Polymyositis and diffuse interstitial lung disease. A review of the pulmonary histopathologic findings.

A retrospective analysis was performed of 105 patients with polymyositis for eight years. Roentgenographic evidence of pulmonary interstitial disease was present in ten adult patients (9%) with polymyositis unassociated with other connective-tissue disorders. Review of the pulmonary histopathologic findings indicated a spectrum of pulmonary diffuse interstitial infiltrates and fibroplasia of the alveolar septae. Response to glucocorticoids with regard to pulmonary symptoms was variable in the patients studied. Therapeutic response seemed to be influenced by both the cellularity of the chronic interstitial infiltrates and the degree of fibroplasia of the alveolar septae. Electron microscopic studies of the lung tissue from two patients with polymyositis and diffuse interstitial lung disease failed to demonstrate either immune complexes or viral particles.

Malignant pleural effusions. A clinical cytopathologic study.

From 1978 to 1982, 620 pleural fluid cytology specimens were examined, of which 80 were positive in 64 patients. Of these 64, three (0.5%) specimens had false-positive results. Adenocarcinoma of the lung was the most frequent (25 of 61) primary site, followed by breast (12 of 61), ovary (six of 61), and pancreas (five of 61). Comparing cytology with pleural core needle biopsy specimens in 26 patients, the cytology results were positive in 96%, while the needle biopsy specimens alone were positive in only 69%. Following the diagnoses of malignant pleural effusions, the patients receiving combined chemotherapy and radiotherapy had a mean survival of 328 days, compared with only 79 days for those who received no therapy. In conclusion, cytologic examination of Papanicolaou-stained smears yielded a greater percentage of positive diagnoses than either cell block preparations or pleural needle biopsy specimens. Over the past 25 years, the mean survival after the diagnosis of malignant pleural effusions has shown no improvement.

Trimellitic anhydride Toxicity. A cause of acute multisystem failure.

A person exposed to trimellitic anhydride (TMA) an epoxy resin widely used in industry, experienced respiratory failure, anemia, and gastrointestinal bleeding. A lung biopsy specimen demonstrated intra-alveolar hemorrhage and damage to alveolar lining cells. The patient and six co-workers were examined. Results indicated the presence of hemolytic antibodies directed against TMA-haptenized erythrocytes, IgG, IgA, and IgM antibodies directed against TMA-erythrocyte complexes, and antibodies against TMA-human serum albumin. Antibody levels in the patient were greater than in the co-workers. The elevated antibody levels demonstrate the antigenic potential of TMA. However, the cause of the pulmonary and hematologic damage remains uncertain and may represent either immunologic or direct toxic effects of TMA. In patients with multisystem failure of this nature, occupational hazards should be added to the differential diagnosis.

Beta-Carotene, vitamin A, and lung cancer chemoprevention: results of an intermediate endpoint study.

A randomized, placebo-controlled clinical trial of beta-carotene and retinol was conducted with 755 former asbestos workers as study subjects. The targeted endpoint for the intervention study was a reduction in the incidence and prevalence of sputum atypia. The dosage of 50 mg beta-carotene/d and 25,000 IU retinol/d on alternate days resulted significant increases in serum concentrations of both agents with no clinically significant toxicity. Skin yellowing was observed in approximately 35% of patients and may have contributed adversely to protocol adherence. Baseline analysis revealed that smoking and drinking were associated with lower concentrations of serum beta-carotene, even after dietary carotene intake was adjusted for (P < 0.0001). Baseline concentrations of retinol were apparently lowered by smoking (P < 0.002) and increased by drinking (P < 0.0001). Drinking and smoking also were significantly related to lower beta-carotene concentrations after supplementation (P < 0.001). No significant reduction in sputum atypia was observed after treatment.

Epidemiology of bronchioloalveolar carcinoma.

