Illustration of a number of atypical computed tomography manifestations of active pulmonary tuberculosis

Abstract

Tuberculosis is a serious public health challenge facing mankind and one of the top ten causes of death. Diagnostic imaging plays an important role, particularly for the diagnosis and treatment planning of tuberculosis patients with negative microbiology results. This article illustrates a number of atypical computed tomography (CT) appearances of pulmonary tuberculosis (PTB), including (I) clustered micronodules (CMNs) sign; (II) reversed halo sign (RHS); (III) tuberculous pneumatocele; (IV) hematogenously disseminated PTB with predominantly diffuse ground glass opacity manifestation; (V) hematogenously disseminated PTB with randomly distributed non-miliary nodules; (VI) PTB changes occur on the background of emphysema or honeycomb changes of interstitial pneumonia; and (VII) PTB manifesting as organizing pneumonia. While the overall incidence of PTB is decreasing globally, the incidence of atypical manifestations of tuberculosis is increasing. A good understanding of the atypical CT imaging changes of active PTB shall help the diagnosis and differential diagnosis of PTB in clinical practice.

Keywords: Pulmonary tuberculosis (PTB); cluster of micronodules; emphysema; interstitial pneumonia; miliary tuberculosis; organizing pneumonia (OP); pneumatocele; reversed halo sign (RHS); sarcoid galaxy sign.

Figure 1

Diagrams showing characteristic findings of centrilobular micronodules and tree-in-bud lesions (A) and clustered micronodules (CMNs) (B,C,D). Note that CMNs originate from a few discrete micronodules (1–3 mm) which primarily distribute around small airways distal to the level of segmental bronchus (B). Over time, localized aggregation of multiple discrete micronodules associated with small airway wall thickening and bronchiolectasis gradually progress to CMNs (C). Unlike tree-in-bud lesions which suggest small airways filled with caseous materials (A), the CMNs may have association with thickened walls of small airways maintaining luminal patency. The CMNs may merge into a larger nodule or consolidation either initially or later as CMNs progress and can obscure small airways (D). Dotted line: normal bronchiole; solid line: bronchiectasis; thickened solid line: bronchiectasis with bronchial wall thickening. Reproduced with permission from (6).

Figure 2

Clustered micronodules (CMNs) computed tomography (CT) manifestation of pulmonary tuberculosis. (A) A 31-year-old male patient with pulmonary tuberculosis. CMNs distributes in the left upper lobe, with reticular lines. The edge of the lesion is surrounded by a line shadow (white arrow), indicating the thickened lobular interval. This is called the “marginal sign”. Moreover, tree-in-bud sign is seen at the edge of the lesion (black arrow). (B) A 24-year-old female patient with pulmonary tuberculosis. High resolution CT shows CMNs in the posterior segment of the left upper lobe, with clear linear edges visible (white arrow) on the front border of the lesions.

Figure 3

Clustered micronodules (CMNs) computed tomography (CT) manifestation of pulmonary tuberculosis. (A) A 31-year-old female patient with pulmonary tuberculosis. CMNs in both lungs partially merged to form lung consolidations. (B) A 55-year-old male patient with pulmonary tuberculosis and positive sputum microbiology. CT shows non-segmentally distributed cluster-like CMNs in the right upper lobe, with merged consolidation and a thick-walled cavity in the center as well as thickened and dilated bronchial walls. Thickening of the interlobular septum can be seen at the pleural surface of the lesions (black arrow).

Figure 4

Clustered micronodules (CMNs) computed tomography (CT) manifestation of pulmonary tuberculosis. A 27-year-old female patient with pulmonary tuberculosis and positive sputum microbiology. CT showed multiple CMNs in both lungs, dominant in upper and middle lungs. Fusion and necrosis occurred in the CMNs area of the left upper lung, forming a thick-walled cavity (A). There are fewer lesions in the middle and lower lung fields (B), with the CMNs roughly the same in shape.

