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Papilloma of the lung is a rare benign entity and can be solitary or multiple. Solitary papilloma is subclassified into three categories: squamous papilloma, glandular papilloma, and mixed squamous and glandular papilloma. Glandular papilloma is the rarest subtype among them and occurs mostly in the sixth decade without any relation to smoking, syndrome, or infection. Histology is characterized by mixture of pseudostratified, columnar, nonciliated, mucinous epithelium-lined papillary fronds without any mitoses, necrosis, or atypia. The differential diagnosis can be broad depending upon the histologic features present in a particular case and may include both benign and malignant entities. We present here a patient with glandular endobronchial papilloma showing unusual clinical history and atypical histologic features, which required extensive immunohistochemical evaluation to establish a final diagnosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

SARS-Cov-2 infection is not limited to the respiratory tract and can involve other organs including the heart, blood vessels, kidneys, liver, gastrointestinal tract, placenta, and skin. Covid-19 patients with cardiac involvement usually have higher morbidity and mortality compared to those without cardiac involvement. The frequency and the specificity of the myocardial pathological changes in patients who die after documented infection with SARS-Cov-2 is uncertain. Macrophages can be found in the normal heart (interstitium, around the endothelial cells and in the epicardial adipose tissue), and they are considered part of the major immune cell population in the heart. In this case-control autopsy study, we compare the gross and microscopic cardiac findings, and the available clinical characteristics between a group of 10 Covid-19 decedents and a control group of 20 patients who died with non-SARS-Cov-2 severe bronchopneumonia and/or diffuse alveolar damage. The objectives of this semi-quantitative study are to study single myocyte necrosis and its relation to the strain on the heart caused by lung injury as a causative mechanism, and to study the density of myocardial and epicardial macrophages in Covid-19 hearts in comparison to the control group, and in Covid-19 hearts with single myocyte necrosis in comparison to Covid-19 hearts without single myocyte necrosis. Lymphocytic myocarditis was not identified in any of the hearts from the Covid-19 or the control group. Single myocyte necrosis is more frequent in the Covid-19 group compared to the control group, suggesting that it is unrelated to the strain on the heart caused by underlying lung injury. The density of the macrophages in the epicardium and myocardium in the hearts of the Covid-19 group is higher compared to those in the control group. The density of epicardial macrophages is higher in the Covid-19 hearts with single myocyte necrosis than in those without. These observations contribute to our increasing appreciation of the role of macrophages in the pathophysiologic response to infection by SARS-CoV-2., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

A perplexing right middle lobe lesion in a young woman. Peace of mind now or later? https://bit.ly/3veB5wE., Competing Interests: Conflict of interest: I. Kourouni has nothing to disclose. Conflict of interest: C.M. Abramovich has nothing to disclose. Conflict of interest: S.W. Tamarkin has nothing to disclose. Conflict of interest: J.F. Tomashefski Jr has nothing to disclose. Conflict of interest: E.D. Sivak has nothing to disclose., (Copyright ©ERS 2021.)

Carcinoid tumorlets are peribronchiolar proliferations of neuroendocrine cells often associated with lung scars. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a non-Hodgkin's lymphoma that frequently involves the gastrointestinal tract but less commonly is described in the lung. Simultaneous occurrence of neuroendocrine neoplasms and MALT lymphoma is extraordinarily rare and has predominately been reported in the gastrointestinal tract. In this article, we describe the case of a 73-year-old female with coexisting pulmonary MALT lymphoma and carcinoid tumorlets of the right middle lobe. Retrospective series of 8 pulmonary MALT lymphomas are evaluated for neuroendocrine neoplasia by immunohistochemistry. No correlation between MALT lymphoma and neuroendocrine neoplasia was identified in this case series. While the concurrence of these distinctive neoplasms is most likely coincidental, the presence of a common risk factor, or one neoplasm as a risk factor for the other, deserves study of a larger group of pulmonary MALT lymphomas.

In this study, we hypothesized that the granulomatous disorder sarcoidosis is not caused by a single pathogen, but rather results from abnormal responses of Toll-like receptors (TLRs) to conserved bacterial elements. Unsorted bronchoalveolar lavage (BAL) cells from patients with suspected pulmonary sarcoidosis and healthy non-smoking control subjects were stimulated with representative ligands of TLR-2 (in both TLR-2/1 and TLR-2/6 heterodimers) and TLR-4. Responses were determined by assessing resulting production of tumour necrosis factor (TNF)-α and interleukin (IL)-6. BAL cells from patients in whom sarcoidosis was confirmed displayed increased cytokine responses to the TLR-2/1 ligand 19-kDa lipoprotein of Mycobacterium tuberculosis (LpqH) and decreased responses to the TLR-2/6 agonist fibroblast stimulating ligand-1 (FSL)-1. Subsequently, we evaluated the impact of TLR-2 gene deletion in a recently described murine model of T helper type 1 (Th1)-associated lung disease induced by heat-killed Propionibacterium acnes. As quantified by blinded scoring of lung pathology, P. acnes-induced granulomatous pulmonary inflammation was markedly attenuated in TLR-2(-/-) mice compared to wild-type C57BL/6 animals. The findings support a potential role for disordered TLR-2 responses in the pathogenesis of pulmonary sarcoidosis., (Published 2013. This article is a U.S. Government work and is in the public domain in the USA.)

Case-control studies have demonstrated that the ThinPrep Pap test may provide improved detection of endometrial carcinoma. The purpose of this study is to prospectively examine the diagnostic potential of the ThinPrep Pap test in the detection of endometrial carcinoma. ThinPrep Pap test slides were collected from high-risk patient groups. Pap-stained slides were reviewed and the cytological diagnosis was rendered independently by investigators. Each case was assigned to one of the four diagnostic categories: within normal limit (WNL); atypical glandular cells (AGC); atypical endometrial cells (AEC); or adenocarcinoma, probably endometrial origin. After cytological diagnosis was made, the histological follow-up diagnosis was obtained through the laboratory information system and the cyto-histological correlation was analyzed. Of 106 patients identified, 60 had histological follow-up. For all eight cases interpreted by cytology as positive, endometrial carcinoma was confirmed histologically. Among 25 patients with normal endometrial cells present, histological follow-up showed benign endometrium. Among 17 cases interpreted cytologically as AEC, 14 cases (82.4%) had benign histological follow-up and 3 cases (17.6%) had endometrial carcinoma. All 11 cases (100%) classified as AGC had benign histological follow-up. The sensitivity and specificity of detecting endometrial malignancy were 72.7% and 100%, respectively. The positive predictive value was 100%. In this prospective study, we demonstrated that the Thin Prep Pap test had a reasonably high sensitivity and/or specificity in detecting endometrial carcinoma., (Copyright © 2012 Wiley Periodicals, Inc.)

