Eosinophilic globules in a classic ependymoma: evidence of a possible secretory role.

A number of neoplasms of the central nervous system can demonstrate diffuse eosinophilic globules, known to be secretory products of the corresponding cell type, but they have not been a salient feature in descriptions of classic ependymoma. Here, we present a case of a posterior fossa ependymoma demonstrating glassy PAS-positive, diastase-resistant, eosinophilic globules with light microscopic and ultrastructural features resembling Reissner fiber, the secretory product of the subcommissural organ. While there has been a single published description of an ependymoma with intra- and extracellular granulofibrillary material suggested to be evidence of secretory differentiation, ours is the first case to demonstrate diffuse eosinophilic globules in an ependymoma. The extent of globules allowed full study by electron microscopy to provide new insight into the secretory material and the surrounding structures. Our findings suggest that neoplastic ependymal cells can recapitulate the secretory capacity of the subcommissural organ.

Rhabdomyomatous mesenchymal hamartoma presenting as a sacral skin tag in two neonates with spinal dysraphism.

Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare congenital malformation involving the dermis and subcutaneous tissue, of which there were 62 reported cases through 2014. We report RMH in two neonates presenting as a sacral skin tag. In both cases, magnetic resonance imaging (MRI) of the spine showed evidence of spinal dysraphism, including a lipomyelomeningocele and a tethered cord. Surgical repair of the defects was performed. Histopathologic examination of the skin tags showed a haphazard arrangement of mature skeletal muscle fibers and adnexal elements, consistent with RMH. The second patient also had a hemangioma on the sacrum and was diagnosed with LUMBAR (lower body hemangioma and other cutaneous defects, urogenital anomalies/ulceration, myelopathy, bony deformities, anorectal/arterial anomalies, and renal anomalies) syndrome, an association between cutaneous infantile hemangiomas of the lower body and regional congenital anomalies. The apparent association of paraspinal RMH with spinal dysraphism suggests that aberrant migration of mesodermally derived tissues (including skeletal muscle fibers) during neural tube development may be responsible for the pathologic findings in the skin. Additional study of patients with spinal dysraphism and congenital cutaneous lesions may further support this hypothesis.

An Extraordinary Association of Glomus Tumor and Pacinian Hyperplasia in the Hand of a Female Patient.

BACKGROUND: Glomus tumor is a benign neoplasm of the glomus body, a neuromyoarterial structure that regulates temperature and pressure in the cutaneous vasculature. Approximately 1%-4.5% of glomus tumors present in the hands of females; of these, 65% are seen in the subungual region of the index and long fingers. Pacinian hyperplasia is a benign lesion of the Pacinian corpuscle, a mechanoreceptor located in the subcutis of the hands and feet. METHODS: A 65-year-old woman with a history of hand trauma and a 1-year chief complaint of tingling, pain, and burning sensations in her proximal thumb underwent exploration of the digital nerve after an x-ray and 2 magnetic resonance imaging examinations failed to detect a mass. Two lesions immediately adjacent to each other were excised. RESULTS: Microscopic examination showed Pacinian hyperplasia, and a second proliferation of solid epithelioid cells related to benign blood vessels. Immunohistochemistry confirmed the epithelioid cells to be strongly positive for smooth muscle actin, CD34, and type 4 collagen, which is consistent with the phenotype of a glomus tumor. The cells were negative for S100 protein. CONCLUSIONS: The association of glomus tumor with Pacinian hyperplasia has rarely been reported in the literature. We present another rare case to bring awareness to this differential diagnostic consideration.

Diagnostic Algorithm for Patients With Suspected Giant Cell Arteritis.

BACKGROUND: To identify clinical and laboratory factors contributing to the diagnosis of giant cell arteritis (GCA) and develop a diagnostic algorithm for the evaluation of GCA. METHODS: Retrospective review of 213 consecutive cases of temporal artery biopsy (TAB) seen at a single academic center over a 10-year period (2000-2009). Pathologic specimens were re-reviewed and agreement between the original and second readings was assessed. A composite clinical suspicion score was created by adding 1 point for each of the following criteria: anterior extracranial circulation ischemia, new onset headache, abnormal laboratory results (erythrocyte sedimentation rate, C-reactive protein (CRP), or platelet count), jaw claudication, abnormal or tender superficial temporal artery, constitutional symptoms, and polymyalgia rheumatica; one point was subtracted if a comorbid condition could explain a criterion. RESULTS: Of the 204 TABs analyzed, pathologic findings were confirmatory in 49 (24.0%) and suggestive in 12 (5.9%). TAB-positive patients were more likely to be older (age 75.2 ± 7.8 vs 69.7 ± 11.0 years, P = 0.0002), complain of jaw claudication (relative-risk = 3.26, P = 0.0014), and have thrombocytosis (relative-risk = 3.3, P = 0.0072) and elevated CRP (relative-risk = 1.8, P = 0.037). None of the patients with a clinical score less than 2 had a positive TAB. Diabetes mellitus and kidney disease were often the explanation for the symptoms and abnormal clinical finding(s) that led to a negative TAB. CONCLUSIONS: We propose a clinical algorithm that is highly predictive for a positive TAB and can be valuable in the evaluation process of suspected cases of GCA.

