Intradural "limited drill" technique of anterior clinoidectomy and optic canal unroofing for microneurosurgical management of ophthalmic segment and PCOM aneurysms-review of surgical results.

To evaluate the safety and efficacy of intradural "limited drill" technique (ILDT) of anterior clinoidectomy (AC) and optic canal unroofing (OCU) for microneurosurgical management of ophthalmic segment and posterior communicating artery (PCOM) aneurysms. All the patients with ophthalmic segment and PCOM aneurysms who underwent AC and OCU by ILDT for microneurosurgical management of ophthalmic segment and PCOM aneurysms during 4-year period (2013-2016) at our Institute were included in this study. In ILDT of AC and OCU, the use of power drill is restricted to AC only and OCU is done exclusively with 1-mm Kerrison punch. AC and OCU by ILDT were done in 24 patients with 29 ophthalmic segment and 7 PCOM aneurysms. AC and OCU by ILDT helped in mobilization of optic nerve/internal carotid artery (ICA) and provided excellent exposure for all these aneurysms. There was no injury to ICA or optic nerve during drilling. AC and OCU facilitated clip ligation of 34 of these aneurysms. Remaining 2 aneurysms were considered not suitable for clipping. Check angiogram done for 33 aneurysms revealed complete obliteration of 26 aneurysms, very small residual neck in 5 aneurysms, and small residual aneurysm in 2 aneurysms. Deterioration in vision was noted in 1 patient (4.1%). In 6 patients with preoperative visual deficits, significant improvement in vision was noted in 4 patients (4/6-66.6%) after surgery. Good outcome (MRS < 2) was noted in 91.6% (22/24) of these patients. ILDT is a safe and effective technique of AC and OCU which provide good exposure for ophthalmic segment and PCOM aneurysms.

Deep flexor sarcopenia as a predictor of poor functional outcome after anterior cervical discectomy in patients with myelopathy.

BACKGROUND: Paraspinal muscle morphometry has been recognized to be a prognostic factor across various surgical conditions, but its utility in predicting disease-specific outcomes in spine surgery remains under-explored. METHODS: A prospective cohort study was performed on 45 consecutive patients undergoing anterior cervical discectomy (ACD) for single-level, symptomatic cervical degenerative disc disease causing radiculomyelopathy or myelopathy. Previously described predictors of outcome such as age, gender, smoking, comorbidities, duration of symptoms, preoperative Nurick grade, extent of cord compression, and signal intensity change in the cord were recorded. Additionally, MRI-based morphometrics of the superficial and deep paraspinal muscles were recorded. Logistic regression (LR) analysis was performed using a purposeful variable selection process to identify variables that independently predicted Nurick grade improvement (NGI). RESULTS: At a mean follow-up of 20.02 ± 8.63 months after ACD, 37 (82.22%) patients demonstrated NGI. LR analysis yielded three predictors of NGI of which two were related to the deep flexor muscles. While a worse preoperative Nurick grade negatively predicted NGI, a deep flexor area and deep flexor/deep extensor area ratio positively predicted NGI. The regression model demonstrated a good fit and was statistically significant (χ2(3) = 22.18, p < 0.0001). The model explained 64% of the variance in NGI and correctly classified 89% of cases. CONCLUSIONS: This study has for the first time identified the utility of paraspinal morphometrics in predicting disease-specific functional outcome after cervical spine surgery. Our results indicate that in addition to preoperative Nurick grade, an already accepted outcome predictor, the deep flexor cross-sectional area, and the deep flexor/deep extensor ratio are strong predictors of NGI following ACD for single-level, symptomatic cervical degenerative disc disease with myelopathy. Deep muscle morphometrics could be included in future risk stratification algorithms for patients with cervical disc disease.

Comparison of telemedicine with in-person care for follow-up after elective neurosurgery: results of a cost-effectiveness analysis of 1200 patients using patient-perceived utility scores.

