A Rare Prolactin-secreting Pituitary Carcinoma With Epidural and Thecal Metastases.

Pituitary carcinomas are rare but associated with significant morbidity and mortality. They remain challenging to diagnose and manage. In this case, we describe a 56-year-old man who presented with erectile dysfunction and binocular vertical diplopia. He had central hypogonadism, secondary adrenal insufficiency, and central hypothyroidism on biochemical testing. His serum prolactin was 1517 mcg/L (1517 ng/mL; reference range 4-15 mcg/L), and his sellar magnetic resonance imaging showed a 2.0 × 2.2 × 3.1 cm pituitary tumor. Pathology revealed a prolactin-secreting carcinoma. Despite treatment with a high-dose dopaminergic, 2 transsphenoidal resections, and 1 course of radiation, prolactin levels continued to rise. He developed metastases to the epidural space and thecal sac from the thoracic to sacral spine, for which he received 12 cycles of temozolomide chemotherapy with initial clinical and biochemical response. This was followed by disease escape and progression. We discuss the clinical and imaging features that warrant a high index of suspicion for pituitary carcinoma and review contemporary treatment.

Embolized cerebral arteriovenous malformations: a multivariate analysis of 101 excised specimens.

OBJECTIVE: Endovascular approaches have evolved from a technique practiced at very few centers to a widely available option in the management of arteriovenous malformations (AVMs) of the central nervous system. Embolization can be employed as definitive therapy or as an adjunct to surgical excision. A wide variety of embolic agents have been successfully developed and used in the clinical setting. In addition to facilitating vascular occlusion, embolic agents induce a number of reactive and destructive changes in vessel walls and the surrounding tissue. However, studies examining the pathological changes induced by different embolic agents and varying times of exposure are scarce. The goal of the present study was to compare embolic agents and time of exposure on the pathology in excised specimens. METHODS: The records of the Department of Pathology at the London Health Sciences Centre were searched for embolized AVMs for the 35-year period 1980-2015. All cases were reevaluated for clinical and technical variables and standardized histopathological findings. Cases were grouped by embolic agent, volume of agent used, and time to excision. RESULTS: A total of 101 specimens were identified. Embolic agents were invariably associated with a range of pathological findings, some of which may affect the integrity of vessel walls or the reestablishment of flow, thrombosis, acute and chronic inflammatory changes, angionecrosis, extravasation, and recanalization. The type of embolic agent did not predict differences in the incidence or severity of histopathological changes. Larger volumes of embolic agent were associated with a greater proportion of vessels containing embolic material. AVMs excised early (< 1 week postembolization) contained more acute vasculitis, while those excised later (≥ 1 week postembolization) were more likely to exhibit recanalization and foreign body giant cell infiltrates. CONCLUSIONS: Embolic agents induce a predictable range and temporal progression of pathological changes in cerebral AVMs. The embolic agents studied are indistinguishable in terms of the range and frequency of pathological reactions induced. Greater volumes of embolic agent are associated with more abundant agent within the lesion, but the proportion of vessels and vascular cross-sectional areas containing agent is small. Several changes are significantly associated with time postembolization. Acute vasculitis is a more common finding in the 1st week, while recanalization and foreign body-type granulomatous inflammation are more common at 1 week and beyond.

Incisional Seeding of Metastatic Squamous Cell Carcinoma Following Carotid Endarterectomy: An Unusual Case of an Unknown Primary Cancer Presenting as a Presumed Neck Abscess.

BACKGROUND: Carotid endarterectomy (CEA) is a safe and effective procedure, with a low risk of complications when performed by experienced surgeons. Postoperative infections are particularly rare, reportedly affecting less than 1% of cases. Incisional metastases have not been described. OBJECTIVE: To describe a previously unreported complication, the incisional seeding of metastatic squamous cell carcinoma (SCC) during neck dissection, which presented and was treated as a presumed postoperative neck abscess. METHODS: Clinical records were reviewed regarding a 73-yr-old female who underwent routine CEA and presented 2 mo postoperatively with neck induration and erythema. Tissue submitted during the initial CEA was reexamined given the updated clinical history. RESULTS: Postoperatively, a complex, multi-cystic fluid collection beneath the incision was identified and percutaneously drained. Although cultures were negative, an infection was favored and antibiotic therapy initiated. The patient's symptoms worsened prompting surgical exploration, and tissue sent for pathological examination was consistent with metastatic SCC. Retrospective analysis of a lymph node excised during the initial dissection also revealed tumor deposits, indicating that the surgical site had been seeded during exposure. A primary origin was not identified. CONCLUSION: The time from initial presentation of postoperative complications to a final diagnosis of metastatic SCC was 2 mo, during which time the patient was treated as having a postoperative infection. Further investigations were consistent with diffuse and incurable metastatic disease. This report highlights the diagnostic challenges and potential avoidance strategies when dealing with rare complications following CEA.

