Autopsy Files Research Articles

Lack of apparent excess of malignant mesothelioma but increased overall malignancies of peritoneal cavity in Japanese autopsies with Thorotrast injection into blood vessels.

The carcinogenicity of thorium dioxide sol (Thorotrast), an X-ray contrast medium used in 1930-1955, in the liver and bone marrow has been established and agrees well with the effects of a high dosage of alpha radiation in the organs. Recently, however, German and Danish epidemiologic studies have shown excess mesotheliomas in the pleura and peritoneum that are unlikely to have been heavily irradiated by alpha particles. To confirm these observations, we examined the incidence of the cancer in those who underwent Thorotrast injections into blood vessels (n = 370) by using autopsy files of the Japanese Thorotrast study. Only one malignant mesothelioma of the peritoneum was registered, whereas three peritoneal or retroperitoneal sarcomas were observed. Thus, our study did not find any increment of mesothelioma in Thorotrast patients. However, when we took the pleuroperitoneal and retroperitoneal malignancies altogether, the incidence (4/370 = 1.1%) was five times more frequent than that (344/162,000 = 0.2%) in the controls (P < 0.005). Clinicopathological data of the four cases are also presented.

‘Creche coronary’ - A paediatric variant of café coronary syndrome

Sudden collapse due to acute upper aerodigestive tract obstruction in infants and young children is most often caused by ingested food or toy parts. The following cases taken from the autopsy files of the ACH demonstrate particular risk factors associated with young children who are otherwise completely well and who attend child care centers (CCCs). Case 1: A 19- month-old boy collapsed and died at a CCC while eating a sausage. At autopsy a large bolus of sausage was recovered from the lower oesophagus. Case 2: An 18-month old boy choked while eating raw carrot at a second CCC. Although resuscitation was performed and a piece of carrot was removed from the trachea, severe hypoxic ischaemic cerebral damage was followed by death five days later. The “cafe coronary” syndrome in adults classically refers to accidental asphyxia in an individual with dentures who has imbibed alcohol and who is dining out on meat. Major predisposing factors are alcohol and sedative drugs, with other risk factors being impaired motor coordination, for example due to Parkinson disease, and impaired mentation due to senility. Similarities exist between the classical “cafe coronary” syndrome of adults and fatal food asphyxia in young children at CCCs; these include the presentation of collapse due to choking on food while eating away from home, inadequate dentition and underappreciation of appropriate food bolus size. Features which separate the two entities are the young age of the victims and absence of alcohol intoxication or drug ingestion in the latter group. Given that second molar teeth erupt 12 to 20 months after the incisor teeth, there is a significant period of time during which a young child is able to bite off fragments of hard food without being able to properly masticate prior to swallowing. It is therefore helpful at autopsy in such cases to accurately record the stage of dental development and the condition of the teeth.

Pulmonary thromboembolism and unexpected death in infancy

Review of the Department of Histopathology autopsy files over a 30 year period from 1962 to 1991 revealed only three cases in which unexpected death occurred in infants under 1 year of age due to massive pulmonary thromboemboli. Predisposing factors included necrotizing enterocolitis with gut perforation and sepsis, a ventriculoatrial shunt and idiopathic arterial calcification. Diagnosis of the latter autosomal recessive condition was only made at autopsy. These cases demonstrate that pulmonary thromboembolism is a possible, although exceedingly rare, cause of sudden infant death, that some predisposing factors are unique to infancy and that the source of the pulmonary thromboembolus may be difficult to determine at autopsy. Massive pulmonary thromboembolism in infancy may point to the presence of other significant, clinically-unsuspected, disorders.

Unexpected Death Due to Acute Airway Obstruction in Daycare Centers

Sudden collapse due to acute upper aerodigestive tract obstruction in infants and young children is most often caused by ingested food or toy parts.1,2 Although attention has been previously drawn to the different pattern of food asphyxiation in children compared with adults,2 the following two cases taken from the autopsy files of the Adelaide Children's Hospital over a 20-year period demonstrate particular risk factors associated with young children eating in daycare centers. CASE REPORTS Case 1 A 19-month-old healthy boy was eating a sausage happily in a daycare center when last observed by a caretaker who was then absent for several minutes.

