Lymphangitic Carcinomatosis Imaging
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The lungs are one of the most common targets for metastatic disease. [1] Most pulmonary metastases are nodular, but a significant minority is interstitial. Lymphangitic carcinomatosis (LC) refers to the diffuse infiltration and obstruction of pulmonary parenchymal lymphatic channels by tumor. Various neoplasms can cause lymphangitic carcinomatosis, but 80% are adenocarcinomas. [2] The most common primary sites are the breasts, lungs, colon, and stomach. [3, 4, 5, 6, 7, 8, 9] Other sources include the pancreas, thyroid, cervix, prostate, and larynx. [10, 11, 12, 13, 14] LC can also arise from choriocarcinoma, melanoma, or metastatic adenocarcinoma from an unknown primary cancer. [15] Radiographic characteristics of lymphangitic carcinomatosis are presented in theimages below.
In a patient with a known malignancy, the usual presenting complaint is breathlessness. Occasionally, patients have a dry cough or hemoptysis. Symptoms often precede the development of any radiographic abnormality. [16, 17, 18]
Plain chest radiography is the initial investigation of choice in patients presenting with any respiratory symptoms, and this examination is used in staging most cancers. [19, 20]
In the appropriate clinical circumstances or when the chest radiographic findings are equivocal, the next investigation employs high-resolution computed tomography (HRCT) scanning. [21, 22] Although the appearance of LC on HRCT scans is nonspecific, the observation of certain features in a symptomatic patient with an appropriate history of malignancy is highly suggestive of LC; in such instances, further investigation is generally not required.
Fragmented scintigraphic perfusion defects have been reported in LC, as have ventilation-perfusion (V/Q) mismatches. [23, 24] However, a diagnosis of LC cannot be reliably based on the presence of these features.
The radiographic features of LC are essentially nonspecific, with a diagnostic accuracy of 23%. Furthermore, chest radiographic findings are normal in as many as 50% of patients with histologic evidence of disease.
In comparison, HRCT scanning has higher sensitivity, although, as with radiography, the findings may not be diagnostic. The differential diagnosis includes other malignant conditions, such as lymphoma and Kaposi sarcoma, as well as benign entities, such as sarcoidosis. [21]
With LC, perfusion defects on a V/Q scan are nonspecific and are also described in various pulmonary pathologies, the most important of which is pulmonary embolism.
On radiographs, LC appears as reticular or reticulonodular opacification, often with associated septal lines (Kerley A and B lines), peribronchial cuffing, pleural effusions, and mediastinal and/or hilar lymphadenopathy (20-50% of cases). The images below demonstrate the radiographic characteristics of LC. [20, 25, 26, 27]
Chest radiographic findings are normal in most patients with LC, with the accurancy of chest radiography in this disease being only 23%. In addition, a false-positive diagnosis may occur with other interstitial lung diseases. On chest radiographs, the linear pattern of Kerley A and B lines has a variety of causes, the most common of which is hydrostatic interstitial edema. Besides LC, other causes include sarcoidosis and interstitial pneumonias. All of these conditions have a similar appearance to congestive heart failure; thus, the differentiation is largely clinically based. LC and interstitial pneumonias are often asymmetrically distributed, a characteristic that may be useful in distinguishing these from pulmonary edema. (See the image below.) [28]
The mainstay of LC detection is HRCT scanning. Although HRCT scanning is a sensitive technique, the findings may not be diagnostic. HRCT scan findings include the following [21, 22, 29, 30, 31, 32, 33, 34] :
Irregular, nodular, and/or smooth, interlobular septal thickening
Thickening of the fissures as a result of the involvement of the lymphatics concentrated in the subpleural interstitium
Preservation of normal parenchymal architecture at the level of the secondary pulmonary lobule
Peribronchovascular thickening
Centrilobular peribronchovascular thickening, which predominates over interlobular septal thickening in a minority of patients
Polygonal arcades or polygons with prominence of the centrilobular bronchovascular bundle in association with interlobular septal thickening (50%)
Mediastinal and/or hilar lymphadenopathy (30-50%)
Pleural effusions (30-50%)
Findings may be unilateral or bilateral, focal or diffuse, and symmetrical or asymmetrical. [35] Focal, unilateral disease accounts for 50% of cases. This pattern is associated in particular with underlying bronchogenic carcinoma. All of the changes described above are often associated with nodular opacities.
The HRCT scan characteristics of lymphangitic carcinomatosis are demonstrated below.
Although the appearance of LC on HRCT scans is nonspecific, the development of HRCT scan features in a symptomatic patient with an appropriate history of malignancy is highly suggestive of LC, and further investigation is usually not required.
LC may not be recognized in the presence of normal radiographic chest findings. HRCT scan findings of LC also are nonspecific and may be misinterpreted.
