Suprasellar Germinoma Research Articles

Imaging in malignant germ cell tumors involving the hypothalamo-neurohypophyseal axis: the evaluation of the posterior pituitary bright spot is essential

PurposeMalignant intracranial germ cell tumors (GCTs) are rare diseases in Western countries. They arise in midline structures and diagnosis is often delayed. We evaluated imaging characteristics and early tumor signs of suprasellar and bifocal GCT on MRI.MethodsPatients with the diagnosis of a germinoma or non-germinomatous GCT (NGGCT) who received non-contrast sagittal T1WI on MRI pre-therapy were included. Loss of the posterior pituitary bright spot (PPBS), the expansion and size of the tumor, and the expansion and infiltration of surrounding structures were evaluated. Group comparison for histologies and localizations was performed.ResultsA total of 102 GCT patients (median age at diagnosis 12.3 years, range 4.4–33.8; 57 males; 67 in suprasellar localization) were enrolled in the study. In the suprasellar cohort, NGGCTs (n = 20) were noticeably larger than germinomas (n = 47; p < .001). Each tumor showed involvement of the posterior lobe or pituitary stalk. A PPBS loss (total n = 98) was observed for each localization and entity in more than 90% and was related to diabetes insipidus. Osseous infiltration was observed exclusively in suprasellar GCT (significantly more frequent in NGGCT; p = .004). Time between the first MRI and therapy start was significantly longer in the suprasellar cohort (p = .005), with an even greater delay in germinoma compared to NGGCT (p = .002). The longest interval to treatment had circumscribed suprasellar germinomas (median 312 days).ConclusionA loss of the PPBS is a hint of tumor origin revealing small tumors in the neurohypophysis. Using this sign in children with diabetes insipidus avoids a delay in diagnosis.

Methionine metabolism and endocrine function of the pituitary gland in patients with suprasellar germinoma.

The aim of this study was to investigate the association between methionine (MET) metabolism and endocrine function of the pituitary gland in patients with suprasellar region tumor. Twenty patients with intracranial germinoma were included in this study. Initial staging and all surveillance MET PET/CT scans and comparable serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid stimulating hormone (TSH) were analyzed. The patients were divided into two groups according to tumor location, with tumors in the suprasellar region (condition) or not (control). MET uptake of the pituitary gland (i.e., SUVR [standardized uptake value ratio]) and levels of FSH, LH, TSH were compared in the condition and control groups and in the before and after treatment phases of each group. The SUVR in the control group was like that found in normal pituitary glands in previous studies, whereas the SUVR of the untreated condition group was high and that of treated condition group was low with significance compared to the control group. Serum levels of pituitary hormones in before and after treatment condition groups were significantly lower than those in the control group. The FSH and LH levels of curatively treated patients in the control group were positively correlated with SUVR with respective ß values of 3.71 and 0.98 (p < .001). The TSH level of the treated condition group was negatively correlated with SUVR (ß = -1.02, p < .001). This study is the first known investigation to examine the association between MET metabolism and endocrine function of the pituitary gland, and it confirmed that MET metabolism reflects endocrine function. A future study validating the result of correlation analysis is warranted.

0972 The Utility of CSF Orexin Testing in Investigating for Narcolepsy Type-1 in a Patient with Diencephalic Mass

Abstract Introduction Narcolepsy type 1 (NT1) is characterized by pathologic hypersomnolence, REM intrusion phenomena, including cataplexy, and orexin deficiency. The diagnosis of NT1 is established based on the presence of bone fide cataplexy and supportive PSG and MSLT testing which requires patients to achieve sufficient sleep duration and regularity and discontinue centrally acting medications that might alter REM sleep. In cases where there is a high index of suspicion for NT1, CSF orexin deficiency is helpful to support the diagnosis of NT1. This is particularly true when PSG-MSLT are not feasible, CNS medication cannot be discontinued, or cataplexy cannot be validated. Report of case(s) A 16 year old girl presented for evaluation of excessive daytime sleepiness in the setting of suprasellar germinoma which was resected and treated with chemoradiation at age 11. She subsequently developed panhypopituitarism and severe hypersomnolence in the setting of sleep-wake schedule irregularities, variability of sleep duration, refractory delayed sleep phase disorder, and snoring. She reported episodic weakness in the setting of negative triggers, which was atypical for cataplexy. Her medications included modafinil, amphetamine-dextroamphetamine, and the SSRI fluoxetine. Physical examination depicted normal airways. Epworth Sleepiness Scale score was 18. Screening polysomnography showed a sleep efficiency of 78%, sleep latency of 46.5 minutes, REM latency 2 hours, AHI of 0/hr, and periodic limb movements of 35/hr without arousals. While the REM latency on polysomnography was inconsistent with NT1, the clinical history of a diencephalic mass and chemoradiation was suggestive of secondary NT1. She was unable to proceed with PSG-MSLT due to her psychiatrist's advice against discontinuing her SSRI and her difficulty in maintaining sleep-wake regularity. An evaluation for CSF orexin was performed establishing a normal level of 337 pg/mL (reference level of 200 pg/mL in healthy individuals), ruling out orexin deficiency /narcolepsy type 1. The patient was subsequently improved with wake-promoting antidepressants and light therapy in the AM. Conclusion This case illustrates the value of CSF orexin testing in the setting of diencephalic lesions in patients unable to undergo formal narcolepsy testing. Support (if any)