Incidence of Leukemia in Olmsted County, Minnesota, 1975 Through 1989

To determine the incidence of leukemia in Olmsted County, Minnesota, for a recent 15-year period and to compare the data with reported rates for the previous 40 years. We conducted a population study of leukemia diagnosed between 1975 and 1989 in residents of Olmsted County by review of medical records identified through diagnostic indexes, death certificates, autopsy files, and histologic preparations. Diagnoses of leukemia were categorized into various subtypes, and age- and sex-specific incidence rates were calculated for leukemia as a whole and for each subtype. In addition, incidence rates were age- and sex-adjusted to the 1970 US white population for comparison with earlier published rates. Age and annual trends as well as sex differences were assessed with the generalized linear interactive model approach. During 1975 through 1989, the mean annual incidence rate for leukemia was 12.3 per 100,000 population in Olmsted County. When adjusted for age and sex, the rate per 100,000 was 13.6, in comparison with a similarly adjusted rate of 11.8 for the previous decade (1965 through 1974). The rates for chronic myelogenous leukemia and acute lymphocytic leukemia remained stable throughout the entire study period; however, rates for acute myelogenous leukemia and chronic lymphocytic leukemia increased, most prominently in patients 50 years of age or older. This increased rate occurred in both males and females, but the incidence rates for both subtypes began increasing earlier for males than for females. Although we cannot rule out an actual increase in incidence rates for these types of leukemia in the elderly population, we believe that the increase in persons older than 50 years of age reflects social change in improved health care and its better utilization by elderly persons, as well as the ability to diagnose leukemia earlier than in the past.

PULMONARY HEMORRHAGE AS A CAUSE OF DEATH IN ALLOGENEIC BONE MARROW RECIPIENTS WITH SEVERE ACUTE GRAFT-VERSUS-HOST DISEASE

Acute graft-versus-host disease (GVHD) has recently been associated with endothelial cell injury. The potential clinical significance was explored here in an autopsy review. Thirty-seven allogeneic bone marrow recipients were identified in the autopsy files at The Johns Hopkins Hospital with no evidence of systemic infection. Forty-one percent (15/37) of these patients were found to have extensive recent pulmonary hemorrhage at autopsy which was thought to have led to terminal respiratory failure and death. The 37 patients were divided into 2 groups: those with significant acute GVHD (stage 2 or greater) and those without GVHD (stage 0 or 1). Fifty-nine percent (10/17) of the patients with significant acute GVHD died of acute respiratory failure due to recent pulmonary hemorrhage as opposed to 25% (5/20) of those without acute GVHD (P = 0.032, Fisher's exact test). Terminal pulmonary hemorrhage was also associated with preparation for BMT, with 67% (12/18) of those prepared with total body irradiation (TBI) having pulmonary hemorrhage as opposed to 15% (3/19) of those prepared with chemotherapy using Busulphan (P = 0.002). There was no significant difference in posttransplant survival, engraftment, or final platelet count between the patients stratified by GVHD or preparative protocol. The data support a strong association between significant acute GVHD and terminal hemorrhage, as well a possible association between TBI and pulmonary hemorrhage. Analysis of variance demonstrates that GVHD and TBI are independently associated with increased pulmonary hemorrhage (P < 0.01 for GVHD, P < 0.001 for TBI). We propose that GVHD contributes to terminal pulmonary hemorrhage by injuring the endothelium. However, this association could also be a secondary effect, i.e., toxicity from therapy for GVHD, or an abnormality in cytokines or growth factors. The pathogenic relationship between significant GVHD and terminal hemorrhage is discussed briefly.

