Central airway pathology: clinic features, CT findings with pathologic and virtual endoscopy correlation
Insights Imaging
Central airway pathology: clinic features, CT findings with pathologic and virtual endoscopy correlation
Daniel Barnes 0 1 2 3
José Gutiérrez Chacoff 0 1 2 3
Mariana Benegas Rosario J. Perea 0 1 2 3
Teresa M. de Caralt 0 1 2 3
José Ramirez 0 1 2 3
Ivan Vollmer 0 1 2 3
Marcelo Sanchez 0 1 2 3
0 Radiology Department, Clínica Dávila de Santiago , Santiago , Chile
1 Radiology Department, Hospital Clinic de Barcelona , Villarroel 170, 08036 Barcelona , Spain
2 Daniel Barnes
3 Pathology Department, Hospital Clinic de Barcelona , Barcelona , Spain
Objectives To describe the imaging features of the central airway pathology, correlating the findings with those in pathology and virtual endoscopy. To propose a schematic and practical approach to reach diagnoses, placing strong emphasis on multidetector computed tomography (MDCT) findings. Methods We reviewed our thoracic pathology database and the central airway pathology-related literature. Best cases were selected to illustrate the main features of each disease. MDCT was performed in all cases. Multiplanar and volumerendering reconstructions were obtained when necessary. Virtual endoscopy was obtained from the CT with dedicated software. Results Pathological conditions affecting the central airways are a heterogeneous group of diseases. Focal alterations include benign neoplasms, malignant neoplasms, and nonneoplastic conditions. Diffuse abnormalities are divided into those that produce dilation and those that produce stenosis and tracheobronchomalacia. Direct bronchoscopy (DB) visualises the mucosal layer and is an important diagnostic and therapeutic weapon. However, assessing the deep layers or the adjacent tissue is not possible. MDCT and post-processing techniques such as virtual bronchoscopy (VB) provide an excellent evaluation of the airway wall.
Respiratory tract diseases; Tracheal diseases; Tuberculosis; Relapsing polychondritis; Tracheobronchomegaly
Introduction
Large-airway pathological conditions are a heterogeneous group
of diseases that include focal and diffuse lesions. Although
tracheobronchial neoplasms are uncommon, there is a high
incidence of malignancy [
1
]. Furthermore, most of the benign
neoplasms and inflammatory conditions are usually symptomatic
and need treatment. Focal lesions may be subdivided into benign
neoplasms (papilloma, hamartoma, and carcinoid), malignant
neoplasms (squamous cell carcinoma, adenoid cystic
carcinoma, other primary neoplasms such as lymphoma or
haemangiopericytoma, and secondary malignancy), and
nonneoplastic conditions (tuberculosis, post-intubation stenosis,
idiopathic subglottic stenosis, post-inflammatory pseudotumour,
trauma, and foreign body). Diffuse lesions can be classified into
lesions with dilatation of the tracheobronchial lumen
(MounierKuhn syndrome and acquired tracheobronchomegaly), lesions
with stenosis (rhinoscleromatosis, granulomatous bronchitis,
amyloidosis, sarcoidosis, granulomatosis with polyangitis, relapsing
polychondritis, osteochondroplastic tracheobronchopathy), and
lesions with respiratory collapse (tracheobronchomalacia).
Multiple detector computed tomography (MDCT) plays a
key role in the identification and characterisation of various
large-airway diseases, and post-processing tools, such as
virtual bronchoscopy, may improve the performance of the study
[
2
]. An MDCT study of the airways needs axial thin sections
(ideally 1 mm sections with 80% overlap), multiplanar
reformations, minimum intensity projections, volume-rendering
images, virtual bronchoscopy images, and sometimes
dynamic studies with inspiration and espiration acquisition. The
whole set of images and reformations is necessary to make
an adequate interpretation of an airways CT study. Intravenous
contrast is usually not necessary in benign pathology and is
useful in cases of neoplasm.
We describe the pathological conditions that affect the
trachea, its clinical characteristics and MDCT features, and
propose a schematic diagnostic approach that allows directing the
study.
Focal lesions
Benign neoplasms
Papilloma Papilloma represents an abnormal proliferation of
the squamous epithelium in the respiratory tract, secondary to
infection with human papilloma virus (HPV). Most of the
cases correspond to juvenile onset form with upper respiratory
tract infection. Tracheobronchial compromise is most
common in the adult-onset form and involves just 5% of patients,
generally between 20 and 40 years of age, infected by sexual
transmission (oral contact), with a male:female ratio of 4:1 [
3
].
HPV-6 and HPV-11 are responsible for airway infections and
have low risk of cancer compared to HPV-16 and HPV-18,
which cause the majority of cervical cancers [
4
].
MDCT shows nodules arising from the mucosal surface,
with intraluminal growth (Fig. 1). Lesions may be unique or
multiple and may cause atelectasis of the underlying lung,
with symptoms of an obstructive pneumonia. One per cent
of the patients have pulmonary spread, which manifests on
CT as multiple pulmonary nodules with air trapping areas.
