Prothrombin G20210A mutation and sudden death

The authors present a case of sudden death in a previously healthy 36-year-old male. At autopsy there were bilateral pulmonary thromboemboli and right ventricular dilatation. Histologic findings in the lungs included recanalized, old thrombi and evidence of pulmonary hypertension. Genetic analysis for hereditary risk factors was heterozygous positive for the prothrombin G20210A mutation. Implications of this finding, its history and the diagnostic technique shall be discussed. The authors recommend that all cases of deep venous thromboses and pulmonary thromboemboli lacking known risk factors be evaluated for newly described genetic variations associated with an increased risk for venous thrombosis.     

Sarcoidosis and mechanisms of unexpected death

Sarcoidosis is a multisystem disease of uncertain etiology characterized by multifocal areas of discrete and confluent granulomatous inflammation that may rarely be responsible for sudden and unexpected death. Two cases are reported to demonstrate disparate pathological features in fatal cases, one involving cardiac sarcoidosis, and the other neurosarcoidosis with hypothalamic infiltration. Sarcoidosis in individuals dying suddenly may be completely unrelated to the death, contributory or causal. Cardiovascular causes of sudden death in sarcoidosis include arrhythmias associated with cardiomyopathy and ischemia, ventricular rupture, and cor pulmonale due to pulmonary hypertension; respiratory causes include hemorrhage and upper airway obstruction; central nervous system causes include arrhythmias from infiltration of autonomic centers, epilepsy, and obstructive hydrocephalus from brainstem involvement; and gastrointestinal deaths may be due to hemorrhage from esophageal varices associated with portal hypertension. The diagnosis relies on the demonstration of typical noncaseating granulomas and the exclusion of other infective and environmental diseases with similar histopathological findings.     

Sudden Death by Occult Metastatic Carcinoma

A 33-year-old female collapsed and died suddenly after presenting with acute dyspnea and increasing cough over the preceding several months. Autopsy revealed poorly differentiated linitis plastica adenocarcinoma of the stomach. Microscopic examination of the lungs showed features consistent with pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is a well-described complication in patients with adenocarcinoma. The typical presentation involves acute pulmonary hypertension, right-sided heart failure, and sudden death, often before the adenocarcinoma is discovered. The pathophysiology of PTTM remains elusive; it has been suggested that carcinoma cells may produce substances that influence pulmonary vasculature. Our patient had classic clinical and histologic features of PTTM in addition to prominent extravascular compression by intralymphatic tumor cells. These features undoubtedly caused her precipitous decline and lethal pulmonary hypertension, induced by underlying adenocarcinoma. This case demonstrates that sudden death can occur from pulmonary hypertension induced by metastatic carcinoma with remarkably little prior symptomatology.     

Sudden death as a complication of bacterial endocarditis

Three cases are reported to demonstrate the range of possible lesions and wide variation in lethal mechanisms that may be found in cases of unexpected death subsequently shown to be due to bacterial endocarditis. Case 1: A 36-year-old man was found dead on his bedroom floor surrounded by drug paraphernalia. At autopsy, acute myocardial ischemia was present caused by coronary artery ostial occlusion complicating acute bacterial endocarditis of the aortic valve. Case 2: A 54-year-old man with chronic renal failure was found dead in bed at home. At autopsy, a left middle cerebral artery territory cerebral infarct was present due to septic embolization from bacterial endocarditis involving the aortic valve. Case 3: A 23-year-old man was found collapsed in a pool of blood. At autopsy, upper airway hemorrhage from an arteriobronchial fistula was present caused by septic pulmonary infarction from previous endocarditis of a congenital ventricular septal defect. This report demonstrates that bacterial endocarditis may still be a cause of sudden and unexpected death presenting to forensic mortuaries and that the underlying mechanisms may involve complex sequences of pathological changes that compromise vascular function.     

