Professional Documents
Culture Documents
Pleomorphic Carcinoma of The Lung: Relationship Between CT Findings and Prognosis
Pleomorphic Carcinoma of The Lung: Relationship Between CT Findings and Prognosis
Fujisaki et al.
CT of Pleomorphic Carcinoma of the Lung
Cardiopulmonary Imaging
Original Research
Downloaded from www.ajronline.org by 103.125.234.201 on 10/01/20 from IP address 103.125.234.201. Copyright ARRS. For personal use only; all rights reserved
P
and Environmental Health School of Medicine,
1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555,
subtype of sarcomatoid carcino- the sarcomatoid lung tumor patients (24.5%)
Japan. Address correspondence to T. Aoki
(a-taka@med.uoeh-u.ac.jp). ma that contains a component of was significantly less than that of the patients
sarcoma or sarcomalike (spindle with other types of NSCLC (46.3%).
2
Department of Pathology, National Hospital Organization cells, giant cells, or both) differentiation. Ac- Although several clinicopathologic studies
Kinki-Chuo Chest Medical Center, Sakai, Japan. cording to the criteria of the World Health of lung PC have been reported in the litera-
3
Department of Pathology and Oncology, University of
Organization classification [1], PC of the lung ture, there are few studies about its radiologic
Occupational and Environmental Health School of is defined as a poorly differentiated non– features [7, 8]. Moreover, to our knowledge,
Medicine, Kitakyushu, Japan. small cell lung carcinoma (NSCLC) contain- the correlation of CT findings with prognosis
4
ing spindle cells, giant cells, or both or a car- has not been described to date. The purpose
Cancer Therapy Center, Tobata Kyoritsu Hospital,
cinoma consisting of only spindle and giant of our study was to assess the radiologic and
Kitakyushu, Japan.
cells. At least 10% of the carcinoma should be clinical findings of lung PC and to evaluate
5
Second Department of Surgery, University of composed of spindle cells, giant cells, or both whether there are any characteristic features
Occupational and Environmental Health School of for it to be classified as a PC. This tumor is that predict the prognosis.
Medicine, Kitakyushu, Japan. rare, and its incidence has been reported to be
6
Department of Respiratory Medicine, University of
0.1–0.4% of all lung malignancies [2, 3]. Pa- Materials and Methods
Occupational and Environmental Health School of tients with PC tend to present at a more ad- Our institutional review board approved this
Medicine, Kitakyushu, Japan. vanced stage and to have a poorer prognosis study, and informed consent was waived for ret-
than those with a common type of NSCLC rospective review of patient records and images.
AJR 2016; 207:289–294 [3–5]. Martin et al. [6] compared the 5-year
0361–803X/16/2072–289
survival rate of 63 sarcomatoid lung tumor Patients and Clinical Findings
patients with that of propensity score– The medical records of 59 Asian patients with
© American Roentgen Ray Society matched patients with other types of NSCLC a diagnosis of lung PC at our hospital between
June 1995 and December 2013 were retrospective- resection (n = 1), segmentectomy (n = 5), lobecto- gle-detector helical CT unit. For the MDCT ex-
ly reviewed, and patients who had undergone sur- my (n = 35), or pneumonectomy (n = 3) was per- aminations, the following parameters were used:
gical resection of the lung tumor, had undergone formed. Eight patients had undergone CT more 2.0-mm section width with 2.0-mm reconstruc-
contrast-enhanced CT before surgery, and had than 2 months before surgery in addition to the tion interval, pitch (ratio of table travel per rota-
not been given any anticancer drugs before sur- preoperative CT study; therefore, tumor growth tion to total beam width) of 15, 120 kVp, and 300
