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CT scanning of bronchioloalveolar carcinoma: specific appearances
LUNG CANCER Lung
ELSEVIER
Cancer
12 (1995)
221-230
CT scanning of bronchioloalveolar carcinoma: specific appearances Soichi Akata*, Department
Akihiro of Radiology,
Fukushima, Dai Kakizaki, Saburo Amino Tokyo
Medical Tokyo
College, 6-7-l 160, Jupan
Nishi-Shinjuku,
Kimihiko
Abe,
Shinjuku-ku,
Received2 September1994;revision received7 December 1994;accepted I3 December 1994
Abstract We reviewed CT scans in 38 cases with pathologically proved bronchioloalveolar carcinoma. CT revealed three CT patterns: solitary, pneumonic and diffuse forms. The solitary pattern (22 patients) had a high percentage of air bronchograms (95%), pleural indentation (77%) and spiculation (68%). The pneumonia-like pattern (16 lesions in 10 patients) had air bronchograms in all cases (lOO%), low attenuation (88%) and protrusion of interlobar fissures (63%). The diffuse form (six patients) had 2 or 3 mm diffuse small nodules scattered throughout the entire lung. CT of bronchioloalveolar carcinoma revealed many findings and was useful in recognizing the tumor distribution and extent. We conclude that CT is helpful for the diagnosis and evaluation of bronchioloalveolar carcinoma. Keywords:
Bronchioloalveolar carcinoma; Computed tomography
1. Introduction
Bronchioloalveolar carcinoma is considered by most to be a histologically and radiologically distinct variant of adenocarcinoma, composing up to 10% of all primary lung cancers [ 1,2]. It remains one of the most enigmatic types of lung cancer, with miscellaneous growth patterns, mixed histologic features, and confusing clinical clues [3]. Histologically, this type of carcinoma is characterized by growth of malig* Corresponding author. 0169~5002/95/$09.500 1995Elsevier ScienceIreland Ltd. All rights reserved SSDI
0169-5002(95)00445-7
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nant cells along alveolar walls [4]. Although it most often occurs as a small focal mass, its varied appearances include pneumonia-like and diffuse forms. While the features of bronchioloalveolar carcinoma on plain radiography and conventional tomography have been extensively described, the CT features have not been reviewed, or have been limited to case reports or small series of studies 151. We analyzed the CT scans of 38 patients with pathologically proved bronchioloalveolar carcinoma, in order to identify distinctive CT features of this ambiguous primary lung neoplasm. 2. Materials and methods Thirty-eight histologically proven cases of bronchioloalveolar carcinoma treated from April 1986 to March 1993 in Tokyo Medical College were analyzed radiologically. There were 21 females and 17 males ranging from 36 to 80 years of age (mean, 57.5). Pathologic proof was based on transbronchial lung biopsy in 11 patients and on lobectomy in 27. Macroscopic and/or gross pathologic specimens were reviewed by pathologists paying special attention to the dominant tumor cell type and to the production of mucin. The pathologic designation of bronchioloalveolar carcinoma was based on the normally accepted criterion of a characteristic appearance of tumor cells, either columnar (bronchiolar type) or cuboidal (alveolar type) [6], growing along the alveolar walls, with preservation of the normal underlying architecture [7]. Cytology, which determines the nature of these cells (pneumocyte II or Clara cell), is not specific but remains important as regards phylogenesis. Patients were excluded if a primary adenocarcinoma was present elsewhere, because metastatic adenocarcinema from another organ is not always distinguishable from bronchioloalveolar carcinoma. CT scans were obtained with either a GE CT-9800, (2-s scanning time; 140 mA; 120 kVp) or a TCT-900s (l-s scanning time; 200 mA; 120 kVp). Contiguous scans with l-cm thickness were obtained covering the entire thorax using intravenously administered contrast material. Scanning was performed after a bolus injection of 60 ml of meglumine sodium 61% and during drip infusion of 40 ml of contrast medium in all patients. All scans were photographed at window and level settings suitable for the mediastinum (level = 40 HU, width = 300 HU) and lung parenchyma (level = -400 HU, width = 2000 HU). Each case was interpreted by chest radiologists in the CT division. We did not evaluate the plain radiograms and conventional tomograms in this study. 3. Results Bronchioloalveolar carcinoma typically had one of three radiologic patterns: solitary nodule, pneumonic, and diffuse forms. The prevalence of these patterns in this series was 58% (22/38), 26% (10/38), and 16% (6/38), respectively ‘(Table 1). Pleural effusion was found in 16% (6/38) of our cases and mediastinal and/or hilar lymphadenopathy in 5% (2/38). No pleural effusion or lymphadenopathy was seen in
S. Akara
Table 1 Prevalence of bronchioloalveolar Pattern
n
Solitary Pneumonic Diffuse
22 (58) 10 (26)
Total
38 (100)
er al. /Lung
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223
carcinoma patterns
6 (16)
Numbers in parentheses are percentages.
