CT Findings of Surgically Resected Pleomorphic Carcinoma of the Lung in 30 Patients

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1 Kim et al. CT of Pleomorphic Carcinoma of the Lung Chest Imaging Clinical Observations Tae Sung Kim 1 Joungho Han 2 Kyung Soo Lee 1 Yeon Joo Jeong 1 Seo Hyun Kwak 1 Hong Sik Byun 1 Myung Jin Chung 1 Hojoong Kim 3 O Jung Kwon 3 Kim TS, Han J, Lee KS, et al. Received June 3, 2004; accepted after revision September 22, Supported by grant R from the Korea Science & Engineering Foundation. 1 Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul , Korea. 2 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul , Korea. Address correspondence to J. Han. 3 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul , Korea. AJR 2005;185: X/05/ American Roentgen Ray Society CT Findings of Surgically Resected Pleomorphic Carcinoma of the Lung in 30 Patients OBJECTIVE. The objective of our study was to assess the CT features of surgically resected pleomorphic carcinoma of the lung. CONCLUSION. The CT features of pleomorphic carcinoma of the lung appear to be dictated by the epithelial component of the tumor. Among the various subtypes of pleomorphic carcinoma, the large cell and giant cell subtype showed constant CT features including subpleural location, peritumoral areas of ground-glass attenuation, and extensive central low-attenuation areas. leomorphic carcinoma of the lung P is a poorly differentiated epithelial neoplasm predominantly composed of pleomorphic giant tumor cells, spindle tumor cells, or both [1]. According to the criteria of the World Health Organization (WHO) classification, pleomorphic carcinoma of the lung is defined as a non small cell lung cancer (carcinomatous or epithelial component) combined with neoplastic spindle or giant cells (sarcomatous or mesenchymal component) or a carcinoma consisting only of spindle and giant cells [2]. Several clinicopathologic studies about pleomorphic carcinoma of the lung including immunohistochemical studies have been reported [1 3]. Recently, Kim et al. [4] reported the CT features of pleomorphic carcinoma of the lung in 10 cases. We assessed the CT features of surgically resected pleomorphic carcinoma of the lung in 30 patients to identify any specific imaging characteristics that may help in the diagnosis of this disease entity. Materials and Methods Between 1995 and 2003, 30 patients (male-tofemale ratio, 27:3; age range, years; mean age, 57 years) with surgically resected pleomorphic carcinoma of the lung were identified from the files of the department of pathology in our institute. Approval from the institutional review board at our institute was not needed to review pathologic reports and radiologic images. The histologic population consisted of the adenocarcinoma and giant cell subtype (n = 3), adenocarcinoma subtype (n = 4), adenosquamous cell subtype (n =1), squamous cell subtype (n =9), large cell subtype (n = 4), and large cell and giant cell subtype (n = 9). We retrospectively reviewed the clinical, CT, and pathologic findings. The chief complaints of the patients were cough (n = 12), blood-tinged or hemoptysis (n = 11), dyspnea (n = 4), or chest pain (n =2). Seven patients were asymptomatic. Unenhanced and contrast-enhanced helical chest CT images were obtained in all patients using a single-detector CT scanner (HiSpeed Advantage, GE Healthcare). The parameters of chest CT were 7-mm collimation and a table feed of 10 mm/sec. Contrast-enhanced chest CT scans were obtained after injection of 30 g of iodinated contrast medium (100 ml of iopamidol [Iopamiron 300, Bracco]) at a rate of 3 ml/sec with a power injector (OP 100, Medrad). Chest CT scans were analyzed retrospectively and jointly by two experienced chest radiologists with 7 and 14 years experience in chest radiology, respectively. The reviewers assessed the scans in terms of the margin (well defined, ill defined, lobulated, or spiculated), size, and location of the tumors; attenuation after contrast enhancement; and presence or absence of intratumoral cavitation and chest wall invasion. Central tumors were defined as those that involved the carina or a main segmental bronchus. Peripheral tumors were defined as those surrounded by lung parenchyma or distal to the subsegmental bronchi. The decisions on the CT findings were reached by a consensus. All patients underwent curative resection with mediastinal lymph node dissection (pneumonec- 120 AJR:185, July 2005

