SPN

Solitary Pulmonary Nodule

(SPN(
 A Solitary Pulmonary Nodule is an
approximately round lesion that is less than 3 or
4 cm in diameter and that is completely
surrounded by aerated lung. There is no
associated atelectasis, hilar enlargement, or
pleural effusion.
 It is usually detected incidentally on a plain
chest radiograph or computed tomographic (CT)
scan.
Etiology of Solitary Pulmonary Nodule
 GENERAL APPROACH 
The ideal approach to a SPN would result in
definitive resection of all malignant nodules,
while avoiding resection of all benign nodules
that do not require therapy.
 Unfortunately, a foolproof means to
implement such a strategy does not exist.
  Approaches that remove most malignant
nodules tend to result in frequent removal of
benign nodules, whereas approaches that leave
most benign nodules intact tend to leave some
malignant nodules unresected.
 The former approach is generally preferred.
Definitive diagnosis of
solitary pulmonary
nodules can only be made
by tissue diagnosis.
 DIAGNOSTIC EVALUATION
 Clinical features
 Radiographic features
 Quantitative models
  Clinical features
 Patient age:
The probability of a SPN being malignant rises
with increasing patient age
 Risk factors:

e.g. smoking, asbestos exposure

  Radiographic features
 Size:
Larger lesions are more likely to be malignant
than smaller lesions.
 Border:

Malignant lesions tend to have more irregular

and spiculated borders, whereas benign lesions
often have a relatively smooth and discrete
border.
 This smooth
nodule turned out
to be a solitary
metastasis from a
primary bladder
cancer in a 45 yr
old woman

1 cm diameter,
coin-shaped,
smooth peripheral
nodule
Lobulated, well-
marginated
nodule of the
right lower lobe

This is an A-V
malformation in a
34 yr old male with
hereditary
hemorrhagic
telangiectasia
This is
bronchioloalveolar
cell carcinoma in a 68
yr old female

Poorly marginated
nodule with small
focal areas of low
attenuation
(pseudocavitation)
in the right lung
 Calcification
 The presence of calcification does not exclude
malignancy. As an example, "eccentric"
calcification (ie, asymmetric calcification)
should raise concern about carcinoma arising
in an old granulomatous lesion (ie, a "scar"
carcinoma(
 Certain patterns of calcification, however,
strongly suggest that a SPN is likely benign.
Benign pattern of calcification
Benign pattern of calcification
in a solitary pulmonary nodule
with characteristic popcorn
configuration suggestive of
a hamartoma
Benign pattern of calcification in a solitary pulmonary nodule.
There is central, target-like calcification
in this right lower lobe granuloma.
Benign pattern of calcification
in a solitary pulmonary nodule.
There is diffuse calcification
in this subpleural nodular
granuloma
 Density
 Increased density of a SPN argues against
malignancy. Although density measurement
was at one time considered to be a promising
technique, it is no longer used as part of the
routine evaluation of a SPN.
 Growth
 Growth is evaluated by Doubling Time (DT) =
the time required for nodule to double in Volume
 Volume = (4πr^3) / 3
 Doubling the volume of a 1 cm diameter nodule
equates an increase in diameter by 3 mm (26%)
 2 cm  increase by 5 mm
 3 cm  increase by 8 mm
 Lesions that are malignant tend to have a volume
doubling time between 20 and 400 days.
 Benign lesions usually have a DT that is
either:
1. < 20 days: infectious causes, etc.
2. > 400 days: old granulomatous lesions
Volumetric 3D analysis demonstrating growth
.of a nodule. Doubling time 210 days
 Ground glass appearance
 SPNs that have a ground glass appearance are
frequently malignant.
 The typical histology for a malignant SPN with
ground glass morphology is bronchioloalveolar
carcinoma.
 Bronchioloalveolar carcinomas with a ground-glass
appearance are often slow growing, such that
apparent stability over time may be misleading.
Lung nodules demonstrating peripheral ground
glass opacity with solid central components
 Cavitation
 Cavitation can be seen in both benign and
maligant nodules
 Benign cavitary nodules usually have smooth, thin
walls
 Malignant cavitary nodules usually have thick,
irregular walls
 Most cavitary lesions with a wall thickness >
16 mm are malignant
 Wall thickness < 4 mm are usually benign
Thin-walled cavitary
nodule. Aspergillis in a
48 yr old male with
leukemia
Spiculated
nodule with
eccentric
cavitation in
right upper lobe

