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Bcl-2-associated athanogene 3 (BAG3) myopathy is a rare myofibrillar myopathy characterized by toe walking and clumsiness in the first decade with rapid progression to cardiomyopathy and restrictive lung disease in the second decade. Most patients (18 patients) have the c.626C >T (p.Pro209Leu) mutation. We describe BAG3 myopathy due to p.Pro209Leu in a 13-year-old girl with initial prominent neuropathic phenotype and no cardiac or respiratory involvement. Parents reported toe walking and clumsiness since 3 years old. Examination at the age of 13 years showed findings suggestive of Charcot-Marie-Tooth disease. Nerve conduction studies revealed demyelinating polyneuropathy. Next-generation sequencing panel for inherited neuropathies was unrevealing. Whole exome sequencing identified a de novo mutation in BAG3. Muscle biopsy confirmed myofibrillar myopathy. No cardiac involvement or symptoms of respiratory involvement at the age of 14 years. This case emphasizes the phenotypic variability of BAG3 myopathy and the importance of thorough electrophysiological examination and muscle pathology for establishing a precise diagnosis.

Background SMARCB1-deficient sinonasal carcinoma (SDSC) is an aggressive subtype of head and neck cancers that has a poor prognosis despite multimodal therapy. We present a unique case with next generation sequencing data of a patient who had SDSC with perineural invasion to the trigeminal nerve that progressed to a brain metastasis and eventually leptomeningeal spread. Case presentation A 42 year old female presented with facial pain and had resection of a tumor along the V2 division of the trigeminal nerve on the right. She underwent adjuvant stereotactic radiation. She developed further neurological symptoms and imaging demonstrated the tumor had infiltrated into the cavernous sinus as well as intradurally. She had surgical resection for removal of her brain metastasis and decompression of the cavernous sinus. Following her second surgery, she had adjuvant radiation and chemotherapy. Several months later she had quadriparesis and imaging was consistent with leptomeningeal spread. She underwent palliative radiation and ultimately transitioned quickly to comfort care and expired. Overall survival from time of diagnosis was 13 months. Next generation sequencing was carried out on her primary tumor and brain metastasis. The brain metastatic tissue had an increased tumor mutational burden in comparison to the primary. Conclusions This is the first report of SDSC with perineural invasion progressing to leptomeningeal carcinomatosis. Continued next generation sequencing of the primary and metastatic tissue by clinicians is encouraged toprovide further insights into metastatic progression of rare solid tumors. Electronic supplementary material The online version of this article (10.1186/s12885-019-6043-0) contains supplementary material, which is available to authorized users.

We report a child with hypotonia, optic atrophy, progressive encephalopathy and intractable infantile spasms who was diagnosed with PEHO syndrome. Extensive investigation was performed to diagnose an underlying etiology. Electron transport chain activities in muscle biopsies showed an isolated complex IV deficiency. Genetic examination focused on complex IV genes such as mtDNA and relevant nuclear DNA analysis was unremarkable. Whole exome sequencing with trio revealed a heterozygous de novo mutation at c.757G>A (p.E253K) in the KIF1A gene. The protein encoded by this gene functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. The relation between this genetic mutation and decreased activity of the mitochondrial respiratory chain complex is discussed in details. Our study further confirmed that the molecular basis of PEHO syndrome at least in a subset of patients is a dominant KIF1A variant affecting the motor domain of the protein. This is the first description of the decreased activity of mitochondrial respiratory chain complex in association with either PEHO syndrome or KIF1A mutation. This study emphasizes that the results of the mitochondrial enzymes should be interpreted with caution and clinicians should be actively looking for other underlying diagnoses with further comprehensive studies.

Neuro-oncology biobanks are critical for the implementation of a precision medicine program. In this perspective, we review our first year experience of a brain tumor biobank with integrated next generation sequencing. From our experience, we describe the critical role of the neurosurgeon in diagnosis, research, and precision medicine efforts. In the first year of implementation of the biobank, 117 patients (Female: 62; Male: 55) had 125 brain tumor surgeries. 75% of patients had tumors biobanked, and 16% were of minority race/ethnicity. Tumors biobanked were as follows: diffuse gliomas (45%), brain metastases (29%), meningioma (21%), and other (5%). Among biobanked patients, 100% also had next generation sequencing. Eleven patients qualified for targeted therapy based on identification of actionable gene mutations. One patient with a hereditary cancer predisposition syndrome was also identified. An iterative quality improvement process was implemented to streamline the workflow between the operating room, pathology, and the research laboratory. Dedicated tumor bank personnel in the department of neurosurgery greatly improved standard operating procedure. Intraoperative selection and processing of tumor tissue by the neurosurgeon was integral to increasing success with cell culture assays. Currently, our institutional protocol integrates standard histopathological diagnosis, next generation sequencing, and functional assays on surgical specimens to develop precision medicine protocols for our patients. This perspective reviews the critical role of neurosurgeons in brain tumor biobank implementation and success as well as future directions for enhancing precision medicine efforts.

This study reports the results of the first brain tissue banking experience of Turkey in the Unit for Aging Brain and Dementia at Dokuz Eylul University, Department of Geriatric Medicine, Izmir. Here, we have briefly described our efforts on brain banking in our country, which consist of six brains from autopsies that had at least two years of clinical follow-up in the 2015-2017 period. The evaluation led to the diagnosis of two Alzheimer's disease (AD) with cerebral amyloid angiopathy, one AD with dementia with Lewy bodies, one corticobasal degeneration, one multiple system atrophy, one vascular dementia. We believe that the study is of a special importance because of its potential of becoming a brain banking center in the region and because of its contributing to the international knowledge of the neuropathological features of dementia, while characterizing the epidemiology of these diseases in the region.

