A 36-year-old lifetime non-smoker obese man with no history of smoking was referred to our office due to a 9-year history of progressive exertional dyspnea and yellow productive cough accompanied by occasional hemoptysis. He reported being able to climb two flights of stairs before becoming dyspneic. His medical history was significant for childhood asthma, hypertension, and impaired glucose tolerance. Outpatient medications included Lisinopril 10 mg daily orally. He works as a security guard in a hospital five days per week and is relatively high functioning. He denied any workplace exposure or alcohol consumption. He migrated from Cuba at the age of seven. And there was no relevant family history.
Vital signs and physical exam were unremarkable. Initial chest radiograph (Fig. 1) showed innumerable pulmonary nodules in both lungs, up to 4 mm in greatest dimension, predominantly involving the middle to lower lung fields. Findings were concerning for miliary tuberculosis (TB) given a history of positive purified protein derivative (PPD) skin test, which might also be attributed to Bacille Calmette-Guerin (BCG) vaccination during childhood. High-Resolution Computed Tomography (HRCT) (Fig. 2, Fig. 3) showed innumerable pulmonary nodules scattered throughout the lungs and along the broncho-vascular bundles measuring 2-5 mm. Differential diagnosis included miliary TB, granulomatous diseases, pneumoconiosis, certain deposition diseases (such as amyloidosis), or alveolar microlithiasis in the appropriate clinical setting. The findings also were suggestive of dystrophic calcifications in the setting of scarring from prior infection/inflammation. A presumptive diagnosis of pulmonary alveolar microlithiasis (PAM) was at this time presumed, given radiographic progression and clinically indolent presentation. Pulmonary function tests (PFT) revealed a total lung capacity (TLC) of 5.37 L (89% predicted), forced vital capacity (FVC) 3.57 L (87% predicted [normal >=80%]), forced expiratory volume in 1 second (FEV1) 3.19 L (94% predicted [normal >=80%]), FEV1/FVC 90% (normal >=70%), diffusing capacity for carbon monoxide (DLCO) 69% (normal >=70%). In summary, normal lung volumes and a mild isolated decrease in DLCO was found.
Bronchoscopy, bronchoalveolar lavage, and transbronchial lung biopsy revealed no abnormalities. The Quantiferon TB test was negative, ruling our active or miliary TB. Histoplasma antibody test was also negative. Genetic testing for SLC34A2 mutation was negative, lowering suspicion for PAM. The patient subsequently underwent a right video assisted thoracoscopic surgery (VATS) (Fig. 4) and segmentectomy of the basilar segment of the right lower lobe, the medial segment of the right middle lobe, and the anterior segment of the right upper lobe without any complications.
Upon gross examination, palpation of the specimen revealed multiple firm sub-pleural nodules. Sectioning through the specimen revealed innumerable calcified nodules. Microscopically (Fig. 5, Fig. 6), diffuse ramifying spicules of mature woven bone arranged in a serpentine fashion along the alveolar septa associated with fatty bone marrow were identified, confirming the diagnosis of DPO. Although bone marrow was present, extensive sampling failed to reveal hematopoiesis. Of note, there was no evidence of significant underlying pathologic findings, such as interstitial fibrosis, granulomas, organizing pneumonia, or significant inflammation in the background lung parenchyma.