Primary suprasellar germinoma: A series of 15 cases

Primary suprasellar germinoma (PSG) is a rare malignant tumor of the central nervous system. This study aimed to explore the clinical characteristics, treatment protocol, and prognosis of patients with PSG. This case series retrospectively analyzed the clinical data of patients with PSG in Tianjin Huanhu Hospital diagnosed between January 2016 and December 2021. Fifteen patients with an average age of 19.6 years were included, in which nine of them were males. The mean duration between initial symptoms and admission was 17.0 months. The mean follow-up was 40.8 months. Ten patients had polydipsia and polyuria, visual impairments were observed in 8 patients, and 2 cases (13.3%) had symptoms both from suprasellar and pineal regions. All 15 cases were histopathologically confirmed as germinoma through craniotomy or biopsy. Most patients (80%) underwent radiotherapy combined with chemotherapy. During follow-up, all the patients showed a reduction in tumor size, especially in the bifocal cases. Symptoms of polydipsia, polyuria, and visual impairment were markedly relieved to different degrees. All patients had recovered well at discharge. Patients with polydipsia and polyuria took desmopressin daily. A histological confirmation by open biopsy through craniotomy or endoscopic biopsy might be recommended for PSG to start the appropriate treatments. Patients with PSG will usually have a good prognosis, but attention should be paid to the treatment of endocrine deficiencies.

Endocrine manifestations of paediatric intracranial germ cell tumours: from diagnosis to long-term follow-up.

We examined endocrine manifestations in a cohort of paediatric patients with IC-GCTs at diagnosis and during follow-up, integrating clinical, radiological, histopathological and laboratory data. Diabetes insipidus (DI), growth hormone deficiency (GHD), hypothyroidism, adrenal insufficiency, precocious puberty (PP)/hypogonadism were diagnosed clinically and biochemically. The prevalence of endocrine manifestations was compared to survival rates. Our population included 55 children (37 males, 18 females) diagnosed with IC-GCT with a median follow-up of 78.9 months from diagnosis (range 0.5-249.9). At tumour diagnosis, 50.9% patients displayed endocrinopathies: among them, 85.7% were affected by DI, 57.1% central adrenal insufficiency, 50% central hypothyroidism, 28.5% GHD, 10.7% hypogonadotrophic hypogonadism, 10.7% PP. These patients presented predominantly with suprasellar germinoma. If not diagnosed previously, endocrine disorders arose 15.15 months (1.3-404.2) after end of treatment (EOT) in 16.4% patients. At least one endocrinopathy was identified in 67.3% of subjects at last follow-up visit, especially GHD and adrenal insufficiency. DI, hypothyroidism, and adrenal insufficiency occurred earlier than other abnormalities and frequently preceded tumour diagnosis. Subjects with and without endocrine manifestations who survived beyond 12 months after EOT did not show significant difference in overall survival and progression-free survival (p = 0.28 and p = 0.88, respectively). Endocrinopathies were common presenting symptoms in our population. If present at diagnosis, they often persisted hence after. The spectrum of endocrinopathies expanded during follow-up up to 33.7 years after EOT. Although they did not seem to affect survival rate in our cohort, close lifelong surveillance is mandatory to provide the best care for these patients.

