Pulmonary Alveolar Microlithiasis (PAM) is characterized by deposition of calcium phosphate within the alveolar airspaces (calcospherites).
PAM was first described by Marcello Malpighi (1628-1694), an Italian scientist and physician, in 1686, but its histopathology was first carefully described by F. Harbitz in 1918. The disease was named “Microlithiasis Alveolaris Pulmonum” by the Hungarian pathologist L. Puhr in 1933.
Over 1200 patients with this disorder have been reported worldwide.
Most likely to be autosomal recessive disorder with high rate of familial occurrence (>50%) but without clear gender predilection. There is a higher incidence in Turkey, India, Japan, and Italy.
Mechanism or cause unknown. At least 30 different mutations have been described in the SLC34A2 gene mapped on 4p15. It encodes a sodium-phosphate co-transporter called Npt2b. In the absence of Npt2b activity, phosphate levels likely rise in the alveolar lining fluid and form complexes with calcium, resulting in the formation of lamellated microliths. Microliths or calcospherites are intraalveolar and interstitial deposits of calcified granules with a diameter of 0.05 to 3.0 mm, consisting of laminated calcium and phosphate complexes in a ratio similar to hydroxyapatite in bone. Groups of multinucleated osteoclast-like macrophages surround the microliths, which are sometimes completely embedded in woven bone or lamellar structured bone containing osteocytes. Apoptotic bodies can be found in the nuclear chromatin and cytoplasm of modified Type II alveolar pneumocytes. Microliths seem to act like autologous osteoconductive material when implanted in pulmonary parenchyma and serve as a substrate on which bone can easily be formed. PAM has also been described in association with mitral stenosis; however, the microliths are more uneven and bosselated. Interstitial pulmonary fibrosis is common and pulmonary arterial hypertension may develop.
The radiographic appearance with apical bullae and diffuse micronodular shadows (representing multiple minute calcifications located in the alveoli) is pathognomonic and results in a “sandstorm” or “snowstorm” picture in the chest radiograph. Most of the lesions occur in the posterior part of the lung bases. Heart border and diaphragm often appear obliterated. Bronchoalveolar lavage, transbronchial or open lung biopsy, or sputum analysis are used to confirm the diagnosis. The discrepancy between impressive radiological findings and the lack of clinical symptoms can be striking. At autopsy the lungs are enlarged, heavy, and nonbuoyant.
Children with the disease are usually asymptomatic or present either with chronic cough or gradually decreasing exercise tolerance. The physical examination is usually unremarkable. The disease has already been described in premature twins; however, the reduction in pulmonary function usually starts in adulthood and progresses until death results from pulmonary failure in early or mid-adult life. Hitherto, no effective therapy ...