Cerebral swelling caused by deep venous thrombosis immediately after cranioplasty.

Recently, different groups have reported a rare, unexplained complication of sudden death with massive cerebral oedema immediately after cranioplasty.Case presentation: A 34-year-old woman underwent decompressive hemicraniectomy after traumatic brain injury. She was reportedly on oral contraceptives. She developed massive cerebral swelling immediately after an uneventful cranioplasty. After surgery, her pupils became fixed and dilated, and brain MRI revealed massive brain oedema. Magnetic resonance venography displayed occlusion in the deep venous sinus. The oedema was believed to be caused by venous sinus thrombosis. The patient's family declined to avail any surgical and medical treatment, and the patient died on the second postoperative day.Conclusions: Fatal massive cerebral oedema is an uncommon complication after cranioplasty in patients who had previously undergone decompressive craniectomy. Our patient was using oral contraceptives and was thus susceptible to the development of venous sinus thrombosis. Neurosurgeons must be aware of the complications associated with venous sinus thrombosis and discuss it with the patients and their families.

A subarachnoid pleural fistula with massive crystal-clear pleural fluid caused by a lumbar epidural teratoma.

A subarachnoid pleural fistula - a connection between the pleural cavity and the subarachnoid space - generally presents after trauma or surgery. A 1-year 11-month-old girl without a history of trauma or surgery presented with fatigue, cyanosis and dyspnoea. A chest radiograph and computed tomography (CT) demonstrated a massive pleural effusion in the right hemithorax. About 300 ml of a crystal-clear pleural effusion, which looked like pure water, was removed by insertion of a chest drain, but it continued to collect. Cisternography and CT myelography confirmed leakage of cerebral spinal fluid into the right pleural cavity around the thoracolumbar region. Magnetic resonance imaging demonstrated an 11-mm enhanced nodule in the epidural space around the right lumbar (L) 1/2 intervertebral foramen. The patient underwent surgery and epidural tumours attached to the L1 nerve root foramen were completely resected and a fistula of the dura adjacent to the tumour was sutured. Histopathological examination demonstrated a mature teratoma containing a pancreatic component. On retrospective analysis of stored pleural fluid, a raised level of pancreatic enzymes was detected. It is presumed that digestive enzymes secreted by the pancreatic component of the teratoma lysed the dura, resulting in formation of the fistula. When a crystal-clear pleural effusion is present, even in the absence of trauma or surgery, a subarachnoid pleural fistula should be considered. As far as we know, this is the first report of a subarachnoid pleural fistula caused by a paravertebral teratoma.Abbreviations: CSF: cerebrospinal fluid; CT: computed tomography; 111In-DTPA: indium-111 diethylene triamine penta-acetic acid; MRI: magnetic resonance imaging; NIPPV: non-invasive positive pressure ventilation.

Spinal cord subependymoma mimicking syringomyelia in a child: a case report.

Spinal cord subependymomas (SCSEs) in children are extremely rare, and no reports distinguishing SCSEs from syringomyelia have been published. We report a case of a 10-year-old boy who presented with torticollis, scoliosis, as well as pain that had begun in the posterior portion of the neck and progressed to the right shoulder and upper arm. Magnetic resonance imaging showed an intramedullary cyst-like lesion with the same signal intensity as that of cerebrospinal fluid. Idiopathic syringomyelia with scoliosis was first suspected, and a syrinx-subarachnoid space shunt was performed. After surgery, the lesion was slightly smaller; however, 2 years after surgery, it had re-grown, causing excruciating pain but no other symptoms. A second surgery was performed, and gross total resection was achieved. Pathological evaluation revealed SCSE. SCSE needs to be considered as a differential diagnosis for spinal centric cyst-like lesions in children.

