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We describe the case of a 29-year-old male who presented with new-onset seizures. He was subsequently found to have an orbital encephalocele containing a focus of pilocytic astrocytoma. We believe that this is the first report of a pilocytic astrocytoma located within the orbit that did not originate from the optic pathway. It is also the first case of a pilocytic astrocytoma completely contained within an encephalocele. This case suggests a close pathological examination of encephaloceles for underlying diseases.

Intracranial melanotic schwannomas (IMSch) are extremely rare nerve sheath tumors with features of Schwann cells that produce melanin. After a thorough review of the available literature since 1967, we report not only the 20th case of IMSch but a comprehensive modern-era analysis of radiographic and histological key-points to be considered when diagnosing and treating patients with this rare known entity. This is the case of a 43 years-old woman who presented with severe headaches 9 years ago (2008). At that time, MRI of the brain showed a 1.5 × 1.4 cm lesion at the level of the left cerebellar peduncle without any evidence of edema, mass effect or hydrocephalus. Given that the patient was neurologically intact, a conservative management with serial MRIs was recommended. Patient stopped following up due to the absence of symptoms. Over the course of the past year, patient noted mild left sided hearing loss and facial weakness, as well as some balance instability that progressed over the last 3 months. Given the presentation and progression of these signs and symptoms, a new MRI was performed in which considerable growth of the lesion was identified, measuring 2.5 × 2.8 × 2.6 cm with mass effect on the pons and the inferior fourth ventricle. She underwent a far lateral approach without a C1 hemilaminectomy for the resection of this lesion. Final pathology was consistent with a non-psammomatous melanotic schwannoma (NPMS) with areas of necrosis. Besides this case, only two other cases of IMSch with findings of necrosis have been reported in the literature, all of them reporting a subtotal resection. Evaluation of all previously reported cases of IMSch shows a male prevalence with a 1.6:1 male to female ratio. IMSch is radiographically T2 hypointense and can be differentiated from Schwannomas that are classically T2 hyperintense. In this case, only a subtotal resection was feasible due to the tumor’s overwhelming inherent attachment to vital structures such as cranial nerves (CN), brainstem, and vasculature. While MSch is considered histologically benign, several factors including localization, surrounding structures, the rate of growth, tumor volume resection and histological necrosis should be considered in determining prognosis and further adjuvant treatment planning.

This study determines the extent of deposition in gadolinium-based contrast agent–exposed pediatric population and whether prior observations were related to age-dependent breakdown of the blood blood-brain barrier.

Introduction Vestibular schwannoma (VS) behavior following subtotal resection (STR) is highly variable. Overall progression rates have been reported as high as 44%, and optimal treatment is controversial. Correspondingly, identification of a reliable clinical or pathologic marker associated with progression after STR would help guide decision-making. Methods A prospectively maintained institutional VS registry from 1999 to 2014 was retrospectively reviewed for sporadic VS patients who underwent primary STR without preceding stereotactic radiosurgery (SRS) by a single neurosurgery-neurotology team. Primary endpoints included tumor progression and postoperative facial nerve function. Pathologic specimens were stained for Ki67, CD68, S100, and SOX10 and were quantitated by digital imaging analysis. Macrophage density was defined as the ratio of CD68+ macrophages to S100+ macrophages and Schwannian tumor cells. Clinical outcomes were correlated with pathologic markers. Results Forty-six patients met the study inclusion criteria. Thirteen (28%) progressed during a mean 57 months of follow-up (range 15–149). Favorable postoperative facial nerve function (House–Brackmann I–II) was achieved in 37 (80%). CD68+ cells were present at significantly higher concentrations in tumors that progressed (p = 0.03). Higher macrophage density was significantly associated with both tumor progression (p = 0.02) and unfavorable facial nerve function (p = 0.02). Ki67 percent positivity was not significantly associated with either primary endpoint (p = 0.83; p = 0.58). Conclusions Macrophage density may provide an important marker for individuals at the highest risk for progression of VS after STR, potentially prompting closer surveillance or consideration for upfront SRS following STR. This finding supports preceding conclusions that an intratumoral macrophage-predominant inflammatory response may be a marker for tumor growth and a potential therapeutic target.

