Eur Radiol (2003) 13:17711785 DOI 10.

1007/s00330-002-1612-y

CHEST

P. Van Dyck F. M. Vanhoenacker P. Van den Brande A. M. De Schepper

Imaging of pulmonary tuberculosis

Received: 5 February 2002 Revised: 25 June 2002 Accepted: 25 June 2002 Published online: 10 August 2002 Springer-Verlag 2002

P. Van Dyck F.M. Vanhoenacker () A.M. De Schepper Department of Radiology, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium e-mail: filip.vanhoenacker@planetinternet.be Tel.: +32-3-8213532 Fax: +32-3-8252026 F.M. Vanhoenacker Department of Radiology, AZ St. Maarten, Rooienberg 25, 2570 Duffel, Belgium P. Van den Brande Department of Pneumology, AZ St. Maarten, Rooienberg 25, 2570 Duffel, Belgium

Abstract Tuberculosis, more than any other infectious disease, has always been a challenge, since it has been responsible for a great amount of morbidity and mortality in humans. After a steady decline in the number of new cases during the twentieth century, due to improved social and environmental conditions, early diagnosis, and the development of antituberculous medication, a stagnation and even an increase in the number of new cases was noted in the mid-1980s. The epidemiological alteration is multifactorial: global increase in developing countries; minority groups (HIV and other immunocompromised patients); and elderly patients due to an altered immune status. Other factors that may be responsible are a delayed diagnosis, especially in elderly patients, incomplete or inadequate therapy, and the emergence of multidrug-resistant tuberculosis. The course of the disease and its corresponding clinicoradiological pattern depends on the interaction between the organism and the

host response. Classically, pulmonary tuberculosis has been classified in primary tuberculosis, which occurred previously in children, and postprimary tuberculosis, occurring in adult patients. In industrialized countries, however, there seems to be a shift of primary tuberculosis towards adults. Furthermore, due to an altered immunological response in certain groups, such as immunocompromised and elderly patients, an atypical radioclinical pattern may occur. The changing landscape, in which tuberculosis occurs, as well as the global resurgence, and the changed spectrum of the clinical and radiological presentation, justify a renewed interest of radiologists for the imaging features of pulmonary tuberculosis. This article deals with the usual imaging features of pulmonary tuberculosis as well as the atypical patterns encountered in immunodepressed and elderly patients. Keywords Pulmonary tuberculosis

Introduction
During the twentieth century, in industrialized countries, tuberculosis (TB) has evolved from a frequent and possible lethal disease to a treatable, preventable, and eradicable disease [1]. For this reason, TB has disappeared from the spotlight. Together with the decrease in TB incidence, the control programs became victims of their own success: in the U.S., the number of

TB clinics and TB beds decreased to one-third in 1988 [2]. However, since the mid-1980s, the decrease of many years standing of TB infection has come to an end, and in some countries there has been a slight increase [3]. In 1993 the World Health Organization (WHO) declared TB a global emergency: 1.7 billion of people were infected with M. tuberculosis, every year 3 million of people died from TB, and approximately 8 million new

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cases occurred. In developed countries, 80% of patients are 50 years or older. There is no doubt, however, that the HIV epidemic has played an important role in the resurgence of TB [3]. Furthermore, these patients often present with atypical clinical and radiological presentations, often resulting in late even postmortem diagnosis and hence therapy [4]. In developing countries, in which almost more than 90% of the TB cases worldwide occur, the situation is dramatic, and TB is still an evolving disease [5]. The number of cases continues to increase: between 19841986 and 19891991, the number of cases increased with more than 20 and 80% of cases involving persons in their productive years (1559 years) [6]. Also in developing countries, TB is related mainly to poverty and HIV epidemic [7]. Finally, global emergence of multidrug-resistant (MDR) strains of M. tuberculosis in recent years has greatly complicated the management and control of transmission of active cases [8]. A thorough understanding of the pathogenesis of TB is a prerequisite to the interpretation of the clinical and radiographic behavior. Pulmonary tuberculosis (PTB) can be classically divided into primary and postprimary (or reactivation) TB, each with corresponding radiological patterns. This classification, however, refers to a period of high TB prevalence (in the pre-antibiotic era). Due to the changing epidemiology, considerable overlap in the radiological presentations of those entities may exist. For didactical reasons, pathogenesis and corresponding radiographic patterns are discussed, followed by a discussion of atypical patterns.