Reversible cerebral vasoconstriction syndrome concomitant with cerebral venous sinus thrombosis following ovarian tumor resection: A report of two cases.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) presents with characteristic clinical, brain imaging, and angiographic findings. The most common clinical feature of RCVS is a severe acute headache, which is often referred to as a thunderclap headache due to the nature of its presentation. It may occur spontaneously or may be provoked by various precipitating factors. We present a rare case of RCVS concomitant with cerebral venous sinus thrombosis (CVST) in a woman who underwent resection of an ovarian tumor. CASE DESCRIPTION: Case 1 - A 42-year-old woman was admitted to our hospital with severe headache radiating to the neck, with associated vomiting. She revealed a medical history of ovarian cancer and underwent an operation for the resection of the tumor, a month before presentation. After resection, her estradiol (E2) levels were reduced from 288 pg/ml to 31 pg/ml (normal range, 0-49 pg/ml). Initial imaging on admission to our hospital revealed the left posterior convexity subarachnoid hemorrhage. Magnetic resonance angiography (MRA) showed findings consistent with RCVS affecting the left posterior cerebral artery. Magnetic resonance venography (MRV) showed CVST of the left transverse and sigmoid sinuses. Single-photon emission computed tomography (SPECT) showed a left posterior ischemic lesion. These findings improved following treatment with nimodipine and anticoagulant. Case 2 - A 39-year-old woman presented with holocranial headache associated with vomiting. She was diagnosed with an ovarian tumor. She underwent an operation 3 months before presentation. After tumor resection, her E2 level decrease from 193 pg/ml to 19 pg/ml (normal range, 0-49 pg/ml). Magnetic resonance angiography (MRA) confirmed the presence of a vasospasm involving the right anterior cerebral artery. Magnetic resonance venography (MRV) confirmed the presence of thrombosis involving the superior sagittal sinus. She was discharged on postpartum day 31 without neurological deficits after treatment with anticoagulants. At her 3-month follow-up, both MRA and MRV were within the normal limits. CONCLUSION: This is the first report of two women diagnosed with RCVS with concomitant CVST following ovarian tumor resection. Marked reductions in postoperative E2 levels could have contributed to the development of CVST and RCVS.

The Importance of STAT6 in a Schwannoma-like Grade III Solitary Fibrous Tumor/Hemangiopericytoma Located in the Cerebellopontine Angle and Meckel's Cave.

BACKGROUND: Hemangiopericytoma (HPC) is a rare mesenchymal tumor of the brain that occurs in the central nervous system as a solitary fibrous tumor. Surgical treatment of HPC is known to be beneficial, but results on the role of complete resection and adjuvant radiation are conflicting. However, it is often difficult to detect a central nervous system solitary fibrous tumor/HPC before surgery. We describe a presumed left trigeminal schwannoma that was histopathologically shown to be an HPC. CASE DESCRIPTION: A 65-year-old man presented with paresthesia of the second and third branches of the left trigeminal nerve. Magnetic resonance imaging showed a tumoral lesion in the left cerebellopontine angle and Meckel's cave. We suspected a schwannoma and performed surgery, which resulted in only a partial resection because of tumor bleeding and unexpected intraoperative histologic findings. We could not achieve a definitive diagnosis. However, we observed local recurrence and disseminated lesions 5 and 6.5 years later, respectively. We performed a second surgery and were able to definitively diagnose the lesion as a grade III HPC based on the positive expression of STAT6 during immunostaining. CONCLUSIONS: As solitary fibrous tumor/HPC requires gross total resection for effective resolution, it is imperative to consider it in the differential diagnoses of similar tumors. If an unusual pathologic image is found, we recommend rapid immunostaining for STAT6 to reach a definitive conclusion regarding the tumor type. This case highlights the importance of considering HPC when screening or diagnosing central nervous system lesions, especially in this rare location.

Radiation-Induced Spinal Cord Cavernous Malformations Associated with Medulloblastoma: Case Report and Review of the Literature.

BACKGROUND: Radiation-induced spinal cord cavernous malformations (CMs) are rare pathologies compared with radiation-induced cerebral CMs. We present a case of a radiation-induced spinal cord CM developed 31 years after radiation therapy for medulloblastoma. CASE DESCRIPTION: A 37-year-old man developed a symptomatic spinal hemorrhagic lesion 31 years after radiation therapy for medulloblastoma. Magnetic resonance imaging revealed an intramedullary cystic lesion with a fluid-fluid level in the C7 area. Surgery was performed leading to an unclear diagnosis. Two years later, the patient had a relapse and underwent a second operation, allowing a definitive diagnosis of radiation-induced spinal cord CM. This is believed to be the second case of de novo intramedullary CM formation following spinal radiation therapy for medulloblastoma. CONCLUSIONS: Radiation-induced spinal cord CMs should be recognized as a possible late adverse effect in patients treated with radiation therapy for medulloblastoma.

Intracranial Low-Grade Fibromyxoid Sarcoma: Findings on Electron Microscopy and Histologic Analysis.

