Cardiovascular and Pulmonary Pathology in Systemic Disease
Case 5 -
Severe, Acute, and Chronic Bronchiolitis
Associated with Extensive Organizing Endogenous Lipoid Pneumonia;
and Rare Non-necrotizing Granulomas
Henry D. Tazelaar and Marie-Christine Aubry
PDF File (3.6 MB)
A 58-year-old man with a history of sarcoidosis presented with
persistent cough and symptoms of bronchitis. These had been recurrent over the past ten years and
developed approximately six months following a diagnosis of Crohn's disease of the colon. Throughout the
past ten years, he has had a persistent cough productive of five to eight teaspoons of thick, tan,
yellow, "chunky" sputum and has had numerous hospitalizations for pulmonary infections with fever and
chills. He underwent an open lung biopsy because his sputum was growing aspergillus and the possibility
of invasive aspergillosis was raised.
Slides illustrating Case 5 are in the accompanying PDF of the Powerpoint presentation.
Diagnosis: Severe, acute, and chronic bronchiolitis
with bronchiolectasis associated with extensive organizing endogenous lipoid pneumonia; and rare
non-necrotizing granulomas. The features are consistent with lung disease occurring in association with
inflammatory bowel disease (Crohn's disease).
Sections show those features outlined in the diagnosis. The
presence of airway dilatation is best appreciated by comparing the airway diameter to that of its
adjacent vessel. They should be about the same size. In this case, the bronchioles are three to four
times the size of the adjacent arteries. Although one cannot make a diagnosis of bronchiectasis the
small airway changes suggest that bronchiectasis may be present.
Patients with inflammatory bowel disease (IBD) may have a variety of extra intestinal manifestations,
including arthritis, ankylosing spondylitis, erythema nodosum, pyoderma gangrenosum, dermatitis, aphthous
stomatitis, conjunctivitis, episcleritis, uveitis, hepatitis, pericholangitis, sclerosing cholangitis,
primary biliary cirrhosis, pancreatitis, thyroiditis, pyelitis, and pericarditis. Pulmonary
complications also occur and although more common in ulcerative colitis, have also been reported in
Crohn's disease. The landmark article was published by Camus, et. al., in 1993. They summarized the
results of 33 patients with inflammatory bowel disease, predominantly ulcerative colitis (n=27). A
number of features emerged from this study. Most patients (84%) developed respiratory involvement
following the onset of IBD by nine years (range one week to 36 years). The bowel disease activity at the
time of the respiratory illness was variable, many having inactive disease or being post-colectomy. In
only 10% was the inflammatory bowel disease active. In a few patients, severe bronchopulmonary
involvement developed suddenly and unexpectedly a few days or weeks following proctocolectomy. Rarely,
the bowel disease and lung symptoms developed concurrently and in four patients the bronchopulmonary
disease developed prior to the IBD.
The patterns of pulmonary involvement can be divided into those which consisted predominately of
airway disease (60%), interstitial lung disease (35%), parenchymal nodules (5%). (See Table 1).
Large airway involvement, as seen in this case, is characterized histologically by the
presence of remarkably airway centered disease. The submucosa usually contains a dense cuff of
lymphocytes and plasma cells. Occasionally, neutrophils may be present. The mucosa sometimes shows
squamous metaplasia. In lobectomy specimens, where large airway involvement can be better appreciated,
the inflammatory infiltrate often involves bronchial submucosal glands. Usually, germinal centers are
absent from the lymphoid aggregates, an overall pattern unusual for ordinary bronchiectasis. Mucous
stasis, as seen in this case, may also be prominent The current case also shows a fairly dramatic
endogenous lipoid pneumonia, a manifestation of this patient's inability to adequately clear his
In biopsies lacking bronchi, similar changes may be identified in bronchioles. While some may show
simply a chronic bronchiolitis without fibrosis, luminal, and mural fibrosis have also been
reported. Such cases could be classified as showing bronchiolitis obliterans (without the organizing
pneumonia). In our recent review of eight patients with noninfectious pulmonary complications associated
with Crohn's disease (Casey et. al.), the bronchiolitis has taken two forms; one, a chronic bronchiolitis
with non- necrotizing granulomatous inflammation within bronchiolar walls and second, a more acute
bronchiolitis with bronchopneumonia-like features in the surrounding pulmonary parenchyma.
The interstitial changes associated with IBD have been variable and have been classified as
bronchiolitis obliterans organizing pneumonia (BOOP), with or without giant cells and
non-necrotizing granulomas, nonspecific interstitial pneumonia (NSIP), and eosinophilic
pneumonia. Camus, et. al., have commented that the BOOP associated with IBD may be associated with a
distinctive marked septal edema which is infiltrated by chronic inflammatory cells and modest numbers of
eosinophils, not characteristic of idiopathic BOOP.
