Case Reports

Pulmonary Alveolar Proteinosis: Report of Four Cases

中華放射醫誌　Chin J Radiol 1999；24(6)：243-247

Chien-Yi Lin　Chin-Yin Sheu　Pei-Jan Chen1

Department of Radiology and Internal Medicine1, Mackay Memorial Hospital, Taipei Taiwan

ABSTRACT

Pulmonary alveolar proteinosis (PAP) is an uncommon disease of the lung. Clinical manifestations and imaging findings of 4 cases of PAP are reviewed: 3 primary and 1 secondary. Clinical symptoms are usually nonspecific and long term. Characteristic imaging findings are of an alveolar consolidation process involving different areas at different times. The condition is commonly misdiagnosed as pneumonia. Bronchoalveolar lavage is the best treatment up to now. PAP should be considered first in patients with characteristic imaging findings whose clinical symptoms are usually long term and nonspecific and too mild when correlated with imaging findings.

Key words: Proteinosis; Lung, Consolidation; Lung, lavage

INTRODUCTION

Pulmonary alveolar proteinosis (PAP) is a rare condition characterized by the accumulation of surfactant-derived phospholipoproteinaceous material in alveolar spaces. Such accumulation leads to an elevated shunt fraction and respiratory failure. PAP may occur in an idiopathic form with no identifiable cause (primary PAP) or may be associated with other diseases, such as dust inhalation, pulmonary infection, or immunocompromised status (secondary PAP). [1] We describe the imaging findings of 4 cases of PAP, 3 primary and 1 secondary, in order to consider findings that may aid in early diagnosis.

CASE REPORT

Case 1 　A 38-year-old male mechanic with a smoking history (1PPD for many years) suffered from intermittent cough and chest pain for more than 10 years. He had been treated for pulmonary tuberculosis (TB), bronchiectasis, and pneumoconiosis in vain. The patient had been admitted twice previously due to exacerbation of the above symptoms. 　Physical examination revealed an increased respiratory effort and moist rales over the entire lung field. Prominent clubbing of the fingers was also noted. 　Posterior-anterior (PA) chest films showed confluent patchy consolidation and ill-defined nodular densities in both lung fields. The alveolar pattern remained essentially unchanged from 1982 to 1988, but the involved lung areas varied over time (Fig. 1A and 1B). 1a 1b Fig 1. a. Chest plain film: multiple ill-defined patchy consolidations and nodular opacities in both lungs especially the perihilar region due to alveolar proteinosis.b. Chest plain film of the same patient: multiple ill-defined patchy consolidation and nodular opacities mainly on right lower and left upper lung fields due to alveolar proteinosis. 　Chest CT scan demonstrated multiple patchy areas of alveolar consolidation with air bronchograms in both lung fields. (Fig. 2) No tumor growth or mediastinal lymphadenopathy was noted. 　Pulmonary function tests showed a moderate restrictive lung defect and a severe decrease in diffusion capacity on the second admission, and a mild obstructive lung and moderate restrictive lung defect on the third admission. Fig 2. Chest CT scan (WL: -500 WW: 1150): multiple individual and confluent alveolar consolidation in geographic distribution with air bronchogram in bilateral lung fields due to air space filling by proteinaceous material 　Laboratory data on the third admission revealed a white blood cell count of 12900/mm with 71% segmented cells, 2% eosinophils, 9% monocytes, and 17% lymphocytes. Blood chemistries including serum LDH (lactic dehydrogenase) were within normal limits. Sputum cytology and culture for AFB (acid- fast bacillus) were negative. 　PAP was diagnosed by transbronchial biopsy with the presence of PAS (periodic acid-Schiff)-stain-positive infiltrates within the alveolar space (Fig. 3). He received right and left lung bronchoalveolar lavage respectively that resulted in some clinical improvement. Fig 3. Pathology finding (400x): alveolar space filled by PAS-stain-positive material. Case 2 　A 37-year-old male with a smoking history (1PPD for 20 years) suffered from intermittent fever and chills for 3 years. Productive cough with yellow sputum for more than 10 years and occasional hemoptysis were noted. TB, pneumonia, and bronchiectasis with secondary infection were suspected previously, and anti-TB drugs and antibiotics had been prescribed but without effect. 　