Multi-institutional analysis of treatment modalities in basal ganglia and thalamic germinoma.

BACKGROUND: Central nervous system (CNS) germinomas are treatment-sensitive tumors with excellent survival outcomes. Current treatment strategies combine chemotherapy with radiotherapy (RT) in order to reduce the field and dose of RT. Germinomas originating in the basal ganglia/thalamus (BGTGs) have proven challenging to treat given their rarity and poorly defined imaging characteristics. Craniospinal (CSI), whole brain (WBI), whole ventricle (WVI), and focal RT have all been utilized; however, the best treatment strategy remains unclear. METHODS: Retrospective multi-institutional analysis has been conducted across 18 institutions in four countries. RESULTS: For 43 cases of nonmetastatic BGTGs, the 5- and 10-year event-free survivals (EFS) were 85.8% and 81.0%, respectively, while the 5- and 10-year overall survivals (OS) were 100% and 95.5%, respectively (one patient fatality from unrelated cause). Median RT doses were as follows: CSI: 2250 cGy/cGy(RBE) (1980-2400); WBI: 2340 cGy/cGy(RBE) (1800-3000); WVI: 2340 cGy/cGy(RBE) (1800-2550); focal: 3600 cGy (3060-5400). Thirty-eight patients (90.5%) received chemotherapy. There was no statistically significant difference in the EFS based on initial field extent (p = .84). Nevertheless, no relapses were reported in patients who received CSI or WBI. Chemotherapy alone had significantly inferior EFS compared to combined therapy (p = .0092), but patients were salvageable with RT. CONCLUSION: Patients with BGTGs have excellent outcomes and RT proved to be an integral component of the treatment plan. This group of patients should be included in future prospective clinical trials and the best RT field should be investigated further.

Antibodies Against Hypothalamus and Pituitary Gland in Childhood-Onset Brain Tumors and Pituitary Dysfunction.

Purpose: To detect the presence of antipituitary (APA) and antihypothalamus antibodies (AHA) in subjects treated for brain cancers, and to evaluate their potential association with pituitary dysfunction. Methods: We evaluated 63 patients with craniopharyngioma, glioma, and germinoma treated with surgery and/or radiotherapy and/or chemotherapy at a median age of 13 years. Forty-one had multiple pituitary hormone deficiencies (MPHD), six had a single pituitary defect. GH was the most common defect (65.1%), followed by AVP (61.9%), TSH (57.1%), ACTH (49.2%), and gonadotropin (38.1%). APA and AHA were evaluated by simple indirect immunofluorescence method indirect immunofluorescence in patients and in 50 healthy controls. Results: Circulating APA and/or AHA were found in 31 subjects (49.2%) and in none of the healthy controls. In particular, 25 subjects out of 31 were APA (80.6%), 26 were AHA (83.90%), and 20 were both APA and AHA (64.5%). Nine patients APA and/or AHA have craniopharyngioma (29%), seven (22.6%) have glioma, and 15 (48.4%) have germinoma. Patients with craniopharyngioma were positive for at least one antibody in 39.1% compared to 33.3% of patients with glioma and to 78.9% of those with germinoma with an analogous distribution for APA and AHA between the three tumors. The presence of APA or AHA and of both APA and AHA was significantly increased in patients with germinoma. The presence of APA (P = 0.001) and their titers (P = 0.001) was significantly associated with the type of tumor in the following order: germinomas, craniopharyngiomas, and gliomas; an analogous distribution was observed for the presence of AHA (P = 0.002) and their titers (P = 0.012). In addition, we found a significant association between radiotherapy and APA (P = 0.03). Conclusions: Brain tumors especially germinoma are associated with the development of hypothalamic-pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.

Reversible hypothalamic dysfunction in optic nerve germinoma.

