ORIGINAL ARTICLE
The Pseudocavitation Sign of Lung Adenocarcinoma
A Distinguishing Feature and Imaging Biomarker of Lepidic Growth
Tina D. Tailor, MD,* Rodney A. Schmidt, MD, PhD,w Keith D. Eaton, MD, PhD,z
Douglas E. Wood, MD,y and Sudhakar N. J. Pipavath, MD*
Purpose: Our purpose was to evaluate whether pseudocavitation,
characterized by round or oval areas of low attenuation in a lesion
on computed tomography (CT), can help distinguish adenocarci-
noma from other types of non–small cell lung cancer (NSCLC). We
also sought to determine whether pseudocavitation is associated
with lepidic growth on histopathology.
Materials and Methods: This retrospective HIPAA-compliant study
was approved by our institutional review board. The need for
informed consent was waived. CT scans and pathology records
from 158 NSCLCs in 149 patients were retrospectively reviewed.
The frequency of pseudocavitation was compared among types of
NSCLC, specifically adenocarcinoma versus other types of
NSCLC. Subgroup analysis of adenocarcinomas was performed to
identify any difference in the frequency of pseudocavitation
between adenocarcinomas with reported lepidic growth and those
without lepidic growth.
Results: There was a significantly greater frequency of pseudoca-
vitation in adenocarcinomas versus other types of NSCLC [19/86
(22.1%) vs. 4/72 (5.6%), P = 0.007]. The sensitivity and specificity
of the pseudocavitation sign for adenocarcinoma were 0.22 and
0.94, respectively. Among adenocarcinomas, the pseudocavitation
sign was more frequent in tumors with lepidic growth versus those
without lepidic growth [10/24 (41.7%) vs. 9/62 (14.5%), P = 0.015].
Conclusions: Pseudocavitation at CT is more common in primary
lung adenocarcinoma than in other types of NSCLC. It is also
more common in adenocarcinomas with lepidic growth, suggesting
a correlation between the imaging finding of pseudocavitation and
the pathologic finding of lepidic growth. As the subtype of NSCLC
guides treatment, predicting tumor pathology by imaging may
improve diagnostic workup for patients with NSCLC.
Key Words: non–small cell lung cancer, pseudocavitation, lepidic
growth, computed tomography, adenocarcinoma
(J Thorac Imaging 2015;30:308–313)
B ecause of the growth of targeted treatments for lung
cancer, there is increased need to distinguish adeno-
carcinoma from other non–small cell lung cancers (NSCLCs),
particularly squamous cell carcinoma (SCC).1–3 Unlike
SCCs, adenocarcinomas undergo routine testing for driver
mutations for which targeted agents, such as epidermal
From the Departments of *Radiology; wPathology; zMedicine, Divi-
sion of Oncology; and yDepartment of Surgery, University of
Washington Medical Center, Seattle, WA.
The authors declare no conflicts of interest.
Correspondence to: Sudhakar N. J. Pipavath, MD, Department of
Radiology, University of Washington, 1959 NE Pacific Street, Box
357115, Seattle, WA 98195-7115 (e-mail: snjp@u.washington.edu).
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/RTI.0000000000000168
308 | www.thoracicimaging.com J Thorac Imaging  Volume 30, Number 5, September 2015
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
growth factor receptor (EGFR) inhibitors, offer treatment
advantage.4–9
A multidisciplinary approach for distinguishing ade-
nocarcinoma from SCC is central to the recent adeno-
carcinoma classification proposed by the International
Association for the Study of Lung Cancer (IASLC),
American Thoracic Society (ATS), and European Respi-
ratory Society (ERS).10 These criteria also recommend
characterizing invasive adenocarcinomas by the predom-
inant histologic subtype. Of these subtypes, adenocarcino-
mas with lepidic-predominant growth, namely growth
along alveolar walls, may carry better prognosis.10,11
In light of the IASCL/ATS/ERS recommendations and
the rising use of computed tomography (CT) for lung cancer
screening, accurate radiologic assessment of NSCLC is
important. Further, as adenocarcinoma is the most common
lung cancer type, and with emerging knowledge that its
diagnosis potentially implies different treatment and prog-
nosis than other NSCLCs, there is an impetus to identify
radiologic features that reflect lesion pathology.3,12 In this
way, quantitative studies correlating imaging features and
histology can improve radiologic characterization.