Hamartoma Endobronchial hamartoma is a lesion with a true
neoplastic origin, which represents 3–20% of all lung
hamartomas [
5
]. The most frequent types of endobronchial
hamartoma are chondromatous and lipoid [
6
]. There is also
an extremely rare osteochondromatosis variety [
7
].
The hamartoma is composed of chondroid cartilage,
observed as a popcorn calcification within the lesion on CT,
fat, represented by areas of low attenuation, and fibrous and
epithelial tissue, both with soft-tissue attenuation [
8
]. The
combination of fat attenuation areas and popcorn
calcifications is considered diagnostic for hamartoma on CT [
9
]
(Fig. 2). Bronchial hamartomas tend to have more fat than
pulmonary hamartomas because the bronchial wall is rich in
fat [
6
] and popcorn calcification helps to differentiate
hamartomas from malignant tumours.
Unlike lung hamartomas, bronchial hamartomas are
generally symptomatic because of bronchial obstruction or
bleeding, manifested as obstructive pneumonia (with cough and/or
dyspnoea) or haemoptysis [
8, 9
].
Carcinoid The carcinoid is part of the spectrum of
neuroendocrine cell neoplasms, and the respiratory tract is the second most
common location (20–30% of all carcinoids), behind the
gastrointestinal tract [
10
]. Most carcinoids compromise the central
bronchus, and tracheal carcinoids are extremely rare [
11
].
Those tumours arise from Kulchitsky cells, and two
different biological behaviours are recognised. The typical
carcinoid has less than two mitoses per ten high-power fields
(HPF), and no necrosis, whereas atypical carcinoids have from
two to ten mitoses per HPF or necrosis [
12
]; 80–90% of
bronchial carcinoids are typical [
10
].
Although carcinoids may secrete active substances, such as
serotonin, carcinoid patients rarely have carcinoid syndrome
[
13
], since excess serotonin is broken down by the liver.
Characteristically, the patients with liver metastases (1–5%
of the cases) may develop carcinoid syndrome because they
lose the hepatic filter [
14
]. Other paraneoplasic presentations,
such as Cushing syndrome, are seen in less than 2% of the
cases. Up to 50% of the patients with carcinoid syndrome may
develop carcinoid heart disease, consisting of right-side heart
failure, secondary to valvulopathy [
15
].
At CT, a carcinoid tumour in the tracheobronchial tree
appears as a well-defined spherical or ovoid nodule with a slightly
lobulated border, with important contrast enhancement [
13, 16
]
(Fig. 3). Punctate or diffuse calcifications may be present in up to
30% [17]. Carcinoids tend to produce different degrees of
bronchial obstruction, which are detected at CT as indirect signs,
from air trapping or a mucoid bronchogram to lobar or
segmental atelectasis [
17
]. There are cases in which the bronchial
carcinoid presents as an Biceberg tumour^, with a small intraluminal
lesion, undetectable even by direct bronchoscopy, and a large
extraluminal component, easily detected by CT [
10
].
Malignant neoplasms
Squamous cell carcinoma (SCC) SCC is the most common
primary tracheobronchial tumour. It develops mainly in the
6th and 7th decades of life, being two to four times more
common in men than in women, and it is strongly related to
smoking [
18
].
Tracheobronchial SCC is histologically identical to lung
SCC, and metachronous or synchronous lesions are common
Fig. 1 Endobronchial papilloma
of a 50-year-old patient. (i)
Contrast-enhanced CT scan of the
chest in mediastinal window
shows a mildly enhancing nodule
(arrow). (ii) Lung window
confirms its endobronchial origin
(arrow). Diagnosis was made
after resection. (iii) Photograph of
the resected lung shows a
polypoid irregular intrabronchial
lesion. (iv) Photomicrograph
(original magnification, ×2;
haematoxylin-eosin stain) shows
an exophytic lesion with benign
keratinized squamous epithelium
(stars) covering an irregular
stroma (arrowheads)
in the oropharynx, larynx, and lungs in up to 40% of the cases
[
18
].
It is commonly infiltrative in nature, with exophytic or
ulcerative lesions, which may produce haemoptysis. When
the tumour produces stenosis larger than 50% of the airway
diameter, it generates obstructive symptomatology, with
cough, dyspnoea and wheezing.
CT imaging often shows a polypoid intraluminal mass with
irregular, smooth, or lobulated contours in the lower third of
the trachea [
11, 13
] (Fig. 4), but it can also be seen as an
eccentric narrowing of the airway or as circumferential wall
thickening. Mediastinal adenopathies or pulmonary
metastases are present in about one-third of patients at the time of
diagnosis [13].
Adenoid cystic carcinoma This is the second most common
tracheal malignancy after squamous cell carcinoma [
13, 19
],
Fig. 2 Hamartoma in a
62-yearold patient. (i) Contrast-enhanced
CT scan showing a lesion
(arrowhead) with popcorn-like
calcification and fat-tissue
attenuation, consistent with
hamartoma. (ii) Endobronchial
involvement produces air
trapping in the anterobasal
segment because of valve effect.