Lower extremity deep venous thrombosis with fatal pulmonary thromboembolism caused by benign pelvic space-occupying lesions--an overview

Venous stasis predisposes to thrombosis. One hundred and sixty cases of fatal pulmonary thromboembolism were reviewed to determine how many cases had deep venous thromboses associated with venous blood flow reduction caused by external pressure from benign pelvic masses. Three cases were identified, representing 2% of cases overall (3/160): a 44-year-old woman with a large uterine leiomyoma (1048 g); a 74-year-old man with prostatomegaly and bladder distension (containing 1 L of urine); and a 70-year-old man with prostatomegaly and bladder distension (containing 3 L of urine). Although a rare cause of fatal deep venous thrombosis and pulmonary thromboembolism, space-occupying pelvic lesions can lead to extrinsic pressure on adjacent veins reducing blood flow and causing stasis and thrombosis. Individuals with large pelvic masses may, therefore, be at increased risk of pulmonary thromboembolism from deep venous thrombosis, particularly in the presence of concurrent risk factors such as immobility, thrombophilias, malignancy, and significant cardiopulmonary disease.     

Fatal cyclobenzaprine overdose with postmortem values

There are only two published cases of overdose with postmortem blood cyclobenzaprine concentrations, both with confounding factors. We report two additional cases of fatal cyclobenzaprine overdose with postmortem values. Case 1: a 56-year-old female was found in full cardiopulmonary arrest after a verbal suicide threat to a friend. Postmortem blood concentrations were cyclobenzaprine 0.96 mg/L and diazepam 0.3 mg/L. Case 2: a 37-year-old male was found in full arrest by a family member after an intentional ingestion of cyclobenzaprine. Postmortem blood concentrations were cyclobenzaprine 0.8 mg/L and ethanol 0.174 gm/dL. The concentrations of diazepam and ethanol reported in these two patients were not found in quantities usually associated with a fatal outcome, suggesting that the cyclobenzaprine was the primary cause of the fatality. Additionally, the blood was drawn from a femoral site, so that postmortem redistribution is not a likely factor. Blood concentration of > or = 0.8 mg/L cyclobenzaprine may be associated with a fatal outcome.     

Sickle cell lung disease and sudden death: a retrospective/prospective study of 21 autopsy cases and literature review

Sudden death in the setting of sickle cell lung disease (SCLD), is periodically seen in the practice of medical examiners. The goal of the present study was to identify the most common pathologic findings of SCLD associated with sudden or unexpected death. A retrospective/prospective review of 21 autopsy cases from sickle cell patients between 1990 and 2004 was performed. Review of medical records, autopsy reports, and H&E-stained slides of lung tissue was performed. Oil-Red-O and elastic staining of lung tissue were evaluated. All cases were screened for both acute and chronic forms of SCLD. Patients admitted for sickle cell pain crisis ranged in age from 8 months to 65 years. Fifteen out of 21 cases (71.4%) showed significant pulmonary pathology. The most frequent lung findings included pulmonary edema (47.6%), pulmonary thromboembolism (38.1%), fat emboli (33.3%), pulmonary hypertension, grades I-IV (33.3%), and microvascular occlusive thrombi (28.5%). Our study demonstrates higher-than-expected percentages of acute and chronic sickle cell-related lung injury such as fat embolism (33.3%) and pulmonary hypertension (33.3%), with right ventricular hypertrophy (33.3%). Therefore, we propose a simple and high-yield autopsy algorithm of ancillary procedures that should be applied on all known and suspected autopsy cases of sickle cell disease.     

