Sudden death during struggle in the setting of heterozygosity for a mutation in calsequesterin 2.

Instances of sudden and unexpected death while in police custody remain complex and controversial cases in forensic pathology, and provide unique diagnostic challenges. In general, the circumstances of these cases have resulted in two major theories to account for these deaths: "excited delirium syndrome", and positional (restraint) asphyxia. However, some cases that are not easily explained by one of these theories may be best explained by a theory from another emergent area in forensic pathology, non-structural genetic heart disease. We present one such case, a sudden arrhythmic death during struggle/restraint. A 45 year old man with developmental delay was walking outdoors as part of his daily routine. He was misidentified as a criminal suspect by police officers, who attempted to take him into custody. He resisted this arrest violently. He was taken to the ground, and restrained in a face-down position. Both police and civilian witness state that he was pushing his chest off the ground with his arms, when he suddenly collapsed and died. The interaction with police lasted approximately 3 min. There was no prior excited delirium. At autopsy, minor external blunt force injuries were observed. The heart showed mild cardiomegaly with concentric left ventricular hypertrophy, and sub-occlusive coronary atherosclerosis. Toxicological testing was negative for common drugs, including cocaine and its metabolites. Post-mortem molecular testing demonstrated this man to be heterozygous for a catecholaminergic polymorphic ventricular tachycardia (CPVT) associated mutation (Phe189Leu) in the calsequestrin 2 (CASQ2) gene. This mutation was classified as a class I mutation (deleterious), that may cause disease in a heterozygous state. The cause of death was given as cardiac arrhythmia precipitated by struggle/restraint in a man with CPVT. This case illustrates the difficulty assigning a scientific cause of death in rare and controversial cases, and the value of the molecular autopsy in identifying disease causing mutations.

CD99 expression in Merkel cell carcinoma: a case series with an unusual paranuclear dot-like staining pattern.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine cancer of the skin. The utility of CD99 (MIC-2) in the diagnosis of MCC has been previously studied, with reported rates of expression ranging from 13 to 55%. When specified, a membranous or cytoplasmic staining pattern was considered significant. Recent studies of CD99 have identified a paranuclear dot-like expression pattern in certain non-neuroendocrine pancreatic and colonic lesions. We recently noted paranuclear dot-like staining in several cases of MCC, including cases lacking cytokeratin 20 (CK20) expression. METHODS: Fourteen cases of MCC were stained with CK20 and CD99 antibody, and the pattern and intensity of staining were recorded. Seven cases of pulmonary small cell carcinoma (PSCC) and one case of primitive neuroectodermal tumor (PNET) were used for comparison. RESULTS: All 14 cases of MCC showed at least focal CD99 staining, with both membranous and paranuclear dot-like staining patterns identified. CK20 staining was present in 12/14 cases, with the characteristic dot-like pattern identified. Four of seven cases of PSCC showed CD99 staining, with two showing a finely granular dot-like staining pattern. CONCLUSIONS: We report an unusual pattern of paranuclear dot-like expression of CD99 in 14 cases of MCC, two of which did not express CK20. This previously unrecognized expression pattern may be of use in differentiating MCC from other cutaneous malignancies, especially when CK20 expression is limited or absent.

Suicide by Fatal Pentobarbital Intoxication in Ontario, Canada, from 2012 to 2015.

A fatal concentration of pentobarbital found in a coroner's case where the history had not indicated use of this drug prompted a review of fatalities in Ontario from 2012 to 2015. Coroner's case files, including police and toxicology reports, were reviewed in twenty deaths, in which pentobarbital was identified as the primary cause of death. In all of the deaths (11 females, 9 males), the blood concentration of pentobarbital was greater than 10 mg/L. There were three to eight deaths per year and each was classified as suicide. In 11 cases, there was clear evidence that the drug was purchased over the internet from Mexico or China and imported into Canada. In four cases, it appears that the pentobarbital was labeled as a different, innocuous chemical to facilitate crossing the border without scrutiny. The findings underscore the value of a thorough scene investigation, including details of evidence that may be considered unrelated.