Keywords
tuberculosis - lymphadenopathy - imaging - computed tomography - MRI
Introduction
Tuberculosis (TB) remains one of the leading contributors of disease burden in our
country with varied presentations involving various organ systems. It can involve
a single organ system or present in disseminated form. Pulmonary TB is by far the
most common form, followed by nodal TB. Nodal TB is the most common form of extrapulmonary
TB.
Patients of nodal TB often have a past history of inadequately treated or clinically
silent pulmonary TB. Although most patients may also show pulmonary involvement on
further examination and investigations, it is not uncommon to have isolated regional
lymphadenopathy, most commonly seen in the cervical region.[1] Nodal TB can practically involve any region in the body.
Imaging Modalities
It is critical to use the imaging modalities judiciously, keeping in mind the issue
of availability, as well as economic and radiation costs.
Radiographs
Chest radiograph (CR) is useful in the evaluation of thoracic lymphadenopathy for
which it is the primary initial modality. A lateral radiograph improves the diagnosis
of enlarged lymph nodes at several sites including hila. Large cervical lymph nodes
can also be appreciated on radiographs of the neck.
Ultrasonography
It is a very useful modality when the target region is superficial/easily accessible
and thus plays a major role in cervical lymphadenopathy. Abdominal lymphadenopathy
can also be evaluated and subjected to guided-sampling on ultrasound (US). In specific
situations, ultrasonography (USG) can be used in visualizing upper mediastinal lymph
nodes (right and left paratracheal, prevascular, subaortic, subcarinal). In addition
to superior characterization of nodal characteristics, it can be used as a valuable
tool in guided sampling and follow-up of patients.
Computed Tomography
Contrast-enhanced computed tomography (CECT) is the most important imaging modality
in intrathoracic diseases. The nature of contrast enhancement, presence or absence
of calcification, and conglomeration are some of the parameters that need to be assessed
on CT images. Characteristic appearance on CT includes necrotic nodes with peripheral
rim enhancement, conglomerate lymphadenopathy, perinodal fat streakiness, and calcification
(more prominent on treated nodes). Additional advantage includes the ability to evaluate
the lungs and the osseous structures. CECT abdomen and CT enterography are useful
in abdominal involvement.
Magnetic Resonance Imaging
On magnetic resonance imaging (MRI), three patterns can be seen—discrete, matted,
and confluent. Necrosis is seen as an area of T2 hyperintensity and T1 hypointensity.
Contrast administration is crucial, as presence or absence of necrosis can be confidently
commented upon only on a CE-MRI. Most of the patients suffering from tubercular lymphadenopathy
have to undergo repeated imaging. While superficial lymphadenopathies can be followed
up on US, deeper lesions need alternate imaging modality. MRI can fit in this situation,
in both abdominal as well as thoracic lymphadenopathies.
Fluorodeoxyglucose-Positron Emission Tomography CT
It can help in mapping the extent of the disease accurately before the initiation
of therapy and also aid in confirmation of TB. Maximum standardized uptake value can
be useful in monitoring treatment response.[2]
[3] Major drawback of fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging
is that it fails to distinguish between other similar etiologies of lymph node involvement
like metastases, sarcoidosis, and lymphoproliferative disorders. Lymphoma is the most
common misdiagnosis. However, it can suggest the site for successful biopsy and differentiate
between active and inactive nodes.[4]
Imaging Characteristics and Differentials in Tubercular Lymphadenopathy
The imaging findings and differentials are discussed site-wise (cervical, thoracic,
and abdominal lymphadenopathy) below.
Cervical Lymphadenopathy
Tubercular cervical lymphadenopathy, like any other sites, classically presents with
matted/conglomerated lymph nodes with or without necrosis. The main differential diagnoses
include other infective causes (bacterial/viral), malignant causes (lymphoma, metastases),
Kimura's disease, histiocytic disorders (Rosai–Dorfman disease), and inflammatory
causes (Kawasaki disease).
While imaging is not fool proof, several imaging characteristics have been described
for differentiating tubercular lymphadenopathy from other causes ([Fig. 1]). Besides gray scale USG, color Doppler USG has also proved to have diagnostic benefits
in differentiating tubercular lymphadenopathy from other causes. Pattanayak et al
studied the US characteristics of cervical lymph nodes in predicting the benign and
malignant etiologies. Statistically significant features are listed in [Table 1].[5]
Fig. 1 (A–C) Variable appearances of cervical lymphadenopathy in tuberculosis in three different
patients. Gray scale ultrasound (US) (A) of a 24-year-old male showing nonnecrotic supraclavicular lymphadenopathy. Axial
contrast-enhanced computed tomography (CECT) in a 17-year-old male showing enlarged
homogeneous left supraclavicular lymph nodes (asterisk in B). Another patient, 24-year-old male showing multiple conglomerate necrotic cervical
lymphadenopathy (arrow in C).
