Pulmonary lymphomas simulating lymphomatoid granulomatosis.

Twenty cases of malignant lymphoma presenting in the lung and 10 cases with secondary pulmonary involvement were studied. All cases shared the feature of prominent vascular infiltration by lymphoid cells, and in the 20 cases presenting with pulmonary involvement, this feature led to confusion with lymphomatoid granulomatosis. Both the primary and secondary lymphomas showed similar histologic features including vascular infiltration, extensive necrosis, and foci of a histologically polymorphous and benign infiltrate. The diagnosis of lymphoma was based on the identification of monomorphous foci of atypical lymphoid cells except in the cases of Hodgkin's disease. The malignant cells were occasionally focal and microscopic and surrounded by an extensive histologically benign infiltrate. Examination of several blocks was often required in such cases before a diagnosis of lymphoma could be made. The clinical and radiologic findings at presentation were nonspecific. Radiologic findings included unilateral or bilateral nodules and infiltrates. The prognosis of the 20 patients who presented with pulmonary lymphoma was poor; half were dead in less than 2 years.

Sclerosing hemangioma of the lung: a clinicopathologic study of 51 cases.

The clinical and pathologic features of 51 sclerosing hemangiomas of the lung are reviewed. This tumor is benign and occurs predominantly in women. It has a variegated histologic appearance characterized by an admixture of four major histologic patterns: solid, hemorrhagic, papillary, and sclerotic. Characteristic uniform round cells are found within the stroma in all patterns and are unique to this tumor. Sclerosing hemangioma is a distinct clinicopathologic entity and should be distinguished from other benign neoplasms or inflammatory lesions of the lung.

Pulmonary involvement of malignant histiocytosis: a clinicopathologic spectrum.

We described five patients in whom pulmonary malignant histiocytosis was histologically confirmed during life. Pulmonary symptoms dominated the clinical presentation in three patients, and one patient had a 5-year history of pulmonary malignant histiocytosis controlled by steroids. Radiologic features were nonspecific. Most patients had bilateral reticulonodular or fluffy infiltrates. Recurrent pulmonary histiocytosis in one patient was manifest by bilateral pulmonary nodules. Pathologically, pulmonary infiltration by malignant histiocytosis followed the normal lymphatic pathways of the lung along bronchovascular rays, in interlobular septa, and within the pleura. Unusual features included marked septal edema and fibrosis out of proportion to the degree of infiltration, and in one case, the marked predilection fo the infiltrate to occlude small airways ("malignant histiocytosis bronchiolitis"). Three patients had microscopic nondestructive nodules adjacent to lymphatics. A pulmonary recurrent in one patient was composed of large monomorphous nodules with central necrosis and prominent vascular infiltration by malignant cells. The pulmonary infiltrate of malignant histiocytosis was often heterogeneous, and included variable numbers of lymphocytes and plasma cells intermingled with alveolar macrophages and metaplastic alveolar lining cells. The cytologic features of the infiltrate varied from benign to pleomorphic and obviously malignant. Histologic features which may obscure the correct diagnosis, as they did initially in three of our cases, include: malignant histiocytic bronchiolitis, marked septal edema and fibrosis; the heterogeneous cellular infiltrate; and in one case, benign cytologic features. The most valuable initial clue to the correct diagnosis was the tendency of the infiltrates to follow lymphatics of the lung.

Pulmonary lymphomas: current concepts.

The shift from a clinical definition (aggressive behavior) to an immunologic definition (clonal proliferations of cells) of lymphomas has led to a reinterpretation of most pulmonary pseudolymphomas as indolent lymphomas. The recognition of the diverse histologic appearance of lymphomas and the acceptance of extranodal lymphomas support the view that most cases of lymphomatoid granulomatosis are malignant lymphomas. Criteria for the recognition and classification of pulmonary lymphoid lesions are discussed.

Follicular bronchitis/bronchiolitis.

Nineteen open lung biopsies demonstrating follicular bronchitis/bronchiolitis were reviewed with special attention to clinical manifestations. Morphologically, follicular bronchitis/bronchiolitis was represented by coalescent reactive germinal centers adjacent to airways in the absence of clinical or pathologic evidence of chronic obstructive pulmonary disease or bronchiectasis. Three clinicopathologic groups were identified: 1) patients with collagen vascular diseases, especially rheumatoid arthritis and Sjögren's syndrome; 2) patients with a familial form of the disease or with immunodeficiency syndromes; and 3) a heterogeneous group of patients with frequent peripheral blood eosinophilia, suggesting a hypersensitivity reaction. Prognosis was related to age at the time of biopsy and, to some extent, to the clinical group. Steroid therapy had inconsistent effects in all groups identified. The differential diagnosis of lymphoid lesions in the lung is also discussed.