Although many radiologic signs have been described
in pulmonary adenocarcinoma, few studies quantify fea-
tures distinguishing adenocarcinoma from other NSCLCs.
Pseudocavitation is a CT feature characterized by round or
oval areas of low attenuation in a pulmonary nodule,
consolidation, or mass (Fig. 1).13 In contrast to true cav-
itation, which may have an air-fluid level and reflects
pathologic necrosis, per the Fleischner Criteria Glossary of
Terms for Thoracic Imaging, pseudocavitation represents
spared parenchyma, normal or ectatic bronchi, or focal
emphysema.13–16 Unlike cavitation, which generally implies
a single area of low attenuation in a lesion that is usually
centrally located (reflecting a necrotic or hypoxic core),
pseudocavities are often multiple, typically small (< 1 cm in
diameter), and may be scattered throughout a lesion.13,14,17
Because of these characteristics, pseudocavitation is some-
times referred to as “bubble-like lucencies” or “cystic air
spaces” in a lesion.
Although pseudocavitation has been described in
adenocarcinoma, few quantitative studies have evaluated
this sign as a feature distinguishing adenocarcinoma from
NSCLC types. Our purpose was to evaluate whether
pseudocavitation is a feature distinguishing adenocarci-
noma from other NSCLC types. As a secondary aim, we
sought to evaluate whether pseudocavitation was asso-
ciated with lepidic growth at histology.
MATERIALS AND METHODS
This HIPAA-compliant study was approved by our
institutional review board. The requirement for informed
J Thorac Imaging  Volume 30, Number 5, September 2015 Pseudocavitation in Lung Adenocarcinoma

FIGURE 1. Pseudocavitation and cavitation on CT scan. A, Transaxial CT scan in lung window of a 64-year-old woman with a history of
lung adenocarcinoma shows a mass in the right upper lobe with a large eccentrically located pseudocavity (arrowhead). Adjacent to this
are multiple smaller bubble-like lucencies, consistent with smaller pseudocavities (arrows). Biopsy revealed adenocarcinoma with lepidic
features. The lesion was compatible with the clinical stage IA. B, Transaxial CT scans of an 84-year-old woman with a spiculated left
upper lobe mass shows that the lesion contains multiple subcentimeter-size areas of low attenuation, compatible with pseudocavitation.
Lesion pathology was compatible with stage IIB adenocarcinoma with lepidic features. C, Transaxial CT in lung window of an 82-year-
old woman with a history of SCC of the lung shows a spiculated left upper lobe mass with a large central cavitation (arrow). Biopsy was
compatible with poorly differentiated SCC.

consent was waived because this was a retrospective
analysis.
Patients and Lesions
Three hundred thirty-three subjects with a pathologi-
cally proven diagnosis of NSCLC were randomly selected
from our institutional tumor board registry of 1648 patients
with NSCLC between the dates of January 2000 to April
2009. Subjects with all stages (IA to IV) of NSCLC were
included, and the medical records and imaging results for
each patient were reviewed by the primary author. Patients
were included only if (a) there was a pathology report in the
medical record confirming a diagnosis of NSCLC [including
adenocarcinoma variants formerly known as bronchioalveo-
lar cell carcinoma (BAC)], and (b) a CT scan with transaxial
sections <3 mm performed before biopsy or treatment with
surgery, chemotherapy, and/or radiation was available for
review. Subjects were excluded if (a) a pathology report was
not available, (b) a CT scan was not available, or (c) the
tumor was a primary endobronchial lesion, adenocarcinoma
of unknown primary, metastatic adenocarcinoma from an
extrapulmonary site, or mesothelioma. For subjects having
>1 lesion, only lesions with a pathologic tissue diagnosis
were included. A total of 158 lesions in 149 patients fulfilled
the inclusion criteria (86 adenocarcinomas and 72 NSCLCs
other than adenocarcinoma).
