Radiology/Pathology Correlation

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The patient is a 65-year-old woman with a chronic, non-productive cough.

Radiology

Figure 1. Chest Radiographic Findings

The frontal chest radiograph shows large lung volumes with bilateral, linear opacities suggesting bronchial wall thickening or bronchiectasis. No evidence of pleural effusion or lymphadenopathy is present.

Figure 2. HRCT Findings

HRCT shows extensive bronchiectasis predominantly within the right middle lobe and lingula, with distal bronchiolar impaction characterized by a branching pattern. Small, centrilobular nodules and airway thickening are also evident within the lower lobes bilaterally.

middlebronchiec1bronchiec2clncentrallingula

 

Find the middle lobe bronchiectasis. Click on the structure in the image to get verification.

Find the lingular bronchiectasis.

Find 3 examples of peripheral bronchiectasis in the right lower lobe. (Note adjacent artery giving a signet ring appearance.)

Find a cluster of central airways with wall thickening in the right lower lobe.

Find 3 adjacent centrilobular nodules in the right lower lobe.

What is the differential diagnosis of small nodules, bronchiectasis, and parenchymal opacities? Answer


Pathology

Figure 3. Gross Appearance: Slice of lung from a 79-year-old woman with the same disease. This view of the lower lobe shows nodules with pale centers and thin, translucent walls. The central material had the appearance and consistency of crumbly cheese.

nod2nod1nod3br1br2

 

The largest nodule has a dilated bronchiole near its upper margin. This bronchiole is a branch of a dilated bronchus with a thin wall. A second dilated bronchus is also present.

Find 3 nodules.

Find two dilated bronchi.

airway1airway2airway3pnod1pnod1pnod1pnod2pnod3pnod4pnod5pnod5

Figure 4. Overview of a Lung Biopsy

Biopsy from another patient, a 62-year-old woman, shows parenchymal nodules with pink centers surrounded by lymphoid infiltrates. Some of the nodules are coalescing. The nodules vary in size up to 5 mm in diameter, but larger conglomerates occur. The bronchioles are dilated. One dilated airway is surrounded by a lymphoid infiltrate. The surrounding alveolar parenchyma is normal. The pleura lies at the top.

Find the parenchymal nodules.

Find 3 dilated airways.

 

Figure 5. High-power View of Edge of Nodule: This nodule from the same patient shows central pink fibrosis with a fibroblastic wall infiltrated by lymphoid cells. A lymphoid follicle with a germinal center lies at the top. Here, the surrounding parenchyma shows a chronic inflammatory infiltrate. No organisms were found with the Ziehl-Neelsen stain or the GMS stain.

 

This lesion is a fibrosing granuloma.

How does it differ from an active granuloma found in tuberculous or fungal infections?

Answer

 

Figure 6. Dilated Airway

What internal marker indicates that this airway is dilated?

Answer

What histologic feature in the wall indicates that the diagnosis is post-inflammatory bronchiectasis?

Answer

What is the histologic differential diagnosis?

Answer

Scroll down after answering the questions.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Nontuberculous Mycobacterial (NTM) Disease, Especially M. avium-intracellulare Complex Disease

Discussion: Pulmonary disease caused by the ubiquitous (soil and water) nontuberculous mycobacteria, which are less virulent than M. tuberculosis, has been increasing in frequency [1, 2-Marras, p 553]. Unlike tuberculosis, NTM disease does not occur via person-to-person transmission; rather, it occurs via environmental exposure by inhalation or ingestion of the organism. Several clinical-radiographic syndromes associated with M. avium-intracellulare complex, the most common pathogen, have emerged [2-Levin, p 603]. These include the classic pattern, which resembles that seen in post-primary tuberculosis, and nonclassic patterns including asymptomatic solitary nodules, the Lady Windermere syndrome (LWS), and patchy opacities in immunocompromised patients, including those with AIDS. Click here for a patient's perspective of this disease.