GCT-01. Pediatric intracranial germ cell tumors and primary polyuria-polydipsia syndrome: a 13-year single institutional experience

Abstract Intracranial germ cell tumors (IGCTs) represent about 4% of all childhood brain tumors. They are common in both the pineal and pituitary regions and sometimes they can be bifocal. Suprasellar and bifocal IGCTs usually present stereotypical symptoms, including primary polyuria-polydipsia syndrome (PPS). Consolidated IGCTs’ therapy is based on the International Society of Pediatric Oncologic (SIOP) CNS GCT II protocol consisting of primary pre-radiation chemotherapy combining etoposide, carboplatin and/or cisplatin and ifosfamide. PPS management in these patients requires monitoring of electrolytes and fluids during chemotherapy, especially for cisplatin and/or ifosfamide-based cycles, for which hyperhydratation is required. We report the results of our single-center cohort of patients with IGCTs treated between 2008 and 2021, focusing on the clinical presentation, treatment and long-term follow-up. Thirty-one patients were analyzed (median age=13 years, 87% male). Twelve children (39%) presented a PPS and needed desmopressin treatment, maintained at long-term follow-up data update in all. Over these PPS patients, 6 had bifocal germinomas, 4 suprasellar germinomas, 1 metastatic germinoma and 1 non-germinomatous IGCT. Eleven PPS children (92%) received cisplatin and/or ifosfamide-based chemotherapy: all of them had optimal biochemical urine and blood investigations before, during and after chemotherapy. None of them presented serious complications during treatment. After a median follow-up of 5 years, two patients (6.5%) died (1 IGCT-related, 1 non-cancer related) and one had a second malignancy (parotid gland mucoepidermoid carcinoma, 6 years after IGCT diagnosis). Childhood IGCTs have an excellent prognosis, but present a significant risk of long-lasting severe endocrine sequelae which may be worsened by the primary oncological strategy, requiring careful management of complications related to fluid and electrolytes disturbances. In order to avoid post-treatment pituitary insufficiency, guidelines for diabetes insipidus management when cisplatin and/or ifosfamide-based protocols are used should be established and all patients should receive meticulous endocrine follow-up.

Epidemiology, Management, and Long-Term Survival Outcomes of Intracranial Typical Site Germinomas: An Analysis of the Surveillance, Epidemiology, and End-Results (SEER) Database

BackgroundThe correlations of epidemiological characteristics and clinical outcomes with different tumor sites in patients with intracranial typical site germinomas (ICTSGs) have not yet been well established. We analyzed ICTSGs using a multicenter database, focusing on its demographic, management patterns, and long-term survival outcomes.MethodsPatients diagnosed with ICTSGs were selected from the Surveillance, Epidemiology, and End-Results (SEER) database. Demographic information and management patterns of ICTSGs were extracted for data analysis stratified by different tumor sites. Kaplan–Meier curves were used to evaluate the survival outcome stratified by treatment, tumor site and tumor size.ResultsAmong the 327 patients enrolled in the study, 16.21% had tumors located in the suprasellar region and 83.79% in the pineal region. The proportion of males was significantly higher among pineal germinomas (94.16 vs 66.04%; P < .001). Smaller tumors (<24 mm) were more common in the suprasellar region (37.74 vs 18.87%; P < .001). A higher percentage of patients with suprasellar germinomas underwent surgery. Radiotherapy (RT) and chemotherapy (CT) was, respectively, administered to 82.97 and 60.61% of patients during the treatment period, with no significant difference between suprasellar and pineal germinomas. CT plus RT was the most common treatment modality for both pituitary (30.19%) and pineal (33.94%) germinomas. Both RT and CT were associated with improved long-term survival. No survival difference was observed between suprasellar and pineal germinomas.ConclusionsDespite significant differences in epidemiology and management, pineal and suprasellar germinomas had a similar long-term clinical outcome.