Histology
Pathologic reports from the medical records were retro-
spectively reviewed to document the histologic type of NSCLC
(ie, adenocarcinoma, SCC, large cell, NSCLC not otherwise
specified, etc.). For all cases of adenocarcinoma, the presence
of lepidic growth (formerly known as bronchioalveolar
growth) was documented. Specifically, adenocarcinomas were

Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. www.thoracicimaging.com | 309
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Tailor et al
considered to have lepidic growth if the presence of lepidic
growth (or bronchioalveolar growth) was explicitly stated in
the pathology report. Because this was a retrospective study,
the pathology reports did not consistently follow the IASLC/
ATS/ERS adenocarcinoma classification, in that dominant
histologic subtypes were not consistently assigned. Thus,
documented lepidic growth in the pathology report was not
taken to imply lepidic-predominant growth. Sixty-three of the
lesions underwent needle biopsy, 142 had a surgical wedge
biopsy with or without surgical resection, and 47 underwent
both. For subjects receiving both needle biopsy and surgical
biopsy and/or resection, the pathology from the surgical
specimen was accepted as the final tissue diagnosis.
CT Examinations and Interpretation
Chest CT examinations performed at our institution
were obtained with the following parameters: 100 to
120 kVp, 100 to 200 mAs, pitch 1.35 to 1.375, 0.4 to 0.8
seconds/helical rotation, and axial reconstruction thickness
2.5 mm (GE LightSpeed VCT 64, GE Discovery CT750
HD, GE LightSpeed QX/i, GE LightSpeed Ultra 8, GE
HSA Highspeed; GE Healthcare). For outside CT exami-
nations, subjects were included if transaxial CT sections
with a slice thickness of 3 mm or less were available. Eighty-
eight CT scans were performed at our institution, and 60
were performed at an outside hospital. Images were viewed
with a sharp reconstruction algorithm in standard lung
windows (window 1500, level 600). The mean interval
time between the chest CT and histologic diagnosis by
needle or surgical biopsy was 34 days (range, 0 to 452 d).
Interpreting radiologists were blinded to the patho-
logic diagnosis at the time of CT interpretation. The first
author, a radiologist in training with 4 years of experience
in chest CT interpretation, recorded lesion size, location,
and the presence or absence of either a pseudocavitation or
cavitation. The senior author, a board-certified chest radi-
ologist with >15 years of experience in chest CT inter-
pretation, independently read all cases of pseudocavitation
or cavitation, as determined by the first reader. For dis-
cordant cases, a decision was reached by consensus.
Statistical Analysis
The Pearson w2 test was used to evaluate the differ-
ences between CT features, namely pseudocavitation and
cavitation, and type of NSCLC (ie, adenocarcinoma vs.
other types of NSCLC). The 2-tailed Pearson w2 test was
also used to evaluate for differences in the frequency of
pseudocavitation between adenocarcinomas with lepidic
growth and those without lepidic growth. The Fisher exact
test was used for the subgroup analysis of clinical stage. The
TABLE 1. Tumor Characteristics
Stage
Type of NSCLC IA IB IIA IIB
Adenocarcinoma 16 23 9 13
SCC 8 6 4 15
NSCLC, NOS 4 2 2 1
Adenosquamous 0 1 0 1
Large cell 0 1 0 2
Total [n (%)] 28 (17.7) 33 (20.9) 15 (9.5) 32 (20.3)
Note: all numbers in the second column reflect the number of lesions, not the number of patients.
NOS indicates not otherwise specified.
310 | www.thoracicimaging.com Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Thorac Imaging  Volume 30, Number 5, September 2015
2-tailed Student t test was used to determine differences in
tumor diameter between adenocarcinomas with pseudoca-
vitation and those without pseudocavitation, as well as
NSCLCs with cavitation and those without cavitation. The
statistical methods did not take into account clustering
effects of patients with multiple lesions because some
patients had >1 primary lesion, and other published
studies quantifying imaging features of malignancy have
regarded multiple lesions as independent for the purposes
of statistical analysis. Statistical analysis was performed
with the use of R version 3.1.1. A P-value of <0.05 was
considered statistically significant.