Context: Microcrystalline cellulose (MCC) is extensively used as a filler material in pharmaceutical tablets. When injected intravenously in aqueous tablet suspensions, MCC may contribute to embolic pulmonary hypertension and be identified histologically in lung tissue samples. In this study, we evaluated a modified Russell Movat pentachrome stain (MMPS) as a means of recognizing MCC and distinguishing it from other birefringent crystals in lung specimens., Objective: To study the staining properties of MCC versus other crystalline materials using the MMPS stain., Design: Archival, formalin-fixed, paraffin-embedded lung specimens that contained birefringent crystals, including MCC (3 cases of intravenous drug abuse), talc (2 cases of intravenous drug abuse, 1 talc pleurodesis), mixed silicates (1 case of silicate pneumoconiosis), and calcium oxalate (1 case of aspergillosis from Aspergillus niger infection), were evaluated with MMPS. Crystal identification was confirmed by morphology, other histochemical stains, infrared spectroscopy (1 case), and cellulose controls., Results: The MMPS stained the MCC bright yellow in tissue and control specimens. Talc stained light greenish-blue; mixed silicates appeared either greenish-blue or unstained. Oxalate crystals stained sea-green. Crospovidone, a nonbirefringent tablet filler substance, stained yellow to dark green with MMPS and was easily distinguished from MCC. Starch granules were unstained by MMPS., Conclusions: The MMPS is an excellent method for the histochemical identification of MCC in tissue and its separation from other birefringent crystals with which MCC might be confused. The MMPS is especially useful in the evaluation of pulmonary foreign body embolization in cases of suspected intravenous substance abuse.

The biological effects of only a finite number of tobacco toxins have been studied. Here, we describe exposure of cultures of human bronchial epithelial cells to low concentrations of tobacco carcinogens: nickel sulphate, benzo(b)fluoranthene, N-nitrosodiethylamine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). After a 24-hour exposure, EGFR was expressed in cell membrane and cytoplasm, BCL-2 was expressed only in the irregular nuclei of large atypical cells, MKI67 was expressed in nuclei with no staining in larger cells, cytoplasmic BIRC5 with stronger nuclear staining was seen in large atypical cells, and nuclear TP53 was strongly expressed in all cells. After only a 24-hour exposure, cells exhibited atypical nuclear and cytoplasmic features. After a 48-hour exposure, EGFR staining was localized to the nucleus, BCL-2 was slightly decreased in intensity, BIRC5 was localized to the cytoplasm, and TP53 staining was increased in small and large cells. BCL2L1 was expressed in both the cytoplasm and nuclei of cells at 24- and 48-hour exposures. We illustrate that short-termexposure of a bronchial epithelial cell line to smoking-equivalent concentrations of tobacco carcinogens alters the expression of key proliferation regulatory genes, EGFR, BCL-2, BCL2L1, BIRC5, TP53, and MKI67, similar to that reported in biopsy specimens of pulmonary epithelium described to be preneoplastic lesions.

Pulmonary diseases associated with tobacco smoking are a complex group of disorders ranging from chronic obstructive pulmonary disease (COPD) to lung cancer. Interstitial lung diseases (ILDs) have only recently been linked to smoking. The ILDs related to smoking include respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and pulmonary Langerhans cell histiocytosis. The relationship of smoking with each of these entities has been largely established on the weight of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these 3 entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. The importance of making the distinction between them lies in the different clinical management strategies used. Further experimental evidence, including genetic information, may be important in improving our understanding of these diseases.

Pulmonary Langerhans' cell histiocytosis (PLCH) is a disease characterized by the occurrence of complex fibro-cellular interstitial lesions dominated by Langerhans' cells (LC), which occurs predominantly in young adult smokers. We undertook this retrospective study to better define the lymphohistiocytic cell populations in PLCH in order to obtain a greater insight into its pathogenesis. Formalin-fixed, paraffin-embedded, surgically excised, archival lung tissue from seven patients (two males, five females; average age 34.9 years) was immunostained with a panel of antibodies for lymphohistiocytic markers: CD1a, CD3, CD4, CD8, CD15, CD20, CD56, TIA-1, CD68-PGM1, Mac387, and mast cell tryptase. Double immunolabeling was performed with CD1a/Mac387. Leder cytochemical stain for chloroacetate esterase was also performed. A moderate number of lymphocytes, predominantly T lymphocytes, were scattered diffusely within the lesions. The mean CD4/CD8 ratio was 0.1/1. The CD3/CD8 ratio (1.18/1) substantiated the CD4/CD8 ratio. The CD8 subset was CD56-negative and TIA-1-positive, indicating a cytotoxic T lymphocyte phenotype. CD68-PGM1 was strongly positive in alveolar macrophages (AM) and weakly stained LC. Mac387, a marker of activated macrophages, weakly stained AM, while highlighting other interstitial cells. These interstitial cells appeared not to be LC (substantiated by CD1a/Mac387 dual labeling) or CD68-PGM-1-positive macrophages. Having excluded mast cells (positive with mast cell tryptase) and neutrophils (positive with CD15 and Leder stains), there appeared to be a residual population of non-Langerhans cell monocytoid cells (NLMC), which were Mac 387+, CD68-PGM1-, Mast cell tryptase-, CD15-, and CD1a-. Our results showed a predominance of CD8+, TIA-1+ cytotoxic T lymphocytes among the lymphocyte subsets which appear to interact with LC and AM in PLCH lesions. A small sub-population of NLMC was also present. Further studies are required to better define and to evaluate the role of cytotoxic T cells and NLMC in the pathogenesis of PLCH.

The aim of this retrospective study was to correlate cytological diagnoses of endometrial cancers in ThinPrep Pap tests with the histological diagnoses. ThinPrep specimens from 67 patients within 12 mo of the histological diagnosis of endometrial cancer were studied. Of this study sample, 89.6% had abnormal Pap tests. Abnormal Pap tests occurred in 96.8, 68.4, and 100% of patients with grades 1, 2, or 3 endometrial cancers, respectively. Of patients with endocervical involvement, 88.9% had positive or suspicious Pap tests, compared with 41.1% without endocervical involvement (LR = 7.85, P < 0.01). Of patients with > or =50% myometrial invasion, 78.9% had positive or suspicious Pap tests, compared with 34.8% with less than 50% invasion (LR = 10.97, P < 0.01). Positive or suspicious Pap tests were found in 59.5 and 32.1% of those with tumors > or =3 cm or <3cm, respectively (LR = 4.85, P < 0.05).