Primary optic apparatus germ cell tumors are rare. There have been only 6 cases reported in the literature. Although they often disturb the hypothalamus-pituitary-adrenal axis and cause progressive visual loss, the influence of treatment outcomes on hypothalamic autoregulation has never been mentioned. Here, we report a patient with an optic nerve germinoma who presented with reversible visual and hypothalamic dysfunction, and we discuss the possible mechanisms and pathogenesis.

Hypothalamic germinoma masquerading as superior mesenteric artery (SMA) syndrome.

OBJECTIVE: To report a case of superior mesenteric artery (SMA) syndrome secondary to hypothalamic germinoma. METHODS: We describe the clinical presentation, diagnostic work-up, management, and clinical course of a patient admitted with SMA syndrome who was subsequently found to have a hypothalamic germinoma. RESULTS: An adolescent boy was admitted to the surgical ward with progressive weight loss over a 2 year period and postprandial vomiting. He was diagnosed with SMA syndrome based on evidence of proximal duodenal dilatation, extrinsic compression of the distal duodenum, and a narrowed aortomesenteric angle (16°). Investigations performed to exclude thyrotoxicosis unexpectedly revealed secondary hypothyroidism and further evaluation demonstrated evidence of pan-hypopituitarism. Psychiatric evaluation excluded anorexia nervosa and bulimia. Magnetic resonance imaging (MRI) of the brain revealed a heterogeneously enhancing hypothalamic lesion, but a normal pituitary gland. Hormone replacement with hydrocortisone, desmopressin, testosterone, and thyroxine resulted in weight gain and resolution of gastrointestinal symptoms. A transventricular endoscopic biopsy subsequently confirmed a hypothalamic germinoma and he was referred to an oncologist. CONCLUSION: SMA syndrome secondary to severe weight loss is an uncommon cause of upper gastrointestinal obstruction. While there have been reports of poorly controlled diabetes mellitus and thyrotoxicosis manifesting as SMA syndrome, there are no published reports to date of SMA syndrome secondary to hypothalamic/pituitary disease. Management of SMA syndrome is conservative, as symptoms of intestinal obstruction resolve with weight gain following treatment of the underlying cause. Awareness of this uncommon presentation of endocrine cachexia/hypothalamic disease will prevent unnecessary laparotomies and a misdiagnosis of an eating disorder.

Probability of metachronous testicular cancer in patients with biopsy-proven intratubular germ cell neoplasia depends on first-time treatment of germ cell cancer.

PURPOSE: To evaluate the probability of subsequent testicular cancer (STC) in patients with intratubular germ cell neoplasia unclassified (IGCNU) treated for first-time invasive germ cell cancer. PATIENTS AND METHODS: Sixty-one patients with germ cell testicular cancer or extragonadal germ cell cancer received follow-up from diagnosis of IGCNU to development of STC, initiation of IGCNU-definitive treatment (orchiectomy/radiotherapy), emigration, death, or end of follow-up. The probability of STC was assessed in subgroups according to chemotherapy burden. RESULTS: The probability of STC in the nonexposed patients was significantly increased compared with those exposed to chemotherapy (P = .05; 5-year probability of 54% [95% CI, 33% to 78%] and 23% [95% CI, 11% to 45%], respectively). In the group of patients treated with one to three cycles or no chemotherapy, the probability of STC was significantly increased compared with those exposed to four or more cycles (P = .03; 5-year probability of 42% [95% CI, 27% to 62%] and 22% [95% CI, 8% to 54%], respectively). Twenty-two of 22 patients were tumor-free and alive at a median of 56 months (range, 2 to 184 months) after diagnosis of STC. CONCLUSION: Platinum-based chemotherapy may reduce the probability of STC in patients with IGCNU, particularly in those treated with four or more cycles of chemotherapy. A watch-and-wait strategy for patients with IGCNU may be justified in selected patients with future plans for paternity.

[The early diagnosis of juvenile germinoma originating from the basal ganglia and thalamus].

