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Clinical Observations |
1 Department of Radiology and Center for Imaging Science, Samsung Medical
Center, Sungkyunkwan University School of Medicine, Seoul 135-710,
Korea.
2 Department of Pathology, Samsung Medical Center, Sungkyunkwan University
School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710, Korea.
3 Division of Pulmonary and Critical Care Medicine, Department of Medicine,
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul
135-710, Korea.
Received June 3, 2004;
accepted after revision September 22, 2004.
Supported by grant R11-2002-103 from the Korea Science & Engineering
Foundation.
Abstract
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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.
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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.
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The histologic population consisted of the adenocarcinoma and giant cell subtype (n = 3), adenocarcinoma and spindle cell subtype (n = 4), adenosquamous cell and spindle cell subtype (n = 1), squamous cell and spindle cell subtype (n = 9), large cell and spindle 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 sputum 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 (pneumonectomy 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].
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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 spindle cell subtype, six (86%) of seven tumors were located peripherally (Figs. 1A, 1B, and 1C). For the squamous cell and spindle cell subtype, all nine tumors were located centrally (Figs. 2A, and 2B). For the large cell and spindle or giant cell subtype, all 13 tumors were located peripherally (Figs. 3A, 3B, 3C, 3D, and 3E).
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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 tumor necrosis on contrast-enhanced CT scans (Figs. 3A, 3B, 3C, 3D, and 3E). 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).
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).
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...a poorly differentiated nonsmall cell lung cancer, namely squamous cell carcinoma, adenocarcinoma, or large cell carcinoma, containing spindle cells and/or giant cells, or a carcinoma consisting only of spindle and giant cells.
At least 10% of spindle cells, 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 (spindle cell 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 and spindle cell subtype and a strong predilection for central location (100%) of the squamous cell and spindle cell subtype correlate well with the general predilection of 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 spindle cell) 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.
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