Spreading pattern and CT findings of very early-stage peripheral small-cell lung cancer

Takeshi Terashima, Tatsu Matsuzaki, Shotaro Chubachi, Fumio Sakamaki, Minako Satoh, Eri Tomioka, George Horio, Rika Ogawa, Asuka Naitoh, Hiroya Ojiri

Department of Radiology, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan.
Department of Respiratory Medicine, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japa.
Department of Respiratory Medicine, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan.
Department of Respiratory Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan.

DOI: 10.4236/alc.2013.24010                

Abstract

Chest CT frequently reveals small pulmonary lesions. If there is no associated hilar or mediastinal lymphadenopathy, small-cell lung cancer (SCLC) is considered to be very early-stage. Few studies, however, have described the characteristic CT findings of very early-stage SCLC. Clarifying these findings would reduce diagnostic delay. The purpose of this study was to determine the characteristic CT findings of very earlystage SCLC. Computed tomography images obtained from 547 consecutive patients with lung cancer between 2003 and 2012 at Tokyo Dental College Ichikawa General Hospital were reviewed retrospectively. One hundred of these patients had SCLC and 447 had non-SCLC (NSCLC). These CT images, along with any that had also been obtained prior to the one on which the final diagnosis was based, were reviewed. In 5 of the cases reviewed, specific findings and a characteristic spreading pattern were identified on CT images that might have allowed a diagnosis of SCLC to have been made sooner. The findings included a sub-pleural, small nodule accompanied by daughter nodules spreading longitudinally along the bronchovascular bundle, no air bronchogram or cavitation, and background emphysematous change. These were not identified on CT images of very earlystage NCSLC, however (n = 22). Awareness of the relevance of these findings would help physicians and radiologists arrive at a differential diagnosis of small pulmonary nodules.

Keywords

SCLC; Small Pulmonary Nodules; Beaded Appearance; Bronchovascular Bundle; CT Scan

1. INTRODUCTION

Small-cell lung cancer (SCLC) usually grows very rapidly. The majority of SCLC patients are symptomatic at first visit to a hospital, and extended disease (ED) with distant metastases is diagnosed in two thirds of these cases. The prognosis for limited disease (LD)-SCLC treated with the standard combination of chemotherapy and radiation is better than that for ED-SCLC. If there is no associated hilar or mediastinal lymphadenopathy in LD-SCLC, it is usually designated as “very early-stage” [1]. This type of peripheral, very early-stage SCLC has a good prognosis when treated with surgery followed by chemotherapy, although some uncertainly remains as to if and when the surgical component best fits into the treatment modality [2-4]. The earlier the disease is diagnosed, the more successful treatment is likely to be. Therefore, knowing the radiological characteristics of very early-stage SCLC is crucial in reducing diagnostic delay.

The recent increase in the clinical application of thoracic computed tomography (CT) has led to a marked rise in incidental detection of small peripheral pulmonary nodules. A set of guidelines has been established to help physicians in the management of such nodules [5-11]. These guidelines, however, contain very little information on the characteristic CT imaging features of very early-stage SCLC.

The purpose of this study was to determine the characteristic CT findings of very early-stage SCLC by reviewing CT images, including those obtained prior to diagnosis of the disease. We believe that such information would prove invaluable in the early diagnosis of this disease, including from CT scans initially aimed at a wide range of other diseases.

2. MATERIALS AND METHODS

Computed tomography images obtained from 547 consecutive patients with lung cancer between 2003 and 2012 at Tokyo Dental College Ichikawa General Hospital were reviewed retrospectively. Patients with SCLC (n = 100) included 86 men and 14 women (30 - 91 years old; mean age, 69.7 years; LD/ED, 31/69). Patients with nonSCLC (NSCLC) (n = 447) included 338 men and 109 women (34-92 years old; mean age, 69.7 years; stage IA/ IB/IIA/IIB/IIIA/IIIB/IV, 43/29/8/14/49/103/201, respectively). When available, earlier CT images obtained prior to that on which final diagnosis of lung cancer was made were also examined. A 64- or 16-row, multi-slice, helical CT scanner (Brilliance 64, Philips, Medical Systems, Cleveland, Ohio; and Mx-8000 IDT, Philips, Medical Systems, respectively) was used. The images obtained were reviewed by two radiologists. The study protocol was approved by the Ethics Committee of our institute.

