Hyaline protoplasmic astrocytopathy in epilepsy.

Hyaline protoplasmic astrocytopathy (HPA) describes a rare histologic finding of eosinophilic, hyaline cytoplasmic inclusions in astrocytes, predominantly in the cerebral cortex. It has mainly been observed in children and adults with a history of developmental delay and epilepsy, frequently with focal cortical dysplasia (FCD), but the nature and significance of these inclusions are unclear. In this study, we review the clinical and pathologic features of HPA and characterize the inclusions and brain tissue in which they are seen in surgical resection specimens from five patients with intractable epilepsy and HPA compared to five patients with intractable epilepsy without HPA using immunohistochemistry for filamin A, previously shown to label these inclusions, and a variety of astrocytic markers including aldehyde dehydrogenase 1 family member L1 (ALDH1L1), SRY-Box Transcription Factor 9 (SOX9), and glutamate transporter 1/excitatory amino acid transporter 2 (GLT-1/EAAT2) proteins. The inclusions were positive for ALDH1L1 with increased ALDH1L1 expression in areas of gliosis. SOX9 was also positive in the inclusions, although to a lesser intensity than the astrocyte nuclei. Filamin A labeled the inclusions but also labeled reactive astrocytes in a subset of patients. The immunoreactivity of the inclusions for various astrocytic markers and filamin A as well as the positivity of filamin A in reactive astrocytes raise the possibility that these astrocytic inclusions may be the result of an uncommon reactive or degenerative phenomenon.

Neuropathology Evaluation of in Utero Correction of Myelomeningocele and Complications of Late-Onset GBS Infection.

Background: Myelomeningocele (MMC) causes significant morbidity and mortality. Efforts have been directed to correct this defect in utero. The neuropathology literature on antenatally repaired MMC and associated complications in humans is limited. Case report: A 12-day-old female, who underwent prenatal MMC repair via a two-layer closure (dural replacement patch, primary skin closure), was born at 34 weeks' gestation. Her group B streptococcus positive mother received appropriate antepartum prophylactic antibiotics. She remained stable until day 11 of life when she underwent rapid clinical deterioration. Despite aggressive intervention, she expired on day 12. Review of placental pathology showed maternal and fetal inflammatory response. Autopsy revealed Gram-positive cocci and inflammation within the basilar leptomeninges and lumbosacral region. Neural and dermal elements were present within the MMC repair. Conclusion: This case documents integration of the dermal matrix patch to neural elements, adhering the spinal cord to scar tissue, the clinical implications of which remain unclear.

Intraoperative Diagnosis for Pediatric Brain Tumors.

Central nervous system (CNS) tumors are now the most common type of solid tumor in individuals aged 0-19 years, with an incidence rate in the United States around 5 per 100,000, accounting for about 1 out of 4 childhood cancers. Pediatric pathologists encounter brain tumor cases with varying frequency, but many of these encounters begin in the context of intraoperative consultation or "frozen section." This review provides an overview of the technical aspects of intraoperative consultation specific to, or more helpful in, CNS tumors, emphasizing helpful cytologic and histologic features of the more commonly encountered pediatric CNS tumors, and illustrating some common diagnostic pitfalls and how these may be avoided.

Pediatric Metastatic Hepatoblastoma With an ARID1A Mutation and Rhabdoid Cells.

The small cell undifferentiated component of hepatoblastoma is an uncommon histologic component and is distinguished from small cell undifferentiated like pattern (originally called hepatoblastoma and now recognized to be malignant rhabdoid tumor) by the bi-allelic SMARCB1 mutations or copy number alterations in the latter. AT-rich interactive domain-containing protein 1A (ARID1A) is a part of the ATP-dependent switch/sucrose non-fermentable complex assembly, but mutations have not been reported as drivers of malignant rhabdoid tumor. ARID1A mutations in hepatocellular carcinoma are associated with poor prognosis but its significance in hepatoblastoma is unknown. We report a unique case of hepatoblastoma in a 19-month-old female with an unusual/atypical small cell undifferentiated component with ARID1A and beta-catenin mutations. It had an aggressive clinical course despite treatment, with metastases to the left psoas muscle, perihepatic and paratracheal lymph nodes, spinal cord, and leptomeninges. Leptomeningeal metastases resulted in diffuse cerebral edema and death. The initial diagnostic biopsy did not reveal rhabdoid cells while all metastatic foci showed cells with rhabdoid morphology in the autopsy specimens. Although this rhabdoid component resembled malignant rhabdoid tumor morphologically, molecular analyses failed to show mutations or deletions of SMARCB1.

Catastrophic congenital hemangioma with severe coagulopathy leading to fatal cardiac failure: Case report and review.

We present a complex case of a neonate, delivered urgently for hydrops fetalis, with a large vascular mass of the extremity, diagnosed postnatally as a congenital hemangioma. The patient suffered immediate cardiac compromise and severe coagulopathy atypical for the diagnosis and subsequently died from these complications. Treatment was imperative but challenging due to a lack of a standardized treatment approach and few historical reports of equally critically ill patients. In this report, we review potential medical and surgical interventions and discuss treatment considerations in similar, life-threatening cases of congenital hemangiomas.

