2021 WHO Classification of Lung Cancer: Molecular Biology Research and Radiologic-Pathologic Correlation.

The 2021 World Health Organization (WHO) classification system for thoracic tumors (including lung cancer) contains several updates to the 2015 edition. Revisions for lung cancer include a new grading system for invasive nonmucinous adenocarcinoma that better reflects prognosis, reorganization of squamous cell carcinomas and neuroendocrine neoplasms, and description of some new entities. Moreover, remarkable advancements in our knowledge of genetic mutations and targeted therapies have led to a much greater emphasis on genetic testing than that in 2015. In 2015, guidelines recommended evaluation of only two driver mutations, ie, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions, in patients with nonsquamous non-small cell lung cancer. The 2021 guidelines recommend testing for numerous additional gene mutations for which targeted therapies are now available including ROS1, RET, NTRK1-3, KRAS, BRAF, and MET. The correlation of imaging features and genetic mutations is being studied. Testing for the immune biomarker programmed death ligand 1 is now recommended before starting first-line therapy in patients with metastatic non-small cell lung cancer. Because 70% of lung cancers are unresectable at patient presentation, diagnosis of lung cancer is usually based on small diagnostic samples (ie, biopsy specimens) rather than surgical resection specimens. The 2021 version emphasizes differences in the histopathologic interpretation of small diagnostic samples and resection specimens. Radiologists play a key role not only in evaluation of tumor and metastatic disease but also in identification of optimal biopsy targets. ©RSNA, 2024 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Lung Cancer Staging: Imaging and Potential Pitfalls.

Lung cancer is the leading cause of cancer deaths in men and women in the United States. Accurate staging is needed to determine prognosis and devise effective treatment plans. The International Association for the Study of Lung Cancer (IASLC) has made multiple revisions to the tumor, node, metastasis (TNM) staging system used by the Union for International Cancer Control and the American Joint Committee on Cancer to stage lung cancer. The eighth edition of this staging system includes modifications to the T classification with cut points of 1 cm increments in tumor size, grouping of lung cancers associated with partial or complete lung atelectasis or pneumonitis, grouping of tumors with involvement of a main bronchus regardless of distance from the carina, and upstaging of diaphragmatic invasion to T4. The N classification describes the spread to regional lymph nodes and no changes were proposed for TNM-8. In the M classification, metastatic disease is divided into intra- versus extrathoracic metastasis, and single versus multiple metastases. In order to optimize patient outcomes, it is important to understand the nuances of the TNM staging system, the strengths and weaknesses of various imaging modalities used in lung cancer staging, and potential pitfalls in image interpretation.

Spectrum of Imaging Patterns of Lung Cancer following Radiation Therapy.

Radiation therapy using conventional or newer high-precision dose techniques, including three-dimensional conformal radiotherapy, intensity-modulated radiation therapy, stereotactic body radiation therapy, four-dimensional conformational radiotherapy, and proton therapy, is an important component of treating patients with lung cancer. Knowledge of the radiation technique used and the expected temporal evolution of radiation-induced lung injury, as well as patient-specific parameters such as previous radiotherapy, concurrent chemoradiotherapy, or immunotherapy, is important in image interpretation. This review discusses factors that affect the development and severity of radiation-induced lung injury and its radiological manifestations, as well as the differences between conventional and high-precision dose radiotherapy techniques.

Multimodality imaging of mediastinal masses and mimics.

A wide variety of neoplastic and nonneoplastic conditions occur in the mediastinum. Imaging plays a central role in the evaluation of mediastinal pathologies and their mimics. Localization of a mediastinal lesion to a compartment and characterization of morphology, density/signal intensity, enhancement, and mass effect on neighboring structures can help narrow the differentials. The International Thymic Malignancy Interest Group (ITMIG) established a cross-sectional imaging-derived and anatomy-based classification system for mediastinal compartments, comprising the prevascular (anterior), visceral (middle), and paravertebral (posterior) compartments. Cross-sectional imaging is integral in the evaluation of mediastinal lesions. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to characterize mediastinal lesions detected on radiography. Advantages of CT include its widespread availability, fast acquisition time, relatively low cost, and ability to detect calcium. Advantages of MRI include the lack of radiation exposure, superior soft tissue contrast resolution to detect invasion of the mass across tissue planes, including the chest wall and diaphragm, involvement of neurovascular structures, and the potential for dynamic sequences during free-breathing or cinematic cardiac gating to assess motion of the mass relative to adjacent structures. MRI is superior to CT in the differentiation of cystic from solid lesions and in the detection of fat to differentiate thymic hyperplasia from thymic malignancy.

Interstitial lung abnormalities after hospitalization for COVID-19 in patients with cancer: A prospective cohort study.

