Right Middle Lobe Atelectasis Associated with Endobronchial Silicotic Lesions

Original Articles

Right Middle Lobe Atelectasis Associated With Endobronchial Silicotic Lesions

Hsiu-Ping Chien, MD; Tao-Ping Lin, MD; Hsiao-Ling Chen, MD; Thomas W. Huang, MD

● Background.—In a period of 18 months, we have en- been excluded by careful radiographic and computed to- countered 4 cases of right middle lobe atelectasis associ- mographic image analysis. ated with endobronchial silicotic lesions of right middle Results.—The endobronchial silicosis does not appear to lobe bronchi. All patients had occupational exposure to correlate with the degree of pneumoconiosis of the lung parenchyma. The endobronchial silicosis may cause bron- mineral dusts (3 coal miners and 1 sand blaster) for months chial obstruction in the absence of radiographic evidence to decades. of pulmonary silicosis. Methods.—The nature of the endobronchial silicotic le- Conclusion.—The endobronchial silicosis and conse- sions that caused the bronchial obstruction has been con- quent lung atelectasis may be associated with silica expo- ﬁrmed by endobronchial biopsies and energy-dispersive sure. spectrometry of the lesions. Extrinsic compression has (Arch Pathol Lab Med. 2000;124:1619–1622)

he accumulation of mineral dusts in lung parenchyma, The endobronchial biopsy specimens from all 4 cases were T causing pneumoconiosis, is a well-known occupation- fixed in sodium acetate–buffered 10% formalin solution and pro- al hazard. The translocation of mineral dusts through the cessed for paraffin embedding. Four-micrometer sections were tracheobronchial-epithelial barrier into lamina propria of cut and stained with hematoxylin-eosin for light microscopy. For energy-dispersive x-ray microanalysis, multiple 10-␮m-thick sec- the bronchial mucosa has been well documented. Silica tions were obtained from the paraffin block of case 1, collected crystals may accumulate in the bronchial mucosa and in- in a test tube, and deparaffinized with Hemo-De (Fisher Scien- 1–4 duce local pathological alterations. They rarely cause tific, Pittsburgh, Pa). The tissue pellets were obtained by centri- clinically significant disease. We describe 4 cases of right fugation, and Hemo-De was substituted with ethanol followed middle lobe (RML) syndrome associated with obstructive by repeated washing in Tris-buffered saline. The tissues were silicotic nodules of bronchial mucosa. The narrowing and further digested with pronase (Fluka Chemika-Biochemica, obstruction of the RML bronchi were presumably caused Buchs, Switzerland). The residues after pronase digestion were by silicosis of bronchial mucosa. The possibilities of ex- repeatedly washed with double-distilled water. A drop of the sus- trinsic compression by enlarged lymph nodes had been pension of the residues was applied to a stub, air-dried, and car- excluded by careful radiographic and computed tomo- bon coated. The specimens were subjected to element analysis by an energy-dispersive spectrometer (Kevex, level 4). graphic (CT) image analysis. METHODS RESULTS After encountering the first case of RML atelectasis associated Case Studies with obstructive endobronchial silicotic lesions in February 1996, we had seen a total of 4 cases during an 18-month period, from Case 1. A 64-year-old man, a nonsmoker and a coal February 1996 to August 1997. The cases were among those seen miner for more than 30 years, visited our outpatient de- at the Taiwan Provincial Chronic Disease Bureau, an institute es- partment with the chief complaint of productive cough off tablished to care for occupational lung diseases, pulmonary tu- and on for approximately half a year. Chest radiographs berculosis, and other chronic thoracic diseases. showed RML atelectasis with minimal fibrotic change over Chest radiography (both posteroanterior and lateral views), the right upper lung field. Chest CT scan also revealed bronchoscopy with brushing cytologic tests, smears for acid-fast similar features. There was no evidence of lymphadenop- bacilli (AFB), and biopsies were performed on all patients. Spu- athy, which may compress or invade into the RML bron- tum cultures for AFB were also routinely performed. Pneumo- chus (Figure 1). No evidence of pneumoconiosis was not- coniosis of the lung parenchyma was diagnosed and classified ed by CT scan and chest x-ray films according to ILO according to the International Labour Office (ILO) classification of 1980.5 Three patients also received chest CT scans. classification. Bronchoscopy showed near-total occlusion of orifice of RML bronchus, which showed markedly inflamed mucosa with anthracotic pigmentation. Brush cy- Accepted for publication May 10, 2000. tologic test results and acid-fast staining were nonreveal- From the Taiwan Provincial Chronic Disease Control Bureau (Drs ing. The results of 3 consecutive sputum cultures for AFB Chien and Lin) and Taipei Institute of Pathology (Drs Chen and Huang), Wan-Shun-Liau, Shen-Keng Shiang, Taipei County, Taiwan. were also negative. Chest x-ray films showed no signifi- Reprints: Hsiu-Ping Chien, MD, Taiwan Provincial Chronic Disease cant change after 18 months of follow-up. Control Bureau, 67–1, Wan-Shun-Liau, Shen-Keng Shiang, Taipei Case 2. A 76-year-old man, a coal miner for 7 years, County, Taiwan 222. was a former 30-pack-year cigarette smoker. He visited our Arch Pathol Lab Med—Vol 124, November 2000 Atelectasis and Endobronchial Silicosis—Chien et al 1619 Figure 1. Computed tomogram of the chest of case 1 showed right middle lobe atelectasis. The mediastinal nodes were not enlarged, and the evidence of potential external compression was absent. Figure 2. Large collections (indicated by arrows) of anthracotic pigment–laden macrophages in right middle lobe bronchial mucosa of case 1 beneath the basement membrane of respiratory epithelium (arrowheads) (hematoxylin-eosin, original magnification ϫ480). Figure 3. Polarizing microscopy of Figure 2 revealed numerous needle-shaped birefringent crystals in the macrophages (original magnification ϫ135 [a] and ϫ480 [b]).

