Cardiopulmonar y Imaging • Original Research

Fujisaki et al.
CT of Pleomorphic Carcinoma of the Lung

Cardiopulmonary Imaging
Original Research
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Pleomorphic Carcinoma of the

Lung: Relationship Between CT
Findings and Prognosis
Akitaka Fujisaki1 OBJECTIVE. The objective of our study was to assess the radiologic and clinical findings
Takatoshi Aoki1 of pleomorphic carcinoma (PC) of the lung and to evaluate whether there are any character-
Takahiko Kasai2,3 istic features that can be used to predict prognosis.
Shunsuke Kinoshita1 MATERIALS AND METHODS. Forty-four consecutive patients whose diagnosis of
Yoshinori Tomoda4 PC was histologically confirmed through resection of the lung tumor were included in this
study. The clinical and CT findings of these patients were retrospectively reviewed. Two tho-
Fumihiro Tanaka5
racic radiologists evaluated the CT findings including the size, location, internal character-
Kazuhiro Yatera6 istics, and margin characteristics of the tumors and the presence of chest wall invasion, me-
Hiroshi Mukae 6 diastinal invasion, and surrounding lung abnormalities. A multivariate analysis by the Cox
Yukunori Korogi1 proportional hazards regression model was used to identify variables that can be used to pre-
dict overall survival and disease-free survival.
Fujisaki A, Aoki T, Kasai T, et al.
RESULTS. In the patients with PC, a central low-attenuation area or cavity (40/44, 91%),
chest wall invasion (19/44, 43%), and pulmonary emphysema (30/44, 68%) were frequently
observed on CT. On multivariate analysis, a massive central low-attenuation area or cavity
Keywords: CT, lung cancer, pleomorphic carcinoma,
prognosis
(> 25% of the lesion) on CT indicating necrosis was the only significant independent factor for
overall survival and disease-free survival (p < 0.05). Clinical findings, the presence of lymph
DOI:10.2214/AJR.15.15542 node metastasis at surgery, and postoperative pathologic stage were not significant predictors
of overall survival and disease-free survival.
Received August 30, 2015; accepted after revision
CONCLUSION. A massive central low-attenuation area or cavity on CT was the only
February 1, 2016.
predictor of overall survival and disease-free survival in patients with lung PC.
1
Department of Radiology, University of Occupational
leomorphic carcinoma (PC) is a and showed that the 5-year survival rate of

and Environmental Health School of Medicine,
1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555,
Japan. Address correspondence to T. Aoki
(a-taka@med.uoeh-u.ac.jp).
2
Department of Pathology, National Hospital Organization
Kinki-Chuo Chest Medical Center, Sakai, Japan.
3
Department of Pathology and Oncology, University of
Occupational and Environmental Health School of
Medicine, Kitakyushu, Japan.
4
Cancer Therapy Center, Tobata Kyoritsu Hospital,
Kitakyushu, Japan.
5
Second Department of Surgery, University of
Occupational and Environmental Health School of
Medicine, Kitakyushu, Japan.
6
Department of Respiratory Medicine, University of
Occupational and Environmental Health School of
Medicine, Kitakyushu, Japan.
AJR 2016; 207:289–294
0361–803X/16/2072–289
© American Roentgen Ray Society
P
subtype of sarcomatoid carcino-
ma that contains a component of
sarcoma or sarcomalike (spindle
cells, giant cells, or both) differentiation. Ac-
cording to the criteria of the World Health
Organization classification [1], PC of the lung
is defined as a poorly differentiated non–
small cell lung carcinoma (NSCLC) contain-
ing spindle cells, giant cells, or both or a car-
cinoma consisting of only spindle and giant
cells. At least 10% of the carcinoma should be
composed of spindle cells, giant cells, or both
for it to be classified as a PC. This tumor is
rare, and its incidence has been reported to be
0.1–0.4% of all lung malignancies [2, 3]. Pa-
tients with PC tend to present at a more ad-
vanced stage and to have a poorer prognosis
than those with a common type of NSCLC
[3–5]. Martin et al. [6] compared the 5-year
survival rate of 63 sarcomatoid lung tumor
patients with that of propensity score–
matched patients with other types of NSCLC
the sarcomatoid lung tumor patients (24.5%)
was significantly less than that of the patients
with other types of NSCLC (46.3%).
Although several clinicopathologic studies
of lung PC have been reported in the litera-
ture, there are few studies about its radiologic
features [7, 8]. Moreover, to our knowledge,
the correlation of CT findings with prognosis
has not been described to date. The purpose
of our study was to assess the radiologic and
clinical findings of lung PC and to evaluate
whether there are any characteristic features
that predict the prognosis.
Materials and Methods
Our institutional review board approved this
study, and informed consent was waived for ret-
rospective review of patient records and images.
Patients and Clinical Findings
The medical records of 59 Asian patients with
a diagnosis of lung PC at our hospital between