INTRODUCTION: Survivors of SARS-CoV-2 pneumonia often develop persistent respiratory symptom and interstitial lung abnormalities (ILAs) after infection. Risk factors for ILA development and duration of ILA persistence after SARS-CoV-2 infection are not well described in immunocompromised hosts, such as cancer patients. METHODS: We conducted a prospective cohort study of 95 patients at a major cancer center and 45 patients at a tertiary referral center. We collected clinical and radiographic data during the index hospitalization for COVID-19 pneumonia and measured pneumonia severity using a semi-quantitative radiographic score, the Radiologic Severity Index (RSI). Patients were evaluated in post-COVID-19 clinics at 3 and 6 months after discharge and underwent comprehensive pulmonary evaluations (symptom assessment, chest computed tomography, pulmonary function tests, 6-min walk test). The association of clinical and radiological factors with ILAs at 3 and 6 months post-discharge was measured using univariable and multivariable logistic regression. RESULTS: Sixty-six (70%) patients of cancer cohort had ILAs at 3 months, of whom 39 had persistent respiratory symptoms. Twenty-four (26%) patients had persistent ILA at 6 months after hospital discharge. In adjusted models, higher peak RSI at admission was associated with ILAs at 3 (OR 1.5 per 5-point increase, 95% CI 1.1-1.9) and 6 months (OR 1.3 per 5-point increase, 95% CI 1.1-1.6) post-discharge. Fibrotic ILAs (reticulation, traction bronchiectasis, and architectural distortion) were more common at 6 months post-discharge. CONCLUSIONS: Post-COVID-19 ILAs are common in cancer patients 3 months after hospital discharge, and peak RSI and older age are strong predictors of persistent ILAs.

Imaging of Malignant Pleural, Pericardial, and Peritoneal Mesothelioma.

Malignant mesothelioma is a rare tumor arising from the mesothelial cells that line the pleura, pericardium, peritoneum, and tunica vaginalis. Imaging plays a primary role in the diagnosis, staging, and management of malignant mesothelioma. Multimodality imaging, including radiography, computed tomography (CT), magnetic resonance imaging (MRI), and F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), is used in a variety of scenarios, including diagnosis, guidance for tissue sampling, staging, and reassessment of disease after therapy. CT is the primary imaging modality used in staging. MRI has superior contrast resolution compared with CT and can add value in terms of determining surgical resectability in equivocal cases. MRI can further assess the degree of local invasion, particularly into the mediastinum, chest wall, and diaphragm, for malignant pleural and pericardial mesotheliomas. FDG PET/CT plays a role in the diagnosis and staging of malignant pleural mesothelioma (MPM) and has been shown to be more accurate than CT, MRI, and PET alone in the staging of malignant pleural mesothelioma. PET/CT can also be used to target lesions for biopsy and to assess prognosis, treatment response, and tumor recurrence.

Imaging of Immune Checkpoint Inhibitor Immunotherapy for Non-Small Cell Lung Cancer.

The normal immune system identifies and eliminates precancerous and cancerous cells. However, tumors can develop immune resistance mechanisms, one of which involves the exploitation of pathways, termed immune checkpoints, that normally suppress T-cell function. The goal of immune checkpoint inhibitor (ICI) immunotherapy is to boost T-cell-mediated immunity to mount a more effective attack on cancer cells. ICIs have changed the treatment landscape of advanced non-small cell lung cancer (NSCLC), and numerous ICIs have now been approved as first-line treatments for NSCLC by the U.S. Food and Drug Administration. ICIs can cause atypical response patterns such as pseudoprogression, whereby the tumor burden initially increases but then decreases. Therefore, response criteria have been developed specifically for patients receiving immunotherapy. Because ICIs activate the immune system, they can lead to inflammatory side effects, termed immune-related adverse events (irAEs). Usually occurring within weeks to months after the start of therapy, irAEs range from asymptomatic abnormal laboratory results to life-threatening conditions such as encephalitis, pneumonitis, myocarditis, hepatitis, and colitis. It is important to be aware of the imaging appearances of the various irAEs to avoid misinterpreting them as metastatic disease, progressive disease, or infection. The basic principles of ICI therapy; indications for ICI therapy in the setting of NSCLC; response assessment and atypical response patterns of ICI therapy, as compared with conventional chemotherapy; and the spectrum of irAEs seen at imaging are reviewed. An invited commentary by Nishino is available online. ©RSNA, 2022.

Imaging of Lung Cancer Staging.

