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Sarcoidosis of the Upper Lung Fields Simulating Pulmonary Tuberculosis Alvin S. Teirstein, M.D., F.C.C.P." and Louis E. Siltzbach, M.D., F.C.C.P."" Fifty-four of 616 patients (9 percent) with sarcoidosis exhibited upper lung field radiographic abnormalities, which mimicked adult tuberculosis. Difficulty in diagnosis occurred when patients presented with residual upper zonal shadows, which had persisted after clearing of lower and midzooal densities. The abnormal- ities of sarcoidosis appeared as streaks and nodules simulating acinonodose tu- berculosis. Contraction of the upper zones with retraction of the mediastinal structures may be just as prominent as in fibrotic tuberculosis. Bube can some- times be mistaken for tuberculous cavities, and small multiple radiolucencies may be mistaken for tuberculous bronchiectasii Awareness that upper zonal sarcoidosis rewesents a residual manifestation of the more usual att tern of hilar adenopathy a;ld diffuse lower and midzonal infiltrations, aids in dkkngnishing this radiographic pattern from that of adult tuberculosis. Obtaining a radiograph dating back tian earlier stage can be crucial in making this differentiation. when confronted with upper lung field abnormalities, the diagnosis of sarcoidosis as well as tuberculosis should come to mind and appropriate clinical support should be sought. he radiographic patterns of pulmonary sarcoido- Tsis when localized to the upper lung zones may closely mimic the typical appearance of pulmonary tuberculosis, often leading to confusion in diagnosis. Symmetrical bilateral hilar and right paratracheal lymphadenopathy is recognized as the hallmark of early intrathoracic sarcoidosis ( stage 1 ).I Later, in approximately one half of the patients, pulmonary mottling appears and may assume either a micro- nodular, reticular or confluent patchy configuration (stage 2). These radiographic shadows may be diffusely distributed or they may be localized. Final- ly, in the third stage, the enlarged mediastinal lymph nodes regress and only the pulmonary components of intrathoracic involvement may remain2 When in the third stage, residual parenchymal infiltrations are predominantly localized to the upper lung zones, 'Associate Clinical Professor of Medicine, The Mount Sinai School of Medicine, New York. "Clinical Professor of Medicine, The Mount Sinai School of Medicine, New York. The work was supported by USPHS, National Heart and Lung Institute Grant No. HL 13853, and The Sadie and Louis Elow Foundation. Manuscript received December 21, 1972; revision accepted March 28. 1973. Reprint requests: Dr. Teirstein, 70 East 90th Street, New York City 10028 CHEST, VOL. 64, NO. 3, SEPTEMBER, 1973 they may easily be confused radiographically with the lesions of pulmonary tuberculosis, especially when earlier radiographs have not as yet become available. Among 616 patients with a tissue-con- firmed diagnosis of sarcoidosis observed at the Mount Sinai Hospital, New York, we found 54 pa- tients (9 percent ) whose radiographs disclosed such pulmonary densities in the upper zones without the accompanying tell-tale hilar adenopathy. All 54 subjects had histologic findings compatible with sarcoidosis on organ biopsy or a positive Kveim test reaction or both. Tuberculin skin testing was carried through the second-strength purified protein derivative (PPD) (250 TU [tuberculin units] ) or to 1.0 mg of old tuberculin ( OT) ( 100 TU). Cultures of sputa and gastric contents for acid-fast bacilli were perfonned as required and all proved to be sterile. Other studies included determinations of serum pro- tein, calcium, phosphorus, and alkaline phosphatase levels as well as slit lamp examination of the eyes. Radiologic views of the bones of the hands and feet were performed, mainly in patients with chronic cutaneous sarcoidosis. Obseruations There were three fairly distinct radiogra'phic patterns of upper zone localization of sarcoidosis, each of which simn- Downloaded From: http://publications.chestnet.org/ on 01/07/2013 TEIRSTEIN, SILTZBACH FIGURE la. Chest radiograph of 31-year-old white woman demonstrating bilateral upper zonal linear densities simulating shadows of pulmonary tuberculosis. lated those of pulmonary tuberculosis: (1) unilateral or bilateral micronodular, patchy or linear densities occupying the apical and subapical region of the upper lobes (30 patients); (2) opacification with shrinkage of the upper lobes, often with considerable upward retraction of the lung roots and deviation of the trachea to the more affected side (five patients ); and ( 