Two cases of rheumatoid meningitis.

Central nervous system (CNS) involvement by rheumatoid arthritis (RA) in the form of rheumatoid meningitis (RM) is rare and most commonly occurs in the setting of longstanding severe RA. Due to a wide range of clinical presentations and nonspecific laboratory findings, it presents a diagnostic challenge often requiring brain biopsy. Only a few histopathologically confirmed cases have been described in the literature. Our aim is to describe two cases of RM and review the literature. The first case is of a previously healthy 37-year-old man who presented with severe headaches and focal neurologic deficits. Magnetic resonance imaging demonstrated abnormal leptomeningeal enhancement in the left frontal and parietal sulci. The second case is of a 62-year-old woman with a history of mild chronic joint pain who presented with confusion, personality changes and seizures. Both patients ultimately underwent brain biopsy which demonstrated RM on pathologic examination. Administration of corticosteroids resulted in significant clinical improvement in both cases. To our knowledge, our unusual case of RM in the young man is the fifth reported case of rheumatoid meningitis in a patient with no prior history of RA. Such an atypical presentation makes diagnosis even more difficult and highlights the need for awareness of this entity in the diagnostic consideration of a patient presenting with unexplained neurologic symptoms. Our literature review underscores the clinical and pathologic heterogeneity of CNS involvement in RA.

Magnetic resonance imaging and histology correlation in the neocortex in temporal lobe epilepsy.

OBJECTIVE: To investigate the histopathological correlates of quantitative relaxometry and diffusion tensor imaging (DTI) and to determine their efficacy in epileptogenic lesion detection for preoperative evaluation of focal epilepsy. METHODS: We correlated quantitative relaxometry and DTI with histological features of neuronal density and morphology in 55 regions of the temporal lobe neocortex, selected from 13 patients who underwent epilepsy surgery. We made use of a validated nonrigid image registration protocol to obtain accurate correspondences between in vivo magnetic resonance imaging and histology images. RESULTS: We found T1 to be a predictor of neuronal density in the neocortical gray matter (GM) using linear mixed effects models with random effects for subjects. Fractional anisotropy (FA) was a predictor of neuronal density of large-caliber neurons only (pyramidal cells, layers 3 and 5). Comparing multivariate to univariate mixed effects models with nested variables demonstrated that employing T1 and FA together provided a significantly better fit than T1 or FA alone in predicting density of large-caliber neurons. Correlations with clinical variables revealed significant positive correlations between neuronal density and age (rs = 0.726, pfwe = 0.021). This study is the first to relate in vivo T1 and FA values to the proportion of neurons in GM. INTERPRETATION: Our results suggest that quantitative T1 mapping and DTI may have a role in preoperative evaluation of focal epilepsy and can be extended to identify GM pathology in a variety of neurological disorders.

Registration of in-vivo to ex-vivo MRI of surgically resected specimens: a pipeline for histology to in-vivo registration.