BACKGROUND: Low-grade fibromyxoid sarcoma is a rare tumor that manifests as a deep soft tissue mass characterized by a benign histology, but with potentially aggressive clinical behavior and a high rate of recurrence; primary intracranial sarcomas are even rarer. We present a case of primary intracranial low-grade fibromyxoid sarcoma, emphasizing its clinical, radiologic, and histologic features. CASE DESCRIPTION: A 39-year-old woman presented with a recent history of headache and seizures. A right parietal mass was detected on computed tomography and magnetic resonance imaging, and she was subsequently operated on to remove the intracranial mass. Histologic examination of the resected tumor revealed mildly atypical fibroblastic cells embedded within a myxoid matrix. The diagnosis was confirmed by electron microscopy and cytogenetic analyses. CONCLUSIONS: This report describes electron microscopic evaluation of intracranial low-grade fibromyxoid sarcoma, which has an extremely rare occurrence.

Transient ischemic attack in elderly patient with PHACE syndrome.

BACKGROUND: Posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (PHACE) is a rare congenital anomaly with a broad spectrum of clinical manifestations. CASE DESCRIPTION: We describe a 75-year-old male with PHACE anomaly, aortic anomaly, malformation of brain, aplastic right carotid artery, and cervical vasculopathy. He presented with a transient ischemic attack with the left hemiparesis, a rare clinical presentation of the PHACE syndrome. He had an uneventful recovery and recently completed a 2-year follow-up after the superficial temporal artery to middle cerebral artery anastomosis. CONCLUSION: PHACE syndrome should be kept in mind, even in individuals of advanced age, in the instance of a TIA, especially in situations which may involve induced hypoperfusion.

Nocardia paucivorans cerebellar abscess: Surgical and pharmacotherapy.

BACKGROUND: Nocardia species are ubiquitous in nature and mainly cause pulmonary disease in humans; however, they can also infect the central nervous system and skin. The management of cerebellar nocardiosis is troublesome and requires multiple considerations of the severity of the underlying systemic disease, difficulties in identifying the bacterium, and frequent delay in initiating adequate therapy. CASE DESCRIPTION: We report a 52-year-old diabetic female patient with Nocardia paucivorans cerebellar abscesses. Brain magnetic resonance imaging (MRI) revealed innumerable small ring-enhancing lesions of posterior fossa. In this report, we present a case of primary single cerebellar abscesses due to N. paucivorans. Early diagnosis and surgical interventions were significant for the patient. The diagnosis was confirmed by DNA sequencing and the organism was susceptible to trimethoprim-sulfamethoxazole (TMP/SMX). The patient was successfully treated with drugs and surgical excision. CONCLUSION: According to the literature, surgical excision or aspiration of cerebellar abscess seems to provide favorable outcomes. In our experience, a successful outcome was achieved with subtotal resection and prolonged adequate antibiotic therapy.

Deep Venous Thrombosis with Decreased Cerebral Blood Flow to the Thalamus was Completely Restored by Factor Xa Inhibitor.

BACKGROUND: Cerebral venous thrombosis is rare and an uncommon cause of stroke and has diverse etiologies and varied clinical presentations. Here, we report 2 cases of deep cerebral venous thrombosis. CASE DESCRIPTION: A 64-year-old woman presented with cerebral venous thrombosis due to a hypercoagulable state associated with ovarian tumor. On initial fluid-attenuated inversion recovery and diffusion-weighted imaging, there was a diffuse high-intensity lesion in the bilateral thalamus. Computed tomography angiography showed occlusion of the straight sinus, vein of Galen, and internal cerebral vein. Single-photon emission computed tomography showed decreased cerebral blood flow in the bilateral thalamus. After 3 weeks of factor Xa inhibitor therapy, the patient's consciousness gradually improved and eventually became clear enough to leave the hospital. She had no neurological deficit. Another patient was a 47-year-old man who presented with splitting headache and drowsiness. Magnetic resonance venography confirmed deep thrombosis of the vein of Galen. He completely recovered after 4 weeks of factor Xa inhibitor therapy. CONCLUSIONS: This study reports on 2 rare cases of decreased cerebral blood flow in the bilateral thalamus on single-photon emission computed tomography, which improved following the administration of factor Xa inhibitor.

Endoscopic Surgery for Thalamic Hemorrhage with Intraventricular Hemorrhage: Effects of Combining Evacuation of a Thalamic Hematoma to External Ventricular Drainage.