solitary pattern cases. Pneumothorax, calcification in the lesion, chest wall destruction and mediastinal involvement were not present in any case. 3.1. Solitary pattern
Fifty-eight percent (22/38) of our bronchioloalveolar carcinoma showed a solitary pattern. Solitary nodules ranged in size from 0.8 to 3.0 cm (average, 1.6 cm). The lesions were typically located in the periphery of the lungs. Fifty-nine percent (13122) of all solitary bronchioloalveolar carcinomas were discovered in the upper lobes. Seven lesions (32%) were located in the right upper lobe and six (27%) in the left upper lobe. Typical CT findings of solitary bronchioloalveolar carcinoma included air bronchogram (21 cases; 95%), pleural indentation (17 cases; 77%), spiculation (15 cases; 68%), non-visualization in the mediastinal window and level settings (10 cases; 45%) and pseudocavitation (six cases; 27%) (Fig. 1). Table 2 summarizes the prevalence of these features on CT scans in solitary bronchioloalveolar carcinoma cases. 3.2. Pneumonicpattern
Twenty-six percent (10/38) of bronchioloalveolar carcinoma cases showed a pneumonic pattern. Consolidation was segmental or lobar in a total of 16 lesions in 10 patients. Mucus secretion was present in 81% (13/16) in sufficient amounts to produce mucoid pneumonia. Protrusion of the interlobar fissure was seen in 63% (10116) (Fig. 2). In 19% (3/16), the tumor extended across the fissure into an adjacent lobe. Air bronchogram was seen in every lesion (16/16) (Fig. 3), and 25% (4/16) of them had irregular margins. Only one case had pleural effusion and mediastinal lymph nodes swelling recognizable on CT. In 69% of pneumonic lesions (1 l/16), branching pulmonary vessels extended more than 3 cm along the vicinity of the bronchi within the consolidated lung. This was especially recognizable after administration of intravenous contrast material (Fig. 4). Table 3 summarizes these features on CT scans. 3.3. Diffuse pattern
Sixteen percent of our bronchioloalveolar carcinoma (6/38) were multicentric or diffuse. All lesions were about 2 or 3 mm diameter and the size of the lesions in each case was similar. The distribution was slightly more predominant in the upper lung
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Fig. 1. CT scan through the upper lobe. of the right lung shows peripheral bronchioloalveolar carcinoma with prominently air bronchogram. Distinct pleural indentation is seen adjacent to the mass. This lesion was not visualized at mediastinal window and level settings.
fields (50%) (Fig. 5). Pleural effusion was found in three cases (50%), and lymph node swelling in another case (17%). Two cases of diffuse pattern had associated segmental consolidation and one had a 3-cm diameter mass lesion with the characteristic features of solitary bronchioloalveolar carcinoma (i.e. air bronchogram, pleural indentation and spiculation) in the left lower lobe.
Table 2 Typical findings
of solitary
pattern
Findings
n
Air bronchogram Peripheral or subpleural location Pleural indentation Spiculation Non visualization on mediastinal setting Pseudocavitation
21 20 17 15 10
level and width
Total Numbers
(95) (91) (77) (68) (45)
6 (27) 22 (loo)
in parentheses
are percentages.
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225
Fig. 2. CT scan through both lungs at the level of the lower lobes shows lower lobar consolidation, with protrusion of major fissures and heterogeneous attenuation within consolidation. This variable attenuation represents areas of mucus secretion, which have lower attenuation than tumor mass. Air bronchogram is also evident.
Fig. 3. CT scan through both lungs at the level of the lower lobes shows lobar consolidation middle and left lower lobes. Air bronchograms with irregular margins are evident within solidation.
in the right areas of con-
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Fig. 4. Contrast-enhancement CT scan through both lungs at the level of the lower lobes shows consolidation of the right lower and left lower lobes. In the right lower lobe, linear and slightly high attenuations along the vicinity of the bronchi within the consolidated lung, which are considered to be pulmonary vessels are readily visualized (arrow).