Neuropathological effects of chronically implanted, intracortical microelectrodes in a tetraplegic patient.

Objective.Intracortical microelectrode arrays (MEA) can be used as part of a brain-machine interface system to provide sensory feedback control of an artificial limb to assist persons with tetraplegia. Variability in functionality of electrodes has been reported but few studies in humans have examined the impact of chronic brain tissue responses revealed postmortem on electrode performancein vivo. Approach.In a tetraplegic man, recording MEAs were implanted into the anterior intraparietal area and Brodmann's area 5 (BA5) of the posterior parietal cortex and a recording and stimulation array was implanted in BA1 of the primary somatosensory cortex (S1). The participant expired from unrelated causes seven months after MEA implantation. The underlying tissue of two of the three devices was processed for histology and electrophysiological recordings were assessed.Main results.Recordings of neuronal activity were obtained from all three MEAs despite meningeal encapsulation. However, the S1 array had a greater encapsulation, yielded lower signal quality than the other arrays and failed to elicit somatosensory percepts with electrical stimulation. Histological examination of tissues underlying S1 and BA5 implant sites revealed localized leptomeningeal proliferation and fibrosis, lymphocytic infiltrates, astrogliosis, and foreign body reaction around the electrodes. The BA5 recording site showed focal cerebral microhemorrhages and leptomeningeal vascular ectasia. The S1 site showed focal tissue damage including vascular recanalization, neuronal loss, and extensive subcortical white matter necrosis. The tissue response at the S1 site included hemorrhagic-induced injury suggesting a likely mechanism for reduced function of the S1 implant.Significance.Our findings are similar to those from animal studies with chronic intracortical implants and suggest that vascular disruption and microhemorrhage during device implantation are important contributors to overall array and individual electrode performance and should be a topic for future device development to mitigate tissue responses. Neurosurgical considerations are also discussed.

Corticospinal Wallerian Degeneration Before Myelination: A Case Report.

Wallerian degeneration is defined as axonal fiber and myelin sheath degeneration that affects myelinated axons within the peripheral or central nervous system. Wallerian degeneration or anterograde axonal degeneration before myelination is rarely reported. Involvement of both corticospinal tracts (CSTs) is rarely documented in the literature. We present the postmortem neuropathologic findings of a 1-week-old male neonate born at 23 weeks of gestation with bilateral CST degeneration extending from the posterior limb of the internal capsule through the brainstem into the lumbar spinal cord. Abundant CD68- and CD163-positive macrophages were the prominent histopathology in both CSTs. The cerebrum, brainstem, and spinal cord were unmyelinated, as expected. In contrast, the spinal nerve roots demonstrated early myelination. This case illustrates that Wallerian degeneration occurs in unmyelinated axis cylinders.

Cartilaginous Metaplasia Involving the Atrioventricular Node and Bundle of His Contributing to Sudden Early Neonatal Death.

Cartilaginous metaplasia involving the atrioventricular (AV) node is an uncommon entity that may cause sudden cardiac death secondary to dysrhythmias. We report 2 autopsy cases of full-term male newborns: 1 stillborn and 1 live-born, with antemortem bradycardia who died in the peripartum period. An examination of the cardiac conduction system in both cases demonstrated extensive cartilaginous metaplasia of the central fibrous body and involvement of the AV node and bundle of His. The cases highlight the recognition of cardiac conduction system anomalies as a cause of sudden perinatal death. In cases of perinatal death with preceding arrhythmia, postmortem sections of the cardiac conduction system are recommended to examine for cardiac conduction system anomaly.

Bronchial Mucoepidermoid Carcinoma With the Classic MAML2 Gene Rearrangement in a 2-year-old Boy.

Pulmonary mucoepidermoid carcinoma (PMEC) is rare. To date, primary PMEC has not been reported in a child younger than 3 years of age. We report a case of a 2-year-old boy who presented with 3 episodes of wheezing, cough, and fever over a period of 1 month. Radiologic findings were consistent with foreign body aspiration with consequent bronchial obstruction. Bronchoscopy was performed and attempts to retrieve the foreign body resulted in a biopsy of a fleshy lesion. By histology, the lesion was an epithelial neoplasm comprising cells arranged in a nested pattern. The neoplastic cells were round with round nuclei and amphophilic, vacuolated cytoplasm. Our diagnosis was low-grade salivary gland-type carcinoma of the bronchus. The pneumonectomy specimen showed a well-circumscribed, polypoid intrabronchial mass measuring 2.1 cm in greatest dimension. Histologic examination of the tumor showed an admixture of intermediate cells which were predominant, a small number of mucus cells and rare foci of squamous cells. The final diagnosis rendered was a low-grade mucoepidermoid carcinoma of the bronchus. Accurate diagnosis of PMEC can be challenging on limited biopsy material as seen in the case reported here. The use of molecular studies such as MAML2 gene rearrangement may facilitate diagnosis in difficult cases. Increased awareness of this entity and further molecular studies are needed for a better understanding of the pathogenesis of PMEC. To date, the reported age range for primary bronchial mucoepidermoid carcinoma is between 3 years and 78 years. This case represents the youngest patient reported in the English literature.