OBJECTIVES: Intraventricular hemorrhage (IVH) caused by thalamic hemorrhage leads to hydrocephalus, increased intracranial pressure, and reduced levels of consciousness. The aim of this study was to investigate the efficacy and compare the results of endoscopic surgery for the evacuation of a thalamic and intraventricular hematoma against those of external ventricular drainage (EVD) surgery. MATERIALS AND METHODS: From January 2010 to December 2018, 68 patients with IVH caused by thalamic hemorrhage were treated in our department. Our study was approved by the Institutional Ethics Committee. The included patients were randomly divided into an EVD group and an endoscopic surgery group. The outcome was measured after 3 months using a 30-day mortality rate, pneumonia onset rate, ventriculoperitoneal (VP) shunt dependency rate, and Glasgow Outcome Scale (GOS) score. RESULTS: Thirty-eight of the 68 patients were randomly assigned to the endoscopic surgery group and 30 were assigned to the EVD group. Patients treated with endoscopic surgery had significantly less drainage dependency on day 30 (P = 0.00014 < 0.00005) in comparison to those treated with EVD. The difference in the functional outcomes between the two groups of patients was mainly dependent on the onset of pneumonia and the consciousness level at the time of admission. The onset rate of aspiration-related pneumonia until day 30 was 11% in the endoscopic surgery group and 45% in the EVD group. The VP shunt rates were 27.8% in the endoscopic surgery group and 60% in the EVD group. The endoscopic surgery group had a significantly lower VP shunt rate compared with the EVD group. Intracerebral hemorrhage evacuation late was found to be associated with shunt-dependent rate and hospitalization. CONCLUSIONS: Endoscopic surgery was found to be associated with a lower GOS score and lower onset rates for shunt-dependent hydrocephalus and aspiration-related pneumonia in comparison to EVD. High evacuation rate was associated with lower shunt-dependent rate and short hospitalization.

Cerebellopontine angle epidermoid cysts: clinical presentations and surgical outcome.

Epidermoid cysts constitute less than 1% of intracranial tumors with the majority of them involving cerebellopontine angle (CPA). Although several mechanisms for cranial nerve dysfunction due to these tumors have been proposed, no direct evaluation for hyper- or hypoactive dysfunction has been done. In this case series, pathophysiology of cranial nerve dysfunction in CPA epidermoid cysts was evaluated with special attention to a new mechanism of capsule strangulation caused by stratified tumor capsule. Twenty-two cases with epidermoid cysts of CPA micro-neurosurgically treated in our departments since 2005 were reviewed. Clinical status of the patients before the surgery and post-operative functional outcome were recorded. Available data from the English literature were summarized for comparison. Mass reduction of cyst contents in most cases was usually associated with prompt and marked improvement of the symptoms suggesting neuroapraxia caused by compression of the tumor content and/or mild ischemia. Among them, two cases showed strangulation of the affected nerves by the tumor capsule whose preoperative dysfunction did not improve after surgery in spite of meticulous microsurgical removal of the lesion. Involved facial and abducent nerves in these two cases showed distortion of nerve axis and nerve atrophy distal to the strangulation site. We report the first direct evidence of etiology of cranial nerve dysfunction caused by cerebellopontine angle epidermoid tumors. Young age and rapidly progressive neurological deficit might be the characteristics for strangulation of the affected nerves by the cyst capsule. Even though the number of cases might be limited, immediate decompression and release of the strangulating band might be urged in such patients to prevent irreversible deficits.

Efficacy of monitoring patient's position during neurosurgical procedures: introduction of real-time display and record.

There are many reports on position-related complications in neurosurgical literature but so far, continuous quantification of the patient's position during the surgery has not been reported. This study aims to explore the utility of a new surgical table system and its software in displaying the patient's body positions during surgery on real-time basis. More than 200 neurosurgical cases were monitored for their positions intra-operatively. The position was digitally recorded and could be seen by all the members in the operating team. It also displayed the three-dimensional relationship between the head and the heart positions. No position-related complications were observed during the study. The system was able to serve as an excellent indicator for monitoring the patient's position. The recordings were analyzed and even used to reproduce or improve the position in the subsequent operations. The novel technique of monitoring the position of the head and the heart of the patients and the operating table planes are considered to be useful during delicate neurosurgical procedures thereby, preventing inadvertent procedural errors. This can be used to quantify various surgical positions in the future and define safety measures accordingly.