High-grade diffuse large B-cell lymphoma (HG-DLBCL) refers to DLBCL with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit DLBCL) that exhibits poor prognosis. Double-expressor DLBCL (c-myc+/bcl-2+) has intermediate prognosis when compared to HG-DLBCL. Primary central nervous system lymphoma (PCNSL) has distinct pathophysiology (frequent non-germinal center-like subtype and double-expressor) and has worse prognosis than systemic DLBCL. By fluorescence in situ hybridization (FISH), 25–30% of PCNSLs harbor BCL6 abnormalities with rare alterations in MYC, BCL2, double-hit or triple-hit events. We describe the clinicopathologic features and status of MYC, BCL2 and BCL6 in 12 PCNSLs (7 women, 5 men; median age 63 years; range: 28–79). Six cases showed focal starry-sky pattern. Immunohistochemically, all (100%) were of non-germinal center-like subtype, and 8/10 (80%) cases were double-expressors. Ki-67 ranged from 70 to 100%. FISH was positive in 9/12 (75%) cases: 4 (33%) harbored a BCL6 rearrangement, 3 (25%) had a gain of BCL2, 2 (17%) cases each had a gain of BCL6 and gain of IGH, and gain of MYC and deletion of MYC were observed in 1 case each (8%). Two (16%) cases were MYC/BCL6 double-hit PCNSLs. No MYC/BCL2 or triple-hit cases were identified. Eleven (92%) patients received chemotherapy and one also received whole brain radiation. The median time of follow-up was 4.4 months (range, 0.3–40.3). Seven (58%) patients are alive, 4 (33%) have died, and 1 (8%) had no follow-up. Five alive patients are in remission, including one MYC/BCL6 double-hit PCNSL. Our results add two new cases of rare double-hit PCNSL to the literature.

Aims: Cellular schwannoma is a specific subtype of schwannoma, prone to misinterpretation as a malignant neoplasm. Involvement of the intracranial compartment by these tumours is extremely rare. We aim to characterise this clinicopathological subgroup. Methods and results: We identified a total of 20 cellular schwannomas with predominant intracranial involvement. The mean age of the patients at the time of surgery was 37years (range=16–81), with a slight female predominance (1.5:1 ratio). The most common sites were the eighth (n=8) and fifth (n=6) cranial nerves. Three tumours involved the anterior cranial fossa/olfactory groove, and a single case involved the glossopharyngeal nerve. All tumours met established criteria for cellular schwannoma, and were composed of interlacing fascicles of spindle cells lacking Verocay bodies with minimal Antoni B pattern and variable chronic inflammation and foamy histiocytes. Rare findings included haemosiderin deposition (n=6), necrosis (n=4), brisk mitotic activity (>10 mitoses per 10 high-power fields) (n=2), focal epithelioid morphology (n=2), myxoid areas (n=2), neuroblastoma-like pattern (n=1) and granular cells (n=1). Immunohistochemical stains demonstrated expression of Schwann cell markers (S100 protein, SOX10, collagen IV) and preserved H3 K27 trimethylation in all cases tested. Fourteen patients had postoperative follow-up, ranging from 2months to 21years (mean=66months). In patients with follow-up, local recurrence/persistence developed in six cases; five tumours were initially incompletely resected. No metastatic disease or deaths were reported. Conclusions: Intracranial cellular schwannomas share morphological and immunophenotypical features with cellular schwannomas at others sites may demonstrate locally aggressive growth but appear to lack metastatic potential.

Background. While pituitary tumors are well understood, little research has been done on metastasis from primary tumors into pituitary adenomas, also known as composite tumors. Because only 34 cases of composite tumors have been reported to date, we hope to better characterize these tumors by reviewing cases reported in the literature and reviewed our own documented case, which includes next-generation sequencing. Case Presentation. A 74-year-old man presented to the emergency department with left vision loss for 3 months. He had a history of colon cancer treated with colectomy and clear cell renal carcinoma treated with left nephrectomy. A preoperative MRI demonstrated growth of a peripherally enhancing, centrally necrotic mass with sellar expansion measuring 5.7×3.1×3.0 cm. Given these findings, an endoscopic endonasal transsphenoidal resection was performed. Histological assessment revealed a composite tumor: one neoplasm was a nonfunctioning pituitary adenoma, and another neoplasm was a clear cell carcinoma. Next-generation sequencing demonstrated that the tumors shared mutations in VHL and Notch2. The patient died 2 months later from systemic metastatic cancer. Conclusion. From our literature review, most metastatic lesions in these composite tumors originated from neoplasms of the lung and kidney. Approximately 63% patients presented with ophthalmoplegia as the initial symptom while 23% displayed hormonal abnormalities. Postoperative mortality had a median of 3.5 months. In our patient, the presence of VHL and Notch2 mutations in both tumors highlights the possibility of using next-generation sequencing to help identify therapeutic targets even in complex composite neoplasms.

Objectives We describe a 13-year-old girl with a past medical history of epilepsy, intellectual impairment, dysphagia with gastric tube dependence, and autism spectrum disorder who presented with focal status epilepticus. Methods Video-electroencephalography revealed left occipital pseudoperiodic epileptiform discharges and frequent seizures originating from the left hemisphere. The seizure was refractory to antiepileptic medications and pharmacologic coma. Subsequently, left occipital lobectomy was done. Extensive evaluation including whole exome sequencing, histopathologic examination of brain and muscle samples, mitochondrial DNA content analysis of tissue sample was completed to detect the etiology. Results Skeletal muscle mitochondrial DNA content (qPCR) analysis showed approximately 37% of the mean value of age and tissue matched control group consistent with a mitochondrial depletion syndrome. Microscopic examination of the brain showed cortical abnormalities that largely consisted of infarct-like pathology in a laminar manner, abnormalities of neuronal distribution, and white matter changes. Compound heterozygous mutations of the CARS2 gene were identified by whole exome sequencing; V52G variant [p.Val52Gly (GTG>GGG):c.155 T>G in exon 1] was inherited from the mother and T188M variant[p.Thr188Met (ACG>ATG): c.563 C>T in exon 5] was inherited from the father. Conclusion This is the first detailed clinicopathologic description of the Alpers-Huttenlocher syndrome phenotype from CARS mutations.

Social media use continues to grow among pathologists. Discussions of current topics, posts of educational information, and images of pathological entities are commonly found and distributed on popular sites such as Facebook and Twitter. However, little is known about the presence of neuropathology content in social media and the audience for such content. We designed and distributed a survey to assess the demographics of users viewing neuropathology content and their opinions about neuropathology in social media. User posts on the Facebook group, Surgical Neuropathology, were also analyzed. The results show that there is a demand for neuropathology content of high quality, curated by experts, and that this demand is present among both specialists and nonspecialists. These findings suggest that social media may be useful for rapid dissemination of information in the field of neuropathology. This format also offers a unique opportunity to extend the reach of information to nonneuropathologists who may not receive neuropathology journals or have access to specialty-level neuropathology training, to build networks between professionals, and potentially to influence public opinion of neuropathology on an international scale.