To assess the pathological changes in the lungs and liver of 42 individuals who died while enrolled in the Registry of Individuals with Severe Deficiency of Alpha-1 Antitrypsin (AAT), all available histopathologic surgical or postmortem-derived specimens were reviewed by the pathologist member of the Death Review Committee. The underlying cause of death was emphysema in 34 patients and cirrhosis in 2 patients. Slides of lung were graded for emphysema, and liver specimens were graded for fibrosis, using respective pictorial scoring systems. Correlations between the degree of pathological abnormality and clinical features were evaluated. All lungs exhibited severe panacinar emphysema (mean emphysema score, 7.9 +/- 1.06 [standard deviation], where 10 represents the greatest severity) with a lower lobe predominance. Centriacinar emphysema was minimal. No correlation was found between the pathological severity of emphysema and pulmonary function measurements, and no significant correlation was found between the degree of emphysema and the degree of hepatic fibrosis. Mildly increased bronchial gland-to-wall ratio accompanied mild inflammation and goblet cell hyperplasia. There were minimal changes in small airways. Dilatation of membranous bronchioles was a frequent finding; however, bronchiectasis of larger airways was a minor feature in only 6 patients (15%). Airway morphological features did not correlate with the clinical presence of chronic bronchitis or asthma. Although the lack of correlation between liver and lung pathological changes may reflect different pathogenetic mechanisms of liver disease and lung disease, the lack of correlation between emphysema grade and lung function likely reflects the skewed sample in a series of patients with advanced lung disease.

Crospovidone is an insoluble polymer of N-vinyl-2-pyrrolidone that is used as a disintegrant in pharmaceutical tablets. It can potentially embolize to the lung when aqueous tablet suspensions are injected intravenously. In this report, we identified embolized crospovidone in autopsy-derived lung tissue from three adult IV drug users, 1 man and 2 women, whose ages respectively were 27, 38, and 40 years. Suspected crospovidone was compared with pharmaceutical-grade crospovidone by means of histochemical stains, transmission electron microscopy, and infrared spectroscopy. Similar particles were also observed by light microscopy in a 4-mg tablet of hydromorphone, a preparation prescribed to two of the patients. Two patients had sickle cell disease and were taking methadone and/or hydromorphone for pain management; the third was receiving parenteral hyperalimentation after small bowel resection. Crospovidone appeared as deeply basophilic, coral-like particles within pulmonary arteries and in extravascular foreign-body granulomas. Intrapulmonary crospovidone stained similarly to the pure substance, including intense staining with mucicarmine, Congo red, and Masson trichrome. With Movat pentachrome stain, both intravascular and purified crospovidone appeared orange-yellow, whereas most interstitial particles associated with giant cells stained blue-green. Alcian blue failed to stain intravascular or purified crospovidone but strongly decorated some phagocytized particles. Ultrastructurally, both purified powder and tissue deposits of crospovidone appeared as irregular, electron dense, laminated, and finely granular material. Intrapulmonary crospovidone was associated with inflammatory cells and exhibited degenerative changes. By infrared spectroscopy, crospovidone in tissue had the same spectral characteristics as pharmaceutical grade crospovidone and the library reference, polyvinylpyrrolidone (PVP). We conclude that crospovidone contributes to pulmonary vascular injury in some persons who illicitly inject pharmaceutical tablets. It is readily identifiable histologically and distinguishable from other tablet constituents, such as cornstarch, talc, and microcrystalline cellulose. The variable staining with Alcian blue and Movat suggests that crospovidone is altered in vivo by the inflammatory response.

Observing that the conidia of Stachybotrys chartarum can germinate in the lung of infant rats, it became important to ascertain whether an infection can ensue. Viable conidia of S. chartarum were instilled into the lungs of 4 and 14 day-old rat pups. Germination was observed frequently in the lungs of 4 day-old but rarely in the 14 day-old pups. In the 4 day-old pups, pulmonary inflammation with hemorrhagic exudates was observed and resulted in about 15% mortality rate compared to 0% for the controls instilled with phosphate buffered saline. Acute neutrophilic inflammation and intense interstitial pneumonia with poorly formed granulomas observed three days following exposure were associated with fungal hyphae and conidia. The surviving experimental pups showed significantly slower weight gain for seven days. Dilution plating and quantitative PCR analysis were used to follow total fungal load in the rat pups lung homogenates. In the 4 day-old rat pups viable fungi decreased rapidly and were less than 1% by day seven. Similarly, fungal DNA decreased exponentially and was only 0.03% by fourteen days after exposure. However, 14 day-old rat pups showed neither the lethal effects of exposures to viable conidia of S. chartarum nor the slower weight gain, and the fungal load decreased even more rapidly. We conclude that S. chartarum conidia can initially germinate and form hyphae but even in the immature rat pups do not establish an effective infection, although a very limited persistence cannot be excluded.

In recent years cases of often fatal pulmonary hemorrhage in infants have been associated with water damaged homes and the toxigenic fungus Stachybotrys chartarum. The fungal spores contain mycotoxins which could be injurious to the rapidly developing lung. In order to understand the developmental pathophysiology of this disease we developed an infant rat model of stachybotrytoxicosis describing the effects of fungal spores on survival, growth, histopathology of the lung and respiration. Conidia of S. chartarum were instilled intratracheally (1.0-8.0 x 10(5)/gm wt.) in 4-d old Sprague-Dawley rat pups. Two control groups received either sterile PBS or a suspension of spores extensively extracted with ethanol to remove toxins. Lethal dose response was determined (LD50 = 2.7 x 10(5) spores/gm wt.). All dead pups had extensively hemorrhagic lungs. Growth of surviving animals was impaired in a dose-dependent manner. Changes of pulmonary function parameters in rats treated with 1.1 x 10(5) spores/g were consistent with an increased respiratory resistance. Histology of lungs revealed fresh hemorrhage, sparse hemosiderin-laden macrophages, and evidence of inflammation including thickened alveolar septa infiltrated by lymphocytes and mononuclear cells and intra-alveolar macrophages. Significant increases (p = 0.001) in numbers of macrophages (2-fold), lymphocytes (5-fold) and neutrophils (7-fold) were found in BAL fluid. Hemoglobin was elevated 2-fold (p = 0.004). Proinflammatory mediator IL-1beta increased more than 6-fold and TNF-alpha 30-fold (p = 0.001). Extracted spores had a minimal effect on all examined parameters in BAL fluid indicating that mycotoxins are primarily responsible for the hemorrhagic and inflammatory response.