Fig. 1 Simons foci. Spot film of the right upper lobe showing multiple calcified apical lung lesions (arrow). These lesions may be difficult to differentiate from calcified tuberculomas

Pathogenesis of tuberculosis
Primary tuberculosis After eradication of bovine TB by pasteurization of milk, enterogenous TB infection in developed countries is almost nonexistent, and primary TB infections are respiratory of origin, due to inhalation of droplets, produced when persons with pulmonary or laryngeal TB sneeze, cough, speak, or sing [1]. These droplets (210 m), laden with a few bacilli (14 m), are carried by cilia to the terminal bronchioles. Inoculation takes place most often in the best ventilated areas of the lungs, most frequently in the anterior segments of the upper lobes, middle lobe, and lingula, and the basal segments of the lower lobes. Local alveolar macrophages orchestrate a complex immunopathological process and this results, after a few weeks, in formation of epitheloid granulomas, which can develop into larger tuberculomas. Delayed hypersensitivity becomes manifest approximately 410 weeks after initial infection. At this moment, the tuberculin reaction becomes positive. Primary tuberculosis is a condition

that reflects an individuals conversion from insensitivity to the antigens of the tubercle bacilli [9]. The macroscopic hallmark of hypersensitivity is the development of caseous necrosis in the pulmonary focus and/or in the involved lymph nodes. The primary parenchymal focus is known as the Ghon focus [9]. The combination of the Ghon focus and the enlarged draining lymph nodes form the primary complex: the Ranke or Ghon complex [10]. The further extent of the primary infection, occurring after inhalation of TB bacilli, is dependent on different factors such as number and virulence of the agens, natural and acquired resistance of the host, and hypersensitivity [11]. Finally, many exogenous and endogenous factors may contribute to immunodepression: diabetes mellitus; HIV; malignancy; corticotherapy; alcoholism; and malnutrition. In the immunocompetent patient, development of specific immunity is usually adequate to limit further multiplication of bacilli, the host remains asymptomatic, and lesions heal [12]. In the clinical and radiographic occult cases, conversion from a previously negative to positive tuberculin skin test may be the only witness of primary infection. This is the case in 95% in immunocompetent patients. Healing of TB occurs with resorption of caseous necrosis, accompanied by deposition of collagen (fibrosis) and calcification [13]. This process takes place in the pulmonary foci, the affected locoregional lymph nodes, and extrapulmonary locations (kidneys, metaphyses of long bones, and brain), originating from minimal hematogenous dissemination. The radiological counterpart of these silent, healed lesions are a calcified pulmonary focus and/or mediastinal or hilar node. Proof of hematogenous (minimal) dissemination can be calcifications in the lung apices (Simons foci; Fig. 1) and in peripheral organs.

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These healed pulmonary and extra-pulmonary lesions harbor bacilli in dormant position, at low metabolic rate, but causing continuous antigenic stimulation for maintenance of hypersensitivity to tuberculous antigen. In situations of immunodepression, these bacilli can reactivate. In immunocompromised patients (HIV, alcoholics, diabetics, chronic renal insufficiency), more widespread lymphogenic and hematogenous dissemination can occur and frequently results in adenopathy and peripheral locations, respectively. If immunity is inadequate, clinically active disease can develop within 5 years after infection, called progressive primary tuberculosis [12, 14]. Postprimary disease Postprimary disease results from reactivation of dormant residual foci, in which the T-cell-mediated tissue response is directed towards caseation of those foci [9]. In general, there is clinical, radiological, and epidemiological evidence that postprimary disease can occur from four possible pathways, linking primary infection to postprimary disease. These pathways can occur isolated or combined: 1. Postprimary disease can develop from reactivation of bacilli in the lung apices. These apical lung lesions are the result of hematogenous spread during primary infection a few years earlier, after a symptom-free period. Hematogenous spread and reactivation occurs preferentially in the apical, posterior segments of the upper lobes, and apical segment of the lower lobe, because the oxygen tension is highest in the upper lung zones. Another explanation for this anatomical distribution is the impaired lymphatic clearance. The lymph flow may be restricted in the upper lung zones of the erect lung or in the posterior aspects of the lung due to the relatively greater bellows action of the anterior rib cage during respiratory excursion [9, 10]. These apical lung sites are called Simons foci (Fig. 1). After reactivation, these lesions reach confluence, liquefy, and excavate. This form of postprimary PTB is usually described as hematogenous phtysis [15]. 2. Perforation of a lymph node into a bronchus or a tuberculous bronchitis (well-known complications of gangliopulmonary TB) may cause ulcerations of principal and/or segmental bronchi [5]. Localization of those bronchial anomalies are determined by the localization of the involved bronchopulmonary and tracheobronchial lymph nodes. Frequently, the anterior segment bronchus of the upper lobe and middle lobe bronchus are affected. Other lesions can be bronchiectasis, which are typically central. Aspiration of bacilli in the bronchial lumina cause bronchogenic dis-

Fig. 2 Frhinfiltrat. Spot film of the left upper lobe. Presence of multiple micronodules suggesting bronchogenic spread in the left infraclavicular region (arrow)

semination. A classic finding is reactivation infiltrate in the subapical infraclavicular region (Frhinfiltrat) (Fig. 2). This is called bronchogenic phtysis [15]. 3. As a result of the low TB infection incidence, primary infection occurs at a later age and may affect adolescents or adult patients, whereas it was previously a disease of children. In this patient population, phtysis can occur directly from the primary focus [4]. This is called primary phtysis [16]. 4. Phtysis can also develop after reinfection. In developed countries, with low infection risk, this cause of phtysis is less probable (exogenous-reinfection phtysis) [4, 5]. In conclusion, the presentation is still frequently determined by the age of the individual: neonates and children develop primary tuberculosis. The classic presentation of PTB that occurs in adults is the postprimary TB with infiltrates in the apicoposterior segments of the lungs and formation of cavities; however, due to the changing epidemiology, this strict age-related distinction between primary and postprimary PTB is fading, resulting in possible atypical and mixed radioclinical patterns in adults and immunocompromised patients [17, 18].

