Cavitation in primary lung cancer: characteristic features and mechanisms Yoshie Kunihiro 1,2), Taiga Kobayashi 2), Nobuyuki Tanaka 3), Tsuneo Matsumoto 1), Naofumi Matsunaga 2) 1) National Hospital Organization, Yamaguchi Ube Medical Center 2) Yamaguchi University Graduate School of Medicine 3) Saiseikai Yamaguchi General Hospital Ube, Yamaguchi, JAPAN
All authors confirm that there are no known conflicts of interest associated with this presentation and there has been no significant financial support for this work that could have influenced its outcome.
Introduction Cavitation occurs in approximately 10% to 22% of lung cancer and the previous studies had reported that cavitation occurs in lung cancer commonly with SCC [1-4]. However, the incidence of cavitation in adenocarcinoma has increased with the widespread use of HRCT [5]. In patients with non small cell lung cancer (NSCLC), tumor cavitation would be suggested to be a predictor of poor outcome [4,6]. Characteristic radiologic findings would be needed for the early diagnosis of NSCLC with cavity.
Learning objectives The purpose of this exhibit is: 1. To explain the common mechanisms of cavity formation and their association with prognosis. 2. To review the HRCT and pathological findings of primary lung cancer with cavitation. 3. To discuss the pitfalls in making a differential diagnosis.
Mechanisms of cavity formation Necrosis The bronchial obstruction and vascular involvement by tumor cells leading to ischemia Intratumoral ectatic bronchus including bubble-like appearance Ectatic bronchus inside the tumor Check-valve The infiltration of tumor cells into the bronchiolar lumens leading to elastic retraction [5,7] Two or more mechanisms sometimes coexist.
Necrosis Necrosis is caused by a bronchial obstruction and the vascular involvement of tumor cells leading to ischemia and is a risk factor for poor prognosis [4,6,8]. Cavitation mainly consists of necrosis in squamous cell carcinoma [9]. The wall of cavity tends to be thicker [9].
Case A 77-year-old man with squamous cell carcinoma, moderately differentiated type (pt3n0m0, stage IIB, 37.5 pack years) Figure A HRCT shows a tumor with an irregular-shaped cavity in the right lower lobe. Emphysema is also observed. Figure B Photomicrograph shows the existence of necrosis. A B
Intratumoral ectatic bronchus Intratumoral bronchiectasis with or without alveolar destruction caused by a collapsed tumor is a frequent mechanism of cavity formation, especially in adenocarcinoma [9]. It could be difficult to determine the intratumoral bronchiectasis only by HRCT.
Case A 60-year-old man with invasive adenocarcinoma, papillary predominant (pt2an0m0, stage IB, 40 pack years) A Figure A HRCT shows a tumor with cavities in the right lower lobe. Emphysema is not observed in the adjacent lung parenchyma. Figure B and C Photomicrograph shows cavities formed by bronchiectasis. B C
Case A 62-year-old man with invasive adenocarcinoma, lepidic predominant (pt2an0m0, stage IB, EGFR mutation (+), 5.5 pack years) A Figure A HRCT shows a tumor with multiple cavities and bronchiectasis in the right lower lobe. Emphysema is not observed in the adjacent lung parenchyma. Figure B and C Photomicrograph shows cavities formed by bronchiectasis and distended or destroyed alveolar space. B C
Bubble-like appearance Bubble-like appearance means intratumoral small scattered sites of low attenuation [10]. Bubble-like appearance consists of an ectatic small bronchus and correlated with welldifferentiated tumors and slow growth [7,11,12]. Air bronchogram is also frequently found in the HRCT images of adenocarcinomas.
Case A 78-year-old woman with minimally invasive adenocarcinoma. (pt1n0m0, stage IA) A Figure A HRCT shows a part-solid nodule with small cavitation in the left lower lobe. Figure B, C Photomicrograph shows ectatic small bronchus with the tumor. B C
Check-valve Check-valve is caused by the infiltration of tumor cells into the bronchiolar lumen and the narrowed airway, which lead to elastic retraction. Thin-walled cavities due to check-valve are observed in both adenocarcinomas and squamous cell carcinomas [5,7,13,14]. The relationship with the prognosis is unclear.
