An approach to HRCT assesment and diffrential diagnosis of multiple nodular opacities is based on the consideration of their size, appearance, attenuation and distribution. A consideration of nodule size can be important in differential diagnosis, although it is not always of value. For example, the nodules seen in patients with miliary tuberculosis are usually quite small, and uncommonly exceed 5 mm. On the other hand, nodules in patients with hematogenous metastases are often larger than this.

1. HRCT – Multiple Nodules &
Nodular Opacities
Presented by Dr Vrishit Saraswat.
Guided by Prof. Dr Dharmraj Meena.
Department of Radiodiagnosis

2. • An approach to HRCT assesment and
diffrential diagnosis of multiple nodular
opacities is based on the consideration of
their size, appearance, attenuation and
distribution.

3. Nodule
• Round pulmonary opacity
• Small or large
• Well defined or ill defined.
• Soft tissue or GGO
Micro nodule Small nodule Large nodule Mass
Less than 3mm 3mm -9mm 1cm - 3cm More than 3cm

4. • A consideration of nodule size can be
important in differential diagnosis, although it
is not always of value. For example, the
nodules seen in patients with miliary
tuberculosis are usually quite small, and
uncommonly exceed 5 mm. On the other
hand, nodules in patients with hematogenous
metastases are often larger than this.

5. Nodule appearance and attenuation
• Interestitial or airspace nodule
Interestitial Air-space
Mostly well defined margins ,
of soft tissue attenuation (
Nodule )
Nodules as small as 1-2 mm
can be detected on HRCT
More likely to be ill defined
margins. Can be of either soft
tissue attenuation or hazy and
less dense than vessels (GGO).
Sometimes a cluster or rosette
of nodules is seen.
Sarcoidosis,
silicosis,
LCH,CWP,
metastatis
Bronchiolitis,
Adenocarcinoma,
aspiration,
vasculitis,pulmon
ary oedema, OP

6. • Despite these differences in appearance, a
distinction between interstitial and airspace nodules
on the basis of HRCT findings can be quite difficult,
and in fact, is somewhat arbitrary because many
nodular diseases affect both the interstitial and
alveolar compartments histologically.

7. Secondary lobule.
The centrilobular artery (in blue: oxygen-poor blood) and the terminal
bronchiole run in the center. Lymphatics and veins (in red: oxygen-rich blood) run
within the interlobular septa

8. Centrilobular area in blue (left) and perilymphatic area in yellow (right)

9. Nodule distribution and pattern
• Anatomic distribution or location of nodule is
more important feature on HRCT (than its
appearance).
• 3 types -
A. Perilymphatic
B. Random
C. Centrilobular

11. Perilymphatic or Lymphatic
Distribution
• Mostly associated with sarcoidosis, silicosis,
CWP, lymphangitic spread of carcinoma,
LIP(lym int pneumonia.)
• Perihilar-peribronchovascular, centrilobular-
peribronchovascular, subpleural.
• Because the nodules occur in these specific
regions, the overall involvement of lung
usually appears patchy, with some lung
regions normal and others quite abnormal.

12. Interlobular
septal
Nodules
Centrilobular
Peribronchovascu
lar
Nodules
Subpleural
nodules and
“pseudoplaques”
Peribroncho
vascular
nodules

13. pseudoplaques
• linear areas of subpleural opacity several millimeters
in thickness that mimic the appearance of asbestos-
related parietal pleural plaques

14. SARCOIDOSIS
• Immune response of body for either
infections( bact, fung,ricket) or chemicals,
causing granulomatous infection, leading to
enlarged lymph nodes.
• Genetics also play some role.
• Associated increased levels of calcium( n-PTh)
and ACE.

15. • 95% patients show perihilar peribronchovascular and in
relation to major fissures( sub pleural)
• nodules ranging upto 1cm.
• Nodules are sharply defined , even if they are small.
• Few pts show LN as large as 4cm(conglomerated) that
may show irregular margins, often associated with
adjacent small nodules ( Galaxy sign ).
• Upper lobe predominance with asymmetry.
• Patchy involvement of lung.

19. Silicosis & CWP
• Silicosis A.k.a pneumono-ultramicroscopic-
silicovolcano-coniosis.
• c.a. – fine silica dust, which gets deposited in
lungs, later engulfed by macrophages.
• Nodules on HRCT are usually small ( upto 2-5mm)
• Mostly centrilobular-peribronchovascular and
subpleural ( costal margins).
• Nodules often calcify in pts with silicosis.
• Upper lobe predominance with bilaterally
symmetrical.