Lethal manifestations of neurofibromatosis type-1 in childhood

Neurofibromatosis type 1 (NF-1), also known as von Recklinghausen's disease, is a relatively common, inherited neurocutaneous disorder. Although 37% of patients with the disease die as a result of it, this is usually considered a late feature. Life threatening complications are infrequent before the age of 30, although deaths from NF-1 do occur in the paediatric age group. The following series demonstrates the clinicopathological features of 4 lethal cases taken from the autopsy files at the ACH during the period 1952 to 1991. All patients had café au lait patches and neurofibromas. Case 1: A 2 year-old female with hypsarrhythmia and mental retardation, died from pneumonia. Autopsy demonstrated diffuse gliosis but no tumours. Case 2: An 11 year-old female with NF-1 and a hypothalamic glioma at age 3. This responded well to radiotherapy until the age of 10 when the patient presented with fitting. This was presumed to be due to vascular insufficiency, as angiography showed occlusion of the R. internal carotid. Gradual deterioration was followed by death 9 months later. At autopsy a cystic astrocytoma of the cerebellum was found in addition to the original hypothalamic glioma. Case 3: A 15 year-old male with NF-1 diagnosed at birth. Severe scoliosis required numerous admissions to hospital. At 2 years of age he was noted to have a mediastinal mass but no action was taken at the time. At age 15 the patient developed severe abdominal pain and ultrasound revealed a large tumour displacing the liver and spleen. The patient died unexpectedly whilst in hospital. Autopsy demonstrated haemorrhage into a plexiform neurofibroma, in association with a malignant schwannoma. Case 4: A 13 year-old male with NF-1 diagnosed at the age of 5. No problems occurred until age 12, when he developed a L. thalamic glioma. There was an initial good response to radiotherapy followed by gradual deterioration. Death occurred and at autopsy he was found to have gliomatosls cerebri. These cases demonstrate that death may occur in childhood due to NF-1 by a variety of mechanisms. Malignancy is a significant risk and was seen in two patients, Including two primary brain tumours in Case 2. Although sudden death is not usually considered an outcome of NF-1, it was found in 1 of the 4 patients. Neurofibromatosis type 1 (NF-1), also known as von Recklinghausen's disease, is a relatively common, inherited neurocutaneous disorder. Although 37% of patients with the disease die as a result of it, this is usually considered a late feature. Life threatening complications are infrequent before the age of 30, although deaths from NF-1 do occur in the paediatric age group. The following series demonstrates the clinicopathological features of 4 lethal cases taken from the autopsy files at the ACH during the period 1952 to 1991. All patients had café au lait patches and neurofibromas. Case 1: A 2 year-old female with hypsarrhythmia and mental retardation, died from pneumonia. Autopsy demonstrated diffuse gliosis but no tumours. Case 2: An 11 year-old female with NF-1 and a hypothalamic glioma at age 3. This responded well to radiotherapy until the age of 10 when the patient presented with fitting. This was presumed to be due to vascular insufficiency, as angiography showed occlusion of the R. internal carotid. Gradual deterioration was followed by death 9 months later. At autopsy a cystic astrocytoma of the cerebellum was found in addition to the original hypothalamic glioma. Case 3: A 15 year-old male with NF-1 diagnosed at birth. Severe scoliosis required numerous admissions to hospital. At 2 years of age he was noted to have a mediastinal mass but no action was taken at the time. At age 15 the patient developed severe abdominal pain and ultrasound revealed a large tumour displacing the liver and spleen. The patient died unexpectedly whilst in hospital. Autopsy demonstrated haemorrhage into a plexiform neurofibroma, in association with a malignant schwannoma. Case 4: A 13 year-old male with NF-1 diagnosed at the age of 5. No problems occurred until age 12, when he developed a L. thalamic glioma. There was an initial good response to radiotherapy followed by gradual deterioration. Death occurred and at autopsy he was found to have gliomatosls cerebri. These cases demonstrate that death may occur in childhood due to NF-1 by a variety of mechanisms. Malignancy is a significant risk and was seen in two patients, Including two primary brain tumours in Case 2. Although sudden death is not usually considered an outcome of NF-1, it was found in 1 of the 4 patients.