AJR:207, August 2016 289

 Fujisaki et al.

June 1995 and December 2013 were retrospective-
ly reviewed, and patients who had undergone sur-
gical resection of the lung tumor, had undergone
contrast-enhanced CT before surgery, and had
not been given any anticancer drugs before sur-
gery were included in this study. PET/CT was per-
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resection (n = 1), segmentectomy (n = 5), lobecto-
my (n = 35), or pneumonectomy (n = 3) was per-
formed. Eight patients had undergone CT more
than 2 months before surgery in addition to the
preoperative CT study; therefore, tumor growth
could be evaluated using the previous CT exami-
gle-detector helical CT unit. For the MDCT ex-
aminations, the following parameters were used:
2.0-mm section width with 2.0-mm reconstruc-
tion interval, pitch (ratio of table travel per rota-
tion to total beam width) of 15, 120 kVp, and 300
mA. For the single-detector CT examinations, the

formed in 27 of the 59 patients and detected occult
metastasis in five patients. Fifteen patients were
excluded from the study for the following reasons:
11 patients received neoadjuvant chemotherapy
before CT, two patients underwent needle biopsy
without surgical resection for PC diagnosis, and
two patients did not undergo contrast-enhanced
CT. Thus, 44 patients were included in this study.
The time interval between the final preopera-
tive CT examination and surgery ranged from 2 to
26 days. Surgical resection in the form of a wedge
nation and the preoperative CT examination. CT
observation periods of the eight patients ranged
from 70 to 329 days. The medical record of each
patient was reviewed by two of the authors for the
following: age, sex, smoking habits, treatment, and
long-term clinical status after surgery (i.e., recur-
rence, metastasis, or survival).
CT Analysis
Scanning of the whole lungs was performed
on a 4-, 16-, 32-, or 64-MDCT unit or on a sin-
following parameters were used: 10-mm section
thickness, 120 kVp, 150 mA, and a table speed
of 10 mm/s. For additional scanning of the tumor
using the single-detector CT unit, the following
parameters were used: 2.0-mm section thickness,
120 kVp, and 250 mA. All images were reviewed
on an ultra-high-resolution gray-scale monitor
(20.8 inches [27.4 cm], 2048 × 1560 pixels; Coro-
nis 3MP, BARCO Display Systems) using stan-
dard lung window settings (window width, 1600
HU; window level,  –600 HU) and mediastinal

A B

C D
Fig. 1—63-year-old man with pleomorphic carcinoma (PC) of lung. Liver metastasis was detected 7 months after surgery, and patient died of disease
9 months after surgery.
A, CT image obtained before surgery shows grossly irregular nodule and centrilobular emphysema.
B, CT image obtained before surgery shows central low-attenuation area; this finding indicates necrosis is present within tumor.
C, Low-power photomicrograph of histologic specimen shows extensive necrosis in central portion of tumor.
D, High-power photomicrograph shows predominantly atypical multinucleated giant cells (arrows).