Clinical features: Demographic and clinical features vary depending on the radiographic patterns. Male smokers, 50 to 70 years old, with chronic lung disease (COPD, pneumoconioses, or previous tuberculosis), are at risk for classic disease, believed to result from a disruption of normal defense mechanisms. An increase in cough, sputum production, or hemoptysis; or development of constitutional symptoms or radiographic changes should raise suspicion of MAC disease in these patients [2-Aksamit, p 643].

Solitary pulmonary nodules, 1-5 cm in diameter, may be discovered radiographically in asymptomatic patients [2-Levin, p 603].

A nonclassic pattern, the so-called LWS, occurs predominantly in thin, nonsmoking women over age 50 with no known previous lung disease or immunodeficiency. These patients often have scoliosis, pectus excavatum, and mitral valve prolapse. Symptoms include cough and fatigue, sometimes accompanied by fever, weight loss, hemoptysis, and dyspnea [1, 2-Chalermskulrat, p 675]. The course is prolonged, and drug failure rates are high [3]. Recently, 5 patients with the disease have been shown to have markedly low levels of interferon gamma, the significance of which is unknown [4].

Other nonclassic patterns occur in persons with cystic fibrosis (including variants occurring in older adults), immunodeficiency diseases including AIDS, malignancy, gastric reflux disease, and diabetes mellitus. Patchy radiographic opacities may occur. Although distinction of colonization and disease may be difficult in some of these groups, in patients with cystic fibrosis, CT findings of small nodules (proven to be necrotizing granulomas, histologically) and lack of symptomatic response to conventional antibiotics help to diagnose disease [2-Ebert, p 655)].

Disseminated disease with or without pulmonary radiographic opacities is found in two groups: those with late AIDS and low CD4 counts (usually <50/cu mm), and children with several genetic immune defects involving the interferon gamma receptor or the IL-12 receptor. Fever and night sweats are common. The high mortality in AIDS patients has been decreased by specific prophylaxis as well as by current antiretroviral therapy [1]. The prognosis for children with genetic defects depends on the severity of the defect [5].

Diagnosis of all forms requires suspicion based on clinical, radiographic, culture, and, sometimes, histologic findings [1]. Unless otherwise specified, the images are from patients with MAC disease.

Radiology--Classic disease

Classic MAC pulmonary disease manifests as cavitary disease, favoring the apical and posterior segments of the upper lobes. Evidence of endobronchial spread of infection is often seen (presenting as centrilobular branching opacities), as is scarring, volume loss, and pleural thickening. Pleural effusions and lymphadenopathy are uncommon. Differentiation of this pattern of MAC disease from that of M. tuberculosis requires isolation of the organism (see diagnostic criteria) in addition to imaging findings [2-Levin, p 603, 2-Aksamit, p 643].

Nonclassic disease

On chest radiography and HRCT, nonclassic MAC disease manifests as small (<1 cm) nodules, often associated with bronchiectasis. On HRCT, the centrilobular distribution of these nodules, which are often accompanied by branching opacities representing a "tree-in-bud" pattern, is evident. The bronchiectasis, which is better seen with HRCT than routine CT, usually involves multiple lobes, often predominating within the right middle lobe and lingula [2-Levin, p 603, 6]. While bronchiectasis of the middle lobe and lingula is often suggestive of MAC infection, particularly in older women, other diseases that result in bronchiectasis, especially allergic bronchopulmonary aspergillosis, immotile cilia syndromes, and cystic fibrosis may show a similar distribution. Compared to tuberculosis, thoracic lymphadenopathy is less common with MAC, and, when present, is not usually necrotic.

MAC disease in immunocompromised patients, particularly those with AIDS, has a highly variable appearance. MAC disease occur in AIDS patients even in the presence of normal radiographs. Lower lobe predominant centrilobular nodules, consolidation, ground-glass attenuation, and prominent lymphadenopathy may be seen [2-Levin, p 603].

Pathology--Classic disease

The gross and histologic appearances are similar to those of M. tuberculosis (scroll down when you get there). In one study, granulomatous bronchiectasis and bronchiolectasis, small and large necrotizing or non-necrotizing granulomas, cavities, and alveolar granulomatous consolidation were found in 5 patients with resected upper lobe MAC disease [7].