clinic for regular physical checkups. Chest radiograms re- x-ray films showed no significant change after 9 months vealed atelectasis of RML without hilar lymphadenopathy. of follow-up. The lung field showed category 1 simple pneumoconiosis. Case 3. A 65-year-old man, a coal miner for several Bronchoscopy revealed a total obliteration of RML bron- months, was a former 4-pack-year cigarette smoker who chial orifice, with severely inflamed mucosa and anthra- had productive cough for more than 2 years. Chest radio- cotic pigmentation. Bronchial brush cytologic test results graphs revealed RML partial atelectasis. Chest CT scan and acid-fast staining were nonrevealing. One set of spu- showed RML partial atelectasis without evidence of hilar tum culture for AFB also revealed negative results. Chest lymphadenopathy. No evidence of pneumoconiosis was 1620 Arch Pathol Lab Med—Vol 124, November 2000 Atelectasis and Endobronchial Silicosis—Chien et al Demographic and Clinical Data of Patients* Bronchial Brush Case No./ Cytologic AFB AFB Sex/Age, y Occupation ILO Classes Test Result Smear Culture† 1/M//64 Coal miner Ͼ30 y No pneumoconiosis ϪϪϪ(3) 2/M/76 Coal miner 7 y Category 1 pneumoconiosis ϪϪϪ(1) 3/M/65 Coal miner several months No pneumoconiosis ϪϪϪ(1) 4/M/64 Sand blaster 20 y Category B pneumoconiosis ϪϪϪ(2) * ILO classes indicates International Labour Office lung x-ray classes; AFB smear, bronchial brush acid-fast bacilli smear; AFB culture, sputum acid-fast bacilli culture; minus sign, negative. † Numbers in parentheses indicate the number of patients with this result. noted from image studies. Bronchoscopy with biopsy location of mineral dusts through tracheobronchial epithe- showed near total occlusion of lateral segment of RML lial barrier into the lamina propria of the bronchial mu- bronchus orifice due to elevated mucosa with anthracotic cosa has been observed.1–4 Mineral dusts on the surface of pigmentation. Bronchial brush cytologic test results and the bronchial mucosa can be phagocytized by macrophag- acid-fast staining were nonrevealing. One set of sputum es, which either are expelled by the mucociliary escalator culture for AFB also yielded negative results. The patient or migrate through the epithelial barrier into the bronchial was lost to follow-up thereafter. mucosa. Some of the mineral dusts can directly translocate Case 4. A 64-year-old man, a sand blaster for 20 years, into the bronchial mucosa without the help of macrophag- was a former 15-pack-year cigarette smoker. He had cough es. Even in the absence of dust overload, a certain fraction with exertional dyspnea for 4 years, which worsened in of deposited particles make their way into bronchial mu- recent days. Chest CT scan and plain chest films revealed cosa.6,7 In case of dust overload, a corresponding increase RML and right upper lobe partial atelectasis associated in particle uptake by the bronchial mucosa occurs. The with category B pneumoconiosis of the lung. There was mineral dusts deposited in the bronchial mucosa may pro- no evidence of local lymphadenopathy that may compress voke a local inflammatory reaction with fibrosis.8,9 In our or invade into the bronchi. Bronchoscopy showed stenosis study, microscopic examination of the bronchial mucosa of the orifices of RML bronchus and anterior segment of reveals extensive collections of anthracotic pigment–laden right upper lobe bronchus by inflamed mucosa with an- macrophages in the lamina propria beneath the basement thracotic pigmentation. Bronchial biopsy was performed membrane of the respiratory epithelium. Scattered lym- over the right upper lobe bronchus. Bronchial brush cy- phocytes are intermixed with dust-laden macrophages. Fi- tologic test results and acid-fast staining