(iii) Gross pathology specimen
showing a multilobulated tumour
lesion that combines adipose
(arrowheads), cartilaginous
(stars) and epithelial tissue
invaginations (arrow) consistent
with hamartoma. (iv) Same
findings are shown in the
photomicrograph (original
magnification, 4×;
haematoxylineosin stain)
Fig. 3 (i) Contrast-enhanced CT
scan in a 55-year-old patient
showing a nodule within the right
main bronchus (arrowhead) with
avid contrast enhancement,
suggestive of a carcinoid tumour.
After resection, pathological
analysis (not shown) confirmed
the diagnosis. (ii) Virtual
bronchoscopy depicts the lesion
and it is the most common tumour of salivary glands in the
large airways.
This tumour has no relation with smoking [
20
]. The
patients are generally younger than 40 years of age, and there is
no difference in gender distribution [
19, 21
].
Clinically, these tumours present symptoms related with
obstruction, generally low grade, which may be confused with
asthma or bronchitis [
20
]. Haemoptysis is less common than
in squamous cell carcinoma [
11
].
Adenoid cystic carcinoma arises most frequently in the
lower trachea and main bronchi and has predominantly
submucosal extension [
19
], appearing as a lesion with a smooth
contour and intact mucosa at direct bronchoscopy [
22, 23
]. CT
shows a smooth mass with endoluminal and extraluminal
growth, and soft tissue attenuation, which usually involves
more than 180° of the airway circumference and often
encircles the lumen (Fig. 5) [20]. The longitudinal axis of the
tumour is classically greater than its axial extent [
13, 24
].
Therefore, the use of multiplanar reconstructions is very
useful for not underestimating the tumour size [
25
].
Other neoplastic malignancies There is a group of infrequent
malignant neoplasms, such as haemangiopericytoma (Fig. 6)
or lymphoma (Fig. 7), whose characteristics are not specific.
Their diagnosis is not suspected with imaging, and
histological studies are required.
Secondary malignancy Metastatic compromise of the
tracheobronchial wall is infrequent. Direct invasion usually
comes from lung, thyroid, oesophageal, or laryngeal neoplasm
and may cause obstruction or fistula. Haematogenous spread,
even more rare, may originate from lung, breast, colorectal,
renal, uterine, and skin cancer [
26
]. On CT, they are
undistinguishable from primary tumours and may present as
a solitary tumour or multiple lesions. The possibility of
endotracheal or endobronchial metastasis should be considered if
the patient has a history of malignancy in other organs (Fig. 8).
To be considered secondary, the lesion must be
histopathologically identical to the previously documented primary tumours
[
27
].
Non-neoplastic lesions
Tracheobronchial tuberculosis Some degree of airway
stenosis occurs in up to 90% of patients with endobronchial
tuberculosis despite appropriate therapy [
28
]. However,
tracheobronchial tuberculosis has been reported in 10 to 38.8%
of patients with pulmonary parenchymal tuberculosis through
bronchoscopic examination [
29
]. The development of the
disease may be secondary to direct infection of the mucosa,
submucosal lymphatic spread, or direct extension from infected
adenopathy [24].
Fig. 4 Squamous cell carcinoma in a 63-year-old patient, a heavy
smoker. (i) Axial CT scan shows a nodular lesion (arrowhead) located
on the tracheal carina with an endoluminal and extraluminal component.
(ii) Photomicrograph (original magnification, ×20; haematoxylin-eosin
stain) shows infiltrating groups of atypical squamous epithelial cells
(arrow), with necrotising material in the centre of the epithelial nest (star)
Fig. 5 Cystic adenoid carcinoma
in a 44-year-old patient, with no
smoking history. (i) Axial MDCT
(arrowhead) shows an
endoluminal mass with an
extraluminal solid component that
deforms the left side of the
tracheal wall. (ii) Coronal MDCT
reconstruction demonstrates that
the longitudinal axis of the lesion
is greater than the axial axis.
These are the typical findings in a
cystic adenoid carcinoma. After
resection, pathological analysis
confirmed the diagnosis. (iii)
Photomicrograph (original
magnification, ×4;
haematoxylineosin stain) shows an extensive
interstitial infiltration by groups
of tumoral cells with
pseudoglandular pattern (arrowheads)
Most stenoses are believed to be caused by infectious
necrosis and ulceration of the bronchial mucosa that leads to
granulation and scarring [
23
]. Active lung infection is not
required to develop airway narrowing. Infectious necrosis
and ulceration of the bronchial mucosa lead to granulomatous
scarring, which causes a fibrotic lesion with secondary
stenosis [
28, 30
]. In active tuberculosis, MDCT may show irregular
wall narrowing, with heterogeneous contrast enhancement
(Fig. 9). The fibrotic lesion is seen as a circumferential smooth
stenosis, with minimal wall thickening [28]. The disease tends
to be multifocal, usually with a normal airway between
structures [
11
], and it usually affects the left main bronchus and
distal trachea [
30
].