4. Discussion Bronchioloalveolar carcinoma is known to arise beyond recognizable bronchi with a tendency to spread locally in the peripheral air space, using the lung structures as stroma, without destroying underlying architecture [8]. This mysterious primary Table 3 Typical findings of pneumonic pattern Findings
”
Air bronchogram Low attenuation Bulging of interlobar fissure Extension into an adjacent lobe
I6 (100) I4 (88) IO (63) 3 (19) I6 (100)
Total Numbers in parentheses are percentages.
S. Akata
Fig. 5. CT multinodular predominantly
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scan through both lungs at the level of the lower lobes shows widespread extensive foci of bronchioloalveolar carcinoma, which are about 2 mm in size. The diffuse lesions are located in the upper lung fields.
lung neoplasm has three radiological patterns [9], and we found several features of each of the three patterns on CT scans. At first, regarding the solitary pattern, air bronchograms were seen more commonly in bronchioloalveolar carcinoma than other lung tumors. We saw air bronchograms in 95% of the solitary pattern cases. Other characteristic findings of solitary bronchioloalveolar carcinoma were spiculation, pleural indentation and the presence of bubble-like lucencies of pseudocavitation [lo]. Histopathologic correlation showed that the spiculation and pleural indentation were usually due to infiltrative tumor growth, localized lymphangitic spread, or desmoplastic reaction, resulting in coarse fibrotic strands radiating from the tumor margin into the lung. Although these findings around the tumor were typically seen in pathologic specimens of bronchioloalveolar carcinoma, they can also be found in other peripheral lung malignancies (58%) such as acinar adenocarcinomas, malignant lymphoma and benign inflammatory lesions [lo]. Ten lesions (45%) were not visualized on mediastinal window and level settings, and this may be because of thin proliferation of cancer cells along the alveolar walls. Bubble-like lucencies of pseudocavitation were found to correlate with small bronchi or air-containing cystic spaces associated with papillary tumor architecture. Bubble-
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like lucencies of low attenuation were observed more frequently among bronchioloalveolar carcinomas (27%) than among any other malignant or benign lesions. Although the typical features of solitary bronchioloalveolar carcinoma are nonspecific, the presence of a peripherally located nodule is characteristic enough to suggest the diagnosis. It was reported that thin-section high-resolution computed tomography (HRCT) is suitable for the demonstration of the anatomic fine structure of the lung in detail comparable to that seen on gross tissue inspection [ 1 l-131. HRCT may be highly effective in demonstrating characteristic appearances of solitary pattern. Kuhlman et al. reviewed HRCT images of 30 solitary bronchioloalveolar carcinoma and found irregular margins in 73% of the lesions and pseudocavitation and heterogeneous attenuation in 60% and 57%, respectively [3]. The combination of growth along the alveolar wall and secretion of mucin caused features of air-space consolidation with air bronchogram, i.e. the pneumonia-like pattern. When bronchioloalveolar carcinoma appeared as lobar consolidation, the primary clinical concern was pneumonia, because it simulated lobar pneumonia clinically and radiologically in most cases. Production of mucin can cause uniform low attenuation in more confluent consolidation and swelling of the lobe, leading to protrusion of interlobar fissures. The tumor may extend across the fissure into an adjacent lobe. Slight linear high attenuation considered to be pulmonary vessels along a bronchus within the consolidated lung were easily recognizable especially after administration of intravenous contrast material. This finding was recently described as the CT angiogram sign [14]. We found this sign in 69% of our pneumonic lesions. It is suggestive but not specific for bronchioloalveolar carcinoma. It can be observed in pulmonary consolidation of varying etiologies, i.e. obstructive pneumonia and primary pulmonary lymphoma [ 15,161. Although we found several other features that were characteristic of pneumonic bronchioloalveolar carcinoma at CT, these findings were not highly specific 131. In the diffuse pattern, the diffuse small nodules were distributed with a slight predominance in the