BACKGROUND: Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to develop and evaluate a protocol for deformable image registration of in-vivo to ex-vivo resected brain specimen MRI. This protocol, in conjunction with our previous work on ex-vivo to histology registration, completes a registration pipeline for histology to in-vivo MRI, enabling voxel-based validation of novel and existing MRI techniques with histopathology. NEW METHOD: A combination of image-based and landmark-based 3D registration was used to register in-vivo MRI and the ex-vivo MRI from patients (N=10) undergoing epilepsy surgery. Target registration error (TRE) was used to assess accuracy and the added benefit of deformable registration. RESULTS: A mean TRE of 1.35±0.11 and 1.41±0.33mm was found for neocortical and hippocampal specimens respectively. Statistical analysis confirmed that the deformable registration significantly improved the registration accuracy for both specimens. COMPARISON WITH EXISTING METHODS: Image registration of surgically resected brain specimens is a unique application which presents numerous technical challenges and that have not been fully addressed in previous literature. Our computed TRE are comparable to previous attempts tackling similar applications, as registering in-vivo MRI to whole brain or serial histology. CONCLUSION: The presented registration pipeline finds dense and accurate spatial correspondence between in-vivo MRI and histology and allows for the spatially local and quantitative assessment of pathological correlates in MRI.

Childhood-onset nonprogressive chronic encephalitis.

PURPOSE: The purpose of this study was to describe a series of patients with pathologically proven chronic encephalitis who had a nonprogressive course during a long follow-up, suggestive of a "benign" variant of Rasmussen's encephalitis (RE). METHODS: Four patients who were referred to our Comprehensive Epilepsy Program at London Health Science Centre in London, Ontario, were diagnosed with chronic encephalitis on a pathological basis after epilepsy surgery to treat their partial-onset seizures. RESULTS: None of our four cases followed the typical course of RE despite their childhood-onset seizures between ages 2 and 12years. One was preceded by a mild head trauma and fever at onset. None had epilepsia partialis continua (EPC). Their long-term follow-up revealed a nonprogressive form of the syndrome with respect to the neurological examination, EEG, MRI, and neuropsychological findings. CONCLUSION: These cases extend the spectrum of childhood-onset intractable epilepsy with chronic encephalitis to include nonprogressive variants of RE. The absence of EPC may be a prognostic indicator of a nonprogressive course.

Do epileptic seizures predict outcome in patients with oligodendroglioma?

BACKGROUND: Many patients with an oligodendroglioma (OD) experience seizures, some of which become refractory to anti-epileptic drugs (AEDs). This study aims (1) to quantify the rate of seizures and medically refractory epilepsy in patients with ODs; and (2) to determine if there is any association between short-term and long-term survival, and the presence and drug-responsiveness of seizures. METHODS: A retrospective review was conducted of the medical records of patients who had been pathologically identified as having an OD at the London Health Sciences Centre or the London Regional Cancer Program in London, Ontario from January 1996 to July 2008. Deaths were ascertained by reviewing all hospital records. Survival analysis was performed. RESULTS: One-hundred sixty-six patients met inclusion criteria. Epileptic seizures were the presenting feature or occurred as part of the initial manifestation of the OD in 75.3% of patients, with 90.4% (n=150) experiencing at least one seizure and 76.5% developing epilepsy over the course of observation. Of the 150 patients with seizures, 23 experienced a single seizure (13.9% of the 166), whereas 127 patients experienced multiple seizures (76.5%). In those with multiple seizures, the epilepsy was refractory to drug treatment slightly more than half the time (54.3%). Survival analysis demonstrated consistently superior survival among those with a single seizure. Those without seizures had the worst survival rates over the first few years post-diagnosis; but then no further deaths occurred. Survival among those with refractory seizures tended to be better than among those whose seizures were drug responsive, over the first 10 years post-diagnosis. CONCLUSIONS: Seizures are common and may influence survival in patients with oligodendogliomas. Those who experience just one seizure appear to do best.

Staged transcrusal and transsphenoidal endoscopic resection of an atypical clival melanoma: a case report and literature review.

We present a case of an atypical clival meningeal melanoma treated with a multidisciplinary staged transcrusal and transsphenoidal endoscopic surgical approach. A 45-year-old woman presented with a 15-month history of visual symptoms, neck pain, and unsteadiness. Magnetic resonance imaging of the head revealed a clival mass with both intracranial and extracranial involvement. Endoscopic clival biopsy suggested a melanocytic tumor. Extensive imaging and dermatological workup did not demonstrate a primary source. A multidisciplinary staged surgical resection included a transcrusal approach to resect the intracranial component, followed by transsphenoidal endoscopic resection of the extracranial component. Postoperatively, she received adjuvant radiation. At 1 year following surgery, the patient retains full preservation of hearing, facial nerve function, and extraocular movements. To our knowledge, this is the first case report of a combined surgical approach for a primary clival meningitic melanoma.