290 AJR:207, August 2016

 CT of Pleomorphic Carcinoma of the Lung
window settings (window width, 350 HU; win-
dow level, 50 HU).
Two radiologists with 24 and 10 years of ex-
perience in interpreting thoracic CT, respectively,
evaluated the CT examinations for the size, loca-
tion, internal characteristics (i.e., central low-atten-
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uation area or cavity and calcification), and margin
characteristics of the tumors and for the presence
of chest wall invasion, mediastinal invasion, and
surrounding lung abnormalities (i.e., emphysema
or interstitial pneumonia). A central low-attenua-
tion area or cavity was defined as an internal area
with low attenuation relative to the attenuation of
the surrounding musculature. We used unenhanced
CT images for differentiating a tumor with a cen-
tral low-attenuation area or cavity from a tumor
with rim enhancement. The percentage of the cen-
tral low-attenuation area or cavity was semiquanti-
tatively calculated by dividing the area of the low-
attenuation area or cavity by the total tumor area
in the transaxial plane and was classified into two
groups: 0–25% of the lesion and more than 25% of
the lesion. The reviewers interpreted the images
separately, and a final decision was reached by con-
sensus if their interpretations differed. In the eight
patients who had undergone a previous CT exami-
nation before the preoperative CT examination, the
method originally described by Schwartz [9] was
used to calculate tumor doubling time:
Tdt = tlog2 / 3log(Dt / D0),
where Tdt is the tumor doubling time, t is the time
lapse between the two measurements, Dt is the
mean tumor diameter at the final measurement,
and D0 is the mean tumor diameter at the ini-
tial measurement.
Histopathologic Analysis
All surgical specimens were fixed in the inflated
state by transpleural and transbronchial infusion of
formalin. The specimens were stained with H and
E. Histopathologic findings (i.e., vessel invasion,
lymph node metastasis, and pathologic stage) were
reviewed in the surgical specimens by a lung pa-
thologist for this study. Pathologic staging was per-
formed according to the classification of the Union
for International Cancer Control [10]. The internal
characteristics of the tumors seen on CT scans were
compared with those seen at pathologic examination
of the specimens. The correlations were decided by
consensus of the pathologist and one radiologist.
Statistical Method
Overall survival and disease-free survival were
calculated according to the Kaplan-Meier method.
Univariate analyses were performed to determine
the influence of age, sex, smoking habits, CT find-
AJR:207, August 2016 291
TABLE 1: Thin-Section CT Findings of 44 Patients With Lung
­Pleomorphic  Carcinoma
CT Findings
Tumor size
≤ 30 mm
> 30 mm
Internal characteristics
Central low-attenuation area or cavity  40 (90.9)
> 25% of the lesion
Calcification
Margin characteristics
Sharp and smooth
Some irregular undulations
Grossly irregular with spiculations
Chest wall invasion
Mediastinal invasion
Pulmonary emphysema
Interstitial pneumonia
ings, vessel invasion, lymph node metastasis, and
pathologic stage. Variables with p values < 0.05 by
univariate analyses were chosen as the variables
for the multivariate logistic regression analysis. A
multivariate analysis by the Cox proportional haz-
ards regression model was used to identify vari-
ables that can be used to predict prognosis. In-
terobserver agreement for the CT findings was
analyzed by computing the intraclass correlation
coefficient (ICC). The strength of agreement was
considered slight for an ICC of 0.40 or less, fair for
an ICC of 0.41–0.60, moderate for an ICC of 0.61–
0.80, and excellent for an ICC of 0.81 or greater.
Results
Clinical Features
Of the 44 patients in this study, 36 were
men and eight were women. The age of the
patients at the time of PC diagnosis ranged
from 36 to 91 years, with an average of 67.1
years. Thirty-nine patients (89%) were smok-
ers, and 34 (77%) were heavy smokers (> 20
pack-years). Twenty-two of the 44 patients
died 3–120 months (mean, 27.5 months) af-
ter surgery, and 22 patients were alive 5–80
months (mean, 31.5 months) at the time of
the most recent follow-up. Fourteen of the 22
surviving patients were disease-free, and the
remaining eight had disease progression.
CT Findings
The results of the CT findings in all pa-
tients with lung PC are summarized in Ta-
ble 1. A central low-attenuation area or cavity
No. (%) of Patients
18 (40.9)
26 (59.1)
27 (61.4)
0 (0)
0 (0)
27 (61.4)
17 (38.6)
19 (43.2)
11 (25.0)
30 (68.2)
3 (6.8)
(40/44, 91%), tumor margin with some irreg-
ular undulations (27/44, 61%), chest wall in-
vasion (19/44, 43%), and pulmonary emphy-
sema (30/44, 68%) were frequently observed
on CT (Figs. 1–3). In the majority of cases
with a central low-attenuation area or cavity,
the low-attenuation area or cavity was greater
than 25% of the lesion (27/44, 61%). Interob-
server agreement (kappa value) for the CT
findings was excellent (0.86–1.00). The tumor
doubling times (n = 8) based on CT ranged
from 53 to 139 days, with a mean of 86.7 days.
Histopathologic Findings
The pathologic stage of the PC was IA in
five patients, IB in nine, IIB in 10, IIIA in 11,
IIIB in six, and IV in three. Vessel invasion
was observed in 26 (59%), and lymph node
metastasis was seen in 17 (39%) patients.
Pathologic analysis showed that the areas of
tumor necrosis with hemorrhagic foci corre-
sponded to the massive central low-attenua-
tion area or cavity on CT in most patients and
that the areas of myxoid degeneration also
corresponded to the low-attenuation area or
cavity on CT in two patients.
Correlation Clinical and CT Features
With Prognosis
A univariate analysis of the prognostic
factors influencing overall survival and dis-
ease-free survival is summarized in Table
2. A massive central low-attenuation area or
cavity on CT and advanced pathologic stage
 Fujisaki et al.