upper lung fields, and their sites were in the alveolar wall (axial connective tissue) [17], suggesting that they may spread by dissemination along the airway. Although multiple small metastatic nodules and miliary tuberculosis can simulate bronchioloalveolar carcinoma, these are located on peripheral connective tissue due to arterial dissemination. HRCT may also be helpful to depict the location of diffuse small nodules exactly. Because all our solitary nodules were resected immediately upon pathological demonstration of malignancy, we could not differentiate whether solitary bronchioloalveolar carcinoma develops into pneumonic or diffuse pattern. However, when the natural histories of the lesions were evaluated, variable growth rates were observed, but, in the absence of surgical intervention, there was a transition from a solitary lesion to pneumonic and widespread multinodular patterns in every patient 191. Several investigators also reported that pneumonic and diffuse patterns should be regarded as advanced disease [ 18,191. Although solitary bronchioloalveolar carcinoma had a better outcome than other types of lung malignancy [20], the prognosis in cases of the pneumonic and diffuse
patterns is known to be poor regardless of therapeutic method [21,22]. The survival rate of those who have the solitary pattern was 60% at 5 years, whereas all patients with pneumonic and diffuse patterns die very rapidly [23]. Only the solitary pattern demonstrates a high resectability rate with good long-term prognosis [24]. In patients with pneumonic and diffuse patterns, surgical resection rarely seems warranted [21,25]. Five cases of our pneumonic pattern were resected, and the opposite lung was involved rapidly in all of them. It is therefore important to diagnose bronchioloalveolar carcinoma at an early stage, because early resection may result in cure. No differences existed between the groups as regards surgical treatment, postoperative radiotherapy or chemotherapy [26]. Although clinical information is indispensable in diagnosing bronchioloalveolar carcinoma especially pneumonic and diffuse patterns and the diagnosis can never be reached only on the basis of the CT appearances, we are convinced that CT is a very useful, important, and noninvasive modality for clinical decisions, especially HRCT. If bronchioloalveolar carcinoma is suspected on the basis of clinical findings and CT appearances, transbronchial lung biopsy or needle lung biopsy should be done rapidly. Acknowledgments We thank Professor Harubumi Kato (First Department of Surgery) for his valuable help in performing this study. We also thank Professor J.P. Barron for reviewing the manuscript in English. References 111 Shapiro
R, Wilson GL, Yesner R, Shuman H. A useful roentgen sign in the diagnosis of localized bronchioloalveolar carcinoma. Am J Radio1 1971; 114: 516-524. carcinoma: a clinical overview and 121 Edgerton R, Rao U, Takita H, Vincent RG. Bronchioloalveolar bibliography. Oncology 1981; 38: 269-273. EA. Siegelman SS. 131 Kuhlman JE, Fishman EK, Kuhajda FP, Meziane MM, Khouri NF. Zerhouni Solitary bronchioloalveolar carcinoma: CT criteria. Radiology 1988: 167: 379-382. B, Pietra G. Bronchioloalveolar carcinoma: two clinical [41 Miller WT, Husted J, Firman D, Atkinson entities with one pathologic diagnosis. Am J Radio1 1978; 130: 905-912. CT of bronchioloalveolar carcinoma. 151 Adler B, Padley S, Miller RR, Miiller NL. High-resolution Am J Radio1 1992; 159: 275-277. 161 Belgrad RB, Good CA, Woolner LB. Alveolar cell carcinoma (terminal bronchiolar carcinoma): a study of surgically excised tumors with special emphasis on localized lesions. Radiology 1962; 79: 789-798. carcinoma. Adv Intern Med 1960; IO: 329-358. 171 Liebow AA. Bronchiole-alveolar Is1 Thurlbeck WM. Pathology of the lung. New York: Thieme, 1988; 345-346. carcinoma: a review. Radiology 1984; 150: 15-20. 191 Hill CA. Bronchioloalveolar CT IlO1 Zwirewich CV, Vedal S, Miller RR, Miiller NL. Solitary pulmonary nodule: high-resolution and radiologic-pathologic correlation. Radiology 199 I: 179: 469-476. Kuriyama K, Takeishi R, Doi 0, Kodama K, Tatsuta M. Matsuda M. Mitani T. Narumi Y. Fujita M. CT-pathologic correlation in small peripheral lung cancers. Am J Radio1 1987; 149: 1139- 1143. 1121Meziane MA, Hruban RH, Zerhouni EA, Wheeler PS, Khouri NF. Fishman EK, Hutchins GM. Siegelman SS. High resolution CT of the lung parenchyma with pathologic correlation. Radiographics 1988; 8: 27-54.