A 28-year-old man with a history of HIV infection (genotype 1 subtype B) who was not on antiretroviral treatment presented with 2–3 months of progressive weakness of his extremities. He had been on fluconazole therapy for 8 months for Cryptococcal meningitis. He initially noticed right followed by left lower and bilateral upper extremity weakness. Review of systems was negative for sensory symptoms or dysautonomia. His examination was notable for severe proximal (Medical Research Council [MRC] scale 1–2/5) more than distal weakness, affecting both flexor and extensor muscle groups (MRC scale 3/5), and neck flexion (MRC scale 2/5) weakness. He had left more than right brisk deep tendon reflexes throughout (+3) and sustained clonus in his ankles. He was alert and oriented. His cranial nerve and sensory examination was unremarkable. Negative inspiratory force and vital capacity were −22 cmH2O and 0.7 L, respectively.

Li Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome caused by germline mutations in TP53. TP53 is the most common mutated gene in human cancer, occurring in 30–50% of glioblastomas (GBM). Here, we highlight a precision medicine platform to identify potential targets for a GBM patient with LFS. We used a comparative transcriptomics approach to identify genes that are uniquely overexpressed in the LFS GBM patient relative to a cancer compendium of 12,747 tumor RNA sequencing data sets, including 200 GBMs. STAT1 and STAT2 were identified as being significantly overexpressed in the LFS patient, indicating ruxolitinib, a Janus kinase 1 and 2 inhibitors, as a potential therapy. The LFS patient had the highest level of STAT1 and STAT2 expression in an institutional high-grade glioma cohort of 45 patients, further supporting the cancer compendium results. To empirically validate the comparative transcriptomics pipeline, we used a combination of adherent and organoid cell culture techniques, including ex vivo patient-derived organoids (PDOs) from four patient-derived cell lines, including the LFS patient. STAT1 and STAT2 expression levels in the four patient-derived cells correlated with levels identified in the respective parent tumors. In both adherent and organoid cultures, cells from the LFS patient were among the most sensitive to ruxolitinib compared to patient-derived cells with lower STAT1 and STAT2 expression levels. A spheroid-based drug screening assay (3D-PREDICT) was performed and used to identify further therapeutic targets. Two targeted therapies were selected for the patient of interest and resulted in radiographic disease stability. This manuscript supports the use of comparative transcriptomics to identify personalized therapeutic targets in a functional precision medicine platform for malignant brain tumors.

As its historical name glioblastoma multiforme implies, glioblastoma is a histologically diverse, World Health Organization grade IV astrocytic neoplasm. In spite of its simple definition of presence of vascular proliferation and/or necrosis in a diffuse astrocytoma, the wide variety of cytohistomorphologic appearances overlap with many other neoplastic or non-neoplastic lesions. Here, after a brief review of glioblastoma is provided, the differential diagnostic possibilities with an emphasis on mimics and pitfalls are discussed. To provide an approach applicable to diagnostic practice, these discussions are grouped arbitrarily according to general malignant appearance such as pleomorphic xanthoastrocytoma and ganglioglioma, especially their anaplastic versions, and cellular features such as small cell and epithelioid glioblastoma. Some non-neoplastic lesions that can potentially be mistaken for glioblastoma under certain circumstances are also briefly mentioned. Additional studies, including immunohistochemistry and molecular markers, are included where applicable. Otherwise, exhaustive review of these individual entities, including their epidemiology and molecular biology, is outside the scope of this discussion.

Solitary fibrous tumors of the spine are rare lesions. Their description in the literature is limited to case reports and small case series. While generally benign lesions, they can recur and occasionally occur as malignancies. Here the authors present the case of a 10-year-old boy, the youngest patient and first preadolescent reported thus far, with this condition. In addition, they perform a comprehensive review of all previously published cases of spinal solitary fibrous tumors.

The presence of Alternative lengthening of telomeres (ALT) and/or ATRX loss, as well as the role of other telomere abnormalities, have not been formally studied across the spectrum of NF1-associated solid tumors. Utilizing a telomere-specific FISH assay, we classified tumors as either ALT-positive or having long (without ALT), short, or normal telomere lengths. A total of 426 tumors from 256 NF1 patients were evaluated, as well as 99 MPNST tumor samples that were sporadic or of unknown NF1 status. In the NF1-glioma dataset, ALT was present in the majority of high-grade gliomas: 14 (of 23; 60%) in contrast to only 9 (of 47; 19%) low-grade gliomas (p = 0.0009). In the subset of ALT-negative glioma cases, telomere lengths were estimated and we observed 17 (57%) cases with normal, 12 (40%) cases with abnormally long, and only 1 (3%) case with short telomeres. In the NF1-associated malignant nerve sheath tumor (NF1-MPNST) set (n = 75), ALT was present in 9 (12%). In the subset of ALT-negative NF1-MPNST cases, telomeres were short in 9 (38%), normal in 14 (58%) and long in 1 (3%). In the glioma set, overall survival was significantly decreased for patients with ALT-positive tumors (p

Severe focal motor epilepsy is considered a clinical hallmark of Rasmussen encephalitis (RE). The authors report a 6-year-old girl with progressive right sided hemiparesis, loss of language skills, left sided hemispheric atrophy, and brain pathologic features characteristic for RE. The patient did not experience seizures over a 2year period after symptom onset and for several months during follow-up. This report expands the clinical spectrum of RE and suggests that seizures are not a universal symptom of RE. Our patient's quite remarkable neurologic deficits along with active inflammation in the absence of epilepsy supports that, at least in some individuals, unilateral hemispheric progressive inflammation can occur without active seizure activity.

Patient: Male, 31 Final Diagnosis: Light chain depsotion disease Symptoms: — Medication: — Clinical Procedure: None Specialty: Hematology Objective: Rare co-existance of disease or pathology Background: Light chain deposition disease is a systemic disease characterized by deposition of immunoglobin light chains in various organs. Cardiac involvement of light chain deposition disease, also known as cardiac nonamyloidotic immunoglobin deposition disease (CIDD), is a rare clinical entity, where clinical outcome is very variable and best treatment approaches are not well known. Case Report: We present the case of a 31-year-old man with a solitary thoracic plasmacytoma and cardiac light chain deposition disease with evidence of congestive heart failure by echocardiography and cardiac markers. The patient underwent surgical resection of the plasmacytoma followed by systemic therapy with 50% VDT-PACE and then VRD with near-normalization of his heart function. A melphalan-based stem cell transplant is planned in this young patient to achieve the best possible long-term remission. Conclusions: CIDD is a very rare disease, with previous reports showing diverse manifestations with variable outcome. A high level of clinical suspicion should be maintained in such cases and early intervention, as in our patient, can restore cardiac function. There is very little literature on the optimal management of these patients. A combination of surgery and chemotherapy were pursued in our patient with very good results.