TABLE 2: Univariate Analysis of Prognostic Factors Influencing O­ verall (stage III–IV) predicted poorer overall sur-
­Survival and Disease-Free Survival of Patients With Lung vival (p  < 0.05; Fig. 4). A massive central
­Pleomorphic Carcinoma low-attenuation area or cavity on CT, lymph
p
node metastasis, and advanced stage (stage
III–IV) predicted poorer disease-free surviv-
Disease-Free al (p < 0.05; Fig. 5). A multivariate analysis
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Prognostic Factors Overall Survival Survival of the prognostic factors influencing overall
Age 0.4752 0.4097 survival and disease-free survival is summa-
Sex 0.8856 0.1113 rized in Table 3. A massive central low-at-
tenuation area or cavity on CT indicating ne-
Smoking index > 20 pack-years 0.6352 0.7959
crosis was the only significant independent
Tumor size > 30 mm 0.2706 0.1980 factor for predicting prognosis (p < 0.05).
Central low-attenuation area or cavity > 25% of the lesion 0.0038 0.0133
Margins grossly irregular with spiculations 0.1586 0.7580 Discussion
The results of our study showed that a
Chest wall invasion 0.2836 0.2931
massive central low-attenuation area or cav-
Mediastinal invasion 0.2922 0.6088 ity on CT was the only significant indepen-
Pulmonary emphysema or interstitial pneumonia 0.1648 0.1231 dent factor for predicting prognosis (p <
Vessel invasion 0.1007 0.2317 0.05); pathologic stage was not a significant
predictor. Surgical resection alone is there-
Lymph node metastasis 0.0637 0.0232
fore insufficient in patients with this find-
Stage (I–II vs III–IV) 0.0184 0.0266 ing on CT even if the pathologic stage is not
advanced, and the combination of extensive
TABLE 3: Multivariate Analysis of Prognostic Factors Influencing O
­ verall surgical intervention with aggressive postop-
­Survival and Disease-Free Survival of Patients With Lung erative chemotherapy, radiotherapy, or both
­Pleomorphic Carcinoma needs to be explored. Given that CT is rou-
tinely performed of most patients with lung
Prognostic Factors Relative Risk 95% CI p
PC, this imaging study is readily available
Overall survival and requires no additional cost. A massive
Central low-attenuation area or cavity > 25% of the lesion 4.739 0.060–0.738 0.0149 central low-attenuation area or cavity on CT
Lymph node metastasis 1.815 0.197–1.546 0.2578 may help in selecting a therapeutic strategy
for patients with lung PC.
Stage (I–II vs III–IV) 1.916 0.180–1.513 0.2312
In most cases in our study, the massive
Disease-free survival central low-attenuation area or cavity seen
Central low-attenuation area or cavity > 25% of the lesion 2.475 0.164–0.994 0.0484 on contrast-enhanced CT scans correspond-
Lymph node metastasis 1.923 0.214–1.262 0.1480
ed to areas of tumor necrosis in pathologic
specimens. Tumor necrosis represents a para-
Stage (I–II vs III–IV) 1.357 0.294–1.848 0.5153
doxical relationship whereby evidence of in-

