Surgical resection of granular cell tumor of the sellar region: three indications.

PURPOSE: This case series evaluates the surgical management of granular cell tumor (GCT) of the sellar region. This rare entity presents a unique diagnostic and surgical challenge. METHODS: Institutional neuropathology databases at Brigham and Women's Hospital and Massachusetts General Hospital were searched for cases with a tissue diagnosis of GCT, and with a location in the sellar region. Patient, treatment, tumor, and follow-up data were extracted. RESULTS: Three patients had a diagnosis of GCT of the sellar region occurring over an 18-year period. All three patients were followed postoperatively at our multidisciplinary pituitary center (median follow-up = 30 months; range 12-30 months). Hormonal disturbances, an incidental lesion requiring diagnosis, and neurological symptoms were indications for surgery in these patients. Two patients underwent a craniotomy and one underwent endoscopic transsphenoidal surgery. All three patients were free of tumor recurrence at last follow-up. In one case tested, positive thyroid transcription factor-1 (TTF-1) immunohistochemistry was observed. CONCLUSION: GCT is generally a benign tumor of the sellar region. Surgical resection is the standard treatment, more recently with transsphenoidal surgery when indicated. Surgical resection results in optimal outcome for patients.

Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy.

INTRODUCTION: Congenital hypomyelinating neuropathy (CHN) is a rare congenital neuropathy that presents in the neonatal period and has been linked previously to mutations in several genes associated with myelination. A recent study has linked 4 homozygous frameshift mutations in the contactin-associated protein 1 (CNTNAP1) gene with this condition. METHODS: We report a neonate with CHN who was found to have absent sensory nerve and compound muscle action potentials and hypomyelination on nerve biopsy. RESULTS: On whole exome sequencing, we identified a novel CNTNAP1 homozygous missense mutation (p.Arg388Pro) in the proband, and both parents were carriers. Molecular modeling suggests that this variant disrupts a ß-strand to cause an unstable structure and likely significant changes in protein function. CONCLUSIONS: This report links a missense CNTNAP1 variant to the disease phenotype previously associated only with frameshift mutations. Muscle Nerve 55: 761-765, 2017.

Brain and liver pathology, amyloid deposition, and interferon responses among older HIV-positive patients in the late HAART era.

BACKGROUND: HIV+ patients on highly active antiretroviral therapy (HAART) with suppressed viral loads have a low incidence of HIV-associated dementia, but increased prevalence of milder forms of HIV-associated neurocognitive disorders (HAND). These milder forms of HAND are often associated with minimal histological abnormalities, and their pathophysiology is unclear. Comorbidities, altered amyloid metabolism, accelerated brain aging, and activated interferon responses are suspected to play a role in HAND pathogenesis in HAART-treated persons. METHODS: To investigate associations between liver disease, accelerated brain aging, and HAND in HIV+ patients in the late HAART era (2002-2015), we studied liver and brain autopsy tissues from 53 older subjects evaluated at UCLA and BWH using histopathological stains, a sensitive fluorescent amyloid stain (AmyloGlo), and targeted gene expression profiling (NanoString). RESULTS: The majority of HIV+ subjects (median age 56) were on HAART (89.3%) with last pre-mortem plasma viral load <400 copies/mL (81.5%); 50% had CD4+ counts <200 cells/µL. Compared to HIV- controls (median age 65), HIV+ subjects had more cancer (p = 0.04), illicit drug use (p <0.00001), and HCV co-infection (p = 0.002), less cardiovascular disease (p = 0.03), and similar prevalence of cerebrovascular disease (~40%), hypertension, hyperlipidemia, and diabetes. Deep frontal white matter showed increased gliosis in HIV+ subjects vs. HIV- controls (p = 0.09), but no significant differences in myelin loss, blood vessel thickening, or inflammation. Liver showed more severe fibrosis/cirrhosis (p = 0.02) and less steatosis (p = 0.03) in HIV+ subjects, but no significant differences in inflammation, blood vessel thickness, or pigment deposition. There were no significant associations between liver and brain pathologies. AmyloGlo staining detected large amyloid deposits in only one HIV+ case (age 69 with Alzheimer's disease pathology) and two HIV- controls (ages 66 and 74). White matter from HIV+ cases vs. HIV- seronegative controls showed a trend (p = 0.06) towards increased interferon response gene expression (ISG15, MX1, IFIT1, IFIT2, and IFITM1). CONCLUSIONS: Gliosis and cerebrovascular disease, but not accelerated amyloid deposition, are common brain pathologies among older HIV+ patients in the late HAART era. Although HIV+ subjects had more cirrhosis, liver pathology was not associated with any consistent pattern of brain pathology. Cerebrovascular disease, interferon responses, and neuroinflammation are likely factors contributing to brain aging and HAND in older HIV+ patients on current HAART regimens.