2 CT of Pleomorphic Carcinoma of the Lung tomy or lobectomy with or without en bloc chest wall resection). The time interval between the CT study and surgery was 3 26 days (mean, 10 days ± 5.96 [SD]). Pathologic specimens were carefully reviewed by an experienced pathologist. Staging was evaluated according to the International Union Against Cancer criteria [5]. Results CT Findings The clinical, CT, and pathologic data of 30 pleomorphic carcinomas of the lung are summarized in Table 1. In the 30 patients, 10 central tumors and 20 peripheral tumors were identified, with diameters ranging from 1.5 to 10 cm in longest diameter (mean, A C Fig. 1 Pleomorphic carcinoma of lung (adenocarcinoma subtype) in 46-year-old man (case 4 in Table 1). A, Axial contrast-enhanced CT scan shows peripheral mass in right upper lobe. B, CT image obtained using lung window settings shows marginal spiculation of tumor. C, Photomicrograph shows mixed composition of adenocarcinoma (arrows) and carcinoma (asterisk). (H and E, 100) 4.7 cm). The tumors were located in the right upper lobe (n = 14), left upper lobe (n =9), right lower lobe (n = 2), left lower lobe (n = 4), and right middle lobe (n =1). The upper lobe predilection of pleomorphic carcinoma of the lung was seen in 77% (23/30) of the cases. For the adenocarcinoma and giant or subtype, six (86%) of seven tumors were located peripherally (Fig. 1). For the squamous cell and spindle cell subtype, all nine tumors were located centrally (Fig. 2). For the large cell and spindle or giant cell subtype, all 13 tumors were located peripherally (Fig. 3). The marginal characteristics of the tumors were well defined in 13 patients (43%), ill defined in six (20%), lobulated in six (20%), or spiculated in three (10%). The remaining two patients showed a central mass with distal atelectasis, in which the tumoral margin could not be assessed. All tumors showed mild enhancement similar to the that of the surrounding musculature after contrast enhancement, and inhomogeneous central low-attenuation areas were seen in 15 patients (50%). Tumors with a large cell component showed frequent low attenuation (85% [11/13]) representing central necrosis on histopathologic specimens. Especially, all nine tumors of the large cell and giant cell subtype showed subpleural location and a large area of low attenuation suggestive of extensive B AJR:185, July

3 Kim et al. TABLE 1: Clinical, CT, and Pathologic Data of Pleomorphic Carcinoma of the Lung Case No. Age (yr) Sex Symptoms Involved Lobe Location Size (cm) Inhomogeneous Low Attenuation CT Findings Cavity Peritumoral Area of Ground- Glass Attenuation Histologic Type 1 41 F None Right upper Peripheral 3.5 Adenocarcinoma and giant cell 2 51 M Blood-tinged 3 47 F Blood-tinged Right upper Peripheral 3.5 Adenocarcinoma and giant cell Left lower Peripheral 6 + Adenocarcinoma and giant cell 4 46 M None Right upper Peripheral 3 Adenocarcinoma and 5 58 M None Left upper Peripheral 6 + Adenocarcinoma and 6 74 M None Left upper Peripheral 1.5 Adenocarcinoma and 7 84 M None Right upper Central 3 Adenocarcinoma and 8 76 M Dyspnea Right upper Peripheral Adenosquamous and 9 71 M Cough, bloodtinged M Cough, bloodtinged M Blood-tinged, dyspnea Left upper Central 7 Squamous cell carcinoma Right lower Central Squamous cell carcinoma Left lower Central 4.5 Squamous cell carcinoma M Cough Left upper Central 5 Squamous cell carcinoma M Cough, bloodtinged Right main bronchus M Dyspnea Left main bronchus Central 3 Squamous cell carcinoma Endobronchial 2.5 Squamous cell carcinoma Pathologic Staging T3 N0 M0 T2 N2 M0 T1 N2 M0 T2 N2 M0 T2 N1 M0 T2 N1 M0 T1 N0 M M Cough Right upper Central 4 + Squamous cell carcinoma T3 N0 M M Dyspnea Left upper Central 6 Squamous cell carcinoma M Cough Right upper Central 3.5 Squamous cell carcinoma M None Right upper Peripheral 2.5 Large cell T1 N0 M M None Left lower Peripheral Large cell T3 N0 M M Cough Left upper Peripheral 4 Large cell F Blood-tinged Right upper Peripheral Large cell T1 N0 M M Cough, bloodtinged Left lower Peripheral Large cell and giant cell T2 N1 M M Blood-tinged Left upper Peripheral Large cell and giant cell T3 N0 M M Chest pain Right upper Peripheral Large cell and giant cell T3 N0 M M Cough Right upper Peripheral Large cell and giant cell T3 N0 M M Hemoptysis Right upper Peripheral Large cell and giant cell T3 N2 M M Cough, bloodtinged Right upper Peripheral Large cell and giant cell M Cough Right upper Peripheral Large cell and giant cell M Cough Right lower Peripheral Large cell and giant cell T2 N2 M M Chest pain Left upper Peripheral Large cell and giant cell T3 N0 M0 Note Plus sign (+) = present, minus sign ( ) = absent. 122 AJR:185, July 2005

