Lung cancer associated with cystic airspaces

Lung cancer associated with cystic airspaces, rather than a distinct disease, represents a spectrum of radiological patterns of tumor growth mainly characterized by lesions arising or abutting the walls of cystic airspaces. Attention to this pattern has been brought in recent decades primarily due to the establishment of lung cancer screening programmes.

For a detailed discussion of the different histological subtypes, please refer to the main article on lung cancer.

Epidemiology 

This pattern of lung cancer presentation has been reported to represent less than 4% of all lung tumors . These lesions have been reported to be missed in about a fifth of cases on retrospective analysis .

Clinical presentation 

They are commonly asymptomatic and discovered either incidentally or during active lung cancer screening.

Pathology 

There are two acknowledged theories of lung cancers related to cystic airspaces:

• tumors arising at the interface between the normal parenchyma and the fibrotic/distorted cystic airspace
  • "cystic airspace" can be emphysematous bullae (more common), bronchiectatic airways, fibrotic cysts, or subpleural blebs 
  • remember that patients with emphysema and fibrotic interstitial lung disease are in an increased risk for lung cancer
• microscopic tumor cell growth obstructs a small distal airway and induces the formation of visible cysts on CT due to a check-valve mechanism
  • with the tumor progression, a solid soft-tissue component may become evident on follow-up imaging, and thus this is commonly identified retrospectively 

A pre-existent "cystic airspace" itself can have different histological features depending on background lung disease. The lung cancer components, although capable of being histological type, are predominantly non-small-cell adenocarcinoma.

Note that scar carcinoma, which refers to the development of cancer within acquired parenchymal abnormalities and the consequent scarring related inflammation, is still a controversial matter and is not considered in the discussion of this article.

Some studies have shown an increased risk for mucinous adenocarcinomas related to congenital cystic malformations , but this will not be grouped under the scope of this article, and it is discussed in their specific articles.

Radiographic features

CT

In most cases, early tumors associated with cystic airspaces will present as nonspecific findings such as a focal wall thickening or an adjacent small pulmonary nodule, both of which will require further followup to confirm progression and thus features supporting malignancy. Usually, they start as a focal wall thickening that increase its circumferential involvement, and then a nodule emerges .

Any change in morphology of known cystic airspace or adjacent nodules should be always regarded as suspicious.

An increase in the size of the solid component can cause the cystic airspace to either decrease, increase, or remain stable in diameter .

Classification

The tumors can be classified into four different morphological patterns according to Mascalchi et al. :

• type I: when there is a nodule adjacent to a cystic airspace
• type II: when there is a nodule within the cystic airspace
• type III: diffuse wall thickening of the cystic airspace
• type IV: multiple cystic airspace with interposed solid and non-solid tissues; this particular type has been recognized as a typical pattern seen in lepidic-predominant adenocarcinomas, minimally invasive adenocarcinomas, and adenocarcinoma in situ

Nuclear Medicine 

PET/CT

As those lesions are mostly too small (less than 8-10 mm) or subsolid, PET/CT is often limited in assessing them. Also, some lesions within the airspace, such as those of type IV morphology, have low cellular density, which also precludes an accurate radiotracer uptake measurement .

Radiology report 

• wall thickening in cystic airspace that progress in between interval scans, when in a patient with high-risk for lung cancer, should be considered suspicious and recommendations for further surveillance or additional investigations must be stated on the report
• ideally, nodules adjacent to cystic airspace should be worked up according to the Fleischner Society recommendations for lung nodules. And, for those patients under an established screening protocol, characterization of the nodule according to the Lung-RADS guidelines is recommended 

Differential diagnosis

• lung inflammatory changes or infection
  • bulla wall thickening and nodularity may be present 
    • the multiplicity of lesions and clinical setting are usually supportive of inflammation/infection
  • fungal cavities (mycetoma) tend to have diffuse wall thickening usually showing some nodularity, not common in cancers (in particular, those of type III morphology)
• amyloidosis
  • may also present with pericystic nodules, particularly when within the lymphoid interstitial pneumonia spectrum
• post-treatment lung metastases 
  • lung metastasis may cavitate after treatment (chemotherapeutic or antiangiogenic agents)
  • clinical history and previous imaging are usually enough to distinguish them

Practical points

• clinical information and medical history are essential when interpreting these findings
• always look for other associated findings to help to narrow the differentials
• negative PET/CT does not exclude malignancy 
• be aware that in those high-risk patients, synchronous or metachronous tumors are not that infrequent, and these other lesions are mainly presumed to represent second primary cancers rather than metastases