Rosai-Dorfman disease extending to the brain.

Rosai-Dorfman disease (RDD) is a sporadic idiopathic sinus histiocytosis plausibly reactive in nature and well responsive to pharmacological and surgical treatment. Though it can affect almost any organ system, involvement of the nervous system is exceedingly rare. When it does affect the brain, spinal cord, and meninges, it could have profound clinical presentations. Most commonly, RDD manifests with massive cervical lymphadenopathy and signs and symptoms that mimic systemic inflammatory state. We describe a progressive RDD that was unresponsive to therapy that started as a benign salivary gland lesion, spread to the skin, bilateral breasts, and eventually manifested as multifocal meningeal deposits that prompted the patient to seek urgent neurosurgical treatment. Early diagnosis and better understanding of the pathophysiology of RDD is needed to develop disease-specific medications that will halt this disease in its early stages. Thus far, the surgical approach remains the most successful treatment option when disease extends to complex organ systems like the central nervous system.

Multiple Intracranial Rosai-Dorfman Disease: A Case Report.

Rosai-Dorfman disease is an uncommon lymphoproliferative disorder, and multiple intracranial involvement in disseminated disease is exceedingly rare. We present a case of a 52 year-old female who presented with intractable headaches and a history of Rosai-Dorfman disease unresponsive to chemo- and radiation therapies. She was found to have new multiple intracranial masses that were treated with surgical excision. Pathology confirmed a diagnosis of intracranial Rosai-Dorfman. The disease presentation, radiographic appearance, histology, treatment, and prognosis are briefly reviewed.

A Mobile App to Screen for Neurocognitive Impairment: Preliminary Validation of NeuroScreen Among HIV-Infected South African Adults.

BACKGROUND: Neurocognitive impairment (NCI) is one of the most common complications of HIV infection, and has serious medical and functional consequences. South Africa has 7 million people living with HIV (PLHIV) with up to three-quarters of antiretroviral therapy (ART)-naïve individuals having NCI. South Africa's health system struggles to meet the care needs of its millions of PLHIV; screening for NCI is typically neglected due to limited clinical staff trained to administer, score, and interpret neuropsychological tests, as well as long test batteries and limited screening tools for South African populations. Without accurate, clinically useful, and relatively brief NCI screening tests that can be administered by all levels of clinical staff, critical opportunities to provide psychoeducation, behavioral planning, additional ART adherence support, and adjuvant therapies for NCI (when they become available) are missed. To address these challenges and gap in care, we developed an mHealth app screening tool, NeuroScreen, to detect NCI that can be administered by all levels of clinical staff, including lay health workers. OBJECTIVE: The purpose of this study was to examine sensitivity and specificity of an adapted version of NeuroScreen to detect NCI (as determined by a gold standard neuropsychological test battery administered by a trained research psychometrist) among HIV-infected South Africans when administered by a lay health worker. METHODS: A total of 102 HIV-infected black South African adults who had initiated ART at least 12 months prior were administered NeuroScreen and a gold standard neuropsychological test battery in the participants' choice of language (ie, English or isiXhosa). Three composite z scores were calculated for NeuroScreen: (1) sum of all individual test scores, (2) sum of all individual test scores and error scores from four tests, and (3) sum of four tests (abbreviated version). Global deficit scores were calculated for the gold standard battery where a score of 0.5 or greater indicated the presence of NCI. RESULTS: The mean age of participants was 33.31 (SD 7.46) years, most (59.8%, 61/102) had at least 12 years of education, and 81.4% (83/102) of the sample was female. Gold standard test battery results indicated that 26.5% (27/102) of the sample had NCI. Sensitivity and specificity of age-, education-, and sex-adjusted NeuroScreen scores were 81.48% and 74.67% for composite score 1, 81.48% and 81.33% for composite score 2, and 92.59% and 70.67% for composite score 3, respectively. CONCLUSIONS: NeuroScreen, a highly automated, easy-to-use, tablet-based screening test to detect NCI among English- and isiXhosa-speaking South African HIV patients demonstrated robust sensitivity and specificity to detect NCI when administered by lay health workers. NeuroScreen could help make screening for NCI more feasible. However, additional research is needed with larger samples and normative test performance data are needed.

Management of an unusual, recurrent neurenteric cyst in an infant: case report and review of the literature.

