Pulmonary alveolar microlithiasis
Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by distinctive fine micronodular intraalveolar calcifications. Most documented cases of PAM occur sporadically, however it can also be inherited in an autosomal recessive pattern. Sporadic cases are more common in males, whereas familial forms are more common in females. Affected individuals often become symptomatic in the third or fourth decade, with chest pain, cough and progressive exertional dyspnea. The disease may stabilize at any time, but more often progresses to respiratory failure and cor pulmonale leading to death. In asymptomatic patients, characteristic chest radiograph findings are detected incidentally as part of an unrelated workup, including bilateral sand-like calcifications with predilection for the lower lobes. High resolution CT scan of the chest can highlight the sub-pleural and peri bronchial distribution of the calcifications. CT scan can also show a "crazy paving" pattern that demonstrates ground-glass opacity with superimposed interlobular septal thickening and intralobular reticular thickening.
The pathogenesis of PAM is associated with mutations in the SLC34A2 gene, which encodes a sodium-dependent phosphate transport protein. Mutation of the gene can lead to protein m
alfunction, resulting in the accumulation of phosphate within the airspaces, which predisposes to the formation of calcium phosphate-based microliths. The diagnosis is often confirmed histologically by needle core biopsy in the context of characteristic imaging findings and a negative metabolic workup. Grossly, lungs affected by PAM are heavy and have a sandy or gritty consistency. The histologic findings include spherical lamellated microcalcifications, ranging in size from 250-750 microns, filling alveolar spaces. The surrounding alveolar septae may also demonstrate fibrosis and ossification. Rarely, microcalcifications may be present in the alveolar septa and bronchial mucosa.
The differential diagnosis includes pulmonary blue bodies, which are smaller, scattered and associated with pneumoconioses; pulmonary corpora amylacea, which are scattered and not calcified, and heterotopic ossification, showing osteocytes in lacunae in an interstitial distribution. Importantly, metastatic calcification is also in the differential diagnosis. Metastatic calcifications present in the lungs as irregular calcifications that can involve the air spaces but can also be seen interstitially and within the bronchial walls. They are most often associated with renal failure and parathyroid carcinoma and review of the medical history and laboratory workup is pertinent.
No effective medial treatment is currently available. Systemic glucocorticoids, bronchoalveolar lavage, and disodium etidronate have only limited utility in the prevention of disease progression. Lung transplantation is the only efficacious option for the treatment of pulmonary alveolar microlithiasis.
Gross images courtesy of Russell Silowash, MD; Microscopic images courtesy of Alison van Dyke, MD, PhD
Contributed by Kate M. Serdy, MD and Sanja Dacic, MD, PhD