Pediatric Prostatic Alveolar Rhabdomyosarcoma Presenting with Metastatic Spinal Cord Compression in the Thoracic Spine: A Case Report and Review of the Literature.

Rhabdomyosarcoma (RMS) is a pediatric malignancy with a variable prognosis depending on tumor stage and genotype. There has been a significant improvement in survival rates over the past decades. However, aggressive variants can metastasize to locations that are difficult to treat. We report a case of prostatic alveolar rhabdomyosarcoma with metastases to the bone marrow and thoracic spine in a child. The patient was treated with a multimodal approach that included surgical resection of the epidural mass; the administration of vincristine, dactinomycin, and cyclophosphamide; and radiotherapy. Unfortunately, after six months, the patient showed disease progression and was started on secondary-line treatment. This case illustrates the difficulties in managing end-stage metastatic rhabdomyosarcoma and is the first report of prostatic rhabdomyosarcoma presenting with spinal cord compression in a child.

Expression of Hemangioblast Proteins in von Hippel-Lindau Disease Related Tumors.

Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome that targets a highly selective subset of organs causing specific types of tumors. The biological basis for this principle of organ selectivity and tumor specificity is not well understood. VHL-associated hemangioblastomas share similar molecular and morphological features with embryonic blood and vascular precursor cells. Therefore, we suggest that VHL hemangioblastomas are derived from developmentally arrested hemangioblastic lineage keeping their potential of further differentiation. Due to these common features, it is of major interest to investigate whether VHL-associated tumors other than hemangioblastoma also share these pathways and molecular features. The expression of hemangioblast proteins has not yet been assessed in other VHL-related tumors. To gain a better understanding of VHL tumorigenesis, the expression of hemangioblastic proteins in different VHL-associated tumors was investigated. The expression of embryonic hemangioblast proteins Brachyury and TAL1 (T-cell acute lymphocytic leukemia protein 1) was assessed by immunohistochemistry staining on 75 VHL-related tumors of 51 patients: 47 hemangioblastomas, 13 clear cell renal cell carcinomas, 8 pheochromocytomas, 5 pancreatic neuroendocrine tumors, and 2 extra-adrenal paragangliomas. Brachyury and TAL1 expression was, respectively, observed in 26% and 93% of cerebellar hemangioblastomas, 55% and 95% of spinal hemangioblastomas, 23% and 92% of clear cell renal cell carcinomas, 38% and 88% of pheochromocytomas, 60% and 100% of pancreatic neuroendocrine tumors, and 50% and 100% of paragangliomas. We concluded that the expression of hemangioblast proteins in different VHL-associated tumors indicates a common embryological origin of these lesions. This may also explain the specific topographic distribution of VHL-associated tumors.

Characterization of Microscopic Multicellular Foci in Grossly Normal Renal Parenchyma of Von Hippel-Lindau Kidney.

Background and Objectives: This study aims to describe the earliest renal lesions in patients with von Hippel-Lindau (VHL) disease, especially the multicellular microscopic pathologic events, to get information into the genesis of renal neoplasms in this condition. Materials and Methods: Multicellular events were identified, and 3dimensional reconstruction was performed in grossly normal kidney parenchyma from VHL disease patients by using H&E-stained slides previously prepared. Results: The lesions were measured and the volume of clusters was calculated. Immunohistochemistry was performed for downstream HIF-target protein carbonic anhydrase 9 (CAIX) as well as CD34 for assessment of angiogenesis. We divided lesions into four types according to lesion height/size. The number of lesions was markedly decreased from lesion 1 (smallest) to lesion 2, then from lesions 2 to 3, and again from lesion 3 to 4. Distribution was highly consistent in the four cases, and the same decrement pattern was seen in all blocks studied. The volumes of clusters were measured and divided into three categories according to their volume. The most frequent pathologic event in VHL kidneys was category 1 (smallest volume), then category 2, and then category 3. Conclusion: We demonstrate that tracking histologic and morphologic changes in 3 dimensions of multicellular microscopic pathologic events enabled us to confirm a protracted sequence of events from smaller to larger cellular amplification events in VHL kidney.

Predictors of Seizure Freedom in Pediatric Low-Grade Gliomas.