gery were included in this study. PET/CT was per- could be evaluated using the previous CT exami- mA. For the single-detector CT examinations, the
Downloaded from www.ajronline.org by 103.125.234.201 on 10/01/20 from IP address 103.125.234.201. Copyright ARRS. For personal use only; all rights reserved
formed in 27 of the 59 patients and detected occult nation and the preoperative CT examination. CT following parameters were used: 10-mm section
metastasis in five patients. Fifteen patients were observation periods of the eight patients ranged thickness, 120 kVp, 150 mA, and a table speed
excluded from the study for the following reasons: from 70 to 329 days. The medical record of each of 10 mm/s. For additional scanning of the tumor
11 patients received neoadjuvant chemotherapy patient was reviewed by two of the authors for the using the single-detector CT unit, the following
before CT, two patients underwent needle biopsy following: age, sex, smoking habits, treatment, and parameters were used: 2.0-mm section thickness,
without surgical resection for PC diagnosis, and long-term clinical status after surgery (i.e., recur- 120 kVp, and 250 mA. All images were reviewed
two patients did not undergo contrast-enhanced rence, metastasis, or survival). on an ultra-high-resolution gray-scale monitor
CT. Thus, 44 patients were included in this study. (20.8 inches [27.4 cm], 2048 × 1560 pixels; Coro-
The time interval between the final preopera- CT Analysis nis 3MP, BARCO Display Systems) using stan-
tive CT examination and surgery ranged from 2 to Scanning of the whole lungs was performed dard lung window settings (window width, 1600
26 days. Surgical resection in the form of a wedge on a 4-, 16-, 32-, or 64-MDCT unit or on a sin- 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).
window settings (window width, 350 HU; win- TABLE 1: Thin-Section CT Findings of 44 Patients With Lung
dow level, 50 HU). Pleomorphic Carcinoma
Two radiologists with 24 and 10 years of ex-
CT Findings No. (%) of Patients
perience in interpreting thoracic CT, respectively,
evaluated the CT examinations for the size, loca- Tumor size
tion, internal characteristics (i.e., central low-atten- ≤ 30 mm 18 (40.9)
Downloaded from www.ajronline.org by 103.125.234.201 on 10/01/20 from IP address 103.125.234.201. Copyright ARRS. For personal use only; all rights reserved
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
Downloaded from www.ajronline.org by 103.125.234.201 on 10/01/20 from IP address 103.125.234.201. Copyright ARRS. For personal use only; all rights reserved
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.
Cumulative Survival
of lesion (–)
Downloaded from www.ajronline.org by 103.125.234.201 on 10/01/20 from IP address 103.125.234.201. Copyright ARRS. For personal use only; all rights reserved
0 0
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 PC in our study may be explained by these giogenesis through unregulation of vascular
tumor is a more aggressive tumor. This re- unique clinical features. endothelial growth factor, are significantly
lationship can be explained by rapid tumor The imaging findings of lung PC have been greater in lung PC than in lung adenocarci-
growth to a size at which the tumor has out- reported in only a few articles to date. Kim et noma [19]. Because angiogenesis is essential
grown its blood supply [11]. Hypoxia is a char- al. [7] retrospectively evaluated the CT fea- for tumor growth, the overexpression of HIF-
acteristic of invasive cancers that can lead to tures of 10 patients with lung PC and reported 1α and the increase of MVD of lung PC are
the development of an aggressive phenotype that lung PCs preferentially manifest as large also considered causes of rapid growth.
through a mechanism that is mediated mainly peripheral lung neoplasms with a central low- The current study has several limitations.