Radiological patterns
Classically, as mentioned previously, PTB can be divided into a primary and postprimary pattern, corresponding to the basic pathogenesis, each presenting with a characteristic radiological presentation. In practice, however, it is very difficult to draw distinct lines between those radiographic patterns, and there is considerable overlap in

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the radiological manifestations. The disease and its radiological patterns are rather to interpret as a continuous interaction between the individual patient, with his own immune status and M. tuberculosis [19]. Recognizing the limitations of this radiographic pattern categorization, we discuss firstly the usual radiological presentation of primary (gangliopulmonary TB) and postprimary (phtysis) TB. It is emphasized, however, that the different radiological patterns can present as isolated, combined, or successive in the same patient; therefore, a specific subsection is dedicated to radiological patterns that can be seen in both primary and postprimary PTB. Finally, we focus on some atypical patterns of PTB, as observed in some groups. Typical radiological patterns of primary PTB In Western countries, in the pre-antibiotic era, primary PTB occurred predominantly in children and was particularly prevalent in areas where control measures were inadequate; however, primary TB in the adult is increasing in incidence as a result of new infection being acquired by people residing in areas where prophylactic and therapeutic measures have resulted in low incidence of infection during childhood [20]. Classically, four entities have been described: gangliopulmonary TB; tuberculous pleuritis; miliary TB; and tracheobronchial TB. In this section, only gangliopulmonary TB is discussed and the other entities are discussed in the section Radiological patterns encountered in both primary and/or postprimary PTB, since they are encountered in primary as well as in postprimary PTB. Gangliopulmonary TB is characterized by the presence of mediastinal and/or hilar adenopathies and less conspicuous parenchymal abnormalities (Ghon focus). Because of its preferential occurrence in children, it has been designated as childhood-type PTB; however, in regions with low incidence of TB, it is now a rare entity in children except for nonindigenous children and has been increasingly encountered in adults and elderly patients [4]. Right paratracheal and hilar localizations are the most common sites of nodal involvement in primary PTB, although other combinations have been described (bilateral hilar, isolated mediastinal). The prevalence of adenopathies decreases with age [21]. On contrast-enhanced CT scan, tuberculous adenopathies, often measuring more than 2 cm, show a very characteristic, but not pathognomonic, rim sign consisting of a low-density center surrounded by a peripheral enhancing rim (Fig. 3) [22]. This rim sign has also been found with atypical mycobacteria [23], lymphoma [24], and testis carcinoma [25]. Associated parenchymal infiltrates are encountered on the same side as nodal enlargement in approximately two-thirds of pediatric cases of primary PTB [21].
Fig. 3 Tuberculous adenopathy. Contrast-enhanced CT scan demonstrating an enlarged tuberculous lymph node in the upper mediastinum, with peripheral rim enhancement and low-density center

Parenchymal opacities are typically located in the periphery of the lung, especially in the subpleural areas. They are usually difficult to see on conventional radiographs, because of their small volume; therefore, CT is often necessary to detect these subtle parenchymal infiltrates [26]. In contrast to the age-related occurrence observed with lymphadenopathy, Leung et al. [21] found that the prevalence of radiographically detectable parenchymal involvement was significantly lower in children up to 3 years of age (51%) as compared with that in older children (78%) in whom the prevalence is similar to the previously reported 80% in adults [27]. Generally, the disease is self-limiting and immunocompetent patients remain usually asymptomatic. Frequently, the only radiological evidence is the so-called Ranke complex: the combination of a parenchymal scar (whether calcified or not) the Ghon lesion and calcified hilar and/or paratracheal lymph nodes (Fig. 4). Frequently, physical examination reveals no abnormalities. Gangliopulmonary TB may be complicated by perforation of an adenopathy in a bronchus (cfr. supra), retroobstructive pneumonia, and/or atelectasis (epituberculosis; Fig. 5). A retro-obstructive infiltrate in primary TB most commonly appears as an area of homogenous consolidation. Obstructive atelectasis or overinflation resulting from compression by an adjacent enlarged node have been reported to occur in 930% and 15% of children with primary TB, respectively [21]. Distribution is typically right sided, with obstruction occurring at the level of the right lobar bronchus or bronchus intermedius [28]. In these complicated cases, symptoms such as cough or wheezing are frequent. Retro-obstructive inflammation may resorb and evolve to a fibrotic and/or calcified lesion. Destruction and fibrosis of the lung parenchyma result in formation of traction bronchiectasis within the