22. Lymphangitic spread of tumor
• Nodules most commonly seen in perihilar-
peribronchovascular and interlobular septa
( beaded appearance )
• Subpleural and centri-peribronchovascular
involvement is not seen/rarely seen.
• In a post mortem study 19 of 22 cases with
interstitial pulmonary metastases showed the
appearance of beaded or nodular septal
thickening on HRCT. beaded septa were not
noted in any of the specimens of patients with
pulmonary edema, fibrosis, or in normal lungs.

23. • Diffrential diagnosis for septal thickening
a) Smokers**
b) LIP(lymphoid int pneu) - may result in a
variety of appearances , but in some patients,
it closely mimics the appearance of
lymphangitic spread of carcinoma, with
subpleural, peribronchovascular, and septal
nodules. This is particularly common in
patients with AIDS.

28. Random Distribution
Miliary TB , Miliary fungal and hematogenous metastasis.
Lung is diffusely involved , however
Miliary infection
• Nodules measure upto
several millimeters.
• Diffuse and uniform
distribution on axial
images.
• Along the fissures and
peripheral pleural surface.
• Upper lobe predominance
( Tb)
Hematogenous metastatsis
• Nodules are larger a few
millimeters.
• Have tendency to
predominate in lung
periphery in early stage, later
become diffuse.
• Mostly inside a sec. lobule,
b/w septa and broncho-vas
complex.
• Lower lobe predominance

30. A

31. B

32. Centrilobular Distribution
• Nodules may be dense and of homogenous opacity OR
of GGO.
• Single nodule OR rosette of nodules
• Nodules are often ill-defined.
• Usually separated from pleural surface, fissures and
interlobular septa by a distance of atleast several
millimeters.
• This difference is particularly valuable in distinguishing
centrilobular nodules from perilymphatic and random
nodules.
• When nodules are large, they may touch the pleural
surface, however they do not appear to arise from it.

33. • Nodule is related to centrilobular structures like
small vessels and bronchioles.
• On HRCT the typical centrilobular nodule appear
perivascular or peribronchiolar
( obscuring the smallest visible pulmonary artery
or rounded lucency within a centrilobular nodule
).
• The differential diagnosis of centrilobular nodule
is long. Once a centrilobular pattern is identified,
the presence of Tree in bud should be sought.

36. “Tree in bud”
• Centrilobular nodule may be associated with this important
finding which of great value in differential diagnosis.
• The presence of dilated centrilobular bronchioles with their
lumina impacted with mucus, fluid, or pus, and is often
associated with peribronchiolar inflammation.
• Branching pattern of the dilated bronchiole and the
presence of illdefined nodules of peribronchiolar
inflammation, its appearance has been likened to a budding
or fruiting tree.
• a tree-in-bud pattern can usually be distinguished from
normal centrilobular vessels by their more irregular
appearance, a lack of tapering, and a knobby or bulbous
appearance at the tips of small branches.

37. Associated features with “tree in bud”
• Bronchiolar dilatation and wall thickening can
sometimes be seen in association with tree in-
bud if the dilated bronchioles are air filled;
normal bronchioles should not be visible in
the peripheral 1 cm of the lung.
• In a study 26 of 27 patients with showing tree
in bud on HRCT showed bronchiectasis or
bronchial wall thickening.

41. • Thus, in patients with a centrilobular distribution of
nodules, if tree-in-bud can be recognized, the
differential diagnosis is limited, and these infections
should be strongly considered :-
a) M. Tuberculosis
b) Bronchopneumonia of any cause ( V,B,F)
c) Infectious bronchiolitis
d) Cystic fibrosis
e) Bronchiectasis of of any cause
f) ABPA or asthama
g) FB (asso. with collagen vasc dis or AIDS).

42. • In a study of 141 pateints with centrilobular
opacities with tree in bud appearance, it was
found that a large percentage of patients who
were (a) carriers of human T-lymphotropic virus
type 1 ( HTLV-1; 88 of 99 patients) or (b) had M.
pneumoniae pneumonia (44 of 52 patients),
Mycobacterium tuberculosis (MTB; 38 of 52
patients), MAC (22 of 37 patients),
Mycobacterium kansasii (27 of 33 patients), ABPA
(6 of 9 patients), diffuse panbronchiolitis (DPB; all
of 12 patients), diffuse aspiration bronchiolitis (12
of 13 patients), or FB (5 of 7 patients).