Descriptive features of bronchioloalveolar carcinoma (BAC) are presented using Surveillance, Epidemiology and End Results Program population-based incidence data from 1973 through 1987, along with risk factors from histologically confirmed cases of BAC identified in a hospital-based case-control study conducted in Louisiana between 1979 and 1982. Compared to the rising incidence of lung cancer overall, BAC rates have remained relatively constant, accounting for less than 3% of all lung cancer. BAC incidence rates were higher in males, yet it explained proportionately more of the total lung cancer incidence in females. In the case-control study, 21 of the 33 cases originally ascertained from hospital pathology records were histologically confirmed as BAC. Most cases smoked cigarettes, with a 4-fold risk for ever smoking. Risks tended to increase with smoking intensity (reaching 10-fold for more than 1.5 packs/day) and duration (reaching 5-fold for more than 45 years of smoking). Following 10 or more years of employment, there was a 4-fold risk associated with motor freight occupations, along with nonsignificant excesses among construction workers, petroleum manufacturers, and sugar cane farmers. Cases were more likely than controls to have had emphysema or to have had a close family member with lung cancer. Although based on small numbers, this study suggests that BAC shares many of the epidemiological characteristics of lung adenocarcinoma.

Ultrastructure of the lung in Loeffler's pneumonia.

A case is presented fulfilling the diagnostic criteria of "Loeffler's eosinophilic pneumonia". No etiologic factors could be determined, and the chest roentgenogram returned to normal. Lung biopsy at the peak of the disease demonstrated an interstitial eosinophilic pneumonia without tissue necrosia or vasculitis. By electron microscopy, the alveolar capillary basement membranes were intact and exhibited no immune deposits. Normal appearing eosinophils were abundant in the alveolar capillaries, interstitium and alveolar spaces. Occasional eosinophils released their granules within the alveolar wall. Macrophages were increased in number in both the alveolar wall and alveolar spaces.

Clinical implications of a "nonspecific" transbronchial biopsy.

The diagnostic accuracy of transbronchial biopsy via fiberoptic bronchoscope was reviewed in 127 noncritically ill patients. Biopsy results were analyzed according to whether a "specific" pathologic diagnosis of neoplasm, granuloma or pneumonia, or a "nonspecific" diagnosis of inflammation, fibrosis or normal lung was made. The clinical significance of a "nonspecific" biospy specimen was evaluated by clinical follow-up of at least 12 months (mean 15 months) and by grouping patients according to the type of abnormality found on chest roentgenography. Clinical follow-up was available in 119 of these patients. The over-all "specific" diagnostic yield for biopsy with secretions was 49 per cent, with transbronchial biopsy being the sole means of specific diagnosis in 14 per cent of the patients with a peripheral mass lesion, in 18 per cent of the patients with localized infiltrative processes and in 52 per cent of the patients with diffuse infiltrative processes. In 64 (52 per cent) patients both biopsy specimens and secretions were diagnostically nonspecific. In 16 (77 per cent) patients with peripheral mass lesions but nonspecific biopsy findings and secretions, neoplasm was diagnosed by more invasive procedures. However, 22 (91 per cent) patients with localized and 12 (75 per cent) patients with diffuse infiltrative processes had benign clinical follow-up suggesting that open lung biopsy in such patients should be reserved for patients with obvious clinical or roentgenographic evidence of deterioration.

Lymphocyte subset populations in bronchiolitis obliterans after heart-lung transplantation.

The long-term success of heart-lung transplantation is limited by the development of bronchiolitis obliterans, possibly as a form of chronic lung allograft rejection. In the present study, we have characterized by immunohistochemical staining the lymphocytes infiltrating the lesions of bronchiolitis obliterans in one patient following heart-lung transplantation. The finding that the preponderant cells expressed the CD8 (putative cytotoxic/suppressor) marker lends support to the notion that chronic rejection is at least one mechanism for the development of bronchiolotis obliterans following heart-lung transplantation.

Scanning electron microscopic examination of human asbestos bodies.