Central Versus Extraventricular Neurocytoma in Children: A Clinicopathologic Comparison and Review of the Literature.

BACKGROUND: Central neurocytomas (CN) are rare pediatric CNS tumors most often with a benign clinical course. Occasionally, these tumors occur outside the ventricles and are called extraventricular neurocytomas (EVN). We present a retrospective institutional analysis of children with neurocytoma with prolonged follow-up. PROCEDURE: Twelve patients were diagnosed with neurocytoma at our institution between 1993 and 2004. RESULTS: Six patients were male and the median age at diagnosis was 12 years (1.5 to 16 y). Seven patients had CN and 5 had EVN. Presenting symptoms included headaches (67%), vomiting (50%), nausea (33%), seizures (33%), and mental status changes (25%). Obstructive hydrocephalus was present at diagnosis in 42% of the cases. Younger age and seizures were more common in patients with EVN. Gross total resection (GTR) was achieved in 42% (5/12) of the patients. Patients with GTR received no adjuvant therapy upfront; 1 patient subsequently had recurrence with leptomeningeal disease. Patients with subtotal resection received additional treatment: 1 underwent reoperation (GTR), 2 patients received focal radiation, 2 patients received adjuvant chemotherapy, and 2 patients received craniospinal irradiation followed by chemotherapy. The 20-year overall survival for this cohort was 83% with event free survival of 56%. Overall survival for CNs was 100%, versus 40% for EVN. Event free survival for CNs was 57% and 53% for the EVNs. An MIB-1 fraction >2% was associated with worse prognosis. CONCLUSIONS: Neurocytomas are rare brain tumors in children usually cured with GTR. Adjuvant focal radiation therapy and/or chemotherapy may improve disease control in cases with subtotal resection, but case-by-case analysis should be done. EVNs might be associated with worse outcome due to a higher proliferative index.

Neuromuscular pathology.

In this chapter, we discuss the indications for muscle, nerve, and skin biopsies, the techniques and normal processing of biopsy specimens, normal histological appearance, and the commonest histopathological abnormalities of different myopathies and neuropathies.

Molecular classification of low-grade diffuse gliomas.

The current World Health Organization classification recognizes three histological types of grade II low-grade diffuse glioma (diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma). However, the diagnostic criteria, in particular for oligoastrocytoma, are highly subjective. The aim of our study was to establish genetic profiles for diffuse gliomas and to estimate their predictive impact. In this study, we screened 360 World Health Organization grade II gliomas for mutations in the IDH1, IDH2, and TP53 genes and for 1p/19q loss and correlated these with clinical outcome. Most tumors (86%) were characterized genetically by TP53 mutation plus IDH1/2 mutation (32%), 1p/19q loss plus IDH1/2 mutation (37%), or IDH1/2 mutation only (17%). TP53 mutations only or 1p/19q loss only was rare (2 and 3%, respectively). The median survival of patients with TP53 mutation ± IDH1/2 mutation was significantly shorter than that of patients with 1p/19q loss ± IDH1/2 mutation (51.8 months vs. 58.7 months, respectively; P = 0.0037). Multivariate analysis with adjustment for age and treatment confirmed these results (P = 0.0087) and also revealed that TP53 mutation is a significant prognostic marker for shorter survival (P = 0.0005) and 1p/19q loss for longer survival (P = 0.0002), while IDH1/2 mutations are not prognostic (P = 0.8737). The molecular classification on the basis of IDH1/2 mutation, TP53 mutation, and 1p/19q loss has power similar to histological classification and avoids the ambiguity inherent to the diagnosis of oligoastrocytoma.