were nonreveal- brosis is also noted (Figure 2). Under the polarizing mi- ing. The results of 2 sputum cultures for AFB were also croscope, there are numerous needle-shaped birefringent negative. Chest x-ray films showed no significant change crystals of silica-like particles in the macrophages and after 16 months of follow-up. within the cleftlike space between the collagenous stroma The results of clinical studies are summarized in the (Figure 3, a and b). Silicon is the major component of the Table. crystals and is confirmed by energy-dispersive x-ray spectrometry. The nodular collections of dust-laden macro- Histopathology and Energy-Dispersive X-ray phages and fibrosis constitute the physical basis of airway Microanalysis obstruction. The endobronchial silicosis described does Microscopic examination of all 4 cases revealed similar not appear to correlate with the degree of pneumoconiosis histopathological features. The bronchial mucosa had ex- of the lung parenchyma, which is classified according to tensive collections of anthracotic pigment–laden macro- the ILO classification of 1980. Pulmonary pneumoconiosis phages in the lamina propria underneath the basement is not observed in cases 1 and 3. membrane of the respiratory epithelium (Figure 2). Scat- The middle lobe bronchus is a narrow, long structure tered lymphocytic infiltrates were also noted. The polar- surrounded by lymph nodes. It lies at the apex of the lym- izing microscopy showed numerous needle-shaped bire- phatic pathway from both the upper and lower lobes, fringent silica-like crystals in the macrophages and extra- making it particularly vulnerable to impingement by cellular compartments. The lesions were associated with lymphadenopathy. Poor drainage of the middle lobe bron- moderate degree of fibrosis of the lamina propria of the chus, due to its angular takeoff from the intermediate bronchial mucosa (Figure 3, a and b). bronchus and its small luminal diameter, is also vulner- The energy-dispersive x-ray microanalysis demonstrat- able to bronchial obstruction as a result of inflammation ed the silicon was the major component in the indigestible and mucosal edema.10 Besides, ineffective collateral ven- residues of the specimen. The percentages of the elements tilation is another major factor in the pathophysiology of in the residues were as follows: silicon, 53.61%; aluminum, the middle lobe atelectasis.11,12 In case of silicosis, both ex- 15.81%; potassium, 11.12%; iron, 7.30%; phosphorus, ternal compression by lymphadenopathy and endobron- 6.30%; and sulfur, 5.86%. chial obstruction may contribute to RML atelectasis. Three cases of silicosis complicated with RML atelectasis have COMMENT been reported in the Chinese literature.13 The cause of at- The airway surface is an aerodynamic filter that traps electasis is thought to be due to enlargement of silicotic particles of certain size and shape in the airways.6,7 Al- lymph nodes based on image study. A case report14 de- though most mineral dust particles deposited on the air- scribes silicosis leading to tracheobronchial obstruction, way surface are removed by mucociliary escalator, trans- which is owing to calcified mediastinal lymph nodes com- Arch Pathol Lab Med—Vol 124, November 2000 Atelectasis and Endobronchial Silicosis—Chien et al 1621 pression and erosion (broncholithiasis). In the current 2. Lippmann M, Yeates DB, Albert RE. Deposition, retention, and clearance of inhaled particles. Br J Ind Med. 1980;37:337–362. studies, there is no evidence of mediastinal lymphadenop- 3. Sweeney TD, Brain JD. Pulmonary deposition: determinants and measure- athy that compresses or invades into the RML bronchus. ment techniques. Toxicol Pathol. 