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Study objective: This prospective study was performed in an attempt to evaluate (1) the rate of magnetic resonance imaging (MRI) demonstrating bone marrow (BM) abnormalities, (2) the correlation of these abnormalities with a pathologic malignant BM involvement, and (3) the possible modification of patients' usual disease staging in the light of these abnormalities. Methods: After extensive staging investigations, patients' diseases were classified as limited or extensive. Dorsal and lumbar spine MRI was performed for second staging. Results: Thirty-two patients were eligible for this study. In ten patients (31.2 percent), MRI showed abnormalities; in four of them, the BM sample from the posterior iliac crest was free from malignancy. Three of these four patients had extensive disease. The last patient, because he had limited disease, had biopsy at the site of MRI abnormalities; the biopsy specimen revealed a malignant involvement and therefore this patient, initially classified as having limited disease, was classified in the extensive disease group. In only 1 of 32 patients, BM-MRI data modified initial staging. Conclusions: The metastases disclosure yield of the MRI in the detection of medullar involvement is higher than BM biopsy but especially in patients with extensive disease. Therefore, MRI should not be considered in routine practice, in particular in patients with extensive disease.

To assess the value of bronchoalveolar lavage (BAL) for diagnosis, understanding, and treatment of amiodarone-associated pneumonitis, we examined the results of BAL total and differential cell counts and phenotyping of lymphocytes in 22 patients with this lung disorder and in 33 normal subjects. Overall, the total cell count was found to be almost the same as that seen in control subjects; the macrophage population was significantly reduced, and the lymphocyte, neutrophil, and eosinophil populations were increased in absolute number and percentage. When results were analyzed individually, BAL data appeared to be distributed according to two patterns. In the first pattern, there was no abnormal lymphocytosis. In the second pattern a lymphocyte alveolitis was found in percentage and in absolute number. This lymphocyte alveolitis was present either alone or associated with neutrophil alveolitis or with eosinophil alveolitis. In the first pattern, despite the normal level of the lymphocyte population, the percentage of CD4 T-lymphocytes and the CD4:CD8 T-lymphocyte ratio were significantly lowered. In the second pattern the CD8 T-lymphocyte count was increased in absolute number and percentage, with a low CD4:CD8 ratio. In six patients relavaged two to four months after amiodarone withdrawal, there was a significant fall in alveolar lymphocytosis, but the progressive increase in the neutrophil population over time seemed to be associated with the seriousness and progression of the disease. Finally, these findings closely resembled those obtained in patients with hypersensitivity pneumonitis due to inhalation of organic dust and suggest that an underlying immunologic cell-mediated mechanism may play a role in this iatrogenic pulmonary disease. (Chest 1991; 99:1177-82)

A 79-year-old man was given a cumulative dose of 16.5 g of nilutamide for treatment of prostate cancer. He then presented with a respiratory illness having clinical, radiologic and functional characteristics of interstitial pneumonitis. No other cause of pneumonitis was found. Bronchoalveolar lavage showed a lymphocytic alveolitis with an inverted lymphocyte subset ratio. After an 11-week period of drug withdrawal, clinical, radiologic and functional improvement was observed along with a normal alveolar lymphocytosis. Nilutamide therapy was then resumed for five weeks and induced the recurrence of clinical, functional and alveolar abnormalities. Nilutamide treatment was finally stopped and two months later, clinical and functional abnormalities resolved. This observation seems to exemplify the possible diagnostic value of coupling provocation test with BAL cell data in hypersensitivity pneumonitis induced by drugs. In addition, these data support the role of a cell-mediated immunologic mechanism in the pathogenesis of nilutamide-induced pneumonitis. (Chest 1990; 97:495–98)

Methotrexate-induced pneumonitis is a well-known clinical entity, but the mechanism for the induction of the pulmonary disease is ill defined. In three patients with this disorder, evidence was obtained for elaboration of a lymphokine, leukocyte inhibitory factor (LEF), by peripheral blood lymphocytes after incubation with methotrexate (MTX) in the direct leukocyte migration inhibition test. Control lymphocytes from normal subjects, as well as from patients receiving methotrexate but without pneumonitis, failed to elaborate LIF in the presence of the drug in this test. Along with these results, we obtained bronchoalveolar lavage (BAL) cell data displaying high grade lymphocyte alveolitis with a lymphocyte subset inverted ratio. This production of LIF suggests that pneumonitis associated with methotrexate therapy is also associated with a specific cellular immune response to the drug.

We examined bronchoalveolar lavage (BAL) cell data from 19 patients with a lung disorder presenting clinical, radiologic, functional, and course characteristics of drug-associated interstitial pneumonitis. In each of them, one of 13 different drugs was incriminated and no other cause was found. In one case due to bleomycin, a neutrophil and eosinophil alveolitis was present. In the other 18, the common denominator was a lymphocyte alveolitis, either pure (n = 6) or associated with neutrophilia (n = 5), eosinophilia (n = 3), or neutrophilia and eosinophilia (n = 4). In addition, in all patients, an inverted CD4/CD8 lymphocyte ratio was observed. In eight patients who underwent another BAL, lymphocyte alveolitis decreased but was persistent in two of them two to four months after cessation of treatment with the drug incriminated, whereas interstitial pneumonitis had resolved clinically. In five patients, after resolution of pneumonitis and after an almost normal BAL cell profile was obtained, resumption of treatment with the suspected drug for two to four weeks induced a rise in lymphocyte population in a third BAL. In conclusion, apart from one case of bleomycin lung, the most striking feature of drug-associated alveolitis in this series was expansion of lymphocyte population and imbalance in lymphocyte subsets. When a provocation test was performed, variations in alveolar lymphocyte levels paralleled withdrawal and readministration of the drug responsible for alveolitis. These data could be of value in diagnosing and understanding drug-induced lung disorders. (Chest 1991; 99:98–104)