Objective: To determine the contribution of surfactant protein abnormalities to the development of chronic lung injury in a familial form of interstitial lung disease., Study Design: An 11-year-old girl, her sister, and their mother who were diagnosed with chronic interstitial lung disease underwent laboratory investigation of surfactant protein expression in bronchoalveolar lavage fluid and lung biopsy specimens. Nineteen patients with idiopathic pulmonary fibrosis and 9 patients who were investigated for pulmonary malignancy but who did not have interstitial lung disease served as control subjects., Results: The 3 family members were found to have absent surfactant protein C (SP-C) and decreased levels of SP-A and SP-B in bronchoalveolar lavage fluid (BALF). Immunostaining for pulmonary surfactant proteins in lung biopsy specimens obtained from both children demonstrated a marked decrease of pro-SP-C in the alveolar epithelial cells but strong staining for pro-SP-B, SP-B, SP-A, and SP-D. No deviations from published surfactant protein B or C coding sequences were identified by DNA sequence analysis. All control subjects had a detectable level of SP-C in the BALF., Conclusion: The apparent absence of SP-C and a decrease in the levels of SP-A and SP-B are associated with familial interstitial lung disease.

Lung morphology in ARDS reflects the rapid evolution from interstitial and alveolar edema to end-stage fibrosis consequent to injury of the alveolocapillary unit. This morphologic progression, termed diffuse alveolar damage, has been subdivided into sequentially occurring exudative, proliferative, and fibrotic phases. Pulmonary lesions correlate with the phase of alveolar damage rather than its specific cause. The pathologic features are consistent with the effects of a host of injurious stimuli and the complex interaction of inflammatory mediators on alveolar epithelial and capillary endothelial cells. Although ARDS frequently culminates in "interstitial" fibrosis, the organization of intraluminal exudate dominates the histologic picture in the proliferative phase and establishes the framework for subsequent fibrous remodeling of the lung. Involvement of the pulmonary vasculature is an important aspect of ARDS, from the initial phase of edema to the terminal stage of intractable pulmonary hypertension. Vascular lesions include thrombotic, fibroproliferative, and obliterative changes that, like the parenchymal lesions, correlate with the temporal phase of DAD. Although ARDS is characterized by extensive bilateral lung involvement, alveolar damage can also affect the lung in a localized fashion. RAD is associated with the same clinical risk factors as DAD, suggesting that there is a spectrum in the extent of lung involvement and disease severity in patients at risk for ARDS. The factors that govern which patients will develop the fulminant syndrome are poorly understood. It must be re-emphasized that the lung is stereotyped in its response to injury and, consequently, descriptive, or even quantitative, studies of lung morphology can only provide clues regarding the initiating factors and pathogenetic mechanisms of ARDS. Progress in understanding the pathogenesis of ARDS and development of rational approaches to therapy will ultimately depend on careful clinical and experimental studies and the application of immunohistochemical and molecular biology techniques to unravel basic mechanisms of cellular injury and response.

Objectives: To review retrospectively our experience with peripheral blood eosinophilia (PBE) in sarcoidosis and to analyze histologically lung biopsy specimens for the presence of lung tissue eosinophils., Patients and Methods: We reviewed 140 cases of sarcoidosis diagnosed between May 1975 and January 1998. Ninety-five patients (66.3% women; 70.5% African American; mean age, 35.9 years) met the inclusion criteria. Transbronchial biopsy specimens from 82 patients were divided into 4 morphologic compartments: parenchyma, bronchial wall, parenchymal granulomas, and bronchial wall granulomas. Within compartments, up to 10 high-power fields were scored semiquantitatively for eosinophils, from 0 (none) to 4+ (numerous)., Results: Thirty-nine patients (41%) had PBE. Four had PBE greater than 10%. The highest eosinophil count (21%) occurred in 1 patient. Sixty-five (79%) of 82 patients had no or few (1+) eosinophils in lung tissue; 17 patients had eosinophils scored as 2+ or higher. There was no correlation between peripheral blood eosinophil count and presence of eosinophils in transbronchial biopsy specimens. Eosinophils were least conspicuous in parenchyma but evenly distributed in bronchial wall and parenchymal and bronchial wall granulomas., Conclusions: Peripheral blood eosinophilia occurs frequently in sarcoidosis. However, there appears to be no association between peripheral blood eosinophil count and presence of lung tissue eosinophils. Whether eosinophils participate in the pathogenesis of sarcoidosis requires further study.

Cholestasis has been reported as a rare presentation among patients with severe liver injury secondary to amiodarone hepatic toxicity. We report an unusual case of amiodarone-induced cholestatic hepatotoxicity occurring after amiodarone had been discontinued and the initial abnormal liver function findings had improved. The patient, without jaundice at the initial presentation, developed severe jaundice about 4 months after withdrawal of amiodarone. Light and transmission electron microscopic examination of a specimen secured by computed tomographically guided liver biopsy was consistent with amiodarone hepatic toxicity as the cause of intrahepatic cholestasis. An abdominal ultrasound, endoscopic retrograde cholangiography, and dimethyl iminodiacetic acid and computed tomographic scans of the abdomen all failed to demonstrate any other causes for jaundice other than amiodarone toxicity. Thus, amiodarone hepatic toxicity may occur after drug withdrawal even if results of liver function tests improve. Histopathologic examination of a liver biopsy specimen is of value for diagnosis and prognosis. The liver biopsy findings, clinical course, and liver function test results are discussed, and the English-language literature on amiodarone cholestatic hepatotoxicity is reviewed.

We studied by means of serial sections of intact isolated bronchi, the distribution and morphology of bronchial cartilage in lobar and segmental airways of 6 patients with cystic fibrosis (CF). Findings were compared to those of 4 young adults without CF who served as controls. Compared to the controls, cartilage in CF airways extended for a shorter absolute distance along the bronchial tree and disappeared at a more proximal branching level. Loss of cartilage appeared to correlate with the severity of bronchiectasis. In proximal airways chronic inflammation, destruction and fibrous replacement of cartilage preceded its disappearance. Immunohistochemical staining indicated that cells of monocyte/macrophage lineage (CD68, MAC387 positive) were most closely associated with chondrolysis. Dystrophic calcification and ossification were more commonly seen in CF bronchi and dystrophic calcification was present even in the lobar branches. Destruction of bronchial cartilage is the result of sustained bronchial infection and chronic inflammation and is an additional contributory factor to bronchiectasis and airway instability in patients with CF.