The differential diagnosis of LC includes sarcoidosis and other chronic interstitial lung diseases such as silicosis, coal worker’s pneumoconiosis, extrinsic allergic alveolitis (hypersensitivity pneumonitis), and cryptogenic fibrosing alveolitis, as well as other neoplasms, such as lymphoma and Kaposi sarcoma. Most of these diagnoses can be excluded on the basis of the clinical findings alone. The relative absence of polygons and the presence of architectural distortion at the level of the secondary pulmonary lobule strongly suggest fibrosis rather than LC.
Furthermore, parenchymal involvement in sarcoidosis is typically more central and/or perihilar, as well as more bilaterally symmetrical, than it is in LC. LC never appears as honeycombing, and sarcoid granulomas are often subpleural.
Fragmented scintigraphic perfusion defects have been reported in LC, as have V/Q mismatches. However, these features are not reliable in the diagnosis of LC. [3, 36] FDG-PET scanning is used in the diagnosis and characterization of primary or secondary lung neoplasms, but its value in the characterization of LC is not well documented. [37, 38, 39, 40, 41]
A 2006 study compared findings from FDG-PET scans with those from HRCT scans in 5 patients with pulmonary LC. [42] The FDG-PET scan activity distribution appeared to be identical to abnormal lung areas (which could be segmental, lobar, or diffuse) observed on HRCT scans. In segmental LC, a linear or a hazy area of FDG uptake extending from the tumor could be seen. An earlier study in 7 patients showed similar results, with the intensity of FDG uptake in the diseased lung being significantly greater than in the normal, contralateral lung. [43]
Lung perfusion defects on VQ lung scans have been described as secondary to lymphangitic carcinomatosis or due to tumor microemboli. Charest et al designed a retrospective study to determine the prognostic value of a lymphangitic carcinomatosis pattern on perfusion lung scan. [5] They identified 32 patients from 21 published papers internationally. The perfusion pattern defect was more commonly identified in women (81%) and associated with a progressive dyspnea (69%) and normal or minimal findings on a chest radiograph (58%). Of the 29 patients with available outcome data, 23 (79%) had a progressive course after the lung scan interpretation. In 18 of these 23 cases, the actual interval of survival was given: 12 (67%) of these patients died within the first month.
The study revealed that lymphangitic carcinomatosis perfusion pattern on scintigraphic imaging is associated with an extremely poor prognosis. Physicians caring for oncology patients need to be aware of this finding as it may make a difference to the treatment plan. [5]
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Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR Consultant Radiologist and Honorary Professor, North Manchester General Hospital Pennine Acute NHS Trust, UK
Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR is a member of the following medical societies: American Association for the Advancement of Science, American Institute of Ultrasound in Medicine, British Medical Association, Royal College of Physicians and Surgeons of the United States, British Society of Interventional Radiology, Royal College of Physicians, Royal College of Radiologists, Royal College of Surgeons of England
Disclosure: Nothing to disclose.
Sumaira Macdonald, MBChB, PhD, FRCP, FRCR, EBIR Chief Medical Officer, Silk Road Medical
Sumaira Macdonald, MBChB, PhD, FRCP, FRCR, EBIR is a member of the following medical societies: British Medical Association, Cardiovascular and Interventional Radiological Society of Europe, British Society of Interventional Radiology, International Society for Vascular Surgery, Royal College of Physicians, Royal College of Radiologists, British Society of Endovascular Therapy, Scottish Radiological Society, Vascular Society of Great Britain and Ireland
Disclosure: Received salary from Silk Road Medical for employment.
Carolyn M Allen, MBChB, MRCP, FRCR Consultant Radiologist, Clinical Director, Department of Clinical Radiology, North Manchester General Hospital, UK
Carolyn M Allen, MBChB, MRCP, FRCR is a member of the following medical societies: Society of Thoracic Radiology
Disclosure: Nothing to disclose.
Klaus L Irion, MD, PhD Consulting Staff, The Cardiothoracic Centre Liverpool NHS Trust, The Royal Liverpool University Hospital, UK
Klaus L Irion, MD, PhD is a member of the following medical societies: American Roentgen Ray Society, Radiological Society of North America
Disclosure: Nothing to disclose.
Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.
W Richard Webb, MD Professor, Department of Radiology, University of California, San Francisco, School of Medicine
Disclosure: Nothing to disclose.
Eugene C Lin, MD Attending Radiologist, Teaching Coordinator for Cardiac Imaging, Radiology Residency Program, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine
Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, Society of Nuclear Medicine and Molecular Imaging
Disclosure: Nothing to disclose.
Jeffrey A Miller, MD Associate Adjunct Professor of Clinical Radiology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School; Faculty, Department of Radiology, Veterans Affairs of New Jersey Health Care System
Jeffrey A Miller, MD is a member of the following medical societies: American Roentgen Ray Society, Radiology Alliance for Health Services Research, Society of Thoracic Radiology
Disclosure: Nothing to disclose.
Ramesh Chandra Raja, MBChB, FRCR, Consulting Staff, Department of Radiology, Rochdale Healthcare NHS Trust, assisted with this article.
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