OBJECTIVE: To explore the early diagnosis of germinoma originating from the basal ganglia (BG) and thalamus during juveniles. METHODS: Retrospective analysis was done with the clinical cases of germinomas in BG and thalamus from 2000 to 2009. The symptoms, signs, neuroimaging, cerebrospinal fluid (CSF) findings were analyzed and related literature were reviewed. RESULTS: Eight patents were collected. The main symptoms were hemiplegia, associated with aphasia and/or impaired cognition. Brain CT showed high density and calcification. Abnormal T1 and T2 signal were found in brain MRI frequently associated with ipsilateral hemisphere atrophy. MRS showed increased choline and decreased N-acetylaspartate level. Elevated CSF human chorionic gonadotrophin level were found in two of them. CONCLUSIONS: Germinoma in BG and thalamus predominates in a boy. The neuroimaging features are very informative for early diagnosis.

Transventricular Biopsy of Brain Tumor without Hydrocephalus Using Neuroendoscopy with Navigation

OBJECTIVE: It is usually difficult to perform the neuroendoscopic procedure in patients without hydrocephalus due to difficulties with ventricular cannulation. The purpose of this study was to find out the value of navigation guided neuroendoscopic biopsy in patients with peri- or intraventricular tumors without hydrocephalus. METHODS: Six patients with brain tumors without hydrocephalus underwent navigation-guided neuroendoscopic biopsy. The procedure was indicated for verification of the histological diagnosis of the neoplasm, which was planned to be treated by chemotherapy and/or radiotherapy as the first line treatment, or establishment of the pathological diagnosis for further choice of the most appropriate treatment strategy. RESULTS: Under the guidance of navigation, targeted lesion was successfully approached in all patients. Navigational tracking was especially helpful in entering small ventricles and in approaching the third ventricle through narrow foramen Monro. The histopathologic diagnosis was established in all of 6 patients : 2 germinomas, 2 astrocytomas, 1 dysembryoplastic neuroepithelial tumor and 1 pineocytoma. The tumor biopsy sites were pineal gland (n = 2), suprasellar area (n = 2), subcallosal area (n = 1) and thalamus (n = 1). There were no operative complications related to the endoscopic procedure. CONCLUSION: Endoscopic biopsy or resection of peri- or intraventricular tumors in patients without hydrocephalus is feasible. Image-guided neuroendoscopic procedure improved the accuracy of the endoscopic approach and minimized brain trauma. The absence of ventriculomegaly in patients with brain tumor may not be served as a contraindication to endoscopic tumor biopsy.

Use of 11C-methionine positron emission tomography in basal germinoma: assessment of treatment response and residual tumor.

INTRODUCTION: Prognosis of germinoma arising in the basal ganglia or thalamus is worse compared to that in the pineal or suprasellar region. One of the reasons for poor prognosis is the difficulty in evaluating the efficacy of treatment by conventional neuroimaging tools. PET STUDIES: The usefulness of (11)C-methionine (MET) positron emission tomography (PET) in monitoring the biological nature of brain tumors has been proved in glioma patients. CASE REPORTS: Herein, we describe MET-PET findings in three cases of germinomas in the basal ganglia or thalamus and discuss the use of MET-PET in the assessment of treatment response and residual tumor for the next treatment strategy. The patients showed transient increase of MET uptake in the lesions after the initial treatment. Although we did not perform histological verification, MET- PET findings suggested that active tumor cells were still alive in the lesions after the initial treatment. MET uptake gradually decreased during the course of intensive therapy in these patients. MET-PET also revealed germinoma invasion in the brain before discernible signal abnormality or mass lesion in conventional magnetic resonance images in two patients. DISCUSSION: Further studies including histological verification and long-term follow-up might validate the use of MET-PET in monitoring the treatment efficacy and evaluation of active residual tumor after the treatment. CONCLUSION: Until we understand what MET uptake truly represents, treatment strategy based on MET uptake must be carefully designed to prevent overtreatment and resultant complications.