by hypoxia-inducible factor (HIF)–1 and that attenuation area (80%) and frequently invade First, this study included a relatively small
includes cell immortalization and dedifferen- the pleura or chest wall (70%). Another group number of Asian patients because lung PC
tiation, pH regulation, autocrine growth and of researchers, Kim et al. [8], also assessed is rare. An additional prospective study in a
survival, angiogenesis, invasion and metasta- the CT features of surgically resected lung broader population would yield more com-
sis, and resistance to chemotherapy [12–14]. PC in 30 patients, and a central low-attenua- prehensive results. Second, our study popu-
We speculate that rapid tumor growth leads to tion area or cavity was observed in 50% of the lation did not reflect the entire spectrum of
inadequate blood supply to the central area of patients in their series. In our larger series, a lung PC because we could include only pa-
the tumor, which results in ischemic changes. low-attenuation area or cavity and chest wall tients with surgically resected lung PC and
Extensive necrosis due to ischemic changes invasion were observed in 91% and 43% of because we excluded patients who were
was the most prevalent cause of cavity forma- patients, respectively, and these results con- treated with neoadjuvant chemotherapy.
tion and has been reported to be an indepen- cur with those of previous reports. These re- These factors may have given rise to selec-
dent histologic factor in predicting prognosis sults suggest that lung PC tends to be necrot- tion bias. Third, the difference in surgical
of patients with lung PC [4, 15]. ic, cavitary, and locally invasive. management and the progression of chemo-
Because lung PC is a rare type of lung Rapid growth of lung PC has been sporad- therapy over a relatively long study period
tumor, the studies in the peer-reviewed lit- ically reported [3, 15, 17]; in some cases that may have had an impact on survival. Fourth,
erature on its clinical features are relatively were measurable on CT using the Schwartz in the eight patients who had undergone a
limited. However, several clinical features method, the tumor doubling times were less previous CT examination before the preop-
that are unique to lung PC have been report- than 30 days [3, 15, 17]. In our cases, most erative CT examination, we assessed the CT
ed: PC shows prevalence in male smokers of the tumors grew as rapidly as those in the findings on the preoperative CT examina-
who have a history of heavy tobacco con- past reports, and the tumor doubling times tion (i.e., the later CT examination) because
sumption, and the average age at presenta- were shorter than those of the common types we correlated CT features and postopera-
tion is 60 years [3, 4, 16]. Similar to these of NSCLC [18]. Although the characteristic tive prognosis. Given the aggressive nature
results, our results also showed a male pre- of rapid growth has not fully been explained, of lung PC, the use of the preoperative (later)
dominance (male-female ratio, 4.5:1) and the sarcomatoid elements of lung PC have a images may have biased the CT findings. De-
a clear association with a smoking habit high proliferative activity (MIB1 cell prolif- spite these limitations, we believed that it is
(89% had a history of smoking, the majority eration marker index) and may be related to important to determine the CT findings that
whom were heavy smokers [i.e., > 20 pack- the rapid growth [15]. From another point of can be used to predict prognosis in patients
years]). The high prevalence of pulmonary view, the expression of HIF-1α and microves- with lung PC. Finally, CT software was not
emphysema (68%) surrounding the lung sel density (MVD), which strongly affect an- used in this study for the calculation of tu-
mor doubling time because of the retrospec- dle/giant cell) carcinoma of the lung: a clinico- Taylor SG 4th. Tumor necrosis is a prognostic pre-
tive nature of this study. Further study of a pathologic correlation of 78 cases. Cancer 1994; dictor for early recurrence and death in lymph