Objective: To understand the pathologic and clinical correlates of patients with chronic meralgia paresthetica (MP) undergoing lateral femoral cutaneous nerve (LFCN) neurectomy. Methods: A retrospective cohort approach was utilized to identify 7 patients undergoing LFCN neurectomy for intractable pain. Control autopsied LFCN was obtained. Clinical, radiologic, and electrophysiologic features were reviewed. Results: In identified cases, preoperative symptoms included severe lateral thigh pain and numbness. The duration of symptoms prior to surgery ranged from 2 to 15 years. Body mass index (BMI) varied from 20 kg/m 2 to 44.8 kg/m 2 (normal–morbidly obese), with 6 out of 7 patients being obese. No patients were diabetic. Focal nerve indentation at the inguinal ligament was seen intraoperatively and on gross pathology in 4 of 7 cases. Multifocal fiber loss, selective loss of large myelinated fibers, thinly myelinated profiles, regenerating nerve clusters, perineurial thickening, and subperineurial edema were seen. None of these features were observed in control nerve. Morphometric analysis confirmed loss of large myelinated fibers with small and intermediate size fiber predominance. Five patients had varying degrees of intraneural and epineurial inflammation. Six of 7 reported improved pain after neurectomy, sometimes dramatic. Conclusions: Patients with chronic MP and intractable pain have an LFCN mononeuropathy with loss of nerve fibers. Pathologic and clinical study supports a compressive pathogenesis as the primary mechanism. Abnormal nerve inflammation coexists and may play a role in pathogenesis. These selected patients typically benefited from neurectomy at a site of inguinal ligament compression. Classification of Evidence: This study provides Class IV evidence that patients with chronic MP LFCN neurectomy experience improvement in MP-related pain.

Background Epithelioid glioblastoma (eGBM) is a very rare histologic variant of glioblastoma that has not been studied in isolation and, therefore, its optimal management has been largely assumed, but not confirmed. The aim of this study was to analyze all reported cases describing the presentation and clinical features to better understand the clinical significance of this histologic diagnosis. Methods A comprehensive literature search was conducted from 2005 to April 2019 identifying cases of eGBM that satisfied selection criteria for analysis. Survival was investigated using Kaplan-Meier estimations, and then univariate and multivariate logistic regression analyses for primary end point overall survival (OS) and second end point progression-free survival (PFS). Results A total cohort of 59 eGBM cases from 28 articles were included for final analysis. Median age of patients at diagnosis was 30 years, with 29 (46%) female patients. When reported, 100% (37/37) cases were IDH1-wild-type and 63% (19/30) were positive for the BRAF V600E mutation by immunohistochemistry. Median OS and PFS were estimated to be 11.0 months (95% confidence interval, 6.5–13.0) and 7.0 months (95% confidence interval, 3.0–10.0), respectively. Surgical extent of resection, radiation therapy, and chemotherapy all predicted superior OS and PFS on multivariate analysis (P Conclusions These findings indicate that the histologic diagnosis of eGBM does not deviate from the clinical course of the broader glioblastoma diagnosis, despite being a unique histologic identity. These results argue against the temptation to deviate from the traditional management paradigm of surgery, radiation, and chemotherapy for glioblastoma based on this histology alone.

