ECR 2019 TOPIC PACKAGE
Lymphangiomyomatosis (LAM) is a rare cystic lung disease caused by infiltration of the lung with smooth muscle cells. It occurs in patients with tuberous sclerosis complex (TSC-LAM) and in a “sporadic” form in patients without tuberous sclerosis (S-LAM). S-LAM is seen exclusively in women of reproductive age while TSC-LAM may also be seen in men. Parenchymal lesions in LAM include cysts, which are thin-walled, well-defined, rounded, usually small in size up to 2 cm and may reach large numbers. They have no zonal lung predominance. Nodules are extremely rare in S-LAM and are more commonly seen in TSC-LAM. They may either be solid or ground-glass and usually tiny. They represent multifocal micronodular pneumocyte hyperplasia. Pleural manifestations include chylothorax and pneumothorax. Chylous pericardial effusions may be seen. Recent guidelines for LAM from the European Respiratory Society LAM task force classify LAM as definite, probable and possible. LAM is differentiated by other cystic lung diseases such as Langerhans histiocytosis (PLCH), Birt-Hogg-Dubbe (BHD), lymphocytic interstitial pneumonia (LIP) and amyloidosis. In PLCH the cysts have a bizarre shape, are variable in number and are upper and middle lobe predominant. In LIP the cysts are round and variable in size but usually small and random in distribution surrounded by ground glass opacity. In BHD the cysts are elliptical in shape and have a subpleural, lower zone predominance adjacent to vessels. In amyloid, the cysts are variable in size but usually large and diffusely distributed. Nodules are seen in PLCH and amyloid.
Adenocarcinoma is the most prevalent type of lung cancer, showing a large spectrum of genetics, histologic subtype, CT appearance and prognosis. Activating mutations of EGFR are found in 30%-50% of lung adenocarcinomas in East Asian patients and approximately 15% in Caucasian patients. EGFR mutation status is correlated with nonsmoking status, female sex, lepidic subtype, and a high response rate to EGFR tyrosine kinase inhibitors (TKI). Some CT findings have shown to be associated with EGFR mutation such as nonsolid or mixed ground-glass opacity, air bronchogram, smaller and peripheral tumours. Furthermore, never-smoking patients presenting with diffuse miliary metastatic disease at diagnosis may be diagnosed with adenocarcinoma harbouring EFGR mutation and may show a dramatic response to EGFR-TKI. The most common resistance mechanism to EGFR-TKI is the T790M mutation, against which new irreversible TKIs have been found to be clinically effective, thus increasing demand for rebiopsy in progressive NSCLC to analyse mutational status. Rebiopsies are feasible and informative in most of the patients with acceptable rates of complications. Furthermore, continued EGFR-TKI therapy may be indicated beyond RECIST progression because these tumours grow slowly and some tumour cells remain sensitive to EGFR-TKI. Radiologists should also be aware of the risk of class-effect toxicity of EGFR-TKI, in particular, pneumonitis with an incidence rate of 4-5% in the Japanese population. Finally, European radiologists should keep in mind that a majority of studies dealing with EGFR mutations in adenocarcinomas arise from Asian countries with results that might not be transposable to Caucasian populations.
Immune checkpoint inhibitors are effective in the treatment of many cancers, de-blocking immune pathways; they play an increasing role in the first-line treatment of lung-cancers. This is particularly true when there is evidence for a significant pretreatment tumour lymphocytic infiltration and/or the tumour shows a high expression for PD-L1. As checkpoint inhibitors work through a different mode of action compared to cytotoxic agents, there is a good reason to use therapy response criteria other than RECIST. In contrast to classical chemotherapies anti-tumour response in immunotherapy may take longer, and in the initial phase the response to immune therapies can manifest in a morphologic “progressive disease”, therefore, called “pseudoprogression”. In this situation, early discontinuation of the treatment could be inappropriate, unless PD is confirmed. An initially tolerable PD may even include the detection of new lesions ("unconfirmed progression", iUPD) that may not lead immediately to a discontinuation of the oncologic regiment and has to be reevaluated (iCPD, iSD). The disinhibition of mechanisms normally protecting from autoimmunity and prolonged immunoreactions leads not only to unusual tumour response patterns but also produces atypical toxicities including a broad spectrum of autoimmune diseases. Imaging characteristics of frequent and serious immune-related adverse events will be discussed.