Severe recurrent proximal muscle weakness without neuroleptic malignant syndrome secondary to antidopaminergic medication has rarely been reported. We report a 29-year-old man with history of obsessive compulsive disorder and Tourette syndrome who presented with 2 months of worsening dyspnea 3 weeks after starting ziprasidone 40 mg daily that required mechanical ventilation. A year before, after an increased risperidone dose from 0.5 to 1 mg daily, he had developed proximal muscle weakness that spontaneously improved 2 months after discontinuation of risperidone. On this admission, his creatine kinase (CK) was 3318 units/L, and ziprasidone was discontinued. He fully recovered 2 months after discontinuation of ziprasidone, and his CK was 62 units/L. Genetic testing for limb-girdle muscular dystrophy was negative. This case highlights the importance of evaluating CK level in patients taking antidopaminergic medication with any suggestion of muscle weakness to prevent potentially life-threatening complication.

Central nervous system (CNS) hematologic malignancies, whether primary or secondary, are uncommon and their clinical presentations vary. Intravascular lymphoma (IVL) is a very rare, aggressive systemic malignancy that is often difficult to diagnose and susceptible to early CNS involvement. Blast crisis in myeloid leukemias can cause widespread neoplastic emboli. Here, we report two adult patients (72 years and 22 years of age) who presented with altered mental status followed by rapid decline in their conditions leading to death. No prior significant medical history was present for either patient, while acute myeloid leukemia was diagnosed in the younger patient immediately before death. During autopsy, we performed imprint and squash preparations, and frozen sections of representative cerebral cortex, cerebellum, leptomeninges, and the pituitary gland. In the older patient, presence of IVL was readily detected on cytologic preparations. Diffuse involvement of brain vasculature and perivascular parenchyma with acute myeloid leukemia was identified in the other patient. Although examination of the fresh brain is not routinely performed during autopsy, these cases are presented to illustrate that imprint and squash preparations can provide a rapid and reliable provisional autopsy diagnosis in select patients.

Rosai-Dorfman disease (RDD) is a benign histiocytic proliferation that most commonly presents with painless bilateral lymphadenopathy and constitutional symptoms such as fever, fatigue, and night sweats.1 RDD is considered by many to be a reaction pattern with several different manifestations, especially as clonality has not been documented to support it representing a neoplasm per se. Classic histologic features include histiocytes that are S100 protein positive, are CD1a−, and demonstrate emperipolesis. Cutaneous lesions can occur in about 10% of patients, however, RDD limited only to cutaneous involvement is particularly rare.2, 3 Moreover, concomitant cutaneous RDD (CRDD) and bone RDD has rarely been reported in the English-language literature.4, 5 Here, we presented a case of CRDD on the scalp with underlying bony involvement.

A 73-year-old right-handed man with a history of hypertension and hyperlipidemia presented with an 18-month history of diplopia and unsteady gait. He also noted oscillating vision when turning his head to the left. The diplopia was horizontal and was worse looking at objects on his right or at a distance. Over a year, his balance worsened to the point where he required a walker due to recurrent falls. Six months prior to presentation, he developed dysphagia (liquids more than the solids). He was also noted to have short-term memory problems in the last 3 months. On examination, he had moderate cognitive impairment with a Montreal Cognitive Assessment (MoCA) score of 20/30 with predominant deficits in visuospatial functions and language. Glabellar, bilateral palmomental, and snout reflexes were present. The left pupil was surgical and nonreactive to light, and there was mechanical ptosis on the left. He had left exotropia with full eye movements, bilateral horizontal gaze-evoked nystagmus, and upbeat nystagmus on upgaze. Motor strength and tone were normal. He was diffusely hyperreflexic with bilateral extensor plantar responses. Detailed sensory examination was normal. Dysmetria was present bilaterally, more prominent on the left compared to right, with finger to nose testing and finger chase. His gait was ataxic with wide base and a tendency to fall toward the left side. He was unable to tandem walk (video on the Neurology ® Web site at [Neurology.org][1]). Systemic examination was unremarkable. [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000001975

OBJECT Epidermoid tumors arise from misplaced squamous epithelium and enlarge through the accumulation of desquamated cell debris. Optimal treatment consists of total removal of the capsule; therefore, giant and multicompartmental tumors are particularly challenging. A conservative attitude in handling the tumor capsule is common given concerns about capsule adherence to neurovascular structures, and thus the possibility of recurrence is accepted with the intent of minimizing complications. This study focuses on the outcome of surgery in patients with giant epidermoid tumors for which total capsule removal was the aim. METHODS The authors conducted a retrospective analysis of all patients with giant epidermoid tumors treated by the senior author (O.A.), who pursued total removal of the capsule through skull base approaches. Patients were divided into 2 groups: one including patients with de novo tumors and the other consisting of patients who presented with recurrent tumors. RESULTS Thirty-four patients had undergone 46 operations, and the senior author performed 38 of these operations in the study period. The average tumor dimensions were 55 × 36 mm, and 25 tumors had multicompartmental extensions. Total removal of the tumor and capsule was achieved with the aid of the microscope in 73% of the 26 de novo cases but in only 17% of the 12 recurrent tumor cases. The average follow-up among all patients was 111 months (range 10–480 months), and the average postsurgical follow-up was 56.8 months (range 6–137 months). There were 4 recurrences in the de novo group, and every case had had a small piece of tumor capsule left behind. One patient died after delayed rupture of a pseudoaneurysm. In the de novo group, the average preoperative Karnofsky Performance Scale (KPS) score was 71.42%, which improved to 87.14% on long-term follow-up. In the group with recurrences, the KPS score also improved on long-term follow-up, from 64.54% to 84.54%. In the de novo group, 3 cases (11.5%) had permanent cranial nerve deficits, and 4 cases (15.4%) had a CSF leak. In the recurrence group, 3 cases (25%) had new, permanent cranial nerve deficits, and 1 (8.3%) had a CSF leak. Two patients in this group developed hydrocephalus and required a shunt. CONCLUSIONS Total removal of the capsule of giant epidermoid tumors was achieved in 73% of patients with de novo tumors and was associated with improved function, low morbidity and mortality, and a lower risk of recurrence. Surgery in patients with recurrent tumors was associated with higher morbidity and persistence of the disease.