Case A 66-year-old man with squamous cell carcinoma, poorly differentiated type (pt3n0m0, stage IIB, 90 pack years) Figure A HRCT shows a thin-walled tumor with bronchial wall obstruction ( ) in the right upper lobe. Emphysema is also observed. Figure B Photomicrograph shows a tumor with both cystic lumen and bronchus lined with tumor tissue, suggesting a check-valve mechanism. A B
Squamous cell carcinoma vs Adenocarcinoma [9] Primary lung cancer with cavitation Squamous cell carcinoma Adenocarcinoma HRCT findings Ground-glass opacity Intratumoral bronchiectasis / bubble-like appearance Cavity wall thick thin Pathological findings Necrosis 〇 Check valve Intratumoral bronchiectasis
Prognostic factor The Cavitation due to necrosis in both squamous cell carcinoma and adenocaricinoma could lead to a poor prognosis with rapid tumor growth that exceed the blood supply of the tumor [4,6,8]. Bubble-like or cystic lucencies in stage IA adenocarcinoma have been described as correlating with well-differentiated tumors and slow growth [12,15]. Onn et al. reported that the cavitation was associated with overexpression of EGFR (81%, 13 of 16 tumors) [4]. The formation of those cavities was mainly due to necrosis in squamous cell carcinomas. Zhou et al. reported that the solid nodule with a lower incidence of bubble-like lucency or cavities was the predominant characteristic of ALK rearrangement tumors compared with EGFR mutation tumors in adenocaricnoma [16].
Pitfalls Identifying a cavity is difficult and the diagnostic reliability could be controversial. The evaluation of pre-existing cavity by emphysema, bulla, honeycombing and other cystic lesion would be difficult occasionally. Invasion of adenocarcinoma to the pre-existing cyst with or without check valve mechanism
Air bronchogram could not be determined as a real cavity. Invasive mucinous adenocarcinoma with air bronchogram Two or more mechanisms sometimes coexist.
Differential diagnosis Tuberculosis (Postprimary disease) HRCT findings Patchy peribronchial consolidation Cavitation Discrete centrilobular nodules and tree-in-bud pattern
Cryptococcosis HRCT findings Solitary or multiple nodules Multiple nodules in the lower same lobes are frequently seen [17]. Cavitation Greater extent of lung involvement and greater cavitation in immunocompromised patients (than in immunocompetent patients) [18]
Angioinvasive aspergillosis HRCT findings [Early phase] Ill-defined nodules or consolidation with a surrounding GGA (a CT-halo sign) [Late phase] Cavitary nodules with a marginal crescent-shaped air (an air crescent sign) (Cavitations are strong indicaters of better prognosis [19]) Chronic necrotizing aspergillosis HRCT findings Large nodules Cavitation of consolidation or nodules distributed predominantly in the upper lung.
Bacterial pneumonia HRCT findings Air-space consolidation with a segmental distribution. Centrilobular nodules are also seen. Cavitation can be observed associated with abscess. Granulomatosis with Polyangitis (GPA) HRCT findings[20] Nodules (Multiple > Localized) with or without cavitation Consolidation or ground-glass opacity Bronchial wall thickening
Take-home message The incidence of cavitation in primary lung cancer has increased with the widespread use of HRCT Necrosis is found frequently in squamous cell carcinoma and is a risk factor for poor prognosis. Cavity wall tends to be thick. Intratumoral bronchiectasis is found frequently in adenocarcinoma and is correlated with well-differentiated tumors. Cavity wall due to check valve tends to be thin. Cavitation or bubble-like lucency within the nodules might be associated with overexpression of EGFR in some degree.