Melanocytic Nevus of the Superior Conjunctival Fornix: A Case Report.

Introduction: Conjunctival nevi are benign tumors that are commonly located at the nasal or temporal limbus and rarely in the fornix or tarsus. We report a case of a patient presenting with a solitary compound cystic nevus of the conjunctival fornix in the background of bilateral complexion-associated melanosis. Case Presentation: A 71-year-old African-American female was referred for evaluation of an incidentally noted melanocytic lesion of the right conjunctival fornix. The patient underwent an excisional biopsy, revealing histological features consistent with a compound cystic nevus. Conclusion: This finding is noteworthy due to the rarity of conjunctival nevi originating in the fornix. The case underscores the importance of excisional biopsy in evaluating conjunctival forniceal melanocytic lesions to exclude malignant melanoma, a critical consideration for prognosis.

National pilot of entrustable professional activities in pathology residency training.

Entrustable professional activities (EPAs) are observable clinical skills and/or procedures that have been introduced into medical education at the student and resident levels in most specialties to determine readiness to advance into residency or independent practice, respectively. This publication describes the process and outcomes of a pilot study looking at the feasibility of using two anatomic pathology and two clinical pathology EPAs in pathology residency in 6 pathology residency programs that volunteered for the study. Faculty development on EPAs and their assessment was provided to pilot program faculty, and EPA assessment tools were developed and used by the pilot programs. Pre- and post-study surveys were given to participating residents, faculty, and program directors to gauge baseline practices and to gather feedback on the EPA implementation experience. Results demonstrated overall good feasibility in implementing EPAs. Faculty acceptance of EPAs varied and was less than that of program directors. Residents reported a significant increase in the frequency with which faculty provided formative assessments that included specific examples of performance and specific ways to improve, as well as increased frequency with which faculty provided summative assessments that included specific ways to improve. EPAs offered the most benefit in setting clear expectations for performance of each task, for providing more specific feedback to residents, and in increasing Program director's understanding of resident strengths abilities and weaknesses.

Adult primitive neuroectodermal tumors: the prognostic value of supratentorial location.

Primitive neuroectodermal tumors (PNETs) are tumors which primarily consist of undifferentiated round neuroepithelial cells. Central nervous system PNETs can be divided into two genetically distinct groups: infratentorial PNET (iPNET)/medulloblastoma and supratentorial PNET (sPNET). Currently, the comparative outcome of adult patients with sPNETs and iPNETs is unknown. In this study we have utilized the Surveillance, Epidemiology, and End Results database to perform a comparative analysis of 103 cases of adult sPNET and 669 adult medulloblastoma cases. Additionally we have analyzed various factors to identify their prognostic significance and characterize the optimal treatment for these tumors. Patients with sPNETs were seen to have a significantly worse survival than those diagnosed with medulloblastomas (16 vs. 155 months, p < 0.0001). Elderly patients (15 vs. 114 months, p < 0.0001) and those over the age of 40 (68 vs. 147 months, p < 0.0001) experienced significantly worse survival than younger patients. In contrast, radiotherapy (143 vs. 26 months, p < 0.0001), surgical resection (116 vs. 22 months, p = 0.0010) and the extent of resection (EOR) (173 vs. 81 months, p = 0.0005) resulted in significantly improved patient survival. Multivariate analysis revealed age greater than 40 years (HR: 1.57; 95 % CI: 1.17-2.11; p = 0.0028) and sPNET pathology (HR: 3.41; 95 % CI: 2.47-4.72; p < 0.0001) to be poor prognostic factors for survival while radiotherapy (HR: 0.52; 95 % CI: 0.38-0.71; p < 0.0001) and the EOR (HR: 0.73; 95 % CI: 0.55-0.96; p = 0.023) were associated with significantly improved survival. The treatment of sPNETs should therefore include maximal surgical resection when feasible followed by radiotherapy as these treatments have been demonstrated to confer a survival benefit. Additional studies are needed to identify effective chemotherapeutics and specific treatment regimens for adults with sPNETs.

Rapidly regulating platelet activity in vivo with an antidote controlled platelet inhibitor.

Millions of individuals are prescribed platelet inhibitors, such as aspirin and clopidogrel, to reduce their risk of thrombosis-related clinical events. Unfortunately many platelet inhibitors are contraindicated in surgical settings because of their inherent bleeding risk complicating the treatment of patients who require surgery. We describe the development of a potent antiplatelet agent, an RNA aptamer-termed Ch-9.14-T10 that binds von Willebrand factor (VWF) with high affinity and inhibits thrombosis in a murine carotid artery damage model. As expected, when this potent antiplatelet agent is administered, it greatly increases bleeding from animals that are surgically challenged. To improve this antiplatelet agent's safety profile, we describe the generation of antidotes that can rapidly reverse the activity of Ch-9.14-T10 and limit blood loss from surgically challenged animals. Our work represents the first antidote controllable antiplatelet agent, which could conceivably lead to improved medical management of patients requiring antiplatelet medication who also need surgery.