Pixel-based comparison of spinal cord MR diffusion anisotropy with axon packing parameters.

Water diffusion in nerve fibers is strongly influenced by axon architecture. In this study, fractional diffusion anisotropy and transverse and longitudinal diffusion coefficients were measured in excised human cervical spinal cord with MR line-scan diffusion imaging, at 625 microm in-plane resolution and 3 mm slice thickness. A pixel-based comparison of fractional diffusion anisotropy, transverse diffusion coefficient, and longitudinal diffusion coefficient data with axon packing parameters derived from corresponding stained histological sections was performed for four slices. The axon packing parameters, axon density, axon area-fraction, and average axon size for entire specimen cross-sections were calculated by computerized segmentation of optical microscopy data obtained at 0.53 microm resolution. Salient features could be recognized on fractional diffusion anisotropy, transverse diffusion coefficient, axon density, axon area fraction, and average axon size maps. For white matter regions only, the average correlation coefficients for fractional diffusion anisotropy compared to histology-based parameters axon density and axon area fraction were 0.37 and 0.21, respectively. For transverse diffusion coefficient compared to axon density and axon area fraction, they were -0.40 and -0.36, and for longitudinal diffusion coefficient compared to axon density and axon area fraction, -0.14 and -0.30. All average correlation coefficients for average axon size were low. Correlation coefficients for collectively analyzed white and gray matter regions were significantly higher than correlation coefficients derived from analysis of white matter regions only.

Corticotroph hyperplasia and Cushing disease: diagnostic features and surgical management.

OBJECTIVE: This study was done to compare corticotroph hyperplasia and histopathologically proven adenomas in patients with Cushing disease by analyzing diagnostic features, surgical management, and clinical outcomes. METHODS: Patients with suspected pituitary Cushing disease were included in a retrospective cohort study and were excluded if results of pathological analysis of the surgical specimen were nondiagnostic or normal. Cases were reviewed by two experienced neuropathologists. Total lesion removal was used as a dichotomized surgical variable; it was defined as an extracapsular resection (including a rim of normal gland) in patients with an adenoma, and for hyperplasia patients it was defined as removal of the presumed lesion plus a rim of surrounding normal gland. Bivariate and multivariate analyses were performed. Recurrence-free survival was compared between the two groups. RESULTS: The final cohort consisted of 63 patients (15 with hyperplasia and 48 with adenoma). Normal pituitary acinar architecture was highly variable. Corticotroph hyperplasia was diagnosed based on the presence of expanded acini showing retained reticulin architecture and predominant staining for adrenocorticotropic hormone. Crooke's hyaline change was seen in 46.7% of specimens, and its frequency was equal in nonlesional tissue of both groups. The two groups differed only by MRI findings (equivocal/diffuse lesion in 46% of hyperplasia and 17% of adenoma; p = 0.03). Diagnostic uncertainty in the hyperplasia group resulted in additional confirmatory testing by 24-hour urinary free cortisol. Total lesion removal was infrequent in patients with hyperplasia compared to those with adenoma (33% vs 65%; p = 0.03). Initial biochemical remission was similar (67% in hyperplasia and 85% in adenoma; p = 0.11). There was no difference in hypothalamic-pituitary-adrenal axis recovery or disease recurrence. The median follow-up was 1.9 years (IQR 0.7-7.6 years) for the hyperplasia group and 1.2 years (IQR 0.4-2.4 years) for the adenoma group. Lack of a discrete lesion and diagnostic uncertainty were the only significant predictors of hyperplasia (sensitivity 53.3%, specificity 97.7%, positive predictive value 88.9%, negative predictive value 85.7%). An adjusted Cox proportional hazards model showed similar recurrence-free survival in the two groups. CONCLUSIONS: This study suggests an association between biochemically proven Cushing disease and histopathologically proven corticotroph hyperplasia. Imaging and operative findings can be ambiguous, and, compared to typical adenomas with a pseudocapsule, the surgical approach is more nuanced. Nevertheless, if treated appropriately, biochemical outcomes may be similar.