[Case report of germinoma with synchronous lesions in the thalamus and para lateral ventricle].

A 25-year-old man presented with headache and consciousness disturbance. MRI revealed well enhanced mass lesions using gadolinium at bilateral thalamus and right para lateral ventricle with mild perifocal edema. Obstructive hydrocephalus was observed. On neuroendoscopic observation, the tumor was not appeared on the surface of the ventricle, therefore biopsy of the lesion was not sufficient to make a definitive pathological diagnosis. Third ventriculostomy was successful and the patient's consciousness improved. One week later, a stereotactic biopsy for right para lateral ventricle lesion made possible the histological diagnosis of typical germinoma. Post operative course was uneventful. Chemotherapy (CDDP and etoposide) following 30 Gy whole ventricle irradiation resulted in the complete response of the lesion. Four years later, he has no neurological deficit except for mild disturbance in his eye movement. Our experience suggests that a synchronous lesion at thalamus and para lateral ventricle seems to be due to subependymal infiltration other than CSF dissemination.

The germinomas arising from the basal ganglia and thalamus.

OBJECTIVE: To introduce the features of germinomas arising from the basal ganglia (BG) and thalamus. METHOD: Retrospective analysis was done with the clinical cases of germinomas in BG and thalamus from 1996 to 2000. The data included the symptoms, signs, neuroimaging findings, treatment, and outcomes. RESULT: Fourteen cases were included, only one female was included. The main symptoms are disorder of numbness and weakness in limbs. Neuroimaging showed no or mild peritumor high signal in T2 weighted imaging of magnetic resonance, accompanied with cyst, calcification or bleeding. Total gross resection was obtained in nine cases, subtotal resection in four. Follow-up data were available in 11 cases with average of 56 months. Eight cases underwent only postoperative radiotherapy, one underwent only chemotherapy, and two underwent both. One case died of complication 6 months after chemotherapy, the rest lived good life. CONCLUSION: Germinoma in BG and thalamus predominate in a boy. The neuroimaging features are very informative for diagnosis. Surgical resection should not be the first choice although it is has lesser complications. The long-term outcome is favorable.

[Diagnosis and radiotherapy of germinomas arising in basal ganglia and thalamus].

OBJECTIVE: To summarize the clinical characteristic and radiotherapeutic effect of germinomas arising in basal ganglia and thalamus. METHODS: The clinical data of 13 cases were reviewed retrospectively. All cases were pathologic diagnosis through stereotactic biopsy. Gamma-knife or ordinary irradiation were 2 cases respectively and the combined therapy with interstitial brachytherapy as foundation were 9 cases. RESULT: All cases were male, median age of 16.1 years. Hemiparesis and ataxia were major symptoms, some cases were accompanied with precocious puberty. Imaging manifested intratumoral cystic components represented 76.9% of all lesions, calcification represented 30.8%, ipsilateral cerebral and brain stem hemiatrophy represented 46.2%, cerebral white matter invasion through internal capsule or corpus callosum represented 30.8%. One case died because of late complication and 12 cases had achieved satisfied therapeutic effect (the mean followed-up period was 40.6 months). Tumor-control were effective. CONCLUSIONS: The clinical manifestation and imaging characteristics are helpful to diagnosis. Stereotactic biopsy make the affirmatory diagnosis. Operative total-removal is impossible because of deep location, neighbour of vital structure and invasion. The combined therapy with interstitial brachytherapy was effective.