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1131 Murata K, Khan A, Rajas KA, Herman PG. Optimization of computed tomography technique to demonstrate the tine structure of the lung. Invest Radio1 1988; 23: 170-175. iI41 Im J, Han MC, Yu EJ, Han JK, Park JM, Kim C, Seo JW, Yoon Y, Lee JD, Lee KS. Lobar bronchioloalveolar carcinoma: “Angiogram sign” on CT scans. Radiology 1990; 176: 749-753. [I51 Murayama S, Onitsuka H. Murakami J. Torii Y, Masuda K. Nishikawa K. “CT angiogram sign” in obstructive pneumonitis and pneumonia. J Comput Assist Tomogr 1993; 17: 609-612. iI61 Vincent JM, Ng YY. Norton AJ, Armstrong P. CT “angiogram sign” in primary pulmonary lymphoma. J Comput Assist Tomogr 1992; 16: 829-831. 1171 Weibel ER. Looking into the lung: what can it tell us? Am J Radio1 1979; 133: 1021-1031. 1181 Storey CF, Knudtson KP. Lawrence BJ. Bronchiolar (alveolar cell) carcinoma of the lung. J Thorac Surg 1953; 26: 331-406. iI91 Fitzpatrick HF. Miller RF, Edgar MS Jr, Begg CF. Bronchiolar carcinoma of the lung. A review of 33 patients. J Thorac Cardiovasc Surg 1961; 42: 310-326. PO1 Grover FL, Piantadosi S. Recurrence and survival following resection of bronchioloalveolar carcinoma of the lung - The Lung Cancer Study Group experience. Ann Surg 1989; 209: 779-790. WI Epstein DM, Gefter WB, Miller WT. Lobar bronchioloalveolar carcinoma. Am J Radio1 1982; 139: 463-468. 1221Berkmen YM. The many facets of alveolar-cell carcinoma of the lung. Radiology 1969; 92: 793-798. 1231 Carles P, Fabre J, Des E, Aldegheri C, Lauque D, Berthoumieu F, Dahan M. Histoire naturelle du cancer bronchiole-alveolaire. Rev Pneumol Clin 1989; 45: 64-70. [241 Metzger RA. Mulhern CB Jr, Arger PH. Coleman BG. Epstein DM. Gefter WB. CT differentiation of solitary from diffuse bronchioloalveolar carcinoma. J Comput Assist Tomogr 1981; 5: 830-833. 1251 James EC, Schuchmann GF, Hall RV, Patterson JR, Gillespie JT, Gomez AC. Preferred surgical treatment for alveolar cell carcinoma. Ann Thorac Surg 1976; 22: 157-162. WI Heikkila L. Results of surgical treatment in bronchioloalveolar carcinoma. Ann Chir Gynaecol 1986; 75: 183-191.
ELSEVIER
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CT scanning of bronchioloalveolar carcinoma: specific appearances Soichi Akata*, Department
Akihiro of Radiology,
Fukushima, Dai Kakizaki, Saburo Amino Tokyo
Medical Tokyo
College, 6-7-l 160, Jupan
Nishi-Shinjuku,
Kimihiko
Abe,
Shinjuku-ku,
Received2 September1994;revision received7 December 1994;accepted I3 December 1994
Abstract We reviewed CT scans in 38 cases with pathologically proved bronchioloalveolar carcinoma. CT revealed three CT patterns: solitary, pneumonic and diffuse forms. The solitary pattern (22 patients) had a high percentage of air bronchograms (95%), pleural indentation (77%) and spiculation (68%). The pneumonia-like pattern (16 lesions in 10 patients) had air bronchograms in all cases (lOO%), low attenuation (88%) and protrusion of interlobar fissures (63%). The diffuse form (six patients) had 2 or 3 mm diffuse small nodules scattered throughout the entire lung. CT of bronchioloalveolar carcinoma revealed many findings and was useful in recognizing the tumor distribution and extent. We conclude that CT is helpful for the diagnosis and evaluation of bronchioloalveolar carcinoma. Keywords:
Bronchioloalveolar carcinoma; Computed tomography
1. Introduction
Bronchioloalveolar carcinoma is considered by most to be a histologically and radiologically distinct variant of adenocarcinoma, composing up to 10% of all primary lung cancers [ 1,2]. It remains one of the most enigmatic types of lung cancer, with miscellaneous growth patterns, mixed histologic features, and confusing clinical clues [3]. Histologically, this type of carcinoma is characterized by growth of malig* Corresponding author. 0169~5002/95/$09.500 1995Elsevier ScienceIreland Ltd. All rights reserved SSDI
0169-5002(95)00445-7
222
S. Akutu
et al. /Lung
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nant cells along alveolar walls [4]. Although it most often occurs as a small focal mass, its varied appearances include pneumonia-like and diffuse forms. While the features of bronchioloalveolar carcinoma on plain radiography and conventional tomography have been extensively described, the CT features have not been reviewed, or have been limited to case reports or small series of studies 151. We analyzed the CT scans of 38 patients with pathologically proved bronchioloalveolar carcinoma, in order to identify distinctive CT features of this ambiguous primary lung neoplasm. 