Background The most common neurologic manifestations of fibrous dysplasia (FD) are vision and hearing loss. Optic decompression for progressive vision loss has been shown to yield positive results in terms of visual outcomes; however, emergency optic decompression surgery for sudden loss of vision in FD has not to date been reported in the pediatric population. We report the first case of FD presenting with sudden vision loss and successfully managed with emergency optic decompression. Case Description A 10-year-old male patient known to have FD with a 2-month history of progressive vision loss in his left eye presents with sudden blindness. Emergency decompression surgery restored vision in his left eye to 20/40, which remained stable on long-term follow-up. Conclusion There is no consensus on the benefit and safety of prophylactic optic decompression, yet therapeutic decompression has been shown to prevent vision deterioration. Our findings suggest that therapeutic decompression even when done in the emergency setting yields positive results, while prophylactic decompression carries an inherent risk for loss of vision in a seeing eye.

Object Radiation-associated meningiomas (RAMs) arise after treatment with radiation to the cranium and are recognized as clinically separate from sporadic meningiomas. Compared with their sporadic counterparts, RAMs are often aggressive or malignant, likely to be multiple, and have a high recurrence rate. However, limited information exists about the clinical, pathological, and cytogenetic features of RAMs in pediatric patients. The authors report the findings in 9 children with meningiomas following therapeutic radiation to the cranium. In addition, they performed a critical review of the English language literature on pediatric RAMs. Methods Medical files were searched for patients who demonstrated meningiomas after a history of radiation to the brain. Only those patients in whom a meningioma occurred before the age of 18 years were included in this study. Clinical and demographic data along with the MIB-1 labeling index and cytogenetic studies were evaluated. Results The patients consisted of 5 males and 4 females with a median age of 5 years (range 2–10 years) at radiation therapy. The latency period was a median of 10 years after radiation therapy (range 6–13 years). The MIB-1 labeling index was a median of 6.6% (range 4%–10%). Five patients (55.6%) displayed multiple meningiomas at the first presentation. Histological types included clear cell meningioma in 1 patient, fibroblastic meningioma in 2, chordoid meningioma in 2, meningothelial meningioma in 7 (atypical in 2 cases), xanthomatous meningioma in 1, and chordoid meningioma in 1. Cytogenetic studies showed that the loss of 22q12.2 was the most common abnormality (3 patients), followed by complex cytogenetic abnormalities (2 patients) and rearrangements between chromosomes 1 and 12 (1 patient) and a 1p deletion (1 patient). Conclusions In contrast to RAMs occurring in adults, those in pediatric patients show an increased incidence of multiplicity on first presentation and unusual histological variants, some of which are described here for the first time. There was no difference in the MIB-1 labeling index in children with RAMs as compared with that in children with non-RAMs.

Fragile X tremor/ataxia syndrome (FXTAS) occurs in individuals with moderate CGG expansion of the fragile X mental retardation 1 (FMR1) gene and is associated with intranuclear inclusions in neurons and astrocytes. Although the neuropathologic findings in the brain and spinal cord were described, pathological features in the peripheral nervous system were not reported. Here, we report on novel neuropathological findings in the peripheral nervous system and especially in autonomic ganglia at autopsy in a man with FXTAS. In addition to the characteristic brain and spinal cord findings, typical intranuclear inclusions were identified in the ganglion cells of adrenal medulla, dorsal root ganglia, paraspinal sympathetic ganglia, myenteric ganglia of the stomach and subepicardial autonomic ganglion of the heart. Our findings indicate that FXTAS diffusely involves the central and peripheral nervous systems, which explains the protean neurological symptoms ranging from dementia to dysautonomia.

Malignant peripheral nerve sheath tumors (MPNSTs) arising from cranial nerves or their branches are very uncommon. The literature consists mainly of isolated case reports and small series. We identified 17 such cases in 14 males and 3 females. With one exception, the tumors affected adults (age range 5 to 69y, mean 39, median 32). Sites of involvement included vestibular nerves (n = 6). vagal nerves (n = 4), facial nerves (n = 3) (1 centered in the geniculate ganglion), and 2 unspecified cranial nerves in the posterior fossa. In addition, I tumor involved the optic chiasm (n = 1). Only I tumor arose in brain parenchyma of (frontal lobe). All but 3 lesions were intracranial, live tumors arose in patients who satisfied clinical criteria for neurofibromatosis type 1 (NNI). One patient with a vestibular tumor and presumed NF2 had previously undergone resection of a contralateral vestibular cellular schwannoma. One posterior fossa tumor was a malignant melanotic schwannoma. Four patients had postirradiation malignant peripheral nerve sheath tumors, 2 having been treated for optic chiasm glioma, both being NNI affected. One patient was irradiated for hypothalamic pilocytic astrocytoma and another for cervical Hodgkin disease. Identifiable precursor lesions included schwannoma (n = 4), plexiform neurofibroma (n = 2), and solitary intraneural neurofibroma (n = 2). All tumors were histologically high grade (6 grade III and 10 grade IV). Three tumors showed heterologous elements, 2 osscous, and 1 rhabdomyoblastic. More often scattered than diffuse, S-100 protein staining was noted in 11 of 16 tumors and variable collagen IV staining in 10 of the 16. Immunoreactivity for p53 protein was diffuse and strong in 7 of 11 tumors. Twelve patients died within 17 months to 3 years of diagnosis, 1 was lost to follow-up, 2 are very recent cases, and 2 patients are currently alive, I after 2 recurrences, and another with spinal leptomeningeal metastases. Malignant cranial nerve sheath tumors :ire rare and are associated with the same poor prognosis as those of spinal nerves at other sites.