PURPOSE: Neurenteric cysts are rare congenital remnants formed by a failure of separation between endoderm and ectoderm in utero. METHODS: We describe a case of a 7-month-old male with a large cervical neurenteric cyst presenting with intermittent neck stiffness and irritability. RESULTS: This cyst was resected, recurred, and required repeat surgery. The patient's postoperative course included aseptic meningitis and hydrocephalus requiring ventriculoperitoneal shunt and later management of tethered cord, necessitating detethering. CONCLUSION: Unique features of this case include the presence of intermittent pain symptoms, which may be attributable to cyst filling and emptying. Hydrocephalus is an uncommon finding that may be secondary to aseptic meningitis from cyst rupture. Tethered cord is also an unusual entity that can accompany this diagnosis, warranting additional imaging work-up and monitoring.

Effects of ethanol on pulmonary inflammation in postburn intratracheal infection.

Infectious complications are a major cause of mortality in trauma patients. Burn patients with prior ethanol exposure have a worse prognosis than those who sustain injury but had not been drinking. We examined pulmonary infection and lung pathology in mice given ethanol (1.2 g/kg) 30 minutes before being subjected to 13 to 15% total body surface area scald burn followed by intratracheal inoculation with Pseudomonas aeruginosa (1-2 x 10(3) colony-forming units [CFUs]). Survival was monitored for up to 48 hours. Sham control groups had 100% survival after intratracheal infection regardless of ethanol exposure. Infected burned animals had 55% survival; however, survival of infected mice exposed to ethanol and burn injury was significantly lower (27%, P < .0001). When pulmonary infection was evaluated, the lungs of sham groups were negative for bacterial colonies. In addition, at 24 hours there were no significant differences in lung CFUs from infected burned animals regardless of ethanol exposure (3.0 x 10(4)). However, pulmonary bacterial content significantly decreased (1.2 x 10, P < .02) at 48 hours in mice given burn injury alone, where CFUs from the lungs of mice exposed to ethanol prior to burn did not decline (5.4 x 10(5)). At the same time point, lungs from animals given ethanol and burn injury had about a 2-fold (P < .02) increase in leukocyte infiltration and vascular congestion, as well as decreased pulmonary oxygen saturation (82.8%, P < .02), when compared with other treatment groups. In summary, ethanol exposure in postburn intratracheal infection results in the inability to clear pulmonary infection marked by a prolonged pulmonary leukocyte accumulation and a decrease in pulmonary function.

Intraventricular schwannoma in a 15-year-old adolescent: a case report.

INTRODUCTION: Schwannomas are benign tumors that originate from the myelin-forming Schwann cells of peripheral nerves or at the Obersteiner-Redlich zone of the vestibular division of the eighth cranial nerve. Intraventricular schwannomas are rare, particularly among children. DISCUSSION: This case report illustrates a right occipital horn schwannoma in a 15-year-old adolescent boy who was successfully treated with surgical resection and discusses the possible origins of the tumor in this unique location.

Identification of patients with low-risk for aneuploidy: comparative discriminatory models using linear and machine-learning classifiers in prostate cancer.

BACKGROUND: Prostate needle biopsy (PNB) ploidy status has proven utility to predict adverse outcomes after prostatectomy. We sought to develop models to predict ploidy status using clinicopathologic variables. METHODS: We identified a cohort of 169 patients with a diagnosis of prostatic adenocarcinoma on PNB, and estimated ploidy status (determined using Feulgen stained biopsy tissue) using four predictors, including age, prebiopsy PSA, highest Gleason score (GS), and the percentage of involvement by carcinoma at the biopsy site with the highest GS (PCARBX). Logistic regression (LR), Neural Network (NN), and CART classifiers were constructed. RESULTS: Univariate analyses revealed all four predictors to be significantly associated with ploidy status. On multivariable analyses, LR identified a 2-parameter model, including GS and PCARBX that had a significant ability to predict ploidy status with a 74% and 75% correct classification rate (CCR), respectively. Using the same variables, CART and NN yielded similar CCRs of 70.4%. Within GS = 6 cohort, the CART model classified over 90% of biopsies as diploid when patients had a PCARBX < 55% and a log(PSA) < 1.7. CONCLUSIONS: Our study demonstrates that models using GS and PCARBX are able to predict PNB ploidy status with acceptable accuracy. While machine learning classifier-derived models yield similar accuracy as LR-derived models, the latter methodology has the distinct advantage of being applicable in future datasets to estimate case-specific predictions. This information may be useful in identifying potentially aneuploid patients, who can then be targeted for more aggressive therapy.