43. • The distribution of tree-in-bud may be of some
value in diagnosis. In the study by Okada et al.
(66), tree-inbud predominated in the peripheral
lungs in about 70% of patients Patients with ABPA
were an exception abnormal findings were
predominantly central in 77.8%.
• Tree-in-bud associated with acute or chronic
bacterial infection often shows a lower lobe
predominance, and is often patchy in
distribution.

44. Bronchiolar and peribronchiolar
diseases.
• Endobronchial spread of tuberculosis, non tumberculous
mycobact. Diseases and other granulomatous infections.
Nodules or clusters of nodules are most often solid
appearing, typically patchy in distribution, may be focal or
multifocal.
Upper lobe predominance is typical for TB. Nodules in TB
may predominate in relation to cavitatory infection.
Non TB myco. (MAC) may predominate in lung bases,
middle lobe and lingula.
• Bronchopneumonia
HRCT findings quite similar to endobronchial spread of tb.
Except that, there will be no cavitation

45. Centrilobular nodules in a patient with bacterial bronchopneumonia, clusters
of centrilobular nodules are present in the lower lobes. The most peripheral
of these are centered a few millimeters from the pleural surface

46. Endobronchial spread of infection in a patient with multidrug-resistant
tuberculosis. A cavity is associated with multiple centrilobular nodules. The
largest of these touch the pleural surface, but they are centered about 5 mm
from it.

47. • Infectious bronchiolitis
Nodules are often of GGO. With diffuse involvement.
Child, fever, dysnea, wheezing. RCV
• Cystic Fibrois
three in bud opacity with central bronciectasis with
mucus or pus-filled bronchioles. Typically predominate
upperlobe.
• Bronchiectasis
findings similar to cystic fibrosis. Nodules usually seen
in areas of abnormal bronchi.

49. Centrilobular bronchiolar abnormality with tree-in-bud in a patient with cystic fibrosis.
Fluid-, mucus-, or pus-filled centrilobular bronchioles result in a tree-in-bud
appearance in several lung regions (arrows). These are associated with findings of
bronchiectasis.

50. • Asthama and ABPA
Centrilobular nodules or TIB
Bilateral ,patchy, upper lobe predominance.
Nodules are more common in ABPA*.
• Hypersensitivity Pneumonitis
Centrilobular nodule of GGO
Diffuse Bilateral involvement with upper lobe
predominance.
H/O allergy to various allergens.

51. HP

52. • Langerhans histiocytosis
A combination of nodules, cavitatory nodules
and cysts is very typical. Upper lobe
predominance.
• Organizing pneumonia
ill-defined solid or GGO nodules upto 1cm
seen , with lower lobe predominance.
Frank consolidation with larger areas of GGO
in lower lobe is more common with OP.

53. LCH

55. • Bronchiolitis Obliterans
Nodules may occasionally be seen , but is not a
common feature.
Airway obstruction with air trapping is much
more frequent.
• Respiratory Bronchiolitis
Non specific reaction to inhaled irritants,
usually in association with cigarette smoking.

56. In symptomatic patients, macrophages and
inflammatory cells extend into the peribronchiolar
airspaces and alveolar walls.When associated with
symptoms, the term respiratory bronchiolitis-
interstitial lung disease ( RB-ILD) is used.
• Multifocal ground-glass nodules with a centrilobular
distribution that reflects the peribronchiolar nature of
this disease . During follow-up, centrilobular nodules
may evolve into areas of centrilobular emphysema.
Patchy ground-glass opacities can also be seen and
tend to increase in frequency with follow-up. An upper
lobe predominance is typical.

58. H/O smoking

59. • Asbestosis
fibre deposition -> cellular response -> fibrosis
Ill defined centrilobular nodule, usually at lung bases.
• Pneumoconiosis
Nodules, in case of silicosis are often solid in
appearance and sharply marginated. CWP and
pneumoconiosis associated with other inhaled
minerals (e.g., siderosis) can result in similar histologic
and imaging abnormalities, but nodules may be less
dense (i.e., ground-glass opacity) and less well-defined
than those of silicosis. Upper lobe predominance is
common

60. • Follicular Bronchiolitis
Characterized by hyperplastic lymphoid
follicles along the walls of centrilobular
bronchioles.
Small well defined nodules less than 3mm
two types – primary :asso with AIDS,RA.
- Secondary: asso with infection.

