Everyone is scared of cancer. This applies to all cancers, especially lethal killers like lung and pancreatic cancers. For chronic smokers, they might be able to tolerate that persistent sense of discomfort arising from the inability for the lungs to puff and suck air properly. However, once you raise the possibility of lung cancer, it's very likely that they'll get themselves off smoking as quick as they can. This applies to those who have smoked for over twenty to thirty years. As with most pulmonary pathologies, the first-line radiological modality is the Chest X-Ray. However, it is by no means the only modality. Nor is it the most useful modality. Having said that, it's cheap and readily available. That's as good as it gets, given that the NHS is feeling the pinch under Austerity Britain. Moreover, X-Rays can be obtained within a relatively short period of time. This is significant in a fast-paced environment, such as the wards. You can get an X-Ray within a few seconds, while for MRI, thirty minutes are required.
The major caveat is: it lies. Although inherent, at the end of the day, in all imaging modalities, Chest X-Ray can be very misleading at times and radiologists are very careful to distinguish one diagnosis from another by picking up numerous signs, rather than blithely relying on one or two key clues. This article is going to focus on a rare pathology which appears 'like' cancer. Remember - it doesn't have to be cancer. Once it looks like it, it's all it takes to give a patient spontaneous panic attacks. Here are the Chest X-Rays I've extracted from a paper published by the BMJ that illustrate my point:
Scan A: A Chest X-Ray - Posterior-Anterior (PA) view showing a sneaky lesion over the right lower lung field (remember, in radiology, most things are flipped).
Scan B: A Chest X-Ray - Lateral View showing the same lesion (yes, it's probably from the same patient) located over the anterior aspect of the chest, at vertebral levels T6 to T8. If in doubt, look at the tracheal bifurcation which is at the level T4.
Both scans are extracted from [1].
Although we can already see the obvious mass and it's very tempting to stop right here and assert boldly that it's a cancer and investigations have to be performed, it's better to follow the age-old algorithm we use when reading Chest X-Rays (quite specific, since X-Rays of different systems have different algorithms but the general principles remain the same). I call it the 'ABCDE' approach:
Airway
Breathing (examination of Lung Fields, including the costophrenic angles, and the mediastinum, which is in the centre of the X-Ray film);
Circulation (looking at the heart - size, shape, position, as well as the major vessels, most prominently the aortic knuckle);
Disability (broken ribs or pneumothorax);
Extra Features - this includes the presence of any pacemakers, artificial valves and surgical implants; these might tell us more about the patient's previous medical and surgical history, thus aiding us in narrowing our list of differential diagnoses.
Let's analyse the above scans using this set of criteria. We'll start with the PA first.
Airway - the trachea is not deviated and, as far as I can tell, there is not mucous plugging; in some cases of airway obstruction, there is a sign called 'Glove in Hand' - common in cystic fibrosis and bronchiectasis where the bigger airways are filled with mucus. There is also no lobar collapse, which can result from airway obstruction.
Lung Cancer- S Sign of Golden is a special sign which involves upper lobar collapse and enlarged lymph nodes, giving rise to a wider mediastinum (the middle, opaque portion of the CXR). This contributes to an S-like contour of the opaque lesion. This is due to that the cancerous lesion obstructs the upper main bronchus, leading to upper lobe collapse. Lymph node metastasis or reactive lymphadenopathy (cancer cells are deemed as foreign, triggering an immune-mediated attack by the body, thus lymph nodes get enlarged) lead to widened mediastinum.
PA CXR showing S Sign of Golden (Lung Cancer) (Courtesy of Radiopaedia)
2. Breathing - there is a round, well-circumscribed mass over the right lower lung field, which is not associated with cavitation or adjacent consolidation. Other lung fields, including the apices and costophrenic angles (the sharp edges at the lower peripheral corners of the lung fields) are clear;
The mediastinum is also not widened (below 6 to 8 centimetres) [3].
Lung Cancer: Apart from increased mediastinal width secondary to lymphadenopathy, there is also consideration of the pleura. Lung cancer, being an inducer of inflammation, can lead to pleural effusion.
CXR (PA) showing the 'Meniscus' Sign on the left side of the chest - indicative of pleural effusion (extracted from: http://photos1.blogger.com/blogger/5772/1083/1600/cxr-effusion.jpg)
Note that there are different causes of the elevation of the hemidiaphragm (half of the diaphragm which forms the base of the thorax, dividing it from the abdomen) - the others are reduced lung volume (due to lobar collapse or retraction secondary to fibrosis), presence of liver (physiologically normal, right hemidiaphragm), and phrenic nerve palsy (the nerve which innervates the diaphragm; if it's not functioning properly, it's likely that it will shrivel up).
Moreover, some lung cancers do not appear as homogenous as the one shown in the index scan. They have rougher contours (poorly circumscribed) and may present with cavitation - meaning that there is fluid contained within the lesion, characterised by thick walls. Cavitation usually occurs in a subtype of lung cancer called squamous cell carcinoma.
CXR (PA) showing a cavitating lung lesion in the right upper lobe encompassing the fourth to sixth ribs; diagnosis after pathological assessment is squamous cell carcinoma of the lung (extracted from: http://www.svuhradiology.ie/wp-content/uploads/2015/04/cxrcavitatingscc.jpg)
3. Circulation - The heart is normal in size, shape (globular) and position (if it's flipped to the right, it's called dextrocardia and may be associated with a condition called Kartagener's Syndrome). In terms of size, we use the cardiothoracic ratio - if the heart > 1/2 of the thorax, there can be cardiomegaly and this points towards diseases like congestive heart failure. Remember, this only works on PA (not Anterior-Posterior, or AP) films. The aortic knuckle is not particularly prominent;
4. Disability - no identifiable pneumothorax or rib fractures (both anterior and posterior);
Lung Cancer: sometimes, there can be rib metastases from the cancerous lesion; moreover, as lung cancer (in line with liver and breast cancers) is osteolytic, such metastases manifest in the form of decreased bone density.