Solitary Fibrous Tumors in Pediatric Patients: A Rare and Potentially Overdiagnosed Neoplasm, Confirmed by STAT6 Immunohistochemistry.

Pathological diagnosis of solitary fibrous tumor (SFT) in the pediatric population is challenging, as it occurs uncommonly in this age-group and resembles other spindle cell neoplasms. SFT contains a NAB2-STAT6 fusion gene, which can be reliably detected using STAT6 immunohistochemistry. Positive staining is highly sensitive and specific. We sought to investigate the utility of STAT6 immunohistochemistry, to show how commonly SFT was historically recognized at 3 academic pediatric institutions, to reclassify them when appropriate, and to demonstrate features of major mimics of SFT. Our series included cases with a previous diagnosis of SFT or for which SFT was among key considerations, from 3 major academic pediatric hospitals seen over the past 30 years. Of 18 tumors identified, only 3 tumors from 2 patients demonstrated positive STAT6 staining as well as the typical histology and immunophenotype seen in SFT. The remaining 15 tumors were reclassified based on morphology, additional immunohistochemistry and fluorescence in situ hybridization as desmoid-type fibromatosis (3 tumors), nerve sheath/neural tumors (3 tumors), low-grade fibromyxoid sarcoma, medallion-like dermal fibroma, poorly differentiated Sertoli cell tumor, nodular/proliferative fasciitis, calcifying fibrous tumor, aneurysmal bone cyst of soft tissue, STAT6-negative SFT with adipocytic differentiation, undifferentiated small round blue cell tumor, and scar (1 tumor each). Our study confirms that SFT is rare in the pediatric population and that it is potentially overdiagnosed. STAT6 immunohistochemistry is recommended to confirm the diagnosis of SFT in the pediatric population.

Quadruple Neoplasms following Radiation Therapy for Congenital Bilateral Retinoblastoma.

PURPOSE: The aim of this study was to describe a 34-year-old male with hereditary bilateral retinoblastoma treated with radiotherapy as a child who developed 4 distinct tumors within the radiation field. METHODS: A 34-year-old male with bilateral retinoblastoma status postradiation therapy and recurrence requiring enucleation presented with left-eye visual acuity changes. Magnetic resonance imaging demonstrated a left orbital mass and a right parasellar complex lobulated mass (right sphenoid and right cavernous sinus). Two weeks later, the patient underwent excision of the orbital mass and biopsy of an upper-lid nodule. This was followed by craniotomy for removal of the complex mass. RESULTS: Histology revealed 4 distinct tumors, including an undifferentiated pleomorphic sarcoma (left orbit), a radiation-induced meningioma (right sphenoid), a schwannoma (right cavernous sinus), and a basal-cell carcinoma (left lid). CONCLUSION: Although occurrence of a second neoplasm is a well-known outcome following radiation treatment in patients with hereditary retinoblastoma, the diagnosis of 4 additional neoplasms is rare. Pleomorphic sarcoma, radiation-induced meningioma, and schwannoma are uncommon tumors and not well represented in the literature describing irradiated retinoblastoma patients. Secondary malignancies are a leading cause of early death in retinoblastoma survivors, and long-term follow-up is crucial for patient care.

Suicidal Drug Overdoses in New Mexico: A 5-year Retrospective Review.

To better understand the changing toxicology trends in suicidal drug overdoses in the setting of an increased national trend of multidrug overdoses, a retrospective review of electronic records from New Mexico's Office of the Medical Investigator database was performed between 2008 and 2012 to assess the drug type and current risk factors in suicide deaths. Information on demographics, circumstances, suicide risk factors, toxicology findings, and death certificates was collected and analyzed. Three hundred and forty-two suicide cases of suicide overdoses were identified. Decedents were predominantly female (61.8%). Scene investigation revealed risk factors including suicide ideation (47.4%), previous suicide attempts (38%), and suicide note (38%). Psychiatric illness was present in 72% of cases, with depression being the most common illness. Chronic pain was seen in 27.2% of cases. Most deaths were attributed to multiple drugs (76%). Utilizing the toxicology information will assist in creating public awareness and provide a framework to support targeted efforts to attempt to prevent future suicides.

Discordant Streptococcus agalactiae (Group B streptococcus) gestational infection in monochorionic/diamniotic and dichorionic/diamniotic twins.

Infection due to Streptococcus agalactiae or Group B streptococcus may be acquired during parturition or gestation. Discordant twin gestational Group B streptococcus infections are rarely reported. We describe two cases of fatal discordant gestational Group B streptococcus infection in both a monochorionic/diamniotic pregnancy and in a dichorionic/diamniotic pregnancy. In both instances, cultures, examination of the placentae, and autopsy findings demonstrated infection by Group B streptococcus in only the presenting fetus. Despite the ubiquity of this organism, this is the first documented case of discordant gestational Group B streptococcus infection in monochorionic/diamniotic twins and only the third case documented in dichorionic/diamniotic twins.