Mechanisms of laryngeal obstruction in cases of paediataic sudden death

Obstruction of the larynx may cause death at any age. There are, however, a number of relatively unique obstructive entities that are found predominantly within the paediatric age group. Retrospective review of the autopsy files at the ACH was undertaken over a thirty year period (1962 -91) to characterise more clearly the range and clinicopathological presentations of these conditions, as well as the mechanisms by which laryngeal obstruction may be caused. Less than 1 % of fatal episodes involved laryngeal obstruction. The two most common causes of airway occlusion were acute epiglottitis (when cultured, most often due to Haemophilis influenzae infection), and foreign body inhalation. Children who had died unexpectedly from acute epiglottitis often had only a several hour history of a mild non-specific febrile illness reported. Foreign bodies impacted at the glottis included vegetables and a single case with a wood screw. Congenital malformations of the upper aerodigestive tract with mandibular hypoplasia, in the form of Pierre-Robin, Treacher-Collins and Goldenhar syndromes, occasionally resulted in acute respiratory obstruction and death from compression of the epiglottis by posterior displacement of the tongue. Similar backward displacement of the epiglottis occurred in an infant with a large lingual thyroglossal duct cyst. Congenital deformities of the epiglottis and laryngeal hypoplasia also predisposed to upper airway obstruction. A single case of an extensive cystic hygroma involving the epiglottis and aryepiglottic folds resulted in airway obstruction in a 7 month old infant, and a 1 year old child with treated neuroblastoma and Pseudomonas sp. septicaemia died from airway obstruction due to spontaneous interstitial haemorrhage around the laryngeal inlet. These cases demonstrate a wide range of disorders capable of causing sudden death in the paediatric age group due to obstruction of the larynx. In a number of these patients antemortem symptoms and signs were either absent, or were relatively minor and nonspecific, and so history was of no assistance in directing the autopsy examination. All levels of the upper airway should be carefully examined in cases of paediatric sudden death. Obstruction of the larynx may cause death at any age. There are, however, a number of relatively unique obstructive entities that are found predominantly within the paediatric age group. Retrospective review of the autopsy files at the ACH was undertaken over a thirty year period (1962 -91) to characterise more clearly the range and clinicopathological presentations of these conditions, as well as the mechanisms by which laryngeal obstruction may be caused. Less than 1 % of fatal episodes involved laryngeal obstruction. The two most common causes of airway occlusion were acute epiglottitis (when cultured, most often due to Haemophilis influenzae infection), and foreign body inhalation. Children who had died unexpectedly from acute epiglottitis often had only a several hour history of a mild non-specific febrile illness reported. Foreign bodies impacted at the glottis included vegetables and a single case with a wood screw. Congenital malformations of the upper aerodigestive tract with mandibular hypoplasia, in the form of Pierre-Robin, Treacher-Collins and Goldenhar syndromes, occasionally resulted in acute respiratory obstruction and death from compression of the epiglottis by posterior displacement of the tongue. Similar backward displacement of the epiglottis occurred in an infant with a large lingual thyroglossal duct cyst. Congenital deformities of the epiglottis and laryngeal hypoplasia also predisposed to upper airway obstruction. A single case of an extensive cystic hygroma involving the epiglottis and aryepiglottic folds resulted in airway obstruction in a 7 month old infant, and a 1 year old child with treated neuroblastoma and Pseudomonas sp. septicaemia died from airway obstruction due to spontaneous interstitial haemorrhage around the laryngeal inlet. These cases demonstrate a wide range of disorders capable of causing sudden death in the paediatric age group due to obstruction of the larynx. In a number of these patients antemortem symptoms and signs were either absent, or were relatively minor and nonspecific, and so history was of no assistance in directing the autopsy examination. All levels of the upper airway should be carefully examined in cases of paediatric sudden death.