PAX-2 is a homeogene expressed during kidney development. Although immunohistochemical expression of PAX-2 has been described in a variety of primary renal cell carcinoma (RCC) subtypes and in metastatic RCC, its specificity as a marker of renal lineage in a metastatic setting has not been fully evaluated. In addition, its utility has not been directly compared with the most widely used antibody in this setting, renal cell carcinoma marker (RCCma). We studied PAX-2 expression in metastatic clear cell renal cell carcinoma (CC-RCC) and in a variety of nonrenal neoplasms with clear cytoplasm that may potentially mimic CC-RCC. Archival material from 27 CC-RCCs metastatic to various organs and 50 close morphologic mimics of CC-RCC were retrieved. Immunohistochemistry with PAX-2 and RCCmapi antibodies was performed on each case. Nuclear staining (PAX-2) or membranous staining (RCCma) was scored semiquantitatively. Twenty-three of 27 (85%) metastatic CC-RCCs showed nuclear immunoreactivity for PAX-2, whereas RCCma reactivity was found in 19 of 27 (70%). The immunoprofiles of the metastatic CC-RCC were PAX-2+/RCCma+: 19 of 27 (70%), PAX-2+/RCCma-: 5 of 27 (19%), PAX-2-/RCCma+: 2 of 27 (7%), and PAX-2-/RCCma-: 1 of 27 (4%). Five of the 50 mimics of CC-RCC (10%) had at least focal nuclear reactivity with PAX-2, including 1 of 3 parathyroid carcinomas (33%), 3 of 7 clear cell carcinomas of the ovary (43%), and the 1 clear cell papillary cystadenoma of the epididymis. Membranous RCCma reactivity was identified in 26 of the 50 mimics (52%). We conclude that PAX-2 is a useful marker for distinguishing metastatic CC-RCC from its potential morphologic mimics, but caution must be used in certain differential diagnostic settings where nonrenal tumors such as parathyroid carcinoma, ovarian clear cell carcinoma, and clear cell papillary cystadenoma of the epididymis were shown to express both PAX-2 and RCCma.

Pax-2 is a homeogene expressed during kidney development. Its expression in renal cell carcinoma (RCC) has been previously evaluated in histologic samples with a high sensitivity and specificity. Here, we investigated the utility of Pax-2 immunohistochemistry (IHC) for RCC in cytologic material, in comparison with a variety of other neoplasms. Pax-2 IHC was performed on cell block sections of 33 RCCs (14 primary, 19 metastatic) and 35 non-RCC malignancies, including 26 carcinomas, five mesenchymal tumors, one neuroblastoma, two melanomas, and one lymphoma, from fine-needle aspirations and body fluids. The presence or absence of nuclear staining and its intensity and distribution in positive cases were evaluated. Of 33 RCCs, Pax-2 was positive in 20 (61%) and negative in 13 (39%). All staining was nuclear, with an admixture of weakly or strongly staining nuclei. Only an endometrial adenocarcinoma was positive in the non-RCC group. The sensitivity and specificity of Pax-2 IHC for RCC were 61 and 97%, respectively. Pax-2 is a moderately sensitive and highly specific marker for RCC in cytologic material, with a lower sensitivity compared with tissue sections, likely due to a patchy expression pattern, and should be included in the immunohistochemical work-up of malignancies.

Ipilimumab is a novel humanized monoclonal antibody directed against cytotoxic T lymphocyte antigen 4, a T-cell surface molecule involved in down-regulation and suppression of the T cell response to stimuli. Patients treated with ipilimumab are at risk for immune-related adverse events involving the skin, digestive tract, liver and endocrine organs. Few case reports of immune-related adverse effects involving central or peripheral nervous system due to ipilimumab are published. These include inflammatory myopathy, aseptic meningitis, severe meningo-radiculo-neuritis, temporal arteritis, Guillain-Barre syndrome, and posterior reversible encephalopathy syndrome. We report the first case of ipilimumab-induced progressive necrotic myelopathy.

We report a case of orbital metastasis from a neuroendocrine dedifferentiated prostate cancer during progression from hormone-sensitive to hormone refractory stage. A patient receiving androgen deprivation for hormone-sensitive prostate cancer presented with sudden-onset rightsided ptosis and an increasing serum prostate-specific antigen level. Imaging studies revealed a mixed blastic and lytic lesion involving the right orbital wall and the right cavernous sinus. Comparison of the metastatic histology with the original pathology confirmed a histologic change to poorly differentiated prostate adenocarcinoma with neuroendocrine features. Local radiation of the lesion and palliative systemic chemotherapy resulted in marked short-term improvement of all presenting symptoms. Because prostate cancer metastasis involves hematogenous and lymphatic routes, we also evaluated expression of the vascular endothelial growth factor (VEGF) and receptors (VEGFR-1, VEGFR-2, and VEGFR-3) in the metastatic deposit by immunohistochemistry. Strong expression of VEGFR-2 and VEGFR-3 restricted to the malignant epithelium was noted. We recommend a second biopsy of atypical prostate metastasis associated with sudden change to aggressive clinical behavior in order to evaluate for dedifferentiation features before planning appropriate treatment interventions especially in patients who are candidates for systemic chemotherapy.

Small-cell carcinoma (SmC) and high-grade non-Hodgkin's lymphoma (NHL) are aggressive neoplasms that require prompt diagnosis and treatment. An immediate diagnosis can be obtained using fine-needle aspiration biopsy (FNAB) material from lymph nodes (LNs), which are clinically or radiologically suspicious for tumor involvement. However, in aspirates from LNs, the cytologic distinction of SmC from NHL can be challenging. The purpose of this study was to evaluate the usefulness of various cytologic features that can be used during a rapid on-site evaluation to differentiate these two entities. Twenty-seven metastatic SmC and 50 NHLs cases diagnosed by FNAB of LNs were reviewed. All NHL diagnoses (neck, 29; abdomen, 9; axilla, 6; groin, 5; and parotid, 1) were confirmed with tissue sections, flow cytometry, or immunohistochemistry. These cases were classified as follicular, 21 (42%); diffuse large B cell, 13 (26%); small lymphocytic, 7 (14%); mantle cell, 4 (8%); anaplastic large cell, 2 (4%); and 1 each (2%), Burkitt, lymphoplasmacytic, and peripheral T-cell lymphomas. Immunochemistry confirmed the cytologic diagnoses of all SmC cases (neck, 16; mediastinum, 9; abdomen, 1; and axilla, 1) with either positive chromogranin or synaptophysin. All specimens were reviewed independently by three cytopathologists who were unaware of the original diagnoses. The presence and proportion of single (noncohesive) tumor cells, lymphoglandular bodies, nuclear fragments, paranuclear blue inclusions, nuclear molding, evenly dispersed fine-granular chromatin, crush artifact, and composition of cell clusters (monomorphic vs. polymorphic) were statistically evaluated. The presence of evenly dispersed fine-granular chromatin, paranuclear blue inclusions, and nuclear fragments was each statistically significant in differentiating SmC when compared with NHL (P < 0.01). The remaining features were not significant in distinguishing SmC from NHL in LN aspirates. The identification of distinct cytologic findings such as evenly dispersed fine-granular chromatin, paranuclear blue inclusions, and nuclear fragments can be a valuable aid to accurately diagnose and differentiate metastatic SmC from NHL in FNAB preparations from LNs. Diagn. Cytopathol. 2004;31:229–234. © 2004 Wiley-Liss, Inc.