Prolactinomas are primarily treated with medical therapy. Given the efficacy of dopamine agonists (DAs), surgery has remained a second-line treatment option. Despite medical therapy, some tumors display resistance and/or patients maybe intolerant of DA and require alternative treatment options. We examined the indications, efficacy, and safety of pituitary surgery for the treatment of prolactinomas.We performed a retrospective analysis of all patients who had surgery for a prolactinoma at our institution from January 1993 to October 2014.Seventy-eight patients (46 females, mean age 32 years) with a median follow-up of 12 months were analyzed. Macroprolactinomas accounted for 65% (51/78) of tumors. The most common indication for surgery in microprolactinomas was medication intolerance (37%, 10/27) and medication failure (33%, 17/51) in macroprolactinomas. DA therapy had been tried in 76% (59/78) patients prior to surgery. Following surgery, long-term remission was seen in 72% (18/25) of micro-adenomas and 20% (10/49) of macro-adenomas (32% [10/32] in those without cavernous sinus invasion). Despite persistent disease in those with macro-adenomas (34% [13/38]) were able to remain off medication. Early surgical failure was more common in males (P = .004) and those with large (P≤.001) or atypical (P = .003) adenomas.Surgery can result in prolonged remission in 72% of microprolactinomas. Despite lower remission rates among macroprolactinomas, a third of patients with persistent disease did not require medical therapy. Therefore, surgery remains an alternative effective treatment option, particularly for those who are intolerant or resistant to medical therapy.ACTH = adrenocorticotropic hormone CI = confidence interval CSF = cerebrospinal fluid DA = dopamine agonist IQR = interquartile range MIB-1 = methylation inhibiting binding protein-1 VF = visual field.

Intraneural perineuriomas are benign peripheral nerve sheath tumors that cause progressive debilitating focal extremity weakness. The etiology of perineuriomas is largely unknown. We utilized whole exome sequencing, copy number algorithm evaluation, and high-resolution whole genome microarray to investigate for a genetic causal link to intraneural perineuriomas. Ten of 16 (60%) tumor cases had mutations in the WD40 domain of TRAF7, the same location for causal mutations of meningiomas. Two additional perineurioma cases had large chromosomal abnormalities in multiple chromosomes, including chromosome 22q. This study identifies a common cause for intraneural perineuriomas and an unexpected shared pathogenesis with intracranial meningiomas. Ann Neurol 2017;81:316-321.

Primary hypothyroidism causes adenohypophysial hyperplasia via stimulation by hypothalamic thyrotropin-releasing hormone (TRH). The effect was long thought to simply result in thyroid-stimulating hormone (TSH) and prolactin (PRL) cell hyperplasia, an increase in TSH and PRL blood levels with resultant pituitary enlargement, often mimicking adenoma. Recently, it was shown that transformation of growth hormone (GH) cells into TSH cells takes place in both clinical and experimental primary hypothyroidism. Such shifts from one cell to another with a concomitant change in hormone production are termed "transdifferentiation" and involve the gradual acquisition of morphologic features of thyrotrophs ("somatothyrotrophs"). We recently encountered a unique case of pituitary hyperplasia in a 40-year-old female with primary hypothyroidism wherein increased TSH production was by way of PRL cell recruitment. The resultant "lactothyrotrophs" maintained TSH cell morphology (cellular elongation and prominence of PAS-positive lysosomes) but expressed immunoreactivity for both hormones. No co-expression of GH was noted nor was thyroidectomy cells seen. This form of transdifferentiation has not previously been described.

OBJECTIVEDesmoid-type fibromatosis (DTF) presents a therapeutic dilemma. While lacking metastatic potential, it is a locally aggressive tumor with a strong propensity for occurrence near nerve(s) and recurrence following resection. In this study, the authors introduce the association of an occult neuromuscular choristoma (NMC) identified in patients with DTF.METHODSAfter experiencing a case of DTF found to have an occult NMC, the authors performed a retrospective database review of all other cases of biopsy-proven DTF involving the extremities or limb girdles in patients with available MRI data. Two musculoskeletal radiologists with expertise in peripheral nerve imaging reviewed the MRI studies of the eligible cases for evidence of previously unrecognized NMC.RESULTSThe initial case of a patient with an occult sciatic NMC is described. The database review yielded 40 patients with DTF—18 (45%) in the upper limb and 22 (55%) in the lower limb. Two cases (5%) had MRI findings of NMC associated with the DTF, one in the proximal sciatic nerve and the other in the proximal tibial and sural nerves.CONCLUSIONSThe coexistence of NMC may be under-recognized in a subset of patients with extremity DTF. This finding poses implications for DTF treatment and the likelihood of recurrence after resection or biopsy. Further study may reveal crucial links between the pathogenesis of NMC and DTF and offer novel therapeutic strategies.