The pathogenesis of craniopharyngiomas.

OBJECTIVE: The objective of the study is to review the pathogenesis of craniopharyngiomas. METHODS: A literature review of articles relating to the embryogenesis of the pituitary gland and sella and the pathogenesis of craniopharyngiomas was performed. CONCLUSIONS: Craniopharyngiomas are benign, epithelial neoplasms of the sella and parasellar region seen in children and adults that may arise from neoplastic transformation of ectoderm-derived epithelial cell remnants of Rathke's pouch and the craniopharyngeal duct.

Efficacy of manual dissection of lymph nodes in colon cancer resections.

The adequacy of lymph node dissection of colonic resection specimens influences the clinical and pathologic staging, leading to important postsurgical treatment decisions. Although manual lymph node dissection is the current standard at most institutions, recent statistical studies indicate that all lymph nodes, including those measuring 1-2 mm, should be recovered to be assured of lymph node negative status. Thus, we tested the efficacy of gross dissection by submitting the entire residual mesenteric fat. We analyzed 15 randomly chosen colonic resections (2 pT1, 1 pT2, 11 pT3, 1 pT4). After standard gross dissection of lymph nodes and submission of colonic material for diagnosis, the entire remaining mesenteric material was dehydrated over several days by serial washing in alcohol and acetone. All of the mesenteric tissue was submitted for histology. The average number of nodes found by original gross inspection was 20.8, while the average number of additional nodes found after clearing was 68.6. In all, 83% of the additional nodes were 2.0 mm or less in size. There were seven pN0 cases; one was upstaged by additional findings that may have been artifactual. There were four pN1 cases; three were upstaged to pN2 after submission of the mesenteric material. All four pN2 tumors had additional metastases identified. In all, 75% of all positive nodes were under 2.0 mm in size. In this limited sample, standard gross dissection proved sufficient for most pN0 tumors to remain node negative. However, our findings within the pN1 group show that examination of all of the mesenteric material may be necessary to be assured of correct pN status.

Orbital hemangioblastoma arising in a rectus muscle.

We describe the clinical and histologic features of the first case, to our knowledge, of hemangioblastoma of the orbit arising from an extraocular muscle. We examined a 73-year-old woman with conjunctival injection, 2 mm of proptosis, and limitation of abduction of the right eye. A medial-lateral orbitotomy was used to approach the medial rectus enlargement noted on orbital imaging. Histopathologic examination with light microscopy and immunohistochemistry demonstrated the characteristic findings of a hemangioblastoma.

Radiosensitive orbital inflammation associated with temporal arteritis.

A 75-year-old woman developed acute loss of vision in the OD, ipsilateral periocular pain, an afferent pupillary defect, sectoral optic disc edema, and later ipsilateral proptosis and an intraconal mass. She denied any symptoms of temporal arteritis, and a sedimentation rate was normal. Orbital biopsy demonstrated chronic granulomatous inflammation with perivasculitis. A temporal artery biopsy disclosed findings consistent with temporal arteritis. Following 2000 cGy of external beam radiation, her visual function and orbitopathy completely resolved. This unusual presentation of orbital inflammation in association with temporal arteritis demonstrates that pathologic findings of temporal arteritis may be clinically nonspecific and that external beam radiation may be an effective therapy in this setting.

Molecular characterization of human meningiomas by gene expression profiling using high-density oligonucleotide microarrays.

Meningiomas are common central nervous system neoplasms that exhibit remarkably diverse histopathology and biological behavior. Compared to astrocytomas, the most common central nervous system tumor, little is known about the molecular pathways critical for meningioma tumor formation and malignant progression. As an initial step toward characterizing the genetic basis of meningioma pathogenesis, we assessed cancer-related gene expression profiles of nonneoplastic leptomeningeal specimens and human meningiomas of varying World Health Organization (WHO) grade using high-density oligonucleotide microarrays. Although expression profile differences between nonneoplastic and meningioma specimens were readily discernible, the expression profile of a subset of genes could also distinguish WHO grade I from WHO grades II and III tumors. Altered expression levels of several genes identified in this study have been previously noted in meningiomas (eg, growth hormone receptor, IGFBP-7, endothelin receptor A, IGF2). However, we also identified a number of novel genes whose expression was associated with WHO grade and was confirmed by reverse transcriptase-polymerase chain reaction in a larger, independent set of meningeal tumors (n = 47). This report represents the first gene expression profiling studies of meningiomas and identifies some initial candidate genes that may provide further insights into the genetic basis for meningioma pathogenesis.