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Fig. 4a, b Calcified Ranke complex. a Spot film of the right upper and middle lung region shows a calcified paratracheal lymph node (small arrow), associated with a calcified parenchymal scar (large arrow). b A CT scan in another patient shows associated calcified hilar adenopathy and a nodular calcified lesion within the left lung Fig. 5a, b Epituberculosis. a Posteroanterior chest radiograph. There is marked enlargement of the right hilum, due to adenopathy, with associated consolidation in the anterior segment of right upper lobe. b A CT scan in another patient. Retro-obstructive consolidation in the anterior segment of the left upper lobe, due to mediastinal adenopathies

fibrotic region. Evolution to cavitary disease is rare in children. On the contrary, primary infection in adults most frequently results in parenchymal consolidation without adenopathy. These infiltrates can excavate and lead to phtysis. Immunodeficient and elderly patients can present with the childhood type (hilar/mediastinal adenopathies and parenchymal abnormalities), frequently combined with formation of cavities (mixed type) [29]. Postprimary PTB or phtysis Postprimary PTB is one of the many terms (reactivation TB, secondary TB, adulthood TB, etc.) applied to the form of TB which develops and progresses under the influence of acquired immunity. It results from the reactivation of dormant residual foci, spread at the time of the primary infection. It is usually, but not always, a disease

of adults [30]. When observed in the pediatric age group, it is most often a disease of adolescence, particularly in girls at menarche [21]. Phtysis defines a form of respiratory TB that is characterized by the following: 1. Liquefaction of caseous necrosis 2. Formation of cavities 3. Progressive fibrosis and lung destruction Typically, lesions are located in the apicoposterior lung segments and to a lesser degree in the apical segments of the lower lobes [31]. In the first stage of disease, regions of caseous necrosis liquefy and communicate with the

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Fig. 6 Postprimary pulmonary tuberculosis with cavity formation. High-resolution CT scan of the lungs shows a thick-walled cavity in the apical segment of the left lower lobe, with small air-fluid level (arrow). Note also extensive fibroproductive lesions in the apical segment of the right and left lower lobes

Fig. 7 Airfluid level in tuberculous cavity. Posteroanterior chest radiograph revealing a large, irregularly delineated cavity in the left hilar region, with associated airfluid level

Fig. 8a, b Tracheobronchial tuberculosis. a High-resolution CT at the level of the right middle and lower lobe bronchi shows mural bronchial wall thickening. Multiple centrilobular nodular and branching linear structures are seen in the middle lobe, laterally (small arrow), and in the apical segment of the lower lobe (large arrow), suggesting bronchogenic spread. Also note the airspace consolidation along the major fissure (open arrow). b High-resolution CT at the level of the middle and right lower lobe: multiple centrilobular nodules and sharply marginated linear branching opacities (large arrow), better known as the tree-in-bud sign, are seen. Note also fuzzy marginated areas of consolidation in the apical segment of the right lower lobe. Some secondary lobules are consolidated entirely along the major fissure, with a patent bronchiole (small arrow)

tracheobronchial tree to form cavities. Higher oxygen tension results in exponential growth of bacilli. Coughing may result in bronchogenic spread in the ipsi- or contralateral lung segments and/or contamination of other patients, via inhalation of bacilli-laden droplets. The whole process can take months to years. The clinical presentation is variable and ranges from asymptomatic to insidious or acute. Cough, anorexia, weight loss, fatigue, and fever are nonspecific complaints, which are frequently disregarded by patient or his envi-

ronment, and are attributed to senile decay (patients delay). Hemoptysis is sometimes the first alarming symptom and diagnosis is suggested on radiographs. Symptoms can be more acute when phtysis occurs immediately after primary infection or exogenic reinfection or reactivation: patients present with a flu-like syndrome, e.g., fever, sputa, and night sweats. This variety of nonspecific symptoms can mimic more frequent pathology such as bacterialviral pneumonia, neoplasia, or thrombo-embolic disease; therefore, recognition by phy-

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Fig. 9 Tuberculous laryngitis. Non-enhanced CT scan of the larynx at the level of the vocal cord. Thickening of the right true vocal cord, with obliteration of the right pyriform sinus

sicians is often delayed (doctors delay). Physical examination is nonspecific as well. Radiographs may show extensive abnormalities, such as apicoposterior infiltrates, cavities, pleural exudates, fibro-productive lesions causing distortion of lung parenchyma, elevation of fissures and hila, pleural adhesions, and formation of traction bronchiectasis [19]. Cavitation in one or multiple sites is radiographically evident in 40% of cases of postprimary disease (Fig. 6). The cavity walls may range from thin and smooth to thick and nodular. It can be difficult to distinguish thinwalled cavities from bullae, cysts, or pneumatoceles [32]. When multiple apical cavities are encountered, the possibility that cystic bronchiectases are present in addition to necrotic cavities must be considered [32]. Air-fluid levels in the cavity occur in 10% of cases (Fig. 7) [25]. According to some authors, air-fluid levels can be due to superimposed bacterial or fungal infection of the cavity [33]. Bronchogenic spread is radiographically identified in 20% of cases of postprimary TB and manifests as multiple, ill-defined micronodules, distributed in a segmental or lobar distribution, distant from the site of the cavity formation and typically involving the lower lung zones [34]. On CT scan, it is identified in 95% of cases [35]. High-resolution (HR) CT is the imaging technique of choice to reveal early bronchogenic spread [36] and typical findings are 2- to 4-mm centrilobular nodules and sharply marginated linear branching opacities which have been shown to represent caseous necrosis containing bacilli within and around terminal and respiratory bronchioles (tree-in-bud sign; Fig. 8b) [36]. Ascending contaminations producing tracheitis and laryngitis can be seen (Fig. 9). Because of effective antituberculous treatment of primary TB during the 1960s, the overall incidence of endobronchial TB has decreased in western Europe [4];