Use of Second Window ICG in spinal cord biopsy of a mildly contrast-enhancing lesion: Technical note and review of the literature

IntroductionIndocyanine green (ICG) is commonly used to visualize cerebral vasculature, particularly in the management of cerebral aneurysms. There have also been attempts to use ICG for visualization of tumors. Injection of ICG followed by immediate fluorescence microscopy is limited by the short time window for imaging and administration and restricted depth of imaging. Second Window Indocyanine Green (SWIG) addresses these issues by allowing for longer contrast times and the imaging of deeper regions of brain tissue. Biopsy of spinal cord lesions is often difficult for a variety of reasons, including the delicate nature of the tissue and differentiating normal from lesional tissue visually, especially in lesions with heterogeneous enhancement. MethodsIn this case report, we describe the use of second window ICG to facilitate the visualization of a spinal cord lesion and subsequent biopsy of the lesion. ResultsThis patient is a 24-year-old female who had recurrence of a suprasellar germinoma. An MRI of the rest of the neuraxis was performed to assess for the presence of drop metastases. The spinal cord from C2-5 was expanded with areas of patchy enhancement; however, this lesion was asymptomatic. The patient's oncologist requested a biopsy of this lesion to help direct subsequent care of her recurrent germinoma. The day before surgery, the patient had an intravenous injection of ICG dye. She then underwent a C3-5 laminectomy for biopsy of her cervical intramedullary lesion. After opening of the dura, no visible abnormality of the spinal cord could be identified. A Stryker endoscope showed an area of ICG uptake in the cord at approximately the C3-4 level. A midline myelotomy was centered over the ICG demarcated area and several samples were taken for pathology. Final biopsy results determined the lesion to be spinal cord parenchyma with perivascular and intraparenchymal lymphocytes – not consistent with spinal cord tumor or germinoma. ConclusionSecond Window ICG is effective in visualizing otherwise visually unremarkable spinal cord lesions. This technology can facilitate biopsy of these lesions and possibly their surgical resection.

Panhypopituitarism Presenting as Progressive Visual Acuity Deterioration Secondary to Suprasellar Germinoma

Background: Overall the incidence of germ cell tumors worldwide is 0.1% with 60% comprising of germinomas. These may present in the suprasellar region a third of the time and thus impart variability in its presenting characteristics. Clinical Case: A 27-year male presented with progressive blurring of vision with incongruent visual acuity and refraction grade with optic disc pallor assessed with normal angiography. Patient also presented with increasing docility, sluggishness and more withdrawn behavior paired with polyuria, polydipsia and cold intolerance. Progressive worsening of vision led to cranial CT revealing an enhancing hyper density in the right caudate head later elucidated via MRI with several interspersed non-enhancing foci in the right caudate nucleus, both internal capsules with associated mild mass effect. The largest component located in the right capsular region with measurement of 21 x 21 x 16 mm with enhancing lesions in the hypothalamus and pituitary stalk. Endocrine evaluation revealed low serum cortisol at 91.03nmol/L (NV 138-685 nmol/L), responsive to ACTH stimulation test (65.94nmol/L to 387nmol/L), high prolactin at 856.9 mIU/L (42.4-296.8mIU/L) and low FT4 8.62pmol/l (9.01-19.05 pmol/L) despite normal TSH 1.528uIU/ml (0.35-4.94 uIU/mL). Optic nerve atrophy was now attributed to compressive intracranial mass. Secondary adrenal insufficiency was managed with hydrocortisone 50mgIV every 8 hours, and central hypothyroidism was managed with levothyroxine 75mcgtab 1tab once a day. Increased urinary output assessed as diabetes insipidus was given desmopressin 60mcg/tab ½ tab 2x a day at this time. Stereotactic biopsy of the brain revealed a germinoma of the right caudate lobe. Given the nature of the intracranial mass with high sensitivity to chemotherapeutic and radiotherapy, a multidisciplinary approach to treatment was taken with radiotherapy, hormonal and steroid replacement. Patient underwent external beam radiation therapy of the brain and spine for a total of 51 treatments allowing for improvement of visual acuity to counting, with polyuria less than 2-3 diaper changes per day. Conclusion: Optic disc pallor is a clinical sign that indicates optic nerve atrophy reflective of the optic tract. This may be an important clinical sign to increase clinical suspicion for intracranial mass lesion especially with correlation to manifestation of pituitary hormone deficiencies.