Meningiomas represent ~30% of primary neoplasms in adults but only 0.4–4.6% in children. Due to the paucity of cases, relatively few studies have addressed pediatric meningiomas and there are insufficient cell lines to conduct in vitro studies. We have established and characterized a new cell line (PED-24) from a 12-year-old male who presented with headaches and subsequently underwent gross total resection of a sporadic, large left frontal meningioma, WHO grade 2. The tumor was focally positive for EMA and GFAP. Whole-exome sequencing of the patient was negative for NF-2. Compared to three high grade glioma lines (two H3K27M DIPG tumors and one adult GBM), PED-24 showed significantly increased growth kinetics as assessed by real-time live-cell analysis. The cells were also successfully cultured as neurospheres in neurobasal medium. Ultrastructural analysis with SEM and TEM demonstrated unique cellular morphology. Average cellular diameter was 3.2 ± 0.3 µm and the cells had a microvilli-covered smooth surface. There was a high burden of transport vesicles and an extensive network of endoplasmic reticulum with evidence of autophagy events. This line provides a resource for further exploration of pathogenic mechanisms involved in sporadic pediatric meningiomas. One novel avenue of interest is the potential presence of a stem-like subpopulation within sporadic pediatric atypical meningiomas.

Introduction Pineoblastomas are uncommon primitive neuroectodermal tumors that occur mostly in children; they are exceedingly rare in adults. Few published reports have compared the various aspects of these tumors between adults and children. Methods The authors report a series of 12 pineoblastomas in adults from 2 institutions over 24 years. The clinical, radiologic, and pathologic features and clinical outcomes were compared with previously reported cases in children and adults. Results Patient age ranged from 24 to 81 years, and all but 1 patient exhibited symptoms of obstructive hydrocephalus. Three patients underwent gross total resection, and subtotal resection was performed in 3 patients. Diagnostic biopsy specimens were obtained in an additional 6 patients. Pathologically, the tumors had the classical morphologic and immunohistochemical features of pineoblastomas. Postoperatively, 10 patients received radiotherapy, and 5 patients received chemotherapy. Compared with previously reported cases, several differences were noted in clinical outcomes. Of the 12 patients, only 5 (42%) died of their disease (average length of survival, 118 months); 5 patients (42%) are alive with no evidence of disease (average length of follow-up, 92 months). One patient died of unrelated causes, and one was lost to follow-up. Patients with subtotal resections or diagnostic biopsies did not suffer a worse prognosis. Of the 9 patients with biopsy or subtotal resection, 4 are alive, 4 died of their disease, and 1 died of an unrelated hemorrhagic cerebral infarction. Conclusions Although this series is small, the data suggest that pineoblastomas in adults have a less aggressive clinical course than in children.

Perineural spread is a well-known mechanism of dissemination of head and neck malignancies. There are few reports of melanoma involving the brachial plexus in the literature. To their knowledge, the authors report the first known case of perineural spread of malignant melanoma to the brachial plexus. Clinicoradiological and anatomopathological correlation is presented, highlighting the importance of peripheral nerve communications in perineural spread.

