Correspondence

Pulmonary Alveolar Microlithiasis

N Engl J Med 2002; 347:69-70July 4, 2002

Article

To the Editor:

Pulmonary alveolar microlithiasis is a rare disease of unknown pathogenesis, characterized by widespread laminated calcispherites in alveolar spaces in the absence of any known disorder of calcium metabolism.1 It usually occurs in a sporadic form, but an autosomal recessive form has been described, especially in patients from the Mediterranean countries.2-5 We report on two initially asymptomatic, nonsmoking siblings: a 38-year-old woman and her 41-year-old brother, both of whom were given a diagnosis of pulmonary alveolar microlithiasis. In both patients, chest x-ray films and a computed tomographic scan (Figure 1Figure 1Computed Tomographic Scan of the Chest of a 41-Year-Old Man, Showing Bilateral Calcific, Micronodular Opacities.) showed diffusely scattered, bilateral, micronodular areas of radiopacity of calcific densities throughout the lungs with the classic “sandstorm” pattern.

The sister subsequently had a mild restrictive respiratory defect, but she is still alive and her condition is unchanged after 13 years of follow-up. Her brother's clinical condition worsened rapidly, and he died of respiratory failure 10 years after diagnosis, despite bilateral lung transplantation. The parents of the patients were unaffected. Examination of open-lung–biopsy specimens from both patients revealed intraalveolar and interstitial deposits of concentrically laminated calcified bodies. Numerous macrophages surrounded the microliths, and there was interstitial fibrosis. Microradiology showed microliths (measuring 50 to 750 μm in diameter) that were almost spherical in shape and were sometimes completely surrounded by woven bone or by lamellar structured bone containing typical ellipsoidal osteocytes. In this case, the microliths were highly indented owing to peripheral osteoclastic activity. X-ray microanalysis showed that the microliths consisted of calcium and phosphorus and a small amount of magnesium. The ratio of calcium to phosphorus indicates that the microliths may consist of hydroxyapatite-like material, similar to bone. Ultrastructural examinations showed that groups of multinucleated osteoclast-like macrophages were always present in the areas surrounding the calcified tissue, and many of them displayed shrinkage necrosis. The nuclear chromatin and cytoplasm of modified type II alveolar pneumocytes also included apoptotic bodies. Moreover, this apoptotic activity was confirmed by immunohistochemical expression of BAX protein (Figure 2Figure 2Detected by Immunohistochemical Staining Showing Overexpression of BAX Protein in the Alveolar Macrophages of a 41-Year-Old Man (Rabbit Polyclonal Anti-BAX Protein, ×100).) and bcl-2 protein and by the terminal deoxynucleotidyl transferase–uridine triphosphate nicked-end labeling technique.

On the one hand, our observations appear to support previous suggestions that a genetic trait is involved in a great proportion of patients with pulmonary alveolar microlithiasis. On the other hand, we first would stress that, by promoting the formation of calcified lamellar bodies, apoptosis has a crucial role in the pathogenesis of pulmonary alveolar microlithiasis. Finally, microliths act like autologous osteoconductive material when they are implanted in pulmonary parenchyma and serve as a substrate on which bone is easily formed.

Giuseppe Barbolini, M.D.
Giulio Rossi, M.D.
University of Modena and Reggio Emilia, I-41100 Modena, Italy
rossi.giulio@unimo.it

Alberto Bisetti, M.D.
University La Sapienza, I-00151 Rome, Italy

5 References

1. 1

   Moran CA, Hochholzer L, Hasleton PS, Johnson FB, Koss MN. Pulmonary alveolar microlithiasis: a clinicopathologic and chemical analysis of seven cases. Arch Pathol Lab Med 1997;121:607-611
   Web of Science | Medline

2. 2

   Esguerra Gomez G, Lichtemberger E, Santamaria A, et al. Familial pulmonary alveolar microlithiasis: four cases from Colombia, S.A.: is microlithiasis also an environmental disease? Radiology 1959;72:550-561
   Web of Science | Medline

3. 3

   Mariotta S, Guidi L, Papale M, Ricci A, Bisetti A. Pulmonary alveolar microlithiasis: review of Italian reports. Eur J Epidemiol 1997;13:587-590
   CrossRef | Web of Science | Medline

4. 4

   Senyigit A, Yaramis A, Gurkan F, et al. Pulmonary alveolar microlithiasis: a rare familial inheritance with report of six cases in a family: contribution of six new cases to the number of case reports in Turkey. Respiration 2001;68:204-209
   CrossRef | Web of Science | Medline

5. 5

   Ucan ES, Keyf AI, Aydilek R, et al. Pulmonary alveolar microlithiasis: review of Turkish reports. Thorax 1993;48:171-173
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Guilherme Abdalla, Edson Marchiori, Gláucia Zanetti, Antonio Mucillo, Mariana Leite Pereira, Nina Ventura, Pedro Martins, Carolina Pesce Lamas Constantino, Rodrigo Canellas, Viviane Brandão, Romulo Varella de Oliveira. (2010) Pulmonary Alveolar Microlithiasis: A Case Report with Emphasis on Imaging Findings. Case Reports in Medicine 2010, 1-4
   CrossRef

2. 2

   Anita Tahlan, Amanjit Bal, Harsh Mohan, Varinder Saini, Anirban Deb. (2003) Pulmonary Alveolar Microlithiasis: A Case Report. Clinical Pulmonary Medicine 10:6, 353-354
   CrossRef

3. 3

   (2003) Pulmonary Alveolar Microlithiasis Revisited. New England Journal of Medicine 348:1, 84-85
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