Figure 5

Computed tomography (CT) reversed halo sign (RHS) manifestation of pulmonary tuberculosis (PTB). (A) A 54-year-old male patient with PTB and negative sputum smear. He was asymptomatic and the PTB was noted during physical examination. CT shows a large single RHS in the upper left lobe distributed across lung segments. The ring wall is formed by the accumulation of micro-nodules with ground grass opacity and micro-nodules seen inside the ring. (B) A 25-year-old male patient with PTB and negative sputum smear. CT shows multiple RHS manifestations in both lungs, with high similarity in shape among the lesions.

Figure 6

Computed tomography (CT) reversed halo sign (RHS) manifestation of pulmonary tuberculosis in a 26-year-old male pulmonary tuberculosis patient with right sided heart. (A,B,C): Multiple RHS in both lungs. The upper and middle regions of the lungs fused to form consolidation, and there are cavities in some consolidation areas. This case of RHS has appearance similar to CMNs. There are more lesions in upper lobes, and lesions have similar appearance. (D) CT-guided lung biopsy on the “ring” of RHS shows granulomas with caseous necrosis (HE stain, ×100).

Figure 7

CT reversed halo sign (RHS) manifestation of pulmonary tuberculosis. An 18-year-old female patient with pulmonary tuberculosis involving the lungs, intestines, and meninges. (A) There are multiple RHS in both lungs, with clusters of micro-nodules and ground grass opacities distributed inside. (B) After anti-tuberculosis treatment, micro-nodules and ground grass opacities inside the wall were firstly absorbed. CT, computed tomography.

Figure 8

Pulmonary tuberculosis cases with co-existence of clustered micronodules (CMNs) and reversed halo sign (RHS). (A) A 26-year-old male tuberculosis patient. Multiple CMNs are seen in both lungs with a round-shape and faint consolidation ring visible in the periphery showing RHS resemblance. (B) A 36-year-old female tuberculosis patient with positive sputum smear. There are two lesions in the anterior and posterior parts of the right upper lobe. The anterior lesion shows a RHS pattern, and the posterior lesion shows a CMNs pattern. Tree-in-bud sign (black arrow) can be seen on the edge of the lesion. (C) A 58-year-old male multiple drug resistant (MDR) tuberculosis patient with positive sputum smear. CT shows multiple RHS in the right lung and CMNs in the upper lobe of the left lung. CT, computed tomography.

Figure 9

A 26-year-old male patient with pulmonary tuberculosis. Lung CT shows diffusely distributed nodules and cystic changes in both lungs, and the lower lung air sacs are small and distributed in clusters. Thickening of the airway wall can be seen in the diseased area. A bronchoscopy lung biopsy revealed chronic inflammation and a small extent of necrosis of the bronchial mucosal tissue, and positive acid-fast staining. CT, computed tomography.

Figure 10

A 40-year-old male tuberculosis patient. Pathogen smear was positive during the initial diagnosis. There are multiple clusters of pneumatocele shown in the upper lobes of the lungs, with septal breaks in the larger cysts. GGO and multiple nodules are scattered around. GGO, ground grass opacity.

Figure 11

A 46-year-old male tuberculosis patient. Pathogen smear was positive during the initial diagnosis. Confluent lung consolidations with local honeycomb changes (A). After anti-tuberculosis treatment, consolidation was gradually replaced by pneumatoceles, and ground grass opacities gradually decreased (B: week-2 of treatment, C: week-4 of treatment). After 20 weeks of anti-tuberculosis treatment, most of the cystic degeneration area returned to normal, with nodules, fiber streaks and a small number of air sacs still remaining (D).

Figure 12

A 25-year-old male patient with blood-borne tuberculosis. (A,B) Diffuse asymmetrical distribution of GGO in both lungs, and local miliary micronodules. Lesions are more substantial in right lung and accompanied by right pleural effusion and consolidation of the right lower lung. (C) Percutaneous lung biopsy: focal epithelioid granulomatous lesions without apparent necrosis (HE stain ×100). (D) A sign of positive acid-fast staining in biopsied sample (×400).