Post-intubation stenosis Luminal stenosis of the upper
trachea can occur in patients with a history of tracheal intubation.
High pressure in the tube balloon for prolonged periods may
produce necrosis of the tracheal mucosa, leading the
development of scar fibrosis, which produces luminal stenosis
[
16
]. The phenomenon may be seen with orotracheal and
tracheostomy tubes and is the most common cause of acquired
tracheal stenosis.
The use of low pressure cuffs has reduced the incidence of
tracheal stenosis post-intubation to less than 1% [
28
].
MDCT has 100% specificity for the diagnosis of
postintubation stenosis, characteristically showing a concentric
narrowing with an hourglass shape, located in the subglottic
area and measuring less than 2 cm [
16, 28, 31
] (Fig. 10).
Idiopathic tracheal stenosis Rare inflammatory cicatricial
stenosis of the upper trachea, without known cause. The
disease affects almost exclusively females, which some authors
explain by the absence of receptors from the sites of stenosis,
allowing the increased release of fibroblast growth factor [
32
].
Another factor that has been involved is gastroesophageal
reflux, and although its role is still undetermined,
Fig. 6 Haemangiopericytoma. (i)
Axial MDCT showing an
intratracheal mass (arrowhead)
with irregular margins, with no
specific features. (ii)
Volumerendering reconstruction showing
the important irregular stenosis.
After surgery and pathological
analysis, the diagnosis of
haemangiopericytoma was made
improvement in idiopathic tracheal stenosis with treatment for
reflux has been reported [
33
].
Most patients indicate having had symptoms for 1 to
3 years, presenting progressive dyspnoea, stridor, wheezing,
and dry cough, and they have usually been treated for
bronchitis before [
34
].
To establish the diagnosis of idiopathic tracheal stenosis
other causes of tracheal stenosis must be ruled out [
34
].
Bronchoscopy, spirometry, and MDCT are important for the
diagnosis and management of the disease. MDCT shows focal
stenosis in the subglottic trachea, very similar to
postintubation stenosis [
35
] (Fig. 11).
Inflammatory pseudotumour This is a rare inflammatory
mass composed of a polymorphous inflammatory cell
infiltrate and variable amounts of fibrosis, necrosis,
granulomatous reaction, and myofibroblastic spindle cells [
36
], which
may mimic, clinically and radiologically, a neoplastic lesion.
Pseudotumour has been associated with IgG4-related
sclerosing disease and with other inflammatory states such as
trauma, surgery, and immune alterations [
37
].
Patients can be asymptomatic or present a cough, chest
pain, fever, dyspnoea, haemoptysis, and obstructive
symptoms [
38
]. MDCT generally shows a rounded, well-defined
endoluminal lesion on the trachea or main bronchi, with
smooth contours that may have calcifications [
36, 38
], which
Fig. 8 A 58-year-old patient with
metastatic colon cancer. (i)
Multiplanar coronal
reconstruction showed a newly
appeared small nodular lesion
within the left bronchus wall
(arrowheads), highly suggestive
of progression of the disease. (ii)
Virtual bronchoscopy showed
more irregularities in the
bronchus wall
bronchus. Note the air trapping at the upper lobe of the left lung and the
loss of volume of the inferior lobe (arrow). Histological analysis (not
shown) yielded the diagnosis of lymphoma
enhances with the use of contrast, with a tendency to increase
in delayed phases due to the fibrotic nature of the lesion
(Fig. 12). An invasive behaviour is extremely rare.
The final diagnosis is made by bronchoscopic biopsy. Once
the diagnostic has been confirmed, the elective treatment is
endoscopic resection [
38
], with the exception of cases with
transmural compromise, which must be resolved surgically.
Foreign body aspiration Foreign body aspiration into the
tracheobronchial tree is common and usually self-inflicted in
children. In adults, however, it is rare and generally related to
an iatrogenic or traumatic event [
39
]. Food and broken
fragments of teeth are the most common foreign bodies aspirated,
which tend to lodge in the right or left main bronchus with a
similar frequency [
40
].
Penetration syndrome is the most common clinical
presentation of foreign body aspiration and consists of sudden onset
of choking, intractable cough, and vomiting, which may or
may not be associated with wheezing, dyspnoea, and fever
[
41
]. However, the clinical presentation varies, depending of
the size of the foreign body, from the absence of symptoms to
immediate asphyxiation and death when a large foreign body
obstructs the trachea [
42
].
Chest radiography has low sensitivity for the diagnosis of
foreign body aspiration, especially when the object is
radiolucent, detecting 5–15% of cases [
42
].