A B
Fig. 2—36-year-old man with pleomorphic carcinoma of lung. Patient was alive without evidence of recurrence Fig. 3—76-year-old woman with pleomorphic
at 3-year follow-up. carcinoma of lung. Lung metastasis was detected
A and B, CT images obtained before surgery show mass with some irregular undulations (A) and chest wall and 7 months after surgery, and patient died of disease
mediastinal invasion (B). 19 months after surgery. CT image obtained before
surgery shows necrotic cavity within mass.

292 AJR:207, August 2016

 CT of Pleomorphic Carcinoma of the Lung

Central low-attenuation area or

1.0 cavity that is greater than 25% 1.0
of lesion (–)

0.8 0.8 Central low-attenuation area or

cavity that is greater than 25%
Cumulative Survival

Cumulative Survival
of lesion (–)
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0.6 p = 0.0038 0.6 p = 0.0133

Central low-attenuation area or

0.4 cavity that is greater than 25% 0.4 Central low-attenuation area or
of lesion (+) cavity that is greater than 25%
of lesion (+)
0.2 0.2

0 0

0 20 40 60 80 100 120 0 20 40 60 80 100 120

Survival (mo) Survival (mo)

Fig. 4—Graph shows overall survival according to CT finding of central low- Fig. 5—Graph shows disease-free survival according to CT finding of central low-
attenuation area or cavity that is greater than 25% of lesion. attenuation area or cavity that is greater than 25% of lesion.