Objective: We studied at autopsy a distinctive obliterative bronchitis in three persons with pneumoconiosis and hilar node fibrosis., Methods: Lungs were evaluated macroscopically, microscopically, and with energy-dispersive spectroscopy., Results: Chest roentgenogram demonstrated right middle lobe syndrome in one patient; bronchostenosis was seen at bronchoscopy in another. The stenotic sites were in perihilar bronchi and showed an upper lobe predominance. Fibrosis with silicotic nodules involved the bronchus, peribronchial tissue, and adjacent lymph nodes. Simple coalworkers' pneumoconiosis was observed in two patients; the third had complicated, mixed dust fibrosis., Conclusion: Obliterative bronchitis represents an unusual fibrotic response to free crystalline silica. The process may occur simultaneously in the adjacent lymph node and the bronchial wall; however, it need not be associated with complicated pneumoconiosis. Clinically, obliterative bronchitis may masquerade as bronchogenic carcinoma.

We report a case in which pulmonary Intralobar Sequestration (ILS) was an incidental finding at autopsy in an adult with Cystic Fibrosis. Two aberrant arteries from the descending thoracic aorta supplied a bronchial cystic lesion in the right lower lobe. Termination of the segmental bronchus and scar formation proximal to the cyst suggested prior bronchial obliteration. The elastic configuration of the aberrant aortic-derived vessels of the sequestration contrasted sharply with massively hypertrophied, muscular, bronchial arteries which supplied the bronchiectatic upper lobe. Sections of inferior pulmonary ligament were studied in five additional patients with CF but without ILS. Small muscular arteries were consistently noted within the inferior pulmonary ligament. These histologic findings support the concept that the vascular portion of ILS is congenital, whereas the bronchocystic component, in some cases, may be acquired.

We reviewed clinical data, autopsy reports, and microscopic slides on 10 patients with sleep apnea/obesity hypoventilation syndrome (SA/OHS) to define the cardiopulmonary pathological features and establish clinicopathologic correlations. Ten obese (>136 kg) patients without SA/OHS were studied as controls. Patients with SA/OHS exhibited biventricular cardiac failure and pulmonary hypertension with a higher prevalence of moderate/severe pulmonary hemosiderosis (8 v 0 patients), alveolar hemorrhage (7 v 4 patients), capillary proliferation (4 v 0 patients), iron encrustation of elastica (1 v 0 patients) and medial hypertrophy of muscular pulmonary arteries (11.9 +/- 2.4 v 9.7 +/- 1.6%) (P < .05). In two patients capillary proliferation resembled capillary hemangiomatosis. Mean right ventricular thickness was higher in the SA/OHS group (0.71 +/- 0.17 v 0.42 +/- 0.1 cm) (P < .01). Four patients with SA/OHS and three controls had moderate/severe myocardial fibrosis. Biventricular cardiac failure caused death in seven patients with SA/OHS. Hypoxia is probably the most important cause of pulmonary hypertension, arterial muscularization, and right ventricular hypertrophy in SA/ OHS. Left ventricular failure in some SA/OHS patients may be the result of hypertensive cardiac disease. In others, the etiology of left ventricular failure was not determined morphologically, suggesting functional abnormalities related to obesity and/or apneic episodes.

We retrospectively studied lung and hilar lymph nodes at autopsy in 18 patients with cystic fibrosis (CF) who had antemortem sputum cultures positive for nontuberculous mycobacteria (NTM). Histologic features were compared with those of 18 patients with CF who had negative antemortem cultures. The most frequent species isolated was M. chelonae group (10 patients). Multiple cultures were positive for NTM in six patients. Three patients were clinically considered to be infected, and two received antimycobacteria drugs. Necrotizing pulmonary granulomas associated with granulomatous organizing pneumonia were found at autopsy in two patients, each of whom had multiple positive sputum cultures and clinical evidence of infection. In one of these, mycobacterial infection was considered to be an important factor in her terminal illness. Neither necrotizing granulomas nor granulomatous organizing pneumonia were seen in the lung tissue of patients whose antemortem cultures were negative for mycobacteria. There was no difference in the prevalence of other granuloma-like lesions between those with and those without positive sputum cultures. No mycobacteria-related granulomas occurred in hilar lymph nodes, although histoplasma granulomas involved hilar lymph nodes of three patients. We conclude that granulomatous mycobacterial lung disease is present in a minority of patients (two of six patients in this study) who have multiple positive cultures. Histologic evidence of infection was not found in patients who had only one of multiple sputum cultures positive for NTM.

Objective: To determine the frequency of positive microbiologic cultures in patients with epithelioid granulomas and negative histochemical stains for microorganisms in transbronchial biopsy specimens. Secondary objectives were to compare the histologic features of sarcoidosis with those of infectious granulomas and to assess the reliability of histology in establishing the diagnosis of sarcoidosis., Design: Retrospective study. Specific histologic features of transbronchial biopsy specimens were correlated with clinical and microbiologic data, final diagnosis, and an estimate of the probability, on admission, that the patient had sarcoidosis., Setting: A large, urban, tertiary-care, university-affiliated hospital., Patients: Ninety-two adult patients in whom epithelioid granulomas, negative for microorganisms on Ziehl-Neelsen and Gomori methemaine silver stain, were found in transbronchial biopsy specimens. Patients were identified through a search of surgical pathology files from 1975 to 1987., Results: Ten patients (10.9%) had mycobacterial or fungal granulomas, while 82 had sarcoidosis. In all patients with a high clinical probability of sarcoidosis, the diagnosis was confirmed. Transbronchial biopsy specimens from patients with infectious granulomas had fewer granulomas (2.0 +/- 1.7 (SD) versus 7.1 +/- 6.6; P<.01), which involved a smaller proportion of lung tissue per case (9.5 +/- 10.0% versus 26.6 +/- 24.0%; P<.01). Sarcoid granulomas often exhibited Schaumann bodies (69.5% versus 10%; P<.01). Necrosis tended to predominate in infectious granulomas (19.5 versus 40%; not significant)., Conclusions: Numerous granulomas, Schaumann bodies, and a high clinical probability of sarcoidosis are significantly associated with that diagnosis. Necrosis does not exclude sarcoidosis. Clinicopathologic assessment of transbronchial biopsy specimens is useful in predicting the final diagnosis of sarcoidosis but does not obviate the need for microbiologic cultures, which were positive in 10.9% of patients in this study.