RESULTS
Patients and Lesions
Table 1 summarizes the clinical and pathologic fea-
tures of lesions included in this study. A total of 158 lesions
in 149 patients fulfilled the inclusion criteria. Of the 158
NSCLCs, 86 (54%) were pathologically proven adeno-
carcinoma and 72 (46%) were other types of NSCLC. Of
the 86 adenocarcinomas, 24 had reported lepidic growth at
pathology. The average tumor diameter was 3.1 ± 1.9 cm
(2.8 ± 1.7 cm for all adenocarcinomas, 3.5 ± 2.0 cm for
NSCLCs other than adenocarcinomas). Forty-five of the
lesions were located in the right upper lobe, 6 were in the
right middle lobe, 26 were in the right lower lobe, 60 were in
the left upper lobe, 17 were in the left lower lobe, and 4
involved >1 lobe.
CT Features and Tumor Histology
Table 2 demonstrates the CT features of lesions
included in the study. Twenty-three of 158 tumors (14.6%)
demonstrated pseudocavitation. Of these 23 lesions, 19
were adenocarcinoma and 4 were other types of NSCLC.
Eleven of 158 tumors (7.0%) demonstrated cavitation, of
which 4 were adenocarcinomas and 7 were other types of
NSCLC. The overall interreader concordance for the
presence of pseudocavitation and cavitation on CT was
87.2% (the second reader was in agreement with 34 of 39
cases deemed by the first reader as having pseudocavitation
or cavitation). For the CT finding of cavitation, the con-
cordance was 100% (11 of 11 cases). For the CT finding of
pseudocavitation, the concordance was 82.1% (23 of 28
cases).
There was a statistically significant difference in the
presence of pseudocavitation between adenocarcinoma and
other types of NSCLC (P = 0.007), with pseudocavitation
being more likely in adenocarcinomas than in other types of
NSCLC (22.1% vs. 5.6%) (Table 2). The sensitivity and
IIIA IIIB IV Total [n (%)]
13 9 3 86 (54.4)
6 5 3 47 (29.7)
2 4 4 19 (12.0)
0 0 0 2 (1.3)
0 1 0 4 (2.5)
21 (13.3) 19 (12.0) 10 (6.3) 158
J Thorac Imaging  Volume 30, Number 5, September 2015 Pseudocavitation in Lung Adenocarcinoma

TABLE 2. CT Findings of NSCLCs

CT Characteristic Adenocarcinoma [n (%)] Other NSCLCs [n (%)] P Odds Ratio 95% CI
Pseudocavitation 19/86 (22.1) 4/72 (5.6) 0.007 4.82 1.56-14.92
Cavitation 4/86 (4.7) 7/72 (9.7) 0.351 0.44 0.13-1.61
Note: other NSCLCs in the third column refer to all NSCLCs that were not adenocarcinomas. Of the NSCLCs with pseudocavitation, 3 were SCC, and
1 was NSCLC not otherwise specified.
CI indicates confidence interval.

specificity of the pseudocavitation sign for adenocarcinoma platinum-based chemotherapy).22,23 Similarly, treatment
were 0.22 and 0.94, respectively. with targeted TKIs is associated with prolonged PFS in
There was no significant difference in the presence patients with chromosomal rearrangements involving ana-
of cavitation between adenocarcinomas and other NSCLC plastic lymphoma kinase.24,25 As knowledge of molecular
types (Table 2, P = 0.351). There was no significant pathways in adenocarcinoma continues to emerge, targeted
difference in average tumor diameter between NSCLCs therapies will undoubtedly continue to evolve. Thus,
with cavitation and those without cavitation (3.8 ± 2.4 imaging features suggest that pathology may facilitate the
vs. 3.0 ± 1.7 cm, P = 0.288), or adenocarcinomas with pseu- proper biopsy for conventional histology and molecular
docavitation versus those without pseudocavitation (3.3 ± 2 testing and expedite diagnosis and treatment.