Objective: To assess, in a surgical biopsy cohort of active demyelinating lesions, the diagnostic utility of aquaporin-4 (AQP4) immunohistochemistry in identifying neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD) and describe pathologic features that should prompt AQP4 immunohistochemical analysis and AQP4–immunoglobulin G (IgG) serologic testing. Methods: This was a neuropathologic cohort study of 20 surgical biopsies (19 patients; 11 cord/9 brain), performed because of diagnostic uncertainty, interpreted as active demyelinating disease and containing 2 or more of the following additional features: tissue vacuolation, granulocytic infiltrates, or astrocyte injury. Results: AQP4 immunoreactivity was lost in 18 biopsies and increased in 2. Immunopathologic features of the AQP4 loss cohort were myelin vacuolation (18), dystrophic astrocytes and granulocytes (17), vascular hyalinization (16), macrophages containing glial fibrillary acid protein (GFAP)–positive debris (14), and Creutzfeldt-Peters cells (0). All 14 cases with available serum tested positive for AQP4-IgG after biopsy. Diagnosis at last follow-up was NMO/NMOSD (15) and longitudinally extensive transverse myelitis (1 each relapsing and single). Immunopathologic features of the AQP4 increased cohort were macrophages containing GFAP-positive debris and granulocytes (2), myelin vacuolation (1), dystrophic astrocytes (1), Creutzfeldt-Peters cells (1), and vascular hyalinization (1). Diagnosis at last follow-up was multiple sclerosis (MS) and both tested AQP4-IgG seronegative after biopsy. Conclusions: AQP4 immunohistochemistry with subsequent AQP4-IgG testing has diagnostic utility in identifying cases of NMO/NMOSD. This study highlights the importance of considering NMOSD in the differential diagnosis of tumefactive brain or spinal cord lesions. AQP4-IgG testing may avert biopsy and avoid ineffective therapies if these patients are erroneously treated for MS.

Object Swallowing dysfunction is common following transoral (TO) odontoidectomy. Preliminary experience with newer endoscopic transnasal (TN) approaches suggests that dysphagia may be reduced with this alternative. However, the reasons for this are unclear. The authors hypothesized that the TN approach results in less disruption of the pharyngeal plexus and anatomical structures associated with swallowing. The authors investigate the histological and gross surgical anatomical relationship between pharyngeal plexus innervation of the upper aerodigestive tract and the surgical approaches used (TN and TO). They also review the TN literature to evaluate swallowing outcomes following this approach. Methods Seven cadaveric specimens were used for histological (n = 3) and gross anatomical (n = 4) examination of the pharyngeal plexus with the TO and TN surgical approaches. Particular attention was given to identifying the location of cranial nerves (CNs) IX and X and the sympathetic chain and their contributions to the pharyngeal plexus. S100 staining was performed to assess for the presence of neural tissue in proximity to the midline, and fiber density counts were performed within 1 cm of midline. The relationship between the pharyngeal plexus, clivus, and upper cervical spine (C1-3) was defined. Results Histological analysis revealed the presence of pharyngeal plexus fibers in the midline and a significant reduction in paramedian fiber density from C-2 to the lower clivus (p < 0.001). None of these paramedian fibers, however, could be visualized with gross inspection or layer-by-layer dissection. Laterally based primary pharyngeal plexus nerves were identified by tracing their origins from CNs IX and X and the sympathetic chain at the skull base and following them to the pharyngeal musculature. In addition, the authors found 15 studies presenting 52 patients undergoing TN odontoidectomy. Of these patients, only 48 had been swallowing preoperatively. When looking only at this population, 83% (40 of 48) were swallowing by Day 3 and 92% (44 of 48) were swallowing by Day 7. Conclusions Despite the midline approach, both TO and TN approaches may injure a portion of the pharyngeal plexus. By limiting the TN incision to above the palatal plane, the surgeon avoids the high-density neural plexus found in the oropharyngeal wall and limits injury to oropharyngeal musculature involved in swallowing. This may explain the decreased incidence of postoperative dysphagia seen in TN approaches. However, further clinical investigation is warranted.