Asbestos bodies represent the product of the macrophage's attempt to detoxify inhaled asbestos fibers. The process of asbestos body maturation was examined by scanning electron microscopy of material isolated from lungs of former asbestos workers. The results suggest that the progression from a membrane-bound, smooth coating of the fiber, to the typically beaded form may be caused by cracking and subsequent erosion due to the inspiratory and expiratory forces of the lung on the asbestos body.

Asbestos body phagocytosis by human free alveolar macrophages.

Phagocytosis of asbestos bodies by human free alveolar macrophages (FAMs) was documented employing light microscopy. This process was more carefully studied utilizing scanning electron microscopy (SEM) which demonstrated morphological and surface membrane changes in FAMs following phagocytosis of asbestos bodies. FAM viability was also evaluated following 24--72-h incubation of cells with asbestos bodies at a final concentration of 250 micrograms/ml. Slight, but significant, cytotoxicity was observed following the initial 24-h culture period (P = 0.032, paired, 2-tailed t-test). No further cytotoxicity was observed, however, when cells were further incubated for 48-h and 72-h intervals (P greater than 0.05 in all instances). These studies demonstrate asbestos bodies are readily phagocytized by cultured FAMs, and are only slightly cytotoxic to these human lung cells.

Recent advances in pulmonary cytopathology.

During the past five years, advances in pulmonary cytopathology have made possible the achievement of several goals, including the diagnosis of pneumonias in immunocompromised hosts, the detection and localization of occult lung cancers in high-risk cigarette smokers, the diagnosis of lesions of the lungs and chest wall by fine-needle aspiration, and the detection of asbestos exposure by sputum cytologic studies. Significant progress has also been made in the application of cell image analysis to the detection of premalignant bronchial epithelial cells in sputum. For the most part, these advances are based on such well-known cytologic procedures as the preparation of thin and evenly distributed smears, prompt fixation, properly controlled and monitored Papanicolaou staining, and thorough screening of slides. Such diligence in laboratory techniques remains the backbone of excellence in pulmonary cytopathology. Cytologic findings should be interpreted with the clinical features of each case in mind, for the practice of pulmonary cytopathology remains an art as well as a science.

Pulmonary histopathology in cocaine abusers.

Lung histopathology was reviewed from 52 autopsies with positive toxicologic tests for cocaine from the medical examiners' offices in Dallas and Austin, TX. The median patient age was 34.7 years, and the male to female ratio was 2:1. Twelve individuals primarily used the drug intravenously and six primarily smoked it, but in most patients usage history was not known. The most frequent manner of death was accidental, consisting predominantly of cocaine overdoses. Other frequent manners of death included both natural causes and homicides. Subjects with chest trauma were excluded from the study. Twenty-three age-matched control cases with negative cocaine histories and toxicologic tests also were obtained from medical examiner autopsies. Histopathologic findings in the cocaine abuse group included acute hemorrhage, 58% (P = .05); chronic hemorrhage, 40% (P < .01), interstitial pneumonitis/fibrosis, 38% (P < 0.01); congestion, 88% (P < .01); and intra-alveolar edema, 77% (P < .01). These changes were remarkably consistent regardless of locale or method of use. Our findings demonstrate that pulmonary hemorrhage is more frequent than suggested by clinical hemoptysis and that chronic pulmonary diseases such as interstitial fibrosis may develop in long-term users.

Potential utility of p53 immunopositivity in differentiation of adenocarcinomas from reactive epithelial atypias of the lung.

Reactive atypia of alveolar epithelium occurs in many types of lung injury and may sometimes raise suspicions of adenocarcinoma or bronchioloalveolar carcinoma. To assess whether there is sufficient difference in the frequency of p53 protein immunopositivity in these lesions to provide a practical basis for differentiating malignancy from reactive atypia, we immunostained 110 malignant and inflammatory/fibrotic lung specimens for p53 protein. Paraffin-embedded sections were immunostained with p53 protein antibody (clone BP53-12; BioGenex, San Ramon, CA) and standard capillary gap (Microprobe; Fisher Scientific, Fairlawn, NJ) avidin- biotin complex technique with antigen retrieval solution. Percent of immunopositive cells was semiquantitatively categorized as follows: 0%, less than 1%, 1% to 10%, 10% to 50%, more than 50%. Of reactive atypias, 94% are negative or show p53 immunopositivity in less than 10% of cells. Of p53 positive malignancies, 86% are positive in more than 10% of cells. When p53 immunopositivity occurs in more than 10% of atypical cells, the lesion is usually a malignancy, primarily adenocarcinoma. Most reactive atypias are immunopositive in less than 10% of atypical cells. Important caveats were noted. Rare reactive atypias are p53 immunopositive in greater than 10% of cells. Bronchioloalveolar carcinomas are infrequently p53 immunopositive. Therefore, this approach would be less useful in their differentiation from reactive atypias.