Fig. 9 Tuberculosis in the left
main bronchus of a 31-year-old
female. (i) Axial MDCT scan
shows a significant stenosis of the
main left bronchus, without the
presence of a mass. (ii) Coronal
MinIP reconstruction shows a
short area of stenosis located at
the left main bronchus (arrow)
CT is able to identify the level of obstruction and show the
endobronchial foreign body (even low density objects), and it
also allows the recognition of post-obstructive atelectases and
air trapping areas. Multiplanar reconstructions and virtual
bronchoscopy are very useful in the anatomic evaluation and
planning of the extraction of the foreign body.
Tracheobronchial trauma Tracheobronchial injuries are
uncommon and include lacerations due to penetrating trauma
and ruptures from blunt airway injury, particularly when the
glottis is closed.
Blunt tracheobronchial injuries are generally located at
about 2.5 cm of the carina, and they are the result of
compression of the airway against the closed glottis [
43
].
Bronchial lacerations have a parallel direction to the
bronchial cartilaginous ring [
43
] and commonly cause
pneumomediastinum and pneumothorax. (Fig. 13) A
pneumothorax refractory to evacuation by a correctly placed thorax
tube also suggests bronchial rupture [
44
]. Complete transverse
rupture may manifest by posterolateral displacement of the
lung on the supine CT, also named the Bfallen lung sign^ [
45
].
Tracheal lacerations are less common and typically follow
a vertical direction on the junction line of the cartilaginous and
membranous portions of the tracheal wall. The presence of
cervical subcutaneous emphysema and pneumomediastinum
suggests a tracheal lesion. CT identifies the point of laceration
in 70–100% of cases [
46
].
Bronchoscopy allows confirming the diagnosis and
suturing the gap in some cases. However, surgical repair is
required to prevent complications, such as infections and
airway stenosis [
44
].
Diffuse lesions
Mounier-Kuhn syndrome
Congenital tracheobronchomegaly is defined as
significant dilation of the large airway, affecting the trachea
Fig. 10 A 20-year-old patient
developed dyspnoea after a long
period of intubation. MDCT was
performed. (i) Multiplanar
coronal reconstruction and (ii)
volume rendering showing
stenosis in the upper trachea
(arrowhead). Planimetry, not
shown, yielded stenosis of 54%.
(iii) Virtual bronchoscopy
showing the lesion
Fig. 11 A 51-year-old female
with a long history of progressive
dyspnoea and stridor. (i)
Multiplanar sagittal
reconstruction showing a severe
subglottic stenosis (arrowhead).
(ii) Lateral view of a
volumerendering reconstruction of the
same study. No other causes were
found, and an exclusion diagnosis
of idiopathic stenosis was made
and bronchi up to the fourth branch [
45
], secondary to
severe atrophy of the longitudinal elastic fibres and
thinning of the muscularis mucosa of the affected
segments [
16
].
Typically, the diagnosis is made in males between 20
and 40 years of age with a history of recurrent
pulmonary infections. Although most of the cases are
sporadic, a familial susceptibility exists, and the syndrome has
been associated with connective-tissue diseases, such as
Ehlers-Danlos in adults or cutis laxa in children [
46
].
CT shows diffuse and symmetrical dilatation of the
large airway, generally a tracheal diameter greater than
3 cm and main bronchi diameter greater than 2.4 cm,
associated with central bronchiectasis (Fig. 14) .
Expiratory collapse is common, and the presence of
tracheal diverticula gives the trachea a corrugated
appearance [
45
].
Acquired tracheobronchomegaly
Tracheobronchial dilatation secondary to destruction of the
muscular wall of the trachea and the main bronchi, as a
tuberculosis sequela.
Tracheal and proximal bronchi dilatation associated with
pulmonary tuberculosis sequelae at CT and/or history of
treated tuberculosis strongly suggests the diagnosis (Fig. 15).
Rhinoscleromatosis
Rhinoscleroma is a chronic, slowly progressive inflammatory
disease of the upper respiratory tract, secondary to Klebsiella
rhinoscleromatis infection [
47
]. Rhinoscleroma is found
predominantly in rural areas with poor socioeconomic
conditions, where infection is facilitated by crowding and poor
hygiene and malnutrition.
Fig. 12 Inflammatory
pseudotumour in the left main
bronchus of a 50-year-old male,
with a history of cough and
wheeze for about 6 months. (i)
Axial MDCT scan in the
pulmonary window, showing a
partially occlusive endobronchial
nodule, located on the left main
bronchus. (ii) Bronchoscopic
image shows a hypervascular
lesion, obstructing 95% of the
bronchial lumen of the left main
bronchus. Final diagnosis was
made after resection. (iii)
Photomicrograph (original
magnification, ×4;
haematoxylineosin stain) demonstrates an
inflammatory infiltrate,
composed mainly of
myofibroblasts, characteristic of
inflammatory pseudotumour
The establishment of the disease is related to disabled
macrophages, which allow bacterial multiplication within them,
producing an ineffective delayed hypersensitivity response.