Treatment outcomes in patients with central nervous system germinoma (neuro-ophthalmic aspects)

The analyze the neuro-ophthalmic outcomes in patients with pineal and suprasellar germinoma after complex treatment. There were 125 patients (88 males, 37 females) with primary CNS germinoma for the period 2008-2017. All patients were divided into 3 groups depending on the tumor localization: pineal area - 62 patients, suprasellar neoplasm - 38 patients, bifocal germinoma - 25 patients. Treatment was performed in accordance with the «Germinoma-2008» protocol. Tumors were histologically patients (partial - 32 cases, subtotal - 16 cases). Surgery was followed by postoperative chemotherapy and stereotactic radiotherapy. The results were evaluated by neuro-ophthalmological examination at all stages of complex treatment. Pineal germinoma resulted oculomotor and pupillary disorders (58 patients - 94%) and papilledema. The last one completely regressed under the treatment. Partial reduction of oculomotor and pupillary abnormalities occurred throughout chemotherapy (6 patients - 10%). More than half of patients (n=24, 63%) with suprasellar germinoma had visual impairment. Improvement of visual functions including severe visual disturbance was observed in 14 patients (58%). Predominantly, functional recovery occurred under chemotherapy (12 patients - 86%). Bifocal germinoma was followed by various combinations of oculomotor, pupillary and/or visual impairments. We observed regression of only mild visual disorders. Stereotactic radiotherapy did not ensure any changes in neuro-ophthalmic symptoms in all groups.

OTHR-14. DIENCEPHALIC SYNDROME SECONDARY TO PITUITARY STALK THICKENING

BACKGROUNDDiencephalic syndrome (DS) is a rare condition associated with neoplastic lesions of the sellar-suprasellar region, whose pathophysiological mechanisms are still unclear. DS occurs in <10% of hypothalamic gliomas and has also been described in suprasellar germinomas, craniopharyngiomas, epidermoid cysts, rarely with non-suprasellar lesions such as brainstem gliomas. DS has not been associated with isolated pituitary stalk thickening. Isolated pituitary stalk thickening (IPST) presents a diagnostic challenge, ranging from benign (craniopharyngioma) to malignant lesions (germinoma, metastasis, histiocytoses of the Langerhans group). The coexistence of diabetes insipidus (DI) with anterior pituitary dysfunction and IPST implies more risk to harbor neoplasia. CASE REPORT: A 6-year old girl presented with DI and inadequate weight gain (despite regular caloric intake) and preservation of linear growth. Neurological examination showed no abnormalities. However, physical examination revealed a malnourished patient (both weight-for-age value and body-mass-index below the third percentile). Blood tests and negative IgA anti-endomysial antibodies excluded malabsorption as a cause of her malnutrition; endocrine work-up excluded thyroid dysfunction, growth hormone deficiency, and adrenal insufficiency. Magnetic resonance imaging (MRI) showed thickening of the pituitary stalk with a transverse diameter of 7 mm. The patient underwent a biopsy through a supraorbital eyebrow approach. Histopathological examination revealed lymphocytic hypophysitis, with tissue markers all negative for germinoma. The girl is currently under follow up with serial MRI every three months.CONCLUSIONDS should be considered as a differential diagnosis in any child with failure to thrive, and imaging studies should be performed even if there are no additional neurological symptoms.

Could Aberrant Migration Explain Metachronous Germ Cell Tumors?

Background Extragonadal germ cell tumors (GCTs) are thought to arise as a result of local transformation of primordial gonadal cells (PGCs) that become misplaced during embryogenesis. With the exception of bilateral testis tumors, metachronous GCT (i.e., occurring at a site classically described for primary GCTs) are rare events. Patients and Methods The clinical, radiological, and molecular data (if available) of patients with metachronous GCT were analyzed. Results Three Caucasian males were identified: case 1 presented with a pineal germinoma 19 years after a mediastinal seminoma that had been treated with chemotherapy, case 2 presented with a pineal non-seminomatous GCT (NSGCT) that occurred three years after a mediastinal seminoma treated with chemotherapy, and case 3 presented with a mediastinal seminoma concomitant with a suprasellar germinoma that occurred two years after a stage I testicular NSGCT treated exclusively with surgery. None of these patients had a positive family history or disorder of sex development. Molecular data were available for cases 2 and 3. In case 2, a CHEK2 gene biallelic inactivation in the second tumor suggested chemoresistance to cisplatin. This was further confirmed by tumor progression during second-line treatment. In case 3, the molecular analysis revealed different profiles in the three tumors, thus suggesting distinct tumor cell origins. Conclusion These rare cases should alert clinicians of the possibility of multiple GCTs that should not be considered to be relapses. The underlying physiopathology is unknown, but multiple PGC mismigrations is a likely cause. Initial treatment with cisplatin may select chemo-resistant clones, thereby making the subsequent treatment more of a challenge.