OBJECTIVE: Pediatric low-grade gliomas (LGGs) are found in approximately one to three percent of patients with childhood epilepsy. Epilepsy in these patients is often medically refractory and therefore represents a unique cohort with significant morbidity from concomitant pathology. Similar studies in adult patients with low-grade gliomas have identified predictors of seizure freedom including gross-total resection, preoperative seizure control on antiepileptic medication and duration of seizures of less than one year. This study aims to identify similar predictors of seizure freedom in operatively managed pediatric LGGs. METHODS: A retrospective chart review was performed for patients diagnosed with World Health Organization (WHO) Grade I and II gliomas in patients ≤18 years old at a single institution (Indiana University School of Medicine at Riley Hospital for Children in Indianapolis, IN) from 2007-2017. Infratentorial and purely intraventricular lesions were excluded. WHO classification and histologic diagnosis were based on surgical pathology. Tumor grade, location, laterality, seizure status at presentation, and AED requirements pre- and post-operatively were recorded. Chi-squared analyses for independence were performed controlling for age at presentation, resection extent, seizure type, and Engel Class for seizure freedom post-operatively. RESULTS: Forty-two patients met the inclusion criteria. Preoperative seizures were observed in 23 patients (55%). Presentation with preoperative seizures was highly associated with continued seizure burden post-operatively, independent of the extent of surgical resection. Supratentorial location and the administration of prophylactic pre- and post-operative AEDs were associated with Engel Class I seizure freedom. Temporal location was not significantly associated with medically refractory epilepsy compared with extra-temporal locations. CONCLUSIONS: In our cohort of pediatric LGGs, we find that patients that did not initially present with seizures and those who were treated with prophylactic pre- and post-operative AEDs, were more likely to achieve Engel Class I seizure freedom post-operatively. Tumors located in the temporal location were not significantly associated with a higher seizure burden than other supratentorial, extra-temporal tumors. Neither extent of resection nor electrocorticography-guided resection correlated with improved seizure freedom outcomes during glioma resection.

Kidney in VHL disease: Early clear cell proliferation occurs in the distal tubular system.

Renal clear cell carcinoma commonly occurs in patients with von Hippel­Lindau disease (VHL). Kidneys of VHL disease patients (VHL kidneys) contain an abundance of independent clear cell proliferation events that have been hypothesized to represent precursor structures of clear cell carcinoma. In the present study, it was tried to identify the site of origin of clear cell proliferation, and the immunophenotype of clear cells. Using 3D histological tracking, the topographic origin of microscopic clear cell proliferation was investigated by identification of informative structures of interest and immunohistochemical staining for cluster of differentiation 10 (CD10) and cytokeratin 7 (CK7) in consecutive serial sections. In addition, the CD10/CK7 immunophenotype of proliferating clear cells was evaluated. Clear cell proliferation uniformly occurred in the distal tubular system. Some clear cell proliferation, however, revealed proximal tubule immunophenotype. It was concluded that early proliferation of VHL­deficient clear cells occurs in the distal tubular system. Despite the association with the distal tubular system, the immunohistochemical profile of early clear cell proliferation may be inconsistent with its distal tubular origin.

Developmentally Arrested Basket/Stellate Cells in Postnatal Human Brain as Potential Tumor Cells of Origin for Cerebellar Hemangioblastoma in von Hippel-Lindau Patients.

von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary cancer disorder caused by a germline mutation in the VHL tumor suppressor gene. Loss of the wild-type allele results in VHL deficiency and the potential formation of cerebellar hemangioblastomas, which resemble embryonic hemangioblast proliferation and differentiation processes. Multiple, microscopic, VHL-deficient precursors, termed developmentally arrested structural elements (DASEs), consistently involve the cerebellar molecular layer in VHL patients, indicating the tumor site of origin. Unlike hemangioblastomas, however, cerebellar DASEs do not express brachyury, a mesodermal marker for hemangioblasts. In this study, neuronal progenitors occupying the molecular layer were investigated as tumor cells of origin. By immunohistochemistry, cerebellar DASEs and hemangioblastomas lacked immunoreactivity with antibody ZIC1 (Zic family member 1), a granule cell progenitor marker with concordance from oligonucleotide RNA expression array analyses. Rather, cerebellar DASEs and hemangioblastomas were immunoreactive with antibody PAX2 (paired box 2), a marker of basket/stellate cell progenitors. VHL cerebellar cortices also revealed PAX2-positive cells in Purkinje and molecular layers, resembling the histological and molecular development of basket/stellate cells in postnatal non-VHL mouse and human cerebella. These data suggest that VHL deficiency can result in the developmental arrest of basket/stellate cells in the human cerebellum and that these PAX2-positive, initiated cells await another insult or signal to form DASEs and eventually, tumors.