Congenital ectropion uvea and mechanisms of glaucoma in neurofibromatosis type 1: new insights.

OBJECTIVE: To describe the clinicopathologic features of congenital ectropion uvea associated with glaucoma in neurofibromatosis-1 (NF-1). DESIGN: Retrospective case series. PARTICIPANTS AND CONTROLS: Five cases of NF-1 associated with glaucoma, from which enucleated eyes were available, and 2 eye bank eyes used as controls. METHODS: The clinical features and courses of these patients were reviewed. Formalin-fixed, paraffin-embedded eyes were examined by light and electron microscopy. Immunohistochemistry using antineurofibromin, anti-glial fibrillary acidic protein, and antivimentin was performed in 3 patients. Gene expression of the mitogen-activated protein kinase (MAPK) signaling pathway was examined in corneal endothelial cells in 1 patient. MAIN OUTCOME MEASURES: Cause of glaucoma in patients with ectropion uvea and NF-1. RESULTS: The age of patients at the time of glaucoma diagnosis ranged from birth to 13 years. Four of the 5 patients had megalocornea and buphthalmos at presentation. Ectropion uvea was noted clinically in 2 patients, but was demonstrated histopathologically in all 5 patients. On histopathologic examination, all patients had varying degrees of angle closure secondary to endothelialization of the anterior chamber angle. Uveal neurofibromas were noted in all patients; anteriorly displaced ciliary processes were noted in 4 of 5 patients who demonstrated ciliary body involvement with neurofibromas. Absence of Schlemm's canal was observed. The endothelial cells lining the closed angle demonstrated positive stain results with the vimentin antibody. Positive antineurofibromin immunolabeling was detected in normal control corneal endothelium, but was absent in corneal endothelium in patients with endothelialization of the angle. Upregulation of genes from the MAPK signaling pathway was demonstrated in the corneal endothelial cells isolated from the NF-1 eyes. CONCLUSIONS: Ectropion uvea in NF-1 glaucoma is secondary to endothelialization of the anterior chamber angle and is associated commonly with severe pediatric glaucoma in NF-1 patients. The endothelial cell proliferation may be related to overexpression of the Ras (Rat sarcoma)-MAPK genes in these eyes.

Inflammatory pseudotumor of the lateral ventricle in a pediatric patient.

Inflammatory pseudotumor (IP) is a benign process that most commonly occurs in the lung and orbit. Extension into the central nervous system is extremely rare, and primary intraventricular lesions of the lateral ventricles are even more infrequent with only 2 cases reported in pediatric patients to date. Here, the authors present an unusual case of IP occurring in a 16-year-old female presenting with a 2-week history of progressive headaches and vomiting, without focal neurological deficits or radiographic evidence of hydrocephalus. The patient underwent left parietal craniotomy and complete resection of the tumor, with no signs of recurrence at 3-month follow-up. Although the rarity of intraventricular IP in pediatric patients can make its initial identification difficult, IP should be considered as a potential diagnosis in this population wherein good outcomes may be achieved following surgical resection.

Transformation of juvenile pilocytic astrocytoma to anaplastic pilocytic astrocytoma in patients with neurofibromatosis type I.

Patients with juvenile pilocytic astrocytoma (JPA) and neurofibromatosis type I (NF-1) tend to have a more indolent course than those with sporadic tumors. In rare circumstances, transformation to anaplastic pilocytic astrocytoma (APA) has been known to occur in sporadic cases and is associated with exposure to ionizing radiation. We present 2 patients with NF-1 who were initially diagnosed with JPA that later transformed to APA. Both patients were not exposed to ionizing radiation but instead received alkylator chemotherapy before transformation. Possibility of conversion to APA should be considered in patients with NF-1 and JPA who have rapid tumor recurrence.

Hematolymphoid malignancies with intraocular intravascular involvement: report of 2 cases.

The interaction between the endothelium and malignant hematolymphoid cells within vessels of the eye can result in focal or diffuse intravascular pathology. As a result, correlation of these findings with specific clinical and ophthalmologic features can vary. We review the ophthalmic findings in two cases of hematolymphoid malignancies limited to the intravascular space and review published literature on this topic. In cases of intravascular large B-cell lymphoma, underexpression of ß1-integrin and intercellular adhesion molecule-1 by the cells of intravascular large B-cell lymphoma results in diffuse ocular vascular involvement. The widespread degree of intravascular involvement correlates with clinical ophthalmologic findings and may lead to retinal and choroidal detachment that is observed postmortem. Conversely, in the context of acute leukemia, induced overexpression of certain adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) in the endothelium of certain vascular beds may result in leukostasis with only selective (choroidal) ocular vessel involvement. As a result of only focal vascular activation and adhesion in the orbit, the gross findings in these cases are minimal and may not correlate with clinical ophthalmologic findings.

Primary meningeal rhabdomyosarcoma.

Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI) demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13). Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC) systemic therapy.