Total anomalous pulmonary venous drainage (TAPVDI) associated with fatal outcome in infancy and early childhood - an autopsy study of 53 cases

TAPVD results from developmental failure of the common pulmonary vein with retention end dilatation of various embryonic collateral vessels running between the lungs and systemic veins. We present 53 autopsy cases of TAPVD taken from paediatric autopsy files from Adelaide, Oxford and Edinburgh between 1957 and 1990. The patients ranged In age from a stillborn female to a 15 m.o. male with 43 cases (81%) dying In the first 3 months of life. The sex radio was nearly equal with 25 males 147%) and 28 females (53%). While many patients had signs of a congenital cardiovascular anomely prior to death, including techypnoes, techycardie, central cyanosis, cardiac failure and difficulties in feeding, it is noteworthy that 12 patients (23%) presented as sudden and unexpected death in the absence of significant antemortem symptoms and signs. Anomalous pulmônery venous drainage was unsuspected prior to death in s total of 28 cases (53%). 12 infants (23%) underwent surgical correction, none of whom survived mors than several weeks. TAPVD was isolated in 27 cases (51%) and was associated with other cardiac or congenital anomalies in 26 patients (49%). Just over one third of non-isolated ceses comprised the asplenia-heterotaxy syndrome. The points of drainage of the anomalous pulmonary veins were to the subdiaphragmatic veins (N = 21, 40%), L. innominate vein (N = 12, 23%), coronary sinus (N = 6, 11%), superior vena cava (N = 5, 9%), inferior vena cava (N = 3, 6%), L. innominate vein and coronary sinus (N = 2, 4%), azygous vein (N = 1, 2%), persistent L. superior vene cava (N = 1, 2%), R. atrium (N - 1, 2%) and R. innominale vein (N - 1, 2%). Nineteen cases (36%) revealed obstruction of the pulmonary veins or pulmonary hypertensive vascular changes on histology. Sixteen karyotypic studies performed revealed 15 normal keryotypes and 1 Trisomy 21. Given the age range of the patients, these results suggest that TAPVD needs to be excluded et autopsy as a causal factor in cases of sudden infant death, even in the ebsence of entemortem symptoms and signs. Clues at autopsy include abnormal mobility of the heart, visceral <i>situs inversus</i> and poly/asplenia. The diversity of pulmonary-systemic venous anastomoses necessitates careful <i>in situ</i> dissection above and below the diaphragm and consideration of postmortem angiography.

Liver cell dysplasia: A DNA aneuploid lesion with distinct morphologic features

Liver cell dysplasia is characterized by hepatocellular foci with nuclear atypia. It is often seen in cirrhosis and may be a precursor of hepatocellular carcinoma (HCC). To determine whether liver cell dysplasia is DNA aneuploid, 72 sections of 33 cirrhotic livers from the autopsy files of The Johns Hopkins Hospital were studied, and 14 foci of dysplasia from 13 cirrhotic livers were selected. Patients ranged in age from 32 to 70 years. Histologically, there were 10 foci of low-grade dysplasia and four foci of high-grade dysplasia. Nine HCCs served as positive controls; seven autopsy livers with no morphologic or clinical evidence of primary liver disease served as negative controls. One focus of HCC and one focus of dysplasia were unsatisfactory for analysis. Flow cytometric examination demonstrated subpopulations with DNA abnormality in four of nine (44%) foci of low-grade dysplasia, of which three were aneuploid. Three of four (75%) foci of high-grade dysplasia were aneuploid. Six of eight (75%) HCCs showed DNA abnormality, of which five were aneuploid. DNA aneuploidy was not present in the seven control livers; however, one showed DNA abnormality. We conclude that liver cell dysplasia is a morphologic entity that contains DNA aneuploid cells, a feature that supports the role of liver cell dysplasia in the evolution of HCC.

Xanthogranulomatous pyelonephritis (XGP) in childhood and infancy - clinicopathological features of five cases