Pediatric thalamic glioblastoma associated with Ollier disease (multiple enchondromatosis): a rare case of concurrence.

Ollier disease and Maffucci syndrome are rare syndromes in which there is deforming dysplasia of cartilage, primarily but not exclusively involving the metaphyses and diaphyses of long bones. In a minority of patients, dysplasia can lead to sarcomatous degeneration, producing chondrosarcomas. There also appears to be an association with other neoplasms. Little has been written about the association between Ollier disease and intracranial tumors, and these papers have largely consisted of case reports in adults. The authors present the case of a 6-year-old girl with left arm osseous changes consistent with Ollier disease and a biopsy-proven thalamic glioblastoma multiforme. They then examine the co-occurrence of brain tumors in conjunction with a dyschondroplasia syndrome in children and adolescents to assess the presentation, treatment offered, and disease course of similar cases. Eight other such cases were identified, 6 in patients with Ollier disease (ranging in age from 7 to 18 years), and 2 with Maffucci syndrome (both in late adolescence). Including our own patient, 7 of the 9 cases of comorbid dyschondroplasia and intracranial malignancy occurred in girls. Some patients presented soon after the acute onset of symptoms, and others had a more subtle, protracted course over as many as 2 years. Some tumors were deemed resectable and others not. In only 1 instance was follow-up beyond 1 year reported.

Percutaneous muscle biopsies: review of 900 consecutive cases at London Health Sciences Centre.

OBJECTIVE: In the present study we review our experience with 900 consecutive percutaneous muscle biopsies over the period 1993 to 2007. We examined the advantages and limitations of the procedure, biopsy site preferences, diagnostic range, frequency of diagnoses and quality of histopathology. Demographics, referral patterns and patients' perceptions of the procedure were also assessed. METHODS: Cases were identified through the London Health Sciences Centre Department of Pathology database. Standard biopsy procedures were followed using a manual trocar style instrument. With a neuropathology technologist in attendance at all biopsies, biopsies were oriented in the fresh state and snap frozen. RESULTS: Most referrals for muscle biopsy were from neuromuscular neurologists. The procedure was found to be efficient, well-tolerated and produced high quality specimens in all diagnostic categories. No major complications occurred. Failure to obtain an adequate tissue sample, although uncommon (< 2%), was usually due to marked obesity, edema or muscle wasting. Bleeding at the site was rarely problematic and no wound infections were reported. CONCLUSIONS: Needle muscle biopsies represent an efficient alternative to open biopsies when peripheral nerve sampling is not required and when large tissue samples are not needed for extensive biochemical analyses.

Pathophysiological implications of focal cortical dysplasia of end folium for hippocampal sclerosis.

Dual pathology is a well-known cause of temporal lobe epilepsy (TLE), but TLE associated with dual pathology within the hippocampus has rarely been reported. We describe a patient with medically refractory TLE due to a focal cortical dysplasia of the end folium of the left hippocampus (i.e. CA4) and left hippocampal sclerosis (HS) that was successfully treated with left anterior temporal lobectomy and speculate on the interaction between end folium sclerosis and HS.

A 15 year old boy with a posterior fossa tumor.

A 15 year old male presented with hydrocephalus from a tectal mass obstructing the cerebral aqueduct and upper fourth ventricle. The solid-cystic partly enhancing mass proved to be a pigmented pleomorphic xanthoastrocytoma, the third such example reported. The lesion revealed typical features of a PXA with the unusual addition of intracytoplasmic melanin in select lesional cells. Melanin pigment production is uncommon in glial tumors and of uncertain significance. The present case is recurrence-free one year post-operatively.

A stronger approach to weakness in the intensive care unit.

ICU-acquired limb and respiratory muscle weakness is a common, serious ICU syndrome, increasing in frequency with prolonged ICU stay and sepsis. A systematic approach facilitates precise localization of the problem within central or peripheral nervous system. Most cases relate to critical illness polyneuropathy or myopathy or a combination of both (critical illness neuromyopathy). Within the latter entity, the relative contribution of neuropathy versus myopathy varies considerably among affected patients. Muscle enzyme testing, electromyography-nerve conduction and muscle biopsy are valuable investigative tests. Nerve biopsy is less commonly needed, but is useful when vascultis is suspected.