We reviewed the clinical, radiographic, and histologic features of nine patients with AIDS and pulmonary disease due to Mycobacterium avium complex (MAC). Pulmonary MAC disease was defined by (1) the isolation of MAC from two or more lower respiratory tract specimens or from a single lung biopsy sample, (2) an infiltrate revealed by chest radiography, and (3) the absence of other identified pulmonary pathogens or malignancies. Pulmonary MAC disease was present in five (2.5%) of 200 patients with disseminated MAC infection and in four additional patients without evidence of dissemination, as assessed by blood culture. The median CD4 cell count at the time of presentation was 90/microL. Pulmonary MAC disease was the initial AIDS-defining infection in five patients and presented within a median of 5 months after the initial infection in four patients. Radiographic patterns for these nine patients included consolidating or nodular infiltrates and cavitation. The histopathology of pulmonary MAC disease was characterized by granulomatous inflammation, often associated with necrosis and few evident organisms. The conditions of all patients treated with multidrug regimens clinically improved.

Synchronous cutaneous T-cell lymphoma and low-grade B-cell lymphoproliferative disorders have rarely been reported in the same patient. Coexpression of each phenotype in the same lymph node has not, to our knowledge, been previously documented. We describe an 86-year-old man with chronic pruritus and erythroderma and recent-onset peripheral lymphadenopathy and lymphocytosis. Lymph node biopsy provided morphological and immunohistochemical evidence of concurrent small B lymphocytic lymphoma and small pleomorphic T-cell lymphoma. Immunophenotyping of nodal lymphocytes demonstrated two distinct clones: IgM-kappa B-cells with CD5 positivity and CD7 negative T-helper cells. Both immunoglobulin (heavy and light chains) and T-cell receptor (beta I and beta II) gene rearrangements were detected by Southern blot analysis of the lymph node. In contrast, the immunophenotype of lymphocytes from peripheral blood and bone marrow was exclusively that of T-helper cells with atypical CD7 deletion. Electron microscopic examination of circulating lymphocytes revealed small cerebriform Sezary cells. This case demonstrates that small lymphocytic lymphoma may coexist intranodally with cutaneous T-cell lymphoma as a unique form of composite T- and B-cell lymphoma.

We evaluated the findings on transbronchial biopsy specimens in reference to open lung biopsy specimens from 12 patients with pulmonary eosinophilic granuloma. Features in transbronchial biopsy specimens were further contrasted to those of patients with interstitial fibrosis and nondiagnostic biopsy specimens for localized lesions. Transbronchial biopsy specimens were randomized and graded for histologic features and cellularity. Patients with eosinophilic granuloma had more macrophages (P < .05) but equivalent numbers of eosinophils, neutrophils, and Langerhans' cells compared with those of the other two groups. Only two endoscopic biopsy specimens were histologically diagnostic or highly consistent with eosinophilic granuloma. We conclude that the diagnosis of eosinophilic granuloma is possible on transbronchial biopsy but requires a high index of suspicion. The demonstration of Langerhans' cells by immunohistochemical staining for S100 protein is a useful adjunct. The low diagnostic yield for eosinophilic granuloma on transbronchial biopsy results from inadequate sampling and from the nonspecific appearance of discrete lesions in small tissue samples.

We studied the histopathology and clinicopathologic correlates of invasive cavitary pulmonary aspergillosis in 11 immunosuppressed patients with disseminated malignancy. In most patients cavities were produced by separation of necrotic from viable lung, resulting in an intracavitary sequestrum ("lung ball"). Central dissolution of large necrotic areas and suppurative granulomatous aspergillary pneumonia were additional causes of cavities in three patients. In four patients with chronic cavities sequestra had been replaced by intracavitary mycetomas ("fungus balls"). Neutrophils usually were numerous at the interface of the sequestrum and adjacent lung, but were minimally present in three patients with prolonged severe neutropenia. The lack of neutrophils in some patients suggests that factors other than neutrophil-derived proteases may be important in cavity formation. A prominent giant cell reaction was seen in three patients with chronic cavities. Hemoptysis occurred in five patients and massive hemoptysis due to a bronchoarterial fistula caused the death of one patient. The "air-crescent" sign was not observed radiographically in any patient and is therefore considered to be an insensitive marker for lung cavitation in invasive aspergillosis. Persistent intracavitary fungal growth may serve as a reservoir for recurrent fungal invasion in patients with prolonged or repeated episodes of severe neutropenia.

An endobronchial tumor, resected from a 77-year-old man, had an endometrioid histologic pattern consistent with fetal adenocarcinoma. A distinctive feature of the neoplasm was prominent neuroendocrine differentiation, including single, discrete neuroendocrine cells; aggregates of neuroendocrine cells resembling miniature carcinoid tumors; and a single focus of undifferentiated small cell carcinoma. Immunohistochemical staining of neuroendocrine cells revealed the presence of neuron-specific enolase, chromogranin, somatostatin, insulin, and serotonin. The heterogeneous cell populations caused problems in differential diagnosis and histologic classification. This case demonstrates that fetal adenocarcinoma may occur as a central endobronchial mass and express a variable degree of neuroendocrine differentiation.

Prominent nonnecrotizing eosinophilic inflammation of muscular pulmonary arteries was seen in resected lung tissue from two patients with spontaneous pneumothorax. Other histologic features included reactive eosinophilic pleuritis (REP) and fibrobullous disease. Eosinophilic vascular infiltration was not contiguous to REP. In neither patient was there a specific and recognized cause of eosinophilic vasculitis. Both patients are without pulmonary symptoms 1 and 4 years after pneumothorax. Eosinophilic vascular infiltration initially suggested the diagnosis of allergic angiitis or pulmonary eosinophilic granuloma. These diagnoses were excluded by clinical and morphologic data. We subsequently reviewed 30 cases of lung tissue resected from patients with pneumothorax and found REP in 18 patients (60%) and mild pulmonary vascular and perivascular eosinophilia in five patients (17%). REP was present in all cases with eosinophilic vascular infiltration. We conclude that this eosinophilic vascular lesion is an unusual reaction in patients with REP and pneumothorax. Occasionally this lesion mimics allergic angiitis or eosinophilic granuloma. The pathogenesis is probably related to vascular transport of eosinophils to the injured pleural surface.