vs. 2.7 ± 1.6 cm, P = 0.253). Prior studies, consisting primarily of small retro-
Of the 86 pathologically proven adenocarcinomas spective case series, describe pseudocavitation in 19% to
included in the study, there was no significant relationship 29% of lung adenocarcinomas, similar to its frequency in
between the clinical tumor stage and the presence of pseu- our study.14,26 In adenocarcinoma variants formerly known
docavitation (P = 0.757) (Table 3). Subgroup analysis of as BAC (now considered to be a spectrum of pathologies
clinical stage revealed no significant difference in the from preinvasive lesions to invasive carcinomas), pseudo-
frequency of pseudocavitation between those lesions con- cavitation has been reported with a frequency of
ventionally considered surgically resectable (stages IA-IIIA) >50%.14,18 In a retrospective series of 26 patients with lung
and surgically unresectable (stages IIIB-IV) (P = 0.723). adenocarcinomas having a bubble-like appearance on CT,
At pathology, 27.9% (24 of 86) had lepidic growth. Kojima et al17 reported a 100% 5-year survival after sur-
There was a statistically significant difference in the pres- gical resection, suggesting that adenocarcinomas with this
ence of pseudocavitation between adenocarcinomas dem- CT feature have may have unique and potentially favorable
onstrating lepidic growth and those without lepidic growth, histopathologic features. Our results extend the existing
with pseudocavitation being more likely in adenocarcino- literature by demonstrating that pseudocavitation on CT
mas with lepidic growth [10/24 (41.7%) vs. 9/62 (14.5%), may distinguish adenocarcinoma from other NSCLC types
P = 0.015]. The sensitivity and specificity of the pseudoca- (ie, SCC) and by suggesting a correlation between pseu-
vitation sign for predicting lepidic growth of adenocarci- docavitation and lepidic growth at pathology. The latter is
noma were 0.42 and 0.85, respectively. Figure 2 shows a important because the IASLC/ATS/ERS adenocarcinoma
representative example of pseudocavitation on CT in a classification recommends characterization of invasive
patient with lepidic growth at histology. adenocarcinomas into histologic subtypes.10
At histology, lepidic growth refers to neoplastic
growth along alveolar walls without pleural, stromal, or
DISCUSSION vascular invasion.10 Among invasive adenocarcinomas,
In this study, we demonstrate that pseudocavitation which constitute most resected cases, Warth and colleagues
on CT is more common in lung adenocarcinoma than in
other types of NSCLC. Although pseudocavitation has low
sensitivity for adenocarcinoma, the specificity is >90%.
TABLE 3. The Presence of Pseudocavitation and Lepidic Growth
Thus, the presence of pseudocavitation on CT makes ade- by Clinical Stage of Adenocarcinoma
nocarcinoma likely, but its absence does not rule out ade-
nocarcinoma. Our results also demonstrate that pseudoca- Adenocarcinomas
vitation on CT is associated with lepidic growth at With Adenocarcinomas
histopathology. Adenocarcinoma No. Pseudocavitation With Lepidic
These results are important because it is now known Stage Lesions [n (%)] Growth [n (%)]
that the subtype of NSCLC has implications for patient IA 16 4 (25.0) 11 (68.8)
treatment and prognosis.2 Specifically, distinguishing ade- IB 23 7 (30.4) 6 (26.1)
nocarcinoma from SCC is important because current IIA 9 2 (22.2) 1 (11.1)
guidelines recommend molecular testing for adenocarcino- IIB 13 1 (7.7) 2 (15.4)
mas to match individual therapy to precise genetic muta- IIIA 13 2 (15.4) 1 (7.7)
tions.6,10,18 Certain EGFR mutations expressed in adeno- IIIB 9 2 (22.2) 2 (22.2)
IV 3 1 (33.3) 1 (33.3)
carcinomas, such as exon 19 deletions and point mutations Total 86 19 (22.1) 24 (27.9)*
on exon 21, are considered “sensitizing” because they pre-
dict response to EGFR tyrosine kinase inhibitors (TKIs), *Pseudocavitation was more common in adenocarcinomas with lepidic
such as erlotinib and gefinitib.7,8,19–21 In the presence of growth than in adenocarcinomas without lepidic growth [10/24 (41.7%) vs.