Utility of intraoperative consultation touch preparations.

Although intraoperative touch preparations (TPs) often are performed in conjunction with frozen sections, the comfort level of using TPs in actual practice and the effect of TP quality and cytologic experience on diagnostic accuracy have not been measured. To investigate the utility of intraoperative TPs and to compare them with that of frozen sections, five pathologists of differing levels of cytologic experience retrospectively reviewed 122 intraoperative TPs and frozen sections. Accuracy rates for individual pathologists were calculated and the accuracy using TPs was compared to that of frozen sections. TP accuracy was correlated with TP quality and cytologic experience. The mean rates of correct, incorrect, and atypical TP diagnoses were 88.5%, 4.1%, and 7.4%, respectively. The mean rates of correct, incorrect, and deferred frozen section diagnoses were 86.1%, 2.5%, and 11.9%, respectively. For the four pathologists with cytologic experience, both TP and frozen section diagnostic accuracy rates were similar; however, the pathologist who lacked cytologic experience had lower TP diagnostic accuracy. All pathologists who had cytologic experience requested a frozen section for cases with an atypical or incorrect TP diagnosis. In cases with a correct TP diagnosis a frozen section was requested 46.3% of the time. TPs of greater technical quality were associated with higher diagnostic accuracy. In conclusion, the use of performing TP and frozen section are complementary and result in increased diagnostic accuracy. For some pathologists, TPs may replace frozen sections in over 50% of cases.

Clinicopathologic evaluation of the Mueller muscle in thyroid-associated orbitopathy.

PURPOSE: To study the histopathologic features of the Mueller muscle in chronic eyelid retraction caused by thyroid-associated orbitopathy. To investigate if the degree of eyelid retraction correlates with any histopathologic finding. METHODS: A prospective case series of 23 consecutive patients with thyroid-associated orbitopathy was studied. Specimens were obtained during a standard muellerectomy. Formalin-preserved specimens were studied with the use of hematoxylin-eosin, periodic acid-Schiff, Masson trichrome, and Giemsa stains. Immunostaining against leukocyte common antigen, L26, CD3, and KP-1 was performed. Three control specimens were also evaluated in a similar fashion. Fresh tissue was placed in cold glutaraldehyde overnight, postfixed, dehydrated, and infiltrated with epoxy resin. Silver (70 nm) sections were cut and stained with uranyl acetate and lead citrate for electron microscopic examination. RESULTS: On light microscopy, fibrosis and mast cell infiltration was present in all 23 specimens. Fat infiltration was noted in 16 of 23 specimens and did not correlate with increasing age of the patient. Interstitial edema and lymphocytic infiltration were not observed. On immunohistochemistry, leukocyte common antigen was positive, confirming the presence of inflammation. L26, CD3, and KP1 were negative. Electron microscopy demonstrated fibrosis, mast cells, and abundant contracting Mueller cells. The degree of clinical retraction in millimeters did not correlate with fibrosis, inflammation, or fat infiltration. The control specimens demonstrated rare fat and mast cell infiltration and no fibrosis. CONCLUSIONS: Contrary to previous reports, the Mueller muscle is involved in the inflammation and fibrosis that characterizes thyroid-associated orbitopathy. The Mueller muscle is grossly enlarged. On histopathologic inspection, fibrosis, fatty infiltration, and increased mast cell presence accompany focal atrophy of the Mueller muscle. In concordance with prior descriptions, many Mueller cells are in an actively contracting state on electron microscopy.

Force Modulation Elasticity Mapping of Plastic-embedded, Thin-sectioned Skeletal Muscle.

We have been researching the capability of atomic force microscopy to reveal nontopographic properties of tissue embedded in plastic and sectioned with standard electron microscopic techniques. We present topography and elasticity maps of plastic-embedded, thin sections of muscle tissue. The images show topography correlated with the normal repeating structure of the sarcomere. Elasticity mapping using force modulation revealed contrast between the actin- and myosin-rich areas. We attribute the observed contrast in elasticity to the difference in local concentrations of biological material in embedding plastic.