Nonclassic disease

Bronchiectasis and nodules (Lady Windermere syndrome or "thin-woman syndrome"): The bronchiectasis and bronchiolectasis are caused at least in part by granulomatous inflammation that destroys smooth muscle and cartilage of airway walls. Infection with pyogenic bacteria, especially pseudomonas, may be superimposed and contribute to the bronchiectasis. The nodules, usually small and centrilobular, may be parenchymal or bronchiolocentric, and non-necrotizing or necrotizing. The parenchymal nodules represent peribronchiolar invasive disease. As in lesions of M. tuberculosis, organisms, which are found in the necrotic areas, are sparse or absent with routine acid-fast stains. Histologic changes also include foci of organizing pneumonia with or without granulomas.

Comment: The predominant involvement of the middle lobe and lingula may be related to poorly-defined factors that predispose to the "middle lobe syndrome" (includes lingula), which histologically consists of organizing pneumonia, chronic airway inflammation, and bronchiectasis. Nontuberculous mycobacteria are one of multiple causes of this syndrome.

Predominant organizing alveolar pneumonia (immunocompromised patients) corresponds to polygonal or irregular radiographic opacities and may occur adjacent to, or apart from, caseating granulomas in patients with MAC disease [8]. In one study, organizing pneumonia in five patients (3 female), most with underlying systemic disease and radiographic bilateral diffuse interstitial disease, showed non-necrotizing granulomas in 1. Three other patients with multiple discrete opacities also showed organizing pneumonia with or without granulomas. Caseous necrosis and cavitation were absent [9]. This pattern can also be seen in some AIDS patients [10].

Collections of histiocytes: In late AIDS, the response often consists of ill-defined collections of histiocytes with striate, bluish cytoplasm that is packed with organisms [11]. Inflammatory cells, giant cells, and necrosis are often absent although sometimes parenchymal organizing pneumonia may be present along with necrotizing or non-necrotizing granulomas [10].

Similar poorly-defined collections of histiocytes filled with bacilli have also been described in children with genetic defects in interferon-gamma and IL-12 receptors [5].

To summarize, the nonclassic histologic patterns associated with MAC disease differ from the classic forms in having a wider distribution of lesions and in the usual absence of cavitation. Organisms are usually sparse in both classic and nonclassic disease except for those with severe immunocompromise and a histiocytic response in which intracellular organisms are numerous.

Summary of HRCT Features of Nonclassic MAC Infection--Lady Windermere syndrome

Summary of Pathologic Features of Nonclassic MAC Infection--Lady Windermere syndrome, immunocompromised patients, AIDS

Diagnosis: Nonclassic MAC infection (Lady Windermere syndrome)

References: To return to reference section after viewing abstract, click here before clicking on "abstract".

1. American Thoracic Society. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am J Respir Crit Care Med 1997; 156:S1-S25.

2. Clinics in Chest Medicine. Lung Disease Due to Nontuberculous Mycobacterial Infections. A Catanzaro and C Daley, eds, WB Saunders, 23, No 3, 2002.

3. Huang J, Kao P, Adi V, Ruoss S. Mycobacterium avium-intracellulare pulmonary infection in HIV-negative patients without preexisting lung disease. Diagnostic and management limitations. Chest 1999; 115:1033-1040. Abstract

4. Safdar A, White D, Stover D, Armstrong D, Murray H. Profound interferon gamma deficiency in patients with chronic pulmonary nontuberculous mycobacteriosis. Am J Med 2002; 113:756-759.