Accuracy of apparent diffusion coefficient values and magnetic resonance imaging in differentiating suprasellar germinomas from chiasmatic/hypothalamic gliomas.

The aim of this study was to differentiate suprasellar germinomas from chiasmatic/hypothalamic gliomas (CHGs) using apparent diffusion coefficient (ADC) values and magnetic resonance imaging (MRI) characteristics. A cross-sectional study was conducted on 11 patients with suprasellar germinomas and 11 patients with CHGs who underwent pretreatment MRI. The ADC values (minimum and average ADC values) of the tumors were measured and the MRI characteristics were evaluated. The average and minimum ADC values of suprasellar germinomas were significantly lower than those of CHGs (p = 0.016 and 0.004 respectively). The selection of 941.15 × 10-6 mm2/s as a cutoff value of the minimum ADC value was used to differentiate suprasellar germinomas and CHGs; the best results were obtained with area under the curve of 0.889, sensitivity of 87.5%, specificity of 77.8% and accuracy of 82.4%. MRI characteristics suggested the diagnosis of suprasellar germinomas were T2W hypointensity and involvement of pituitary gland and/or stalk. MRI characteristics suggested the diagnosis of CHGs was higher degree of contrast enhancement and presence of macrocysts. ADC values have a role in differentiating suprasellar germinomas and CHGs, especially when imaging findings on conventional MRI are inconclusive. Furthermore, some MRI features are in favor of differentiation between these tumor entities including tumor location, cyst pattern, T2W hypointensity, degree of contrast enhancement, stalk and pituitary gland involvement.

Neuro-ophthalmological symptoms in patients with pineal and suprasellar germinoma

To analyze neuro-ophthalmology symptoms in patients with germinomas located in pineal and suprasellar regions. The study analyzed 133 patients with germinoma who were receiving treatment in Burdenko Neuro-surgical Institute from 2008 to 2017. Assessment of results was performed by neuro-ophthalmology examination, a computerized oculograph was used for the objectification of the severity of ocular-motor and pupillary disorders. Among the patients of the study, 65 had pineal germinoma, 42 - suprasellar germinoma and 26 - bifocal germinoma. Among patients with pineal germinomas, males prevailed, while more females had suprasellar germinomas. No statistical difference was found between gender and bifocal germinoma. Pineal germinomas were manifested predominantly by the development of the dorsal midbrain syndrome in the form of oculomotor and pupillary dysfunction (75%) and the development of papilledema (53%). Germinomas of suprasellar localization are most often presented by asymmetric chiasmatic syndrome (24%). Dorsal midbrain syndrome in patients with bifocal germinomas was detected in 76% cases, combination of oculomotor and pupillary dysfunction with visual impairments was found in 38% cases. Neuro-ophthalmological symptoms of germinoma of these regions manifest in the early stages of the disease and require ophthalmological examination during all stages of diagnosis and treatment.

Management of hydrocephalus in a pediatric bifocal germinoma

Germinomas represent the most frequent tumour type in the pineal region. However, the synchronous involvement of the suprasellar region, frequently termed bifocal intracranial germinoma (BFG) is quite rare. A literature search identified a further of 48 pediatric cases with a median age of 12.9 years. BFG is known to be highly radiosensitive. We presented a clinical case of pediatric bifocal germinoma. A 14-year-old boy presented with clinical features of progressive headaches since three months associated with vomits. MR showed two distinct lesions in the pineal and suprasellar regions. Neuroaxis spine MR was normal. Tumor markers for germ cell tumors from blood and cerebrospinal fluid were within the normal range. An endoscopic procedure was performed to treat the hydrocephalus (endoscopic third ventriculostomy) and, in the same procedure the suprasellar lesion was biopsied and the histology revealed a germinoma. She received chemotherapy and a focal radiotherapy covering the sites of primary disease and the ventricular system. Three months after the completion of treatment, the patient achieved a complete clinical and radiological response, which was maintained during the 5-years follow-up period. The optimum management of primary intracranial pineal and suprasellar (bifocal) germinomas still remains controversial. The definition as either localized or disseminated disease has major implications on required treatment and its associated late morbidity. Prospective studies with large cooperative groups worldwide and consensus meetings may reduce uncertainties regarding available management options.