XGP is an unusual chronic inflammatory condition, which most often affects women between 50-60 years of age. Predisposing factors include infection, calculi and obstructive uropathy. Due to its rarity in children, it is not often considered as a cause of chronic renal inflammatory disease. Review of surgical and autopsy files at the AMCWC over a 28 year period from 1964-91 revealed only 5 cases, the clinicopathological details of which are detailed below. 1) A 3mo malnourished boy with a duplex ureter, vesicoureteric reflux, and renal cytomegalovirus (CMV) infection 2) A 3mo girl with multiple urinary tract infections, a duplex ureter, hydroureter, distal ureteric stricture and upper pole abscess, 3) A 6mo boy with hydroureteronephrosis and renal scarring, 4) A 6yo girl with multiple urinary tract infections, hydroureteronephrosis and renal scarring, and 5) A 13 yo girl with chronic pyelonephritis. 3 total, and 2 partial, nephrectomy specimens were received, 4 of which showed yellow areas on sectioning. All cases demonstrated typical features of XGP with renal parenchyma effaced by a mixed acute and chronic inflammatory infiltrate which included prominent aggregates of foamy histiocytes containing eosinophilic inclusions. Other changes included tubular atrophy, glomerular sclerosis and interstitial fibrosis. No Michaelis-Gutman bodies were seen and staining for iron and calcium was negative. No calculi were present. This study, 1) confirms the association of XGP with chronic infection and reflux in childhood and infancy, 2) raises the possibility of an altered immune response in the pathogenesis of XGP in the infant with malnutrition and concomitant CMV infection, and 31 demonstrates that XGP should be considered in the differential diagnosis of chronic inflammatory conditions of the kidney in very early infancy.

Pure Subcortical Arteriosclerotic Encephalopathy (Binswanger’s Disease): A Clinicopathologic Study

We studied 14 cases of pure subcortical arteriosclerotic encephalopathy selected from the autopsy files (c.f. part 2) in order to single out the characteristic clinical features (average age: 80.9 years). Nine cases were from a prospective study of dementia. The longest observation time was 18 years. The main findings were: (i) previous chronic hypertension, variable and declining blood pressure and a high ischemic score in the late symptomatic phase; (ii) bilateral multifocal decreases in cerebral blood flow; (iii) gradually progressive, fluctuating mental changes (forgetfulness, abulia, emotional lability, impaired higher cortical functions) and disorders of motility (small-stepped gait, pseudobulbar palsy, urinary incontinence), pure motor strokes, with later dementia and immobility. We conclude that insidious disorders of mentation and motility combined with lacunar strokes in elderly individuals are diagnostic clues to subcortical arteriosclerotic encephalopathy.

Ethnic differences in the anatomical location of colorectal adenomatous polyps

The ratio of right- to left-sided colonic cancer is increasing, but data on the distribution of its usual precursor lesion, the colorectal adenoma, are contradictory. Therefore, we investigated the prevalence of right- and left-sided colorectal adenomatous polyps from January 1, 1970, to September 30, 1989, using the study design of "epidemiologic necropsy" and the autopsy files of The Johns Hopkins Hospital. Compared with the decade of the 1970's, the 1980's showed a slight decrease in the overall prevalence of right-sided adenomas (6.4 per 1,000, 95% confidence limits 4.7-8.8 vs. 5.1 per 1,000, 95% CL 3.6-6.5), but a marked decrease occurred in left-sided adenomas (11.8 per 1,000, 95% CL 9.3-14.3 vs. 6.7 per 1,000, 95% CL 4.8-8.6). As a result, the ratio of right-sided to left-sided adenomas increased from 0.55 in the 1970's to 0.77 in the 1980's. This increased ratio occurred in both sexes, although prevalences were lower in females, and in whites. Unexpectedly, blacks had a ratio of right-sided to left-sided adenomas greater than unity in both the 1970's and 1980's (1.19 vs. 1.79) due to a relatively high prevalence of right-sided adenomas (5.8 per 1,000, 95% CL 3.6-8.0 in 1970's; 5.8 per 1,000, 95% CL 3.3-8.3 in 1980's), but low prevalences of left-sided adenomas (4.9 per 1,000, 95% CL 3.0-6.8 in 1970's; 3.2 per 1,000, 95% CL 1.2-5.2 in 1980's). The overall adenoma prevalence in blacks was lower than in whites. We conclude that the right-sided predominance of colorectal adenomas in blacks suggests ethnic differences in the pathogenesis of colorectal adenomas. This observation may have important implications for secondary prevention of colorectal cancer.