Diagnosis and radiotherapy of germinomas arising in basal ganglia and thalamus / 中华外科杂志

<p><b>OBJECTIVE</b>To summarize the clinical characteristic and radiotherapeutic effect of germinomas arising in basal ganglia and thalamus.</p><p><b>METHODS</b>The clinical data of 13 cases were reviewed retrospectively. All cases were pathologic diagnosis through stereotactic biopsy. Gamma-knife or ordinary irradiation were 2 cases respectively and the combined therapy with interstitial brachytherapy as foundation were 9 cases.</p><p><b>RESULT</b>All cases were male, median age of 16.1 years. Hemiparesis and ataxia were major symptoms, some cases were accompanied with precocious puberty. Imaging manifested intratumoral cystic components represented 76.9% of all lesions, calcification represented 30.8%, ipsilateral cerebral and brain stem hemiatrophy represented 46.2%, cerebral white matter invasion through internal capsule or corpus callosum represented 30.8%. One case died because of late complication and 12 cases had achieved satisfied therapeutic effect (the mean followed-up period was 40.6 months). Tumor-control were effective.</p><p><b>CONCLUSIONS</b>The clinical manifestation and imaging characteristics are helpful to diagnosis. Stereotactic biopsy make the affirmatory diagnosis. Operative total-removal is impossible because of deep location, neighbour of vital structure and invasion. The combined therapy with interstitial brachytherapy was effective.</p>

Pineal germinoma presenting as anorexia nervosa: Case report and review of the literature.

OBJECTIVE: Tumors of the hypothalamic-pineal region may present with a wide variety of symptoms, including disturbed eating. We present a case where such a tumor was misdiagnosed as anorexia nervosa. METHOD: We describe a case of pineal germinoma invading the hypothalamus, which was initially diagnosed as anorexia nervosa. RESULTS: Clinical features included weight loss, vomiting, pyrexia, hypernatraemia, and visual disturbance and the typical psychopathology of anorexia nervosa was absent. CONCLUSION: Organic disorder should always be considered before making a diagnosis of anorexia nervosa, particularly if the presentation is atypical.

A Case of Basal Ganglia Germinoma Presenting Only with Cerebral Hemiatrophy Diagnosed by Using 11C-Methionine Positron Emission Tomography / 대한소아신경학회지

We present a case of cerebral germinoma that occurred in the basal ganglia with progressive hemiparesis. A 10-year-old boy was referred to our hospital complaining of progressive right hemiparesis and decreased mental functions. Brain MRI showed left cerebral hemiatrophy and high signal intensity in left thalamus, basal ganglia, cerebral peduncle, and pons. However, no mass or enhancement was observed. 11C-Methionine positron emission tomography showed discernable hot uptake in the left basal ganglia and thalamus. Stereotactic biopsy, with a guide of 11C-Methionine positron emission tomography, was performed and the diagnosis of pure germ cell tumor was determined. 11C-Methionine positron emission tomography is useful for localization of a suspicious tumor in patients with cerebral hemiatrophy without overt mass or enhancing lesions in brain MRI.

Auditory agnosia caused by a tectal germinoma.

The authors describe a patient with auditory agnosia caused by a tectal germinoma. Despite having normal audiometric tests, the patient failed to recognize words and musical characters. On head MRI, the inferior colliculi were infiltrated by tumor. Neuropsychological tests revealed severe impairment in recognition of environmental sounds and words, defective musical perception, and stop consonant-vowel discrimination. Inferior colliculus may play a role in the analysis of sound properties.

Differential diagnosis of suprasellar tumors in children.

In contrary to the adult age the most common suprasellar tumors in children are with decreasing frequency craniopharyngiomas, chiasmatic/hypothalamic low-grade gliomas, germinomas and lesions attributable to a Langerhans cell histiocytosis. For differential diagnostic purposes also the rare hypothalamic hamartoma and meningeal metastases in the infundibular recess of the third ventricle are included. The typical aspects of the various tumors on computed tomography (CT) and magnetic resonance imaging (MRI) together with important clinical differences are illustrated. On the basis of imaging results and clinical symptoms differential diagnosis between the various tumor entities should be feasible in many cases. Of course, only in strictly defined cases like typical chiasmatic/hypothalamic and optic pathway gliomas or bilocular germ cell tumors a histological confirmation is dispensable.