4 CT of Pleomorphic Carcinoma of the Lung tumor necrosis on contrast-enhanced CT scans (Fig. 3). The attenuation values of the central low-attenuation areas of this subtype on contrast-enhanced CT scan ranged from 5 to 45 H (mean, 23 H), and tiny intratumoral cavities were noted in four patients (44%). In this particular subtype, a poorly defined margin with surrounding areas of ground-glass attenuation was noted in all tumors. The tumor size was slightly larger (mean diameter, 5.8 cm) than that of the remaining subtypes (mean diameter, 4.3 cm). Regional invasion into the adjacent chest wall (n = 4) or mediastinal fat (n = 1) was seen or suggested in five (56%) of nine tumors on CT. No pleural change was noted in all 30 patients except a small amount of ipsilateral pleural effusion in one patient, which proved to be transudate. Pathologic Findings At histopathologic examination, all nine tumors of the large cell and giant cell subtype showed subpleural location, and five of them showed invasion of the adjacent chest wall (n = 4) or mediastinal fat (n = 1) on pathologic specimen. All tumors of this subtype showed various degrees of necrosis (20 90% area) on microscopic examination. On radiologic pathologic correlation, the peritumoral areas of ground-glass attenuation seen on CT scans represented areas of intraalveolar macrophage collection and alveolar wall thickening with inflammatory cell infiltration and mild fibrosis (Fig. 3D). A Fig. 2 Pleomorphic carcinoma of lung (squamous cell subtype) in 58-year-old man (case 10 in Table 1). A, Axial contrast-enhanced CT scan shows central cavitary mass with marginal irregularity in right lower lobe superior segment. Note enlarged hilar lymph node (arrow). B, Photomicrograph shows mixed composition of squamous cell carcinoma (arrows) carcinoma (asterisk). (H and E, 100) In postoperative pathologic tumor staging, the incidence of T3 disease was 56% (5/9) for the large cell and giant cell subtype owing to frequent chest wall invasion, whereas that of the remaining subtypes was 14% (3/21). Discussion The recent WHO classification of lung tumors defines pleomorphic carcinoma as follows [2]: a poorly differentiated nonsmall cell lung cancer, namely squamous cell carcinoma, adenocarcinoma, or large cell carcinoma, containing s and/or giant cells, or a carcinoma consisting only of spindle and giant cells. At least 10% of s, giant cells, or both should be present to classify a carcinoma as pleomorphic carcinoma [2, 6 8]. According to Rossi et al. [2] in a clinicopathologic and immunohistochemical study of 75 cases of pulmonary carcinoma with pleomorphic, sarcomatoid, or sarcomatous elements, the male female ratio was 9.7:1, and 92% of the patients were smokers. Pleomorphic carcinoma presented as a large, frequently peripheral, necrotic mass that mainly involved the upper lobes. Forty-eight percent showed a predilection for the upper lobes, and 33% were located in the right upper lobe. More than 70.7% of the cases were peripheral tumors. Their results also revealed that pleomorphic carcinoma of the lung showed a worse prognosis than conventional non small cell lung cancer at surgically curable stage I, justifying separation as an independent histologic type in the WHO classification. According to Fishback et al. [3] in a clinicopathologic study of 78 cases of pleomorphic ( and giant cell subtype) carcinoma of the lung with various carcinomatous components, 65% of the tumors were located in the upper lobes and 47% of the total were in the right upper lobes. Their study also showed that 60% of the tumors were peripheral masses, and 24% showed chest wall invasion. Ninety-one percent contained foci of necrosis on light microscopic examinations. According to Kim et al. [4] in a recent study of 10 cases of pleomorphic carcinoma of the lung, the tumors preferentially manifest as large peripheral lung neoplasms (n = 9) with a central low-attenuation area and frequently invade the pleura (n = 7) and chest wall (n =2). Our results also showed a predilection of the tumor to affect the upper lobes (77% [23/30]) and particularly the right upper lobe (47% [14/30]). The high incidence (86%) of peripheral location of the adenocarcinoma and giant cell subtype and the adenocarcinoma subtype and a strong predilection for central location (100%) of the squamous cell subtype correlate well with the general predilection of B AJR:185, July

5 Kim et al. A C Fig. 3 Pleomorphic carcinoma of lung (large cell and giant cell subtype) in 63-yearold man (case 30 in Table 1). A, Axial contrast-enhanced CT scan shows peripheral low-attenuation mass with marginal irregularity in left upper lobe. Note small intratumoral cavities and adjacent chest wall invasion (arrow). B, CT image obtained using lung window settings shows peritumoral areas of ground-glass attenuation. C, Photograph of gross specimen shows large round peripheral necrotic mass. D, Photomicrograph of histopathologic specimen shows solid tumor (T) with poorly defined margin and central necrosis. Surrounding lung parenchyma (H) shows intraalveolar macrophage aggregation and interstitial thickening due to inflammatory cell infiltration. (H and E, 12) E, Photomicrograph shows mixed composition of large cell carcinoma and pleomorphic multinucleated giant cells (arrows). (H and E, 200) B D E 124 AJR:185, July 2005