CXR (AP; since it's taken from the bedside) of Bone Metastases from Lung Cancer (extracted from: http://www.svuhradiology.ie/wp-content/uploads/2015/04/CXRrmzmassPathFrac-1024x742.jpg). From the scan, you can see signs of dehiscence between the bony ends, indicating the presence of fractures.
5. Extra Features - none.
It seems that, at this stage, apart from the weird mass, there isn't much to comment on. In fact, even if we look at the Lateral Chest X-Ray, apart from confirming that we surely do have a mass (located lateral to the heart and anterior to the trachea), there is nothing much to talk about. However, what if we zoom in the original scan?
Arrows indicating the vascular connections between the lesion and the right hilum. (Originally I wanted to make the arrows red, but somehow they turned grey as I saved them)
Those connections between the lesion and the blood vessels from the right hilum (the place where the airways and vessels enter the lung) do look fishy. This is not a common presentation of lung cancer. Also, although they seem like vascular connections, are they truly? What can we do further to confirm our hypothesis?
We do a CT (plus contrast) of the thorax to see what that lesion is.
Axial CT Scan of the Thorax showing a tubular, contrast-enhanced structure on the right (upper lobe) which is linked with the right hilum (advice: also consult other images in the same stack) (Extracted from: https://radiologypics.files.wordpress.com/2013/02/pulmonary-avm.jpg)
Although the above CT Scan is not reflective of the location of the lesion in the original patient (since it's extracted from a different source), both show the same pathology. CT Scans are very valuable in identifying different pathologies. Once contrast is added, if the lesion lights up, it's likely that it's associated with blood.
Diagnosis: Pulmonary Arteriovenous Malformation.
Arteriovenous malformations (AVMs) are not inherent to the lungs - they can arise anywhere, as long as there are vessels. They are vascular masses, better described as 'tangled-up', comprising a feeding artery and a draining vein. There can be multiple feeding arteries and draining veins, depending on the configuration. They are benign conditions and do not normally become cancers. However, it doesn't mean that they're less lethal. Over 80 per cent of patients have a condition called Hereditary Haemorrhagic Telangiectasia (HHT), which can be associated with genetic mutations in the TGF-beta pathway (development of blood vessels - to be more specific, smooth muscle cell proliferation) and, more recently-discovered, GDF2 (associated heavily with the functioning of TGF-beta pathway). Patients can present with haemoptysis (coughing with blood) and iron-deficiency anaemia owing to excessive blood loss. Disorderly blood vessel masses elsewhere can also lead to intracerebral haemorrhage and increased intracranial pressure (AVMs in the brain), as well as epistaxis (nosebleeds) (AVMs in the Little's Area). Luckily, HHT is rare and occurs in 1 per 5000 individuals. Moreover, about half of all HHT patients present with only small AVMs.
The lesson remains significant. Although common things come first and we should be considering about more common diagnoses rather than obsessing over pathologies that we may never encounter in our lifetime, I think it's also fair to say we should not be blind-sighted by the common ones since the rare ones are only 'rare', not 'totally non-existent' or fantastical. When reviewing patient details and X-Ray scans, it's better to appreciate the actual signs shown in the tests. It's no use seeing a lesion and jumping straight to the conclusion, hallucinating and fabricating stuff on the X-Ray to support a conclusion of lung cancer even though there is nothing apart from the hyperattenuated mass. It is recommended to check the age - since the median age at diagnosis for pulmonary AVMs is approximately 43 years, while lung cancer is the most prevalent in patients above and including the age of 71 years. Smoking also counts - if a patient has smoked daily for the past thirty years, lung cancer is not a remote possibility. Coming up with lung cancer as a working diagnosis only when there is heavy suspicion is crucial to avoid unnecessary patient anxiety and the performance of more invasive tests, such as endobronchial ultrasound (EBUS).
References and Further Reading:
[1] Khurshid I, Downie GH. (2002). Pulmonary arteriovenous malformation. Postgraduate Medical Journal. 78:191-197.
[2] Clarke C, Dux A. (2020). Chest X–Rays for Medical Students: CXRs Made Easy (2nd ed.). Wiley-Blackwell. (my absolute favourite and go-to book for thoracic radiology)
[3] Gutierrez A, Inaba K, Siboni S, et al. The utility of chest X-ray as a screening tool for blunt thoracic aortic injury. Injury. 2016;47(1):32-36. doi:10.1016/j.injury.2015.08.003.
[4] Gullette D, DeClerk L. (2019). Overview of Pulmonary Arteriovenous Malformations and Hereditary Hemorrhagic Telangiectasia. The Journal For Nurse Practitioners, 15(4), 286-289. https://doi.org/10.1016/j.nurpra.2019.01.002.
[5] Topiwala K, Patel S, Nouh A, Alberts M. (2020). Novel GDF2 Gene Mutation Associated with Pulmonary Arteriovenous Malformation. Journal Of Stroke And Cerebrovascular Diseases, 29(12), 105301. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.105301.
[6] Girit S, Senol E, Karatas Ö, Yıldırım A. (2020). Hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations. Respiratory Medicine Case Reports, 30, 101137. https://doi.org/10.1016/j.rmcr.2020.101137.
[7] Cottin V, Chinet T, Lavolé A, et al. (2007). Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: a series of 126 patients. Medicine (Baltimore). 86(1):1-17. doi:10.1097/MD.0b013e31802f8da1.