5. Newport M. The genetics of nontuberculous mycobacterial infection. Exp Rev Mol Med 2003; 5. Abstract

6. Miller W Jr. Spectrum of pulmonary nontuberculous mycobacterial infection. Radiology 1994; 191:343-350. Abstract

7. Fujita J, Ohtsuki Y, Suemitsu I, Shigeto E, Yamadori I, Obayashi Y, Miyawaki H, Dobashi N, Matsushima T, Takahara J. Pathological and radiological changes in resected lung specimens in Mycobacterium avium intracellulare complex disease. Eur Respir J 1999; 13:535-540. Abstract

8. Takada Y, Sakai F, Suzuki K, Nagai A, Suzuki A. CT features of pulmonary nontuberculous mycobacterial infection: effects of underlying pulmonary disease. Radiation Med 2000; 18:167-175. Abstract

9. Marchevsky A, Damsker B, Gribetz A, Tepper S, Geller S. The spectrum of pathology of nontuberculous mycobacterial infections in open-lung biopsy specimens. Am J Clin Pathol 1982: 78:695-700. Abstract

10. Hocqueloux L, Lesprit P, Herrmann J-L, La Blanchardiere A, Zagdanski A-M, Decazes J-M, Modai J. Pulmonary Mycobacterium avium complex disease without dissemination in HIV-infected patients. Chest 1998; 113:542-548. Abstract

11. Solis O, Belmonte A, Ramaswamy G, Tchertkoff V. Pseudogaucher cells in Mycobacterium avium intracellulare infections in acquired immune deficiency syndrome (AIDS). Am J Clin Pathol 1986; 85:233-235. Abstract

 

TOP----Rad/Path Home Page

Last modified 5/5/03

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Right middle lobe bronchiectasis

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Lingular bronchiectasis

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Peripheral bronchiectasis

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Centrilobular nodules in right lower lobe

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Central airways with wall thickening

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Differential diagnosis: The major findings on the HRCT study are centrilobular nodules and bronchiectasis. Either of these two findings alone is useful for generating differential diagnoses on HRCT studies.

The differential diagnosis of centrilobular nodules is broad, but when one notes the presence of centrilobular nodules with a branching configuration, the differential diagnosis is primarily limited to pyogenic infections. Centrilobular nodules and bronchiectasis suggest a differential diagnosis in which the predominant distribution of the bronchiectasis--middle lobe and lingula in this case--is of paramount importance. This differential diagnosis should include cystic fibrosis, allergic bronchopulmonary aspergillosis, infection with Mycobacterium avium complex, post-infectious bronchiectasis, and immotile cilia syndromes. The differential diagnosis may often be narrowed significantly by integrating the clinical history and demographics of the patient with the HRCT disease pattern. The parenchymal opacities, while present, are not useful in formulating a differential diagnosis.

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Dilated bronchus

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Parenchymal nodule

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Dilated bronchiole

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In the cellular wall, an active granuloma would show multinucleated giant cells and palisaded histiocytes. Instead of central fibrosis, there would be granular, necrotic material.

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The pulmonary artery. The airway is much larger than the pulmonary artery. Normally, they are both about the same size.

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The normal wall structures--cartilage and smooth muscle--have been replaced by chronic inflammatory cells.

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Differential diagnosis: Parenchymal granulomas with crumbly cheese-like material (caseous granulomas) and bronchiectasis in the lower lung suggest infection with nontuberculous mycobacteria. Other diagnoses to be considered for nodular parenchymal granulomas include tuberculosis, which usually involves the upper lung, chronic fungal infections, in which organisms are usually easily found with the GMS stain, and rheumatoid nodules.

In the setting of parenchymal granulomas, the bronchiectasis was probably caused by the same pathogen (peribronchiolar granulomas were found elsewhere in the biopsy). Granulomatous bronchiectasis occurs in allergic bronchopulmonary aspergillosis, as well as in tuberculous and nontuberculous mycobacterial and fungal infections. The differential diagnosis of bronchiectasis/bronchiolectasis without granulomatous inflammation is extensive and includes cystic fibrosis, collagen vascular diseases, post-infectious disease, the immotile cilia syndromes, post-obstruction disease, toxic inhalation, and gastric aspiration syndromes.

Note: Active granulomas, as seen in the slice of lung, would be expected to show histologic central necrosis and surrounding multinucleated giant cells and palisaded histiocytes. The histologic sections from the other cases show "inactive," fibrosing granulomas and non-specific inflammation, without demonstrable organisms, but Mycobacterium-avium complex was grown from all specimens.

Diagnosis: Nonclassic MAC infection: Lady Windermere syndrome

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