The lung in cystic fibrosis. A quantitative study including prevalence of pathologic findings among different age groups.

The autopsies of 82 patients with cystic fibrosis were reviewed with respect to pathologic changes in the lungs and their respective prevalence among different age groups. Although bronchitis, mucopurulent plugging, and bronchopneumonia were almost universally present among children of all ages, epithelial metaplasia and bronchiectasis were rarer among infants and progressively more prevalent in older age groups. Emphysema was absent in patients under two years of age and affected 11 per cent of the patients two to six years of age and 40 per cent of the patients older than six years, but was never of a severe degree by the point count method. Pulmonary hemorrhage, although uncommon, was usually associated with prominent arterial vessels in walls of bronchiectatic airways. Quantitative assessment of bronchial glands revealed Reid indices significantly higher in patients with cystic fibrosis when compared to noncystic fibrosis patients, but there was no increase in these indices with the age of the patients. Glandular hypertrophy, predominance of mucous acini within glands, and goblet cell hyperplasia of the bronchial mucosa all suggest an explanation for the copious mucous secretion of patients with cystic fibrosis. However, it was not possible to ascertain whether these findings reflect a general exocrine defect of such patients or whether they were merely a response to chronic airway infection, even though the latter is a more plausible assumption.

Prognostic significance of histopathologic subtype and stage in small cell lung cancer.

A study of 149 light microscopic tissue slides from 147 patients with recorded initial diagnoses of small cell lung cancer (SCLC) (114 cases) and undifferentiated carcinoma (35 cases) was undertaken to test the reproducibility and prognostic impact of a new histopathologic subclassification of SCLC proposed by the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). This study was further designed to test the impact of clinical stage, age, sex, and race on survival. The tissue slides were blindly reclassified as SCLC or non-SCLC by a panel of five pathologists with no knowledge of the initial diagnosis. The SCLCs were divided into the three subtypes outlined by the IASLC pathology panel: small (classic or pure), mixed (small cell/large cell), and combined (small cell/squamous carcinoma or small cell/adenocarcinoma). Small cell lung cancer was clinically staged as local, regional, or distant. Consensus diagnosis (defined as agreement by at least three of the five pathologists) was achieved in 144 (96.6%) of the 149 cases. Of these 144 cases, 124 were reclassified as SCLC (115 [92.8%] small, five [4.0%] mixed, and four [3.2%] combined) and 20 were classified as non-SCLC. The median lengths of survival for the small, mixed, and combined subtypes were 225, 1,110, and 203 days, respectively (P = .025). Adequate staging data were available in 123 of the 124 SCLC cases. Of the 123 SCLC cases, 27 (21.9%) were local, 22 (17.9%) were regional, and 74 (60.2%) were distant stage. The median lengths of survival for the local, regional, and distant stages were 428, 251, and 111 days, respectively. This association was highly significant (P = .0001). We conclude that stage is the major determinant of survival in SCLC. Mixed subtypes had significantly longer survival times than the small or combined subtypes (P = .025). Survival times were longer for women than for men, and the survival time difference between men and women was significant (P = .0028). We found no significant differences in survival according to age or race.

Lung cancer heterogeneity: a blinded and randomized study of 100 consecutive cases.