9/62 (14.5%), P = 0.015].
such mutations, EGFR-TKIs are associated with prolonged There was no significant relationship between the stage of adenocarci-
progression-free survival (PFS) (9.7 to 13.1 mo for patients noma and the presence of pseudocavitation (P = 0.757).
receiving erlotinib, 4.6 to 5.2 mo for patients receiving

Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. www.thoracicimaging.com | 311
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Tailor et al J Thorac Imaging  Volume 30, Number 5, September 2015

FIGURE 2. Pseudocavitation on CT scan in an 84-year-old female patient with lung adenocarcinoma demonstrating lepidic growth at
histology. A, Transaxial CT scan in lung window shows a spiculated right upper lobe mass with multiple peripherally located bubble-like
lucencies, compatible with pseudocavitation. B, Representative pathologic slide (stained with hematoxylin and eosin) shows adeno-
carcinoma with lepidic growth (arrows), that is, neoplastic cell growth along the normal alveolar framework. The overall lung archi-
tecture is preserved, and there is lack of angiolymphatic invasion. An asterisk (*) marks an alveolar space.

reported that predominant histologic pattern influences
overall survival, disease-specific survival, and disease-free
survival, with lepidic-predominant adenocarcinoma having
the most favorable prognosis. Warth et al11 also suggested
that histologic subtype may affect treatment response.
Similarly, Anami et al27 reported that in patients with
mixed subtype adenocarcinomas, the presence of lepidic
growth was associated with prolonged overall survival and
that lepidic growth was a more reliable prognostic indicator
than nodal status. Thus, the ability to suggest histologic
features of adenocarcinoma by CT could help predict
clinical course.
Although a direct radiologic and pathologic inves-
tigation to correlate the CT finding of pseudocavitation to
histologic findings was not performed in this study, prior
studies, consisting mainly of retrospective case series, report
that pseudocavitation reflects air spaces or air broncho-
grams in a lesion, which may be accentuated by cicatrical
contraction.15,18,26 Originally described in adenocarcinoma
variants formerly known as BAC, it is thought that pseu-
docavitation reflects the propensity of tumor cells to grow
along alveolar walls without disrupting lung archi-
tecture.15,26,28 As this type of proliferation is characteristic
of lepidic growth, our results, which suggest a correlation
between pseudocavitation and lepidic growth, support these
prior reports. Conversely, because nonlepidic growth is
thought to compress or obliterate small airways, pseudo-
cavitation in nonlepidic adenocarcinomas is reportedly
rare.18
Unlike pseudocavitation, true cavitation, which as
above reflects necrosis, is rare in lung adenocarcino-
mas.14,16,29 In a retrospective study of 353 patients with
primary lung cancer, Mouroux et al29 reported that <6%
of cavitary lung cancers were adenocarcinomas and that
cavitary tumors were 1.5 times larger than noncavitary
tumors. Although there is ample evidence supporting that
cavitation is more frequent in SCC, our study showed no
significant difference in the presence of cavitation between
adenocarcinomas and other types of NSCLC.26,29,30
Further, no significant size difference was observed between
cavitary and noncavitary lesions, or between pseudocavi-
tary and nonpseudocavitary lesions.
