Case 1 -

Necrotizing Granulomatous Inflammation Caused by Aspiration of Gordonia Species and Lipid, Secondary to Esophageal Motility Disorder Andrew Churg University of British Columbia British Columbia

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Clinical History This is a 50 yo man with a history of traumatic perforation of the esophagus in 2003 in a motor vehicle accident. The esophagus was repaired with a colonic interposition. In early 2008 the patient presented with an upper lobe pneumonia and cultures grew an organism identified as Rhodococcus. The patient was HIV negative and had normal T cell counts. He improved on antibiotic therapy. In late 2008 the patient presented with a clinical picture of bilateral pneumonia and a lung biopsy was performed. Culture of the biopsy grew an organism identified as a Gordonia species. Case 1 - Figure 1 CT scan from the December 2008 admission showing patchy areas of peripheral consolidation and a pleural effusion. Case 1 - Figure 2 Progressively higher power views showing necrotizing granulomas containing large lipid droplets Case 1 - Figure 3 Progressively higher power views showing necrotizing granulomas containing large lipid droplets Case 1 - Figure 4 Progressively higher power views showing necrotizing granulomas containing large lipid droplets Case 1 - Figure 5 Non-necrotizing granuloma containing a lipid droplet in the center Case 1 - Figure 6 Non-necrotizing granuloma containing a lipid droplet in the center Introduction: Case History: A 50 yo man was admitted in late 2008 with a clinical diagnosis of pneumonia. He was well until 2003 when he sustained a traumatic esophageal perforation in an automobile accident. This required a partial esophagectomy and colonic interposition for repair. Early in 2008 he presented with what appeared to be a community acquired upper lobe pneumonia. No biopsy was performed but culture grew an organism identified as Rhodococcus. He improved on antibiotics. HIV status at this point was negative, and his T cell counts were in the normal range. On admission in late 2008 there was bilateral patchy consolidation, predominantly in the lower zones. A small right pleural effusion was also present. A VATS biopsy was performed. Culture of the biopsy grew a Gordonia species. The biopsy was signed out as necrotizing granulomatous inflammation with a single acid fast organism identified. However, the clinician thought the patient had an aspiration pneumonia. The case was referred in consultation. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: Necrotizing and non-necrotizing granulomas containing large lipid droplets Final Diagnosis: Necrotizing granulomatous inflammation caused by aspiration of Gordonia species and lipid, secondary to esophageal motility disorder. Discussion: Patterns of Aspiration Aspiration is a very common event and one which, judging by referred consultation material, is frequently not recognized by pathologists. Imaging studies are often helpful in suggesting a diagnosis of aspiration; they may show consolidation (Figure 1 in the posted images) or merely fine centrilobular lines or tree-in-bud patterns indicative of in a process in/around bronchioles. Aspiration most commonly occurs with the subject supine and hence aspirated material tends to end up in the superior segments of the lower lobes or posterior segments of the upper lobes. Occasionally aspiration can produce solitary nodular lesions radiologically suggestive of a neoplasm; sometimes the lower density of lipid can be seen in the mass leading to the radiologic diagnosis of lipid aspiration. Rarely aspiration may produce a pattern of miliary nodules. When aspiration is largely gastic acid, ground glass opacities/consolidation typical of ARDS may be present. Aspiration of pure gastric acid typically leads to diffuse alveolar damage (ARDS), and any pattern of diffuse alveolar damage ranging from hyaline membranes to different forms of organization can be seen, depending on the time of biopsy (Table 1). If no food particles are present, it is usually impossible to make a specific diagnosis of aspiration from the morphology alone, although one helpful hint is that the radiologic opacities corresponding to diffuse alveolar damage secondary to gastric acid aspiration may be quite focal, as opposed to the diffuse infiltrates seen on imaging in most cases of ARDS. When very large particles such as a peanut are aspirated, they will lodge in a fairly large airway. If not removed infection and bronchiectasis develop behind the obstructing material. A wide variety of microscopic appearances may be seen in aspiration (Tables 1,2), and these can be broken down by reaction pattern and by the type of foreign material visible. In all forms of