Neuropathology of central nervous system arterial syndromes. Part I: the supratentorial circulation.

The objective of this review is to illustrate the principal cerebrovascular arterial pathoanatomical syndromes using the unique collection of whole brain sections in the Raymond Escourolle Neuropathology Laboratory at Salpêtrière in Paris. The arterial supratentorial syndromes are presented in Part I; the infratentorial and spinal cord syndromes will be presented subsequently in Part II. No attempt is made to be all-inclusive in the review of the literature; rather, we cite only those bibliographic references that are historically noteworthy and with some exceptions that particularly emphasize the neuropathologic rather than radiographic/imaging aspects of the vascular syndromes. From these studies and our own archival material, we have synthesized the salient clinicopathologic aspects of the individual syndromes.

An absorbable local anesthetic matrix provides several days of functional sciatic nerve blockade.

BACKGROUND: Functional blockade of peripheral nerves is the primary objective of local anesthesia, and it is often desirable to have a persistent blockade, sustained throughout and beyond a surgical procedure. Current local anesthetics give effective analgesia for <8-12 h after a single bolus injection. We report on an implantable, controlled-release drug delivery system intended for use in bone and consisting of a Food and Drug Administration-approved matrix containing lidocaine that is capable of local delivery for several days. METHODS: Xybrex, an absorbable, controlled-release delivery system containing 16% (w/w) lidocaine, was implanted next to the sciatic nerve of male rats (300-350 gm), at lidocaine doses of 5.3, 10.6, 16, and 32 mg lidocaine per rat. For comparison, a lidocaine HCl solution (0.2 mL, 2% = 4 mg) was injected in close proximity to the sciatic nerve. Rats were assessed behaviorally for analgesia by a forceps pinch of the lateral digits, and for motor block by quantifying the extensor postural thrust. Potential neurotoxicity of sciatic nerves was evaluated histologically at 24 h, 4 days, and 4 wk after implantation. The kinetics of lidocaine's release from the matrix was measured in vitro by ultraviolet detection of lidocaine in samples collected at 2.5, 6.5, 20, and 24.25 h. RESULTS: Xybrex at the highest doses (300 and 600 mg/kg, containing 16 and 32 mg of lidocaine free base, respectively) provided complete analgesia to an intense pinch for 7.0 +/- 2.0 h, 6.9 +/- 1.7 h and partial analgesia for 60.0 +/- 5.4 h, 58.8 +/- 4.2 h, respectively, compared to 0.61 +/- 0.03 h of complete analgesia and 0.96 +/- 0.03 h of partial analgesia by sciatic block from the 2% lidocaine solution (containing 4 mg lidocaine). These same high doses of Xybrex produced complete motor block for 17.0 +/- 3.3 h, 17.6 +/- 3.3 h with full recovery in 352.0 +/- 55.7 h (14.7 +/- 2.3 days), 579.0 +/- 36.1 h (24.1 +/- 1.5 days) respectively. Data are reported as mean +/- SE. P < 0.001 for all Xybrex groups compared to the 2% lidocaine group. Minor local tissue inflammation/pathology, primarily in the connective tissue and muscle 0.1 mm adjacent to the nerve, was observed equally in animals treated with Xybrex and 2% lidocaine solution. There were no behavioral signs of systemic toxicity. The in vitro release followed exponential kinetics and its comparison to the time-course of functional nociceptive deficit implied that the duration of nociception represented the local, immediate interaction of lidocaine between the nerve and the matrix and not a cumulative effect of previously released drug. CONCLUSIONS: Xybrex is an absorbable, controlled-release drug delivery system that provides several days of analgesia for rat peripheral nerves without apparent significant local neurotoxicity or systemic toxicity.

