1

What is a solitary pulmonary nodule?

A solitary pulmonary nodule (SPN) is a discrete radiological lesion less than 3cm in diameter, surrounded completely by normal lung parenchyma, in the absence of a pleural effusion, enlarged mediastinal lymph nodes or atelectasis.

This excludes multinodular disease and lesions with smaller satellite nodules.

By definition, an SPN is diagnosed on a chest X-ray (Figure 1) or computed tomography (CT) scan (Figure 2).

It is an incidental finding in 0.09-0.2% of all chest X-rays (150,000 chest X-rays or CTs/per annum in the United States).

2

What is the aetiology of an SPN?

Benign conditions

Congenital:

a)

arteriovenous malformations (AVM), hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome);

b)

mucocoele within atretic bronchi.

Acquired:

a)

infection or abscess:

i)

acute bacterial or viral infections;

ii)

bronchiolitis obliterans organising pneumonia (BOOP);

iii)

fungal, such as aspergillosis, histoplasmosis, coccidioidomycosis or actinomycosis;

b)

inflammatory:

i)

intrapulmonary enlarged lymph node or lymphoid tissue;

c)

granulomatous:

i)

Mycobacterium tuberculosis;

ii)

histiocytoma (plasma cell granuloma or plasmacytoma) – which is the commonest benign cause in the USA;

iii)

collagen vascular disease, such as rheumatoid nodules (Figure 3), granulomatosis with polyangiitis or systemic lupus erythematosus (SLE);

iv)

autoimmune or idiopathic granulomas, such as sarcoidosis, amyloidosis and histiocytosis X;

d)

pseudotumours – round atelectasis caused by enfolded lung rotating on a fixed point of pleural disease, chronic scarring or asbestos-related plaque (Blesovsky syndrome, Figure 4). The benign nodule usually gives no symptoms;

e)

ischaemic – lung infarction;

f)

developmental:

i)

chondroid hamartoma (15%);

ii)

sclerosing haemangioma;

iii)

bronchogenic cyst;

iv)

lung sequestration.

Malignant conditions (approximately 50% of all SPN are malignant)

Primary lung carcinoma:

a)

non-small cell carcinoma, such as adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, large cell carcinoma (Figure 5) and primary pulmonary lymphoma;

b)

small cell carcinoma;

c)

carcinoid neuroendocrine pulmonary tumours.

Secondary lesions, metastasising from the colon (commonest site, accounting for 30-40% of all metastatic SPN), kidney (Figure 6), breast, prostate, thyroid, endometrium, skin melanomas and long bone sarcomas.

3

What are the important features in the clinical history of a patient with an SPN?

Symptom status – although an SPN is usually asymptomatic, any symptomatic SPN should be considered malignant until proven otherwise and should be investigated further.

Age – primary lung cancer is unlikely in non-smokers below the age of 40.

Smoking – increases the risk of primary lung cancer by 3.5 times and is proportional to the number of pack years. In ex-smokers, the risk of adenocarcinoma remains elevated for up to 30 years.

Haemoptysis – is highly suggestive of malignancy in a smoker, over 40 years of age. Benign causes for haemoptysis include pneumonia (Klebsiella), tuberculosis (TB), bronchiectasis, AVMs, lung sequestration and sclerosing haemangioma (Figure 7).

Constitutional symptoms – including fever, night sweats, malaise, weight loss, arthralgia and myalgia, generally point to an inflammatory or infectious aetiology, such as lung abscesses, TB or vasculitis.

Drug history – especially of immunosuppressive medications.

Acquired immune deficiency status.

Travel history – including a recent exposure to TB or histoplasmosis.

Occupational risk factors – including exposure to asbestos or toxic fumes.

History of extrapulmonary malignancy – especially colon, breast, kidney, thyroid, uterus, prostate, seminoma, removed skin lesion (melanoma) and long bone sarcoma.

Previous mediastinal radiotherapy – which may result in post-radiation fibrosis and scar adenocarcinoma.

Paraneoplastic syndromes – including hyperpigmentation and Cushingoid features that may suggest lung carcinoid.

Previous radiology – increase in size over time is highly suggestive of malignancy, although a sclerosing haemangioma, may also increase in size (Figure 8).

4

What are the important features in the clinical examination of a patient with an SPN?

Clubbing – which is found in lung cancer, chronic inflammatory conditions (such as bronchiectasis and lung abscess) and congenital AVMs.

Cyanosis, clubbing, skin naevi, lip telangiectases and a pulmonary murmur might suggest a pulmonary AVM or familial haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome).

Heart murmur in a drug abuser might suggest tricuspid valve endocarditis, septic emboli and subsequent lung abscess formation.

Weight loss and cachexia may indicate underlying malignancy.

Epistaxis and skin lesions, such as a purpuric rash over the hands or legs, may suggest vasculitis.

Metastases from previous malignancy may be suggested by scars of a previous operation, such as mastectomy, or the presence of a leg prosthesis following long bone sarcoma.

5

What are the important radiological characteristics of an SPN?

Based on the Fleischner Society glossary of terms for thoracic imaging:

Size – with lesions subdivided into those <8mm (which are managed by surveillance) and those between 8-30mm (which are managed by further investigation).

Shape – usually rounded (coin lesion) or oblong but can be lobulated.

Margins – smooth, irregular or spiculated (suggestive of cancer until proven otherwise).

Radiodensity – which can be radiodense (white) or radiolucent (grey or black) with high, low or indeterminate attenuation.

CT density – which is measured in Hounsfield Units, where the density of air is -1000 HU (black), fat -80 HU, water 0 HU, calcification >+165 HU and bone +700 HU.

Enhancement (with iodine contrast):

a)

benign diseases – which normally show an absence of enhancement (≤15 HU);

b)

malignant diseases – which usually ‘light up’ 5 minutes after injecting the contrast.

Rim enhancement (or ring enhancement sign) – an area of decreased radiodensity surrounded by an enhanced ring is suggestive but not conclusive of a benign pathology. The enhancing rim is due to fibrotic inflammatory tissue surrounding a necrotic centre.

PET activity – which is referred to as ‘FDG avidity’ and measured in SUV_max (maximum standard uptake value). An SUV ≥2.5 is considered ‘hypermetabolic’ and indicative of malignancy (lesion ‘lights up’). It should be emphasised that the absence of FDG avidity does not mean the lesion is definitely benign.

Calcification – which is the only finding that reliably indicates a benign lesion.

6

What is a ground-glass opacity?

A ground-glass opacity (GGO) is defined as a hazy focal density, with ill-defined margins, but preserved bronchial and vascular markings.

The differential diagnosis of GGO ranges from inflammatory lesions to early primary lung cancer, with around 60% of GGOs being malignant.

Histologically, the ground-glass component typically corresponds to a lepidic pattern and the solid component to invasive patterns. Solid components usually arise from the airways. Bubble-like, cystic lucencies and bronchograms can appear within the GGO and are associated with well-differentiated adenocarcinoma.

GGOs are classified as:

a)

part-solid GGO (Figure 9A) – which is seen with mixed mucinous and non-mucinous adenocarcinoma;

b)

pure GGO (non-solid, Figure 9B) – which is seen in pre-invasive lesions, such as adenocarcinoma in situ (AIS) and atypical adenomatous hyperplasia (AAH).