Diffuse alveolar damage (DAD) is the morphological prototype of acute interstitial pneumonia and is characterised by a rapid and fatal clinical course. DAD manifests clinically as acute respiratory distress syndrome (ARDS). It can be seen in sepsis, shock, trauma, severe ARDS, and idiopathic cases with undetected aetiological factors as well as acute exacerbations of chronic interstitial lung diseases [
In addition to experimental animal studies, hospital autopsies or open-lung biopsies are needed to histopathologically monitor common alveolar damage and hyaline membrane (HM) development. A reduction in the rate of alveolar damage has been known for a long time [
The aim of this study was to detect DAD and HM frequency in adult forensic autopsies, examine the histopathological profiles of these cases, and identify other accompanying histopathological changes to determine the characteristics of cases in which these assessments were made and to recognise the case spectrum that we may encounter in future forensic autopsies.
We reviewed 6813 reports with histopathological samples in 12,504 cases on which an autopsy was performed between 2006 and 2008 at the Ministry of Justice, Institute of Forensic Medicine, Morgue Specialization Department. Sixty-six individuals >18 years of age and diagnosed with DAD were included. Demographic information and cause of death were recorded from the autopsy reports. Hematoxylin- and eosin- (H&E-) stained lung samples obtained from each case were evaluated again by a pathologist (HNU) under a light microscope. During this evaluation, cases were examined in line with the 2002 American Thoracic Society/European Respiratory Society (ATS/ERS) idiopathic interstitial pneumonia consensus criteria (Table
Distribution of the diffusion intensity of histopathological lesions according to diffuse alveolar damage (DAD) phase.
Histopathological lesion | Stage | Diffusion |
Total |
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None | Mild | Medium | Intense | ||||
Alveolar exudate/oedema |
Exudative | 1 | 15 | 32 | 2 | 49 (98) | 0.003 |
Proliferative | 4 | 8 | 4 | 0 | 12 (75) | ||
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Alveolar acute inflammation |
Exudative | 7 | 39 | 3 | 1 | 43 (86) | 0.16 |
Proliferative | 7 | 9 | 0 | 0 | 9 (56) | ||
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Alveolar fibrin |
Exudative | 17 | 25 | 8 | 0 | 33 (66) | 0.01 |
Proliferative | 0 | 9 | 6 | 1 | 16 (100) | ||
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Neutrophilic abscesses |
Exudative | 47 | 2 | 0 | 1 | 3 (6) | 0.064 |
Proliferative | 14 | 0 | 2 | 0 | 2 (13) | ||
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Histiocyte desquamation |
Exudative | 1 | 33 | 15 | 1 | 49 (98) | 0.037 |
Proliferative | 1 | 4 | 10 | 1 | 15 (94) | ||
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Alveolar epithelial cell desquamation |
Exudative | 2 | 35 | 12 | 1 | 48 (96) | 0.061 |
Proliferative | 0 | 6 | 9 | 1 | 16 (100) | ||
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Eosinophilia |
Exudative | 49 | 0 | 1 | 0 | 1 (2) | 0.75 |
Proliferative | 16 | 0 | 0 | 0 | 0 (0) | ||
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Hyaline membrane |
Exudative | 23 | 12 | 14 | 1 | 27 (54) | 0.42 |
Proliferative | 4 | 6 | 6 | 0 | 12 (75) | ||
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Type II pneumocyte hyperplasia |
Exudative | 32 | 14 | 4 | 0 | 18 (36) | 0.41 |
Proliferative | 8 | 5 | 3 | 0 | 8 (50) | ||
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Alveolar chronic inflammation |
Exudative | 22 | 28 | 0 | 0 | 28 (56) | 0.20 |
Proliferative | 2 | 14 | 0 | 0 | 14 (88) | ||
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Alveolar septal fibrosis |
Exudative | 47 | 3 | 0 | 0 | 3 (6) | 0.017 |
Proliferative | 11 | 5 | 0 | 0 | 5 (11) | ||
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Alveolar organising fibrosis |
Exudative | 50 | 0 | 0 | 0 | 0 (0) | 0.00 |
Proliferative | 0 | 13 | 3 | 0 | 16 (100) |
Prevalent hyaline membrane, H&E ×100.
Alveolar organizing fibrosis, H&E, ×100.
Fisher’s exact test was used to evaluate the relationship between DAD and death, and logistic regression was used for the DAD phase assessment of the histopathological lesions.