Our study has limitations. First, the population is
limited to biopsied or resected NSCLCs. Therefore, to
translate these results to the evaluation of an indeterminate
pulmonary nodule or mass with pseudocavitation, the
suspicion for NSCLC must be high before adenocarcinoma
can be suggested. In practice, however, the differential
diagnosis for lung malignancy and, more specifically, the
type of malignancy, depends on a number of consid-
erations, such as patient risk factors, other imaging fea-
tures, location (ie, central vs. peripheral), and lesion sta-
bility. In this way, the presence of pseudocavitation is
complementary to other imaging features, and in a patient
with high suspicion for NSCLC, our results suggest that it
is a predictor of adenocarcinoma. Further, interreader
concordance for pseudocavitation on CT was high (82.1%),
supporting the notion that the sign can be generally agreed
upon and is thus useful in suggesting adenocarcinoma. If
there is low suspicion for NSCLC, other non-neoplastic
differential considerations for lesions with pseudocavitation
include inflammatory diseases, such as granulomatosis with
polyangitis, and infection.14
This study did not quantify the amount of pseudoca-
vitation in a lesion or evaluate for relationships between the
amount of pseudocavitation and pathology. As with other
signs in imaging, in the absence of robust quantitative
analysis techniques, quantification is invariably affected by
some degree of interpreter subjectively.31 In this same
regard, in clinical practice, the differentiation between
cavitation and pseudocavitation is also subject to some
degree of interpreter variability. As above, cavitation and
pseudocavitation imply different pathologic features; how-
ever, there is some extent of overlap in their definitions that
may make differentiation of these 2 signs challenging in
select cases.13
Finally, pathologic specimens of NSCLCs included in
this retrospective study were not directly reevaluated to

312 | www.thoracicimaging.com Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Thorac Imaging  Volume 30, Number 5, September 2015
classify lesion histology. Hence, we cannot define a precise
relationship between pseudocavitation on CT and its his-
tologic counterpart, nor can we determine whether pseu-
docavitation on CT reflects the same underlying histology
in adenocarcinomas of differing stages. Further, because of
the retrospective study design, lesion pathology did not
consistently follow the IASLC/ATS/ERS adenocarcinoma
classification, in that dominant histologic subtypes were not
consistently assigned.10 Therefore, we can only conclude
that pseudocavitation is correlated with lepidic growth and
not necessarily lepidic-predominant growth. Future studies
may investigate the relationship between pseudocavitation
and the IASLC/ATS/ERS classification, EGFR status,
clinical tumor stage, and patient outcomes.
In conclusion, our results suggest that pseudocavita-
tion is a useful CT feature distinguishing adenocarcinoma
from other types of NSCLC. The pseudocavitation sign is
more common in adenocarcinomas than other types of
NSCLC and is a potential predictor of lepidic growth at
histology.
REFERENCES
1. Austin JH, Garg K, Aberle D, et al. Radiologic implications of
the 2011 classification of adenocarcinoma of the lung. Radio-
logy. 2013;266:62–71.
2. Nishino M, Hatabu H, Johnson BE, et al. State of the art:
response assessment in lung cancer in the era of genomic
medicine. Radiology. 2014;271:6–27.
3. Nishino M, Jackman DM, Hatabu H, et al. Imaging of lung
cancer in the era of molecular medicine. Acad Radiol. 2011;
18:424–436.
4. Gazdar AF. Personalized medicine and inhibition of EGFR
signaling in lung cancer. N Engl J Med. 2009;361:1018–1020.
5. Lee CK, Brown C, Gralla RJ, et al. Impact of EGFR inhibitor
in non-small cell lung cancer on progression-free and overall
survival: a meta-analysis. J Natl Cancer Inst. 2013;105:
595–605.
6. Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing
guideline for selection of lung cancer patients for EGFR and
ALK tyrosine kinase inhibitors: guideline from the College of
American Pathologists, International Association for the Study
of Lung Cancer, and Association for Molecular Pathology.
J Thorac Oncol. 2013;8:823–859.
7. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in
the epidermal growth factor receptor underlying responsive-
ness of non-small-cell lung cancer to gefitinib. N Engl J Med.
2004;350:2129–2139.
8. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung
cancer: correlation with clinical response to gefitinib therapy.
Science. 2004;304:1497–1500.
9. Shi Y, Au JS, Thongprasert S, et al. A prospective, molecular
epidemiology study of EGFR mutations in Asian patients with
advanced non-small-cell lung cancer of adenocarcinoma
histology (PIONEER). J Thorac Oncol. 2014;9:154–162.
10. Travis WD, Brambilla E, Noguchi M, et al. International
association for the study of lung cancer/american thoracic
society/european respiratory society international multidisci-
plinary classification of lung adenocarcinoma. J Thorac Oncol.
2011;6:244–285.