Table 1
Imaging differentiation of tubercular versus other causes of cervical lymphadenopathy
|
Etiology
|
Ultrasound characteristics
|
|
Tuberculous lymph nodes
|
• Absent hilum
• Unsharp nodal border
• Hypoechoic echotexture
• Intranodal necrosis
• Presence of ancillary features like soft tissue edema and matting
• Peripheral vascularity
|
|
Reactive lymph nodes
|
• Oval shape
• Presence of hilum
• Unsharp nodal border
• Absence of ancillary features like soft tissue edema, matting
• Absence of intranodal necrosis
• Central vascularity
|
|
Lymphomatous nodes
|
• Round shape
• Absent hilum
• Sharp nodal borders
• Hypoechoic echotexture
• Soft tissue edema
• Peripheral vascularity
|
|
Metastatic
|
• Round shape
• Hypoechoic echotexture
• Soft tissue edema
• Peripheral vascularity
|
Newer imaging modalities such as shear wave elastography (SWE) and CEUS have been
studied for their applications in tubercular lymph nodes. Patterns of enhancement
in CEUS is studied for its utility in US classification of tuberculous lymph nodes
to aid in better assessment of the disease stage.[6] More than half area of nonenhancement was found to be predictor for lymph node rupture
in cervical tubercular lymphadenopathy.[7] SWE along with conventional US can help in differentiating benign from malignant
lymph nodes.[8]
[9]
Thoracic Lymphadenopathy
Thoracic lymphadenopathy is the most common site involved in lymph nodal TB. Both
mediastinal as well as hilar lymph nodes can be affected. Uncommon sites include internal
thoracic, epicardial, and intercostal lymph nodes.
Chest Radiograph
CR can detect mediastinal and hilar lymphadenopathy. Right paratracheal lymphadenopathy
is evident by widening of right paratracheal stripe; subcarinal adenopathy is reflected
by widening of the carinal angle ([Table 2], [Fig. 2]). One of the nonspecific and less described signs on lateral radiograph, “dough
nut sign” refers to the radiopaque ring formed in the presence of enlarged subcarinal
and hilar lymph nodes where the trachea/upper lobe bronchi form the central radiolucency.
Aortic arch and pulmonary arteries form the superior and anterior aspect of the ring
which is completed by the presence of enlarged lymph nodes inferiorly.
Table 2
Radiographic features of tubercular lymphadenopathy ([Fig. 2])
|
Nodes involved
|
Imaging finding
|
|
Right paratracheal
|
Widening of right paratracheal stripe (> 5 mm)
|
|
Hilar
|
Increased density and outward convex contour of hila
|
|
Subcarinal
|
Widening of carinal angle, straightening of the left main bronchus
|
|
Azygo-esophageal
|
Displacement of the azygo-esophageal line
|
Fig. 2 (A, B) Thoracic lymphadenopathy in tuberculosis. (A) Right paratracheal (asterisk) lymphadenopathy seen as widening of right paratracheal
stripe. Right hilar adenopathy seen as hilar enlargement on postero-anterior (PA)
projection (arrow in A) and “doughnut sign” on lateral radiograph (arrow in B).
Ultrasonography
USG has an additive value in differentiation of lymph nodes from a normal or enlarged
thymus. Although the lower mediastinal stations are not amenable to USG evaluation.
Upper stations (4A, 4B, 3, 5, and 7) can be visualized under USG using proper technique[10] ([Fig. 3]). The technique of USG in the chest is described in [Table 3].
Fig. 3 (A, B) Mediastinal ultrasonography for lymph node assessment. Right parasternal approach
with linear transducer. Color Doppler images (A) and (B) show vascularity within consolidated lung. Hypoechoic (necrotic) right paratracheal
lymph node with hilar vascularity is shown (A).
Table 3
Mediastinal ultrasound technique
|
Surface location
|
Supraclavicular
|
Parasternal
|
Suprasternal
|
Suprasternal with caudal tilt
|
|
Anatomic landmark
|
Triangle between
• IJV
• SCV termination
• BCV
|
• Sternum
• trachea
• Heart and aortic origin
|
Trachea
|
• Aortic arch and branches
• Carina
|
|
Transducer
|
Linear probe axial - station 1
|
Linear probe axial - station 3A
longitudinal - station 4, 3A (medial)
|
Linear probe - axial - station 2, 3P
Endocavitatory probe
axial oblique - station 4
|
Endocavitatory probe
longitudinal - station 3A, 5, 6 (lateral sweeps)
|
Abbreviations: BCV, brachiocephalic vein; IJV, internal jugular vein; SCV, subclavian
vein.
CECT
CECT remains the workhorse of imaging in intrathoracic lymphadenopathy ([Fig. 4]). Intrathoracic lymphadenopathy, in addition to the causes listed elsewhere in the
body, has a few unique differential diagnoses such as enlarged thymus or developmental
cysts.
