Histopathologic Analysis of Surgically Resected Lungs of Patients with Non-tuberculous Mycobacterial Lung Disease: a Retrospective and Hypothesis-generating Study

Abstract

Non-tuberculous mycobacterial lung disease (NTM-LD) is most commonly due to species within the Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MAbC). Surgical lung resection, typically a lobectomy or segmentectomy, is occasionally undertaken for individuals with recalcitrant but localized NTM-LD. Since the growth characteristics of MAC (slow growers) and MAbC (rapid growers) as well as their drug susceptibility patterns are significantly different, the objective of this study is to characterize and compare the histopathologic features of the resected lungs due to these two major NTM groups. From 1996 to 2017, 356 patients with NTM-LD due to MAC (n=270), MAbC (n=54), or both (n=32) underwent a total of 404 lobar resections (with the lingula counted as a separate lobe) at the University of Colorado Hospital. We analyzed by microscopy the existing surgical lung tissue sections for bronchiolitis, bronchiolectasis, bronchiectasis, non-necrotizing granuloma (airway, parenchymal, and total), necrotizing granuloma (airway, parenchymal, and total), peri-airway fibrosis, fibrous pleuritis, and lymphoid follicles. There were no significant differences in the presence or absence of most of the histopathologic features of surgically removed lungs due to MAC, MAbC, or both MAC + MAbC. However, there were significantly more necrotizing granulomas (airway, parenchymal, and total) and fibrous pleuritis in MAC compared to MAbC lung diseases. Since necrotizing granulomas may be a sign of inadequate control of the infection, we posit that their presence may be an indication of increased chronicity, increased virulence of MAC compared to MAbC, and/or impaired host immunity against the NTM. Futures studies to determine the root cause of such differences in histopathologic findings in MAC versus MAbC lung disease may spawn new leads on differential pathogenic mechanisms with different NTM, with the goal of aiming for more targeted therapy against both the NTM and the lung damage induced by them.

Keywords: granulomas; histopathology; lung disease; mycobacteria; pathology.

Figure 1

Representative examples of specific lung histopathologic findings. (A) Bronchiolitis is represented by the infiltration of the walls of small airways by chronic inflammatory cells (white arrow). (B) Bronchiolectasis and (C) bronchiectasis are diagnosed when the diameter of the bronchus and bronchiole (white arrows), respectively, are greater than that of the lumen of the accompanying pulmonary artery branch (red arrows). Bronchi have cartilage (black arrow) and submucosal glands. (D) Necrotizing granulomas of the airways with areas of central necrosis (black arrows) surrounded by a palisading layer composed of epithelioid histiocytes admixed with several giant cells (asterisks) adjacent to and involving the airway walls. (E) Non-necrotizing granulomas of the airways with many giant cells (asterisks) but without necrosis. (F) Lymphoid follicle (arrow) in the wall of a dilated airway.