Prognostic value of tumor microinvasion and metalloproteinases expression in intracranial pediatric ependymomas.

Ependymomas are common pediatric intracranial neoplasms that often appear well circumscribed on imaging but may recur when they are treated by surgical resection alone. The current World Health Organization histological grading system does not accurately predict clinical behavior. The aim of this study was to identify histological and immunohistochemical features that correlate with clinical course in patients with ependymomas treated by gross total resection. We analyzed 41 pediatric ependymomas for microinvasion and correlated immunostaining for the metalloproteinase (MMP)-2 and MMP14 and for ezrin and bcl-2 with clinical outcome. Gross total resection had a significantly positive effect on overall survival and progression-free survival. In 28 patients who underwent gross total resection, microinvasion correlated with poor overall survival (p = 0.003) and progression-free survival (p = 0.03). Gross totally resected tumors with high expression of MMP2 and MMP14 had significantly shorter overall survival. Ezrin staining identified tumor cells invading the adjacent white matter that were not identified by routine stains, but Ezrin staining and bcl-2 staining did not provide strong prognostic correlations. The data indicate that tumor microinvasion into adjacent brain and tumor expression of MMP2 and MMP14 predict both overall and progression-free survival in pediatric ependymomas, and these are useful prognostic markers that may help stratify patients for adjuvant therapies.

Fatal Powassan Encephalitis (Deer Tick Virus, Lineage II) in a Patient With Fever and Orchitis Receiving Rituximab.

Importance: Powassan virus is a rare but increasingly recognized cause of severe neurological disease. Objective: To highlight the diagnostic challenges and neuropathological findings in a fatal case of Powassan encephalitis caused by deer tick virus (lineage II) in a patient with follicular lymphoma receiving rituximab, with nonspecific anti-GAD65 antibodies, who was initially seen with fever and orchiepididymitis. Design, Setting, and Participants: Comparison of clinical, radiological, histological, and laboratory findings, including immunohistochemistry, real-time polymerase chain reaction, antibody detection, and unbiased sequencing assays, in a single case report (first seen in December 2016) at an academic medical center. Exposure: Infection with Powassan virus. Main Outcomes and Measures: Results of individual assays compared retrospectively. Results: In a 63-year-old man with fatal Powassan encephalitis, serum and cerebrospinal fluid IgM antibodies were not detected via standard methods, likely because of rituximab exposure. Neuropathological findings were extensive, including diffuse leptomeningeal and parenchymal lymphohistiocytic infiltration, microglial proliferation, marked neuronal loss, and white matter microinfarctions most severely involving the cerebellum, thalamus, and basal ganglia. Diagnosis was made after death by 3 independent methods, including demonstration of Powassan virus antigen in brain biopsy and autopsy tissue, detection of viral RNA in serum and cerebrospinal fluid by targeted real-time polymerase chain reaction, and detection of viral RNA in cerebrospinal fluid by unbiased sequencing. Extensive testing for other etiologies yielded negative results, including mumps virus owing to prodromal orchiepididymitis. Low-titer anti-GAD65 antibodies identified in serum, suggestive of limbic encephalitis, were not detected in cerebrospinal fluid. Conclusions and Relevance: Owing to the rarity of Powassan encephalitis, a high degree of suspicion is required to make the diagnosis, particularly in an immunocompromised patient, in whom antibody-based assays may be falsely negative. Unbiased sequencing assays have the potential to detect uncommon infectious agents and may prove useful in similar scenarios.

Predicting survival of children with CNS tumors using proton magnetic resonance spectroscopic imaging biomarkers.

