Fatalities Due to Failure of Continuous Subcutaneous Insulin Infusion Devices: A Report of Six Cases.

Diabetes mellitus type 1 and type 2 are diseases characterized by impaired regulation of blood glucose due to decreased insulin production and insulin resistance, respectively. Management of diabetes mellitus often requires injection of exogenous insulin. Continuous subcutaneous insulin infusion (CSII or insulin pump) is a diabetes treatment modality utilizing a device to aid in regulation of glycemic control. Malfunctions in device components can have rare fatal consequences. Described in this report are six fatalities due to one such malfunction, the failure of plastic cannulas of CSII devices to penetrate the skin and deliver insulin, resulting in fatal diabetic ketoacidosis (DKA). The cases derive from four different death investigation systems. For each case, scene and autopsy findings are presented, as well as selected toxicology and histology findings. These cases illustrate the importance of careful examination of CSII devices in death investigations and introduce a discussion on discrepant manner of death classifications.

Quantifying Macrophages and Hemosiderin in Pediatric Dura Mater.

Determining the age of a subdural hematoma at autopsy is of great interest for medicolegal purposes. The appearance of pigment-laden macrophages is often referenced as evidence that the subdural hematoma is 3-4 days old. However, understanding the significance of macrophages and hemosiderin requires understanding the histology of infant dura. Samples of grossly unremarkable dura taken from 17 pediatric autopsies were identified and histologically confirmed to lack subdural neomembrane. CD68 immunostaining and Prussian blue staining was performed. The CD68-positive cells per high-power field were quantified, and the presence of iron-containing cells was recorded. CD68-positive cells were present in all cases, even in the dural border layer. Iron-containing cells were identified in 59% of cases, and in the dural border layer in 29%. Therefore, CD68-positive and iron-containing cells can be present in pediatric dura without neomembrane or macroscopic subdural hemorrhage, and this requires consideration when estimating the age of a subdural hematoma.

National Association of Medical Examiners Position Paper: Recommendations for the Investigation and Certification of Deaths in People with Epilepsy.

Sudden unexpected death of an individual with epilepsy (SUDEP) can pose a challenge to death investigators, as most deaths are unwitnessed and the individual is commonly found dead in bed. Anatomic findings (e.g., tongue/lip bite) are commonly absent and of varying specificity, limiting the evidence to implicate epilepsy as a cause of or contributor to death. Thus, it is likely that death certificates significantly underrepresent the true number of deaths in which epilepsy was a factor. To address this, members of the National Association of Medical Examiners, North American SUDEP Registry, Epilepsy Foundation SUDEP Institute, American Epilepsy Society, and the Centers for Disease Control and Prevention convened an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of autopsy and toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance of epilepsy-related deaths. The recommendations provided in this paper are intended to assist medical examiners, coroners, and death investigators when a sudden, unexpected death in a person with epilepsy is encountered.

Embolic Foreign Material in the Central Nervous System of Pediatric Autopsy Patients With Instrumented Heart Disease.

Upon detection of foreign-body embolization to the central nervous system (CNS) following a specific invasive cardiovascular procedure in 1 autopsied child, we undertook a quality assurance analysis to determine whether other patients had had similar events. Autopsies of all infants and children with history of cardiac catheterization, heart surgery on cardiopulmonary bypass, and/or extracorporeal membrane oxygenation over a 5-year period at a single tertiary care institution were reviewed for light-microscopic evidence of foreign material. Of the 24 patients meeting clinical criteria (13 females, 11 males; ages 6 days to 20 years, median age 7.5 months), 8 (33%) had foreign embolic material to the CNS. The material was associated with a cellular inflammatory reaction in all cases, with a subset associated with infarcts. No embolic foreign material was detected in 14 age-matched patients without history of cardiovascular procedures. Particles acquired from ex vivo manipulation of a catheter type utilized in at least 1 of the affected patients demonstrated similar histologic characteristics. We conclude that, in addition to recognized risks of hypoxic-ischemic brain damage in congenital cardiopulmonary disease, potential brain insult exists in the form of instrumentation-related foreign emboli to the cerebral vasculature. Cardiac catheters are a potential source of foreign embolic material.

Fatal Rotavirus Infection in a 4-Year-Old with Unsuspected Autoimmune Adrenal Insufficiency.

The diagnosis of adrenal insufficiency is often delayed, as the presenting symptoms of fatigue, abdominal pain, and anorexia are vague and nonspecific. However, timely diagnosis and treatment with replacement steroids are needed to prevent fatal adrenal crisis. While the most common cause of primary adrenal insufficiency in childhood is congenital adrenal hyperplasia, a significant minority (13-23%) is caused by autoimmune destruction of the gland. We present a case of a 4-year-old, previously healthy child who had a one-day history of nausea and vomiting, and was found unresponsive by her caretaker. Despite emergency rescue and transport to the hospital, she was pronounced dead. At autopsy, the adrenal glands were atrophied. Histologic examination revealed lymphocytic infiltration of the adrenal glands consistent with autoimmune adrenal insufficiency. Fecal viral antigen testing was positive for rotavirus. The cause of death was determined to be adrenal crisis in the setting of rotavirus gastroenteritis due to adrenal insufficiency (Addison disease).

Analysis of MT-45, a Novel Synthetic Opioid, in Human Whole Blood by LC-MS-MS and its Identification in a Drug-Related Death.

MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) is just one of the many novel psychoactive substances (NPS) to have reached the recreational drug market in the twenty-first century; it is however, one of the first designer opioids to achieve some degree of popularity, in a market currently dominated by synthetic cannabinoids and designer stimulants. A single fatality involving MT-45 and etizolam is described. A method for the quantitation of MT-45 in whole blood using liquid chromatography-tandem mass spectrometry was developed and validated. The linear range was determined to be 1.0-100 ng/mL with a detection limit of 1.0 ng/mL, and the method met the requirements for acceptable linearity, precision and accuracy. After analyzing the sample on dilution and by standard addition, the concentration of MT-45 in the decedent's blood was determined to be 520 ng/mL, consistent with other concentrations of MT-45 reported in drug-related fatalities. Etizolam was present at a concentration of 35 ng/mL. This case illustrates the importance of considering non-traditional drugs in unexplained apparent drug-related deaths.

Splenic Artery Aneurysm Invaded by Desmoid-Type Fibromatosis.

Despite the benign histologic appearance and negligible metastatic potential, desmoid tumors can be locally aggressive, invading into adjacent structures and organs. We report an unusual case of desmoid-type fibromatosis causing the death of an otherwise healthy individual by rupturing the splenic artery.

Hybrid schwannoma/perineurioma: clinicopathologic analysis of 42 distinctive benign nerve sheath tumors.

Benign nerve sheath tumors include neurofibromas, schwannomas, and perineuriomas. In recent years, nerve sheath tumors showing discrete areas of more than one histologic type have been described. We have recently recognized tumors showing hybrid features of schwannoma and soft tissue perineurioma. To characterize the clinicopathologic and immunohistochemical features of these lesions, 42 cases received between 1994 and 2008 were retrieved from authors' consult and surgical pathology files. Clinical details and follow-up were obtained from referring pathologists. Hematoxylin and eosin-stained sections were reexamined, and immunohistochemistry was performed. On 10 cases, double labeling with epithelial membrane antigen (EMA) and S100 protein was performed. Twenty-two patients were female and 20 were male (mean age, 38 y; range: 2 to 85; 71% second to fifth decades). Most patients presented with a solitary painless nodule. The tumors arose in a wide distribution: 19 lower limb, 12 upper limb, 6 head and neck, 4 trunk, and 1 colon. None of the patients showed signs of neurofibromatosis. Tumor size ranged from 0.7 to 17.5 cm (mean, 3 cm). Most tumors involved superficial subcutis (11 also dermis); only 3 were intramuscular. Histologically, the tumors were usually well circumscribed but unencapsulated, and composed of spindle cells with plump, tapering nuclei, and palely eosinophilic cytoplasm with indistinct cell borders, arranged in a storiform, whorled, and/or lamellar architecture. Only 1 tumor showed infiltrative margins. One tumor showed a plexiform growth pattern. Antoni A and B zonation and hyaline vessels were absent. Six tumors showed focally myxoid stroma and 11 contained scattered cells with degenerative nuclear atypia. Mitoses ranged from 0 to 4 per 30 high power fields; 32 tumors had no mitoses. All tumors showed staining for S100 protein and EMA; 98% were positive for CD34, 84% for GFAP, and 80% for claudin-1. Fourteen tumors contained rare neurofilament protein-positive axons. Double staining for EMA and S100 protein revealed parallel layers of alternating S100 and EMA-positive cells with no coexpression of antigens by the same cells. Most tumors were composed of approximately 60% to 70% of Schwann cells and 30% to 40% of perineurial cells. After a mean follow-up of 24 months (range, 6 to 60 mo), 1 tumor recurred locally, after incomplete excision. Benign nerve sheath tumors showing predominantly schwannian cytomorphology and perineurioma-like architecture are composed of an admixture of both cell types. These tumors usually arise in the dermis and subcutis and occur over a wide age range and anatomic distribution. Degenerative nuclear atypia (akin to that seen in ancient schwannoma and atypical neurofibroma) is relatively common. Hybrid schwannoma/perineuriomas have no evident association with neurofibromatosis and rarely recur. The pathogenetic basis of the dual pattern of differentiation in these lesions remains poorly understood at this time.

Immunohistochemical staining for claudin-1 can help distinguish meningiomas from histologic mimics.

The histologic distinction between meningiomas and other tumors of the central nervous system occasionally can be difficult. Claudin-1 is a tight junction-associated protein recently shown to be expressed in anaplastic meningiomas. The purpose of this study was to determine whether immunohistochemical staining for claudin-1 could help distinguish meningiomas from histologic mimics, compared with commonly used markers. Tissue sections from 10 meningothelial meningiomas, 20 fibrous meningiomas, 10 atypical meningiomas, 7 solitary fibrous tumors of the meninges, 5 meningeal hemangiopericytomas, and 7 vestibular schwannomas were stained immunohistochemically for claudin-1, epithelial membrane antigen, S-100 protein, CD34, and glial fibrillary acidic protein. In total, 21 (53%) of 40 meningiomas were immunoreactive for claudin-1, whereas none of the other tumors were positive. In contrast, there was considerable overlap in the distribution of the other antibodies evaluated. Claudin-1 seems to be a specific marker for meningiomas in this context. Although its sensitivity is relatively low, claudin-1 may be helpful in a panel of immunostains to distinguish meningiomas from histologic mimics.