Pulmonary arterial fibromuscular dysplasia: a rare cause of fulminant lung hemorrhage

Arterial fibromuscular dysplasia (FMD) represents a collection of noninflammatory and nonatherosclerotic vascular diseases with a poorly understood etiology. Classically occurring in renal and cerebral arteries, this entity has also been reported in coronary, carotid, and other medium and small arteries. One case occurring in the pulmonary vasculature has been reported. Fatal hemothorax and lung hemorrhage have multiple causes, including other vascular malformations and connective tissue disorders; however, cases of pulmonary FMD are exceedingly rare. We report what appears to be the second such association, occurring in a 69-year-old man. The patient presented with a 3-week history of increasing dyspnea, fatigue, and productive cough; 3 days of increasing back and chest pain; and syncope. Chest radiograph showed a "white-out" of the left lung. The patient died shortly after admission from a fulminant respiratory disease of undetermined etiology. At autopsy he was found to have a massive left hemothorax resulting from an unsuspected pulmonary arterial fibromuscular dysplasia.     

Pulmonary artery perforations as typical complication in the use of Swan-Ganz catheters

Two cases of pulmonary artery perforation are reported in association with the use of the Swan-Ganz catheter. A 71- and a 95-year-old woman were monitored by a flow-directed catheter pre- and intraoperatively. Both of them died. After taking other cases in the literature into consideration, this severe complication can be classified as "typical" for this examination technique. Possible means of prevention, diagnosis, and treatment of these complications are discussed. A review of incidence and genesis is given.     

Sudden death due to dissecting pulmonary artery aneurysm: a case report and review of the literature

Pulmonary artery aneurysm and pulmonary artery dissection are rare antemortem diagnoses, most often associated with sudden death. These pathologic entities are strongly associated with chronic pulmonary hypertension due to structural cardiac defects, either congenital or acquired. We report the case of a 49-year-old woman who died suddenly due to dissection and rupture of a large pulmonary trunk aneurysm, with subsequent cardiac tamponade. Key historical and physical findings are described. Additionally, we present a discussion of the incidence, clinical presentation, pathogenesis, and pathologic diagnostic features of pulmonary artery dissection.     

Coronary arteritis diagnosed at autopsy: three case reports and review of the literature

Coronary arteritis is rare but can be fatal either by itself or in conjunction with other diseases. The authors report cases of three men in whom coronary arteritis was an interesting finding that may have caused or contributed to death. One 45-year-old man collapsed at work, another 56-year-old man was found dead in his parked car, and one 80-year-old man had a recent cerebrovascular accident. All three men had coronary arteritis, arteriosclerotic cardiovascular disease, some form of myocardial disease, and fatty liver change. Two had different lung diseases. The findings suggest that coronary arteritis may be an independent cause of death, part of a systemic disease, or, as these three cases illustrate, part of a constellation of cardiac and cardiovascular pathologies with a possible relation to other medical conditions. Coronary arteritis is an important finding in forensic pathology and merits consideration in a case of unexplained death.     

An Analysis of Possible Mechanisms of Unexpected Death Occurring in Hydatid Disease (Echinococcosis)

Abstract:  Most cases of hydatid disease in human populations are due to Echinococcus granulosus. The hydatid life cycle involves passage between definitive hosts such as dogs and intermediate hosts such as sheep. Humans become accidental intermediate hosts following ingestion of food or water contaminated with eggs or by contact with infected dogs. Although hydatid disease may remain asymptomatic, occasional cases of sudden and unexpected death present to autopsy. Causes of rapid clinical decline involve a wide range of mechanisms including anaphylaxis (with or without cyst rupture), cardiac outflow obstruction or conduction tract disturbance, pulmonary and cerebral embolism, pericarditis, cardiac tamponade, myocardial ischemia, pulmonary hypertension, peritonitis, hollow organ perforation, intracerebral mass effect, obstructive hydrocephalus, seizures, cerebral ischemia/infarction, and pregnancy complications. The autopsy assessment of cases therefore requires careful examination of all organ systems for characteristic cystic lesions, as multiorgan involvement is common, with integration of findings so that possible mechanisms of death can be determined. Measurement of serum tryptase and specific IgE levels should be undertaken for possible anaphylaxis.     