RARE-28. HYPOTHALAMIC GERMINOMA AND NEUROSARCOIDOSIS: A TALE OF TWO PATHOLOGIES

Abstract CASE 1: 30-year-old Caucasian male with a history of hereditary cavernomas, testicular germ cell tumor s/p orchiectomy 2017 presented next year with a chief complain of increasing lethargy. MRI Brain showed a new expansile, homogenously enhancing hypothalamic lesion causing obstructive dilatation of the lateral ventricles. MRI of neuraxis was not concerning for leptomeningeal spread. Initial differentials included suprasellar germinoma vs chiasmatic hypothalamic glioma vs metastatic lesion. Biopsies X2 showed gliosis and granulomatous inflammation. Despite radiation treatment for the hypothalamic mass clinical course continued to deteriorate. CSF results showed RBC - 1,200; WBC - 51 with 77% lymphocytes, 3% neutrophils, 20% monocytes. FDG-PET did not reveal evidence of metastatic disease. He was treated presumptively for neurosarcoidosis with high-dose corticosteroids and azathioprine and later transitioned to methotrexate and infliximab. Follow up MRI scans showed a reduction in the hypothalamic mass. CASE 2: A 23-year-old African American male treated for ADEM in 2010 presented to clinic with behavioral problems in 2017. Initial presentation included lethargy with imaging showing an incidental hypothalamic mass. Initial differentials included germinoma vs infundibular hypophysitis vs granulomatous process. He was treated with immunotherapy (corticosteroids and IVIG) with partial resolution of the growth. He was later diagnosed with suprasellar germinoma on biopsy subsequently treated with 2 cycles chemotherapy and proton beam radiotherapy in 2012. In 2017. to exclude tumor recurrence an LP showed elevated ACE however remainder of the clinical picture was not suggestive of neurosarcoidosis. DISCUSSION: Multiple case series have been described wherein hypothalamic germinoma mimics isolated neurosarcoidosis and vice-versa. Because of similar clinical picture and radiographic findings, the diagnosis is challenging. ACE is a nonspecific test for neurosarcoidosis, and it can be positive in the setting of germinoma as well. Hence specific molecular markers may be helpful in the diagnosis.

Is there variable neuronal susceptibility to compression?

A 12-year-old boy with suprasellar germinoma complicated by hydrocephalus was found to have dorsal midbrain syndrome and bilateral compressive optic neuropathy. Following a third ventricular neuroendoscopic biopsy and the initiation of chemotherapy, a follow-up magnetic resonance imaging scan of the brain showed significant regression of the tumor with resolution of hydrocephalus. On smooth pursuit, there was significant improvement in upgaze. However, light-near dissociation of his pupillary defect was persistent. Fundal examination showed persistent temporal pallor of the optic discs bilaterally, associated with a suboptimal best-corrected visual acuity of 20/40 and bilateral centrocecal scotoma.The differential recovery of neuronal function following relief of compression is poorly understood. In this case, both the optic nerve and pretectal axonal fibers responsible for pupillary reflex, with their neuronal cell bodies residing outside the direct compressive site at the midbrain, showed poor functional recovery. However, relief of pressure at the rostral interstitial medial longitudinal fasciculus and posterior commissure nuclear complexes resulted in significant clinical improvement in upgaze.&#x0D; This case suggests that, for neurons, axons are apparently more susceptible to pressure than cell bodies. The predominant transmission of nerve impulses takes place through the length of axons, and thus is more sensitive to pressure changes, with the associated microvascular compromise and demyelination.&#x0D; &#x0D;

Neuropsychological Consequences for Survivors of Childhood Brain Tumor in Malaysia.

Objective: This study aimed to evaluate neuropsychological consequences in survivors of childhood brain tumor.Method: A case-control study was conducted over a period of 4 months in a tertiary referral center in Kuala Lumpur, Malaysia. Fourteen survivors of childhood brain tumor aged 7–18 years, who were off-treatment for at least 1 year and were in remission, and 31 unrelated healthy controls were recruited. The median age at diagnosis was 8.20 years (range: 0.92–12.96 years). The diagnoses of brain tumors were medulloblastoma, germ cell tumor, pineocytoma, pilocystic astrocytoma, suprasellar germinoma, and ependymoma. Eleven survivors received central nervous system irradiation. Seven tasks were selected from the Amsterdam Neuropsychological Tasks program to evaluate alertness (processing speed), and major aspects of executive functioning, such as working memory capacity, inhibition, cognitive flexibility, and sustained attention. Speed, stability and accuracy of responses were the main outcome measures.Results: Survivors of childhood brain tumor showed statistically significant poorer performance on all tasks compared to healthy controls. Both processing speed and accuracy were impaired in the survivors, in particular under more complex task conditions. The survivors demonstrated deficits in alertness, sustained attention, working memory capacity, executive visuomotor control, and cognitive flexibility. Longer duration off treatment appeared to be correlated with poorer alertness, memory capacity, and inhibition.Conclusion: Survivors of childhood brain tumor in our center showed impaired neuropsychological functioning. Development of less toxic treatment protocols is important to prevent late effects of cognitive deficits in survivors of childhood brain tumor.