aspiration, finding the aspirated material is the best guide to the diagnosis. Of these materials, vegetable particles, typically rounded or serpiginous structures with thick dPAS positive refractile walls, are probably the most common. Fibers of meat (which look like striated muscle, microscopically) and relatively large birefringent particles, frequently derived from drug tablets, may also be found; polarization is often helpful in confirming a diagnosis of aspiration. Some organisms are relatively specific to aspiration, including the tetrads of Sarcina, an oral commensual, and the sulfur granules of Actinomyces. However, many cases of aspiration pneumonia involve oral commensuals that are not visible microscopically. These particulates and organisms produce a range of reactions including bronchopneumonia which may be necrotizing, particularly if the organisms are anerobes, acute bronchiolitis, organizing pneumonia (BOOP), and bronchiolar scarring, sometimes to the point of constrictive bronchiolitis (bronchiolitis obliterans). Foreign body granulomas or individual giant cells are common in aspiration, and the combination of foreign body granulomas with one of the patterns just listed, in particular with BOOP, is strongly suggestive of aspiration. Lipid aspiration can be identified by the characteristic holes of dissolved lipid; early on there may be giant cells around the lipid droplets, but with time these give way to irregular scars containing lipid droplets, particularly when the aspirated lipid is mineral oil intended to relieve constipation. The present case illustrates a very unusual and distinctive pattern of aspiration and an unusual organism. While necrotizing granulomas always raise the question of mycobacterial and fungal infections, necrotizing granulomas should not have lipid droplets in their centers, and this finding suggests some unusual form of aspiration. There are some 20-odd cases in the literature of aspiration pneumonias caused by rapidly growing mycobacteria and related species in patients with esophageal motility disorders, most commonly achalasia (Hadjiliadis et al 1999). These infections seem to be associated with lipid aspiration and it has been suggested that the lipid provides a particularly favorable growth medium. Reported organisms have included M. fortuitum, chelonae, abcessus, and massiliense. The present case is even more unusual in that the organism is a Gordonia species. Gordonia, Rhodococcus, and Nocardia are closely related organisms that in turn are related to some forms of mycobacteria. Gordonia are soil organisms that very rarely produce human infections. Gordonia are weakly acid fast and are difficult to separate on culture from Rhodococcus. Given that this patient was not immunocompromised (the usual setting for Rhodococcus infections), it is likely that the organism identified on culture in early 2008 in the present case was Gordonia and not Rhodococcus. Review of the Literature/Treatment Options (if applicable): Table 1: Pathologic Reaction Patterns in Aspiration Diffuse alveolar damge (ARDS) Bronchopneumonia, sometimes necrotizing Organizing pneumonia (BOOP) (often with giant cells or granulomas) Foreign body granulomas Granulomas containing neutrophils (suppurating granulomas) Necrotizing granulomas (rare) Bronchiolitis with granulomas in/around bronchiolar walls Lipid droplets with giant cell reaction Irregular patterns of fibrosis (especially with lipid aspiration) Bronchiectasis (with large particles obstructing airways only) Table 2: Aspirated Material Visible in Histologic Sections Vegetable particles (typically dPAS positive, sometimes birefringent) Meat fibers (muscle) Birefringent particles Relatively specific organisms Sarcina Actinomyces Rapidly growing mycobacteria and related species Lipid droplets with/without giant cell reaction and/or scars ` Conclusion(s): Take Home Lessons Necrotizing granulomas shouldn't have holes in the middle! Chronic aspiration due to esophageal motility disorders can be associated with infections by atypical mycobacteria and related organisms, particularly when lipid is repeatedly aspirated References: Hadjiliadis D, Adlakha A, Prakash UB. Rapidly growing mycobacterial lung infection in association with esophageal disorders. Mayo Clin Proc 1999; 74:45-51. [summarizes the literature to 1999] Mukhopadhyay S, Katzenstein AL. Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens. Am J Surg Pathol 2007; 31:752-759 Cramer JP, Sudeck H, Burchard GD. Pulmonary infection with rapidly growing mycobacteria in a singer with achalasia: a case report. J Infect 2007;54:e219-21 Brust JC, Whittier S, Scully BE, McGregor CC, Yin MT. Five cases of bacteremia due to Gordonia species. J Med Microbiol 2009; 58(Pt 10):1376-1378