Lung cancer is a leading cause of cancer-related mortality worldwide. Imaging is integral in accurate clinical staging to stratify patients into groups to predict survival and determine treatment. The eighth edition of the tumor, node, and metastasis (TNM-8) staging system proposed by the International Association for the Study of Lung Cancer in 2016, accepted by both the Union for International Cancer Control and the American Joint Committee on Cancer, is the current standard method of staging lung cancer. This single TNM staging is used for all histologic subtypes of lung cancer, including nonsmall cell lung cancer, small cell lung cancer, and bronchopulmonary carcinoid tumor, and it addresses both clinical and pathologic staging. Familiarity with the strengths and limitations of imaging modalities used in staging, the nuances of TNM-8, its correct nomenclature, and potential pitfalls are important to optimize patient care. In this article, we discuss the role of computed tomography (CT) and positron emission tomography/CT in lung cancer staging, as well as current imaging recommendations pertaining to TNM-8.

Pitfalls in Oncologic Imaging of the Pericardium on CT and PET/CT.

In the oncologic setting, misinterpretation of fluid in pericardial recesses as mediastinal adenopathy or benign pericardial findings as malignant can lead to inaccurate staging and inappropriate management. Knowledge of normal pericardial anatomy, imaging features to differentiate fluid in pericardial sinuses and recesses from mediastinal adenopathy and potential pitfalls in imaging of the pericardium on CT and PET/CT is important to avoid misinterpretation.

Pitfalls in the imaging of pulmonary embolism.

Pulmonary embolism (PE) can present with a wide spectrum of clinical symptoms that can overlap considerably with other cardiovascular diseases. To avoid PE related morbidity and mortality, it is vital to identify this disease accurately and in a timely fashion. Several clinical criteria have been developed to standardize the diagnostic approach for patients with suspected PE. Computed tomographic pulmonary angiogram has significantly improved the detection of pulmonary embolism and is considered the imaging modality of choice to diagnose this disease. However, there are several potential pitfalls associated with this modality which can make diagnosis of PE challenging. In this review, we will discuss various pitfalls routinely encountered in the diagnostic work up of patients with suspected PE, approaches to mitigate these pitfalls and incidental pulmonary embolism.

Pearls and Pitfalls in Lung Cancer CT Screening.

Annual LDCT lung cancer screening is recommended by the United States Preventive Services Task Force (USPSTF) for high-risk population based on the results from the National Lung Cancer Screening Trial (NLST) that showed a significant (20%) reduction in lung cancer-specific mortality rate with the use of annual low-dose computed tomography (LDCT) screening. More recently, the benefits of lung cancer screening were confirmed by the Dutch- Belgian NELSON trial in Europe. With the implementation of lung screening in large scale, knowledge of the limitations related to false positive, false negative and other potential pitfalls is essential to avoid misdiagnosis. This review outlines the most common potential pitfalls in the characterization of screen-detected lung nodules that include artifacts in LDCT, benign nodules that mimic lung cancer, and causes of false negative evaluations of lung cancer with LDCT and PET/CT studies. Awareness of the spectrum of potential pitfalls in pulmonary nodule detection and characterization, including equivocal or atypical presentations, is important for avoiding misinterpretation that can alter patient management.

Pearls and pitfalls in imaging of mediastinal masses.

In imaging of the mediastinum, advances in computed tomography (CT), and magnetic resonance imaging (MRI) technology enable improved characterization of mediastinal masses. Knowledge of the boundaries of the mediastinal compartments is key to accurate localization. Awareness of distinguishing imaging characteristics allows radiologists to suggest a specific diagnosis or narrow the differential. In certain situations, MRI adds value to further characterize mediastinal lesions.

Two unusual fat-containing mediastinal entities: Pearls and pitfalls in imaging of Morgagni hernia and fat necrosis.

This review focuses on 2 fat-containing entities in the mediastinum that may raise a diagnostic challenge: Morgagni's hernia and Epipericardial (mediastinal) fat necrosis. Familiarity with the typical imaging findings of these 2 entities is vital for the radiologist to recognize and accurately characterize unusual mediastinal pathological conditions.

Invasive Fungal Pneumonia in Immunocompromised Patients.

Fungal pneumonia is the most frequent presentation of invasive fungal infections (IFIs) in patients with hematologic malignancies (HM) and hematopoietic stem cell transplantation (HSCT) recipients. The most common causes include Aspergillus, Mucor, Fusarium, and Candida species. The high incidence and high morbidity and mortality rate of fungal pneumonias in HM/HSCT populations arise from severe immune dysfunction that may be caused by both the underlying disease and/or its treatment. CT is routinely used when pulmonary complications are suspected after HSCT. Appropriate image interpretation of the posttransplant patient requires a combination of pattern recognition and knowledge of the clinical setting. In this article, we provide an overview of the clinical manifestations and CT imaging features of the most common invasive fungal pneumonias (IFPs) seen in severely immunosuppressed hosts.

Imaging Primer on Chimeric Antigen Receptor T-Cell Therapy for Radiologists.