Pulmonary nodules and rheumatoid factor in the absence of arthritis.

Bilateral pulmonary parenchymal nodules were detected in a 41-year-old woman in 1964. These lesions gradually enlarged over a ten-year period. In 1974, the diagnosis of rheumatoid pulmonary disease was based on her clinical course, the presence of rheumatoid factor in the serum, interpretation of a biopsy of a cutaneous nodule, and review of a lung biopsy performed in 1964. The patient never developed arthritis.

Necrotizing sarcoid granulomatosis.

Twelve cases of necrotizing sarcoid granulomatosis are presented as a retrospective study. The population of patients consisted of ten women and two men, with an average age of 50 years. Nine patients initially had a variety of pulmonary and nonpulmonary complaints, while three were asymptomatic. Chest roentgenograms demonstrated bilateral nodules in seven patients, solitary nodules in four, and a miliary pattern progressing to nodules in one. Enlarged hilar nodes were found in six. Histologically, all biopsies showed a combination of individual granulomas, confluent masses of granulomas which formed the nodular masses seen on the roentgenograms, a variable amount of necrosis of tissue and hyalinization, and a granulomatous vasculitis. Follow-up periods ranged from four months to 11 years. Eleven patients are alive and asymptomatic. The sole death occurred in a patient treated with an immunosuppressive agent (cyclophosphamide). We conclude that the clinical behavior of necrotizing sarcoid granulomatosis is not similar to that of the other angiocentric granulomatoses and that most patients with this disease can be left untreated or be treated with steroids alone. We suggest the possibility that necrotizing sarcoid granulomatosis may be the histologic counterpart of so-called nodular sarcoid.

Crackles (rales) in the interstitial pulmonary diseases.

There is renewed interest in the classification and methods of recording adventitious pulmonary sounds. This is a study of the importance of fine crackles (rales) in the diagnosis and estimation of the severity of diffuse infiltrative pulmonary disease. Among 272 cases documented by lung biopsy, bilateral fine crackles were heard in 60 percent of those with interstitial pneumonias and asbestosis but in only 20 percent of those with sarcoidosis and other granulomatoses. These incidences were identical in 335 patients diagnosed clinically. In 322 selected ambulatory patients with chronic obstructive pulmonary disease, fine crackles were recorded in only 10 to 12 percent, while coarse crackles were not uncommon in patients with chronic bronchitis. In workers exposed to asbestos, crackles correlated with exposure. In serial studies of such workers, the occurrence of crackles alone appeared to be a random event, while among those with crackles together with one other of five criteria, almost one-half developed asbestosis within four to six years. Fine crackles correlated with pathologic severity, with radiographic honeycombing, and with physiologic abnormalities.

A radiographic classification for sarcoidosis: physiologic correlation.

The chest roentgenogram is frequently used to judge severity and course of sarcoidosis. The only widely used method for staging, suggested by Siltzbach, does not provide for such judgments. Therefore, we devised a scheme for objective description of type and quantity of opacities based on the ILO/UC Classification for the Pneumoconioses. We added a "reticulonodular" category (x y z) to the present "rounded (p q r) and "linear-irregular" (s t u) categories. We retained the 11 point scale for profusion (severity) and added notations to describe ground glass (alveolar) patterns, size of nodes, and hilar retractions. Among 211 patients, x y z (35%) and p q r (33%) opacities predominated while s t u opacities (19%) were unusual. Radiographic severity correlated best with vital capacity (rs = -0.49) and the diffusing capacity (rs = -0.32). With the Siltzbach classification these correlations were not as good (rs = -0.27 and -0.19). Siltzbach Stage III (fibrosis) was a distinct group with poor function and frequent airway obstruction. There was no correlation between radiographic appearance and pathologic severity because the latter grading, on a scale from 0 to 10, never exceeded 3. Sequential studies in 64 patients showed that, when individuals are used as their own controls, overall profusion correlated highly with physiologic changes over time.

Structure and function in sarcoidosis.