Fig. 10a, b Tuberculoma. a Posteroanterior chest radiograph shows a well-delineated, solitary nodule in the left perihilar region, with central calcification. b High-resolution CT scan in another patient shows a nodular lesion in the apical segment of the left lower lobe, surrounded by small noncalcified (satellite) lesions (large arrow). Note also the tree-in-bud appearance laterally (small arrow)

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however, recently, there has been an increased incidence of endobronchial TB in HIV-positive patients [37] and in elderly subjects [38]. Although pulmonary tuberculomas are most often the result of healed primary TB, they are seen in 36% of cases of postprimary tuberculosis as the main or only abnormality on chest radiographs (Fig. 10a) [39]. This is discussed later in Radiological patterns encountered in both primary and/or postprimary PTB. Cicatrization atelectasis is a common finding after postprimary TB. Up to 40% of patients with postprimary TB have a marked fibrotic response, which manifests as atelectasis of the upper lobe, retraction of hilum, compensatory lower lobe hyperinflation, and mediastinal shift towards the fibrotic lung. Apical pleural thickening associated with fibrosis may reveal proliferation of extrapleural fatty tissue and peripheral atelectasis on CT [40]. Complete destruction of a whole lung or a major part of a lung is not uncommon in the end stage of TB. Such damage results from a combination of parenchymal and airway involvement. Secondary pyogenic or fungal infection may supervene. Once the lung is destroyed, the activity is difficult to assess with radiological studies [32]. Diagnosis of postprimary TB is made bacteriologically. After antituberculous therapy, radiographs show disappearance of infiltrates and fibrosis develops. Fibrosis can be stable or regress. When sputum is negative, but with CT findings suggestive of bronchogenic spread, a guided fibroscopy may be proposed to assess the correct diagnosis of active TB. If staining and/or culture remain negative and the imaging features remain stable, the process can be considered as inactive TB. Radiological patterns encountered in both primary and/or postprimary PTB Several radiological patterns are not exclusively seen in either primary or postprimary TB. For didactical reasons, these patterns are discussed in detail separately. Miliary tuberculosis Miliary tuberculosis results from the acute hematogenous dissemination of TB bacilli in lungs and other organs, where innumerable small tuberculous granulomas develop. It can be seen in primary or postprimary disease. Although classically seen in children, within a few months after first contact, there is increasing incidence of miliary TB in adults and elderly subjects [41]. The clinical presentation varies with age and immunological situation. Children mostly present with acute illness: fever; malaise; anorexia; dyspnea; and sometimes meningeal symptoms. Adults can present with a

Fig. 11a, b Miliary tuberculosis. a Posteroanterior chest radiograph. Innumerable tiny nodules are seen throughout both lungs. Note also enlarged hila and mediastinum due to gangliopulmonary tuberculosis. b Chest CT scan (lung window setting). Widespread micronoduli in both lungs. These nodules are uniform in size and their distribution bears no relation to the airways

more insidious clinical image. Immunodeficient adults and elderly patients can present with variable clinical findings, ranging from hyperacuterespiratory insufficiency to slowly, insidious, and progressive clinical presentation, and diagnosis is often made only post mortem [4]. Physical examination may reveal hepatosplenomegaly, lung crepitations, and choriodeal tubercles. The tuberculin skin test is usually positive, but in severe, hyperacute cases, it can remain negative. Initially, standard radiographs are normal in 2540% of cases [42]. Computed tomography can demonstrate miliary disease (Fig. 11b) before it becomes radiographically apparent. At thin-section CT, a mixture of both sharply and poorly defined, 1- to 4-mm nodules, are seen in a diffuse, random distribution often associated with intra- and interlobular septal thickening [43]. The more widespread location of these micronodules, including subpleural location, excludes the diagnosis of lymphangitis carcinomatosa and bronchiolitis [44].

