The small subsolid pulmonary nodules. What radiologists need to know.

The small subsolid pulmonary nodules. What radiologists need to know. Poster No.: C-1250 Congress: ECR 2016 Type: Educational Exhibit Authors: L. Fernandez Rodriguez, A. Martín Díaz, A. Linares Beltrán, C. Martínez Gamarra, L. F. Rodriguez-Gijon, I. Pinilla Fernández, M. Fernandez Velilla Peña, E. Cuesta López, M. Torres Sanchez; Madrid/ES Keywords: Thorax, Lung, Management, CT, Diagnostic procedure, Education, Cancer DOI: 10.1594/ecr2016/C-1250 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 24

Learning objectives 1. Describe what a subsolid nodule is and review the appropriate terminology involving its description and etiology. 2. Review the new classification for lung adenocarcinoma and establish the relation between it and subsolid nodules. 3. Present the Fleishner Society Guideliness regarding the proper management of subsolid pulmonary nodules detected on CT scan. Background A lung nodule is a rounded opacity, at least moderately well marginated and no greater than 3cm in maximum diameter. They can be solid and subsolid. Subsolid nodule is a focal area of increased attenuation through which normal parenchymal structures can be visualized. They are frequently encountered in computed tomography of the chest. However the standard for managing SSNs has not previously been established. Fig. 1 on page 2 The term subsolid includes "pure ground glass nodules" (GGN) and "part-solid GGN". "Part solid nodules"are those that include a combination of both ground-glass and solid component, the latter obscuring underlying lung architecture. Fig. 2 on page 3 Subsolid nodules have different etiologies and they can be transient or persistent. A susbstantial proportion of subsolid nodules are benign and transient. Benign etiologies include infectious and inflammatory conditions and most of them disappear spontaneously (Fig. 3 on page 4). But they can also be persistent and researchers have determined that the most common causes of persistent subsolid nodules are lesions that fall within the pathologic spectrum of lung adenocarcinoma or its precursors histologic subtypes. Adenocarcinoma is now the most common histologic subtype of lung cancer in smokers and non-smokers that's why a standardized approach to the interpretation and management of subsolid nodules remains critically important. ( Fig. 4 on page 5 ) Images for this section: Page 2 of 24

Fig. 1 Page 3 of 24

Fig. 2 Page 4 of 24

Fig. 3: Figure 3: axial contrast enhanced CT shows a subsoild lesion (it incorporates both solid and ground glass elements) in the right lower lobe that was due to an infection by Aspergillus. Transient subsolid nodules are due to a variety of nonspecific infectious and inflammatory conditions, most often the precise etiology remains unknown. Aspergillum is one reported potential etiology for transient subsoil nodule. In this image we see the typical halo sign. Page 5 of 24

Fig. 4: Subsolid nodule with solid component. Histopathologic examination following resection revealed invasive adenocarcinoma. Page 6 of 24

Findings and procedure details SSNs are considerate as a category separate from purely solid lesions from a management perspective, as established by the Fleischner Society in its six specific recommendations (three regarding solitary subsolid nodules and three regarding multiple subsolid nodules). Fig. 5 on page 10 The CT manifestations of SSN help radiologists manage these lesions. They have variable growth patterns and thin section imaging is Important in the assessment of such nodules. A new classification of lung adenocarcinoma has been proposed and divides adenocarcinomas into premalignant and malignant lesions. Premalignant lesions include AAH( atypical adenomatous hyperplasia) and AIS (adenocarcinoma in situ). Malignant lesions are: minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (divided into lepidic, acinar, papillary, solid or micropapillary histologic subtypes) and invasive mucinous adenocarcinoma. The old term "bronchioalveolar carcinoma" has been eliminated and replaced for the term "adenocarcinoma with lepidic growth. RECOMEDATIONS FOR MANAGING SUBSOLID LUNG NODULES: -Initial considerations: 1. We will use the same recommendations for smokers, ex-smokers and those who have never smoke (because adenocarcinoma is also frequent in younger and nonsmoking individuals). 2. We don`t take into account other known lung cancer risk factors like family history of lung cancer or exposure to carcino.genic agents for the management of this nodules. 3. We use different considerations for solitary subsolid nodules and multiple nodules. 4. To avoid pitfalls of interpreting this lesions as subsolid when they are actually solid it becomes critically important using contiguous thin CT sections (1mm thick) -RECOMENDATION 1) "Solitary pure GGNs measuring 5mm or less do not require follow-up surveillance CT examination". Fig. 6 on page 10 Even if these nodules may be preinvasive lesions like AAH, they are typically very stable and indolent lesions with very long doubling time; To detect a relevant increase in size becomes very difficult. Page 7 of 24