The histopathology, ultrastructure, and clinicopathologic correlations in six patients with cardiac failure and iron encrustation of lung elastic tissue were examined at autopsy. Transmission electron microscopy (TEM) and energy dispersive x-ray analysis were applied to two cases. Of the group, five patients had cardiac failure due to systemic hypertension (4 patients), valvular disease (4 patients), or coronary atherosclerosis (4 patients). Biventricular failure in one patient was associated with sleep apnea. Both iron and calcium, identified by histochemical stains, impregnated degenerated alveolar and vascular elastic fibers and were associated with a foreign body reaction and focal interstitial fibrosis. Energy dispersive x-ray analysis and TEM demonstrated iron and calcium on the microfibrillar portion of elastin. Morphometry indicated vascular changes of pulmonary venous hypertension. The authors concluded that mineral deposition probably represents nonspecific precipitation of metallic ions on altered elastic fibers in patients with cardiac failure. "Mineralizing elastosis" potentially contributes to lung restriction and, occasionally, can be a source of diagnostic confusion.

Although rounded atelectasis was recognized in 1928, its relationship to fibrotic pleural disease almost has gone unnoticed. We present four cases of lobar rounded atelectasis that help to clarify this relationship. Rounded atelectasis is part of the spectrum of fibrous pleural disease. Any portion of lung may become entrapped by the pleural process. When focal areas are involved rounded atelectasis results. When a larger portion of the thorax is involved with this process, lobar rounded atelectasis may occur. Very extensive disease is recognized as fibrothorax.

In order to evaluate the risk for proteolytic destruction of lung parenchymal elastic fibers in ventilated premature infants, the concentrations of elastase were determined in tracheal aspirates of 65 infants from whom we obtained a total of 327 sequential samples. Elastase was detected at least once in 39 of the 65 infants studied. Eleven of these infants were ventilated with greater than 60% oxygen for greater than 5 days. In 19 infants, the presence of elastase was associated with positive bacterial and/or viral cultures and/or elevated ratios (greater than 0.22) of immature neutrophils to total neutrophils. Elastase was not detected in the lung secretions of 26 infants ventilated with greater than 60% oxygen for less than 3 days, suggesting minimal risk for elastic fiber destruction in the intubated infant who neither has pneumonia nor requires prolonged hyperoxic ventilation. The risk for elastic fiber destruction was further evaluated by analyzing sequential urine and tracheal aspirate samples for the presence of an elastolytic degradation product of elastin (desmosine). The biochemical data indicated a potential risk for proteolytic destruction of elastic fibers in association with infection and/or prolonged hyperoxic exposure. In addition, autopsy specimens obtained from three of the infants revealed structurally abnormal lung parenchymal elastic fibers. Because elastic fibers are believed to provide the structural support for alveolar septal development, proteolytic degradation of these fibers may be a significant factor in the impaired lung development that occurs in infants with bronchopulmonary dysplasia.

Previous studies have suggested that immune mechanisms contribute to lung injury in cystic fibrosis (CF); however, there have been no comprehensive studies of immunofluorescent staining patterns in CF lung tissue. We performed immunofluorescence (IF) studies for immunoglobulins, C3, and fibrinogen on autopsy frozen lung tissue from 21 CF patients. Results were compared with lung findings in patients without CF. In CF-derived lung tissue fibrinogen was ubiquitous along the alveolar wall, alveolar space, and interstitium. Free immunoglobulin G (IgG) and IgA coated the alveolar surface segmentally in 14 and 6 cases, respectively. Unequivocal interstitial deposits were infrequent and IgM was present in blood vessels in one patient only. Intra-alveolar and interstitial inflammatory cells demonstrated cytoplasmic IgG, IgA, and IgM, respectively, in 18, 14, and 6 patients. C3 was seen only segmentally along the alveolar wall in two patients and in blood vessels in one. Antinuclear antibody (ANA) staining of interstitial cells for C3 and immunoglobulins was seen in five patients, four of whom had interstitial pneumonitis. Insignificant amounts of alveolar or interstitial fibrinogen and immunoglobulins in inflammatory cells were seen in controls in the absence of lung inflammation. The IF patterns were similar in the inflammatory lesions of CF and control specimens. The IF patterns observed in CF lung tissue are consistent with nonspecific vascular leakage and chronic inflammation with little evidence of immune complex deposition in the interstitium or blood vessels. This study confirms previous reports of ANA activity in CF patients, although the significance of this finding is unknown.

Background: Metastatic pulmonary calcification, a complication of uraemia and disordered calcium metabolism, may be diffuse or localised. The factors that determine calcium precipitation are complex, but tissue alkalosis is thought to be important. As obstruction of the pulmonary artery theoretically causes local alkalosis a retrospective necropsy study was carried out to examine the relation between metastatic pulmonary calcification and vascular obstruction., Methods: Five patients with focal and two with diffuse metastatic calcification in the lungs were identified over eight years. Lungs were studied macroscopically and by light microscopy, haematoxylin and eosin and histochemical stains being used for calcium., Results: Underlying risk factors for calcification in these patients included renal failure in six and disseminated malignancy in five. In the five patients with localised calcification obstruction of the pulmonary artery by thrombus or tumour was found proximal or adjacent to areas of calcium deposition. In two patients metastatic calcification was confined to a lung with unilateral pulmonary artery thromboembolic occlusion. Calcification was not specifically associated with infarction, pneumonia, or diffuse alveolar damage. Lesions of the pulmonary artery were not seen in the two patients with diffuse bilateral metastatic calcification., Conclusion: In this small series there was a spatial association between pulmonary artery obstruction and localised metastatic calcification. It is proposed that pulmonary artery obstruction alters the microchemical environment of the lung, favouring tissue alkalosis and thereby enhancing parenchymal calcification in patients predisposed to this condition.

