Radiologic-Pathologic Correlation in Lung Cancer Presenting as a Subsolid Nodule : Room for Improvement ?

Pulmonary nodules are a common finding on Computed Tomography (CT) imaging studies. Nodules are becoming more frequently encountered in daily practice due to widespread use of CT and increasing interest in lung cancer screening by low dose CT. In 2011, the term bronchioloalveolar carcinoma was abandoned and the new IASLC/ATS/ERS classification system of lung adenocarcinoma and its precursors was introduced. In 2015, this new classification system was adopted by the World Health Organization (WHO). In this new classification findings on histopathology are correlated with imaging studies. This correlation holds imperfections, leaving room for improvement. A correct classification of pulmonary nodules into solid or subsolid is key to precise nodule management. Furthermore, morphological assessment of subsolid nodules is mandatory and essential for follow-up and assessing likelihood of invasiveness. A significant group of lesions that are pure ground glass without a solid component and hence suspicious for Atypical Adenomatous Hyperplasia (AAH) or Adenocarcinoma In Situ (AIS) on imaging grounds, turn out to be invasive adenocarcinoma. Other lesions that are part-solid on CT and suspicious for invasive adenocarcinoma turn out to be only AIS at resection. Moreover, nodule classification and morphological assessment are prone to variability among radiologists. Computer aided techniques and quantitative CT-analysis are on the rise. These techniques will create room for standardization and will make prospective studies regarding radiologic-pathologic correlation in subsolid nodules more precise and reliable. More accurate radiologic-pathologic correlation will lower the risk of over-/underdiagnosis and will aid in optimal patient selection for surgical treatment. Annemie Snoeckx1*, Pieter Reyntiens1, Patrick Pauwels2, Paul E. Van Schil3, Maarten J. Spinhoven1, Paul M. Parizel1 and Jan P. van Meerbeeck4 1Department of Radiology, Antwerp University Hospital and University of Antwerp, Wilrijkstraat, Belgium 2Department of Pathology, Antwerp University Hospital and University of Antwerp, Wilrijkstraat, Belgium 3Department of Thoracic and Vascular Surgery, Antwerp University Hospital and University of Antwerp, Wilrijkstraat, Belgium 4Department of Thoracic Oncology, Antwerp University Hospital and University of Antwerp, Wilrijkstraat, Belgium Annemie Snoeckx, et al., Clinics in Oncology Thoracic Oncology Remedy Publications LLC. , | http://clinicsinoncology.com/ 2017 | Volume 2 | Article 1290 2 nodules [5]. The 2011, IASLC/ATS/ERS classification defines 4 types of lesions in the adenocarcinoma spectrum in relation to subsolid nodules with a maximum diameter of 3cm: Atypical Adenomatous Hyperplasia (AAH), Adenocarcinoma In Situ (AIS), Minimally Invasive Adenocarcinoma (MIA) and Lepidic Predominant Adenocarcinoma (LPA). Each of these adenocarcinoma subtypes has a CT-image correlate (Figure 1) AAH and AIS are believed to be pre-invasive lesions for lung adenocarcinoma, presenting on CT as pure ground glass lesions. AAH is usually smaller than 5mm and AIS larger than 5mm on any view of the CT image. Both AAH and AIS show no solid component on thin-section CT. AIS can be discretely more opaque than AAH. Neither AAH nor AIS are invasive on histopathology. Any pure ground glass lesion larger than 3cm is considered to be LPA. MIA represents a lesion smaller than 3cm with a solid component (on imaging) and invasive component (on histopathology) of 5mm or smaller. LPA is a subsolid lesion that is also not larger than 3cm with a solid or invasive component of more than 5mm [3,4]. Nowadays, ground glass and part-solid nodules are more frequently encountered in daily practice than years ago. It is unclear if this is only a perception or that this represents a real increase in incidence. The widespread use of CT in clinical practice and the use of multidectector CT-scanners with finer CT collimation certainly are important factors for the increase in detection of subsolid nodules. Furthermore, numerous large lung cancer screening trials have been initiated in the past 10 to 15 years. These trials have given more insight in the incidence, evolution and prognosis of these adenocarcinoma precursors. In the Early Lung Cancer Action Project (ELCAP), 2892 part-solid lesions were found among 5% of 57,496 participants [7]. In the National Lung Cancer Screening Trial (NLST), which is the largest randomized lung cancer screening trial, 9.4% of 26,722 participants presented with one or more subsolid nodules [8]. In the first round of the large Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON), 2.0% of the total of 8673 nodules found in 7557 participants were subsolid nodules (both pure ground glass and partsolid) [9]. Although the incidence of subsolid nodules is significantly lower than that of solid nodules and masses, these lesions cannot be ignored and pose future challenges. A correct classification of pulmonary nodules is important since the likelihood of malignancy is larger in subsolid nodules compared to solid nodules [10]. Since subsolid nodules have a different prognosis than solid nodules, they require a different management approach. Moreover, invasive adenocarcinomas are more aggressive than adenocarcinoma precursor lesions [8,11]. The size (or absence) of a solid component on CT is correlated with the prevalence of an invasive component and is therefore crucial for clinical decision guidance. Furthermore survival in subsolid lesions depends on the invasive (or solid) component and not on the lepidic (or ground glass) component [12-16]. For this reason in the 8th edition of the TNM classification only the solid part is considered to measure the size of a lesion and determine the T descriptor [17]. The largest unidimensional size is measured using the lung window setting on chest CT scan. Current guidelines for management and follow-up of subsolid lesions are fully based on CT-imaging criteria. When assessing the morphology of subsolid nodules, it is important to characterize these lesions on contiguous thin sections (preferably 1.0mm or less than 1.5mm) and to evaluate the evolution comparing the lesions with the oldest images available. In routine practice, the morphology of lesions is visually assessed by a radiologist and measurement of both the solid component and the lesion size is mainly done by manual electronic caliper measurement. The border of the whole lesion as well as the border between the solid component and ground glass component is often hazy, making measuring a difficult task and making reproducible measurements inaccurate. To deal with the lack of detailed consideration of subsolid lung nodules in the 2005 Fleischner guidelines [18], specific recommendations for the management of subsolid pulmonary nodules detected at CT, were published in 2013 [19]. These guidelines were updated for both solid and subsolid nodules in 2017 [20]. The British Thoracic Society also incorporated specific recommendations for subsolid nodules in its guidelines for the investigations and management of pulmonary nodules, published in 2015 [21]. Furthermore, the 8th edition of the TNM staging classification of lung cancer, provides new criteria for cases presenting as multiple nodules with ground glass or lepidic features [22]. This new staging classification is based on CT-imaging findings of subsolid nodules. To address the need of a dedicated classification system for lung nodules in the era of lung cancer screening, the American College of Radiologists (ACR) proposed the Lung-RADSTM or lung imaging reporting and data system [23]. Subsolid nodules are incorporated in this management and follow-up scheme, which is widely used in the United States where – in contrast to Europelung cancer screening is already embedded in daily practice. All these guidelines and criteria are based on the theoretical radiologic-pathologic correlation of this adenocarcinoma sequence, having a major impact on management of subsolid nodules. Six years after the publication of the new IASLC/ATS/ERS classification guidelines, this new classification and the radiologicpathologic correlation have certainly found their way into routine clinical practice. Numerous issues however remain of which some will be addressed in this article.