Analysis of Cystic Lung Disease

Wallace T. Miller, Jr M.D. Professor of Radiology

Most cystic lung diseases can be accurately diagnosed from CT by the typical appearance of the cysts.
In this article we will describe the typical patterns of the four most common cystic lung diseases.

Introduction

Cysts are holes in the lung with a surrounding wall and can be differentiated from emphysema (holes without walls), cystic bronchiectasis (tubes not cysts) and honeycombing (interlocking/stacked cysts).

The most common cystic diseases are:

  • Lymphangioleiomyomatosis (LAM) with simple thin walled round or oval cysts.
  • Birt Hogg Dube syndrome (BHD) with lenticular shaped cyst in a peri-septal location.
  • Langerhans cell histiocytosis (LCH) with irregular shaped cysts
  • Lymphocytic interstitial pneumonia (LIP) with cysts with vascular indentations.

LAM is the most common cause of widespread simple cysts.
We will discuss these features as Simple cysts, BHD-type, LCH-type and LIP-type cysts.
Using these criteria you can usually make a correct 1st choice diagnosis.

When we also include the cheerio-sign and associated ground glass, which we will discuss later, we will get this table.

Cystic lung disease is an uncommon imaging finding that may be clinically insignificant or cause significant morbidity and mortality.
Pulmonary cysts appear as low-attenuation regions with a surrounding wall and are often, round or oval in shape, but other appearances occur (1).

Most diffuse parenchymal lung diseases require clinical information to establish a diagnosis.  
However, the imaging appearance of the most common cystic lung diseases may be diagnostic or near diagnostic, which makes it easy.

Uncommon cystic lung diseases usually do not have typical imaging features and even with clinical information it can be difficult to establish a diagnosis.

Three patients with emphysema

Cysts are holes in the lung with a surrounding wall.

Cysts should be distinguished from:

  1. Holes without walls (centrilobular emphysema)
  2. Cystic bronchiectasis (tubes not cysts)
  3. Honeycombing (interlocking/stacked cysts)

Simple Cysts - predominantly LAM

Simple cysts are thin walled, round or oval and regularly shaped and are most often due to LAM (83%). and LCH (9%).
In general, the presence of only simple cysts (regardless of number) should lead to a diagnosis of LAM, except in men when LCH should be diagnosed.

The presence of simple cysts without any other criteria hasa 88-97% sensitivity, 91-92% specificity and 83% positive predictive value (PPV) for the diagnosis of Lymphangioleiomyomatosis (LAM).

Lymphangioleiomyomatosis (LAM) is an indolent, progressive growth of smooth muscle cells throughout the lungs, pulmonary blood vessels, lymphatics, and pleurae. It is rare and occurs exclusively in young women. Symptoms are dyspnea, cough, chest pain, and hemoptysis; spontaneous pneumothorax is common (ref).

BHD-type cysts

Birt-Hogg-Dube syndrome

BHD is an autosomal dominant genetic disorder that can cause susceptibility to kidney cancer, renal and pulmonary cysts, and noncancerous tumors of the hair follicles, called fibrofolliculomas.
The cyst in the lungs can cause recurrent pneumothorax, but do not affect pulmonary function.

BHD type cysts have some borders defined by interlobular septae (arrows).
The peri-septal location often gives the cysts sharp angles that causes them to have a lenticular shape.
BHD type cysts have 98-100% specificity, 88-100% PPV and 76-81% sensitivity for the diagnosis of Birt-Hogg-Dube syndrome.

BHD is always low profusion (< 50 cysts).
However other diseases may have low profusion of cysts (LIP, LAM, LCH, metastasis, neurofibromatosis).

Some BHD cysts may be adjacent to the pleural (peri-pleural) (red arrows).
However, peri-pleural cysts may be seen in other diseases (LIP, paraseptal emphysema).

Peri-pleural cyts in BHD and LIP are usually lower lung zone predominant but paraseptal emphyseama is upper lung zone predominant.
These features are supportive but not diagnostic of BHD.

