COVID-19 Pneumonia and Lung Cancer: A Challenge for the RadiologistReview of the Main Radiological Features, Differential Diagnosis and Overlapping Pathologies

Abstract

The COVID-19 pneumonia pandemic represents the most severe health emergency of the 21st century and has been monopolizing health systems' economic and human resources world-wide. Cancer patients have been suffering from the health systems' COVID-19 priority management with evidence of late diagnosis leading to patients' poor prognosis and late medical treatment. The radiologist plays a pivotal role as CT represents a non-invasive radiological technique which may help to identify possible overlap and differential diagnosis between COVID-19 pneumonia and lung cancer, which represents the most frequent cancer histology in COVID-19 patients. Our aims are: to present the main CT features of COVID-19 pneumonia; to provide the main differential diagnosis with lung cancer, chemotherapy-, immunotherapy-, and radiotherapy-induced lung disease; and to suggest practical tips and key radiological elements to identify possible overlap between COVID-19 pneumonia and lung cancer. Despite similarities or overlapping findings, the combination of clinics and some specific radiological findings, which are also identified by comparison with previous and follow-up CT scans, may guide differential diagnosis. It is crucial to search for typical COVID-19 pneumonia phase progression and typical radiological features on HRTC. The evidence of atypical findings such as lymphadenopathies and mediastinal and vessel invasion, as well as the absence of response to therapy, should arouse the suspicion of lung cancer and require contrast administration. Ground-glass areas and/or consolidations bound to radiotherapy fields or pneumonitis arising during and after oncological therapy should always arouse the suspicion of radiation-induced lung disease and chemo/immunotherapy-induced lung disease. The radiological elements we suggest for COVID-19 and lung cancer differential diagnosis may be used to develop AI protocols to guarantee an early and proper diagnosis and treatment to improve patients' quality of life and life expectancy.

Keywords: 2021; COVID-19; SARS-CoV-2; WHO; artificial intelligence; cancer; crazy paving; ground glass; lung cancer; omicron; pneumonia; variants.

Figure 1

(a–e) HRTCs showing the four different stages of COVID-19 pneumonia (a–d) and ARDS as a possible complication I. In (a), the first stage is characterized by subpleural ground-glass opacities (white arrows in (a,b)) which co-exist with extensive subpleural crazy paving pattern in stage 2 (black arrows in (b); in (c), consolidations (black circle) are typical of phase 3 and may be surrounded by ground-glass opacities; in (d) parenchymal bands (black-bordered white arrows in (d) are characteristic of the absorption phase); in (e), confluent ground glass opacities with dependent foci of consolidations represent a dire complication of COVID-19 pneumonia: acute respiratory distress syndrome. Lungs: mean window with 1500 HU; mean window level −600. Mediastinum: mean window with 350 HU; mean window level 50 HU.

Figure 2

(a–d) HRTCs showing differential diagnoses of COVID-19 pneumonia stage 1/ground-glass opacities. COVID-19 phase 1 is characterized by subpleural ground-glass areas (white arrow in (a)) with ectasis vessels within (black arrow in (a)). Its main differentials are represented by adenocarcinoma in situ, presenting as a focal area of ground-glass opacity (dotted black arrow in (b)); radiation pneumonitis (acute radiation-induced lung disease) presenting with ground-glass opacities (dotted black arrows in (c)) in the field of radiation; and ground-glass metastases (black arrows in (d)) which appear as multiple focal ground-glass opacities with a random distribution. Lungs: mean window with 1500 HU; mean window level −600. Mediastinum: mean window with 350 HU; mean window level 50 HU.

Figure 3

(a–c) HRTCs showing differential diagnoses of COVID-19 pneumonia stage 2/crazy-paving opacities. In stage 2, extensive, subpleural crazy-paving opacities (black arrows in (a)) coexist with subpleural areas of ground-glass (white arrow in (a)) and should be differentiated by lymphangitis carcinomatosis (b), which represents secondary spread of lung cancer to the lymphatic vessels and is frequently seen together with pleural effusion (black asterisk in (b)), and by radiation pneumonitis (acute radiation-induced lung disease) presenting with crazy-paving pattern (dotted black arrows in (c)) in the field of radiation. Lungs: mean window with 1500 HU; mean window level −600. Mediastinum: mean window with 350 HU; mean window level 50 HU.