-RECOMMENDATION 2) "Solitary, pure GGN, larger than 5mm require an initial follow-up examination in 3months followed by annual surveillance for a minimum of 3 years if persistent and unchanged". These nodules prove to be benign in up to 20% of cases or represent foci of a AAH, AIS or MIA. The problem is that there is overlap in morphology between benign and malignant lesions (adenocarcinomas can manifest as pure GGNs) that's why it's necessary a close monitoring. The initial CT will confirm the persistence of the nodule (subsolid nodules can also disappear if they are benign) and will evaluate for any aggressive behavior or rapid growth. Fig. 7 on page 11 Additional remarks: -We should be aware of this lesions if the nodule size is larger than 10mm and there is a personal history of lung cancer. -PET-CT and biopsy is of limited value in subsolid nodules, particulary in the evaluation of pggns measuring smaller than 10mm. They are not routinely recommended given the lower diagnostic yield. If a pure GGNs is larger than 10mm the decision of resection should reflect the clinical context in which these lesions appear. RECOMMENDATION 3: "Solitary part-solid GGNS, especially those in which the solid component is larger than 5mm, should be considered malignant until proved otherwise". Fig. 8 on page 12. Part-solid GGNs have a higher likehood to be malignant than pure GGNs, that's why they need a close follow up. CT at 3 months confirm persistence and evaluate for growth. The development of a solid component in a GGN (specially if its larger than 5mm), is strong evidence of an invasive adenocarcinoma. Fig. 9 on page 13 Aditional remarks: -How should we measure these nodules? Giving the size of the solid component and the whole nodule. The solid component should be measured in its largest dimension on transverse CT sections with a mediastinal window setting. The whole nodule size should be measured with a lung window setting. Greater the extent of the solid component, the more likely the lesion will be an invasive adenocarcinoma. Fig. 10 on page 14 Page 8 of 24

See also Fig. 11 on page 15 and Fig. 12 on page 16 -For nodules measuring 8-10mm PET-CT could be performed (even if the value of this technique is limited). -Biopsy is not recommended unless surgery is not an alternative. -Malignant nodules could develop fibrosis, which initially will decrease the size of the nodule for increasing later. -Nodule size, internal features such as bubbly lucencies and air bronchograms have been associated with malignancy ( Fig. 13 on page 17 ). RECOMMENDATION 4: "Multiple GGNs all measuring 5mm or less should be conservatively managed with follow-up CT examinations performed at 2 and 4 years". Conservative management is recommended for these nodules. Alternative diagnosis for multiple small ground glass lesions like respiratory bronchiolitis in smokers should be considered. RECOMMENDATION 5: "Multiple pure GGNs> 5mm without a dominant lesion(s) should be managed with an initial follow-up CT at 3months to confirm persistence and then annual surveillance CT for a minimum of 3 years". As we mentioned before with the recommendation 2, FDG PET and biopsy are of limited value an therefore not recommended. ( Fig. 14 on page 18, Fig. 15 on page 19 ) RECOMMENDATION 6: "Multiple subsolid nodules with a dominant nodule(s) with part-solid or solid component. An initial CT examination in 3 months should be performed to confirm persistence. For lesions with solid component>5mm biopsy or surgical resection is recommended". -Multiple subsolid lesions could represent synchronous primary lung carcinomas. - As it was establish in the recommendation 3, with nodules measuring 8-10mm PETCT could be performed. Page 9 of 24

( Fig. 16 on page 20, Fig. 17 on page 21 ) Images for this section: Fig. 5 Naidich DP et al. Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society. Radiology 2013;266:304-17 Page 10 of 24

Fig. 6: Axial chest CT scan with lung window. Small pure GGN <5mm in the superior left lobe that do not require follow up surveillance CT examination. Page 11 of 24