Spindle cell oncocytoma of the adenohypophysis with marked hypervascularity. Case report.

A 68-year-old male presented with a very rare case of spindle cell oncocytoma (SCO), a recently identified very rare neoplasm of the anterior pituitary, manifesting as panhypopituitarism and visual field defect. The pituitary tumor with suprasellar extension was only partially resected via transsphenoidal surgery because of the tumor consistency and bleeding. Histological diagnosis was consistent with schwannoma. The tumor regrew and angiography revealed hypervascularity, so a transcranial approach was employed for the re-operation which only achieved partial resection because of intraoperative extensive bleeding. The tumor cells showed similar histological and immunohistochemical profiles to the previous specimen, but electron microscopy demonstrated that cytoplasm abundantly filled with mitochondria. The final diagnosis of SCO was established and the patient received postoperative conventional radiation therapy of 50 Gy. Only 15 cases of SCO have been reported, and the diagnosis was mistaken in many cases as schwannoma, oncocytic pituitary adenoma, or craniopharyngioma, and multiple surgeries followed by radiation therapy were required.

Central nervous system primitive neuroectodermal tumor of spinal cord developing 20 years after curative treatment of pineal tumor.

A 65-year-old male who had previously received curative treatment for a pineal tumor presented with an extremely rare case of primary central nervous system (CNS) primitive neuroectodermal tumor (PNET) of the spinal cord manifesting as progressive tetraparesis. Although the histology was not verified, highly radiosensitive tumor was suspected because of the benign clinical course for over 20 years after only radiation therapy. Magnetic resonance imaging demonstrated an intramedullary tumor extending from C5 to T1. He underwent partial resection and histological examination revealed blue tumor with undifferentiated small round cells. Immunohistochemically, c-kit was negative but CD99 was strongly and diffusely positive. Therefore, rearrangement of the Ewing sarcoma gene was examined to determine the presence of peripheral type of PNET. The results were negative and systemic workup revealed no other disease. These findings led to the diagnosis of primary intramedullary CNS PNET of the spinal cord, and suggested that the spinal cord tumor occurred independently of the prior pineal disease. The residual tumor was controlled by postoperative local radiation therapy.

Giant subependymoma developed in a patient with aniridia: analyses of PAX6 and tumor-relevant genes.

We observed an unusually large subependymoma in a female patient with congenital aniridia. To analyze the genetic mechanisms of tumorigenesis, we first examined the paired box 6 (PAX6) gene using both tumor tissue and peripheral lymphocytes. Tumor suppressor activity has been proposed for PAX6 in gliomas, in addition to its well-known role in the eye development. Using genomic quantitative PCR and loss of heterozygosity analysis, we identified hemizygous deletions in the 5'-region of PAX6. In lymphocytes, the deletion within PAX6 spanned from between exons 6 and 7 to the 5'-upstream region of the gene, but did not reach the upstream gene, RNC1, which is reported to be associated with tumors. The subependymoma had an additional de novo deletion spanning from the intron 4 to intron 6 of PAX6, although we could not completely determine whether these two deletions are on the same chromosome or not. We also examined other potentially relevant tumor suppressor genes: PTEN, TP53 and SOX2. However, we detected no exonic mutations or deletions in these genes. Collectively, we speculate that the defect in PAX6 may have contributed to the extremely large size of the subependymoma, due to a loss of tumor suppressor activity in glial cell lineage.

Clinical features and management of five patients with supratentorial subependymoma.

Subependymoma is a rare low-grade glioma of the central nervous system that is often asymptomatic and discovered incidentally. If symptomatic, however, its clinical features vary widely. We report and discuss the management of five surgical patients (two males and three females, 27-65 years old). All tumors developed supratentorially around the foramen of Monro, and their diameters ranged from 18 mm to 90 mm. Of the three symptomatic patients, one presented with sudden loss of consciousness despite having only a small tumor, while in contrast, another patient showed only gradual memory disturbance despite having a very large tumor (90 mm diameter). Two patients were asymptomatic but had ventricular dilatation. Gross total resection was achieved via either a transcortical (three patients) or an anterior transcallosal approach (two patients). No recurrence was observed during follow-up. We concluded that as surgery is the only curative treatment for subependymoma, and even a small tumor can present with sudden deterioration, we recommend early and total resection.