Fatal Rocky Mountain spotted fever in Maryland--1901

Rocky Mountain spotted fever (RMSF), an infection caused by Rickettsia rickettsii , is transmitted via tick bite during spring through fall. Rocky Mountain spotted fever is a misonmer because most cases occur in the southeastern and south central United States. 1 The diagnosis is based on clinical suspicion, although the classic triad of fever, headache, and rash exists in only 3% of cases at presentation. 2 A risk for significant morbidity or mortality can occur either from delayed diagnosis or from late or inappropriate therapy. Although known in some western states in the 1870s, RMSF was first described in the eastern United States in 1931. 3,4 This report demonstrates a case of RMSF in the eastern United States in 1901. A search of the autopsy files at The Johns Hopkins Hospital, Baltimore, Md, yielded a single diagnosis coded as typhus fever. Hospital records indicated that an adult male patient was admitted

Fatal Rocky Mountain Spotted Fever in Maryland—1901

Rocky Mountain spotted fever (RMSF), an infection caused by Rickettsia rickettsii , is transmitted via tick bite during spring through fall. Rocky Mountain spotted fever is a misonmer because most cases occur in the southeastern and south central United States. 1 The diagnosis is based on clinical suspicion, although the classic triad of fever, headache, and rash exists in only 3% of cases at presentation. 2 A risk for significant morbidity or mortality can occur either from delayed diagnosis or from late or inappropriate therapy. Although known in some western states in the 1870s, RMSF was first described in the eastern United States in 1931. 3,4 This report demonstrates a case of RMSF in the eastern United States in 1901. A search of the autopsy files at The Johns Hopkins Hospital, Baltimore, Md, yielded a single diagnosis coded as typhus fever. Hospital records indicated that an adult male patient was admitted

Autopsy study of unruptured incidental intracranial aneurysms

The autopsy files and preparations of unruptured incidental intracranial aneurysms seen at the Montefiore Medical Center between 1951 and 1987 were reviewed. There were 84 patients with 102 unruptured aneurysms in a total of 10,259 autopsies, giving a prevalence of 0.8%. Sixteen of the 84 (19%) had multiple aneurysms. The thickness of walls of aneurysms could be estimated in 78 of 102 aneurysms, and was determined to be either thin or thin and thick in 71 aneurysms. In this study, four noteworthy factors were found: (1) the incidence of unruptured aneurysms was higher in elderly patients aged 60 years or older, and the peak percentage was 1.2% in the seventh decade; (2) aneurysms occurred more frequently in females than males, with a ratio of 53: 31; (3) the most common site of aneurysms was the middle cerebral artery; 37 of 102 aneurysms (36%) occurred on it; and (4) the rate of small aneurysms was very high; 50 of 93 aneurysms (54%) were 4 mm or less in diameter, and 33 aneurysms (35%) were 5–9 mm in diameter. However, relationships could not be found between age distribution and location, size, or thickness of walls; between gender and size or thickness of walls; between location and size or thickness of walls; or between size and thickness of walls. Based on published statistics on subarachnoid hemorrhage and this study, the rupture rate of unruptured aneurysms seems to be very low. Although the risk of rupture may be relatively low in small aneurysms, its low risk probably cannot be explained adequately by morphological examination only.

Taxol toxicity. Epithelial necrosis in the gastrointestinal tract associated with polymerized microtubule accumulation and mitotic arrest

Taxol, an antineoplastic agent with a novel mechanism of action, is currently undergoing Phase I trials at The Johns Hopkins Hospital, Baltimore. The authors recently observed striking mitotic arrest associated with epithelial necrosis and ulceration in an esophageal biopsy specimen. The biopsy specimen was taken from a patient who received taxol the day before endoscopy. Review of our autopsy files revealed four other cases in which taxol had been administered. Sections of esophagus, stomach, small intestine, colon, liver, skin, bone marrow, and testes were examined for evidence of mitotic arrest. Mitotic arrest was seen in the two patients who underwent autopsy who received taxol less than 11 days before death, whereas the two autopsy patients who received taxol more than 2 weeks before death did not show these changes. Although mitotic arrest was most prominent in the esophagus, it was also found in the stomach, small intestine, colon, liver, and bone marrow. The mitotic arrest was associated with bundling of intermediate filaments and appeared to be secondary to accumulation of polymerized microtubules. These results suggest that taxol induces a transient mitotic arrest associated with cell necrosis.