2. Materials and methods Thirty-eight histologically proven cases of bronchioloalveolar carcinoma treated from April 1986 to March 1993 in Tokyo Medical College were analyzed radiologically. There were 21 females and 17 males ranging from 36 to 80 years of age (mean, 57.5). Pathologic proof was based on transbronchial lung biopsy in 11 patients and on lobectomy in 27. Macroscopic and/or gross pathologic specimens were reviewed by pathologists paying special attention to the dominant tumor cell type and to the production of mucin. The pathologic designation of bronchioloalveolar carcinoma was based on the normally accepted criterion of a characteristic appearance of tumor cells, either columnar (bronchiolar type) or cuboidal (alveolar type) [6], growing along the alveolar walls, with preservation of the normal underlying architecture [7]. Cytology, which determines the nature of these cells (pneumocyte II or Clara cell), is not specific but remains important as regards phylogenesis. Patients were excluded if a primary adenocarcinoma was present elsewhere, because metastatic adenocarcinema from another organ is not always distinguishable from bronchioloalveolar carcinoma. CT scans were obtained with either a GE CT-9800, (2-s scanning time; 140 mA; 120 kVp) or a TCT-900s (l-s scanning time; 200 mA; 120 kVp). Contiguous scans with l-cm thickness were obtained covering the entire thorax using intravenously administered contrast material. Scanning was performed after a bolus injection of 60 ml of meglumine sodium 61% and during drip infusion of 40 ml of contrast medium in all patients. All scans were photographed at window and level settings suitable for the mediastinum (level = 40 HU, width = 300 HU) and lung parenchyma (level = -400 HU, width = 2000 HU). Each case was interpreted by chest radiologists in the CT division. We did not evaluate the plain radiograms and conventional tomograms in this study. 3. Results Bronchioloalveolar carcinoma typically had one of three radiologic patterns: solitary nodule, pneumonic, and diffuse forms. The prevalence of these patterns in this series was 58% (22/38), 26% (10/38), and 16% (6/38), respectively ‘(Table 1). Pleural effusion was found in 16% (6/38) of our cases and mediastinal and/or hilar lymphadenopathy in 5% (2/38). No pleural effusion or lymphadenopathy was seen in
S. Akara
Table 1 Prevalence of bronchioloalveolar Pattern
n
Solitary Pneumonic Diffuse
22 (58) 10 (26)
Total
38 (100)
er al. /Lung
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223
carcinoma patterns
6 (16)
Numbers in parentheses are percentages.
solitary pattern cases. Pneumothorax, calcification in the lesion, chest wall destruction and mediastinal involvement were not present in any case. 3.1. Solitary pattern
Fifty-eight percent (22/38) of our bronchioloalveolar carcinoma showed a solitary pattern. Solitary nodules ranged in size from 0.8 to 3.0 cm (average, 1.6 cm). The lesions were typically located in the periphery of the lungs. Fifty-nine percent (13122) of all solitary bronchioloalveolar carcinomas were discovered in the upper lobes. Seven lesions (32%) were located in the right upper lobe and six (27%) in the left upper lobe. Typical CT findings of solitary bronchioloalveolar carcinoma included air bronchogram (21 cases; 95%), pleural indentation (17 cases; 77%), spiculation (15 cases; 68%), non-visualization in the mediastinal window and level settings (10 cases; 45%) and pseudocavitation (six cases; 27%) (Fig. 1). Table 2 summarizes the prevalence of these features on CT scans in solitary bronchioloalveolar carcinoma cases. 3.2. Pneumonicpattern
Twenty-six percent (10/38) of bronchioloalveolar carcinoma cases showed a pneumonic pattern. Consolidation was segmental or lobar in a total of 16 lesions in 10 patients. Mucus secretion was present in 81% (13/16) in sufficient amounts to produce mucoid pneumonia. Protrusion of the interlobar fissure was seen in 63% (10116) (Fig. 2). In 19% (3/16), the tumor extended across the fissure into an adjacent lobe. Air bronchogram was seen in every lesion (16/16) (Fig. 3), and 25% (4/16) of them had irregular margins. Only one case had pleural effusion and mediastinal lymph nodes swelling recognizable on CT. In 69% of pneumonic lesions (1 l/16), branching pulmonary vessels extended more than 3 cm along the vicinity of the bronchi within the consolidated lung. This was especially recognizable after administration of intravenous contrast material (Fig. 4). Table 3 summarizes these features on CT scans. 3.3. Diffuse pattern
Sixteen percent of our bronchioloalveolar carcinoma (6/38) were multicentric or diffuse. All lesions were about 2 or 3 mm diameter and the size of the lesions in each case was similar. The distribution was slightly more predominant in the upper lung
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Fig. 1. CT scan through the upper lobe. of the right lung shows peripheral bronchioloalveolar carcinoma with prominently air bronchogram. Distinct pleural indentation is seen adjacent to the mass. This lesion was not visualized at mediastinal window and level settings.