11. Warth A, Muley T, Meister M, et al. The novel histologic
International Association for the Study of Lung Cancer/
American Thoracic Society/European Respiratory Society clas-
sification system of lung adenocarcinoma is a stage-independent
predictor of survival. J Clin Oncol. 2012;30:1438–1446.
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pseudocavitation in Lung Adenocarcinoma
12. Herbst RS, Heymach JV, Lippman SM. Lung cancer. N Engl J
Med. 2008;359:1367–1380.
13. Hansell DM, Bankier AA, MacMahon H, et al. Fleischner
Society: glossary of terms for thoracic imaging. Radiology.
2008;246:697–722.
14. Trigaux JP, Gevenois PA, Goncette L, et al. Bronchioloalveo-
lar carcinoma: computed tomography findings. Eur Respir J.
1996;9:11–16.
15. Weisbrod GL, Chamberlain D, Herman SJ. Cystic change
(pseudocavitation) associated with bronchioloalveolar carci-
noma: a report of four patients. J Thorac Imaging. 1995;10:
106–111.
16. Kim NR, Han J. Pathologic review of cystic and cavitary lung
diseases. Korean J Pathol. 2012;46:407–414.
17. Kojima Y, Saito H, Sakuma Y, et al. Correlations of thin-
section computed tomographic, histopathological, and clinical
findings of adenocarcinoma with a bubblelike appearance.
J Comput Assist Tomogr. 2010;34:413–417.
18. Nakazono T, Sakao Y, Yamaguchi K, et al. Subtypes of
peripheral adenocarcinoma of the lung: differentiation by thin-
section CT. Eur Radiol. 2005;15:1563–1568.
19. Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker
analyses and final overall survival results from a phase III,
randomized, open-label, first-line study of gefitinib versus
carboplatin/paclitaxel in clinically selected patients with
advanced non-small-cell lung cancer in Asia (IPASS). J Clin
Oncol. 2011;29:2866–2874.
20. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or
carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl
J Med. 2009;361:947–957.
21. Pao W, Miller V, Zakowski M, et al. EGF receptor gene
mutations are common in lung cancers from “never smokers”
and are associated with sensitivity of tumors to gefitinib and
erlotinib. Proc Natl Acad Sci USA. 2004;101:13306–13311.
22. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus
standard chemotherapy as first-line treatment for European
patients with advanced EGFR mutation-positive non-small-
cell lung cancer (EURTAC): a multicentre, open-label,
randomised phase 3 trial. Lancet Oncol. 2012;13:239–246.
23. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy
as first-line treatment for patients with advanced EGFR
mutation-positive non-small-cell lung cancer (OPTIMAL,
CTONG-0802): a multicentre, open-label, randomised, phase
3 study. Lancet Oncol. 2011;12:735–742.
24. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus
chemotherapy in advanced ALK-positive lung cancer. N Engl J
Med. 2013;368:2385–2394.
25. Shaw AT, Solomon B. Targeting anaplastic lymphoma kinase
in lung cancer. Clin Cancer Res. 2011;17:2081–2086.
26. Zwirewich CV, Vedal S, Miller RR, et al. Solitary pulmonary
nodule: high-resolution CT and radiologic-pathologic correla-
tion. Radiology. 1991;179:469–476.
27. Anami Y, Iijima T, Suzuki K, et al. Bronchioloalveolar
carcinoma (lepidic growth) component is a more useful
prognostic factor than lymph node metastasis. J Thorac Oncol.
2009;4:951–958.
28. Lee KS, Kim Y, Han J, et al. Bronchioloalveolar carcinoma:
clinical, histopathologic, and radiologic findings. Radiographics.
1997;17:1345–1357.
29. Mouroux J, Padovani B, Elkaim D, et al. Should cavitated
bronchopulmonary cancers be considered a separate entity?
Ann Thorac Surg. 1996;61:530–532.
30. Gadkowski LB, Stout JE. Cavitary pulmonary disease. Clin
Microbiol Rev. 2008;21:305–333.
31. Watadani T, Sakai F, Johkoh T, et al. Interobserver variability
in the CT assessment of honeycombing in the lungs. Radiology.
2013;266:936–944.
www.thoracicimaging.com | 313