Histological Tracking into the Third Dimension: Evolution of Early Tumorigenesis in VHL Kidney.

Using a novel three-dimensional (3D) approach, we tracked histological changes to elucidate the earliest stages of renal clear cell neoplasia in normal kidney tissue of patients with von Hippel-Lindau (VHL) disease. Tissue blocks of interest were procured, serially sectioned, and 3D reconstruction of the entirety of pathologic events was performed. The results reveal an abundance of foci with aberrant clear cell proliferation that initially develop along the tubular lining, but have the potential to aggregate within individual tubules. This stage is followed by the extension of clear cell aggregates beyond the tubular basement membrane, which allows for the recruitment of angiogenesis derived from interstitial vasculature. The results suggest that the most frequent pathologic event in VHL kidneys is the presence of isolated or aggregated clear cells within the tubular epithelium, potentially developing further into a protracted process of neoplasia. The abundance of independent pathologic events in VHL kidneys confirms developmental mechanisms to precede tumor initiation. To our knowledge, this is the first report demonstrating that tracking of histologic changes in the 3rd dimension enables the confirmation of the sequence of events from the earliest pathologic change in the VHL kidney to the neoplastic stage. This approach is not only useful for visualization and quantification of pathologic changes but also for targeted sampling allowing selective analysis of the earliest stages of clear cell carcinogenesis.

Cerebellopontine Angle Primary Choroid Plexus Carcinoma Present in an Adult: Case Report and Literature Review.

Choroid plexus tumors (CPTs) are rare intraventricular neoplasms that primarily occur in children and are rare in adults. Of the CPT subtypes, choroid plexus carcinomas (CPC) are highly aggressive and malignant and of World Health Organization (WHO) Grade III. Dissemination through the cerebrospinal fluid space is the inevitable natural course of the disease. In this case report, we present a 33-year-old female with a past medical history notable for schizophrenia and bipolar disease who suffered from left-sided acute vision loss and hearing loss. Magnetic resonance imaging (MRI) demonstrated multiple enhancing masses found in the left cerebellopontine angle (CPA), right internal auditory canal, the atrium of the left ventricle, and the left foramen of Monroe. After surgical decompression of the CPA tumor, the permanent final pathology was consistent with CPC. To our knowledge, this is the first reported case of a primary CPC occurring within the CPA in an adult. The unique presentation and progression of this rare adult-onset CPC provide insight for the diagnosis and treatment of other rare instances of CPTs.

Developmental vascular malformations in EPAS1 gain-of-function syndrome.

Mutations in EPAS1, encoding hypoxia-inducible factor-2α (HIF-2α), were previously identified in a syndrome of multiple paragangliomas, somatostatinoma, and polycythemia. HIF-2α, when dimerized with HIF-1ß, acts as an angiogenic transcription factor. Patients referred to the NIH for new, recurrent, and/or metastatic paraganglioma or pheochromocytoma were confirmed for EPAS1 gain-of-function mutation; imaging was evaluated for vascular malformations. We evaluated the Epas1A529V transgenic syndrome mouse model, corresponding to the mutation initially detected in the patients (EPAS1A530V), for vascular malformations via intravital 2-photon microscopy of meningeal vessels, terminal vascular perfusion with Microfil silicate polymer and subsequent intact ex vivo 14T MRI and micro-CT, and histologic sectioning and staining of the brain and identified pathologies. Further, we evaluated retinas from corresponding developmental time points (P7, P14, and P21) and the adult dura via immunofluorescent labeling of vessels and confocal imaging. We identified a spectrum of vascular malformations in all 9 syndromic patients and in all our tested mutant mice. Patient vessels had higher variant allele frequency than adjacent normal tissue. Veins of the murine retina and intracranial dura failed to regress normally at the expected developmental time points. These findings add vascular malformation as a new clinical feature of EPAS1 gain-of-function syndrome.

Molecular Classification of Gliomas is Associated with Seizure Control: A Retrospective Analysis.