Pituicytoma is a rare low-grade (WHO grade I) sellar region glioma. Among sellar tumors, pituitary adenomas, mainly prolactinomas, may show amyloid deposits. Gelsolin is a ubiquitous calcium-dependent protein that regulates actin filament dynamics. Two known gene point mutations result in gelsolin amyloid deposition, a characteristic feature of a rare type of familial amyloid polyneuropathy (FAP), the Finnish-type FAP, or hereditary gelsolin amyloidosis (HGA). HGA is an autosomal-dominant systemic amyloidosis, characterized by slowly progressive neurological deterioration with corneal lattice dystrophy, cranial neuropathy, and cutis laxa. A unique case of pituicytoma with marked gelsolin amyloid deposition in a 67-year-old Chinese woman is described. MRI revealed a 2.6-cm well-circumscribed, uniformly contrast-enhancing solid sellar mass with suprasellar extension. Histologically, the lesion was characterized by solid sheets and fascicles of spindle cells with slightly fibrillary cytoplasm and oval nuclei with pinpoint nucleoli. Surrounding brain parenchyma showed marked reactive piloid gliosis. Remarkably, conspicuous amyloid deposits were identified as pink homogeneous spherules on light microscopy that showed apple-green birefringence on Congo red with polarization. Mass spectrometric-based proteomic analysis identified the amyloid as gelsolin type. Immunohistochemically, diffuse reactivity to S100 protein and TTF1, focal reactivity for GFAP, and no reactivity to EMA, synaptophysin, and chromogranin were observed. HGA-related mutations were not identified in the tumor. No recurrence was noted 14 months after surgery. To the knowledge of the authors, amyloid deposition in pituicytoma or tumor-associated gelsolin amyloidosis has not been previously described. This novel finding expands the spectrum of sellar tumors that may be associated with amyloid deposition.

Background Metastatic disease is a well-known sequela of malignant peripheral nerve sheath tumors (MPNSTs). Metastic spread to the brain is unusual. Case Description A 56-year-old man was found to have a high grade MPNST of the sciatic nerve. Despite en-bloc excision of the sciatic nerve mass and local radiation postoperatively, he developed pathologically confirmed systemic metastases. He was found to have lung nodules and received chemotherapy 25 months after the diagnosis, and 32 months after the initial diagnosis, he presented with left leg weakness and sensory changes and was found to have a lesion of the frontal lobe for which he received palliative radiation. He developed systemic metastases and died 35 months after initial presentation. We retrospectively reviewed the charts of 179 patients treated at our institution with MPNSTs since 1994. This was the only case of a pathology proven brain metastasis, resulting in an incidence of 0.5%. Literature review revealed 21 cases. The mean age was found to be 37.5 years, and mean survival after development of a brain metastasis was 9.9 months. Conclusions Brain metastases from MPNSTs are very rare and represent a poor prognosis, with survival after brain metastasis reported to be approximately 10 months. Early and effective initial diagnosis and treatment of MPNSTs likely represent the best opportunity for increased overall survival.

To describe imaging characteristics of neuromuscular choristomas (NMC) and to differentiate them from fibrolipomatous hamartomas (FLH).Clinical and imaging characteristics of six patients with biopsy-proven NMC and six patients with FLH were reviewed by musculoskeletal, a pediatric, and two in-training radiologists with a literature review to define typical magnetic resonance imaging features by consensus. Five radiology trainees blinded to cases and naive to the diagnosis of NMC and a musculoskeletal-trained radiologist rated each lesion as having more than or less than 50% intralesional fat, as well as an overall impression using axial T1 images. Sensitivity, specificity, accuracy, and interobserver agreement kappa were determined.Typical features of NMC include smoothly tapering, fusiform enlargement of the sciatic nerve or brachial plexus elements with T1 and T2 signal characteristics closely following those of muscle. Longitudinal bands of intervening low T1 and T2 signal were often present and likely corresponded to fibrous tissue by pathology. Four of five patients with long-term follow-up (80%) developed aggressive fibromatosis after percutaneous or surgical biopsy. Nerve fascicle thickening often resulted in a "coaxial cable" appearance similar to classic FLH, however, using a cutoff of50% intralesional fat allowed for differentiation with 100% sensitivity by all reviewers and 100% specificity when all imaging features were utilized for impressions. Agreement was excellent with all differentiating methods (kappa 0.861-1.0).NMC can be confidently differentiated from FLH and malignancies using characteristic imaging and clinical features. When a diagnosis is made, biopsy should be avoided given frequent complication by aggressive fibromatosis.