OBJECTIVE: To establish cytomorphologic criteria that might facilitate the identification of malignant melanoma (MM) cells with epithelioid (nevoid) morphology in fine needle aspiration biopsy material from the liver. STUDY DESIGN: Aspirated material from 18 cases of MM with epithelioid features and 24 cases of benign liver lesions (BLL) were examined. The cases were selected based on the availability of corresponding tissue biopsies, adequate cell block material or sufficient number of direct smears to perform immunocytochemical staining. The presence or absence of 7 cytologic criteria were reviewed, and the results were evaluated by multivariate regression analysis. , RESULTS: All evaluated criteria were significant for identifying MM cells and differentiating them from reactive hepatocytes (P

Renal cell carcinoma (RCC) not uncommonly presents with metastases and causes diagnostic difficulty to the cytopathologist who is involved in the initial diagnostic workup of tumors with an unknown primary site. RCC marker (RCC Ma) recognizes a human proximal tubule antigen and was shown to have high specificity and relatively low sensitivity in preliminary studies on routinely processed tissue sections. We investigated the diagnostic usefulness of RCC Ma immunohistochemically in fine-needle aspiration (FNA) samples. A total of 34 FNA samples obtained from the following carcinomas were used: 7 RCCs, 5 metastatic RCCs, 4 hepatocellular carcinomas, 2 non-small cell carcinomas of the lung, 3 metastatic non-small cell carcinomas of the lung, 4 invasive ductal carcinomas of the breast, 2 pancreatic ductal adenocarcinomas, 4 metastatic transitional cell carcinomas of the urinary bladder, and 3 metastatic colon carcinomas. Routinely processed cell block sections of FNA specimens were stained with RCC Ma by using routine immunohistochemistry. Presence and distribution of staining were evaluated. Two of 7 (29%) primary and 2 of 5 (40%) metastatic RCCs showed immunoreactivity in less than 50% of carcinoma cells. Staining was focal, cytoplasmic, and granular. Scattered positive cells were present in two of the four hepatocellular carcinomas. All breast, lung, pancreas, colon, and transitional cell carcinomas were negative. RCC antibody has a low sensitivity (33%), most likely because of its focal staining pattern, and a high specificity (91%) in FNA specimens. Immunoreactivity in metastatic carcinoma of an unknown primary site, especially as part of a panel of antibodies, is useful in diagnostic cytopathology. RCC antibody has not been studied in hepatocellular carcinoma, and the significance of positivity observed in some of our cases is unclear.

Meningiomas are benign tumors derived from arachnoid cells. Most commonly an intracranial lesion, meningiomas may be found extracranially in various anatomic sites. A 23-yr-old white female presented with left-sided palpable mass located submucosally in the floor of the mouth. CT scan revealed no evidence of mass elsewhere in the head and neck region. Fine-needle aspiration cytology (FNAC) showed loose and cohesive cellular fragments with lobular growth pattern and uniform round or ovoid cells. The diagnosis of low-grade salivary gland neoplasm, not further classified, was made. The tumor was locally excised. The differential diagnoses of an extracranial meningioma and pleomorphic adenoma were discussed at the frozen section. Based on light microscopic, immunohistochemical, and electron microscopic (EM) findings, the final diagnosis of an ectopic meningioma was rendered. Ectopic meningiomas may pose a diagnostic challenge to clinicians and cytopathologists. It is easily forgotten in the list of differential diagnosis at an ectopic site. Primary ectopic meningioma in a region containing salivary gland(s) may mimic benign and low-grade malignant salivary gland tumors in FNAC.

Dural based sarcoma is a rare aggressive neoplasm arising from the multipotent primitive mesenchymal stem cells of the dura. A 61-year-old male patient presented with complaints of loss of visual acuity in his right eye for 1 week. Neuroimaging revealed a tumour located at the right temporal lobe. The mass was dural-based. Three years ago dural based lesion was seen. In that period radiological diagnosis was meningioma. Within three years, the lesion has grown and radiologically presumed meningioma view has been disappeared. After surgical resection of the mass pathological diagnosis of primary dural based sarcoma was made. As in soft tissue sarcomas, diagnosis is mainly based on light microscopy, while immunohistochemistry can improve accuracy of diagnosis. In this article we would like to highlight two things: one is dural sarcoma and meningioma cannot be distinguished radiologically, and the other is the patient's three-year history

OBJECTIVE AND IMPORTANCE Giant-cell tumors (GCTs) are primary bone tumors that involve long bones in 75 to 90% of patients. They seldom develop in the cranium and are very rare in patients older than 60 years of age. A GCT rarely occurs with Paget's disease; when it does, however, it is most commonly associated with the polyostotic form and tends to involve the craniofacial bones. Pagetic GCTs are less aggressive than GCTs that are not associated with Paget's disease. CLINICAL PRESENTATION We report the case of an 81-year-old woman with a painless left parietal mass and asymptomatic monostotic parietal Paget's disease. INTERVENTION Surgical resection was performed, and histological examination of the lesion demonstrated Paget's disease with a malignant GCT. An incidental, low-grade, small-cell lymphocytic lymphoma also was noted. The patient experienced local recurrence of the malignant GCT and eventually died after developing pulmonary metastases of the malignant GCT. CONCLUSION This case is the first reported example of a patient with a malignant GCT of the cranium associated with monostotic Paget's disease. It provides evidence that not all pagetic GCTs in the cranium are benign, as has been reported.

✓ Lesions involving the sagittal sinus typically present as masses compressing the sinus externally. The authors describe two cases of lesions entirely within the lumen of the sagittal sinus. In one of the cases, syncope was the presenting symptom and surgical resection of the cyst was performed. An entirely intraluminal cyst, consistent with a dural cyst, was resected, followed by reconstruction of the sinus and resolution of symptoms. Entirely intraluminal lesions of the sagittal sinus have rarely been reported as incidental findings. This represents the first report of symptomatic occlusion of a venous sinus by an intraluminal cyst.

Primary intracranial meningeal melanocytoma (PIMM) is an uncommon, neoplasm of the central nervous system. It is a relatively benign entity and needs to be considered in the differential diagnosis of pigmented, melanin containing intracranial lesions. A case of a 25 year old right handed male, who presented with right side facial numbness, tingling and headaches, is presented. MRI findings suggested a diagnosis of primary meningeal melanocytoma, which was surgically and pathologically confirmed.