Scleroma primarily affects the nasal cavity (95–100%), but
the nasopharynx (18–43%), oropharynx (13–35%), larynx
(15–40%), trachea (12%), and bronchi (2–7%) can also be
involved [
48, 49
].
The disease tends to progress slowly in periods of
remission and relapse through three overlapping stages: the
rhinitic stage, granulomatous stage with plasma cells and
Mikulicz cells (histiocytes containing K. rhinoscleromatis
bacilli) and fibrotic stage, characterised by scar tissue [
28,
50
]. A positive K. rhinoscleromatis bacilli culture is
diagnostic for the disease but occurs in less than 60% of
cases [51].
Tracheal rhinoscleroma is usually seen in continuity
with laryngeal scleroma [
49
] and detected in the fibrotic
stage, generally affecting the subglottic area. CT shows
nodular concentric narrowing of the trachea, which may
extend to the main bronchi. The lesions have soft tissue
behaviour, classically without calcifications (Fig. 16) [
28
].
Fig. 14 Mounier-Kuhn
syndrome in a 45-year-old patient
with a long history of lower
respiratory tract infections. (i, ii)
Axial and coronal MDCT scan,
showing significant
tracheobronchial dilatation and
central bronchiectasis, both
typical findings of Mounier-Kuhn
syndrome
Granulomatous bronchitis is a cicatricial condition, secondary
to a non-tuberculous infection sequela. Usually it is
asymptomatic, but it may predispose the patient to pulmonary
infections.
At MDCT, granulomatous bronchitis presents as central
bronchiectasis in a focal area with wall thickening and diffuse wall
calcifications and normally corresponds to an incidental finding.
Amyloidosis
Amyloidosis is defined as abnormal extracellular deposits of
amyloid protein, which may be idiopathic or associated with
inflammatory, hereditary, or neoplastic disorders [
52
].
Thoracic disease is an unusual manifestation of primary
amyloidosis and may present as tracheobronchial deposits,
diffuse interstitial infiltration of the lungs, and pulmonary
nodules [
28
].
Tracheobronchial amyloidosis is the most common
presentation form of thoracic amyloidosis, and it is characterised by
the deposition of amyloid material as submucosal plaques
Fig. 16 Tracheal rhinoscleroma
in a 47-year-old male. (i) Axial
MDCT scan shows a concentric
irregular thickening of the trachea
wall without evident
calcifications. (ii) Sagittal MDCT
scan demonstrates diffuse
irregular narrowing of the tracheal
wall, including the posterior. (iii)
Bronchoscopy shows nodular
plaques on the mucosal surface of
the trachea
and/or polypoid tumours in the airways [
53
], which may be
localised, diffuse, or multifocal.
Patients are occasionally asymptomatic but often present
with dyspnoea, wheezing, cough, haemoptysis, or recurrent
pneumonia. The symptoms are usually nonspecific, with
recurrent pulmonary infections or mimicking bronchial asthma [
8
].
MDCT shows irregular narrowing of the lumen with a
nodular surface. The lesions may extend to the main bronchi, and
they usually show calcifications and ossifications (Fig. 17).
Furthermore, the lesions do not affect the posterior wall of
the airway, which is an important point in the differential
diagnosis [
28
].
Granulomatosis with polyangitis
Granulomatosis with polyangitis is an idiopathic necrotising
granulomatous vasculitis, which is capable of affecting all
Fig. 17 Tracheal amyloidosis in
a patient with a history of
pulmonary amyloidosis and
episodic dyspnoea. (i) Coronal
MDCT scan shows tracheal
nodules protruding into the
tracheal lumen, which has
calcifications. (ii) Axial MDCT
scan demonstrates the nodular
affectation and the compromised
posterior tracheal wall. (iii)
Virtual endoscopy shows diffuse
nodular narrowing of the tracheal
lumen
Fig. 18 Tracheobronchial
granulomatosis with polyangitis
in a 57-year-old patient with a
long history of multisystemic
disease. (i) Axial MDCT scan
shows a diffuse thickening of the
bronchial wall, including the
posterior wall, which helps to
differentiate it from
polychondritis. (ii) Coronal VRT
reconstruction demonstrates
stenosis on the subglottic area and
left main bronchus. (iii)
Photomicrograph (original
magnification, ×20;
haematoxylin-eosin stain) shows
a necrotising granulomatous
lesion with focal vascular
destruction. The shape of the
granuloma is elongated and the
material in the necrotic centre has
abundant nuclear debris
organs but has a predilection for the upper respiratory tract,
lungs, and kidneys [
54
].
The presentation forms vary from localised granulomatous
disease of the respiratory tract to a medium-sized vessel
vasculitis, with multiorgan compromise, predominantly renal and
pulmonary. Therefore, clinical presentation is usually not
specific and includes upper and lower respiratory tract symptoms,
weight loss, and fever, which lead to a delay in diagnosis.