Using brain proton magnetic resonance spectroscopic imaging (MRSI) in children with central nervous system (CNS) tumors, we tested the hypothesis that combining information from biologically important metabolites, at diagnosis and prior to treatment, would improve prediction of survival. We evaluated brain proton MRSI exams in 76 children (median age at diagnosis: 74 months) with brain tumors. Important biomarkers, choline-containing compounds (Cho), N-acetylaspartate (NAA), total creatine (tCr), lipids and/or lactate (L), were measured at the "highest Cho region" and normalized to the tCr of surrounding healthy tissue. Neuropathological grading was performed using World Health Organization (WHO) criteria. Fifty-eight of 76 (76%) patients were alive at the end of the study period. The mean survival time for all subjects was 52 months. Univariate analysis demonstrated that Cho, L, Cho/NAA and tumor grade differed significantly between survivors and non-survivors (P< or =0.05). Multiple logistic regression and stepwise multivariate Cox regression indicated that Cho + 0.1L was the only independent predictor of survival (likelihood ratio test = 10.27, P<0.001; Cox regression, P=0.004). The combined index Cho + 0.1L was more accurate and more specific predictor than Cho or Cho/NAA. Accuracy and specificity for Cho + 0.1L were 80% and 86%, respectively. We conclude that brain proton MRSI biomarkers predict survival of children with CNS tumors better than does standard histopathology. More accurate prediction using this non-invasive technique represents an important advance and may suggest more appropriate therapy, especially when diagnostic biopsy is not feasible.

Spinal cord.

We first present a brief historic review of developments in the understanding of spinal cord clinical neuroanatomy and neurophysiology over the past 200 years. We then discuss the technical aspects that apply to the examination of the human spinal cord giving details on the interrelations between the spinal cord and the overlying structures, including the meninges and vertebrae. The subsequent discussion focuses on diseases of the spinal cord. Diseases that affect the spinal cord are vascular disease, diseases of spinal column, trauma, developmental abnormalities, central nervous system degenerative disease, inflammatory disease, metabolic and nutritional myelopathies, and tumors. We summarize our knowledge regarding general reactions of spinal cord tissue to disease, in particular Wallerian degeneration of descending/ascending tracts and axonal reaction. Two categories of disease will be covered in depth: vascular disease of the spinal cord, including a review of normal vascular anatomy, and diseases of the vertebral column that can affect the cord secondarily.

Natural history of cranial fibrous dysplasia revealed during long-term follow-up: Case report and literature review.

BACKGROUND: Fibrous dysplasia (FD) is a rare developmental disease characterized by the replacement of bone marrow with proliferating fibro-osseous tissue. There exist three forms of FD-monostotic, polyostotic, and that associated with McCune-Albright syndrome. The disease can present in different locations and with a variety of symptoms. One of the more common locations of FD occurrence is the craniofacial region. Treatment of asymptomatic FD often involves conservative management with serial imaging. Medical management with bisphosphonates is an option, though long-term efficacy data are lacking. Surgical resection is usually reserved for very large or symptomatic lesions. CASE DESCRIPTION: We discuss the most unusual case of a 52-year-old male found to have a left pterional mass while being worked up for sinus headaches. The patient elected to follow this lesion conservatively, and imaging several years later showed obvious growth which accelerated in the last 4 years during an 18-year observational period. He ultimately underwent successful resection of an extradural and intradural FD. CONCLUSIONS: The significant growth potential of these lesions was revealed in this patient, in whom conservative management had been adopted. Despite optimal surgical resection and outcome in this case, the importance of surveillance imaging and perhaps earlier intervention cannot be underestimated when managing cranial FD.

A Woman in Her 40s With Headache and New-Onset Seizures.

A woman in her 40s with a history of plasma cell leukemia presented with 1 month of intermittent headaches followed by a seizure. Results from laboratory studies were notable for a cerebrospinal fluid opening pressure of 28 mm H2O and 8 white blood cells, including 1 atypical plasma cell. Imaging studies revealed confluent bifrontal white matter fluid-attenuated inversion recovery hyperintensities, as well as a contrast-enhancing sellar lesion. The patient underwent a stereotactic biopsy. The differential diagnosis, pathologic findings, and diagnosis are discussed.