This is a non-small
cell lung cancer in
a 61 year old
female
Benign lung abscess
Quantitative models

1- Bayesian Analysis
 Baysian analysis uses likelihood ratios (LR ’s)
for numerous radiologic findings and clinical
features associated with solitary pulmonary
nodules to estimate pCa
Logistic Regression -2

A multivariate logistic regression was

developed by Mayo Clinic investigators
based on a data set of 629 patients with
newly discovered solitary pulmonary
nodules (65% benign, 23% malignant, 12%
indeterminate) using 3 clinical and 3
radiographic parameters
 pCa: Logistic Regression
 Probability of Malignancy = ex / (1 + ex)
 x = 6.8272 + (0.0391 Χ Age) + (0.7917 Χ
Cigarettes) + (1.3388 Χ Cancer) + (0.1274 Χ
Diameter) + (1.0407 Χ Spiculation) + (0.7838 Χ
Upper)
 Age = enter numerical age in years
 Cigarettes = enter 1 for hx of smoking past or present, 0 for none
 Cancer = enter 1 for previous hx of extrathoracic malignancy
diagnosed > 5 yrs ago, otherwise 0
 Diameter = enter numerical value in mm
 Spiculation = enter 1 for presence, 0 for absence
 Upper = enter 1 for upper lobe nodule, 0 for other location

Swensen SJ, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules.
Application to small radiologically indeterminate nodules. Arch Intern Med 1997; 157:849-855.
 MANAGEMENT
 Patients who have a SPN undergo an initial diagnostic
evaluation. During the evaluation, clinical features,
radiographic features, and, occasionally, quantitative
models are used to determine the probability that the
nodule is malignant. Once the probability that the SPN
is malignant has been formulated, initial management
must be chosen. There are many reasonable
approaches to the initial management of a SPN and
significant variation exists among institutions. When
decisions are uncertain, initial management should
carefully consider the patient's preference.
 The Fleischner Society Guidelines
MacMahon H, et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from
the Fleischner Society. Radiology 2005;237:395-400.
www.uptodate.com
 Recommended management algorithm for patients with SPNs that measure 8 to 30 mm in
diameter

Gould M K et al. Chest 2007;132:108S-130S

©2007 by American College of Chest Physicians
Erik E. Folch and Peter J. Mazzone. http://bestpractice.bmj.com/best-practice
Erik E. Folch and Peter J. Mazzone. http://bestpractice.bmj.com/best-practice
 POSITRON EMISSION
 TOMOGRAPHY (PET)
 Positron emission tomography (PET) allows the
imaging of structures by virtue of their ability to
concentrate specific molecules that have been labeled
with a positron-emitting radionuclide. PET scanning
of known or suspected malignancy is usually
performed after administration of a glucose analog
that has been tagged with a positron-emitting isotope
of fluorine, (18)F-2-deoxy-2-fluoro-D-glucose(FDG).
 Metabolically active cells (eg, malignant cells) utilize
and import more glucose than other tissues and thus
take up FDG more.
 False-negative results can occur with tumors that
have low metabolic activity (eg, bronchioloalveolar
carcinomas, carcinoids, and some well-differentiated
adenocarcinomas), small lesions (a critical mass of
metabolically active malignant cells is required for
detection by PET), and uncontrolled hyperglycemia
because the uptake of FDG is retarded by the
hyperglycemia.
 False-positive results can occur in inflammatory
conditions and granulomatous diseases .
 Test performance of FDG-PET for differential
diagnosis of solitary pulmonary nodules is
adequate with specificity values between 80%
and 85%.