OBJECTIVE The utility of telemedicine (TM) in neurosurgery is underexplored, with most of the studies relating to teletrauma or telestroke programs. In this study, the authors evaluate the cost-effectiveness of TM consultations for follow-up care of a large population of patients who underwent neurosurgical procedures. METHODS A decision-analytical model was used to assess the cost-effectiveness of TM for elective post-neurosurgical care patients from a predominantly nonurban cohort in West Bengal, India. The model compared TM care via a nodal center in West Bengal to routine, in-person, per-episode care at the provider site in Bangalore, India. Cost and effectiveness data relating to 1200 patients were collected for a 52-month period. The effectiveness of TM care was calculated using efficiency in terms of the percentage of successful TM consultations, as well as patient-perceived utility values for overall experience of the type of health care access that they received. Incremental cost-effectiveness ratio (ICER) analysis was done using the 4-quadrant charting of the cost-effectiveness plane. One-way sensitivity and tornado analyses were performed to identify thresholds where the care strategy would change. RESULTS The overall utility for the 3 TM scenarios was found to be higher (89%) than for the utility of routine care (80%). TM was found to be more cost-effective (Indian rupee [INR] 2630 per patient) compared to routine care (INR 6848 per patient). The TM strategy "dominates" that of routine care by being more effective and less expensive (ICER value of -39,400 INR/unit of effectiveness). Sensitivity analysis revealed that cost-effectiveness of TM was most sensitive to changes in the number of TM patients, utility and success rate of TM, and travel distance to the TM center. CONCLUSIONS TM care dominates the in-person care strategy by providing more effective and less expensive follow-up care for a remote post-neurosurgical care population in India. In the authors' setting, this benefit of TM is sustainable even if half the TM consultations turn out to be unsuccessful. The viability of TM as a cost-effective care protocol is attributed to a combination of factors, like an adequate patient volume utilizing TM, patient utility, success rate of TM, and the patient travel distance.

Decompressive surgery in malignant cerebral venous sinus thrombosis: what predicts its outcome?

Cerebral venous sinus thrombosis (CVST) is common in Asians, accounting for 15% of all strokes in the young. CVST causing malignant cerebral oedema with brain herniation and death are referred as malignant CVST. This study was aimed at evaluating the outcome of patients and factors predicting the outcome with malignant CVST after decompressive surgery. It was a retrospective, observational, single centre, hospital-based and cross-sectional study. Records of patients with malignant CVST who had decompressive surgery were analysed. Over 5 years (2010-2015), 30 patients (15 men and 15 women) underwent decompressive surgery. In univariate analysis, age more than 50 years (p = 0.05); presence of midline shift of more than 10 mm (p = 0.03) and total effacement of basal cisterns (p = 0.01) had significant correlation with poor outcome. On multivariate analysis, presence of midline shift of more than 10 mm (p = 0.01) was a significant predictor of poor outcome. Decompressive surgery is a life saving therapeutic intervention in patients with malignant CVST and more than two-thirds of patient shows favourable outcome. Age more than 50 years, midline shift >10 mm and total effacement of basal cisterns determine poor outcome following decompressive surgery.

Pneumosinus dilatans of the spheno-ethmoidal complex associated with hypovitaminosis D causing bilateral optic canal stenosis.

INTRODUCTION: Pneumosinus dilatans (PSD) is a rare disorder of undetermined etiology characterized by expansion of the paranasal sinuses without bony erosion. Of the few cases of PSD described in indexed pediatric literature, there has been no reported case of this disorder presenting with optic canal stenosis in the setting of a vitamin deficiency. CASE MATERIAL: A 12-year-old girl presented with a 3-month history of progressive, painless, and asymmetric visual deterioration in her eyes. MRI showed prominent perioptic CSF spaces bilaterally and mild atrophy of both the optic nerves. CT head showed hyperpneumatization of the sphenoethmoidal air cells and both anterior clinoid processes with the optic nerves contained within narrowed intact bony canals. Blood investigations showed reduced vitamin D levels, and a subsequent skeletal survey showed diffuse osteopenia. She underwent endoscopic sphenoidotomy and bilateral decompression of the optic nerves. Following surgery, she reported improvement of vision in her left eye. She was started on vitamin D supplements for the endocrine abnormality. At a follow-up visit 6 months later, her visual acuity in both her eyes had improved. CONCLUSION: Pneumosinus dilatans is an unusual cause of progressive optic nerve dysfunction in the pediatric population. In the absence of any associated intracranial pathologies, conditions like hypovitamosis D should be ruled out.

Glioblastoma-derived Macrophage Colony-stimulating Factor (MCSF) Induces Microglial Release of Insulin-like Growth Factor-binding Protein 1 (IGFBP1) to Promote Angiogenesis.