Table 1 Patterns of thoracic involvement in inflammatory bowel
|Pattern of involvement ||Camus 1993 ||% of total ||Lit review ||% total|
|Subglottic stenosis ||3 ||9.4 ||3 ||5.3|
|Chronic bronchitis ||6 ||18.8 ||12 ||21.0|
|Chronic bronchial suppuration ||3 ||9.4 ||4 ||7.0|
|Bronchiectasis ||6 ||18.8 ||14 ||24.6|
|Chronic bronchiolitis ||2 ||6.3 ||1 ||1.8|
|Bronchiolitis obliterans organizing pneumonia ||6 ||18.8 ||5 ||8.8|
|Interstitial lung disease ||1 ||3.1 ||15 ||26.3|
|Pulmonary infiltrates and eosinophilia ||3 ||9.4 ||0 ||---|
|Necrobiotic nodules - neutrophilic infiltrates ||2 ||6.3 ||3 ||5.3|
|Serositis ||32 ||100 ||57 ||100|
|Myocarditis ||0|| --- ||10 ||24.4|
|Pericarditis ||0|| --- ||15|| 36.6|
|Pleural effusion ||0|| --- ||4|| 9.6|
|Pleuropericarditis ||1|| --- ||12|| 29.3|
|Total ||1|| --- ||41|| 100|
* from Camus P et al, 1993
Cases associated with eosinophilic pneumonia show airspace, septal, and pleural involvement.
The septae may also show marked edematous thickening similar to that seen in cases of BOOP described
above. Nonspecific interstitial pneumonia is characterized by temporal and spatial homogeneity of
both inflammation and fibrosis (if present). A complete description of this entity and its significance
is beyond the scope of this course and handout.
Necrobiotic nodules have been described as resembling necrotic granulomas. Early nodules
appear to consist of dense airspace accumulations of neutrophils and a fibrinous exudate. These nodules
may then undergo central necrosis and cavitation. There is some resemblance of these nodules to
infectious and noninfectious granulomas, particularly Wegener's, but they have a notable absence of giant
cells and vasculitis. These nodules have been described as being reminiscent of dermal pyoderma
Table 2 summarizes our recent experience and the published literature on pulmonary involvement with
Crohn's disease. Although there is some overlap, respiratory involvement may differ in patients with
ulcerative colitis and Crohn's disease. For instance, necrobiotic nodules have not been reported in
Crohn's disease. Conversely, diseases know to occur in conjunction with Crohn's disease, such as
granulomatous involvement of the larynx, trachea, and bronchi have not been reported in patients with
ulcerative colitis. Interestingly, both have been reported to be associated with pulmonary sarcoidosis,
which this patient had in the past. Whether the pulmonary granuloma seen in patients with inflammatory
bowel disease is true sarcoid or a distinct granulomatous process remains unclear.
Table 2. Spectrum of Pulmonary Changes Associated with Crohn's Disease
| Chronic Bronchiolitis with Granulomas|
|Acute bronchiolitis with Bronchopneumonia-like features|
|Non-specific interstitial pneumonia (± giant cells)|
|BOOP with rare granulomas and/or giant cells|
The differential diagnosis for lung disease associated with IBD is fairly lengthy depending on the
exact pattern of involvement. Infection always needs to be excluded with special stains and cultures,
particularly because many patients may be on immunosuppressive therapy. The other main possibility to
consider is a drug reaction. Drugs used to treat IBD, particularly sulfasalazine and 5-ASA, have been
associated with a variety of histologic patterns. Sulfasalazine can cause eosinophilic pneumonia, or
chronic interstitial pneumonia not otherwise specified i.e. nonspecific interstitial pneumonia;
desquamative interstitial pneumonia, BOOP, diffuse alveolar damage, and hypersensitivity pneumonitis.
Although the current patient was not on any medication other than steroids at the time of the biopsy,
predominantly airway centered disease as seen in this case is unlikely to be due to drugs.
Since bronchiectasis and bronchiolectasis are usually secondary, when a pathologic diagnosis is made
the clinical differential will depend on whether the process is focal or diffuse. See Table 3.
Table 3: Bronchiectasis: Clinical Associations
| Localized (Focal) Bronchial "obstruction"|
| Recurrent Pneumonia|
| Middle lobe syndrome (right/lingula)|
| Endobronchial tumor|
| Foreign body|
| Diffuse bronchiectasis|
| Chronic aspiration|
| Recurrent pneumonia|
| Cystic fibrosis|
| Immotile cilia|
| Kartagener's Syndrojme|
| Yellow nail syndrome|
| Inflammatory bowel disease|
| MAC associated|
| Allergic bronchopulmonary fungal disease|
| Congenital: Mounier-Kuhn's syndrome|
In this older adult patient, the combination of airway dilatation, and non-necrotizing granulomatous
inflammation makes mycobacterium-avium complex (MAC) airway disease the most realistic differential
diagnostic consideration. MAC-associated airway disease typically occurs in elderly women. When
it occurs in the right middle lobe or lingula it has been the Lady Windermere syndrome. Whether
bronchiectasis is the primary process or a result of chronic MAC infection is not clear. Patients
typically present with cough with or without some sputum production. High resolution CT scans in this
setting characteristically show the presence of nodules in association with bronchiectasis. Patients
often come to surgical lung biopsy with a diagnosis of "pulmonary fibrosis." Distinction from
Crohn's-related airway disease will depend to a large extent on history (Crohn's, age, gender),and
culture results. Special stains for mycobacteria are almost always negative in MAC airway disease.
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