Chimeric antigen receptor (CAR) T-cell therapy is a recently approved breakthrough treatment that has become a new paradigm in treatment of recurrent or refractory B-cell lymphomas and pediatric or adult acute lymphoid leukemia. CAR T cells are a type of cellular immunotherapy that artificially enhances T cells to boost eradication of malignancy through activation of the native immune system. The CAR construct is a synthetically created functional cell receptor grafted onto previously harvested patient T cells, which bind to preselected tumor-associated antigens and thereby activate host immune signaling cascades to attack tumor cells. Advantages include a single treatment episode of 2-3 weeks and durable disease elimination, with remission rates of over 80%. Responses to therapy are more rapid than with conventional chemotherapy or immunotherapy, with intervening short-interval edema. CAR T-cell administration is associated with therapy-related toxic effects in a large percentage of patients, notably cytokine release syndrome, immune effect cell-associated neurotoxicity syndrome, and infections related to immunosuppression. Knowledge of the expected evolution of therapy response and potential adverse events in CAR T-cell therapy and correlation with the timeline of treatment are important to optimize patient care. Some toxic effects are radiologically evident, and familiarity with their imaging spectrum is key to avoiding misinterpretation. Other clinical toxic effects may be occult at imaging and are diagnosed on the basis of clinical assessment. Future directions for CAR T-cell therapy include new indications and expanded tumor targets, along with novel ways to capture T-cell activation with imaging. An invited commentary by Ramaiya and Smith is available online. Online supplemental material is available for this article. ©RSNA, 2022.

It's Not All in Your Head: Thoracic Manifestations of Neurologic Diseases and Disorders.

Myriad conditions may affect both the neurologic system and the thorax, while other diseases primarily affecting the thorax may manifest with neurologic abnormalities. Correlation of signs, symptoms, and imaging findings in the neurological system with those in the thorax can help diagnose certain conditions and/or guide further diagnostic work-up and treatment. We will review and illustrate the imaging appearance of several systemic/neurological diseases with thoracic manifestations as well as discuss conditions in the thorax that can lead to neurologic symptoms.

Imaging of the mediastinum: Mimics of malignancy.

In the imaging of the mediastinum, benign lesions mimicking malignancy constitute potential pitfalls in interpretation. Localization and characteristic imaging features are key to narrow the differential diagnosis and avoid potential pitfalls in interpretation. Based on certain anatomic landmarks, the mediastinal compartment model enables accurate localization. Depending on the anatomic origin, mediastinal lesions can have various etiologies. The anatomic location and structures contained within each mediastinal compartment are helpful in generating the differential diagnoses. These structures include thyroid, thymus, parathyroid, lymph nodes, pericardium, embryogenic remnants, and parts of the enteric tracts, vessels, and nerves. Imaging characteristics on computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT), including attenuation (fluid, fat, calcification), contrast enhancement, and metabolic activity, aid in narrowing the differential diagnoses. Understanding the roles and limitations of various imaging modalities is helpful in the evaluation of mediastinal masses. In this review, we present potential pitfalls in the imaging of mediastinal lesions with emphasis on the mimics of malignancy.

Pearls and Pitfalls in Lung Cancer Imaging.

Imaging plays an essential role in the diagnosis and staging of pulmonary malignancy. Familiarity of less common manifestations of lung cancer including subsolid nodule, consolidation, and cyst associated lung cancer is important to avoid delayed diagnosis and improve patient outcomes. In this article, we review the staging of multifocal lung cancer, PET negative lung cancers (carcinoid and indolent lung adenocarcinoma), and false positive lymph nodes on PET due to infectious and inflammatory etiologies. Knowledge of these potential pitfalls and pearls in lung cancer imaging and correlation with patients' clinical history are essential to prevent misinterpretation.

Pearls and Pitfalls in the Imaging of Targeted Therapy and Immunotherapy in Lung Cancer.

Most lung cancers are diagnosed at advanced stage when the cancer has metastasized outside the lung. These patients are not eligible for curative surgery or radiation therapy and treated with systemic therapy. Advances in the understanding of the biology of lung cancer has resulted in the development of targeted therapy aimed at specific genetic mutations identified with non-small cell lung cancer and immunotherapy that helps the immune system recognize tumors as foreign, stimulates the immune system, and removes the inhibition that allows growth and spread of cancer cells. Tumors treated with targeted or immunotherapies respond differently when compared with traditional chemotherapy and not captured by conventional response criteria such as the World Health Organization criteria and Response Evaluation Criteria in Solid Tumors. Therefore, several modified criteria have been developed to appropriately address the treatment response when using these novel agents. Numerous treatment-related side effects have been described that are important to recognize to avoid misinterpretation as worsening tumor and to ensure appropriate management.