Classically, histologic grading of gliomas has been used to predict seizure association, with low-grade gliomas associated with an increased incidence of seizures compared to high-grade gliomas. In 2016, WHO reclassified gliomas based on histology and molecular characteristics. We sought to determine whether molecular classification of gliomas is associated with preoperative seizure presentation and/or post-operative seizure control across multiple glioma subtypes. All gliomas operated at our institution from 2007 to 2017 were identified based on ICD 9 and 10 billing codes and were retrospectively assessed for molecular classification of the IDH1 mutation, and 1p/19q codeletion. Logistic regression models were performed to assess associations of seizures at presentation as well as post-operative seizures with IDH status and the new WHO integrated classification. Our study included 376 patients: 82 IDH mutant and 294 IDH wildtype. The presence of IDH mutation was associated with seizures at presentation [OR 3.135 (1.818-5.404), p < 0.001]. IDH-mutant glioblastomas presented with seizures less often than other IDH-mutant glioma subtypes grade II and III [OR 0.104 (0.032-0.340), p < 0.001]. IDH-mutant tumors were associated with worse post-operative seizure outcomes, demonstrated by Engel Class [OR 2.666 (1.592-4.464), p < 0.001]. IDH mutation in gliomas is associated with an increased risk of seizure development and worse post-operative seizure control, in all grades except for GBM.

Pineal teratoma with nephroblastic component in a newborn male: Case report and review of the literature.

Neonatal germ cell tumors are rare and comprise both benign and malignant neoplasms. Teratoma with nephroblastoma is a malignant subset defined pathologically by the presence of nephroblastoma and teratoma elements. Although teratoma with nephroblastoma is most often found in the kidney, 24 of 59 reported cases are associated with extrarenal locations, such as the mediastinum or retroperitoneum. To our knowledge, this is the first patient in the literature with intracranial/pineal teratoma with nephroblastoma, which was managed with staged transcranial approaches resulting in gross total resection and no adjuvant therapy (surveillance observation imaging). We further augmented the patient's management by comprehensive genomic profiling of the tumor to better understand the molecular biology and explore options for targeted therapy.

Von Hippel-Lindau Disease: Current Challenges and Future Prospects.

Understanding of molecular mechanisms of tumor growth has an increasing impact on the development of diagnostics and targeted therapy of human neoplasia. In this review, we summarize the current knowledge on molecular mechanisms and their clinical implications in von Hippel-Lindau (VHL) disease. This autosomal dominant tumor syndrome usually manifests in young adulthood and predisposes affected patients to the development of benign and malignant tumors of different organ systems mainly including the nervous system and internal organs. A consequent screening and timely preventive treatment of lesions are crucial for patients affected by VHL disease. Surgical indications and treatment have been evaluated and optimized over many years. In the last decade, pharmacological therapies have been evolving, but are largely still at an experimental stage. Effective pharmacological therapy as well as detection of biomarkers is based on the understanding of the molecular basis of disease. The molecular basis of von Hippel-Lindau disease is the loss of function of the VHL protein and subsequent accumulation of hypoxia-inducible factor with downstream effects on cellular metabolism and differentiation. Organs affected by VHL disease may develop frank tumors. More characteristically, however, they reveal multiple separate microscopic foci of neoplastic cell proliferation. The exact mechanisms of tumorigenesis in VHL disease are, however, still not entirely understood and knowledge on biomarkers and targeted therapy is scarce.

Isocitrate dehydrogenase 1 mutant glioblastomas demonstrate a decreased rate of pseudoprogression: a multi-institutional experience.

BACKGROUND: Pseudoprogression (psPD) represents false radiologic evidence of tumor progression and is observed in some glioblastoma (GBM) patients after postoperative chemoradiation (CRT) with temozolomide (TMZ). The ambiguity of the psPD diagnosis confounds identification of true progression and may lead to unnecessary interventions. The association between psPD and isocitrate dehydrogenase 1 (IDH1) mutational (mut) status is understudied, and its incidence may alter clinical decision making. METHODS: We retrospectively evaluated 120 patients with IDH1-mut (n = 60) and IDH1-wild-type (IDH-WT; [n = 60]) GBMs who received postoperative CRT with TMZ at 4 academic institutions. Response Assessment in Neuro-Oncology criteria were used to identify psPD rates in routine brain MRIs performed up to 90 days after CRT completion. RESULTS: Within 90 days of completing CRT, 9 GBM patients (1 [1.7%] IDH1-mut and 8 [13.3%] IDH1-WTs) demonstrated true progression, whereas 17 patients (3 [5%] IDH1-muts and 14 [23.3%] IDH1-WTs) demonstrated psPD (P = .004). IDH1-mut GBMs had a lower probability of psPD (hazard ratio: 0.173, 95% CI, 0.047-0.638, P = .008). Among the patients with radiologic signs suggestive of progression (n = 26), psPD was found to be the cause in 3 of 4 (75.0%) of the IDH1-mut GBMs and 14 of 22 (63.6%) of the IDH1-WT GBMs (P = .496). Median overall survival for IDH1-mut and IDH1-WT GBM patients was 40.3 and 23.0 months, respectively (P < .001). CONCLUSIONS: IDH1-mut GBM patients demonstrate lower absolute rates of psPD expression. Irrespective of GBM subtype, psPD expression was more likely than true progression within 90 days of completing CRT. Continuing adjuvant treatment for IDH1-mut GBMs is suggested if radiologic progression is suspected during this time interval.