Zinc- or cadmium-pre-induced metallothionein protects human central nervous system cells and astrocytes from radiation-induced apoptosis.

We have shown the protection of human central nervous system (CNS) cultures by zinc (Zn) or cadmium (Cd)-pre-induced metallothionein (MT) synthesis from radiation-induced cytotoxicity (lactate dehydrogenase (LDH) release and neuronal dendritic injury). The present study is to further define the types of cell death induced by different dose levels of radiation and investigate the effect of MT induction (by Zn or Cd) on radiation-induced apoptosis in primary human CNS and astrocyte cultures. Apoptosis was detected by fragmented DNA electrophoresis, TUNEL technique, and propidium iodide staining. Expression of MT protein was examined by immunofluorescent staining. Results showed that exposure of primary human CNS cultures to 15 and 30 Gy gamma-radiation predominantly induced apoptotic cell death, while exposure to 60 Gy gamma-radiation predominantly induced necrotic cell death. Normal primary human CNS cultures showed weak MT staining, while primary human CNS cultures exposed to Zn or Cd showed intense MT staining. The induced apoptotic cell death by exposure to 30 Gy gamma-radiation increased to a maximum level at 12 and 24 h, and was reduced significantly by Zn or Cd pre-induced MT. Using primary human astrocytes, the induction of MT protein by Zn or Cd was further confirmed. The enhanced MT expression also afforded a significant protection from 30 Gy gamma-ray-induced apoptosis in the primary human astrocytes. These results suggest that MT protected human CNS cells from apoptosis following ionizing radiation, probably through its antioxidant property.

Quantitative assessment of carotid plaque composition using multicontrast MRI and registered histology.

MRI is emerging as a promising modality for monitoring carotid atherosclerosis. Multiple MR contrast weightings are required for identification of plaque constituents. In this study, eight MR contrast weightings with proven potential for plaque characterization were used to image carotid endarterectomy specimens. A classification technique was developed to create a tissue-specific map by incorporating information from all MR contrast weightings. The classifier was validated by comparison with micro-CT (calcification only) and with matched histological slices registered to MR images using a nonlinear warping algorithm (other components). A pathologist who was blinded to the classifier results manually segmented digitized histological images. The sensitivity of the classifier, as determined by pixel-by-pixel comparison with the pathologist's segmentation and micro-CT, was 60.4% for fibrous tissue, 83.9% for necrosis, 97.6% for calcification, and 65.2% for loose connective tissue. The corresponding values for specificity were 87.9%, 75.0%, 98.3%, and 94.9%, respectively. In conclusion, multicontrast MRI was successfully used in conjunction with a supervised classification algorithm to identify plaque components in endarterectomy specimens. Furthermore, this methodology will provide a framework for comparing different classification algorithms, and determining which combination of MR contrasts will be most valuable for in vivo plaque imaging.

Dural cavernous angioma: a preoperative diagnostic challenge.

BACKGROUND: Dural cavernous angiomas are uncommon benign vascular malformations which may present intraoperative difficulties in hemostasis when the diagnosis is not suspected preoperatively. Preoperative diagnosis can be difficult when angiomas show atypical features and share imaging characteristics with other entities. METHODS: A patient presented with a radiographically aggressive lesion, subsequently identified as a dural cavernous angioma. The lesion is reviewed and its clinical, radiographic, and pathological features are compared with other vascular malformations. CASE REPORT: A 40-year-old man presented with new onset seizures and an enhancing lesion infiltrating the floor of the right middle cranial fossa. Due to its aggressive radiographic appearance, initial considerations included chondrosarcoma, meningioma or metastasis. Pathological examination, however, revealed the lesion to be a cavernous angioma of dura. CONCLUSION: This uncommon lesion may present a diagnostic challenge with significant intraoperative implications. T2 sequence hyperintensity in a relevant lesion should raise suspicion of an hemangioma. It is important to be aware of this entity and its potential to mimic other entities on radiographic grounds.