In the last decade, huge improvements in prognosis and quality of life have been granted by molecular characterisation of non-small cell lung cancer (NSCLC). In particular, Anaplastic Lymphoma Kinase (ALK) and ROS1-positive tumours can now be treated by oral tyrosine kinase inhibitors (TKIs), which allow survival outcomes far beyond it could be expected until a decade ago. Notably, these oncogenes are mostly found in adenocarcinoma histology and in never-smokers (about 60% of all ALK-rearranged NSCLC). Target therapy by TKI improves progression-free survival (PFS) compared with previous reference chemotherapy. In the face of a better disease control by TKI, however, it happens that ALK-positive tumours are prone to driver mutation with resistance to first-line TKI, in the first months of therapy. In clinical practice, diagnostic imaging, notably computed tomography (CT), has a high yield in the management of patients under target therapy. The CT evidence of disease progression, either local or systemic (note: brain metastases are relatively common because first-line TKIs have low trespassing coefficient through the hematoencephalic barrier) is paramount for timely adaptation of therapy. Rapid radiologic progression demands prompt TKI swap towards second-line (e.g. ceritinib, brigatinib, or alectinib) or third-line target therapy (e.g. lorlatinib) or otherwise. Re-biopsy is suggested to pitch the optimal second (or further) line therapy by continuous molecular testing. Adverse events occur in a minority of patients under TKI (1% incidence of lung toxicity). Therapy discontinuation is usually sufficient to reduce toxic effects, with only 3-6% of cases lingering after therapy withdrawal.
Lung cancer is a leading cause of cancer-related mortality worldwide. A correct staging is the prerequisite for an adequate management of patients with lung cancer. Recently the 8TH edition of the TNM classification introduced relevant changes of the descriptors T and M. Regarding T, it has been demonstrated by survival analyses that from 1 to 5 cm of diameter every centimetre counts, and those larger tumours are best aligned with either T3 (tumour size of more than 5 to 7 cm) or T4 (tumour size of more than 7 cm). This finding further confirms the common intuition that the larger the tumour, the worse the prognosis. Regarding M, the category of extrathoracic lesions has been distinguished in M1b and M1c to indicate respectively one (oligometastatic disease) and more than one lesion. In this context, it is advisable that radiologists report the number of lesions if only one organ is involved and the number of organs if many. This approach has a relevant clinical impact because oligometastatic disease nowadays is managed and treated differently respect to an extensive M stage disease. Several limitations remain, as the classification of a tumour adjacent to the chest wall, mediastinum and diaphragm, as well as the categorisation of lymphangitic carcinomatosis as an independent descriptor and the evaluation of multiple lung lesions. Certainties and controversies on the topic will be argued in this session, taking into account that cancer staging should be always considered a multidisciplinary process.
Incidental findings are unanticipated findings discovered in the course of medical care, which can affect the way the oncologic disease is managed. Among incidental findings in oncologic patients, incidental pulmonary embolism (PE), lung nodules and adrenal masses are frequent findings. Incidental PE is more frequently peripheral, and thus more difficult to diagnose. The recurrence risk in untreated patients is 12%, versus 6% with anticoagulation. Thus, anticoagulant treatment is recommended for cancer-associated incidental PE. The annual incidence of VTE in patients receiving chemotherapy is estimated at 11%. This risk can climb to 20% or higher depending on the type of drug(s) being administered. Incidental PE is not associated with an increased risk of death when adjusted for tumour stage and performance status. Incidental lung nodules are frequently found in oncologic patients. As indicated in the 2005 Fleischner guidelines for management of small pulmonary nodules, patients should be cared for according to the specific clinical situation. Pertinent factors include the site, cell type, and stage of a primary tumour and whether early detection of lung metastases will affect care. Among differential diagnosis of metastasis, Langerhans cell histiocytosis, DIPNECH (Diffuse Idiopathic Pulmonary Neuro Endocrine Celle Hyperplasia) and infectious nodules should be discussed. Regarding incidental adrenal masses, benign adenoma can be diagnosed if the attenuation on unenhanced CT acquisition is below 10 Hounsfield units. If it is not the case, PET CT should be performed and in case of increased FDG uptake, histological assessment is required.
A cavity is defined as “a gas-filled space, seen as a lucency or low-attenuation area, within pulmonary consolidation, a mass, or a nodule”. The wall thickness may vary considerably. There is a continuous transition from cavities to cysts. Cysts are usually thin-walled (i.e., < 2 mm). A wall thickness < 7 mm is highly specific for the benign disease, a thickness >24 mm is highly specific for malignant disease. However, this is not absolute, as thin-walled carcinomas do exist. An additional indicator for malignancy is the lack of perilesional centrilobular nodules around a cavity. The cavity content is unhelpful in differentiating benign and malignant lesions. Wall rim enhancement on contrast-enhanced CT is common in abscesses. A connecting pulmonary artery may be seen in smaller metastases, but not in larger ones, as the larger nodules tend to compress the vessels, so no feeding artery does not always imply benign nodules. The acute onset of symptoms is sometimes helpful to distinguish malignant and non-malignant disease. Hemoptysis is not a useful symptom to differentiate between benign and malignant cavities. Benign diseases may also cause fatigue and weight loss similar to malignancies. Acute onset of fever is usually helpful to distinguish benign disorders from malignant, but pulmonary cancer may cause a super-infection secondary to the tumour. However, the combination of symptoms, laboratory results, past clinical history, and imaging findings leads to recognition of the correct diagnosis. This presentation will guide you through the most commonly encountered cavitary lung in adults.
The presentation will review the typical and atypical features of Langerhans cell histiocytosis (LCH) on HRCT, and the differential diagnosis when faced with cystic lung disease on CT. The evolution of CT appearances of LCH over time, the complications of LCH, as well as the pathological correlates will be discussed.