Some patients may present with respiratory or renal failure
[
55
]. The serum level of antineutrophil cytoplasmic antibodies
directed against proteinase 3 is elevated in up to 90% of
patients with granulomatosis with polyangitis, and it is
considered an inflammatory activity marker. However, positivity is
not conclusive for the diagnosis and negative test results do
not exclude the disease. Biopsy still remains the standard
means of diagnosis [
56
].
The tracheobronchial tree is the second most commonly
affected area in the thorax in granulomatosis with polyangitis,
involving 15 to 55% of the patients, generally in the context of
multisystemic disease, and it is more common in females
under 30 years of age [
57
].
CT shows focal, multifocal, or diffuse thickening
(nodular or smooth) of the tracheobronchial walls
involving the posterior membrane, without the presence
of calcifications [
45
] (Fig. 18). Circumferential
compromise of the subglottic area of the trachea is the most
frequent airway manifestation of granulomatosis with
polyangitis and leads to stenosis in up to 25% of the
patients [
58
]. Bronchial stenosis is just seen in 18% of
the cases [
58
] and may produce atelectasis and
bronchie c t a s i s . P u l m o n a r y m a n i f e s t a t i o n s ( g r o u n d - g l a s s
o p a c i t i e s , c o n s o l i da t i o n s, a n d s o l i d o r c a v i t a t e d
nodules) may also be present and are useful for the
diagnosis [
11
].
Sarcoidosis
Sarcoidosis is a systemic granulomatous disease without a
known aetiology, characterised histologically by the
infiltration of affected tissue by non-caseating granulomatous
inflammation. Although pulmonary and mediastinal involvement are
the most common manifestation of sarcoidosis, large airway
disease is infrequent, affecting 1–3% of the patients, mainly in
the upper trachea. The distal part of the trachea and main
bronchi are less affected [
59
].
There are two forms of central airway affectation, the
extrinsic compression from hilar or mediastinal adenopathies
and the wall affectation secondary to the formation within
the mucosa and submucosa [
28
].
MDCT allows suggesting the diagnosis when tracheal wall
thickening and narrowing of the lumen are seen in a patient
with another manifestation of sarcoidosis [
24, 31
] (Fig. 19).
Relapsing polychondritis
Relapsing polychondritis is a systemic disease, characterised
by recurrent episodes of cartilaginous inflammation that lead
to cartilage destruction. The disease is characterised by a
chondral and perichondral inflammation secondary to an
immune-mediated reaction of unknown cause, which implies
antibodies against extracellular matrix components such as
collagen type II and matrilin 1 [
60
].
Fig. 19 Tracheal sarcoidosis in a
59-year-old female with a history
of pulmonary sarcoidosis. (i)
Axial MDCT scan shows diffuse
and irregular trachea. (ii) Virtual
bronchoscopy and (iii) direct
bronchoscopy have excellent
correlation. (iv) Photomicrograph
(original magnification, ×2;
haematoxylin-eosin stain) shows
small epithelioid granulomas
without necrosis
This disorder affects not only the cartilaginous
structures of the ears, nose, and tracheobronchial tree but also
the joints, inner ear, eyes, and cardiovascular system
[
60
].
At the time of diagnosis, the respiratory tract involves
only 10% of the patients, but in the course of the disease
it occurs in up to 50% [
61
]. Although the disease affects
men and women equally, the airway affectation is more
common in women [
60
]. Involvement of the respiratory
tract carries a poor prognosis, and mortality is usually
secondary to pneumonia [
62
].
CT shows increased attenuation and thickening of the
tracheobronchial wall, with or without mural
calcifications, and sparing of the posterior membranous wall [
28,
63
] (Fig. 20). At a later stage, fibrosis leads to luminal
irregular narrowing, and loss of the structural support of
the cartilage leads to tracheobronchomalacia, which is
seen as tracheobronchial collapse and air trapping on the
expiratory CT scan [11, 24].
Tracheobronchopathia osteochondroplastica
Tracheobronchopathia osteochondroplastic is a rare idiopathic
benign disorder characterised by multiple submucosal
cartilaginous and osseous nodules in the respiratory tract that can
involve the entire trachea and mainstem bronchi [
64
].
Pathogenesis of this condition is still unclear, with familial
cases and others associated with chronic inflammation or
trauma [
65
]. There is a male predilection (3:1) and it is usually
diagnosed in patients over 50 years of age [
66
].
The bronchoscopic image is usually diagnostic,
displaying multiple papilla-like protrusions from the
anterior and lateral walls of the trachea, which has a
cobblestone appearance, with an intact posterior wall. In
advanced cases, lesions may cause airway deformity
and obstruction [
67
]. Histologically, metaplastic cartilage
and bone are found in the submucosa [
68
].