3) small or large radiolucent areas in the upper zones, with thin walls, but occasionally with fairly thick margins (19 patients). Most of these patients also showed upward retraction of the lung roots. Micronodular and Linear Densities (30 Patients) The micronodular densities of sarcoidosis may assume a unilateral or bilateral upper zonal pattern reminiscent of acinonodose tuberculosis. Figure la is the chest radiograph of a 31-year-old white woman which shows bilateral upper lobe streaks. Six years preuiously, the chest radiograph of the same patient shown in Figure lb displayed disseminated nodules throughout both lungs accompanied by enlarged mediastinal lymph nodes. It was then readily recognized as pulmonary sarcoidosis (stage 2). At that time, the pulmonary nodulation was even more prominent in the midzones than in the upper zones, and continued to grow in prominence over the next year. Tuber- culin skin tests remained negative throughout her course. Cultures of gastric contents were negative, a liver biopsy revealed noncaseating epithelioid granulomas and the Kveim test reaction was positive. As Figure la shows, the midlung lesions cleared over the next five years, but the residual upper zone densities persisted and, in the absence of prior radiographs, one could readily have considered these den- sities to be tuberculous foci. In this instance, the upper zonal densities of sarcoidosis represented residual shadows of diffusely disseminated lung granulomas initially involving all of the lung zones. While lower zonal shadows underwent resolution, the lesions in the upper zones persisted. Localized upper zonal densities in pulmonary sarcoidosis evolve most commonly in this fashion. Another example of micronodular and linear densities in the upper zones is illustrated by the radiograph of a patient with sarcoidosis, whom we could obse~e with multiple chest radiographs over a two-year period. In this instance, the pul- FIGURE lb. Chest radiograph of same patient six years earlier, showing widened mediastinum and diffuse bilateral nodular and linear densities throughout all lung zones, consistent with radiographic stage 2 sarcoidosis. FIGURE 20. Chest radiograph of 24year-old Negro woman with bilateral upper zonal nodular and linear densities, with confluence of shadows in right upper zone suggesting tuber- culosis. CHEST, VOL. 64, NO. 3, SEPTEMBER, 1973 Downloaded From: http://publications.chestnet.org/ on 01/07/2013 SARCOlDOSlS SIMULATING PULMONARY TUBERCULOSIS FIGURE 2b. Chest radiograph of same patient 21 months earlier demonstrating pattern of radiographic stage 1 sarcoi- dosis. monary mottling was confined solely to the upper zones, while the lower and midzonal areas remained clear through- out the course. Figure 2a is the chest x-ray film of a 24-year-old Negro woman which reveals streaky and nodular densities in the subapical portions of both upper lobes, more extensive on the right than on the left. On the basis of this film alone, the likeliest diagnosis would be pulmonary tuberculosis. Twenty- one months earlier (Fig 2b), the chest x-ray film of the same patient had revealed the classic pattern of sarcoidosis, ie, bilateral hilar and right paratracheal lymph node enlarge- ment with clear lung fields. Tuberculin skin tests were negative, gastric aspirates failed to grow tubercle bacilli, and the Kveim test reaction was microscopically positive. Opacification with Shrinkage of the Upper Zones (Fiue Patients) In the second pattern of upper zonal sarcoidosis, the chest radiograph may assume, after several years' duration, an appearance of densely fibrotic pulmonary tuberculosis, with areas of opacification and retraction upwards of the hilar structures, with deviation of the trachea to the more affected side. Figure 3a is the chest radiograph of a 49-year-old Puerto Rican-born woman which reveals such shrinkage and opacificati?n of the right upper lobe, with deviation of the mediastinum and retraction upwards of the right lung root. This radiologic appearance might be regarded as typical of chronic fibroid tuberculosis. However, a chest film made six years earlier (Fig 3b) exhibited normally placed mediastinal structures with mid- and lower zonal pulmonary nodulation, a distribution of x-ray shadows more characteristic of sarcoido- sis. The tuberculin skin tests were persistently negative, repeated gastric aspirates failed to grow acid-fast bacilli and the Kveim test reaction was positive. Small and Large Radiolucencies in the Upper Zones (19 Patients) The scarring of late pulmonary sarcoidosis is accompanied FIGURE 3a. Chest radiograph of 49-year-old