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Fig. 13 Exudative tuberculous pleuritis. Contrast-enhanced CT scan shows a left-sided pleural effusion with enhancement of both visceral and parietal pleura (split-pleura sign) Fig. 12 Acute miliary tuberculosis, complicated by acute respiratory distress syndrome. Posteroanterior chest radiograph reveals a snowstorm appearance with bilateral poorly circumscribed areas of consolidation

After a few weeks, the classic miliary pattern on conventional radiographs is seen (Fig. 11a): innumerable micronodular (1-mm) infiltrates, which are all very similar, diffusely scattered in both lungs, especially the lung apices. Evolution to adult respiratory distress syndrome has been described [45], with a typical snowstorm appearance on plain radiographs (Fig. 12). Exudative pleuritis Until now, exudative pleuritis was seen most frequently in older children and adolescents as a complication of primary TB. It occurs 36 months after infection and is often asymptomatic. Recently, there is an increasing incidence of TB pleuritis in adults and elderly people in countries with low prevalence of TB infection. Bacilli can enter the pleural space from a juxtapleural pulmonary or ganglionary caseating granuloma, or via hematogenous dissemination. Only a few bacilli are necessary to produce a massive pleuritis, because it originates from an immunopathologicalhypersensitivity reaction [12]. Because of paucity of organisms in the pleural space, pleural fluid will yield positive cultures in only 2040% of cases, pleura biopsy substantially increases the diagnostic yield to approximately 75% [46]. The TB pleuritis, typically unilateral, occurs in 18% of patients with postprimary pulmonary disease [25]. In this case, a larger number of bacilli are found in the pleural space, because it originates from rupture of a cavity in the pleural space, and cultures are usually positive [46].

Symptoms are very characteristic: fever; pleural pain; and cough. Tuberculin skin test is usually positive. The diagnosis is made on physico-chemical and microscopic examination of pleural fluid: lymphocytic exudate; low pH; low glucose; and confirmed by bacteriological examination Ziehl-Neelsen staining or culture. Although usually observed in association with parenchymal and/or nodal disease, pleural effusion is the only radiographic finding indicative of primary TB in approximately 5% of adult cases [27]. Air-fluid level in the pleural space indicates presence of bronchopleural fistula [25]. Contrast-enhanced CT scan of patients with postprimary pleural effusion typically shows smooth thickening of visceral and parietal pleura (split-pleura sign; Fig. 13) [47]. This entity is usually self-limited and prognosis is good. Radiographically, sometimes a residual pleurasymphysis and pleural calcifications are seen (Fig. 14) [4]. Tuberculous pleurisy may become localized, causing a tuberculous empyema. This empyema may break through the parietal pleura to form a subcutaneous abscess, so-called empyema necessitatis [48]. In chronic tuberculous empyema, CT shows a focal fluid collection with pleural thickening and calcification and with or without extrapleural fat proliferation. Fibrothorax with diffuse pleural thickening, but without pleural effusion on CT, suggests inactivity [49]. Empyema may also communicate with the bronchial tree by bronchopleural fistula. Diagnosis of bronchopleural fistula is based on an increasing amount of sputum production, air in the pleural space, a changing airfluid level, and contralateral spread of disease. Computed tomography demonstrates directly the communication between the pleural

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tal or lobar atelectasis are radiographically apparent in 6575% and 1925% of cases, respectively [51]. On HRCT scans, acute tracheobronchial TB typically manifests as irregular or smooth circumferential bronchial narrowing associated with mural thickening (Fig. 8a) [54]. Enhancement and enlarged adjacent mediastinal nodes are also common findings in the active stage of stenosis. After healing of this focal infection of the bronchial wall, cicatricial bronchostenosis may occur. The left main bronchus is most frequently involved in fibrotic disease [51]. In the chronic fibrotic stage, CT findings include concentric narrowing of the lumen, uniform thickening of the wall, and involvement of a long bronchial segment [49]. Tuberculoma
Fig. 14 Tuberculous pleural calcifications. Posteroanterior chest radiograph reveals extensive left-sided pleural calcifications, with volume loss and secondary hyperinflation of the right lung

space and bronchial tree or lung parenchyma in patients with bronchopleural fistula [50]. High mortality in the acute phase is due to tension pneumothorax. Tracheobronchial tuberculosis Tracheobronchial tuberculosis occurs in 24% of patients with PTB [51]. It has been documented by clinicians since the introduction of bronchography and bronchoscopy in the 1940s, in patients with chronic cough and positive sputa, but without abnormalities on conventional radiography. It is seen as a complication of primary TB, and most frequently, it originates from a perforation of an adenopathy into a bronchus [52], although it may be caused by lymphogenic and hematogenous spread as well. Bronchoscopically, residual or active fistulas are seen. Typically, different stadia are distinguished [53]: ulcero-granulomatous lesions; regions of infiltrated submucosa; and granulomatous polypoid lesions, which can, in turn, ulcerate. These lesions produce fibrotic stenoses after healing, and postobstructive bronchiectasis. More commonly, bronchiectasis develops after destructionfibrosis of lung parenchyma (traction bronchiectasis). Bronchiectasis located in the apical and/or posterior segments of the upper lobes is highly suggestive of tuberculous origin. In this stage, patients present with cough, wheezing, and fever. Main, upper, and lower lobe bronchi account for threequarters of the involved sites. Plain radiographs can be completely normal; however, associated parenchymal opacities predominating in the upper lobes and segmen-