Glioblastoma (grade IV glioma/GBM) is the most common primary adult malignant brain tumor with poor prognosis. To characterize molecular determinants of tumor-stroma interaction in GBM, we profiled 48 serum cytokines and identified macrophage colony-stimulating factor (MCSF) as one of the elevated cytokines in sera from GBM patients. Both MCSF transcript and protein were up-regulated in GBM tissue samples through a spleen tyrosine kinase (SYK)-dependent activation of the PI3K-NFκB pathway. Ectopic overexpression and silencing experiments revealed that glioma-secreted MCSF has no role in autocrine functions and M2 polarization of macrophages. In contrast, silencing expression of MCSF in glioma cells prevented tube formation of human umbilical vein endothelial cells elicited by the supernatant from monocytes/microglial cells treated with conditioned medium from glioma cells. Quantitative proteomics based on stable isotope labeling by amino acids in cell culture showed that glioma-derived MCSF induces changes in microglial secretome and identified insulin-like growth factor-binding protein 1 (IGFBP1) as one of the MCSF-regulated proteins secreted by microglia. Silencing IGFBP1 expression in microglial cells or its neutralization by an antibody reduced the ability of supernatants derived from microglial cells treated with glioma cell-conditioned medium to induce angiogenesis. In conclusion, this study shows up-regulation of MCSF in GBM via a SYK-PI3K-NFκB-dependent mechanism and identifies IGFBP1 released by microglial cells as a novel mediator of MCSF-induced angiogenesis, of potential interest for developing targeted therapy to prevent GBM progression.

PI3 kinase pathway regulated miRNome in glioblastoma: identification of miR-326 as a tumour suppressor miRNA.

BACKGROUND: Glioblastomas (GBM) continue to remain one of the most dreaded tumours that are highly infiltrative in nature and easily preclude comprehensive surgical resection. GBMs pose an intricate etiology as they are being associated with a plethora of genetic and epigenetic lesions. Misregulation of the PI3 kinase pathway is one of the most familiar events in GBM. While the PI3 kinase signalling regulated pathways and genes have been comprehensively studied, its impact on the miRNome is yet to be explored. The objective of this study was to elucidate the PI3 kinase pathway regulated miRNAs in GBM. METHODS: miRNA expression profiling was conducted to monitor the differentially regulated miRNAs upon PI3 kinase pathway abrogation. qRT-PCR was used to measure the abundance of miR-326 and its host gene encoded transcript. Proliferation assay, colony suppression assay and wound healing assay were carried out in pre-miR transfected cells to investigate its role in malignant transformation. Potential targets of miR-326 were identified by transcriptome analysis of miR-326 overexpressing cells by whole RNA sequencing and selected targets were validated. Several publically available data sets were used for various investigations described above. RESULTS: We identified several miRNA that were regulated by PI3 kinase pathway. miR-326, a GBM downregulated miRNA, was validated as one of the miRNAs whose expression was alleviated upon abrogation of the PI3 kinase pathway. Overexpression of miR-326 resulted in reduced proliferation, colony suppression and hindered the migration capacity of glioma cells. Arrestin, Beta 1 (ARRB1), the host gene of miR-326, was also downregulated in GBM and interestingly, the expression of ARRB1 was also alleviated upon inhibition of the PI3 kinase pathway, indicating similar regulation pattern. More importantly, miR-326 exhibited a significant positive correlation with ARRB1 in terms of its expression. Transcriptome analysis upon miR-326 overexpression coupled with integrative bioinformatics approach identified several putative targets of miR-326. Selected targets were validated and interestingly found to be upregulated in GBM. CONCLUSIONS: Taken together, our study uncovered the PI3 kinase regulated miRNome in GBM. miR-326, a PI3 kinase pathway inhibited miRNA, was demonstrated as a tumour suppressor miRNA in GBM.

Visual Deterioration and Herniation of the Anterior Cerebral Artery: Unusual Presentation of an Empty Sella Syndrome Complicating Decompression of a Rathke Cleft Cyst.