Lethal manifestations of systemic lupus erythematosus in a forensic context

Systemic lupus erythematosus is an autoimmune connective tissue disorder that affects multiple organs. While the clinical manifestations may vary in intensity over time and be associated with chronic disease, occasional cases occur where sudden and unexpected death has occurred. Cardiovascular disease is common, with accelerated atherosclerosis, intravascular thrombosis associated with antiphospholipid syndrome, and hypertensive cardiomegaly. Vasculitis with superimposed thrombosis may result in critical reduction in blood to vital organs, such as the heart and brain with infarction. Mesenteric ischemia may be caused by vasculitis, thrombosis, and accelerated atherosclerosis and may result in lethal intestinal infarction. Other diverse causes of sudden death include myocarditis, epilepsy, pulmonary hypertension, pulmonary thromboembolism, and sepsis. The autopsy evaluation of such cases requires careful examination of all organs with extensive histological sampling to include blood vessels, and microbiological sampling for bacteria, viruses, and fungi.     

Three unusual neuropathologic-related causes of sudden death

We discuss the autopsy findings of three medico-legal cases of sudden death associated with uncommon neuropathologic findings of which the general forensic pathologist may not be familiar. Case 1 was a 43-year-old man who died of a seizure due to malignant melanoma of the temporal lobe associated with neurocutaneous melanosis (NCM). Case 2 was a 57-year-old woman with a history of mental retardation and incoordination because of chronic lead poisoning, who died of a pulmonary thromboembolism due to deep venous thrombosis status post left leg fracture after a fall down a staircase. Autopsy revealed atrophy and gliosis of her cerebellum as a result of childhood lead poisoning. The third patient was a 75-year-old woman who died as a result of acute bacterial leptomeningitis at the cervico-medullary junction with acute inflammation of the connective tissue of her upper cervical spinal column associated with subluxation of her atlantoaxial (AA) joint, also known as Grisel's syndrome.     

Two fatal cases of selenium toxicity

Two patients, a 36-year-old female and a 36-year-old male, separately experienced new onset nausea, vomiting, diarrhea, abdominal pain, muscle weakness and pallor. Over a period of 14-16 h these symptoms continue and progress to include hypotension refractory to therapy, pulmonary edema and cardiovascular collapse. Autopsies show hemorrhagic pulmonary edema, splenomegaly and lack of anatomical cause for sudden death. Postmortem analysis, in one case post-embalming and exhumation, revealed elevated selenium concentrations and a determination of the cause of death. These two cases present several important features associated with selenium toxicity, two of which are previously unreported: (1) selenium as a potential homicidal agent, (2) the toxidrome and time frame of selenium toxicity, (3) selenium determination in exhumed, embalmed tissues, (4) postmortem urinary selenium concentration, and (5) decrease in tissue concentrations over time.     

Urinary incontinence, hyperthermia, and sudden death

An 84-year-old woman is reported whose death was associated with strenuous exercise on an extremely hot day (maximum temperature=43.1 °C, 109.6 °F). At autopsy there was evidence of exposure to high environmental temperatures with early putrefactive changes and mummification. There was underlying cardiomegaly with mild pulmonary emphysema. No significant injuries were detected. Toxicology revealed therapeutic levels of oxybutynin prescribed for urinary stress incontinence. Death was considered to be heat related, exacerbated by oxybutynin therapy, exercise, and cardiomegaly. Given that it has been predicted that there may be an increase in the number of heatwaves and in their intensity and duration, it is possible that such cases may be encountered more often in future. The assessment of all deaths occurring during conditions of extreme heat will require consideration of postmortem toxicology, particularly if there are underlying conditions such as stress incontinence that may be associated with anticholinergic drug therapy.     