Prevalence of thyroid abnormalities is not increased in Alzheimer's disease

The aim of this study was to compare the prevalence of pathologically and clinically documented thyroid disorders in patients with Alzheimer's disease (AD) and nondemented individuals. We reviewed the records of 31 patients with a pathological diagnosis of AD and 31 age-matched nondemented patients selected from autopsy files. We examined the pathological findings in the thyroid gland in both groups. Twenty-four cases (77.4%) with AD and 21 patients (67.7%) in the control group showed pathological abnormalities in the thyroid gland. The prevalence of specific types of thyroid gland abnormalities on pathological examination did not differ significantly between the AD and nondemented cases. For the 19 AD and 18 control patients in whom clinical thyroid function had been documented adequately during life, the percentage of patients with abnormal thyroid function was similar in the AD (15.7%) and control (11.1%) groups. These results do not support a relationship between AD and thyroid abnormalities.

Obstructive Lesions of the Lower Urinary Tract in the Prune Belly Syndrome

The prune belly syndrome is a well-recognized entity consisting of deficient abdominal musculature, cryptorchid testes, and urinary tract abnormalities most consistent with an obstructive phenomenon. However, an obstructive lesion has not been consistently identified in previously reported cases. Retrospective review of the autopsy files of The Johns Hopkins Hospital, Baltimore, identified 18 cases of prune belly syndrome occurring since 1945. In 13 cases, obstructive lesions in the lower urinary tract had been described grossly. A single case, in which the lower urinary tract had been preserved intact and subsequently serially sectioned as 8-micron sections taken at every 120 micron, demonstrated an obstruction consisting of two overriding urethral lumens connected only by a narrow channel. Reconstruction of the sections suggested that this represented a kink in a short segment of the prostatic urethra just above the membranous urethra, leading to the obstructive changes of bladder hypertrophy and dilatation, hydroureter, hydronephrosis, and renal dysplasia seen higher in the urinary tract. The results suggest that examination of the lower urinary tract in cases of prune belly syndrome by serial histologic sectioning of the intact unopened prostatic and penile urethra may be required to demonstrate the presence or absence of an obstructive lesion.

Electromechanical dissociation: Pathologic explanations in 50 patients

Electromechanical dissociation (EMD), defined as electrocardiographically adequate ventricular systolic complexes in the absence of detectable pulse or blood pressure, may occur in the terminal course of patients and is frequently unexplained. The 50 cases in the autopsy files of The Johns Hopkins Hospital in which the patients had died after documented episodes of EMD were reviewed. Four major categories of patients were identified: In 22 of 50 cases (44 per cent) myocardial ischemia appeared to precipitate EMD; in 14 of these 22 cases (64 per cent) myocardial ischemia was global in extent, while in eight (36 per cent) myocardial ischemia was regional, occurring in the distribution of an occluded coronary artery. A subset of ten patients with ischemia had terminal ventricular tachycardia or fibrillation, which was converted to EMD following resuscitation maneuvers. In 12 of 50 cases (24 per cent) systemic shock preceded the development of EMD; in nine of these 12 (75 per cent) hypotension was due to myocardial or arterial rupture, while in three (25 per cent) hypotension was secondary to sepsis. In ten of 50 cases (20 per cent) pulmonary vascular compromise was the apparent cause of EMD. Of these ten cases, eight (80 per cent) were secondary to pulmonary embolization, and two (20 per cent) were due to pneumothorax. In six of 50 cases (12 per cent) the precise cause of EMD could not be determined. The results of this study indicate that in the dying patient with electromechanical dissociation the differential diagnosis should include myocardial ischemia, systemic shock, and pulmonary vascular compromise.