We found a high prevalence of pulmonary and extrapulmonary neoplasms in patients with pulmonary eosinophilic granuloma (PEG) who were studied at our institution. Among 21 patients with PEG, 10 (48%) had associated benign (one patient) or malignant (nine patients) tumors. Patients with tumors were older at the time of diagnosis of PEG (48.9 vs 34.5 years). Tumors included three lung carcinomas, one pulmonary carcinoid tumor, two lymphomas, five extrapulmonary carcinomas, and one mediastinal ganglioneuroma. Two malignant neoplasms developed in each of two patients. Six tumors preceded, three followed, and three occurred concomitantly with the diagnosis of PEG. Slides from eight PEG-associated tumors and 18 control neoplasms from patients without PEG were also stained immunohistochemically for S100 protein. Four PEG-associated (50%) and 11 control (61%) tumors contained S100 protein-positive interstitial cells. Our study suggests, but does not prove, that there may be more than a random association between PEG and neoplasms. Cigarette smoking, moreover, is an important risk factor for both PEG and lung carcinomas. Our immunohistochemical findings indicate that S100 protein-positive cells in tumors usually bear little or no relationship to PEG. In patients with an underlying malignant neoplasm, PEG simulates pulmonary metastases clinically and, occasionally, histopathologically.

We studied lung development in children with or without bronchopulmonary dysplasia (BPD) using light microscopic morphometry and thick lung sections stained for elastic fibers. One lung was obtained at autopsy from each of eight patients with BPD (ages, 2 to 28 months) and six children (ages, 5 days to 51 months) who died without lung disease. Patients with BPD demonstrated severe somatic growth retardation and had reduced lung volumes with abnormal lobar volume proportions. In the central bronchi mean volume proportion of glands and smooth muscle was increased in BPD. Bronchiolar density was also increased, but it tended to normalize with advancing age. Mean bronchiolar diameter was slightly smaller in BPD, and bronchiolar smooth muscle hypertrophy was a constant histologic feature. The most striking change, however, was noted in alveolar structure and development. Total alveolar number was severely decreased in patients with BPD compared with that in control subjects, and there was little evidence of compensatory alveolar development with increasing age. Lung internal surface area was correspondingly reduced, and mean linear intercept was increased. Sections stained for elastic tissue demonstrated in the patients with BPD a simplified acinar structure with thickened, tortuous, and irregularly distributed alveolar elastic fibers. We conclude that in severe, fatal BPD there is marked impairment of lung development with alveolar hypoplasia and reduced internal surface area. In addition, bronchial and bronchiolar smooth muscle hypertrophy and bronchial gland hyperplasia may be important contributing factors to airflow limitation.

The histologic spectrum, pathogenesis, and clinical correlates of tracheobronchial and pulmonary lesions were studied by autopsy in six children and 27 adult burn victims. The burns covered a mean total body surface area of 57.7 +/- 23%. The mean survival time was 17.6 +/- 14.3 days. Patients over 60 years tended to survive longer than younger adults, but older patients had less extensive burns (P less than .01). Moderate or severe renal failure was an important clinical complication in 19 patients (58%). Diffuse alveolar damage (DAD) was observed in 16 patients, acute bronchopneumonia in seven patients, and necrotizing pneumonia in seven patients. Both DAD and pneumonia coexisted in 11 patients. Children most consistently developed pneumonia, 6 out of 6 versus 4 out of 17 younger adults (P less than .05). Factors which may have contributed to the pathogenesis of DAD included septicemia (12 patients), hypotension (nine patients), necrotizing pneumonia (six patients), and oxygen toxicity (four patients), in addition to the common presence of inhalational injury. The onset of DAD appeared late in eight patients with long survival periods, suggesting causal factors other than inhalational injury. However, survival rate did not differ in patients with or without DAD, and there was no correlation between DAD and the extent of burns. Airway lesions reflected the length of survival and showed the following sequence of changes: (1) mucosal necrosis and denudation, (2) acute inflammation and ulceration, and (3) squamous metaplasia. Endotracheal intubation injury and superinfection were confounding factors beyond the first few days of survival.

Lung morphology in ARDS reflects the rapid evolution from interstitial and alveolar edema to end-stage fibrosis consequent to injury of the alveolocapillary unit. This morphologic progression, termed diffuse alveolar damage, has been subdivided into sequentially occurring exudative, proliferative, and fibrotic phases. Pulmonary lesions correlate with the phase of alveolar damage rather than with its specific cause. As suggested by experimental models of acute lung injury, the pathologic features seen in humans are consistent with the effects of a host of injurious stimuli and the complex interaction of inflammatory mediators on alveolar epithelial and capillary endothelial cells. Although ARDS frequently culminates in "interstitial" fibrosis, the organization of intraluminal exudate dominates the histologic picture in the proliferative phase and establishes the framework for subsequent fibrous remodeling of the lung. Involvement of the pulmonary vasculature is an important aspect of ARDS, from the initial phase of edema to the terminal stage of intractable pulmonary hypertension. Vascular lesions include thrombotic, fibroproliferative, and obliterative changes, which, like the parenchymal lesions, correlate with the temporal phase of diffuse alveolar damage. Although ARDS is characterized by extensive bilateral lung involvement, alveolar damage can affect the lung in a localized fashion. "Regional alveolar damage" is associated with the same clinical risk factors as diffuse damage, suggesting that there is a spectrum in the extent of lung involvement and disease severity in patients at risk for ARDS. The factors that govern which patients will develop the fulminant syndrome are poorly understood. It must be re-emphasized that the lung is stereotyped in its response to injury, and, consequently, descriptive, or even quantitative, studies of lung morphology can only provide clues regarding the initiating factors and pathogenetic mechanisms of ARDS. Progress in understanding the pathogenesis of ARDS and the devising of rational approaches to therapy will ultimately depend on careful clinical and experimental studies that unravel basic mechanisms of cellular injury and response. The course of these investigations must be guided by and constantly correlated with the pathologic features that occur in humans.

The currently accepted mechanism to explain traumatic aortic rupture from rapid deceleration involves a combination of traction, torsion, and hydrostatic forces. The authors hypothesize that aortic isthmus lacerations result from a pinch of the aorta between the spine and the anterior bony thorax (manubrium, clavicle, and first ribs) during chest compression caused by abrupt deceleration. Compression of an articulated, normally moving thoracic skeleton containing a synthetic aorta consistently caused transection of the aorta at the isthmus between the spine and anterior bony structures. Analysis of rotation of the first rib in 10 consecutive patients undergoing computed tomography of the chest demonstrated interposition of the distal aortic arch and isthmus between the vertebrae and anterior bony thorax in each instance. Aortas excised from laboratory dogs were pinched between structures simulating bones to reproduce intimal and medial lesions indistinguishable from lesions associated with naturally occurring traumatic disruptions. Although further studies in cadaveric specimens are necessary to confirm this mechanism of injury, the authors believe that their results support the osseous-pinch mechanism of aortic rupture.