Fatal Eastern Equine Encephalitis in a Patient on Maintenance Rituximab: A Case Report.

A 63-year-old woman on rituximab maintenance for follicular lymphoma presented with headaches, vomiting, and fever, and was diagnosed with eastern equine encephalomyelitis by cerebrospinal fluid polymerase chain reaction. Eastern equine encephalomyelitis immunoglobulin (Ig)G/IgM remained negative due to rituximab treatment, and magnetic resonance imaging showed minimal abnormalities, making this a diagnostically challenging case. Despite therapy with intravenous Ig, the patient rapidly declined and died on hospital day 12. Autopsy revealed perivascular and parenchymal chronic inflammation, with an absence of B lymphocytes, and virally infected neurons throughout the central nervous system.

Intramedullary neuroma of the cervicomedullary junction. Case report.

Neuromas typically arise in the peripheral nervous system in response to traumatic injury at the site of partial or complete nerve transection as new axons from the proximal nerve stump sprout to reinnervate the distal segment. In rare cases neuromas have also been described as intramedullary spinal cord lesions. These lesions have been identified as incidental autopsy findings in association with prior trauma and cervical spondylosis, multiple sclerosis, spinal tumors, and syringomyelia. The authors report the case of a 50-year-old man who had been involved in a motor vehicle accident, during which his car was struck from behind as it was stationary at an intersection, more than 5 years before presentation. A workup for syncopal and presyncopal episodes involved magnetic resonance imaging that revealed a 1.1-cm lesion at the cervicomedullary junction (CMJ). The imaging features of the lesion raised the question of an ependymoma or subependymoma. The lesion was excised, and examination of the tissue demonstrated a neuroma with haphazardly arranged interlacing bundles of axons ensheathed by Schwann cells with interfascicular regions of reactive glial cells and Rosenthal fibers, consistent with those present after traumatic injury. This case may represent the first true traumatic intramedullary neuroma of the CMJ diagnosed in a living patient and treated surgically.

Functional Gonadotroph Adenomas: Case Series and Report of Literature.

BACKGROUND: Functional gonadotroph adenomas (FGAs) are rare tumors of the pituitary gland that secrete biologically active gonadotropins. OBJECTIVE: To advance clinical understanding of FGAs. METHODS: We performed a retrospective review of adult patients who underwent resection of a pituitary lesion between August 1997 and October 2014 and remain under care at our center. We identified patients who had pathologic and biochemical confirmation of FGAs, as defined by a lack of serum follicle-stimulating hormone/luteinizing hormone suppression in the setting of elevated gonadal steroids, associated clinical symptoms, or both. RESULTS: FGAs were documented in 7 patients (5 men, 2 women) over a 17-year period. Clinical findings at presentation included visual field deficits in 5 patients, headache in 3, sexual dysfunction in 3, and ovarian cysts in both women. Each patient underwent lesion resection (6 via the endonasal transsphenoidal approach and 1 via a craniotomy with transsphenoidal reoperation). Analysis of tumor samples revealed immunopositivity for follicle-stimulating hormone/luteinizing hormone in 5 patients and FSH only in 2 patients. Postoperative follow-up (median, 10 months; range, 4-213 months) indicated remission in 6 of 7 patients. CONCLUSION: An FGA can pose both a diagnostic and a therapeutic challenge. The tumor is often diagnosed as a nonfunctioning macroadenoma after presenting with nonspecific symptoms and is the cause of significant morbidity. An FGA should be considered in the differential diagnosis of patients harboring pituitary adenomas with reproductive dysfunction. Transsphenoidal resection is the initial treatment of choice and can reduce endocrine dysfunction, resolve headaches, improve visual impairment, and provide tissue for detailed analysis. ABBREVIATIONS: FGA, functional gonadotroph adenomaFSH, follicle-stimulating hormoneLH, luteinizing hormoneTSH, thyroid-stimulating hormone.