greater number of cases of lung PC with CT 73:2936–2945 node-positive breast cancer: a 10-year follow-up
software that can perform 3D volume mea- 4. Rossi G, Cavazza A, Sturm N, et al. Pulmonary study of 728 Eastern Cooperative Oncology
surements is likely necessary to characterize carcinomas with pleomorphic, sarcomatoid, or Group patients. J Clin Oncol 1993; 11:1929–1935
tumor growth of lung PC. sarcomatous elements: a clinicopathologic and 13. Semenza GL. HIF-1 inhibitors for cancer therapy:
Downloaded from www.ajronline.org by 103.125.234.201 on 10/01/20 from IP address 103.125.234.201. Copyright ARRS. For personal use only; all rights reserved
In conclusion, a central low-attenuation immunohistochemical study of 75 cases. Am J from gene expression to drug discovery. Curr
area or cavity in PC that occupies greater Surg Pathol 2003; 27:311–324 Pharm Des 2009; 15:3839–3843
than 25% of the tumor is associated with de- 5. Nakajima M, Kasai T, Hashimoto H, Iwata Y, 14. Hiraoka N, Ino Y, Sekine S, et al. Tumour necrosis
creased overall survival and decreased dis- Manabe H. Sarcomatoid carcinoma of the lung: a is a postoperative prognostic marker for pancre-
ease free-survival, more so than pathologic clinicopathologic study of 37 cases. Cancer 1999; atic cancer patients with a high interobserver re-
stage and lymph node metastases of NSCLC. 86:608–616 producibility in histological evaluation. Br J
Recognition of this prognostic factor may 6. Martin LW, Correa AM, Ordonez NG, et al. Sarco- Cancer 2010; 103:1057–1065
have important clinical implications, and fur- matoid carcinoma of the lung: a predictor of poor 15. Fujioka S, Nakamura H, Adachi Y, et al. Pleomor-
ther large-scale study is encouraged to deter- prognosis. Ann Thorac Surg 2007; 84:973–980 phic carcinoma of the lung in which the sarcoma-
mine the appropriate treatment strategy based 7. Kim TH, Kim SJ, Ryu YH, et al. Pleomorphic car- tous element grew rapidly: a case report. Ann Tho-
on CT findings for patients with lung PC. cinoma of lung: comparison of CT features and rac Cardiovasc Surg 2009; 15:111–114
pathologic findings. Radiology 2004; 232:554–559 16. Mochizuki T, Ishii G, Nagai K, et al. Pleomorphic
References 8. Kim TS, Han J, Lee KS, et al. CT finding of surgi- carcinoma of the lung: clinicopathologic charac-
1. Corrin B, Chang YL, Rossi G, et al. Sarcomatoid cally resected pleomorphic carcinoma of the lung teristics of 70 cases. Am J Surg Pathol 2008;
carcinoma. In: Travis WD, Brambilla E, Müller- in 30 patients. AJR 2005; 185:120–125 32:1727–1735
Hermelink HK, Harris CC, eds. World Health 9. Schwartz M. A biomathematical approach to clin- 17. Ito K, Oizumi S, Fukumoto S, et al. Clinical char-
Organization classification of tumors: pathology ical tumor growth. Cancer 1961; 14:1272–1294 acteristics of pleomorphic carcinoma of the lung.
and genetics of tumours of the lung, pleura, thymus 10. Sobin LH, Gospodarowicz MK, Wittekind C, eds. Lung Cancer 2010; 68:204–210
and heart. Lyon, France: IARC Press, 2004:53–58 International Union Against Cancer (UICC) 18. Detterbeck FC, Gibson CJ. Turning gray: the nat-
2. Chang YL, Lee YC, Shih JY, Wu CT. Pulmonary TNM classification of malignant tumours, 7th ed. ural history of lung cancer over time. J Thorac
pleomorphic (spindle) cell carcinoma: peculiar New York, NY: Wiley-Blackwell, 2010 Oncol 2008; 3:781–792
clinicopathologic manifestations different from 11. Swinson DE, Jones JL, Richradson D, et al. Tumour 19. Tsubata Y, Sutani A, Okimoto T, et al. Compara-
ordinary non–small cell carcinoma. Lung Cancer necrosis is an independent prognostic marker in tive analysis of tumor angiogenesis and clinical
2001; 34:91–97 non–small cell lung cancer: correlation with bio- features of 55 cases of pleomorphic carcinoma
3. Fishback NF, Travis WD, Moran CA, Guinee DG logical variables. Lung Cancer 2002; 37:235–240 and adenocarcinoma of the lung. Anticancer Res
Jr, McCarthy WF, Koss MN. Pleomorphic (spin- 12. Gilchrist KW, Gray R, Fowble B, Tormey DC, 2015; 35:389–394