Figure 13

A female patient of 65 years old. She had myelodysplastic syndrome (MDS), blood-borne tuberculosis, and tuberculous meningitis. The sputum tuberculosis smear was positive. Chest CT shows GGOs diffusely distribute in both lungs, subpleural lung consolidation in the right lung, and no apparent nodule seen. The background of emphysema shows pneumatocele changes against the backdrop of GGO. The patient eventually died of acute respiratory distress syndrome and multiple organ failure. GGO, ground glass opacity; CT, computed tomography.

Figure 14

A female patient of 21 years old with high fever for 2 weeks. Lung CT shows multiple nodules of different sizes in both lungs, with the distribution pattern along blood vessel branches and being non-segmental (consistent with feeling vessel sign). A lung biopsy (black arrow) revealed a granuloma with caseous necrosis and a positive acid-fast stain. Diagnosis: hematogenously disseminated tuberculosis. CT, computed tomography.

Figure 15

A 73-year-old male patient with tuberculosis. The initial sputum spear was negative. (A,B) Multiple symmetrical and random (non-segmental) distribution of nodular lesions of varying sizes in both lungs. (C,D) PET/CT: nodular increased radioactivity in the liver, pancreas, and spleen. Percutaneous lung biopsy: coagulation necrosis with granulomatous lesions, acid-fast staining (+), sputum Mycobacterium tuberculosis DNA: 4.9×10³ copies/mL. PET, positron emission tomography; CT, computed tomography.

Figure 16

A 68-year-old female emphysema patient with tuberculosis and positive sputum smear. (A,B) Computed tomography (CT) shows pan-lobular emphysema and consolidation of the right lung with multiple air-containing cavities. (C,D) In the same case re-examination 9 days later, CT shows the lesions spread along the emphysema area with pseudo-cavity.

Figure 17

A 56-year-old male tuberculosis patient with positive sputum smear. CT showed (A,B) consolidation in the emphysematous area of the lower lobe of the left lung and clustered air sacs appearance. The emphysematous change at the contralateral side (the dorsal side of the right lower lobe) can serve as a control. The re-constructed sagittal plane (C) shows the lesions extend along the pleural surface with a non-segmental distribution. (D) Histology: inflammatory consolidation combined with non-necrotizing granulomatous inflammation, accompanied by multinucleated giant cells (black arrow; HE stain, 200× magnification). PCR positive for Mycobacterium tuberculosis (courtesy of Professor Chuan-Shu Sun, Department of Radiology, Dalian Medical University, China). CT, computed tomography.

Figure 18

A 67-year-old male patient with idiopathic pulmonary fibrosis (IPF). Right lower lobe bronchoalveolar lavage fluid (BALF) tested positive for Mycobacterium tuberculosis. Computed tomography (CT) shows irregular consolidation in the interstitial fibrosis area (black arrow) (A,B). One year after anti-tuberculosis treatment (C,D), the lung consolidations were largely absorbed, revealing the previously existing cellular changes near the pleura of both lungs, in line with IPF.

Figure 19

A 39-year-old male tuberculosis patient with negative sputum test. (A,B) Chest computed tomography (CT): large consolidation and GGO of the right lung, with signs of air bronchogram, no obvious low-density necrosis area is noted. (C) CT-guided percutaneous lung biopsy: lung interstitial fibrous tissue hyperplasia with lymphocyte and plasma cell infiltration in the upper lobe of the right lung, loose emboli of granulation tissue seen in the alveoli and respiratory bronchioles (HE stain, × 400), in line with OP characteristics. (D) Acid-fast staining (×400) of the tissue specimen note Mycobacterium tuberculosis (red arrow). GGO, ground glass opacity.

Figure 20

A 44-year-old male patient with tuberculous organizing pneumonia. The sputum test was negative for Mycobacterium tuberculosis. (A) Computed tomography (CT) shows a large area of consolidation in the right lung with ground glass opacites around the edge of the lesion. (B) Contrast enhanced CT shows uneven enhancement without cavity. (C) CT-guided percutaneous lung biopsy: bronchiolitis, tissue cell deposition in the alveolar cavity, interstitial fibrous tissue hyperplasia. Histopathological consideration: organizing pneumonia (HE stain, × 400). (D) Re-examination of chest CT after 45 days of anti-tuberculosis treatment, the lesion was substantially absorbed.