3. RESULTS

We identified 5 and 22 cases in which CT scans obtained prior to that on which a diagnosis was made might have allowed an earlier diagnosis of SCLC and NSCLC, respectively. The clinical features of the 5 cases with SCLC are listed in Table 1. All were current or past smokers.

Case 1. The initial chest CT scans in May 2005 revealed a tiny nodule in the right upper lobe (Figures 1(a) and (b)). Proximal to this nodule was another, ovoid nodule measuring 5 mm × 3 mm distributed along the bronchovascular bundle (Figures 1(b) and (c)). They were misclassified as inflammatory scars by radiologist. Another set of CT images obtained at one year later, in May 2006, demonstrated that the irregularly-shaped, tiny nodule had grown to 10 mm × 10 mm in size (Figure 1(d)), and that it was accompanied by another polyhedral, elliptical nodule measuring 13 mm × 26 mm (Figures 1(d) and (e)). A positron emission tomography (PET)-CT scan demonstrated increased uptake of fluorodeoxyglucose (FDG) in both the peripheral nodule and elliptical lesion. Cytological examination of transbronchial brushings indicated SCLC.

Case 2. Chest CT scans obtained in July 2009 revealed an irregularly-shaped, lobulated nodule with a polyhedral margin in the right middle lobe (Figure 2(h)). The sub-pleural nodule was accompanied by a well-demarcated, polyhedral, lobulated nodule (Figures 2(e)-(g)).

Table 1. Clinical features of 5 cases.

CABG = coronary artery bypass graft; BPH = benign prostatic hypertrophy.

Figure 1. Initial chest CT scans in May 2005 revealed irregularly-shaped, tiny nodule with spiculation (arrow) measuring 3 mm × 3 mm in periphery of right upper lobe (a, b). Another ovoid nodule (arrowhead) proximal to it measuring 5 mm × 3 mm was distributed along bronchovascular bundle (b, c). Repeat CT scan at one year later in May 2006 revealed lesion, now measuring 10 mm × 10 mm, had reached nodule (arrow)(d); this lesion was accompanied by polyhedral elliptical nodule (arrowhead) measuring 13 mm × 26 mm (d, e).

Coronary CT scans in September 2008 showed a small nodule with a scalloped boarder (Figure 2(d)) accompanied by three well-defined, round nodules, ranging in size from 2 mm to 6 mm (Figures 2(a)-(c)). A PET-CT scan in October 2009 demonstrated increased uptake of FDG in the peripheral nodules and the right hilar and mediastinal lymph nodes. Bronchoscopy and cytological examination of bronchial washings indicated SCLC.

Case 3. Chest CT scans obtained in July 2011 revealed a nodule with a polyhedral margin in the left lower lobe (Figures 3(d) and (e)). The peripheral nodule was connected to another nodule which was distributed along the bronchovascular bundle (Figures 3(d)-(f)). Enhanced CT

                   

Figure 2. Irregularly-shaped, small nodule measureing 11 mm × 6 mm (arrow) observed retrospectively on coronary CT scan in September 2008 (d). Subpleural nodule in right middle lobe was accompanied by three of well-defined, round nodules ranging in size from 2 mm to 6 mm (arrowhead) (a-c). CT scans in July 2009 revealed that sub-pleural nodule had increased to irregularly-shaped, lobulated mass measuring 27 mm × 12 mm with polyhedral margin (arrow) (h). Accompanying nodules developed into one, well-defined polyhedral lobulated nodule (e-g).