Buck AK, , Herrmann K, Shen C, et al. Molecular imaging of proliferation in vivo: Positron emission tomography
with [18F]fluorothymidine. Methods 48 (2009) 205–215
 Metabolic activity — A tumor's metabolic activity can be
measured using the standard uptake value (SUV).
 Quantitative assessment — a numerical value is determined
from the PET scan. An SUV exceeding 2.5 is generally
considered highly suggestive of malignancy or active
inflammation
 Qualitative assessment — FDG uptake by the tumor is
compared to background activity by visual inspection
 The SUV depends on multiple parameters :
1. the activity of the FDG
2. the timing between injection and scanning
3. the size and location of the lesion
As a result, each institution must establish its own cutoff
value.
 PET/CT
 PET/CT is the fusion of techniques in one
scanner that can acquire both anatomic and
functional scans during a single scanning
session provides both morphological (CT
component) and metabolic (PET component)
information for nodule characterization.
 PET can help in identifying high-uptake areas in
these cases, and the CT component can provide
anatomic details to precisely guide the biopsy.
CT FDG-PET FDG-PET/CT
FDG-PET/CT of a 47-year-old male
with diagnosis of NSCLC
 Invasive evaluation
 Two of the most commonly available techniques are:
 Flexible bronchoscopy. Samples can be collected by
washings, brushings, transbronchial biopsy and
transbronchial needle aspiration. The probability of
success depends on the location and size of the nodule,
and the presence of a bronchus leading directly to the
lesion (bronchus sign), as well as local expertise and
availability of fluoroscopy. The sensitivity of this
technique is widely variable, but has been reported to
be 40% to 70% for 2- to 3-cm nodules.
 Recent advances in ultrathin bronchoscopy,
electromagnetic navigation and endobronchial
ultrasound are promising technologies but are
not yet widely available. The most important
advantage of bronchoscopy is the very low
rate of complications when compared with
other sampling techniques.
Bronchus sign on CT
 Transthoracic needle aspiration.
 Various imaging modalities, including fluoroscopy,
ultrasonography, CT, and CT fluoroscopy (CTF) have
been used to guide percutaneous biopsies.
 The choice of imaging modality is based on the
preference of the physician, the size and location of
the target lesion, the potential access routes, the
ability to visualize the lesion, and the equipment
availability and cost.
 Contraindications to Transthoracic Needle
Biopsy:
1. Bleeding diathesis international normalized ratio INRI > 1.3,
platelet count < 50,000
2. Inability of patient to cooperate
3. cannot hold breath
4. cannot maintain prone or decubitus position
5. Contralateral pneumonectomy
6. Bulla or severe emphysema or vascular structure in
anticipated biopsy path
 COMPLICATIONS OF TNB
Common
 Pneumothorax 20%
 Bleeding 5%
Rare
 Vasovagal reaction < 1%
 Systemic air embolism 0.02%
 Needle tract metastases 0.012%
 Successful FNAB without complication
Poorly differentiated non-small cell carcinoma
Unsuccessful FNAB of a solitary
left lower lobe nodule
(a)The procedure was complicated
By a small, stable pneumothorax
and focal subsegmental haemorrhage
(b) before a sufficient sample could
be obtained. The patient proceeded
to surgical wedge resection and
pathology showed metastatic
Nasopharyngeal carcinoma.
  Video-assisted thoracoscopic surgery or open
surgical resection:
Video-assisted thoracoscopic surgery (VATS) or open
surgical resection is indicated for the diagnosis and
potential treatment of a solitary pulmonary nodule
that remains undiagnosed by the above techniques,
yet remains a concern. VATS is a safe alternative to
thoracotomy. VATS is associated with fewer
complications but is limited by the visual
determination of the location of the nodule. If the
nodule is not close to the pleural space, the nodule
may not be accessible.