Figure 4

(a–f) HRTCs showing differential diagnoses of COVID-19 pneumonia stage 2–3/consolidations with ground-glass/crazy paving opacities. The transition between stage 2 and 3 of COVID-19 pneumonia is characterized by confluent consolidative foci (black circle in (a)) in extensive areas of ground-glass (white arrow in (a)) and/or crazy paving opacities (black arrow in (a)). Differential diagnosis with adenocarcinoma should include: minimally invasive adenocarcinoma presenting as a ground-glass area surrounding a solid nodule < 5 mm (dotted black arrow in (b)); invasive non-mucinous adenocarcinoma in which the nodule is >5mm and there is a small surrounding area of ground glass (dotted white circle in (c)); and invasive mucinous carcinoma, in particular the multicentric carcinoma (d) which presents as bilateral intraparenchymal or subpleural consolidations (dotted white arrows in (d)) surrounded by areas of ground-glass/crazy paving (black arrows in (d)) co-existing with extensive areas of ground-glass and crazy paving opacities (black arrows in (d)). Additional findings such as lymphadenopathies (black asterisks in (e)) may guide differential diagnosis. In (f), HRTC of patients presenting with chemotherapy induced organizing pneumonia characterized by extensive areas of ground-glass opacities (white arrows in (f)) coexisting with ill-defined consolidations (dotted black circle). Lungs: mean window with 1500 HU; mean window level −600. Mediastinum: mean window with 350 HU; mean window level 50 HU.

Figure 5

(a–e) Chest CTs showing differential diagnoses of COVID-19 pneumonia stage 3/consolidations. Subpleural ill-defined consolidations are typical of COVID-19 pneumonia stage 3 (black circle) and are generally easy distinguishable from lung cancer, especially if lung tumors present as big masses with spiculated margins, pleural retraction striae (dotted black circle in (b)), cavitations (black arrow in (b)) and lymphadenopathies (black asterisk in (c)). Contrast administration is useful to appreciate the inhomogeneous enhancement of lung tumor and mediastinal tissue infiltration (white arrow in (c)), and/or additional findings such as lobar atelectasis (dotted white arrow in (d)) secondary to bronchial invasion with progressive lobar hypoventilation and secretive stagnation. Solid metastases (e) may be differentiated by COVID-19 consolidations because they appear as roundish nodules with regular margins and a random distribution in relation to hematogenous spread. Lungs: mean window with 1500 HU; mean window level −600. Mediastinum: mean window with 350 HU; mean window level 50 HU.

Figure 6

(a–d) Chest CTs showing differential diagnoses of COVID-19 pneumonia stage 4/absorption phase characterized by parenchymal bands (black-bordered white arrows in (a). Differential diagnoses generally include chemotherapy-induced lung disease (b) and radiation-induced lung disease (c,d). In (b), HRTC of a patient presenting with OP showing pulmonary parenchymal ill-defined bands and consolidations during a chemotherapy cycle (black arrows in (b)); in (c,d), chest CT of a patient who underwent radiotherapy for an apical lung cancer, showing an extensive mass with irregular margins, pleural and mediastinal retraction striae (black dotted arrow) and with some calcification within (dotted white arrows) in the field of radiation. Lungs: mean window with 1500 HU; mean window level −600. Mediastinum: mean window with 350 HU; mean window level 50 HU.

Figure 7

(a–d) Chest CT of an oncologic patient affected by a paramediastinal lung cancer located in the apical segment of the right upper lobe (dotted white arrow) and undergoing chemotherapy and radiotherapy. After admission to the first aid with ageusia, anosmia, and fever, a chest CT scan was performed showing subpleural areas of ground-glass (white arrow in (b)) and crazy paving (black arrow in (c)) with the typical reversed halo sign or atoll sign (dotted black arrow in (d)), parenchymal consolidations (black circle in (a)) and subpleural parenchymal bands together with crazy paving opacities (black-bordered white arrow in (d)). Lungs: mean window with 1500 HU; mean window level −600. Mediastinum: mean window with 350 HU; mean window level 50 HU.