Successful live birth in a patient who underwent cranial radiotherapy and systemic chemotherapy by implantation of a cryopreserved blastocyst on day 7

Preservation of fertility has been recommended for cancer-bearing patients of reproductive age before undergoing cancer treatment. However, there are many considerations and it is difficult to preserve fertility for all patients undergoing therapy for malignancies. Female cancer survivors had lower pregnancy and live birth rates compared with others that underwent assisted reproductive technologies (ARTs). We should continue to consider the issue of infertility in patients who underwent therapies for malignancies. This is the first report of a successful live birth in a patient with a cranial tumor who underwent radiotherapy and chemotherapy after implantation of an autologous embryo. The patient was a 27-year-old Japanese woman. She was diagnosed with suprasellar germinoma at 13 years of age, and she developed panhypopituitarism after radiotherapy and chemotherapy. At 27 years of age, she began infertility treatment with in-vitro fertilization (IVF). The level of anti-Mallerian hormone (AMH) was 4.29 ng/ml. After ovarian stimulation by high purified human menopausal gonadotropin (HP-hMG), she obtained two blastocysts and became pregnant by implantation of a cryopre- served blastocyst. At 37 gestational weeks, she delivered a healthy female baby by cesarean section.

Treatment outcomes of primary suprasellar and pineal germinoma and related therapeutic strategies: an analysis of 41 patients

Objective To investigate the treatment outcomes of 41 patients with suprasellar and pineal germinoma who are treated in our department in recent 18 years, and to explore related therapeutic strategies. Methods A total of 41 patients with concurrent suprasellar and pineal germinoma who were treated in our department from January 1996 to August 2013 were enrolled. There were 35 male patients and 6 female patients, and the median age was 16 years (range 5-39 years). Five patients had pathologically confirmed germinoma and 36 patients had clinically diagnosed germinoma. Conventional radiotherapy was performed for 33 patients, and intensity-modulated radiotherapy was performed for 8 patients. Combined-modality chemoradiotherapy was performed for the 5 patients with pathologically diagnosed germinoma. The 6 MV X-ray was applied for radiotherapy; 6 patients received whole ventricular irradiation and a boost in tumor region, 16 received whole-brain radiotherapy and a boost in tumor region, and 19 received craniospinal irradiation and a boost in tumor region. The median radiation dose for tumor region was 45.0 Gy (37.8-50.0 Gy), and the median dose for prophylactic irradiation was 25.0 Gy (17.8-35.0 Gy). The survival was caculated using Kaplan-Meier method. Results The number of patients followed were 26 at 5-years. The 5-year overall survival rate and relapse-free survival rate were 95% and 85%, respectively. Relapse and metastasis were noted in 8 patients, and 3 of them died. There were 4 patients with spinal cord metastasis, 1 patient with ventricular dissemination, and 3 patients with periventricular relapse. Among the 22 patients who did not undergo spinal irradiation, 4(18.2%) experienced spinal cord metastasis, and all the other 19 patients who underwent spinal irradiation did not experience spinal cord metastasis. The 8 patients undergoing intensity-modulated radiotherapy and the 5 patients undergoing combined-modality chemoradiotherapy did not experience treatment failure during follow-up. Conclusions Radiotherapy for intracranial germinoma has a good therapeutic effect, and the patients with suprasellar and pineal germinoma who do not undergo spinal cord irradiation have a high failure rate. It is suggested to perform spinal cord irradiation for patients with suprasellar and pineal lesions. Key words: Intracranial neoplasms/radiotherapy; germ cell tumor/germinoma; Craniospinal irradiation; Treatment outcome