A Systematic Review of Sellar and Parasellar Brown Tumors: An Analysis of Clinical, Diagnostic, and Management Profiles.

OBJECTIVE: To systematically review and analyze clinical, diagnostic, and management trends in sellar and parasellar brown tumors reported in existing literature. METHODS: In this systematic review, PubMed, Ovid MEDLINE, Scopus, and Google Scholar databases were searched for reported cases of sellar/parasellar brown tumors. Relevant titles and abstracts were screened in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Articles meeting inclusion criteria were subjected to data extraction, summarization, and analysis. A rare case of parasellar brown tumor was also presented. RESULTS: Eight reports (including the current report) were eligible for inclusion. Mean patient age was 42.75 years. Reported symptoms included visual disturbances (n = 6), headache (n = 5), fatigue (n = 3), nausea/vomiting (n = 2), chest pain (n = 1), neck pain (n = 1), and dysphagia (n = 1). In cases where computed tomography findings were provided (n = 6), lesions were noted to be expansile and lytic. Lesions were hyperintense on T2-weighted magnetic resonance imaging (66.7%) and demonstrated contrast enhancement (83.3%). Histology unanimously showed multinucleated giant cells in a fibrovascular connective tissue stroma. Dramatic symptom resolution was noted in all patients who underwent resection of the sellar/parasellar brown tumor (n = 4; 50%). CONCLUSIONS: Sellar/parasellar brown tumors are a rare, tertiary manifestation of hyperparathyroidism and can be elusive to diagnose. Diagnosis requires a high index of clinical suspicion in addition to comprehensive biochemical testing, imaging, and histopathologic analysis. Surgical extirpation is favored in cases where the lesion is causing compressive symptoms, or if it is unresponsive to management of hyperparathyroidism.

Ex vivo Dynamics of Human Glioblastoma Cells in a Microvasculature-on-a-Chip System Correlates with Tumor Heterogeneity and Subtypes.

The perivascular niche (PVN) plays an essential role in brain tumor stem-like cell (BTSC) fate control, tumor invasion, and therapeutic resistance. Here, a microvasculature-on-a-chip system as a PVN model is used to evaluate the ex vivo dynamics of BTSCs from ten glioblastoma patients. BTSCs are found to preferentially localize in the perivascular zone, where they exhibit either the lowest motility, as in quiescent cells, or the highest motility, as in the invasive phenotype, with migration over long distance. These results indicate that PVN is a niche for BTSCs, while the microvascular tracks may serve as a path for tumor cell migration. The degree of colocalization between tumor cells and microvessels varies significantly across patients. To validate these results, single-cell transcriptome sequencing (10 patients and 21 750 single cells in total) is performed to identify tumor cell subtypes. The colocalization coefficient is found to positively correlate with proneural (stem-like) or mesenchymal (invasive) but not classical (proliferative) tumor cells. Furthermore, a gene signature profile including PDGFRA correlates strongly with the "homing" of tumor cells to the PVN. These findings demonstrate that the model can recapitulate in vivo tumor cell dynamics and heterogeneity, representing a new route to study patient-specific tumor cell functions.

Activating KRAS mutations in arteriovenous malformations of the brain: frequency and clinicopathologic correlation.

Arteriovenous malformations (AVM) of the brain are considered congenital. Most AVMs are presumably sporadic; however, rare familial cases occur and they may be observed in certain genetic disorders. We sought to determine the frequency of KRAS mutations and their association with clinicopathologic characteristics. We searched our neuropathology database from 2014-2017 for resected AVMs of the brain or dura mater. Twenty-one AVMs were tested (12 females, 9 males; average age: 32 years). KRAS mutations were found in 6/21 cases (28.5%). Five mutations were p.G12 V, and one p.G12C. The KRAS-mutant group contained 4 females and 2 males, with an average age of 28 years, compared to 34 years in the non-mutant group (P = .54). The average AVM size in the KRAS-mutant group was 3.9 cm, compared to 3.1 cm in the non-mutant group (P = .52). There were no histologic differences between KRAS-mutant and non-mutant cases. In summary, KRAS mutations occur in almost one-third of brain AVMs. KRAS p.G12 V was the most common mutation identified. We also demonstrate the first reported instance of a KRAS p.G12C mutation in a brain AVM. The mean age of patients with KRAS-mutant AVMs was lower than the non-mutant group, and the mean size larger. Histologic characteristics were equally distributed between KRAS-mutant and non-mutant groups.