Puerto Rican-born woman showing shrunken right upper lung zone with devia- tion of trachea and upward retraction of lung root, which prompted radiologic diagnosis of tuberculosis. by the formation of bullae of varying size. Sometimes these bullae may attain giant proportions. Since these lucencies are most often located in the upper zones, they mimic tubercu- lous cavities and associated bronchiectasis.s.4 Confusion between the bullous transformation in the upper zones seen in end-stage pulmonary sarcoidosis ( Fig 4) and giant tuberculous cavities led to the unnecessary codnement of a 34-year-old Negro woman in a tuberculosis sanatorium for five years. Although the tuberculin skin test was positive to 10 TU, repeated cultures of sputa and gastric contents for I d FZGURE 3b. Chest radiograph of same patient six years earlier showing normally placed trachea and lung root with bilateral mid- and lower zone nodulations and hilar node enlargement consistent with sarcoidosis. CHEST, VOL. 64, NO. 3, SEPTEMBER, 1973 Downloaded From: http://publications.chestnet.org/ on 01/07/2013 TEIRSTEIN, SILTZBACH FIGURE 4. Chest radiograph of 34-year-old Negro woman demonstrating bilateral apical lucencies, broad densities in both midzones and basilar nodules, &st thought to be cavi- tary pulmonary tuberculosis. Skin biopsy, positive Kveim test reaction and later postmortem examination established diagnosis of sarcoidosis. tubercle bacilli failed to reveal any organisms. Biopsy of a facial skin lesion demonstrated noncaseating epithelioid cell granulomas without acid-fast bacilli and a positive Kveim test reaction finally established the diagnosis of sarcoidosis. Since patients with extensive pulmonary fibrosis and large bullae usually suffer from markedly impaired pulmonary function, it was not surprising that this patient succumbed to cardiopulmonary failure. At autopsy, the diagnosis of dissem- inated sarcoidosis was con6rnyd and no evidence of tuber- culosis was found. Sometimes the lucencies in the upper zones in pulmonary sarcoidosis are small and assume a honeycombed pattern which also may be confused with posttuberculosis bronchiec task when previous chest x-ray films are not readily available. FIGURE 5u. Chest radiograph of 38-year-old Negro woman showing bilateral upper lobe honeycombing, which mimicked tuberculous bronchiectasis. FIGURE 5b. Chest radiograph of same patient three and one- half years earlier revealing linear densities and lucencies throughout all lung zones conforming to stage 3 sarcoidosis. The chest roentgenograph of a 38-year-old Negro woman (Fig 5u) demonstrates such multiple small lucencies within areas of fibrosis in the upper lobes. However, a series of roentgenographs beginning three and one half years earlier (Fig 5b) was later obtained and on the first film showed infiltrations in all lung zones. In the interval, clearing of infiltrates occurred from below upward, a pattern consistent with the behavior of lesions in sarcoidosis. The patient had negative tuberculin skin tests and sterile gastric cultures for tubercle bacilli. The Kveim test reaction was positive. Hy- percalcemia and hypercalciuria were also present. With mr- ticosteroids and no added antituberculosis drug therapy, the clinical and radiologic manifestations of sarcoidosis improved. In the 6nal example, another diagnostic problem was FIGURE 6. Chest radiograph of 27-year-old Negro woman, with known sarcoidosis. Bilateral upper zonal linear densities and positive tuberculin test gave rise to question of super- imposed tuberculosis. Negative cultures for tubercle bacilli, clearing of densities concomitant with sarcoid skin lesions while receiving adrenocorticosteroid and no antituberculous therapy, and lung biopsy con6rmed only sarcoidosis. CHEST, VOL. 64, NO. 3, SEPTEMBER, 1973 Downloaded From: http://publications.chestnet.org/ on 01/07/2013 TEIRSTEIN, SILTZBACH 10 James DG, Pepys J: Tuberculin in aqueous and oily solutions: Skin test reactions in normal subjects and in patients with sarcoidosis. Lancet 1:602-804, 1956 11 Chusid EL, Shah R, Siltzbach LE: Tuberculin sensitivity in sarcoidosis: Fifth International Conference on Sar- coidosis, ( Levinsky L, Macholda F, eds ) : Karlova, Praha Univ Press, 1971, pp 139-143 12 Lofgren S: Erythema nodosum: Studies on etiology and pathogenesis in 185 adult cases. Acta Med Scand ( Suppl. ) 174: 1-197, 1964 13 James DG: Erythema nodosum: Br Med J 1:853-857, 1961 14 Teirstein AS, Siltzbach LE: Sarcoidosis with accurately dated onset: A study of 100 patients with initial erythema nodosum: Sixth International Conference on Sarcoidosis, Tokyo, 