The heterogeneity of lung carcinomas was recognized in the past, but few previous studies attempted to quantitate this heterogeneity. In the present study 100 consecutive cases of lung carcinoma (65 surgical resections and 35 autopsies) were collected, and either the entire tumor or ten blocks were examined in a blinded and randomized fashion using the revised (1981) WHO classification. At least three of five panelists agreed on the major histologic type present for 94 per cent of the slides. Agreement for the diagnosis of small cell carcinomas (at least four of five observers) was 98 per cent, but only 72 per cent agreement was attained for the subtyping of small cell carcinomas (e.g., oat cell versus intermediate). Only 34 per cent of the cases were homogeneous according to the majority of the panelists. An additional 21 per cent of the cases showed minor (subtype) heterogeneity (e.g., mixtures of acinar and papillary patterns in adenocarcinoma). Forty-five per cent of the cases showed major heterogeneity, i.e., at least one slide from the case showed a major histologic type different from that of the remainder. Seven small cell carcinomas were homogeneous, whereas in eight cases mixtures of small cell and other cell types were seen. In all but one of the cases involving bronchioloalveolar cell patterns, other patterns of adenocarcinoma were present elsewhere in the tumor. In all six cases involving giant cell carcinoma patterns, adenocarcinoma patterns were also present in some sections. Heterogeneity was identified by extensive sampling of the entire tumor and was seldom recognized in biopsy specimens.

Pleural mesothelioma with calcified liver metastases.

This is the second published report of a patient with a malignant pleural mesothelioma who presented with roentgenographic findings of massive liver calcifications. Necropsy examination revealed the hepatic calcifications to be dystrophic calcification within necrotic foci of metastatic malignant mesothelioma.

Small cell carcinoma of the lung treated with irradiation and chemotherapy. Autopsy confirmation of long-term disease-free survival.

A patient survived clinically disease free for 68 months following combination chemotherapy and radiotherapy for small cell carcinoma of the lung. No evidence of tumor was found at autopsy. To our knowledge, this represents the first documentation by autopsy of a greater than five year disease-free survival following treatment of small cell cancer of the lung.

Lupus lung.

The morphologic findings from 18 autopsy lungs of systemic lupus erythematosus were studied. Each case revealed varying degrees of pleuropulmonary disease. A universal feature was visceral pleural thickening, while findings present in more than one half of the cases included pulmonary congestion (17/18) and edema (15/18), pleural adhesions (11/18) and pleural effusions (10/18) and intraalveolar hemorrhage (10/18). Also seen were bronchopneumonia (9/18), interstitial fibrosis (6/18), cytomegalovirus infection (3/18), interstitial pneumonitis (2/18), hyaline membranes (2/18), and acute vasculitis (1/18) and pleuritis (1/18). These results, together with those of previously reported studies of lupus lung, establish that although certain characteristic pleuropulmonary disease processes are frequently found at autopsy, none is a highly specific marker for the disease.

Comparison of light and electron microscopy for defining occupational asbestos exposure in transbronchial lung biopsies.

Since asbestos burden in the lung can very among areas, the usefulness of small tissue samples for identifying past occupational exposure is examined. Simulated transbronchial biopsy samples and open lung biopsy samples were collected from autopsy material from 12 former amosite asbestos workers and ten persons from the general population. Tissue evaluation included (1) paraffin embedment and light microscopy screening for fibrosis and ferruginous bodies, and (2) tissue digestion, which was analyzed by the combination of (A) light microscopy screening for ferruginous bodies and (B) electron microscopy (EM) screening for uncoated fibers. Using standard pathology techniques to classify the small samples was generally unsuccessful, the samples being too small or their size compounding other random sampling problems. The most reliable method of establishing which transbronchial biopsy tissue samples were from the occupationally exposed group occurred when light and EM analyses were used to evaluate digested tissue. The combined data from the EM analysis of two samples per subject indicated controls had two or fewer observed asbestos fibers, while the amosite asbestos workers had six or more fibers. This distinction was valid even in those who, 21 years before sampling, had worked for only a few weeks in the asbestos plant.