Although pulmonary tuberculomas are most often the result of healed primary TB, they are seen in 36% of cases of postprimary tuberculosis as the main or only abnormality on chest radiographs (Fig. 10a) [39]. Lesions range in size from 0.4 to 5 cm in diameter and are solitary or multiple. It is a round or oval granuloma caused by acid-fast bacilli with a wall lined by inflammatory granulomatous tissue or encapsulated by connective tissue [55]. Typically, they are smooth or sharply defined. The central portion of the tuberculoma shows caseation necrosis. A healed filled-in cavity and a rounded-off, contracted healing tuberculous lesion are the reported possible mechanisms of tuberculoma formation [39]. The majority of lesions remain stable in size and may calcify. Calcification is found in 2030% of tuberculomas and is usually nodular or diffuse [55]. In 80% of cases, small round opacities (satellite lesions) are observed in the immediate vicinity of the main lesion (Fig. 10b). Complications of PTB A residual tuberculous cavity can be colonized by Aspergillus species and present as an aspergilloma. Approximately 2555% of patients with aspergilloma have a history of previous cavitary tuberculosis. The prevalence of aspergillum in association with chronic TB has been reported to be 11% [56]. Aspergilloma consists of a cluster of intertwined hyphen matted together with a variable amount of mucus and cellular debris. Thickening of the walls of a tuberculous cavity or of the adjacent pleura is reported to be an early radiographic sign. Hemoptysis occurs in 60% of cases resulting in death in up to 5% of cases. Standard radiographs show a spherical nodule or a mass separated by a crescent-shaped area of decreased opacity or air from the adjacent cavity wall (Fig. 15)

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Fig. 15 Aspergilloma. Spot film of the left upper lobe. A nodular mass is seen within a thick-walled cavity in the left upper lobe. The residual air within the apical region of the cavity creates a socalled crescent air sign (arrow)

[57]. On supine and prone positions, it is obvious that the nodule is often mobile. Bronchogenic carcinoma and PTB often coexist, creating a difficult diagnostic problem. Manifestations of carcinoma can mimic or can be misinterpreted as progression of TB. Tuberculosis may favour the development of bronchogenic carcinoma by local mechanisms (scar cancer), or TB and carcinoma may be coincidentally associated. In addition, carcinoma may lead to reactivation of TB, both by eroding into an encapsulated focus and by affecting the patients immunity; therefore, any predominant or growing nodule should be suspicious for coexisting lung cancer in patients with TB [58]. Pulmonary arteries and veins in an area of active TB infection may demonstrate vasculitis and thrombosis. Bronchial arteries may be enlarged in bronchiectasis associated with TB or in parenchymal TB itself. In patients with bronchiectasis, nodular and tubular structures therefore are suggestive for hypertrophied bronchial arteries (Fig. 16) on HRCT scan. Spiral-CT angiography may be a useful technique to confirm these hypertrophied arteries. A Rasmussen aneurysm is a pseudoaneurysm of a pulmonary artery caused by erosion from an adjacent tuberculous cavity [59]. A review of autopsy findings in patients with a history of chronic cavitary TB showed a prevalence of Rasmussen aneurysms of 5%. Hemoptysis is the usual presenting symptom, which may be minimal, but also massive and life threatening. Arterial embolization has been demonstrated as an effective method to achieve control of bleeding. Broncholithiasis is an uncommon complication, caused by rupture of a calcified pulmonary-peribronchial node into an adjacent bronchus. Cough, wheezing, and recurrent pneumonia can be presenting symptoms.

Fig. 16 Hypertrophied bronchial arteries associated with parenchymal TB. Spot view of the right upper lung after selective bronchial angiography reveals large, hypertrophied bronchial arteries within a pulmonary consolidation area

Right-sided lobar or segmental bronchi are most frequently involved [60]. CT scan shows a calcified lymph node that is either endobronchial or peribronchial and is associated with findings of bronchial obstruction, such as atelectasis, obstructive pneumonitis, branching opacities in V- or W-shaped configuration (obstructive bronchoceles), focal hyperinflation, or bronchiectasis [61]. The most common cause of esophageal TB is secondary involvement from adjacent tuberculous adenitis. It can result in strictures (due to active granulomatous inflammatory tissue and scar tissue after healing), in esophago-tracheobronchial or mediastinal fistulas, and in traction diverticulas [56]. The subcarinal region is preferentially involved, because of the anatomic proximity of the esophagus to the diseased lymph nodes. Presenting symptoms may be fever, cough, dysphagia, and chest pain [62]. Tuberculous pericarditis is reported to complicate 1% of cases of TB. It is commonly caused by extranodal extension of tuberculous adenitis into the pericardium due to the close anatomical relationship between the lymph nodes and the posterior pericardial sac. The pericardium can also be involved in miliary spread of the disease. On CT, adenopathies and a pericardial thickening (with or without effusion) is seen. Constrictive pericarditis with fibrous or calcified constrictive thickening of the pericardium of more than 3 mm occurs as a delayed complication in approximately 10% of patients with tuberculous pericarditis [49]. Pneumothorax secondary to TB occurs in approximately 5% of patients with postprimary TB, usually in severe cavitary disease. It heralds severe and extensive