1991;4:384–397. Therefore, it is reasonable to assume that the local bron- 4. Churg A. The uptake of mineral particles by pulmonary epithelial cells. Am J Respir Crit Care Med. 1996;154:1124–1140. chial silicosis is the primary cause of stenosis and obstruc- 5. International Labour Office. Guidelines for the Use of ILO International tion of the RML bronchi. Classification of Radiographs of Pneumoconioses. Geneva, Switzerland: Interna- Atelectasis of the RML has been known for many years tional Labour Office; 1980. Occupational safety and health series No. 22. 15,16 6. Churg A, Wright JL, Stevens B. Exogenous mineral particles in the human as the middle lobe syndrome. The etiology of middle bronchial mucosa and lung parenchyma, I: nonsmokers in the general population. lobe syndrome in 933 patients collected from 12 reports Exp Lung Res. 1990;16:169–175. has been investigated.4 Benign inflammation (47%), malig- 7. Churg A, Stevens B. Mineral particles in the human bronchial mucosa, II: nant neoplasm (22%), bronchiectasis (15%), and tubercu- cigarette smokers without emphysema. Exp Lung Res. 1992;18:687–714. 8. Morrow PE. Dust overloading of the lung: update and appraisal. Toxicol losis (9%) are the major reasons of the RML syndrome. Appl Pharmacol. 1992;113:1–12. Miscellaneous causes include benign tumors, aspiration, 9. Oberdorster G. Lung particle overload: implications for occupational ex- amyloidosis, sarcoidosis, histoplasmosis, psittacosis, per- posures to particles. Regul Toxicol Pharmacol. 1995;27:123–135. 10. Wanger RB, Johnston MR. Middle lobe syndrome. Ann Thorac Surg. 1983; tussis, cystic fibrosis, bronchographic contrast media, per- 35:679–686. foration of esophagus, and allergic bronchopulmonary as- 11. Inners CR, Terry PB, Traystman RJ, Menkes HA. Collateral ventilation and pergillosis. Silicosis is not included in the literature re- the middle lobe syndrome. Am Rev Respir Dis. 1978;118:305–310. 12. Rosenblum SA, Ravin CE, Putman CE, et al. Peripheral middle lobe syn- viewed. To the best of our knowledge, bronchial silicosis drome. Radiology. 1983;149:17–21. is rarely mentioned to cause RML atelectasis in the En- 13. Xu LY, Yang DN, Shyy JC. Silicosis leading to the development of right glish-language literature.17 middle lobe atelectasis: report of 3 cases. Chin J Prev Med. 1982;16:303–305. 14. Cahill BC, Harmon KR, Shumway SJ, Mickman JK, Hertz MI. Tracheo- The relation among silica exposure and pneumoconio- bronchial obstruction due to silicosis. Am Rev Respir Dis. 1992;145:719–721. sis, pulmonary tuberculosis, lung cancer, obstructive pul- 15. Graham EA, Burford TH, Mayer JH. Middle lobe syndrome. Postgrad Med. monary disease, connective tissue disease, glomerulone- 1948;4:29–34. 16. Lindskog GE, Spear HC. Middle-lobe syndrome. N Engl J Med. 1955;253: phritis, and silicoproteinosis has been well document- 489–495. ed.18,19 Based on our experience, the adverse obstructive 17. Kampalath BN, McMahon JT, Cohen A, Tomashefski JF, Kleinerman J. effect of silica exposure on airways and consequent lung Obliterative central bronchitis due to mineral dust in patients with pneumoconiosis. Arch Pathol Lab Med. 1998;122:56–62. atelectasis may be associated with silica exposure. 18. Silicosis and Silicate Disease Committee. Disease associated with exposure to silica and nonfibrous silicate minerals. Arch Pathol Lab Med. 1988;112: References 673–720. 1. Gerrity TR, Lee PS, Hass FJ. Calculated deposition of inhaled particles in 19. The official statement of the American Thoracic Society: adverse effects of the airway generations of normal subjects. J Appl Physiol. 1979;47:867–873. crystalline silica exposure. Am J Respir Crit Care Med. 1997;155:761–765.

1622 Arch Pathol Lab Med—Vol 124, November 2000 Atelectasis and Endobronchial Silicosis—Chien et al