creased tumor cell death indicates that the
tumor is a more aggressive tumor. This re-
lationship can be explained by rapid tumor
growth to a size at which the tumor has out-
grown its blood supply [11]. Hypoxia is a char-
acteristic of invasive cancers that can lead to
the development of an aggressive phenotype
through a mechanism that is mediated mainly
by hypoxia-inducible factor (HIF)–1 and that
includes cell immortalization and dedifferen-
tiation, pH regulation, autocrine growth and
survival, angiogenesis, invasion and metasta-
sis, and resistance to chemotherapy [12–14].
We speculate that rapid tumor growth leads to
inadequate blood supply to the central area of
the tumor, which results in ischemic changes.
Extensive necrosis due to ischemic changes
was the most prevalent cause of cavity forma-
tion and has been reported to be an indepen-
dent histologic factor in predicting prognosis
of patients with lung PC [4, 15].
Because lung PC is a rare type of lung
tumor, the studies in the peer-reviewed lit-
erature on its clinical features are relatively
limited. However, several clinical features
that are unique to lung PC have been report-
ed: PC shows prevalence in male smokers
who have a history of heavy tobacco con-
sumption, and the average age at presenta-
tion is 60 years [3, 4, 16]. Similar to these
results, our results also showed a male pre-
dominance (male-female ratio, 4.5:1) and
a clear association with a smoking habit
(89% had a history of smoking, the majority
whom were heavy smokers [i.e., > 20 pack-
years]). The high prevalence of pulmonary
emphysema (68%) surrounding the lung
PC in our study may be explained by these
unique clinical features.
The imaging findings of lung PC have been
reported in only a few articles to date. Kim et
al. [7] retrospectively evaluated the CT fea-
tures of 10 patients with lung PC and reported
that lung PCs preferentially manifest as large
peripheral lung neoplasms with a central low-
attenuation area (80%) and frequently invade
the pleura or chest wall (70%). Another group
of researchers, Kim et al. [8], also assessed
the CT features of surgically resected lung
PC in 30 patients, and a central low-attenua-
tion area or cavity was observed in 50% of the
patients in their series. In our larger series, a
low-attenuation area or cavity and chest wall
invasion were observed in 91% and 43% of
patients, respectively, and these results con-
cur with those of previous reports. These re-
sults suggest that lung PC tends to be necrot-
ic, cavitary, and locally invasive.
Rapid growth of lung PC has been sporad-
ically reported [3, 15, 17]; in some cases that
were measurable on CT using the Schwartz
method, the tumor doubling times were less
than 30 days [3, 15, 17]. In our cases, most
of the tumors grew as rapidly as those in the
past reports, and the tumor doubling times
were shorter than those of the common types
of NSCLC [18]. Although the characteristic
of rapid growth has not fully been explained,
the sarcomatoid elements of lung PC have a
high proliferative activity (MIB1 cell prolif-
eration marker index) and may be related to
the rapid growth [15]. From another point of
view, the expression of HIF-1α and microves-
sel density (MVD), which strongly affect an-
giogenesis through unregulation of vascular
endothelial growth factor, are significantly
greater in lung PC than in lung adenocarci-
noma [19]. Because angiogenesis is essential
for tumor growth, the overexpression of HIF-
1α and the increase of MVD of lung PC are
also considered causes of rapid growth.
The current study has several limitations.
First, this study included a relatively small
number of Asian patients because lung PC
is rare. An additional prospective study in a
broader population would yield more com-
prehensive results. Second, our study popu-
lation did not reflect the entire spectrum of
lung PC because we could include only pa-
tients with surgically resected lung PC and
because we excluded patients who were
treated with neoadjuvant chemotherapy.
These factors may have given rise to selec-
tion bias. Third, the difference in surgical
management and the progression of chemo-
therapy over a relatively long study period
may have had an impact on survival. Fourth,
in the eight patients who had undergone a
previous CT examination before the preop-
erative CT examination, we assessed the CT
findings on the preoperative CT examina-
tion (i.e., the later CT examination) because
we correlated CT features and postopera-
tive prognosis. Given the aggressive nature
of lung PC, the use of the preoperative (later)
images may have biased the CT findings. De-
spite these limitations, we believed that it is
important to determine the CT findings that
can be used to predict prognosis in patients
with lung PC. Finally, CT software was not
used in this study for the calculation of tu-