Fig. 7: Axial chest CT scan with lung window. Pure GGN >5mm in the superior right lobe. An initial follow-up CT examination in 3 months should be performed to determine persistance because subsolid nodules have been documented to disappear at short term follow up. If persistance, annual surveillance CT for a minimum of 3 years should be performed. Page 12 of 24

Fig. 8: Axial chest CT scan with lung window. Solitary part-solid GGN in the superior left lobe with a solid component<5mm. This nodule is malignant until proved otherwise. A follow up CT scan at 3months confirmed the persistence of the nodule. It was resected and proved to be a lung adenocarcinoma with lepidic growth. Page 13 of 24

Fig. 9: A)Part solid groud glass nodule on the left superior lobe and B) follow up CT 6 months later. The solid component has increased in size. Left upper lobe lobectomy revealed primary lung invasive adenocarcinoma. Page 14 of 24

Fig. 10: How to measure a subsolid nodule with solid component. The solid component should be measured in its largest dimension on axial CT section with a mediastinal window. The ground glass component is best measured in the lung window. Its necessary to give the two dimensions to detect changes in the size of the nodule or in the size of the solid component (greater the extent of the solid component, the more likely the lesion will be an invasive adenocarcinoma). Page 15 of 24

Fig. 11: A)Part solid groud glass nodule on the left superior lobe with a solid component of 7mm. B) follow up CT 3 months later. The solid component has subtly increased in size. measuring now 9mm. Left upper lobe lobectomy revealed primary lung invasive adenocarcinoma. Page 16 of 24

Fig. 12: A)Part solid ground glass nodule and B) follow-up CT 3 months later. The nodule is now a lesion with bubblelike lucencies. Histopathologic examination following resection revealed invasive adenocarcinoma. Multiplanar reconstruction are important to detect increases in the nodule size. Pulmonary nodules must be seen in multiplanar reconstructions. Page 17 of 24

Fig. 13: Chest CT scan with lung window. Part solid ground glass nodule with bubblelike lucencies in the right superior lobe. A) coronal view B) sagital view. Histopathologic examination following resection revealed invasive adenocarcinoma. Page 18 of 24

Fig. 14: Patient with multiple pure subsolid nodules >5 mm in the left upper lobe and in the left inferior lobe with cavitation. A follow-up CT scan was performed after 3 months that confirmed persistence. A FDG-PET-CT was also performed but the lesions didn't show FDG uptake. Because the lesions were persistent after one year and one of them was 20mm in size, they were resected and the lesion on the inferior lobe was a preinvasive lesion. Page 19 of 24

Fig. 15: PET CT images of the same patient as in figure 13) show that the lesions didn't have FDG uptake. Page 20 of 24

Fig. 16: Patient with multiple subsolid nodules A) and D) with part solid B) pure ground glass nodule and C) pure solid nodule. The dominant lesion is the lesion showed in D) which has a solid component and bubble like lucencies of 26mm. A PET CT was performed and only the lesion in C) showed FDG uptake (see FIGURE ). The lesion in C and the lesion in D) where resected in different interventions and they were synchronous primary cancers. Page 21 of 24

Fig. 17: Same patient as in figure 15) with multiple subsolid nodules. A PET CT was performed and only the solid lesion on the left upper lobe (image C) showed FDG uptake. Page 22 of 24

Conclusion The management plan for SSNs has not previously been made standard. Although these nodules may be transient and benign, a high association with the spectrum of lung adenocarcinoma has been established, rendering subsolid nodules of high clinical importance. Recent Fleischner Society recommendations for incidentally detected SSNs should help radiologists with the follow-up of this lesion frequently observed in clinical practice. Personal information Lucia Fernandez Rodriguez, MD Hospital Universitario La Paz, Madrid, Spain luciafernanro@gmail.com References 1.Naidich DP, Bankier AA, MacMahon H, et al. Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society. Radiology 2013;266:304-17. 2. Godoy MC, Naidich DP. Overview and strategic management of subsolid pulmonary nodules. J Thorac Imaging 2012;27:240-8. 3. 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. Journal Thoracic Oncology 2011;6: 244-85. 4. Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society: glossary of terms for thoracic imaging. Radiology 2008;246:697-722. 5. Roy A. Raad MD, James Suh MD, Saul Harai MD. Nodule characterization. Subsolid nodules. Radiology Clinics North America 2014;52: 47-67 Page 23 of 24

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