1972, in press Australia's Aborigines Scientists are certain that the Aborigines were origi- nally immigrants who came from southeast Asia through Indonesia to Australia's northern coasts possibly 20,000 years ago. One can find Aborigines in the south who are extremely hairy-men with chest and body hair nine inches long, women with very apparent facial hair- while others in the Great Victorian Desert have copper- colored skin, prominent brow ridges and sloping fore- heads. Some Aborigines in the north are taller, heavier and bigger-boned than the thin and wiry people who inhabit the borders of the Northern Territory and West- ern Australia. Except for their dark-brown eyes and chocolate color, they are almost European in appear- ance. In western Arnhem Land, in the north, you can find people less than five feet tall, some small boned and delicately shaped, others thickset and squat. In the Alice Springs area, there are children who are blond. Cultural- ly the Australian Aborigines have traditions which bind them together. But here again the diversity of styles and attitudes, implements and art forms defies generaliza- tion. There was no common language to unite the Ah- origines before the European arrived. It has been esti- mated that anyone who wished to speak to all Aborigines in Australia (before English began to serve as a lingua franca) would have needed to acquire fluency in about 150 separate languages, comprising more than 600 dialects. Cotlow, L: The Twilight of the Primitive, New York, hlacmillan, 1971 CHEST, VOL. 64, NO. 3, SEPTEMBER, 1973 Downloaded From: http://publications.chestnet.org/ on 01/07/2013 TEIRSTEIN, SILTZBACH 10 James DG, Pepys J: Tuberculin in aqueous and oily solutions: Skin test reactions in normal subjects and in patients with sarcoidosis. Lancet 1:602-804, 1956 11 Chusid EL, Shah R, Siltzbach LE: Tuberculin sensitivity in sarcoidosis: Fifth International Conference on Sar- coidosis, ( Levinsky L, Macholda F, eds ) : Karlova, Praha Univ Press, 1971, pp 139-143 12 Lofgren S: Erythema nodosum: Studies on etiology and pathogenesis in 185 adult cases. Acta Med Scand ( Suppl. ) 174: 1-197, 1964 13 James DG: Erythema nodosum: Br Med J 1:853-857, 1961 14 Teirstein AS, Siltzbach LE: Sarcoidosis with accurately dated onset: A study of 100 patients with initial erythema nodosum: Sixth International Conference on Sarcoidosis, Tokyo, 1972, in press Australia's Aborigines Scientists are certain that the Aborigines were origi- nally immigrants who came from southeast Asia through Indonesia to Australia's northern coasts possibly 20,000 years ago. One can find Aborigines in the south who are extremely hairy-men with chest and body hair nine inches long, women with very apparent facial hair- while others in the Great Victorian Desert have copper- colored skin, prominent brow ridges and sloping fore- heads. Some Aborigines in the north are taller, heavier and bigger-boned than the thin and wiry people who inhabit the borders of the Northern Territory and West- ern Australia. Except for their dark-brown eyes and chocolate color, they are almost European in appear- ance. In western Arnhem Land, in the north, you can find people less than five feet tall, some small boned and delicately shaped, others thickset and squat. In the Alice Springs area, there are children who are blond. Cultural- ly the Australian Aborigines have traditions which bind them together. But here again the diversity of styles and attitudes, implements and art forms defies generaliza- tion. There was no common language to unite the Ah- origines before the European arrived. It has been esti- mated that anyone who wished to speak to all Aborigines in Australia (before English began to serve as a lingua franca) would have needed to acquire fluency in about 150 separate languages, comprising more than 600 dialects. Cotlow, L: The Twilight of the Primitive, New York, hlacmillan, 1971 CHEST, VOL. 64, NO. 3, SEPTEMBER, 1973 Downloaded From: http://publications.chestnet.org/ on 01/07/2013 . occupying the apical and subapical region of the upper lobes (30 patients); (2) opacification with shrinkage of the upper lobes, often with considerable upward retraction of the lung roots. Sarcoidosis of the Upper Lung Fields Simulating Pulmonary Tuberculosis Alvin S. Teirstein, M.D., F.C.C.P." and Louis E. Siltzbach, M.D., F.C.C.P."" Fifty-four of. densities in the subapical portions of both upper lobes, more extensive on the right than on the left. On the basis of this film alone, the likeliest diagnosis would be pulmonary tuberculosis.

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