61. Vascular & Perivascular Diseases
• Vascular abnormalities, localized either to the walls of
arteries or to perivascular tissues, can cause a
centrilobular ground glass opacity. Because airways
are not involved, bronchiolectasis and tree-in-bud are
typically absent.
• Pulmonary Edema & Pulmonary hypertension
Mild cases of edema may show hazy, ill-defined
centrilobular opacities, usually of ground-glass opacity.
Increased prominence of the centrilobular artery
resulting from perivascular interstitial thickening is also
commonly visible.

62. •Pulmonary Hemorrhage
Ill-defined centrilobular nodules may occasionally be
seen in patients with acute pulmonary hemorrhage . In
children with idiopathic pulmonary hemorrhage, also
known as idiopathic pulmonary hemosiderosis, recurrent
episodes of pulmonary hemorrhage may result in ill-
defined centrilobular nodules . This finding may be
related to deposition of hemosiderin-laden macrophages
in relation to small vessels and bronchioles. Nodules are
usually of ground-glass opacity.

64. • Centrilobular nodules of GGO typically reflect
processes that produce peribronchiolar
inflammation, infiltration, or fibrosis without
consolidation or obliteration of alveoli.
Typically in HP
RB-ILD if h/o smoking
FB if h/o connective tissue dx (RA)

65. Large Nodule & Masses
• Patients who have diseases characterized by
small nodules (e.g., sarcoidosis, silicosis, CWP,
talcosis, Langerhans histiocytosis)
conglomeration or confluence of many small
nodules can result in large nodules or mass-
like opacities.

66. • Sarcoidosis
• Nodules or masses are often irregular in shape and
surround central bronchi and vessels, with air
bronchograms often being visible.
• In end stage sarcoidosis, conglomerate masses in the
upper lobes associated with central crowding of vessels
and bronchi as a result of peribronchovascular fibrosis -
> Tractional bronchiectasis.
• Adjacent areas of emphysema or bullae are visible in
some cases. D/d TB patient after Tx
• Small satellite nodules adjacent to the large nodules
are often seen - galaxy sign

67. • Silicosis & CWP
complicated pneumoconiosis show conglomerate
masses in the upper lobes, unassociated with
bronchiectasis. Areas of emphysema ,peripheral
to the conglomerate masses are common.
• Lymphoma
Lymphoma involving the lung most commonly
results in airspace consolidation (66% of cases)
and large nodules (41% of cases) (60), often ill-
defined and sometimes containing air
bronchograms.

68. • Lymphoproliferative disorder
The most common abnormality in transplant pt visible on CT
was the presence of multiple, well-defined pulmonary
nodules ranging up to 3 cm in diameter. These nodules, when
multiple, had a basilar and peripheral predominance.
Occur in immunosuppressed patients (e.g., those
with AIDS, congenital immune deficiency, or
receiving immunosuppressive therapy).

69. • Organizing pneumonia
Of 60 lesions found in the 12 patients, 53
(88%) had an irregular margin, 27 (45%) had
an air bronchogram, 23 (38%) had a pleural
tail, and 21 (35%) had a spiculated margin.
Reversed halo sign OR atoll sign is highly
suggestive of OP. d/d- wegners, eosinophillic
pneumonia,coccidiomycosis,sarcoidosis.

72. • Wegners granulomatosis (URL)
Typically manifested by multiple nodules or masses
that are limited in number, range in size from a few
millimeters to 10 cm in diameter, have no zonal
predominance, and have a random distribution.
Cavitation of nodules is common, being present in all
nodules larger than 2 cm; the cavity walls are often
thick and irregular or shaggy, although thin-walled
cavities may also be seen.

73. • Infection
In immunosuppresed patients, usually
representing as a fungal inf ( invasive
aspergillosis), manifest as large nodule or
mass.. These nodules are often ill-defined,
asso with cavitation, or a surrounding halo of
GGO ( Halo sign ).
Large nodule or mass + halo sign + neutropenic
pt = invasive aspergillosis

74. • Rounded atelactasis
 Associated with ipsilat pleural diasease
 Typically contacts the pleural surface
 Commonly in paravertebral space
 Bending and bowing of broncho-vascular component
towards the atelactasis.
 Focal fibrotic masses, usually irregular in shape, have been
described as occurring in the peripheral lung in relation to
pleural abnormalities in patients with asbestos exposure,
described as rounded atelactasis.

76. Axial enhanced CT scan of the chest shows a nodular-area of increased
density (black arrow), associated with pleural thickening. White arrows point
to "comet tail" density that emanates from the lesion.