The patient complained of inspiratory chest pain on admission, and physical examination revealed bilateral mild crackles on auscultation. 　PA chest films showed a large ill-defined patchy alveolar consolidation in the left middle lung field; the right lung field was clear. (Fig. 4) Fig 4. Chest plain film: a large ill-defined patchy alveolar consolidation on the left middle lung field caused by alveolar proteinosis. 　HRCT scan demonstrated alveolar consolidation, ground-glass infiltration, and some septal thickening in both lungs. (Fig. 5A and 5B) 5a 5b Fig 5. a. HRCT scan (WL: -600 WW: 1000): alveolar consolidation, ground-glass infiltrates, and some septal thickening in bilateral lung fields suggesting alveolar proteinosis.b. Magnified HRCT scans: thickened intralobular and interlobular septa creating many polygons with so-called " crazy paving" appearance. 　Pulmonary function tests showed a mild decrease in diffusion capacity. 　Laboratory data showed a white blood cell count of 7000/mm with 77.4% segmented cells, 1.4% eosinophils, 0.4% basophils, 4.1% monocytes, and 20.7% lymphocytes. The LDH isoenzymes showed 14.4% LDH1, 33.3% LDH2, 25.1% LDH3, 13.2% LDH4, and 14.0% LDH5. 　Transbronchial biopsy was performed. Pathology demonstrated alveolar spaces diffusely replaced by eosinophilic granular material strongly stained by PAS, which was consistent with PAP. 　Right and left lung bronchoalveolar lavages were performed respectively after diagnostic wedge resection of the left lower lobe. The patient responded well to the treatment. Case 3 　A 50-year-old male with a smoking history (1PPD for 10 years) complained of cough with sputum for 3 months, as well as shortness of breath, fever, and left lower chest pain. The diagnostic impression on admission was diffuse pneumonitis. 　Physical examination revealed bilateral coarse breath sounds, and no other abnormal findings were noted. 　PA chest films showed extensive alveolar consolidation in both lower lung fields (Fig. 6). Fig 6. Chest plain film: extensive alveolar consolidation in bilateral lower lung fields. 　Chest CT scan showed multifocal alveolar consolidation indicating an air-space filling process (Fig. 7). Fig 7. Chest CT scan (WL: -425 WW: 1044): alveolar consolidation and air bronchogram in bilateral lung fields indicating an air-space filling process by proteinaceous material 　Laboratory data revealed a white blood cell count of 6500/mm with 1% bands, 61% segmented cells, 14% monocytes, and 21% lymphocytes. TB culture was negative. 　The patient then transferred to another hospital where a diagnosis of pulmonary alveolar proteinosis was made by open lung biopsy. Case 4 　A 27-year-old male who had been a sculptor for 10 years complained of dyspnea on exertion for 3 months, along with a productive cough. Orthopnea and paroxysmal nocturnal dyspnea were also found when taking his history. 　Physical examination revealed diffuse rales over both lung fields. 　Laboratory data showed a white blood cell count of 17900/mm with 66% segmented cells, 1% eosinophils, 5% monocytes, and 28% lymphocytes. Culture for TB and serum anti-HIV (human immunodeficiency virus) antibody were negative. Serum LDH was 858 U/L. 　PA chest films showed diffuse nodular and interstitial patterns in bilateral lung fields. Fig 8. Chest CT scan: alveolar consolidation due to both silicosis and proteinosis and septal thickening with honeycombing appearance in bilateral lung and minimal left side pneumothorax. 　Chest CT scan showed minimal pneumothorax in the left upper lung. Multiple ill-defined nodules of different sizes and interstitium thickening with honeycombing appearance were seen in the lung parenchyma (Fig. 8). 　He was transferred to our hospital under the diagnostic impression of silicoproteinosis (secondary PAP).