AJR:207, August 2016 293


mor doubling time because of the retrospec-
tive nature of this study. Further study of a
greater number of cases of lung PC with CT
software that can perform 3D volume mea-
surements is likely necessary to characterize
tumor growth of lung PC.
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In conclusion, a central low-attenuation
area or cavity in PC that occupies greater
than 25% of the tumor is associated with de-
creased overall survival and decreased dis-
ease free-survival, more so than pathologic
stage and lymph node metastases of NSCLC.
Recognition of this prognostic factor may
have important clinical implications, and fur-
ther large-scale study is encouraged to deter-
mine the appropriate treatment strategy based
on CT findings for patients with lung PC.
References
1. Corrin B, Chang YL, Rossi G, et al. Sarcomatoid
carcinoma. In: Travis WD, Brambilla E, Müller-
Hermelink HK, Harris CC, eds. World Health
­Organization classification of tumors: pathology
and genetics of tumours of the lung, pleura, thymus
and heart. Lyon, France: IARC Press, 2004:53–58
2. Chang YL, Lee YC, Shih JY, Wu CT. Pulmonary
pleomorphic (spindle) cell carcinoma: peculiar
clinicopathologic manifestations different from
ordinary non–small cell carcinoma. Lung Cancer
2001; 34:91–97
3. Fishback NF, Travis WD, Moran CA, Guinee DG
Jr, McCarthy WF, Koss MN. Pleomorphic (spin-
294 AJR:207, August 2016
Fujisaki et al.
dle/giant cell) carcinoma of the lung: a clinico-
pathologic correlation of 78 cases. Cancer 1994;
73:2936–2945
4. Rossi G, Cavazza A, Sturm N, et al. Pulmonary
carcinomas with pleomorphic, sarcomatoid, or
sarcomatous elements: a clinicopathologic and
immunohistochemical study of 75 cases. Am  J
Surg Pathol 2003; 27:311–324
5. Nakajima M, Kasai T, Hashimoto H, Iwata Y,
­Manabe H. Sarcomatoid carcinoma of the lung: a
clinicopathologic study of 37 cases. Cancer 1999;
86:608–616
6. Martin LW, Correa AM, Ordonez NG, et al. Sarco-
matoid carcinoma of the lung: a predictor of poor
prognosis. Ann Thorac Surg 2007; 84:973–980
7. Kim TH, Kim SJ, Ryu YH, et al. Pleomorphic car-
cinoma of lung: comparison of CT features and
pathologic findings. Radiology 2004; 232:554–559
8. Kim TS, Han J, Lee KS, et al. CT finding of surgi-
cally resected pleomorphic carcinoma of the lung
in 30 patients. AJR 2005; 185:120–125
9. Schwartz M. A biomathematical approach to clin-
ical tumor growth. Cancer 1961; 14:1272–1294
10. Sobin LH, Gospodarowicz MK, Wittekind C, eds.
International Union Against Cancer (UICC)
TNM classification of malignant tumours, 7th ed.
New York, NY: Wiley-Blackwell, 2010
11. Swinson DE, Jones JL, Richradson D, et al. Tumour
necrosis is an independent prognostic marker in
non–small cell lung cancer: correlation with bio-
logical variables. Lung Cancer 2002; 37:235–240
12. Gilchrist KW, Gray R, Fowble B, Tormey DC,
Taylor SG 4th. Tumor necrosis is a prognostic pre-
dictor for early recurrence and death in lymph
node-positive breast cancer: a 10-year follow-up
study of 728 Eastern Cooperative Oncology
Group patients. J Clin Oncol 1993; 11:1929–1935
13. Semenza GL. HIF-1 inhibitors for cancer therapy:
from gene expression to drug discovery. Curr
Pharm Des 2009; 15:3839–3843
14. Hiraoka N, Ino Y, Sekine S, et al. Tumour necrosis
is a postoperative prognostic marker for pancre-
atic cancer patients with a high interobserver re-
producibility in histological evaluation. Br  J
­Cancer 2010; 103:1057–1065
15. Fujioka S, Nakamura H, Adachi Y, et al. Pleomor-
phic carcinoma of the lung in which the sarcoma-
tous element grew rapidly: a case report. Ann Tho-
rac Cardiovasc Surg 2009; 15:111–114
16. Mochizuki T, Ishii G, Nagai K, et al. Pleomorphic
carcinoma of the lung: clinicopathologic charac-
teristics of 70 cases. Am  J Surg Pathol 2008;
32:1727–1735
17. Ito K, Oizumi S, Fukumoto S, et al. Clinical char-
acteristics of pleomorphic carcinoma of the lung.
Lung Cancer 2010; 68:204–210
18. Detterbeck FC, Gibson CJ. Turning gray: the nat-
ural history of lung cancer over time. J  Thorac
Oncol 2008; 3:781–792
19. Tsubata Y, Sutani A, Okimoto T, et al. Compara-
tive analysis of tumor angiogenesis and clinical
features of 55 cases of pleomorphic carcinoma
and adenocarcinoma of the lung. Anticancer Res
2015; 35:389–394