fields (50%) (Fig. 5). Pleural effusion was found in three cases (50%), and lymph node swelling in another case (17%). Two cases of diffuse pattern had associated segmental consolidation and one had a 3-cm diameter mass lesion with the characteristic features of solitary bronchioloalveolar carcinoma (i.e. air bronchogram, pleural indentation and spiculation) in the left lower lobe.
Table 2 Typical findings
of solitary
pattern
Findings
n
Air bronchogram Peripheral or subpleural location Pleural indentation Spiculation Non visualization on mediastinal setting Pseudocavitation
21 20 17 15 10
level and width
Total Numbers
(95) (91) (77) (68) (45)
6 (27) 22 (loo)
in parentheses
are percentages.
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225
Fig. 2. CT scan through both lungs at the level of the lower lobes shows lower lobar consolidation, with protrusion of major fissures and heterogeneous attenuation within consolidation. This variable attenuation represents areas of mucus secretion, which have lower attenuation than tumor mass. Air bronchogram is also evident.
Fig. 3. CT scan through both lungs at the level of the lower lobes shows lobar consolidation middle and left lower lobes. Air bronchograms with irregular margins are evident within solidation.
in the right areas of con-
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Fig. 4. Contrast-enhancement CT scan through both lungs at the level of the lower lobes shows consolidation of the right lower and left lower lobes. In the right lower lobe, linear and slightly high attenuations along the vicinity of the bronchi within the consolidated lung, which are considered to be pulmonary vessels are readily visualized (arrow).
4. Discussion Bronchioloalveolar carcinoma is known to arise beyond recognizable bronchi with a tendency to spread locally in the peripheral air space, using the lung structures as stroma, without destroying underlying architecture [8]. This mysterious primary Table 3 Typical findings of pneumonic pattern Findings
”
Air bronchogram Low attenuation Bulging of interlobar fissure Extension into an adjacent lobe
I6 (100) I4 (88) IO (63) 3 (19) I6 (100)
Total Numbers in parentheses are percentages.
S. Akata
Fig. 5. CT multinodular predominantly
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221
scan through both lungs at the level of the lower lobes shows widespread extensive foci of bronchioloalveolar carcinoma, which are about 2 mm in size. The diffuse lesions are located in the upper lung fields.