We examined 66 individuals who were autopsied between 2006 and 2008 at the Institute of Forensic Medicine, Morgue Specialization Department and were diagnosed with DAD. Of these cases, 55 (83.3%) were men and 11 (16.6%) were women. The mean age of the cases was 53 years, the median was 54 years, and the range was 19–92 years.
Histopathological examination revealed that 50 (75.7%) cases were in the exudative phase, and 16 (24.2%) were in the proliferative phase. Table
Only the rate of alveolar exudate/oedema was significantly higher in the exudative phase cases (
The distribution of the events causing death is shown in Table
Causes of death and diffuse alveolar damage (DAD) phase distribution.
Causes of death | Total cases |
Exudative phase | Proliferative phase |
---|---|---|---|
Fire | 20 (30) | 16 | 4 |
Physical trauma | 21 (31) | 15 | 6 |
Postoperative complication | 3 (4) | 2 | 1 |
Traffic accident | 5 (7) | 3 | 2 |
Occupational accident | 2 (3) | 2 | 0 |
Drug intoxication | 2 (3) | 1 | 1 |
Firearm | 3 (4) | 2 | 1 |
Mushroom poisoning | 1 (1) | 1 | 0 |
Corrosive substance intake | 1 (1) | 1 | 0 |
Sepsis | 3 (4) | 3 | 1 |
Sharp trauma | 1 (1) | 1 | 0 |
Alcohol intoxication | 1 (1) | 1 | 0 |
Morphine poisoning | 1 (1) | 1 | 0 |
Pesticide intake | 1 (1) | 1 | 0 |
Unidentified | 1 (1) | 1 | 0 |
DAD is difficult to diagnose due to the severity of preoperative histopathological ARDS, but may be diagnosed at autopsy. DAD is seen more frequently in individuals >50 years of age [
DAD is an inflammatory change observed in the alveolocapillary complex [
A second question that comes to mind is how is this lesion distribution affected by the fact that our cases were forensic autopsy cases? No difference in HM distribution has been reported in pulmonary and extrapulmonary DAD, [
As DAD is a common pathological change that may be caused by several factors, rather than a single disease-specific factor, DAD alone is not expected to allow the physician to determine cause of death. Antemortem medical and forensic information should be evaluated jointly [
Establishing a microscopic differential diagnosis is more important than associating the mechanism with the histological profiles of the cases. In this regard, the first group to be discussed in our study includes cases with alveolar organising fibrosis and alveolar fibrin. The HM was also present in varying proportions in all of these cases; therefore, our cases are not consistent with acute fibrosis and organising pneumonia, variants of DAD that lack the HM in alveolar gaps and show wide fibrin accumulation and alveolar organising fibrosis [
Another condition included in the differential diagnosis is the acute exacerbation of UIP. These cases display the same histopathological reaction as DAD; however, patchy interstitial fibrosis and honeycomb-patterned changes in the background can also be identified during autopsy [
The differential DAD diagnosis also includes acute eosinophilic pneumonia (AEP) [
This study had some limitations. Alveolar haemorrhage was not considered in the histopathological examination because alveolar haemorrhage, passive congestion, and cellular degeneration in hypoxia that developed for various reasons are expected morphological findings at autopsy [
Fatal traumatic events are predominant in DAD cases subject to forensic autopsy. The availability of detailed forensic and medical information on the development of the event in such cases would facilitate the establishment of a causal link and illuminate the sequence that caused death. In contrast, when it is considered that not all individuals with DAD die and that some survivors may develop a restrictive pathology in the future, the examination of forensic cases should consider probable late trauma complications in the lung in some situations. The idea that a trauma could have caused lung restriction during the late period, leading to disability and even shortened lifespan, remains to be explored.
The number of forensic autopsies, which gradually increases year by year, has reached an annual average of 4000 in Istanbul today [
In conclusion, DAD exudative and proliferative lesions may be detected during forensic autopsies. However, the detection of all DAD morphological criteria with the same intensity is not always possible in each case. Particularly in trauma and fire cases, several factors such as sepsis and intoxication may play a role in the aetiology of DAD. Cases with traumatic causes are more common. In forensic autopsy cases, the cause of death must be determined to evaluate the event within the context of possible mechanisms and available histopathological findings during the final assessment. If antemortem information is obtained properly and the required consent is obtained from the relatives of the deceased, forensic autopsies may provide a favourable means for expanding our knowledge about acute lung damage, DAD, and interstitial lung disease.