Serum neuron-specific enolase (S-NSE) levels in 43 newly diagnosed untreated patients with small-cell lung cancer (SCLC) were compared with levels in 35 adult controls, 14 patients with non-small cell lung cancer (N-SCLC), and nine patients with noncancerous lung disease (N-CLD). The S-NSE level was raised (≥16 ng/ml) in 28 of 43 patients with SCLC, six of 16 patients with limited stage SCLC, and 22 of 27 of those with extensive stage SCLC. Extensive stage patients with SCLC had a significantly higher mean S-NSE level (50 ng/ml) than did limited stage patients with SCLC (16 ng/ml). Mean S-NSE levels in patients with N-SCLC and in patients with N-CLD were respectively 11 and 7 ng/ml. Serial measurements performed on 19 patients between the three-day-courses of chemotherapy showed an excellent correlation between S-NSE and clinical evolution. In addition, S-NSE was measured during the first three-day course of chemotherapy in 13 other patients; among them, seven had S-NSE levels ≥100 ng/ml (mean: 490 ng/ml); these seven patients were responders; the remaining six had S-NSE levels

Interstitial pneumonitis developed in a patient who had received a cumulative dose of 985 g of amiodarone in nine years. No other cause for pneumonitis was found. The following findings favor an immunologic mechanism of hypersensitivity due to amiodarone: positive skin and basophil degranulation tests with amiodarone; lymphocytosis and inverted ratio of helper/suppressor T lymphocytes in bronchoalveolar lavage fluid; secretion of leukocyte inhibitory factor, as shown by the inhibition of migration of peripheral blood leukocytes; and positive lymphoblastic transformation in the presence of amiodarone.

Amiodarone-associated pneumonitis is now a well-known clinical entity, but the mechanism for the induction of the pulmonary disease is ill defined. In four patients with this disorder, evidence was obtained for elaboration of a lymphokine, leukocyte inhibitory factor (LIF), by peripheral blood lymphocytes after incubation with amiodarone in the direct leukocyte migration inhibition test. Control lymphocytes from normal subjects, as well as from patients receiving amiodarone but without pneumonitis, failed to elaborate LIF in the presence of the drug in this test. This production of LIF suggests that pneumonitis associated with amiodarone therapy is also associated with a specific cellular immune response to the drug.

A patient with a 12-year history of occipital ependymoma was found to have late pleuropulmonary metastases without recurrence of the primary tumor. The pleural metastases were diagnosed by histologic, ultrastructural features and finally by glial fibrillary acidic protein (GFAP) labeling positive reaction. This case is unique because of the long interval between occurrence of the initial tumor and the metastases, and because of the apparent quiescence of the cerebral lesion when the pleuropulmonary metastases were discovered.

We observed 276 HIV-infected patients to determine the frequency, degree, and clinical presentation of the lymphocytic alveolitis in different stages of HIV disease, and also to identify the lymphocyte subsets involved. In 154 patients with proved lung infections or tumors (group A), bronchoalveolar lavage fluid showed lymphocytosis in 78 percent of cases. In 122 subjects (31 AIDS and 91 HIV-infected non-AIDS patients) without evidence of lung tumor or infection (group B), lymphocytic alveolitis was seen in 72 percent of cases. In 61 of 88 (69 percent) group B lymphocytic patients, we observed respiratory symptoms or diffuse interstitial opacities; however, we also observed such alveolitis in 27 of 46 (59 percent) group B patients free of respiratory symptoms and abnormality of chest x-ray film. This alveolitis was seen not only in AIDS or ARC patients but also at earlier stages of HIV infection. T-lymphocyte analysis showed a large majority (40 to 93 percent) of CD8 positive lymphocytes in the 37 patients tested. A dual fluorescence analysis revealed, in 18 subjects, that those cells were phenotypically cytotoxic (CD8 + D44 +). These findings suggest that, regardless of HIV-infection stages and of opportunistic lung infections, a CD8-positive T-lymphocyte alveolitis may be present in HIV-infected patients and could be responsible for cough, dyspnea, interstitial pneumonitis, and abnormalities of pulmonary function tests. (Chest 1988; 94:1264-70)

Two male patients presented with lung disorders with all the characteristics of amiodarone-related pneumonitis. Bilateral exudative pleural effusions were associated with pneumonitis. High lymphocytosis was present in the pleural fluid with a ratio of T-lymphocyte subsets close to that found in peripheral blood; in the blood T-lymphocyte subset ratio was nearly normal. By contrast, and as is usual in similar cases, lymphocytic alveolitis with T-lymphocyte subset imbalance was found in bronchoalveolar lavage fluid. These findings, never published so far to our knowledge, would favor a compartmentalization of the immune response inside the lung.