Sudden death due to a paraganglioma of the organs of Zuckerkandl

A 20-year-old woman died suddenly in a hospital emergency room after presenting with nausea, vomiting, back pain, and hypertension. At autopsy, an extra-adrenal pheochromocytoma (paraganglioma) of the organs of Zuckerkandl was found, with microscopic focal myocardial necrosis similar to that described in death from adrenal pheochromocytomas. Tumors of the organs of Zuckerkandl are extremely rare; less than 100 such cases have been reported in the world's literature, and only six, including the present case, have presented as a sudden, unexpected death. The symptoms of catecholamine storm may mimic those of acute drug intoxications, leading to misdiagnosis by both clinical physicians and pathologists.     

Recovery of human remains after shark attack

Two cases of fatal shark attack are reported where the only tissues recovered were fragments of lung. Case 1: An 18-year-old male who was in the sea behind a boat was observed by friends to be taken by a great white shark (Carcharodon carcharias). The shark dragged him under the water and then, with a second shark, dismembered the body. Witnesses noted a large amount of blood and unrecognizable body parts coming to the surface. The only tissues recovered despite an intensive beach and sea search were 2 fragments of lung. Case 2: A 19-year-old male was attacked by a great white shark while diving. A witness saw the shark swim away with the victim's body in its mouth. Again, despite intensive beach and sea searches, the only tissue recovered was a single piece of lung, along with pieces of wetsuit and diving equipment. These cases indicate that the only tissue to escape being consumed or lost in fatal shark attacks, where there is a significant attack with dismemberment and disruption of the integrity of the body, may be lung. The buoyancy of aerated pulmonary tissue ensures that it rises quickly to the surface, where it may be recovered by searchers soon after the attack. Aeration of the lung would be in keeping with death from trauma rather than from drowning and may be a useful marker in unwitnessed deaths to separate ante- from postmortem injury, using only relatively small amounts of tissues. Early organ recovery enhances the identification of human tissues as the extent of morphologic alterations by putrefactive processes and sea scavengers will have been minimized. DNA testing is also possible on such recovered fragments, enabling confirmation of the identity of the victim.     

Two cases of death associated with the use of lithium carbonate

Two cases of death associated with the use of lithium carbonate are described. The first one concerns a 39-year-old man who was found suddenly dead on his hospital bed. Toxicologic analysis revealed "therapeutic" levels of lithium, nitrazepam, flurazepam, and phenobarbital. The second case involves a 54-year-old woman initially treated for acute cardiac failure and hypertension, who was finally recognized as a case of lithium intoxication; she died of cardiac arrest without evident cardiac lesions and without lithium ions in serum and urine. The medicolegal aspects of both cases are discussed, with reference to the problems of diagnosis, clinical and toxicological correlations, and the medical responsibility.     

Sudden death from pelvic hemorrhage after bilateral central fracture dislocations of the hip due to an epileptic seizure

Fracture and dislocation of major joints may be caused by the forceful tonic muscular contractions of seizure activity. A 77-year-old man who was found dead in bed with no sign of external trauma had bilateral central fracture dislocations of the femoral head through the acetabular floor with fatal pelvic hemorrhage and extensive pulmonary fat and bone marrow embolism. He had epilepsy, but the last seizure was 6 years earlier, and he had long discontinued medication. The fractures were attributed to a new unwitnessed seizure. This is the twentieth case of central fracture dislocation of the hip since 1970, when better anesthesia eliminated convulsive therapy-induced fractures. The authors review these 20 cases. Seizures followed inflammation, infarction or neoplasia of the brain, eclampsia, metabolic or iatrogenic causes, or epilepsy (6 cases, 2 of which had no prior seizures for 5 years). There were 11 men (mean age, 64 years) and 9 women (mean age, 47 years). Fractures were unilateral in 13 and bilateral in 7. Additional fractures (in vertebrae, shoulders, or femur) were present in eight. Only eight had prior bone disease. Local symptoms led to diagnosis in most, but two were identified incidentally on imaging. The current patient was the only one to die suddenly, but six other patients presented with shock and three died (one of whom had injuries that led to a suspicion of manslaughter). Central fracture-dislocation of the hip is a rare and little known consequence of seizures, with strong potential for misdiagnosis and lethal complications.