Clinical manifestations of empty sella syndrome include hypopituitarism cerebrospinal fluid rhinorrhea, headache, and visual abnormalities. A 21-year-old woman reported a 6-month history of worsening vision 3 years after decompression of a sellar-suprasellar Rathke cleft cyst. Her magnetic resonance imaging (MRI) showed a well-defined recurrent cyst in the sellar-suprasellar region causing chiasmatic compression. She underwent an endonasal, endoscopic decompression of the cyst, with subsequent improvement in her vision. A postoperative computed tomography confirmed good decompression of the cyst. Ten days after surgery, she reported sudden loss of vision in both eyes. MRI revealed an empty sella with herniation of both anterior cerebral arteries and optic chiasm into the sella. She underwent transnasal packing of the sellar floor with fat graft and bone plaques, and experienced gradual improvement in vision in her right eye.

Methylation silencing of ULK2, an autophagy gene, is essential for astrocyte transformation and tumor growth.

Glioblastoma (GBM) is the most aggressive type of brain tumor and shows very poor prognosis. Here, using genome-wide methylation analysis, we show that G-CIMP+ and G-CIMP-subtypes enrich distinct classes of biological processes. One of the hypermethylated genes in GBM, ULK2, an upstream autophagy inducer, was found to be down-regulated in GBM. Promoter hypermethylation of ULK2 was confirmed by bisulfite sequencing. GBM and glioma cell lines had low levels of ULK2 transcripts, which could be reversed upon methylation inhibitor treatment. ULK2 promoter methylation and transcript levels showed significant negative correlation. Ectopic overexpression of ULK2-induced autophagy, which further enhanced upon nutrient starvation or temozolomide chemotherapy. ULK2 also inhibited the growth of glioma cells, which required autophagy induction as kinase mutant of ULK2 failed to induce autophagy and inhibit growth. Furthermore, ULK2 induced autophagy and inhibited growth in Ras-transformed immortalized Baby Mouse Kidney (iBMK) ATG5(+/+) but not in autophagy-deficient ATG5(-/-) cells. Growth inhibition due to ULK2 induced high levels of autophagy under starvation or chemotherapy utilized apoptotic cell death but not at low levels of autophagy. Growth inhibition by ULK2 also appears to involve catalase degradation and reactive oxygen species generation. ULK2 overexpression inhibited anchorage independent growth, inhibited astrocyte transformation in vitro and tumor growth in vivo. Of all autophagy genes, we found ULK2 and its homologue ULK1 were only down-regulated in all grades of glioma. Thus these results altogether suggest that inhibition of autophagy by ULK1/2 down-regulation is essential for glioma development.

Extensive anterior skull-base mesenchymal chondrosarcoma: unusual cause of multiple indolent masses on the forehead.

Primary intracranial occurrence of an extraskeletal mesenchymal chondrosarcoma (MC) is unusual. The commonly involved sites are the orbit, clivus and temporo-occipital junction. Occurrence of the lesion in the anterior skull-base (ASB) in an infiltrative manner and with extra-calvarial involvement, is anecdotal. We report the case of a 35-year-old woman who presented with two indolent swellings on the forehead for a duration of 1 year. Examination revealed impaired visual acuity and complete external ophthalmoplegia in the right eye and 5 × 6 cm and 2 × 3 cm sized hard masses on the forehead. CT and MRI revealed a large, intensely enhancing ASB mass with extensions into the right orbit, ethmoid sinus, nasal cavity, and anteriorly, into the subcutaneous tissue of the frontal scalp through erosions in the bone. At surgery via a right frontal recraniotomy, the lesion was found to be firm and very vascular. Owing to its extreme vascularity, decompression was limited to excision of the intracranial and extra-calvarial components of the lesion. Histopathology was consistent with the diagnosis of MC. The patient was advised a second stage surgery for excision of the residual lesion. She, however, opted for radiation therapy and was lost to follow-up. This report, with one of the most extensive ASB MCs described to date, adds to the list of rare differentials of indolent forehead masses in the diagnostic armamentarium of the neuropathologist.

Surgical management of thalamic gliomas: case selection, technical considerations, and review of literature.

