in achieving long-term tumor control, with no recurrence observed over an 11-year follow-up period. However, as a single case, it does not provide definitive evidence for the broader applicability of this approach. The limited number of similar cases restricts the generalizability of these findings. Further research, including larger and prospective studies, is crucial to validate SRS as a standalone treatment option and to optimize therapeutic strategies for this rare presentation.

Ethical approval

The Institutional Review Board approval is obtained by the Ethics Committee of the Medical School of Santa Casa de Misericordia, Vitoria, Espírito Santo, Brazil, number 64695922.1.0000.5060, dated 10/08/12.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

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