CT can depict thickened tracheal cartilage with
irregular nodular calcification, which affects the lower
twoFig. 20 Relapsing polychondritis
of the trachea in a 51-year-old
patient. (i) Axial MDCT shows
wall thickening, sparing the
posterior wall of the trachea. (ii)
Coronal MDCT shows extensive
compromise of the trachea. Note
the high density of the thickening
wall
Fig. 21 Tracheobronchopathia
osteochondroplastica, as an
incidental finding in a 63-year-old
patient. (i) Axial MDCT scan
shows an irregular thickening of
the tracheal wall with
calcifications and sparing the
posterior wall. (ii) VRT
reconstruction demonstrating the
extension of the disease along the
tracheal wall. (iii) Endoscopy
demonstrated a nodular pattern
without compromise of the
posterior wall. (iv)
Photomicrograph (original
magnification, ×2;
haematoxylineosin stain) shows chondroid and
bony material (star) beneath the
ciliated surface (arrows)
thirds of the trachea and proximal portions of the
primary bronchi [
28
]. Multiple nodules, with or without
calcification, may project into the airway lumen, sparing
the posterior membranous wall of the trachea [
24, 28
]
(Fig. 21).
Tracheobronchomalacia
Tracheobronchomalacia (TBM) is characterised by an
excessive expiratory airway collapse due to weakness of the
airway walls secondary to alteration of the cartilaginous
supports and/or redundancy of the posterior tracheal
membranous wall [
69
].
Compromise of both the trachea and bronchi is the most
common type of the disease (63%), followed by isolated
tracheal involvement (22%) and, finally, isolated bronchial
involvement (15%) [
70
].
Authors report that tracheobronchomalacia may be
idiopathic, associated with prematurity and congenital
cartilaginous weakness among other congenital anomalies.
The acquired form is most commonly associated with
prolonged mechanical endotracheal intubation, chronic
airway inflammation including chronic obstructive
pulmonary disease, and relapsing polychondritis [
71
].
Classically the diagnosis requires expiratory collapse
>50%. However, recent studies conducted in healthy
volunteers with normal pulmonary function have reported mean
levels of expiratory collapse >50%, which would indicate
the need to establish new thresholds of collapse for the
diagnosis of the disease [
72
].
MDCT is now considered a first-line screening tool for
clinically suspected TBM and may also serve as an
adjunct to bronchoscopy in preoperative planning and even
as an alternative to bronchoscopy in the paediatric or
elderly populations [
8, 9
]. The acquisition technique is
Fig. 22 Tracheobronchomalacia
in a 67-year-old patient. (i)
Inspiratory axial MDCT shows a
normal tracheal diameter. (ii)
Expiratory axial MDCT scan
demonstrating collapse of the
tracheal wall during expiration,
characteristic of
tracheobronchomalacia
important to maximise the ability of the study in the
diagnosis and classification of patients. At end expiration,
tracheal collapse is submaximal. Therefore, dynamic
acquisition during expiration must be used whenever the
patient can follow instructions [73].
On the inspiratory MDCT scan, a lunate tracheal
configuration (coronal to sagittal diameter ratio >1) is highly specific
for TBM, but it has low sensitivity [
74
]. On the dynamic
MDCT scan, a crescentic tracheal morphology, also called
the Bfrown sign^, is highly specific for tracheobronchomalacia
[
74
], and when it is present it may indicate the need for
tracheoplasty to reinforce the posterior wall [
10, 11
]
(Fig. 22). Concentric collapse of the tracheal lumen is less
common, and it may be associated with relapsing
polychondritis [74].
In patients with mucopolysaccharidosis, upper
respiratory tract involvement due to glycosaminoglycan
deposition in the tracheobronchial cartilages may lead to tracheal
narrowing and tracheomalacia, among other causes, such
as an excess of redundant parapharyngeal tissue that
prolapses into the respiratory tract. It is recommended to
assess the upper respiratory tract in these patients when
C Ts a r e p e r f o r m e d f o r o t h e r r e a s o n s ( c o l u m n ,
craniocervical junction, etc.) [
75
].
Fig. 24 Schematic diagnostic
approach of tracheobronchial
diffuse lesions
Diagnostic approach
Although most of the focal lesions are neoplastic, the
distinction between nodular predominance and stenotic
predominance may allow the differentiation between a neoplastic
origin and non-neoplastic origin. Furthermore, the infiltrative
character of a lesion is highly suggestive of malignancy
(Fig. 23).
Diffuse lesions have a low probability of malignancy. In
these lesions, the affectation of the posterior wall and the
presence of calcification may help to narrow the differential
diagnosis (Fig. 24).
Conclusion
MDCT is an excellent diagnostic method in the detection and
classification of central airway pathologies. To improve
MDCT’s diagnostic accuracy it is necessary to establish
protocols according to clinical suspicion and use appropriate
post-processing tools, such as virtual bronchoscopy.
A schematic diagnostic approach to recognise central
airway disorders prevents unnecessary diagnostic tests and
delays in treatment. However, a biopsy may be required to
make the final diagnosis.
Acknowledgements Neither grant funding nor other financial support
was received by the authors during preparation of the submitted work.
Open Access This article is distributed under the terms of the
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creativecommons.org/licenses/by/4.0/), which permits unrestricted
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to the Creative Commons license, and indicate if changes were made.
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