Fig. 4 (A, B) Thoracic tubercular lymphadenopathy on computed tomography (CT). Two different patients,
15-year-old female showing conglomerate nodes with central nonenhancing (necrotic)
areas (arrow in A). Stippled calcification in mediastinal lymph nodes (arrow in B) in another patient, 10-year-old male with microbiologically proven tuberculosis
on treatment.
MRI
As described earlier, necrosis and peripheral rim enhancement can be appreciated in
MRI ([Fig. 5]).
Fig. 5 (A, B) Thoracic lymphadenopathy on magnetic resonance imaging (MRI) in a 25-year-old male.
Axial T2-weighted image (T2WI) showing hypointense nature with central focus of hyperintensity
(arrow in A). Axial postcontrast T1W image showing rim enhancement (arrow in B).
Differential Diagnoses
There is a myriad of etiologies leading to thoracic lymphadenopathy including the
common bacterial, viral, and fungal infections. TB being the most common reason for
thoracic lymphadenopathy that commonly undergoes cross-sectional evaluation. Malignant
etiologies include metastases from esophageal, breast, and thyroid malignancies. Lymphoma
can involve any site in the body including the mediastinum.
Detailed discussion of all differentials is beyond the scope of this article. [Table 4] describes the imaging differentials in intrathoracic lymphadenopathy ([Figs. 6] and [7]).
Table 4
Imaging differentials in thoracic tubercular lymphadenopathy ([Figs. 6] and [7])
|
Size
|
Findings on ultrasound
|
Findings on CT
|
|
Tuberculosis
|
Enlarged
|
• Central hypoechoic/anechoic areas of necrosis
• Conglomeration
• Loss of fatty hilum
• Calcification
|
• Perinodal fat streakiness
• Peripheral rim enhancement
• Conglomeration
• Calcification
|
|
Normal lymph node
|
Solitary < 15 mm
Multiple < 10 mm
|
Can be oval or round.
Homogeneously hypoechoic with presence of fatty hilum
|
Well-defined margin with clear perinodal fat, preserved hilar fat
|
|
Reactive lymphadenopathy
|
Enlarged
|
Can be oval or round.
Homogenously hypoechoic with presence of fatty hilum
|
Well-defined margin with clear perinodal fat, preserved hilar fat
|
|
Lymphoma
|
Enlarged
|
• Homogeneous, no necrosis
• Compression/encasement of adjacent structures
|
• Nonnecrotic
• Mass effect/compression on adjacent structures
|
|
Metastases
|
Enlarged
|
• Can be either homogeneous or necrotic
• Solid components may appear similar to primary mass
|
• Can be either homogeneous or necrotic
|
Abbreviation: CT, computed tomography.
Fig. 6 (A–C) Imaging differential: Sarcoidosis. Axial (A, B) and coronal multiplanar reconstruction (MPR) (C) contrast-enhanced computed tomography (CECT) images showing conglomerate homogeneous
right paratracheal and symmetrical bilateral hilar nodes.
Fig. 7 (A, B) Imaging differentials: Non-Hodgkin's lymphoma in a 10-year-old male. Axial contrast-enhanced
computed tomography (CECT) images showing conglomerate homogeneous lymph nodal mass
in the visceral compartment (A, B).
Sarcoidosis remains the major imaging differential in intrathoracic tubercular lymphadenopathy.
The major differentiating points include the distribution, presence/absence of necrosis,
and pattern of calcification. The most common nodes affected in thoracic TB are right
paratracheal, hilar, and subcarinal; while bilateral hilar and right paratracheal
are the most common nodes involved in sarcoidosis. Sarcoid lymphadenopathy is typically
symmetrical, unlike TB. Lymph nodes in TB can show conglomeration and peripheral rim
enhancement whereas sarcoidosis shows discrete homogeneous nodes. Pattern of calcification
in tubercular lymph nodes after treatment is usually homogeneous while it is rim-like/egg-shell
or punctate in sarcoidosis.[11] Although less evaluated, “cluster of black pearls” is a finding in thin CECT sections
considered specific for sarcoidosis where multiple small (1–2 mm) hypodense sarcoid
nodules are seen within the homogenously enhancing lymph nodes.[12] This feature is evaluated in a single study limited to thoracic and abdominal lymphadenopathy.
Classical “garland triad” or “1-2-3 pattern” is described in CRs where triad consists
of enlarged right paratracheal, right hilar, and left hilar lymph nodes. Further,
additional presence of left-sided mediastinal/aorticopulmonary window lymph nodes
is considered as “1-2-3-4” pattern.[13]
Abdominal Lymphadenopathy
Abdominal lymphadenopathy in TB can be mesenteric or retroperitoneal.