References 1. Chaudhuri MR. Primary pulmonary cavitating carcinomas. Thorax 1973;28:354-366 2. Mouroux J, Padovani B, Elkaim D, et al. Should cavitated bronchopulmonary cancers be considered a separate entity? Ann Thorac Surg 1996; 61:530-2. 3. Theros EG. Varying manifestations of peripheral pulmonary neoplasms: a radiologicpathologic correlative study. AJR 1977;128:893-914. 4. Onn A, Choe DH, Herbst RS, et al. Tumor cavitation in stage I non small cell lung cancer: epidermal growth factor receptor expression and prediction of poor outcome. Radiology 2005; 237:342-7. 5. Xue X, Wang P, Xue Q, et al. Comparative study of solitary thin-walled cavity lung cancer with computed tomography and pathological findings. Lung Cancer 2012; 78(1):45-50. 6. Kolodziejski LS, Dyczek S, Duda K, et al. Cavitated tumor as a clinical subentity in squamous cell lung cancer patients. Neoplasma 2003;50:66 73. 7. Xue XY, Liu YX, Wang KF, et al. Computed tomography for the diagnosis of solitary thinwalled cavity lung cancer. Clin Respir J. 2015; 9(4):392-8. 8. Miura H, Taira O, Hiraguri S, et al. Cavitating adenocarcinoma of the lung. Ann Thorac Cardiovasc Surg. 1998;4(3):154-8. 9. Kunihiro Y, Kobayashi T, Tanaka N, et al. High-resolution CT findings of primary lung cancer with cavitation: a comparison between adenocarcinoma and squamous cell carcinoma. Clin Radiol. 2016; 71(11):1126-31. 10. Zwirewich CV, Vedal S, Miller RR, Müller NL. Solitary pulmonary nodule: high-resolution CT and radiologic-pathologic correlation. Radiology 1991;179(2):469 476.
11. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244-85. 12. Kojima Y, Saito H, Sakuma Y, et al. Correlations of thin-section computed tomographic, histopathological, and clinical findings of adenocarcinoma with a bubblelike appearance. J Comput Assist Tomogr 2010;34:413-417. 13. Iwata T, Nishiyama N, Nagano K, et al. Squamous cell carcinoma presenting as a solitary growing cyst in lung: a diagnostic pitfall in daily clinical practice. Ann Thorac Cardiovasc Surg. 2009;15: 174.7. 14. Lan CC, Wu HC, Lee CH, Huang SF, Wu YK. Lung cancer with unusual presentation as a thinwalled cyst in a young nonsmoker. J Thorac Oncol. 2010;5: 1481-2. 15. Yabuuchi H, Murayama S, Murakami J, et al. High-resolution CT characteristics of poorly differentiated adenocarcinoma of the peripheral lung: comparison with well differentiated adenocarcinoma. Radiat Med 2000;18:343.347. 16. Zhou JY, Zheng J, Yu ZF, et al. Comparative analysis of clinicoradiologic characteristics of lung adenocarcinomas with ALK rearrangements or EGFR mutations. Eur Radiol. 2015;25(5):1257-66. 17. Ashizawa K, Tsutsui S, Yamaguchi T. CT findings of pulmonary cryptococcosis in 60 patients. Rinsho Hoshasen. 2006 51: 91-5. 18. Chang WC, Tzao C, Hsu HH, et al. Pulmonary cryptococcosis: comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients. Chest 2006 129: 333-40. 19. Brodoefel H, Vogel M, Hebart H, et al. Long-term CT follow-up in 40 non-hiv immunocompromised patients with invasive pulmonary aspergillosis: kinetics of CT morphology and correlation with clinical findings and outcome. AJR Am J Roentgenol. 2006 Aug;187(2):404-13. 20. Lee KS, Kim TS, Fujimoto K, et al. Thoracic manifestation of Wegener's granulomatosis: CT findings in 30 patients. Eur Radiol. 2003 Jan;13(1):43-51.
Thank you for your attention! Author Contact Information Yoshie Kunihiro Email: kyoshie@yamaguchi-hosp.jp We hope that you are also interested in this paper. Kunihiro Y, Kobayashi T, Tanaka N, et al. High-resolution CT findings of primary lung cancer with cavitation: a comparison between adenocarcinoma and squamous cell carcinoma. Clin Radiol. 2016; 71(11):1126-31.