              

Figure 3. A tiny nodule measuring 3 mm × 3 mm (arrow) observed retrospectively on coronary CT scan in April 2010 (a). Tiny nodule was located close to inter-lobular pleura in left lower lobe, accompanied by well-demarcated, ovoid nodule (arrowhead) measuring 11 mm × 4 mm distributed along bronchovascular bundle (b, c). CT scans in July 2011 revealed irregularly-shaped, lobulated nodule measuring 11 mm × 6 mm with polyhedral margin adjacent to inter-lobular pleura in left lower lobe (d, e). Nodule was connected to accompanying nodule (arrowhead) which grew along bronchovascular bundle and measured 13 mm × 12 mm (d-f).

scans showed left hilar and mediastinal lymph node metastases. Coronary CT scans performed in April 2010 showed a tiny nodule in the left lower lobe (Figure 3(a)). The peripheral nodule was accompanied by an ovoid nodule (Figures 3(b) and (c)). Cytological examination of bronchial brushings indicated SCLC.

Case 4. Chest CT scans obtained in March 2012 revealed an irregularly-shaped, lobulated, expansive mass measuring 55 mm × 50 mm in the left lingular lobe, accompanied by left hilar and mediastinal lymph node metastases (Figure 4(c)). Earlier CT scans obtained in March 2011 had revealed a nodule measuring 13 mm × 12 mm. This nodule was observed adjacent to the interlobular pleura together with pleural indentation and connected to three other nodules (Figures 4(a) and (b)). The initial diagnosis by two radiologists was organized pneumonia. Bronchoscopy and bronchial washings for cytology indicated SCLC.

Case 5. Chest CT scans obtained in January 2012 revealed a small nodule adjacent to the right pleura of the upper lobe (Figure 5(a)). The sub-pleural nodule was accompanied by another smaller nodule (Figure 5(b)). Follow-up CT scans in June 2012 showed growth of the lesions (Figures 5(c) and (d)). A PET-CT scan performed in July 2012 demonstrated increased uptake of FDG in both nodules. Percutaneous, fine-needle, aspiration biopsy guided by CT revealed SCLC.

In all 5 cases, scattered, low-density areas were observed on the CT scans, suggesting emphysematous lung tissue. Earlier CT scans had shown primary nodules ranging in size from 3 mm to 13 mm located in the subpleural lesion together with pleural indentation. They had not shown, however, any apparent lymph-node or distant metastases. The CT findings in these 5 cases are listed in

    

Figure 4. Initial CT scans in March 2011 had shown well-demarcated nodule (arrow) measuring 13 mm × 12 mm. Nodule was adjacent to inter-lobular pleura of left lingular lobe and had pleural indentation (a, b). Nodule was connected to three accompanying nodules (arrowhead) ranging in size from 3 mm to 14 mm which were distributed along bronchovascular bundle (a, b). CT scans in March 2012 revealed that sub-pleural nodule had joined with accompanying nodules, increasing in mass and measuring 55 mm × 50 mm (arrow) (c).

       

Figure 5. Initial CT scans in January 2012 had shown well-demarcated, small, round nodule (arrow) measuring 8 mm × 7 mm adjacent to right pleura of upper lobe (a). Sub-pleural nodule was accompanied by well-demarcated, small nodule (arrowhead) measuring 14 mm × 12 mm distributed along bronchovascular bundle (b). Repeat CT scan in June 2012 revealed that size of sub-pleural nodule (arrow) had increased to 18 mm × 14 mm (c), while accompanying nodule (arrowhead) had grown to 18 mm × 15 mm (d).

Table 2. The nodules were solid and irregularly-shaped, with no air bronchogram or cavitation. They were either spiculated (Cases 1 and 5) or had a scalloped border (Cases 2, 3 and 4). Each was accompanied by small nodules which were distributed along the bronchovascular bundle. Doubling time ranged from 54 to 81 days (average, 71 days). The characteristic CT findings are summarized in Table 3. These characteristic findings were not identified on CT images which had been obtained prior to the final diagnosis of NCSLC (n = 22).

Conflicts of Interest

The authors declare no conflicts of interest.

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