A 32-year-old Hispanic woman at 23 weeks gestation presented with right-sided headache, associated with photophobia and right-sided numbness. She denied visual problems, menstrual irregularities and galactorrhoea. Examination revealed visual acuity 20/40 bilaterally with some blurriness on the left side, decreased right V1-V2 facial sensation and preserved 5/5 power, but decreased sensation over the entire right upper extremity (RUE) and right lower extremity (RLE) to touch and pinprick. Laboratories suggested normal pituitary function, but MRI of the brain revealed enlargement of the pituitary (1.7 cm), with layering haemorrhage posteriorly and mild compression of the optic nerve. The patient underwent emergent evacuation of a pituitary haematoma, and histology revealed minute fragments of adenohypophysis with haemorrhage and fibrosis.

This chapter discusses the pathologic features of pituitary adenoma and craniopharyngioma, the two most common and problematic neoplasms of the region of sella turcica. Pituitary adenoma, even when it is small, can present with very diverse clinical and pathological findings owing to its variety of cell types and its location. An increasing number of subtypes are being recognized based on histological and immunohistochemical features. Valuable data can be obtained from the pathologic evaluation in terms of biologic aggressiveness of the adenoma, and its further characterization as invasive and/or atypical. Craniopharyngioma is a low grade neoplasm that can be quite problematic due to its locally invasive nature and recurrences. Histologic subtypes, namely adamantinomatous and papillary, are reviewed; their pathologic features and prognoses are discussed. Finally, the interesting coexistence of these two neoplasms is discussed briefly.

PAX-2, a homeogene expressed during kidney development, has been studied as a marker of renal origin in both primary and metastatic clear cell renal cell carcinoma (RCC), but not in papillary neoplasms or in comparison with RCC marker (RCCma). We studied immunohistochemical expression of PAX-2 and RCCma in 24 papillary RCC (PRCC) and 66 nonrenal cell papillary neoplasms (NRCPN) from a variety of organs. Of the PRCC, 16/24 (67%) were positive for PAX-2; 23/24 (96%) were positive for RCCma. Of the NRCPN, 9/66 (14%) is positive for PAX-2 [4/10 (40%) ovarian papillary serous carcinomas, 5/9 (56%) uterine papillary serous carcinomas]; RCCma was positive in 28/66 (42%), including 9/9 (100%) papillary thyroid carcinomas, 8/10 (80%) ovarian papillary serous carcinomas, 4/9 (44%) uterine papillary serous carcinomas, 1/10 (10%) papillary urothelial carcinomas, 1/2 (50%) intraductal papillary mucinous carcinomas of the pancreas, 3/3 (100%) choroid plexus papillomas, 1/1 (100%) pituitary adenoma with papillary features, and 1/2 (50%) lung adenocarcinomas with papillary features. The sensitivity of PAX-2+/RCCma+ immunophenotype for PRCC was 58% with a specificity of 54%. There is significant overlap between the expressions of these markers in PRCC and NRCPN; however, the positivity of RCCma and/or PAX-2 is 100% sensitive for PRCC and may prove useful in the initial work up of metastases of unknown primary. PAX-2 and RCCma immunohistochemistry should be interpreted with caution in papillary neoplasms, with particular attention to the possibility of ovarian and uterine papillary serous carcinomas, which can express both PAX-2 and RCCma.

Kidney lesions in patients with von Recklinghausen typically include blood vessels with smooth muscle proliferation resulting in hypertension, and perirenal nerve sheath tumors. In the English language literature, there is only 1 report published more than 25 years ago that described a previously unrecognized renal parenchymal lesion, termed sclerosing peritubular nodules, in 3 members of a family affected by von Recklinghausen disease. These nodules were examined by light microscopy, histochemistry, and electron microscopy; they proved to be derived from interstitial cells, and the proliferating cells showed myofibroblastic differentiation by electron microscopy. We report a case of a 22-year-old man with hereditary neurofibromatosis type 2 who died with complications of the disease. He underwent autopsy, and his kidneys showed this unique lesion. We examined these peritubular proliferations with immunohistochemistry, histochemistry, and electron microscopy and compared our findings with the previous report in the literature.

We report successful treatment of cerebral toxoplasmosis in an unrelated donor marrow transplant recipient. The clinical diagnosis was confirmed by polymerase chain reaction (PCR) amplification for T. gondii-DNA performed both on cerebrospinal fluid and blood leukocytes. Retrospective testing of stored blood samples demonstrated positive leukocyte PCR signal detected up to 52 days prior to onset of clinical symptoms. This case highlights the value of PCR in the diagnosis and early detection of cerebral toxoplasmosis.

BACKGROUND Chordoma and chondrosarcoma of the skull base are frequently amalgamated because of similar anatomic location, clinical presentation, and radiologic findings. The chondroid chordoma variant has been reported to carry a better prognosis. The objective of the current study was to investigate the distinctions between these 3 entities. METHODS The data concerning 109 patients with chordoma, chondroid chordoma, and chondrosarcoma who were treated by a single surgeon with maximum surgical resection and frequently by adjunct proton beam radiotherapy between 1990 and 2006 were analyzed retrospectively. Pathologic distinction was established by cytokeratin and epithelial membrane antigen staining. Clinical, radiologic, pathologic, and cytogenetic studies were analyzed in relation to disease recurrence and death. RESULTS The average follow-up was 48 ± 37.5 months (range, 1–191 months). There were no reliable distinguishing clinical or radiologic features noted between the groups. Chondrosarcoma patients had a significantly better outcome compared with chordoma patients with regard to survival and recurrence-free survival (P = .028 and P < .001, respectively), whereas patients with chondroid chordoma had a poor outcome similar to chordoma patients with regard to survival and recurrence-free survival (P = .337 and P = .906, respectively). CONCLUSIONS Chordoma and chondrosarcoma differ with regard to their origin and histology, and differ markedly with regard to outcome. Chondroid chordomas behave in a manner that is clinically similar to chordomas, with the same prognosis. Both chordoma types demonstrate an aggressive clinical course and poor outcome after disease recurrence. The optimal treatment for all groups of patients involves radical surgical resection followed by high-dose radiotherapy in patients with chordomas. Radiotherapy may not be necessary in patients with low-grade chondrosarcoma. Cancer 2007. © 2007 American Cancer Society.