LCH-type cysts

Typical LCH

Typical appearance

Pulmonary Langerhans cell histiocytosis (LCH) is proliferation of monoclonal Langerhans cells in lung interstitium and airspaces. Etiology is unknown, but cigarette smoking plays a primary role. Symptoms are dyspnea, cough, fatigue, and pleuritic chest pain. Diagnosis is based on history and imaging tests and sometimes on bronchoalveolar lavage and biopsy findings.
Treatment is smoking cessation.
Patients are at increased risk of cancer (ref).

LCH type cysts are bizarrely or irregularly shaped cysts (yellow arrows).
In preliminary analysis LCH type cysts have 96-100% specificity and 56-100% positive predictive value (PPV) for LCH.
But are not sensitive (38-39%) for the diagnosis of LCH, because LCH can present in an atypical way.

Typical LCH

Another example of typical LCH.

Not typical LCH: cheerio sign

Atypical appearances of LCH

LCH is the most variable appearing cystic lung disease:

    • 38% with LCH type cysts.
    • 23% appearing as small thick walled cysts (“cheerio sign”)(yellow arrows).
    • 23% appearing as simple cysts (like in LAM).
    • 15% having other appearances.
LCH: cheerio sign

LCH with “cheerio sign”

Thick walls have traditionally been a finding associated with LCH.
When seen as part of a small cyst or cavitary nodule, it is called the “cheerio sign”
However, thick walls have poor sensitivity (23%) and PPV (43%) for LCH.

LCH presenting as simple cysts

LCH with simple cysts

    LCH related simple cysts are prodominantly located in the upper zones, while LAM related simple cysts are more diffuse.

    This however yielded a 96% specificity but only a 50% positive predictive value. i.e. half of patients with upper zone distribution of simple cysts had LAM.
    This is probably because LAM is a much more frequent cause of simple cysts and so “strange LAM” is just as likely as “typical LCH”.

    This atypical case of LCH has so many simple cysts, that the cysts resemble honeycombing.

LIP-type cysts

LIP type cysts have two characteristics

    • Indented by vascular structures (red arrows) and/or
    • Septations (yellow arrows)

LIP cysts are sensitive (73-86%) and specific (93-96%) but has poor PPV (46-60%), ie cause multiple false positive diagnoses 

It is likely that excluding septations as a criterion will reduce specificity but increase specificity and PPV for LIP.

Emphysema

There are three subtypes of emphysema: centrilobular, paraseptal and panlobular.

The early lesions of entrilobular emphysema appear as tiny holes without walls (arrows)

Panlobular

When centrilobular emphysema becomes severe or with panlobular (panacinar) emphysema, the entire lobule becomes destroyed but the interlobular septa often remain.

This appears as large regions of black lung or as polygonal “cysts” (yellow arrows) often with a central dot (red arrows) that is the central artery.

Paraseptal emphysema

Parseptal emphysema appears as a single row of moderate to large diameter cysts (arrows) in the subpleural lung.  
This in some way resembles peripheral honeycombing.  

However in most cases paraseptal emphysema is upper zone predominant and the cystic spaces are usually larger (> 10 mm) than honeycombing (usually < 10 mm).

Cheerio sign

Cheerio sign in LCH

When thick walls are seen as part of a small cyst or cavitary nodule, it is called the “cheerio sign”

The optimal strategy for small thick walled cysts:

  • Diagnose LCH when the cysts are upper zone predominant.
  • Diagnose metastases when cysts are diffuse (uniform upper and lower distribution) or lower zone predominant. 
Cheerio sign in metastases

This patient also has the cheerio sign, but it was the result of metastases.

When the cysts are predominantly in the upper zones, then the most likely diagnosis is LCH.
When the cysts are diffuse in upper and lower zones or predominantly in the lower zones, then metastases is a more likely diagnosis. 

Cysts and Ground Glass pattern

GGO and cysts is a rare combination.
Causes include:

    • Lymphocytic interstitial pneumonia (LIP)
    • Pneumocystis jirovecii pneumonia (PCP)

The image is of a patient with LIP.

PCP

Image of a patient with PCP with a combined cystic and GGO-pattern

LIP

Image of a patient with LIP.