Oligodendroglial tumors may rarely display striking desmoplasia resulting in unusual histologic patterns that have not been completely characterized. We reviewed the clinicopathologic findings of 7 such cases. Patients included 4 men and 3 women. Mean age at the time of primary surgery was 49 years (range, 31 to 57 y). All tumors were of World Health Organization grade III (4 anaplastic oligodendrogliomas and 3 anaplastic oligoastrocytomas). Characteristic morphologic features included tumor nests/nodules with surrounding fibrosis/ desmoplasia (n = 5), cords/single-cell infiltration (n = 2), mini-gemistocytes (n = 5), endothelial hypertrophy (n = 6), and necrosis (n = 1). Mean mitotic index was 9 mitoses per 10 high-power fields. Immunohistochemical studies demonstrated immunoreactivity for PDGFRα 1 to 3 + (5 of 6), PDGFRβ 3 + (n = 3 of 3), and EGFR 1 to 2 + (n = 5 of 6). p53 protein expression was 1-2+ and MIB-1 labeling index was moderate. Four tumors showed 1p19q codeletion, 1 tumor showed 1p deletion only, and 2 tumors showed intact 1p19q loci. t(1:19) was identified in 2 (of 3) tested cases, both also with 1p19q codeletion, and was absent in the case with 1p loss only. IDH1R132H mutant protein was detected in 3 (of 6) cases, and an IDH mutation (R132S) was identified in an additional case by pyrosequencing. Clinical follow-up was available in 6 (of 7) patients (mean follow-up of 64.2 mo). Five (of 6) developed recurrence/progression at a mean interval of 49.2 months after primary diagnosis. Only 1 patient died of disease, 22.5 months after primary diagnosis. Oligodendroglial tumors with prominent desmoplasia are rare. Most cases demonstrate 1p19q codeletion and IDH1 mutations, and behave as expected for anaplastic oligodendroglial tumors.

Sciatic nerve endometriosis (EM) is a rare presentation of retroperitoneal EM. The authors present 2 cases of catamenial sciatica diagnosed as sciatic nerve EM. They propose that both cases can be explained by perineural spread of EM from the uterus to the sacral plexus along the pelvic autonomie nerves and then further distally to the sciatic nerve or proximally to the spinal nerves. This explanation is supported by MRI evidence in both cases. As a proof of concept, the authors retrieved and analyzed the original MRI studies of a case reported in the literature and found a similar pattern of spread. They believe that the imaging evidence of their institutional cases together with the outside case is a very compelling indication for perineural spread as a mechanism of EM of the nerve.

Oncolytic measles virus strains are currently being evaluated in several clinical trials including glioblastoma and ovarian cancer, while clinical application in breast cancer is in development. The role of poliovirus receptor-related 4 (PVRL4), as a measles virus receptor, has been well documented. However the regulation of PVRL4 is not well understood. Immunohistochemistry and western blot analysis shows increased PVRL4 protein levels in glioblastoma and breast tumor clinical samples with no significant change in PVRL4 mRNA levels detected by qRT-PCR, suggesting that PVRL4 is likely post-transcriptionally regulated. Genes can be post-transcriptionally regulated by miRNAs by binding to the 3’UTR of the targeted mRNA causing translational repression or degradation. Thus, we sought to investigate the potential role of miRNAs in PVRL4 post-transcriptional regulation. Algorithms from microRNA. org and RegRNA, predicted that, from the miRNAs that are reportedly down-regulated in glioblastoma and breast cancer, miR-31 and miR-128 binds the 3’UTR of PVRL4. Indeed, luciferase binding assays demonstrated miR-31 and-128binding to the 3’UTR of PVRL4, suggesting that PVRL4 is a miRNA targeted gene. QRT-PCR studies validated that miR-31 and miR-128 are down-regulated in glioblastoma and breast tumor clinical samples, further supporting the hypothesis that PVRL4 are post-transcriptionally regulated by miRNAs. In order to understand the effects of the respective miRNAs on PVRL4 and thus on measles virus infectivity, a viral strain (Leonard et. al, 2010, J. Virol.) that exclusively utilizes PVRL4 as its receptor was employed to infect the cancer cell lines followed by evaluation of virus infectivity via measles viral nucleoprotein (N-protein) levels. Subsequent gain -and loss-of-function experiments showed that overexpression of miR-31and miR-128, via lentiviral-vector transduction, down-regulated the endogenous levels of PVRL4 and measles virus infectivity, while transduction of lentiviral-vectors expressing PVRL4 restored measles virus infectivity. The functional affects were reversed or increased upon transduction with the complementary anti-miRs-128 and anti-miR-31. These results are being further validated in ongoing in vivo mouse models where cancer cell lines stably transduced with miR-128, miR-31 or anti-miR-128, anti-miR-31, are transplanted in mice to evaluate tumor size and survival rates upon measles virus infection. These data suggest that PVRL4 is post-transcriptionally regulated by miR-128 and miR-31, and thus, these represent possible miRNA targets that could modulate PVRL4 levels in order to enhance oncolytic measles virus infectivity.This research is supported by P50 CA 108961-7, P50 CA 136393-4, P50 CA 116201-7 and R01 CA 136547-4.