Efficacy of pre-operative stereotactic radiosurgery followed by surgical resection and correlative radiobiological analysis for patients with 1-4 brain metastases: study protocol for a phase II trial.

BACKGROUND: Stereotactic radiosurgery (SRS) has emerged as a common adjuvant modality used with surgery for resectable brain metastases (BMs). However, the optimal sequence of the multi-modality therapy has not been established. The goal of the study is to evaluate 6-month local control utilizing pre-operative SRS followed by surgical resection for patients with 1-4 brain metastases. METHODS: This prospective, single arm, phase II trial will recruit patients with up to 4 brain metastases and at least one resectable lesion. All lesions will be treated with SRS and symptomatic lesions will be resected within 1-4 days after SRS. Patients will be monitored for 6-month local control, in-brain progression free survival, distant in-brain failure, rate of leptomeningeal spread, radiation necrosis and overall survival. Additionally, we will also perform correlative radiobiological molecular studies to assess the effect of radiation dosing on the tumor tissue and clinical outcomes. We expect that pre-operative SRS to the gross tumor prior to surgical resection will improve local control and decrease leptomeningeal failure. DISCUSSION: Our study is the second prospective trial to investigate the efficacy of pre-operative SRS in the treatment of multiple BMs. In addition, the correlative molecular studies will be the first to investigate early response of BMs at a cellular and genetic level in response to radiation doses and potentially provide molecular prognostic markers for local control and overall survival. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03398694 (registration date: January 12, 2018).

Chordoma of the corpus callosum: case report.

Chordomas are neoplasms that typically arise from midline skeletal structures and rarely originate within the intradural compartment of the CNS. A chordoma arising from the corpus callosum has not been previously described. The authors report the surgical management of a chordoma originating within the splenium of the corpus callosum. To determine the incidence and distribution of intracranial intradural chordoma, a literature search for additional cases was performed. MEDLINE was searched using the MeSH keyword "chordoma," yielding 2010 articles. These articles were screened for cases of primary intradural chordoma rostral to the craniocervical junction, which led to the identification of 46 relevant articles. The authors report the case of a 69-year-old man who initially presented with nonspecific neurological symptoms including spatial disorientation and cognitive decline. These symptoms eventually prompted intracranial imaging, including MRI, which revealed a ring-enhancing, heterogeneous, cystic mass localized within the splenium of the corpus callosum and extending into the bilateral ventricles. The lesion was believed to represent a high-grade glioma and the patient underwent a left interhemispheric approach and subtotal resection. After pathologic evaluation confirmed a diagnosis of an anaplastic chordoma, the patient underwent further resection. A gross-total resection (GTR) was achieved with a transfalcine approach to the contralateral portion of the tumor. Postoperatively, the patient had a partial left homonymous quadrantanopsia, but was otherwise at his neurological baseline. Proton beam radiotherapy was performed to the resection cavity but diffuse intraventricular disease ensued. The results of a literature search suggest that a chordoma arising in the corpus callosum has not been previously described. The present case demonstrates that chordomas can occur in the corpus callosum, and illustrates the utility of a transfalcine approach for GTR of lesions in this location, as well as the need for improved strategies to prevent intraventricular dissemination.

Fatal cryptococcal meningitis in an AIDS patient complicated with immune reconstitution syndrome refractory to prolonged amphotericin B treatment.

Cryptococcus neoformans is a ubiquitous encapsulated environmental yeast that can cause severe central nervous system disease, primarily in immune compromised hosts. In patients with AIDS, the spectrum of cryptococcal central nervous system disease includes meningitis, cystic lesions, and mass-like cryptococcomas. We report a fatal case of meningitis and cerebritis caused by C. neoformans in an AIDS patient refractory to multiple courses of liposomal amphotericin B despite immune recovery with antiretroviral therapy. This case highlights ongoing diagnostic and therapeutic challenges in the face of treatment failure for cryptococcal meningitis and reinforces the need for improved treatment approaches.