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pulmonary involvement by the infectious process, and the onset of bronchopleural fistula and empyema; therefore, if any apical abnormality is seen after reexpansion of a spontaneous pneumothorax, active TB should be considered [63]. Tuberculous fibrosing mediastinitis is an uncommon complication and progresses insidiously without significant clinical symptoms. The mediastinal granulomatous lymph nodes coalesce, and the development of multiple tuberculous granulomas creates both acute inflammatory changes and reactive fibrosis in the mediastinum. The CT findings include a mediastinal or hilar mass, calcification in the mass, tracheobronchial narrowing, pulmonary vessel encasement, and sometimes a superior vena cava syndrome [64]. Tuberculous spondylitis (Potts disease) is a wellknown complication and most commonly affects the lower thoracic and upper lumbar spine. Atypical patterns In developed countries, TB mainly affects the nonindigenous population and risk groups of the indigenous population; among the latter, elderly patients constitute onethird of total TB prevalence, whereas they represent only one-tenth of the total population and an increase in TB incidence in elderly subjects is still to be expected. Furthermore, diagnosis is frequently delayed or even made post mortem. Causes of this delayed diagnosis are nonspecific symptomatology, negative tuberculin skin tests, atypical radiological presentations, and associated diseases mimicking TB [65, 66, 67, 68, 69]. It could be expected that elderly patients present with typical radiological features of postprimary reactivation tuberculosis, i.e., apicoposterior infiltrates and cavitary disease; however, because of the altered cellular immune response in the , unusual pathogenetic mechanisms and atypical presentations for this age group may occur [70]. Several factors may influence the pathogenesis of atypical patterns in the elderly. Firstly, there is deficient cellular immunity in the elderly subject that promotes reactivation TB (typical pattern). Secondly, an exogenic reinfection or second primary infection can take place: elderly patients may have outlived their initial infecting organisms, as manifested by the negative tuberculin skin test, and become vulnerable to a second primary infection [71]. Thirdly, elderly subjects can also be infected for the first time in their life. In cases of exogenic reinfection or primary infection, a shift should be expected from the usual pathogenetic pathway (reactivation) to an unusual pathway for adults, with a presentation similar to that found in children [72, 73, 74]. These atypical findings [ventrobasal infiltrates, hilarmediastinal adenopathy (Fig. 17), and exudative pleuritis] are found more frequently in elderly subjects

Fig. 17 Gangliopulmonary tuberculosis in an adult patient (atypical pattern). Posteroanterior chest radiograph revealing widening of the upper mediastinum and hila. Note also the decreased translucency of the right middle and lower lung field due to proven superimposed tuberculous mastitis

Fig. 18 HIV-related tuberculosis. Posteroanterior chest radiograph shows a pattern of primary tuberculous lingular pneumonia in an adult HIV-positive patient

[67], resulting in frequent initial wrong diagnosis and thus delayed therapy. Recently, with the AIDS epidemic, there is increasing incidence of TB infection in HIV-infected patients. Every year, approximately 10% of the co-infected patients develop TB, whereas the annual risk of developing TB in non-HIV-infected patients is only 0.2% [7]. The AIDS patients can have massive hematogenous dissemination following primary infection, and thus have high risk of more fulminant course. During the first year after infection with TB, the risk of developing progressive primary

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disease is almost 30%, in contrast with the 3% risk of immunocompetent patients [75]. Because of deficient cellular immunity, they are also prone to reactivation TB. Most of the TB infections in HIV patients are postprimary TB. The radiographic appearance of HIV-associated PTB is dependent on the level of immunosuppression at the time of overt disease [76]. In the early stages of disease, radiographic findings are similar to those found in immunocompetent patients [77]. At severe level of immunosuppression, 1020% of patients have normal chest films [78] or demonstrate findings usually associated with primary disease, regardless of prior TB exposure status (Fig. 18) [70]. A miliary pattern of disease has also been reported to be associated with severe immunosuppression [79]. Mediastinal and hilar adenopathy occur in 75% of cases [80]. Extrapulmonary localizations are frequent in HIV-infected patients and involve brain, pericardium, intestine, peritoneum, and testes. Cryptogenic miliary TB is the term used for patients with normal chest films, positive sputum, and disseminated TB [77].

Conclusion
Because of the global increase of TB incidence, especially due to the AIDS epidemic and progressive increase of the geriatric population, the problem of TB has regained actual importance. There is a changing radiological pattern of PTB, with fading of the strict classical distinction between primary and postprimary disease. Atypical presentations are now seen, especially in HIV-infected and elderly subjects, e.g., exudative pleuritis in the elderly, gangliopulmonary forms of TB in HIV-infected adults. This results in late diagnosis and delayed therapy. Chest film is the mainstay in radiographic evaluation of suspected or proven PTB. The HRCT scan has no impact on patient management, but typical findings should suggest diagnosis, e.g., tuberculous adenopathy (rim sign), tuberculoma, and endobronchial TB (tree-in-bud sign). The CT evaluation may be helpful in determination of disease activity in some patients, but definitive diagnosis still requires isolation and identification of M. tuberculosis species in the clinical specimen.

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