6 CT of Pleomorphic Carcinoma of the Lung adenocarcinoma for peripheral location and that of squamous cell carcinoma for central location [9]. Large cell carcinomas of the lung tend to be bulky peripheral masses with multiple foci of necrosis [10], and all 13 cases of the subtypes containing the large cell carcinoma component showed peripheral location in our series. Accordingly, the CT features of pleomorphic carcinomas of the lung appear to be dominated by the epithelial component rather than the mesenchymal component of the tumor. Many other features similar to those of previous reports including male predominance (9:1), peripheral location (67% [20/30]), frequent necrosis (50% [15/30]), and chest wall invasion (27% [8/30]) were also noted in our series. These CT features were more prominent in the large cell and giant cell subtype compared with the remaining subtypes: All patients were male, all tumors showed subpleural location and a large area of low attenuation, and the incidence of chest wall or mediastinal invasion was as high as 56% (5/9). In addition, a peritumoral area of ground-glass attenuation was characteristic of this subtype. Although pleural involvement was frequently noted in a recent study [4], such a finding was not seen in our series. We think the reason is that cases of T4 disease with pleural seeding were not enrolled in our series, for which only surgically resected pleomorphic carcinomas were identified in the first place. The overall CT features of pleomorphic carcinomas of the lung in our series were rather nonspecific and not much different from those of ordinary non small lung cancers, such as central or peripheral mass, marginal lobulation or spiculation, and frequent central necrosis [11]. Although the large cell and giant cell subtype had some different CT features in our series, these findings may not be directly applicable to the whole heterogeneous group of pleomorphic (giant cell and ) carcinoma with various carcinomatous components (adenocarcinoma, squamous cell carcinoma, and mixed types). Our results, however, show that the CT features of pleomorphic carcinoma of the lung appear to be dominated by the epithelial component rather than the mesenchymal component of the tumor, and the possibility of pleomorphic carcinoma should be suggested when a subpleural necrotic tumor is seen with peritumoral areas of ground-glass attenuation and regional invasion to the adjacent chest wall or mediastinum. Owing to its subpleural location with a large area of significantly low attenuation value on contrast-enhanced CT scan, the large cell and giant cell subtype of pleomorphic carcinoma of the lung can simulate benign diseases such as a mediastinal bronchogenic cyst or neurogenic tumor with cystic degeneration or an empyema cavity. In summary, the CT features of pleomorphic carcinoma of the lung appear to be dictated by the epithelial component of the tumor. Among the various subtypes of pleomorphic carcinoma, the large cell and giant cell subtype showed constant CT features including subpleural location, peritumoral areas of ground-glass attenuation, and extensive central low-attenuation areas. This subtype also showed frequent cavitation and invasion into the adjacent chest wall. References 1. Przygodzki RM, Koss MN, Moran CA, et al. Pleomorphic (giant ) carcinoma is genetically distinct from adenocarcinoma and squamous cell carcinoma by K-ras-2 and p53 analysis. Am J Clin Pathol 1996; 106: 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: Fishback NF, Travis WD, Moran CA, Guinee DG Jr, McCarthy WF, Koss MN. Pleomorphic (spindle/giant cell) carcinoma of the lung: a clinicopathologic correlation of 78 cases. Cancer 1994; 73: Kim TH, Kim SJ, Ryu YH, et al. Pleomorphic carcinoma of lung: comparison of CT features and pathologic findings. Radiology 2004; 232: Sobin LH, Wittekind CH, eds. UICC TNM classification of malignant tumors, 5th ed. New York, NY: Wiley, Brambilla E, Travis WD, Colby TV, et al. The new World Health Organization classification of lung tumors. Eur Respir J 2001; 18: Travis WD. Pathology of lung cancer. Clin Chest Med 2002; 23: Travis WD, Colby TV, Corrin B, et al. World Health Organization international histological classification of tumors: histological typing of lung and pleural tumors, 3rd ed. Berlin, Germany: Springer-Verlag, Silverberg E. Cancer statistics. CA Cancer J Clin 1985; 35: Yesner R. Large cell carcinoma of the lung. Semin Diagn Pathol 1985; 2: Fraser R, Müller N, Colman N, Paré P. Diagnosis of diseases of the chest, 3rd ed. Philadelphia, PA: Saunders, 1999: AJR:185, July

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