We have reviewed and compared our clinical, roentgenographic and histological material from 63 patients with sarcoidosis, berylliosis, and biological dust sensitivity. Among the histological features interstitial cellular infiltration proved to be the best for correlation with abnormal function, especially with arterial oxygen pressure and alveolar-arterial oxygen pressure difference at exercise, single-breath pressure and alveolar-arterial oxygen pressure differnce at exercise, single-breath diffusing capacity, forced vital capacity, and a composite index of overall functional impairment. There was also a significant correlation between pathological changes and a composite index of clinical severity. Some of the imperfections in these correlations may be related to strategic locations of granulomata that could alter ventilation-perfusion relationships, but part of the functional change remains unexplained by our histological measurements. Correlations of physiological and pathological features with radiographic parenchymal changes generally was poor except in the most severe cases. The finding of 4 cases with biological dust sensitivity or "allergic alveolitis" in this series reemphasizes that it is worth reviewing all cases of routinely labeled sarcoidosis in which the diagnosis has been based on the histological finding of granulomata. This is especially true in patients whose roentgenograms show no hilar nodes and minimal or "groudn-glass" changes in the lung fields despite significantly abnormal lung function and also in patients who have rapid remissions and exacerbations without therapy. Almost all of the features of berylliosis overlapped those of sarcoidosis and no distinction could be made histologically. The mean values were worse in the berylliosis group and the long-term results in treated patients were not nearly as good as in the sarcoidosis group.

Open biopsy for chronic diffuse infiltrative lung disease: clinical, roentgenographic, and physiological correlations in 502 patients.

Clinical, physiological, roentgenographic, and histological data concerning 502 patients who had open biopsy for chronic "interstitial" lung disease were reviewed. Mortality was 0.3%, the rate of complications was 2.5%, and the diagnostic yield was 92.2%. A modified Chamberlain approach in the second interspace is preferred for easy access to all lobes and mediastinum. Brief tube drainage is mandatory. Atelectasis and hemorrhage in the specimen are prevented by avoiding palpation and clamps, by delineating the wedge during full inflation, and by instant fixation. Customary biopsies of the tip of the lingula or middle lobe are avoided because these are common sites of inflammation, scarring, and passive congestion. Often, the most abnormal regions are biopsied apparently to aid the pathologist. Such selection has been the most important cause of meaningless histological findings and poor pathological, physiological, and roentgenographic correlations because these regions usually show end-stage disease of unrecognizable origin. Average lung is more likely to show an active and recognizable process.

Thoracic surgical problems in asbestos-related disorders.

Among 1,577 persons with asbestos exposure followed up from 3 to 30 years, 113 had thoracic surgical procedures for asbestos-related disorders. Twenty-six individuals suspected of having asbestosis with atypical features underwent open-lung biopsy; a different disease was revealed in 14. Most of the 29 patients with mesothelioma had a small thoracotomy for diagnosis only; chemotherapy in half of them proved entirely ineffective. Experience with 23 patients with bronchogenic carcinoma did not differ from that in persons not exposed to asbestos. Problems of causal relationship are discussed. Most of the 68 individuals with benign asbestos pleural effusion had no symptoms, but because of recurrence, 15 were operated on for decortication or for possible mesothelioma. Hyaline plaques often were mistaken for lung, rib, or diaphragmatic tumors, and sometimes mesothelioma was suspected. Operative intervention in the 24 patients with plaques could have been avoided by obtaining a more detailed occupational history and reviewing previous chest roentgenograms, which invariably showed identical or smaller plaques from 2 to 17 years earlier.

Chronic diffuse infiltrative lung disease. Newer approaches.

A new scheme for description of diffuse infiltrative lung diseases using the graphic terminology of the International Labour Office Classification is described. Conventions for grading the type (rounded, or "pqr," and irregular, or "stu"), severity (profusion in 12 steps), localization of opacities, and pleural disease were retained. Modifications included (a) a third group of opacities, called "xyz," corresponding to reticulonodular patterns; and (b) "ground glass" (alveolar) patterns, subdivided into seven types by character and location. In a study of 365 cases proven by open biopsy, when this scheme was used without any knowledge of clinical data, the first two radiologic diagnostic choices corresponded with the principal histologic diagnosis in 50 per cent of cases. This classification provides an understandable and quantifiable system of communication and a tool for teaching, clinical research, and epidemiologic studies.

Pulmonary hemorrhage and immune-complex deposition in the lung. Complications in a patient with systemic lupus erythematosus.

A patient with systemic lupus erythematosus (LE) was admitted with an acute illness characterized by dyspnea, hemoptysis, fever, and diffuse infiltrates revealed by chest roentgenograms. An open-lung biopsy specimen showed massive intrapulmonary hemorrhage, and immunofluorescence and electron microscopic examinations showed granular deposits of IgG within the alveolar walls and pulmonary vessels. Rare, widely scattered foci of infiltration of vessel and alveolar walls by polymorphonuclear leukocytes were also observed. The patient was treated with large doses of prednisone and her condition improved, but she had a second episode of massive hemorrhage eight days after discharge despite maintenance of the prednisone therapy. Her condition again improved over several days, and she has had no pulmonary symptoms for nine months. In some instances, pulmonary hemorrhage in patients with systemic LE may be mediated by polymorphonuclear leukocytes attracted by immune-complex deposits.