Mesenteric Adenitis
The list of differential diagnosis of mesenteric lymphadenopathy includes a vast range
of abdomino-pelvic inflammatory disorders and malignant lymphadenopathy in metastases
or lymphoma. While differentiating lymph nodes of lymphoma from TB, it can be done
based on the presence of necrosis and calcification in the latter. One of the characteristic
signs described in CT imaging of mesenteric lymphoma is “sandwich/hamburger sign”
where there are homogenous large lymphonodal masses (resembling buns) interspersed
between the mesenteric vessels and mesenteric fat (akin to sandwich filling) with
no necrosis/calcification. It is specially described in non-Hodgkin lymphoma; however,
in patients with history of transplant, possibility of posttransplant lymphoproliferative
disorder needs to be considered.[14] Differentiating TB from various other causes of infective/inflammatory lymphadenopathy
may not be possible on imaging alone but useful associated imaging findings such as
bowel wall thickening and ileocaecal junction involvement can point toward a tubercular
etiology.
Retroperitoneal Lymph Nodes
Similar to mesenteric adenopathy, metastases, lymphoma, and other infective/inflammatory
processes remain the main differential diagnosis in retroperitoneal adenopathy. Tubercular
lymph nodes classically tend to involve the upper retroperitoneal nodes, whereas lymphoma
can involve infrarenal nodes as well ([Fig. 8]).
Fig. 8 (A–C) Abdominal lymphadenopathy in an 11-year-old girl with tuberculosis. Axial contrast-enhanced
computed tomography (CECT) images showing conglomerate necrotic nodes in periportal,
para-aortic, and aortocaval area.
CT remains the preferred modality in evaluation of abdominal TB as it allows adequate
assessment of ascites, peritoneal, and solid organs as well.[15] MRI is a useful alternative, however, with the drawback of lengthy acquisition times,
motion artifacts, and relative difficulty in detection of calcified lymph nodes.[16]
Complications
Long-term caseous necrosis in tubercular lymphadenopathy can result in:
-
Sinus or fistula formation in neck ([Fig. 9])
-
Vascular thrombosis/narrowing: can involve arterial thrombosis, portal vein, or superior
vena cava thrombosis
-
Pseudoaneurysm
-
Fibrosing mediastinitis
-
Erosion of bronchi (node-bronchial fistula, airway narrowing, or stenosis)
Fig. 9 (A–C) Complications: Node-bronchial fistula in tuberculosis. Axial contrast-enhanced computed
tomography (CECT) mediastinal window image (A) showing necrotic right hilar lymph node (LN) (arrow in A). Axial lung window images (B, C) showing extrinsic impression on right lower lobe bronchus (arrow in B) and air density within the lymph node (arrow in C), suggesting fistula.
Response Assessment
Assessing response to treatment is an integral part of any treatment. Ever since the
emergence of the drug-resistant strains, it has become even more important. While
clinical assessment is helpful, isolated nodal disease may be difficult to assess
on clinical examination alone. Therefore, imaging remains crucial in such situations.
Assessing the number and size of lymph nodes has been the traditional method of response
assessment.
On CR, response assessment is done based on a reduction in size and appearance of
calcification.
On US, the nodes may show a reduction in size and area of anechoic necrotic area,
and appearance of calcification on treatment. After adequate treatment, on CT, there
may be appearance of calcification (diffuse, coarse, eggshell) and lack of perinodal
fat streakiness ([Fig. 10]). The presence and pattern of calcification, however, does not always denote good
response to therapy.[17]
Fig. 10 (A, B) Follow-up imaging on computed tomography (CT) in tubercular lymphadenopathy in a
7-year-old male. Initial imaging (A) showing prevascular and right paratracheal lymphadenopathy. Follow-up imaging (B) showed reduction in size and development of coarse calcification.
On MRI, decrease in T1 and T2 signal intensities and change of enhancement pattern
from peripheral/rim to solid or nonenhancement can suggest response to treatment ([Fig. 11]). Some recent studies have explored the importance of nodal signal characteristics
on T1- and T2-weighted images, without the use for CE sequences. It was observed that
with treatment, there is a decrease in T1 and T2 signal in the nodes, along with size
reduction. Additional imaging with apparent diffusion coefficient values were not
contributory in the assessment.[18] Since these patients require repeated imaging, an imaging modality with no radiation
burden as in MRI can be an effective alternative to CT in appropriate cases.
Fig. 11 (A, B) Follow-up magnetic resonance imaging (MRI) in tubercular lymphadenopathy in a 23-year-old
male. (A) Initial imaging showed bilateral hilar lymph nodes with homogeneous enhancement
(arrows). Follow-up imaging (B) showed a reduction in size and rim enhancement (arrow).
18F-FDG-PET can prove useful in equivocal treatment response, or persistent nodal
disease.