Background High frequencies of the BRAF V600E mutation have been reported in pleomorphic xanthoastrocytoma (PXA). Recently, a BRAF V600E mutation-specific antibody has been developed and validated. We evaluated the immunohistochemical (IHC) detection of BRAF V600E mutation in PXA by comparing to gold standard molecular analysis and investigating the interobserver variability of the IHC scoring. We performed BRAF V600E IHC in 46 cases, of which 37 (80%) cases had sufficient tumor tissue for molecular analysis. IHC detection was performed using monoclonal mouse antibody VE1 (Spring Bioscience). IHC slides were scored independently by four reviewers blind to molecular data, including a primary (gold standard) and three additional reviewers. BRAF V600E mutation status was assessed by allele-specific polymerase chain reaction (PCR) with fragment analysis. Results All 46 cases showed interpretable BRAF V600E IHC results: 27 (59%) were positive (strong cytoplasmic staining), 19 (41%) were negative (6 of these cases with focal/diffuse weak cytoplasmic staining, interpreted as nonspecific by the primary reviewer). By molecular analysis, all 37 cases that could be tested had evaluable results: 22 (59%) cases were positive for BRAF V600E mutation and were scored as “IHC-positive”, and 15 (41%) were negative (including 11 cases scored as “IHC-negative” and 4 cases scored as negative with minimal nonspecific staining). IHC detection of BRAF V600E mutant protein was congruent in all 37 cases that were successfully evaluated by molecular testing (sensitivity and specificity of 100%). Agreement for IHC scoring among the 4 reviewers was almost perfect (kappa 0.92) when cases were scored as “positive/negative” and substantial (kappa 0.78) when minimal nonspecific staining was taken into account. Conclusions We conclude that detection of BRAF V600E mutation by immunohistochemistry is highly sensitive and specific. BRAF V600E IHC interpretation is usually straightforward, but awareness of possible nonspecific staining is necessary and training is recommended. It is a practical rapid method that may avoid the need of labor-intensive molecular testing and may be most valuable in small biopsies unsuitable for molecular analysis.

OBJECTIVE: In pregnant women, the pituitary is enlarged and the prolactin (PRL) secreting cells increase in size and number. This PRL cell hyperplasia is associated with hyperprolactinemia. The aim of the present work was to investigate adenohypophysial vascularization and immunoexpression of vascular endothelial growth factor (VEGF) in pituitaries of pregnant and post-partum women and compare the results with age-matched adenohypophyses of non-pregnant women who had no endocrine diseases. DESIGN: Pituitaries (n=18) obtained by autopsy from female patients of reproductive age who had died during pregnancy, after abortion or during post-partum were immunostained for CD-34 and VEGF using the streptavidinbiotin-peroxidase complex method. RESULTS: The results showed that microvessel densities and VEGF immunoexpression in the adenohypophyses of pregnant and post-partum women were similar to those found in the control pituitaries. CONCLUSION: It can be concluded that pituitary enlargement and PRL cell hyperplasia in pregnant women may occur without neovascularization and increased VEGF immunoexpression.