Potential therapeutic effect of glycogen synthase kinase 3beta inhibition against human glioblastoma.

PURPOSE: Glioblastoma represents the malignant brain tumor that is most refractory to treatment and in which the identification of molecular target(s) is urgently required. We investigated the expression, activity, and putative pathologic role of glycogen synthase kinase 3beta (GSK3beta), an emerging therapeutic target for neurodegenerative diseases, in human glioblastoma. EXPERIMENTAL DESIGN: The active fraction of GSK3beta that is phosphorylated at the tyrosine 216 residue (pGSK3betaY216) was identified in glioblastoma cell lines. GSK3beta activity for phosphorylating its substrate was detected in these cells by nonradioisotopic in vitro kinase assay. RESULTS: Higher expression levels of GSK3beta and pGSK3betaY216 were frequently detected in glioblastomas compared with nonneoplastic brain tissues. Inhibition of GSK3beta activity by escalating doses of a small-molecule inhibitor (AR-A014418) or inhibition of its expression by RNA interference induced the apoptosis and attenuated the survival and proliferation of glioblastoma cells in vitro. Inhibition of GSK3beta was associated with increased expression of p53 and p21 in glioblastoma cells with wild-type p53 and with decreased Rb phosphorylation and expression of cyclin-dependent kinase 6 in all glioblastoma cell lines. Administration of AR-A014418 at a low dose significantly sensitized glioblastoma cells to temozolomide and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea, chemotherapeutic agents used in the clinical setting, as well as to ionizing radiation. CONCLUSION: These results indicate that GSK3beta exerts a pathologic role by promoting the survival and proliferation of glioblastoma cells and by protecting them from apoptosis via the inactivation of p53- and/or Rb-mediated pathways. Consequently, we propose that GSK3beta provides a potential therapeutic target in glioblastoma.

Identification of biomarkers from mass spectrometry data using a "common" peak approach.

BACKGROUND: Proteomic data obtained from mass spectrometry have attracted great interest for the detection of early-stage cancer. However, as mass spectrometry data are high-dimensional, identification of biomarkers is a key problem. RESULTS: This paper proposes the use of "common" peaks in data as biomarkers. Analysis is conducted as follows: data preprocessing, identification of biomarkers, and application of AdaBoost to construct a classification function. Informative "common" peaks are selected by AdaBoost. AsymBoost is also examined to balance false negatives and false positives. The effectiveness of the approach is demonstrated using an ovarian cancer dataset. CONCLUSION: Continuous covariates and discrete covariates can be used in the present approach. The difference between the result for the continuous covariates and that for the discrete covariates was investigated in detail. In the example considered here, both covariates provide a good prediction, but it seems that they provide different kinds of information. We can obtain more information on the structure of the data by integrating both results.

C-kit gene mutation: common and widely distributed in intracranial germinomas.

OBJECT: Of the intracranial germ cell tumors (IGCTs), 10% of germinomas and most nongerminomatous tumors remain refractory to multimodality therapy. The authors investigated the mutation of c-kit and the expression of its product KIT in IGCTs to identify tumors susceptible to imatinib mesylate, a synthetic agent targeting KIT. METHODS: The authors investigated 26 IGCTs, including 13 germinomas, five mixed germ cell tumors (MGCTs), four immature teratomas (ITs), and two each of yolk sac tumors and choriocarcinomas. These tumors were examined for the expression of KIT and CD34 by immunohistochemical analysis, and for mutations in exons 2, 8 to 11, 13, and 17 of c-kit. Strong KIT expression was found in the cell membrane of germinomas (100%) and germinomatous cells of MGCTs (80%), as well as in the cytoplasm of epithelial and smooth-muscle cells of ITs. The membranous expression of CD34 was found in the nongerminomatous tumor cells and the chondrocytes of MGCTs (60%), ITs (100%), and a choriocarcinoma (50%), but not in germinomas and germinomatous cells. A total of five missense mutations distributed in exons 2, 11, 13, and 17 of c-kit were detected in three (23%) of the 13 germinomas. The novel mutations E73K, T96M (both in exon 2), and A636V (in exon 13) were detected in a single tumor. The presence or type of c-kit mutation was not correlated with patient prognosis. CONCLUSIONS: Immunohistochemical analysis of KIT expression is useful for the diagnosis of germinoma. This study may help in clarifying the pathogenesis of IGCTs and in identifying tumors susceptible to drugs targeting KIT.