lung neoplasm has three radiological patterns [9], and we found several features of each of the three patterns on CT scans. At first, regarding the solitary pattern, air bronchograms were seen more commonly in bronchioloalveolar carcinoma than other lung tumors. We saw air bronchograms in 95% of the solitary pattern cases. Other characteristic findings of solitary bronchioloalveolar carcinoma were spiculation, pleural indentation and the presence of bubble-like lucencies of pseudocavitation [lo]. Histopathologic correlation showed that the spiculation and pleural indentation were usually due to infiltrative tumor growth, localized lymphangitic spread, or desmoplastic reaction, resulting in coarse fibrotic strands radiating from the tumor margin into the lung. Although these findings around the tumor were typically seen in pathologic specimens of bronchioloalveolar carcinoma, they can also be found in other peripheral lung malignancies (58%) such as acinar adenocarcinomas, malignant lymphoma and benign inflammatory lesions [lo]. Ten lesions (45%) were not visualized on mediastinal window and level settings, and this may be because of thin proliferation of cancer cells along the alveolar walls. Bubble-like lucencies of pseudocavitation were found to correlate with small bronchi or air-containing cystic spaces associated with papillary tumor architecture. Bubble-
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like lucencies of low attenuation were observed more frequently among bronchioloalveolar carcinomas (27%) than among any other malignant or benign lesions. Although the typical features of solitary bronchioloalveolar carcinoma are nonspecific, the presence of a peripherally located nodule is characteristic enough to suggest the diagnosis. It was reported that thin-section high-resolution computed tomography (HRCT) is suitable for the demonstration of the anatomic fine structure of the lung in detail comparable to that seen on gross tissue inspection [ 1 l-131. HRCT may be highly effective in demonstrating characteristic appearances of solitary pattern. Kuhlman et al. reviewed HRCT images of 30 solitary bronchioloalveolar carcinoma and found irregular margins in 73% of the lesions and pseudocavitation and heterogeneous attenuation in 60% and 57%, respectively [3]. The combination of growth along the alveolar wall and secretion of mucin caused features of air-space consolidation with air bronchogram, i.e. the pneumonia-like pattern. When bronchioloalveolar carcinoma appeared as lobar consolidation, the primary clinical concern was pneumonia, because it simulated lobar pneumonia clinically and radiologically in most cases. Production of mucin can cause uniform low attenuation in more confluent consolidation and swelling of the lobe, leading to protrusion of interlobar fissures. The tumor may extend across the fissure into an adjacent lobe. Slight linear high attenuation considered to be pulmonary vessels along a bronchus within the consolidated lung were easily recognizable especially after administration of intravenous contrast material. This finding was recently described as the CT angiogram sign [14]. We found this sign in 69% of our pneumonic lesions. It is suggestive but not specific for bronchioloalveolar carcinoma. It can be observed in pulmonary consolidation of varying etiologies, i.e. obstructive pneumonia and primary pulmonary lymphoma [ 15,161. Although we found several other features that were characteristic of pneumonic bronchioloalveolar carcinoma at CT, these findings were not highly specific 131. In the diffuse pattern, the diffuse small nodules were distributed with a slight predominance in the upper lung fields, and their sites were in the alveolar wall (axial connective tissue) [17], suggesting that they may spread by dissemination along the airway. Although multiple small metastatic nodules and miliary tuberculosis can simulate bronchioloalveolar carcinoma, these are located on peripheral connective tissue due to arterial dissemination. HRCT may also be helpful to depict the location of diffuse small nodules exactly. Because all our solitary nodules were resected immediately upon pathological demonstration of malignancy, we could not differentiate whether solitary bronchioloalveolar carcinoma develops into pneumonic or diffuse pattern. However, when the natural histories of the lesions were evaluated, variable growth rates were observed, but, in the absence of surgical intervention, there was a transition from a solitary lesion to pneumonic and widespread multinodular patterns in every patient 191. Several investigators also reported that pneumonic and diffuse patterns should be regarded as advanced disease [ 18,191. Although solitary bronchioloalveolar carcinoma had a better outcome than other types of lung malignancy [20], the prognosis in cases of the pneumonic and diffuse
patterns is known to be poor regardless of therapeutic method [21,22]. The survival rate of those who have the solitary pattern was 60% at 5 years, whereas all patients with pneumonic and diffuse patterns die very rapidly [23]. Only the solitary pattern demonstrates a high resectability rate with good long-term prognosis [24]. In patients with pneumonic and diffuse patterns, surgical resection rarely seems warranted [21,25]. Five cases of our pneumonic pattern were resected, and the opposite lung was involved rapidly in all of them. It is therefore important to diagnose bronchioloalveolar carcinoma at an early stage, because early resection may result in cure. No differences existed between the groups as regards surgical treatment, postoperative radiotherapy or chemotherapy [26]. Although clinical information is indispensable in diagnosing bronchioloalveolar carcinoma especially pneumonic and diffuse patterns and the diagnosis can never be reached only on the basis of the CT appearances, we are convinced that CT is a very useful, important, and noninvasive modality for clinical decisions, especially HRCT. If bronchioloalveolar carcinoma is suspected on the basis of clinical findings and CT appearances, transbronchial lung biopsy or needle lung biopsy should be done rapidly. Acknowledgments We thank Professor Harubumi Kato (First Department of Surgery) for his valuable help in performing this study. We also thank Professor J.P. Barron for reviewing the manuscript in English. References 111 Shapiro
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