Lung manifestations in an autopsy-based series of pulmonary or disseminated nontuberculous mycobacterial disease

Abstract

Background: Comparisons of lung manifestations in primary pulmonary vs disseminated nontuberculous mycobacterial disease have not been well described. The clinical, histopathologic, and radiologic disease manifestations of primary pulmonary or disseminated nontuberculous mycobacterial disease were compared in an autopsy series.

Methods: Medical and microbiologic records, autopsy reports, histopathologic slides of the lungs, and chest CT scans were reviewed on patients at the National Institutes of Health with nontuberculous mycobacterial disease who died between 1996 and 2010.

Results: The 11 patients with primary pulmonary nontuberculous mycobacterial disease were predominantly female (n = 9), with symptom onset at median 50 (range 35, 71) years and time from onset until death of 12 (3, 34) years. Bronchiectasis with cavity formation and necrotizing bronchocentric granulomatous inflammation predominated but extrapulmonary infection was absent. The five patients with disseminated disease and systemic immune defects were all men with age at onset of 2 (0.33, 33) years and time from onset of disease until death of 9 (1, 31) years. Miliary nodules and/or consolidation with poorly formed granulomatous inflammation were noted in the three disseminated patients with mycobacterial lung involvement. Significant extrapulmonary infection was noted in all five with a relative paucity of lung findings.

Conclusions: Nontuberculous mycobacteria can cause progressive, fatal disease. Primary pulmonary disease is bronchocentric and lacks extrathoracic infection consistent with impaired airway surface defenses. In contrast, fatal disseminated infections involving the lung have hematogenous spread, extensive extrathoracic disease, and a distinct pulmonary histopathology consistent with systemic immune dysfunction.

Figure 1.

A-F, Granulomatous inflammation. Distribution of patterns of granulomatous inflammation by type of nontuberculous mycobacterial disease (A) include both necrotizing (B, hematoxylin and eosin, original magnification × 400) and nonnecrotizing (C, hematoxylin and eosin, original magnification × 100) granulomas seen in pulmonary NTM disease and poorly formed granulomas (D, hematoxylin and eosin, original magnification × 200) seen in disseminated NTM disease. A pattern of diffuse granulomatous consolidation (E, hematoxylin and eosin, original magnification × 400) was seen in both, and miliary distribution (F, hematoxylin and eosin, original magnification × 40) of granulomas was seen in disseminated disease involving the lung. NTM = nontuberculous mycobacteria.

Figure 2.

Microbial invasion. A, Fite stain showing mycobacteria (black arrow) at the edge of a necrotizing granuloma (patient 8) (original magnification × 600). B, Gomori methenamine silver stain showing fungi (black arrow) invading tissue (patient 6) (original magnification × 400).

Figure 3.

A, B, Histopathology and CT scan findings. The panels show poorly formed granulomas (black arrowheads) (A, hematoxylin and eosin, original magnification × 40) and both a miliary radiographic pattern (white circle and black arrows) and consolidation (black circle) (B) from a patient (patient 12) with an interferon-γ receptor defect and disseminated NTM disease. Patterns typical of pulmonary NTM disease from a woman (patient 8) with longstanding pulmonary Mycobacterium avium complex show bronchocentric pathology (C, hematoxylin and eosin, original magnification × 40) with sloughing of the epithelial lining (black arrowheads) and circumferential replacement of the bronchial wall architecture with granulomatous inflammation (black bar) that correlates with bronchiectasis and bronchial wall thickening (white arrowheads) ending in distal cavitary type changes (white arrow) (D). See Figure 1 legend for expansion of abbreviations.