Figures
- FIGURE 1
Radiographic findings in pulmonary alveolar microlithiasis. a) Chest radiograph depicting a fine, sand-like micronodular pattern with basilar predominance. b, c) High-resolution computed tomography with posterior lower lobe and anterior upper lobe micronodules, interlobular septal thickening, subpleural emphysema with predominance of small cysts. d) Mediastinal windows reveal calcific burden in the parenchyma and most concentrated in a peripheral septopleural location.
- FIGURE 2
Pathologic findings in pulmonary alveolar microlithiasis (PAM). a) Lung explant from a 2-year-old boy transplanted for PAM showing lung regions with accentuation of the interlobular septa by microlith accumulations (arrow) and other regions with more diffuse accumulations of granular, gritty microliths (*). b, c) Histological sections showing microliths along interlobular septa (b, arrow) and areas with more diffuse microlith accumulations (c). d) Varying sized microliths are present both in the alveolar spaces and interstitium. e) The microliths are characteristically concentrically laminated calcified spherules. f) Calcium can be demonstrated in the microliths by Von Kossa stain. b–e) Haematoxylin and eosin stain; original magnifications ×20 (b, c), ×200 (d), ×1000 (e, f).
- FIGURE 3
Scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDAX) of pulmonary alveolar microlithiasis (PAM). a, b) Microliths isolated from explanted lungs demonstrating a) the characteristic spherical structure and b) inorganic elemental signature. Microlith (white arrow) in bronchoalveolar lavage (BAL) fluid with SEM (c) and EDAX characteristics that are similar to explant controls, demonstrating feasibility of using SEM and EDAX as a diagnostic BAL test for PAM. Note carbon spike associated with debris from lavage. Kα, Kβ and Lα represent X-rays emitted as electrons return to K and/or L electron shell. d) Inorganic elemental analysis of BAL microliths.
- FIGURE 4
Diagnostic algorithm for patients with suspected pulmonary alveolar microlithiasis (PAM). Obtaining a family and genetic testing history is key. Thereafter, diagnostic modalities progress from least invasive to most invasive. HRCT: high-resolution computed tomography; BAL: bronchoalveolar lavage; VAT: video-assisted thoracoscopic biopsy.
- FIGURE 5
Other examples of diffuse lung calcification. Computed tomography depicting examples of a, d) amyloidosis with calcified masses, lymphadenopathy and rare cysts, b, e) silicosis with peri-lymphatic calcified nodules, eggshell lymph node calcifications and conglomerate fibrosis, c) metastatic pulmonary calcification in chronic renal failure characterised by lobular ground-glass opacity with interlobular septal sparing and f) healed granulomas due to histoplasmosis with maximum intensity projection reformats.
Tables
- TABLE 1
Pathogenetic mutations
Exon Sequence involved Defect First author [ref.] 1–13 195 kb deletion Truncation without synthesis (deletion) Stokman [15] 1 c.-6773_-6588del Truncation without synthesis (deletion) Corut [9] 2–6 5.5 kb deletion Truncation (deletion) Ishihara [16] 2 insT (not specified area) Truncation (frameshift) Dogan [17] 3 c.114delA Truncation (deletion) Corut [9] 3 c.212_224del Truncation (deletion) Vismara [18] 3 c.226 C>T Substitution Corut [9] 4 c.316 G>A Substitution (missense) Jonsson [19] 5 c.IVS4+1452_IVS5+660del Truncation (deletion) of entire exon 5 Dandan [20] 6 c.560 G>A Substitution (missense) Jonsson [19] 6 c.575 C>A Substitution Ma [21] 7 c.560 G>A Substitution (nonsense) Jonsson [19] 7 insdel857-871 Insertion/deletion with truncation Huqun [8] 8 IVS8+1 G>A Truncation by splicing failure Huqun [8] 8 c.906 G>A Substitution (nonsense) Jonsson [19] 8 c.910 A>T Truncation Zhong [22] 10 c.1136 G>A Substitution (missense) Jonsson [19] 11 c.1238 G>A Substitution (nonsense) Jonsson [19] 11 c.1327delC Truncation (deletion) Jonsson [19] 11 c.1328delT Truncation (deletion) Corut [9] 12 c.1333+1 G>A Substitution (nonsense, frameshift splicing) Jonsson [19] 12 c.1342delG Truncation (deletion) Corut [9] 12 c.1363 T>C Substitution Wang [23] 12 c.1390 G>C Unclear result Izumi [24] 12 c.1393-1404delACC Truncation, threonine deletion Jonsson [25] 12 c.1402-1404delACC Truncation, threonine deletion Jonsson [25] 12 c.1456 C>T Truncation Proesmans [26] - TABLE 2
Lung transplantation in cases of pulmonary alveolar microlithiasis
Single versus double Age at transplant years Sex Outcome Complication(s) First author [ref.] Single 32 Male Death, NR PGD, haemodynamic instability Shadmehr [106] Single 47 Female Alive, 12 months Possible acute rejection, bronchial stricture Raffa [87] Single 53 Male Alive, 12 months Bronchial anastomosis granulation with stenosis, bacterial infection Ren [34] Single 53 Female Alive, 90 months None Jackson [107] Single 64 Female Alive, 60 months None Borrelli [108] Double 32 Female Death, 11 days PGD, sepsis Klikovits [35] Double 32 Male Alive, 18 months Bronchial artery bleed, post-operative tracheostomy, CMV/fungal infections Stamatis [27] Double 34 Male Alive, 67 months None Klikovits [35] Double 36 Female Alive, 32 months None Edelman [33] Double 45 Male Alive, 12 months Mild PGD Alrossais [36] Double 46 Female Death, 20 months Bronchiolitis obliterans Bonnette [109] Double 48 Male Alive, 12 months PGD, haemodynamic instability, ARF Samano [57] Double 49 Female Death, 3 months Infection Coulibaly [110] Double 52 Female Alive, 35 months None Klikovits [35] Double 52 Female Alive, 74 months PGD, atrial fibrillation Klikovits [35] Double 53 Female Alive, 12 months None Gucyetmez [111] Double 54 Female Alive, 12 months None Jindal [112] Double 56 Male Death, 5 days Post-operative bleeding Edelman [33] Double 62 Female Alive, 29 months Atrial fibrillation Klikovits [35] Double 63 Female Alive, 24 months None Shigemura [113] NR: not reported; PGD: primary graft dysfunction; CMV: cytomegalovirus; ARF: acute renal failure.