RESULTS

Table 1 demonstrates the clinical course and imaging patterns of our patients. All of our patients had vague symptoms that initially led to other diagnoses such as bronchiectasis or other lung infection. Even though characteristic findings can be seen on plain film and chest CT scan, early diagnosis is still difficult due to the nonspecific symptoms and the rarity of this disease.

DISCUSSION

The clinical syndrome of PAP was first described in 1958 by Rosen et al. as "a remarkable disease of the lung that consists of the filling of the alveoli by a PAS stain positive material". [1, 2] 　The etiology of primary PAP is unknown. The accumulation in alveolar spaces is probably caused by defective clearance of lipoproteinaceous material by alveolar macrophages. [4, 5] Recent animal experiments have suggested that GM-CSF (granulocyte-macrophage colony stimulating factor) deficiency might play a role in the pathogenesis. 　Secondary PAP could be associated with 3 main clinical settings: <1> Infection of the lung, most commonly with Norcardia astroides, TB, Mycobacterium avium-intracellulare, or Pneumocystis carinii. <2> Hematologic malignancies and other conditions that alter the patient's immune status, e.g., lymphoma, leukemia, or AIDS; and <3> Exposure to inhaled chemicals and minerals, e.g., fumes, dusts, silica, aluminum, insecticides, or titanium leading to type II pneumocyte destruction. [1, 2] The material filling alveolar spaces in secondary PAP is mainly cell debris and fibrin. [3] 　Clinical symptoms are usually nonspecific. Shortness of breath and dyspnea on exertion are most common. Coughs, fever, weight loss, clubbing of fingers, hemoptysis, and pleuritic chest pain have also been reported. [1, 3, 4] 　Typical plain film findings are of bilateral air-space disease of an ill-defined nodular or confluent pattern with a bat-wing distribution simulating severe pulmonary edema but with a normal heart size. [1, 4-6] An interstitial pattern is occasionally seen. 　Characteristic CT findings are of an alveolar pattern with varying distribution mimicking geographic patterns. An interstitial pattern is sometimes seen and is caused by septal edema rather than fibrosis. However, this appearance requires differentiation from pulmonary fibrosis due to various causes. [3] 　HRCT shows opacification with a ground-glass appearance, indicating alveolar space filling; reticular-interstitial opacities with variously diffuse, patchy, central, or perihilar distributions are also seen. Intralobular and interlobular septal thickening contribute to a polygonal appearance called "crazy paving". [3, 6] 　CT and HRCT findings can sometimes be so characteristic that they strongly suggest the diagnosis, but PCP (Pneumocystis carinii pneumonia) and sarcoidosis may yield similar air-space and interstitial patterns. Correlation with clinical symptoms is necessary for accurate diagnosis. [1, 3] 　There is typically an elevated serum LDH. Increased surfactant protein A and D ions are found in bronchopulmonary lavage. [1] Abnormal laboratory data could be a less invasive diagnostic modality. 　Common differential diagnoses by plain film include pulmonary edema, pneumonia, toxic gas or liquid inhalation, pulmonary hemorrhage due to various causes, and malignancies such as bronchioalveolar carcinoma, malignant lymphoma, and lymphangitis carcinomatosis, but HRCT provides more details for making a correct diagnosis. 　Bronchoalveolar lavage remains the best treatment of PAP currently available even though bone marrow transplantation and lung transplantation have been suggested. [4, 7] Bone marrow transplantation still needs more experimentation, and recurrence after lung transplantation has been reported. [4] The device for bronchoalveolar lavage is demonstrated in Fig. 9. Bronchoalveolar lavage fluid is shown in Fig. 10. Lavage fluid, i.e., saline clears alveolar spaces by entering the air spaces and physically loosening viscous proteinaceous fluid. The mobilized material then drains out of the lung along with saline and forms precipitates seen within the bottle. [8] The amount of precipitate decreases from the first bottle to the last (Fig. 10). Fig 9. Technique for providing unilateral bronchoalveolar lavage. Fig 10. Fluid drained out from bronchoalveolar lavage: the precipitates decreasing from first to last bottle. 　Chest plain film and CT correlate well with bronchoalveolar lavage and clinical symptoms and can be used to evaluate patients' condition before, during and after lavage. [8] 　In conclusion, PAP is an uncommon disease, and patients usually have nonspecific complaints over a long time. Serial chest plain films show alveolar consolidation with shifting areas of involvement. Bronchiectasis with secondary infection is often an initial consideration, but patients seem to have clinical-radiographic dissociation, i.e., remarkable imaging in the face of relatively mild symptoms. Characteristic imaging findings on HRCT scan associated with clinical symptoms will offer sufficient information for an early and correct diagnosis of PAP.

REFERENCES

Bennet M.W., Eric J.S,, Rodney A.S., David J.P.(1997) Diagnosing pulmonary alveolar proteinosis A review and update. Chest 111: 460-466 Gacouin A., Le Tulzo Y., Suprin E., et al. (1998) Acute respiratory failure caused by secondary alveolar proteinosis in a patient with acute myeloid leukemia: a case report. Intensive Care Medicine 24:265-267 Wendy E.Z., Felix S.C. (1993) Pulmonary alveolar proteinosis. Radiologic-pathologic conferences of the Massachusetts General Hospital. AJR 161: 26 Parker L.A., Debra B.N., (1997) Recurrent alveolar proteinosis following double lung transpl antation Chest111: 1457-1458 Godwin J.D., Nestor L.M., Julie E.T. (1998) Pulmonary alveolar proteinosis: CT findings. Radiology 169: 609-613 Lee K., David L.L., Webb W.R., De Bong C., Maria L.S., Jeffery A.G. (1997) Pulmonary alveolar proteinosis high-resolution CT, chest radiographic, and functional correlations. Chest 1997; 111: 989-995 Aengus S.O. (1998) Pulmonary alveolar proteinosis: lung transplant or bone marrow transplant. Chest 113: 563-564 Gale M.E., Joel B.K., Arthur G.R.(1986) Bronchopulmonary lavage in pulmonary alveolar proteinosis: chest radiograph observation. AJR 146: 981-985

肺泡蛋白質沉積症: 4 例案例報告

林倩薏　許清寅　陳培然1

馬偕紀念醫院　放射線科　胸腔內科1

肺泡蛋白質沉積症是一種少見的肺部疾病.本文討論四位患者的臨床症狀及影像發現:其中三例為原發性,一例為續發性.本症臨床症狀多為長時間且不具診斷性,典型影像發現則為肺泡浸潤且時間不同浸潤區域會有所改變,常會誤診為肺炎.最常用之治療方法是氣管肺泡灌沖法.本病於有典型影像發現之患者但症狀長期且輕微與影像無法配合者應優先考慮.

關鍵詞： 蛋白質沉積症，肺，浸潤，肺，灌洗

Received: February 1, 1999　　 Accepted: September 9, 1999 Correspondence to: Dr. Chien-Yi Lin Department of Radiology, Mackay Memorial Hospital, Taipei 104, Taiwan, R.O.C.