This study aimed to identify (1) the thalamic gliomas suitable for surgical resection and (2) the appropriate surgical approach based on their location and the displacement of the posterior limb of the internal capsule (PLIC). A retrospective study over a 5-year period (from 2006 to 2010) was performed in 41 patients with thalamic gliomas. The mean age of these patients was 20.4 years (range, 2-65 years). Twenty (49 %) tumors were thalamic, 19 (46 %) were thalamopeduncular, and 2 (5 %) were bilateral. The PLIC, based on T2-weighted magnetic resonance axial sections, was displaced anterolaterally in 23 (56 %) cases and laterally in 6 (14 %) cases. It was involved by lesion in eight (20 %) cases and could not be identified in four (10 %) cases. Resection, favored in patients with well-defined, contrast-enhancing lesions, was performed in 34 (83 %) cases, while a biopsy was resorted to in 7 (17 %) cases. A gross total resection or near total resection (>90 %) could be achieved in 26 (63 %) cases. The middle temporal gyrus approach, used when the PLIC was displaced anterolaterally, was the commonly used approach (63.5 %). Common pathologies were pilocytic astrocytoma (58 %) in children and grade III/IV astrocytomas (86 %) in adults. Preoperative motor deficits improved in 64 % of the patients with pilocytic lesions as compared to 0 % in patients with grade III/IV lesions (P value, 0.001). Postoperatively, two patients (5 %) had marginal worsening of motor power, two patients developed visual field defects, and one patient developed a third nerve paresis. Radical resection of thalamic gliomas is a useful treatment modality in a select subset of patients and is the treatment of choice for pilocytic astrocytomas. Tailoring the surgical approach, depending on the relative position of the PLIC, has an important bearing on outcome.

How I do it : anterior clinoidectomy and optic canal unroofing for microneurosurgical management of ophthalmic segment aneurysms.

BACKGROUND: Power drilling commonly used for anterior clinoidectomy and optic canal unroofing can result in thermal injury to the optic nerve. METHODS: The authors describe an intradural "limited drill" technique of anterior clinoidectomy and optic canal unroofing for microneurosurgical management of ophthalmic segment aneurysms, where optic canal unroofing is done with 1 mm Kerrison punch and the use of the power drill is restricted to anterior clinoidectomy to avoid thermal injury to the optic nerve. The optic nerve, internal carotid artery (ICA), and aneurysm are covered with wet gelfoam pieces to prevent any inadvertent contact with the drill. CONCLUSION: "Limited drill technique" is a safe and effective technique of anterior clinoidectomy and optic canal unroofing. KEY POINTS: • Anterior clinoidectomy and optic canal unroofing is an important skull base technique required for safe clipping of the majority of ophthalmic segment aneurysms • Power drilling commonly used for optic canal unroofing can cause thermal injury to optic nerve • More than 2 mm free space is available around the optic nerve in the optic canal • Foot plate of 1 mm Kerrison punch can be safely introduced within a normal optic canal without causing mechanical injury to the optic nerve • Reflection of posteriorly based dural flap acts as a dural barrier, preventing direct contact of drill bit to optic nerve, internal carotid artery and aneurysm during drilling • Entanglement of cottonoids to rotating drill bit is a major problem in intradural anterior clinoidectomy • Wet gelfoam pieces do not get entangled to the rotating drill bit • Structures surrounding the area of drilling can be covered with wet gel foam pieces to prevent direct contact of the drill to neurovascular structures • Opened cisterns can be covered with wet gelfoam pieces during drilling to prevent deposition of bone dust in the subarachnoid space • "Limited drill technique" of anterior clinoidectomy and optic canal unroofing is a safe and effective technique for the exposure of ophthalmic segment aneurysms.

Subgaleo-peritoneal shunt: An effective and safer alternative to lumboperitoneal shunt in the management of persistent or recurrent iatrogenic cranial pseudomeningoceles.

Subgaleo-peritoneal (SP) shunting for pseudomeningoceles (PMCs) is an effective and safer alternative as compared to the lumboperitoneal (LP) shunt. SP shunting was done in six patients (14-60 years) with persistent or recurrent PMCs using the cranial (ventricular part) and the distal parts of a Chhabra shunt connected by a rigid connector without any intervening chamber or valve. Two patients had undergone a prior LP shunt that had failed. One patient was unsuitable for a LP shunt placement. The PMC subsided completely in all the patients following the SP shunt. In one patient, the shunt got displaced and required repositioning. None of the patients developed symptoms of over-drainage or any other complication. All patients were asymptomatic at a mean follow-up of 15 months. These results suggest that SP shunting is a safe, simple, and effective alternative to the traditional LP shunt in the management of persistent or recurrent cranial PMCs.

A nondysraphic paraspinal mass and a ventricular septal defect: unusual components of diabetes-induced mesodermal derangement.

Solitary paraspinal masses in the pediatric age group commonly occur secondary to spinal dysraphism, chronic inflammatory conditions, and tumors. We describe the unusual case of a 10-year-old boy with a nondysraphic, paraspinal mass that had occurred secondary to congenital spinal epidural lipomatosis (SEL) in the setting of poorly controlled maternal type-I diabetes mellitus. The mass was picked up along with a ventricular septal defect (VSD) on an antenatal ultrasonogram. This is the first report in literature of SEL presenting as a solitary paraspinal mass at birth, and in the unusual setting of an antenatal mesodermal derangement that simultaneously engendered a VSD.

Mixed schwannoma with meningioma - report on 2 cases of unusual tumor with review of literature.

We present 2 rare cases of mixed schwannoma with meningioma. The first case was sporadic, in a 38-year-old female in cervical spine (C2). The second case was a 24-year-old female, associated with NF-2, involving bilateral cerebellopontine angle with extension into the left cavernous sinus, sellar region with erosion of the petrous ridge and multiple intradural extramedullary lesions in the spinal cord suggestive of neurofibromas. To date only 12 cases of such tumors are documented in the literature. To the best of our knowledge this is the first case of sporadic mixed schwannoma with meningioma in cervical spine (C2).

Multiple intracranial de-novo chloromas presenting with Garcin's syndrome.

Intracranial occurrence of a chloroma (myeloid sarcoma, MS) in the absence of a preceding hematological malignancy is unusual. We report the case of a 20-year-old man who presented with Garcin's syndrome of short duration. MRI revealed multiple extra-axial contrast enhancing lesions: two mirror lesions on the skull base, and one in the right parietal convexity. The parietal lesion was excised and histologically and immunohistochemically proved to be a differentiated variant of MS. Peripheral blood smear and bone marrow biopsy ruled out an underlying leukemia or myeloproliferative disorder. With a diagnosis of intracranial de-novo MS, he was referred for chemotherapy and radiation therapy. 15 months later, his clinical status remained the same while his imaging showed marginal decrease in size of the lesions. A repeat bone marrow biopsy remained normal. This is a first-of-its- kind report of multiple intracranial lesions of a de-novo MS presenting as Garcin's syndrome. Radiological differentials, immunohistochemical variants and management options related to MS are discussed in the light of the reported case.

Management of oculomotor nerve schwannomas in two different locations: surgical nuances and comprehensive review.

Rare tumors with anecdotal reportage, oculomotor schwannomas are most often seen in the oculomotor cistern close to the anterior clinoidal region. Adding to the small series of reported cases of this unusual lesion, we report two male patients in their second decade who presented with different degrees of oculomotor palsy. The location of the lesion was caverno-cisternal in one case and orbito-cavernous in the other. Intricate neurovascular relationships of this lesion, especially in non-cavernous locations, are discussed. The risk of damage to nerve rootlets enmeshed within the lesion is high with attempts at near-total excision, rendering the anatomical preservation of the nerve an arduous exercise. The authors review literature pertaining to this unusual lesion and elucidate surgical nuances which may have a bearing on outcome.

Fatal leptomeningeal melanoma in neurocutaneous melanosis.

We report an unusual occurrence of a primary dural-based malignant melanoma in a 13-year-old boy with neurocutaneous melanosis. The lesion presented with rapid-onset symptoms characterized by raised intracranial pressure and seizures, had an aggressive clinical course, and proved to be fatal despite two surgeries and adjuvant therapy. There should be a high index of suspicion for the occurrence of such a malignant leptomeningeal tumor in patients with congenital melanocytic nevi presenting with neurological symptoms of recent onset.

Atypical presentation of pediatric mixed germ cell tumors in the sellar-suprasellar region.

Intracranial germ cell tumors constitute a unique group of tumors, more often reported from the Asian region. Amongst them, the non-germinomatous variety occurs with a lesser frequency than the germinomatous variety. We report two children with mixed germ cell tumors with unusual clinical presentations: Central diabetes insipidus and recent-onset oculomotor palsy mimicking pituitary apoplexy. Unlike in adults, suprasellar lesions with a pituitary apoplexy-like picture in the pediatric age group may suggest a possibility of a mixed germ cell tumor.